",isbn:"978-1-83881-111-2",printIsbn:"978-1-83880-992-8",pdfIsbn:"978-1-83881-112-9",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,hash:"acb2875b3bfc189c9881a9b44b6a5184",bookSignature:"Dr. Abdo Abou Jaoudé",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11865.jpg",keywords:"Linear Operators, Normal Operators, Spectral Theorem, Applications, Differential Operators, Integral Operators, Functional Calculus, Complex Variables, Complex Analysis, Theory, Recent Advances, Latest Trends",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 13th 2022",dateEndSecondStepPublish:"May 11th 2022",dateEndThirdStepPublish:"July 10th 2022",dateEndFourthStepPublish:"September 28th 2022",dateEndFifthStepPublish:"November 27th 2022",remainingDaysToSecondStep:"12 days",secondStepPassed:!0,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Abdo Abou Jaoudé is a pioneering Associate Professor of Mathematics and Statistics at Notre Dame University-Louaizé. He holds two PhDs in Mathematics and Prognostics from the Lebanese University and Aix-Marseille University. His research interests are in the field of mathematics.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"248271",title:"Dr.",name:"Abdo",middleName:null,surname:"Abou Jaoudé",slug:"abdo-abou-jaoude",fullName:"Abdo Abou Jaoudé",profilePictureURL:"https://mts.intechopen.com/storage/users/248271/images/system/248271.jpg",biography:"Abdo Abou Jaoudé has been teaching for many years and has a passion for researching and teaching mathematics. He is currently an Associate Professor of Mathematics and Statistics at Notre Dame University-Louaizé (NDU), Lebanon. He holds a BSc and an MSc in Computer Science from NDU, and three PhDs in Applied Mathematics, Computer Science, and Applied Statistics and Probability, all from Bircham International University through a distance learning program. 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1. Introduction
Heart transplant is the gold-standard treatment for end-stage heart failure since the first case, performed by Christiaan Barnard, on December 3, 1967 in Cape Town [1]. This first case was the results of previous works led mainly by Norman Shumway at Stanford. After an initial spread of the technique and the development of different transplant programs, the actual number of heart transplants declined due to impaired outcomes, mostly due to infections and rejection [2]. Only a few groups, mainly Stanford in the USA and the Pitié-Salpêtrière in Europe, continued investigating and working on trying to improve their patients’ outcomes. It was not until the introduction of cyclosporine as an immunosuppressor, that solid organ transplant outcomes significantly improved [3]. This significant change in patient management led to the final expansion of the technique and the development of multiple programs across the world.
Technical and medical developments have caused previously lethal conditions that evolve into chronic ones, increasing the prevalence of end-stage heart failure. This increase, in addition to the aging of the population, has led to a disbalance in the number of donors available, which has remained stable over the last years according to ISHLT data [4]. This disbalance has caused an increase in the waiting time period, leading to the development of different strategies to sustain patients.
This abovementioned shortage of donors, which is common to most countries, forced the transplant programs to expand their acceptance criteria with the such called “extended-criteria donors.” This means that older donors with longer ischemic times were now accepted. Despite the initial concerns, results have been acceptable, with similar survivals at 1-year, 89% vs. 86% in the published reports [5, 6]. The increase achieved in the donor pool was still insufficient, so additional donors were evaluated. The pediatric groups developed the ABO group non-compatible heart transplant [7], while adult groups developed strategies for accepting HCV+ donors [8], treating recipients with the new antiviral in the immediate postoperative period, or started programs of donation after circulatory death (DCD donors) [9, 10]. It is important to remark that these different strategies to expand the donor pool have accomplished similar survival, both short (96% vs. 89% at 1-year) and medium-term (94% vs. 82% at 5 years) results, as the conventional donors [11].
As mentioned, the shortage in the donor pool leads to prolonged times on the waiting list. Some patients, however, would deteriorate during this waiting time. Different support strategies have been developed to sustain declining patients to allow for organ recovery and patient rehabilitation before the transplant. These bridging strategies can be classified into two main groups—short-term support and long-term support. Both of them have particularities that will be further developed.
2. Short-term mechanical circulatory support (ST-MCS)
Short-term support devices are the first line of support in patients who need emergent support, such as INTERMACS 1 patients, as they provide immediate hemodynamic support with an almost immediate deployment time, in some of them, such as ECMO or Impella®. In addition to those, there are other devices, such as Levitronix-Centrimag®, that need a surgical implant. It is worth mentioning that whereas ECMO provides complete circulatory support with one device, the other ones would need two pumps to provide full biventricular support.
Recently, several allocation systems changed their distribution policies aiming at providing a fair allocation of donors. These modifications meant that patients under ST-MCS achieve the highest priority on the waiting list [12].
2.1 Indications
All ST-MCS devices share common indications, the most common ones are as follows [13]:
Postcardiotomy shock
Primary graft failure after transplant
Cardiogenic shock due to acute coronary syndrome
Myocarditis
Peripartum cardiomyopathy
Arrhythmic storm
Cardiac arrest.
The choice of the device would depend mostly on availability and patient factors. The different devices provide variable degrees of support and have inherent implantation requirements; there is general agreement that ECMO would be the device of choice in cases with cardiac arrest as it can be implanted percutaneously at the bedside. It would also be the preferred option in cases of respiratory compromise and biventricular failure.
Impella® support is most commonly used for cardiogenic shock secondary to myocardial infarction; the smaller (2,5 and CP) devices can be inserted percutaneously but the bigger ones (5,0 and 5,5) require insertion through a prosthesis.
Levitronix Centrimag® requires a surgical implant. It is commonly used in postcardiotomy shock, primary graft failure, or isolated right ventricular failure after a long-term ventricular assist device. It allows for the longest support; so, it is the preferable device in cases of the bridge to recovery.
2.2 General management
During the recovery period or the waiting time, it is recommended to extubate patients if possible. If this can be accomplished, oral nutrition is the preferred option. If the patient cannot be extubated, tube feedings would be the best option, above parenteral nutrition; this should be reserved for patients with significant instability and the need for high-dose pressors.
Volume status should be maintained as neutral as possible, initially with diuretics, but it is not uncommon that patients under ST-MCS develop acute kidney injury and need renal replacement therapies (RRT). In our group, we promote early use of RRT to help to manage the volume status and avoid hypervolemia at the time of the transplant.
In addition to recovering the organ, it is important to keep the muscular tone with daily physical therapy, even with static bicycle or ambulation within the unit, whenever possible.
Simultaneously to recovering the patient, special attention should be paid to the management of the device. It should provide enough support to allow for organ recovery minimizing the potential complications. To prevent them, it is recommended to perform daily echocardiograms and keep close monitoring of central venous pressure and pulmonary pressure. Blood pressure control is mandatory to reduce the risk of neurological complications but also to reduce afterload that may interfere with the device function; the higher the afterload, the lower the left ventricular unloading. We would suggest avoiding medications with a long half-life to minimize the risk of vasoplegia during the transplant.
2.3 Specialized management
2.3.1 Anticoagulation
All devices require systemic anticoagulation; unfractionated heparin is the most common anticoagulant used. A single bolus, normally 1 mg/kg, is administered at the time of ECMO or Levitronix implant. Systemic infusion is not started until the coagulation parameters have been normalized and there are no signs of bleeding. For example, in cases of central cannulation, anticoagulation would be started once the chest tube output is less than 50–80 ml/h for 6 hours.
ECMO is a device that requires a higher dose as it has an oxygenator. The patient receives a bolus of heparin at the time of the implant and after that ACT is kept around 180–200 seconds and/or aPTT around 60–80 seconds [14].
Impella systems ® require a heparinized dextrose-based purge solution and systemic heparinization with ACT around 160–160 seconds for its proper functioning. A recent publication by Beavers [15] proposes variations of the purge solution that can be modified depending on the patients’ status.
Levitronix-Centrimag ® also requires systemic anticoagulation; the usual aPTT goal is 50–70 seconds. In all cases, systemic anticoagulation is maintained until the time of the transplant.
During the time on support, careful attention should be paid to the platelet count; in case, a sudden drop is noticed we would recommend to test for heparin-induced thrombocytopenia. Type 2 HITT may be a terrible complication that limits a patient’s options. If suspected, heparin should be immediately replaced by bivalirudin or argatroban.
2.3.2 Infections
There is no general consensus regarding antibiotic prophylaxis while on short-term support. However, most groups administer it, especially if the implant has been performed in emergent circumstances. Regarding the duration of the therapy, the ELSO ID Taskforce [16] does not recommend using antibiotic prophylaxis for more than 48 hours. In cases of central cannulation when the chest is left open, most groups would maintain the prophylaxis while the sternum is open.
Patients on short-term support are highly instrumentalized, with increased transfusion requirements and a higher incidence of renal failure compared to the general intensive care unit population; all these factors increase the risk of systemic infections. Biffi et al. reported bacteriemia rates around 20% and lower respiratory tract infections that oscillated between 4 and 55%. [17].
Due to the higher instrumentalization, the most common pathogens are coagulase-negative staphylococci, followed by Candida spp and Pseudomonas pp. The use of parenteral nutrition in these patients increases the risk of fungal infections.
Infections while on support can significantly impact the patients’ treatment options. A recent publication by the Spanish transplant group proved that infections while of support reduced the options of reaching a heart transplant [18].
2.4 Pretransplant assessment
At the time of the transplant, specific considerations should be taken into account depending on the device the patient is being bridged with:
2.4.1 ECMO or extracorporeal membrane oxygenator
ECMO has increased its use as a bridging device, as it provides immediate support for rapidly declining patients and those unstable or in cardiogenic shock. When using ECMO as a bridging strategy, several aspects should be taken into account. From the technical perspective, there are two key points. The first one is venous cannulation; careful attention must be paid to reduce the ECMO flows at the time of venous cannulation to avoid air entry. If this occurs, the device may stop or the patient may suffer systemic emboli. Secondly, ECMO support has the risk of developing left-sided intracavitary stasis with its inherent risk of systemic emboli. Unnecessary cardiac manipulation should be avoided before applying the aortic clamp.
From the medical standpoint, the team must be aware that ECMO support may cause lung congestion, which may be not evident while on support, but that may appear when trying to abandon cardiopulmonary bypass. This pulmonary impairment may cause hypoxemia or right ventricular failure.
2.4.2 IMPELLA®
This percutaneous axial pump is normally placed through the femoral artery or the axillary artery, inside the left ventricle. When used as a bridge-to-transplant, the axillary artery insertion is preferable as it allows the patient to ambulate and facilitates the patient’s rehabilitation.
At the time of the transplant, as the device crosses the aortic valve, surgeons should remove it into the aorta before applying the aortic clamp. After the implant is performed, attention should be paid to repairing the arterial entry site.
2.4.3 Levitronix-centrimag®
This magnetically levitated device provides up to 8 l/min of support and it is approved for 30 days support. It requires surgical intervention for its implant, in general, through a median sternotomy. However, some minimally invasive strategies have been proposed [19].
Its surgical implant should be performed considering the current patients’ clinical status but also the future transplant. For instance, when tunneling the cannulas, it is recommended to keep the exit site far away from the sternotomy, to avoid any potential cross-contamination. In addition, surgeons should also keep in mind the future transplant; to ease that, it is our preferred approach to place the arterial cannula low in the aortic root; so, the entry site is removed at the time of the implant and we have enough ascending aorta to cannulate and perform the aortic anastomosis. If the patient has some residual ventricular function and the surgical team decides to cannulate the left atrium as an inflow cannula, our suggestion would be to cannulate the left atrial roof. This structure would be removed while doing the cardiectomy and avoid manipulation of the pulmonary veins.
At the time of the transplant, the surgical team must take into account the time needed for surgical dissection; if the patient has been supported for more than 10 days, some extra time might be necessary to isolate the different cardiac structures. In addition, some technical details should also be considered; special attention should be placed to avoid unnecessary manipulation of the cardiac structures before applying the aortic clamp. Some small clots might have formed in the cardiac chambers and there is the risk of systemic emboli in cases of aggressive manipulation.
Cannulation is also an important step, particularly at the time of the double venous cannulation in the patient under biventricular support. In these cases, special attention must be paid to ensure the right-side device flow reduction at the time of the cannula insertion to avoid air entry. Both cannulas should be placed already clamped to prevent air entry.
As mentioned, we prefer to place the outflow cannula low in the aortic root, but if the cannula is placed in the ascending aorta, the surgical team would have to decide if the left side device is interrupted and the arterial cannula reused for the cardiopulmonary bypass (CPB) machine or if a second arterial cannula is necessary.
At the end of the procedure, it is mandatory to achieve careful hemostasis to minimize postoperative bleeding; some groups propose to leave the chest open to reduce the risk of tamponade and bleeding.
2.5 Surgical considerations
Short-term mechanical support is normally implanted in patients under cardiogenic shock. This extremely acute situation, with patients that are usually under mechanical ventilation and who can barely move due to a peripheral device, makes it difficult to complete the detailed transplant evaluation that would be performed in an ambulatory situation. Despite the urgency of the situation, we would encourage to follow a so-called “parallel pathway,” while recovering the patient like in Figure 1, an evaluation as complete as possible is performed, even more, if the patient has not been previously managed by the team. Our group has diagnosed end-stage neoplasm during these preoperative studies (Figures 2 and 3).
Figure 1.
Shows a patient, who is under biventricular temporary support, sitting on a chair during his/her intensive care unit stay. The patient was able to eat by himself/herself and do some physical therapy.
Figure 2.
Shows a lung tumor found in the pre-transplant assessment of patient support with peripheral ECMO.
Figure 3.
(a) shows the entry site of the arterial cannulas from a biventricular Levitronix-Centrimag®. (b) displays the abdominal study of the same patient, where a right renal tumor can be observed.
2.6 Results
Despite the systemic recovery achieved with these devices, several groups have shown their concerns regarding the outcomes of transplants with this ST-MCS bridging strategy. In 2018, the Spanish Transplant working group published a manuscript showing a 33% mortality when patients were bridged with ECMO and 11.9% when bridged with short-term left-sided devices [20]. Other reports have also shown reduced initial survival results when patients are bridged with ST-MCS [21, 22]. In previous publications, ECMO reveals as the bridging strategy with the shortest waiting times but also the worst post-transplant survival results. These worst results may be due to an early transplant with incomplete recovery of the organs in addition to pulmonary impairment due to insufficient left ventricular unloading.
In addition to this increased early mortality, different publications show a higher rate of postoperative transfusions and longer hospital length of stay compared to direct heart transplant or even, transplant with long-term devices [23].
3. Long-term mechanical circulatory support (LT-MCS)
As stated before, the increase in waiting list times may cause the clinical deterioration of patients awaiting a suitable organ. Long-term mechanical circulatory support offers these patients clinical stability and avoidance of multiorgan deterioration during this waiting time. Several devices have been developed, such as the Heartmate XVE®, the Heartmate II®, Heartware-HVAD®, Jarvik®, Syncardia®, and the HeartMate 3®. The last one is the most commonly used nowadays.
Most of them provide only univentricular support, mostly to the left ventricle. In cases where biventricular support is needed, a second device can be used “of-label’ to provide right ventricular support. Syncardia® and Carmart® are also known as “total artificial hearts” providing biventricular support with a single device. The major drawback of all these devices is the need for an additional surgical intervention before the heart transplant.
3.1 Indications
The primary indication of LT-MCS devices is end-stage chronic heart failure. Most left ventricular assist devices require a minimal end-diastolic left ventricular diameter for their implant, which is easily accomplished in cases of ischemic or dilated cardiomyopathy. In cases of restrictive cardiomyopathy, with small left ventricular cavities or cases with biventricular failure, a total artificial heart would be indicated.
The hemodynamic indications according to ISHLT guidelines [13, 24] are as follows:
Stage D refractory heart failure
Systemic hypotension with systolic blood pressure below 90 mm Hg
Cardiac index below 1,8 l/min/m2
Pulmonary capillary wedge pressure above 15 mm Hg
Evidence of end-organ perfusion
Peak oxygen consumption <12–14 ml/kg2.
3.2 Specialized management
3.2.1 Anticoagulation
LT-MCS requires antithrombotic treatment since the early postoperative period to prevent thrombotic events [25, 26]. Each manufacturer has its own specific recommendations; however, in general, most centers follow the below strategy:
Low-dose heparin in the first 12–24 hours if there are no signs of bleeding (chest tube output below 50 ml/h during >4 hours).
Heparin infusion is gradually titrated to achieve full anticoagulation after 48 hours.
Aspirin is started on the second postoperative day.
Vitamin K antagonists are started on the third postoperative day once the patient is stable and tolerates oral intake.
The target INR is 2.0–3.0. The antithrombotic treatment should be tailored to the patient’s clinical status.
In cases of heparin-induced thrombocytopenia, intravenous direct thrombin inhibitors, such as bivalirudin or argatroban, can be used. New oral anticoagulants have not been validated for the treatment of long-term MCS devices.
3.2.2 Infection
Infections will occur in nearly 60% of the implanted patients and the rate increases with the duration of support [27, 28]. The most common pathogens are gram-positive bacteria that colonize the skin and adhere to the implanted material creating biofilms; staphylococci spp account for more than 50% of infections followed by enterococci spp. Between the gram-negative rods, Pseudomonas spp is the most frequent, being responsible for 22–28% of infections [28].
Before a scheduled implant, it is recommended to remove all unnecessary lines and ensure there are no active infections. In cases of active infection, in special if bacteriemia, it is recommended to delay the implant until clearance of the infection, whenever possible.
A few years ago, antibiotic prophylaxis included gram-positive cocci, gram-negative rods, and fungi and it was maintained for days. The most current recommendations moved to the general cardiac surgery prophylaxis, using a cephalosporin that is maintained for 24–48 hours. In addition, MRSA should be discarded with a preoperative nasal swab and nasal mupirocine is applied [25].
Once the device has been implanted if an infection develops, it can be classified as [26, 27]:
Device-specific infections
Device-related infections (result of the surgery, for example, bloodstream infection).
Device-specific infections are the ones that actually involve the device and they vary from driveline infection to pump infection with mediastinitis. The most important aspect is prevention. For example, during the surgical implant, it is recommended to keep all the velour parts of the driveline covered and ensure proper fixation of the driveline to avoid excessive movements.
It is of extreme importance that both the patient and the caregiver learn how to perform the sterile dressing changes of the driveline; patients also need to recognize signs of alarm, such as erythema or purulent discharge. Keeping a photographic diary might be helpful. It is also important that the wound is periodically evaluated during the clinic visits.
Driveline infections should be individually addressed; if the patient has no general symptoms, treatment can start with increased dressing changes and culture-directed antibiotics. On the other hand, in case of systemic symptoms, intravenous antibiotics should be started. In these cases, a PET-CT scan might be performed to assess the extension of the infection. If image tests reveal the presence of collections, re-routing of the driveline might be necessary. If the infection has affected the actual device, pump exchange or transplant might be the only curative option and it is recommended that blood cultures are negative at the time of the surgery.
When transplanting a patient with an infected device, the surgical must minimize deeper contaminations; for example, in cases of driveline infection, the exit site must be sealed from the rest of the surgical fields avoiding contact between infected and non-infected fields. In cases of device-specific infections involving blood contact surfaces, surgeons should minimize the embolic risk by early initiation of cardiopulmonary bypass, stoppage of the pump, and application of the aortic clamp. If active mediastinal infection is found, extensive debridement and antibiotic irrigation are recommended. After that, all surgical materials should be changed. In these circumstances, some groups would leave the chest open with antibiotic irrigation. After the surgery, antibiotic treatment should be targeted to prior cultures.
It may seem controversial to transplant patients with a current infection. However, several reports have shown no differences in survival compared with patients transplanted on LT-MCS support without infection [29].
3.2.3 Blood pressure control
Blood pressure control is mandatory while on long-term support. Hypertension leads to increase afterload, thus reducing the device flows and the left ventricular unloading. In addition, there is a significant relationship between high blood pressure and adverse events, such as stroke or aortic regurgitation [30, 31].
As the devices are continuous flow, it is possible that patients have no pulse; in an intensive care unit, it is recommended to use invasive lines to monitor the blood pressure; whereas if the patient is ambulatory, a doppler measurement of the blood pressure is the preferred system [25]. The doppler reading is equivalent to the mean blood pressure.
For blood pressure control, the current recommendations include the use of renin-angiotensin-aldosterone system antagonists as first-line; beta-blockers are recommended in cases of arrhythmias but should be carefully used if the right ventricular function is poor. Calcium channel blockers would be the third option for blood pressure control [24, 25].
3.3 Surgical implant
When a bridge-to-transplant strategy is considered in a patient who is going to receive an LT-MCS device, the surgical implant must be carefully planned to ease the future heart transplant.
The device could be divided into different components, the inlet cannula and the pump, the outflow graft, and the driveline.
The inlet cannula is placed inside the left ventricle and secured with a sewing ring. Some groups reinforce this ring with surgical glues, which may lead to increased adhesions.
Careful attention should be paid to the length and layout of the outflow graft, in special at the time of the chest closure. It should run smoothly along with the right-side cavities. A short graft would lay immediately under the sternum (Figure 4A), increasing the risk of damaging it during the reesternotomy. An excessively long graft is at risk of twisting, impairing the pump function. Its anastomotic site in the ascending aorta should be performed, taking into account that it should be removed at the time of the transplant and that enough ascending aorta should be left to perform the anastomosis.
Figure 4.
A shows an outflow tract running immediately below the sternum. In this case, the implant was performed minimally invasive, so the risk of injury at the time of the transplant was lower. B shows non-conventional outflow tract layouts; this patient had the outflow anastomosis placed at the descending aorta. This risk of injury was lower at the reesternotomy but achieving control of it might be more difficult.
The driveline should also be carefully placed. Our group does a double route; we exteriorize the driveline into the subcutaneous tissue at the left upper quadrant and then tunnel it to the right upper quadrant, leaving a short intrapericardial portion away from the sternum, to avoid damaging it during the mediastinal reentry at the transplant time.
Reinterventions in patients with long-term devices are challenging due to extensive adhesion formation [32]. Several strategies have been developed to facilitate these reinterventions. The most extended one is covering the device and the outflow tract with PTFE sheets that would reduce the adhesions and, at the same time, might protect the pump components during the dissection [33, 34]. A different approach would be pursuing a less-invasive approach, either with two thoracotomies or a left thoracotomy and a mini-sternotomy. In these less invasive approaches, the avoidance of an extended pericardial opening and limited cardiac manipulation reduces the development of adhesions [35].
3.4 Transplant surgery
Despite the careful surgical implant, we would suggest that every patient with an LT-MCS who is a transplant candidate should have a postimplant computed tomography to know the final position of the different device components (Figure 4A and B).
At the time of the implant, the surgical team must carefully plan the times as surgical dissection may be more difficult and time-consuming than conventional reinterventions. Once we accept the organ, it is our preferred approach to reverse anticoagulation with prothrombin complex to avoid volume overload and start the anesthetic process. Our advice would be to start the reintervention enough in advance to be able to perform an extremely careful dissection in order to minimize intraoperative and postoperative bleeding.
We suggest that both the abdomen and the groins should be prepped; the abdomen should be accessible to remove the driveline and femoral vessel cannulation may be necessary in some cases.
Once the reesternotomy is performed, the main goal is achieving control of the aorta and, both cava veins and the outflow graft, so, cardiopulmonary bypass (CPB) can be started. Most groups suggest completing the device dissection while on CPB support. It is important to stop the LT-MCS device and occlude its outflow graft when starting the CPB machine to avoid backward flow. In cases of different outflow graft implant sites, for example, in the descending aorta, control of it should also be achieved before starting the CPB machine. Once CPB is supported, the pump removal can be performed. The cardiectomy is completed in the usual way, making sure the outflow anastomotic site is removed.
After completion of the implant, it is mandatory to achieve proper hemostasis to minimize the need for blood products and reduce the risk of postoperative tamponade.
Following protamine administration, the driveline should be removed. In cases of driveline infection, as previously mentioned, the driveline exit site would be kept in a different surgical field to minimize the contamination of the mediastinum; thus, the internal part of the driveline would be removed from the inside and the infected part would be pulled once the chest is closed. As all foreign material should be removed, two incisions may be necessary to remove the totality of the driveline; we suggest doing extensive debridement of the exit site in cases of infection and ensure proper closing of the wounds to reduce the risk of collection development, even with the use of vacuum-assisted therapy.
3.5 Results
With the development of LT-MCS, several transplant programs report their concern regarding the impact of this bridging strategy on the transplant outcomes [36, 37]. However, long-term devices have proved themselves as successful bridge-to-transplant devices. Despite being a challenging surgery, survival results are comparable to direct transplant strategies in recent publications [23, 38, 39]and recent publications only showed a higher post-transplant transfusion need in the bridged group [23, 36].
Recent ISHLT data from its transplant registry show 90% 1-year survival in either direct transplant or bridge with left ventricular assist device; these same data showed decreased initial survival if patients were bridged with either biventricular support or total artificial heart, probably due to a worse preoperative status [40].
In addition to survival, the other main concern with this bridging strategy is post-transplant vasoplegia. Contradictory results have been published in this regard [41, 42].
3.6 Bridge-to-bridge
As previously developed, recent changes in the allocations systems give the highest priority to the sickest patients. However, this might lead to transplant patients who have had not enough time to recover organ function or who could have not been fully evaluated worsening transplant results. A way of avoiding this phenomenon would be the bridge-to-bridge strategy, which means that a patient under ST-MCS would be transitioned to a long-term device and transplanted once fully recovered and rehabilitated.
Before the surgery, a careful assessment of right ventricular function and associated valvular lesions, such as significant aortic regurgitation or tricuspid regurgitation, must be performed. The presence of intracavitary thrombi should also be evaluated. The presence of any of these lesions in addition to the initial device would impact the surgical technique and the approach. For example, if the patient is under ECMO support, the long-term device implant could be performed under the same support. In these cases, if concomitant lesions have been discarded, it is even possible to perform a minimally invasive device insertion. However, teams must keep in mind that right ventricular function is difficult to evaluate while on ECMO support. Thus, in addition to potential pulmonary congestion leads to a significantly higher incidence of postoperative right ventricular failure [43].
When the initial device is an Impella®, due to its peripheral implant, it is possible to perform the insertion both through a minimally invasive approach or through a median sternotomy. If the surgical team prefers to follow the minimally invasive approach without CPB support, we would suggest to have the femoral vessels prepared for cannulation in case the patient collapses at the time of stopping the Impella® device.
Once the implant of the new device has been finished, it is important not to forget to repair the cannulation site, ensuring the proper distal flow of the extremity to minimize vascular complications, which may have a high impact on survival.
If the patient is bridged from a Levitronix Centrimag®, the most probable approach would be through a median sternotomy; in these cases, we would suggest to transition the temporary support to cardiopulmonary bypass and then perform the implant. This strategy will allow to lift the heart without instability and to inspect the left ventricular chambers to remove any potential debris.
Despite ST-MCS allowing for rapid recovery, these patients can still be considered the sickest ones. As mentioned, the incidence of post-device right ventricular failure may reach up to 20%, higher than in the non-bridged population [43]. In addition, 1-year survival after the implant is also worse compared to the general LVAD population (1-year survival 70% vs. 91%) [39]. Despite these initial poorer results, when these patients recover and are transplanted, results are as successful as transplant after primary LVAD insertion, with 1-year survival around 90% [39].
4. Discussion
Heart transplant remains the gold-standard treatment for end-stage heart failure since the first case was performed in 1967. Once the initial issues with rejection were solved after the introduction of cyclosporine, results significantly improved and several transplant programs developed.
Simultaneously, several therapeutic advances led to significant improvement of pathologies previously lethal. This new chronicity of several cardiomyopathies in addition to an aging population made heart failure one of the most prevalent diseases, thus increasing the number of heart transplant candidates. On the other hand, the number of potential donors for a heart transplant was actually maintained or even diminished; this situation caused a clear disbalance and the shortage of donors became a reality.
Mechanical circulatory support was initially developed for patients who could not be weaned from CPB, such as the first implant performed by Dr. DeBakey and it became a field in continuous development. However, it was not until the early 2000s when the REMATCH trial [44] showed better survival with LT-MCS than with conventional treatment for end-stage heart failure patients. These results led to a tremendous expansion of the therapy with different devices being developed. Since the first generation XVE to the current HeartMate 3, devices have become smaller and more hemocompatible, significantly improving the results, both of survival and adverse effects. With the huge advances in the field, in addition to the shortage of donors, the heart failure community realized that LT-MCS, despite requiring additional surgery and the inherent technical complexities at the time of the transplant, was the best option to allow patients to reach the transplant in the best clinical situation possible; until the last allocation system modification, nearly 50% of the recipients in the USA had a previous long-term device.
In addition to the chronic heart failure population, as physicians, we face a significant proportion of patients with acute heart failure. In these circumstances, short-term MCS would be the preferred option. Short-term devices allow for rapid patient stabilization and organ recovery. In some cases, patients’ myocardial function would recover and the device would be explanted, while in other cases, patients would need further therapies, such as heart transplants. This situation might be tricky as the transplant evaluation has to be performed under support, which might limit its depth, and the treating physicians should find the appropriate moment to list the patient finding a weak balance between patient recovery and avoidance of complications. As ST-MCS patients can be considered the sickest ones, the different allocations systems give these patients the highest priority on the transplant list, so they can have more opportunities of being transplanted. However, this strategy also increases the risk of transplanting patients not fully recovered or fully evaluated, which has proved to worsen transplant results [45], especially if ECMO is the bridging device.
The initial impairment of survival using the ST-MCS bridging strategy let to consider alternative strategies; the most used one, whenever possible, would be the bridge-to-bridge, which means transitioning a patient from short-term to a long-term device to allow for complete recovery. In these cases, patients undergo an additional surgical procedure, such as the LT-MCS implant, but they can be fully evaluated and be listed when they are completely recovered. Groups that follow this strategy have already published results comparable to the patients bridged directly with an LT-MCS device.
Aside from the device used, their common goal is to ensure the patient reaches the transplant in the best possible clinical condition. To ensure it, it is fundamental that patients’ physical status is improved with adequate nutrition and adapted physical therapy, which should be started as soon as possible, to avoid muscle mass loss. In addition to recovery, the avoidance of adverse effects is of extreme importance; accurate blood pressure control would help to reduce the incidence of neurologic events and also the development of aortic regurgitation. It would also reduce afterload, which would improve the left ventricular unloading and signs of congestion. Prevention of infections is another striking aspect; it starts in the same operating theater with the implant of the driveline and it continues during the whole time on support, with accurate dressing changes and accurate follow-up [25, 26]. In the cases of ST-MCS, the same rules apply; in these cases, removal of unnecessary lines and careful assessment of the cannulas exit site might help in the reduction of infections.
Once at the time of the transplant, the surgical team should be aware of the different particularities of each device and plan the procedure accordingly. Dissection of long-term devices might need additional time compared to other cardiac reinterventions or ST-MCS devices may need an earlier aortic clamp than other cases. As important as surgical timing is planning additional procedures that might be required, such as vascular repair, wound debridement, or removal of an infected driveline. In this last case, special care should be taken to avoid mediastinal contamination.
Post-transplant care has no differences compared to non-bridged patients; immunosuppression regimens and rejection surveillance are kept the same; the only specific situation would be the extension of antibiotic treatment in cases of device infection and it should be individually discussed with the ID team.
Despite the initial concerns regarding transplant outcomes after the use of a mechanical device, results have proved to be excellent, with survival rates similar to the non-bridged population in the case of LT-MCS. ST-MCS might not seem a good strategy due to worse initial results. However, physicians should take into consideration that we are facing the sickest patients and that these temporary devices may be the only option available for these acute patients. [39].
5. Conclusions
Mechanical circulatory support as a bridge-to-transplant strategy allows for patient recovery, increased functional capacity, and a reduction in wait-list mortality.
Despite the surgical challenges the different support strategies associate, post-transplant survival results have proved them a good strategy to safely bridge patients to heart transplant.
Conflict of interest
None of the authors has any conflict of interest regarding this manuscript.
\n',keywords:"heart transplant, short-term mechanical circulatory support, ECMO, long-term mechanical circulatory support, survival",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/80417.pdf",chapterXML:"https://mts.intechopen.com/source/xml/80417.xml",downloadPdfUrl:"/chapter/pdf-download/80417",previewPdfUrl:"/chapter/pdf-preview/80417",totalDownloads:27,totalViews:0,totalCrossrefCites:0,totalDimensionsCites:0,totalAltmetricsMentions:0,impactScore:0,impactScorePercentile:0,impactScoreQuartile:0,hasAltmetrics:0,dateSubmitted:"December 20th 2021",dateReviewed:"January 11th 2022",datePrePublished:"February 10th 2022",datePublished:null,dateFinished:"February 9th 2022",readingETA:"0",abstract:"Heart transplant is the gold-standard treatment for end-stage heart failure. However, the aging of the population, increase in the prevalence of heart failure and the shortage of available donors have led to a significant increase in the wait-list times. This increase in waiting time may cause some patients clinically deteriorate while on the list. Several bridging strategies have been developed to help patients reach heart transplant. It is mandatory to know the current results of these techniques and the specific tips and tricks these different devices may have. Survival results would also be presented to help us decide the best strategy for each of our patients.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/80417",risUrl:"/chapter/ris/80417",book:{id:"11236",slug:null},signatures:"Elena Sandoval and Daniel Pereda",authors:[{id:"337128",title:"Dr.",name:"Daniel",middleName:null,surname:"Pereda",fullName:"Daniel Pereda",slug:"daniel-pereda",email:"dpereda@clinic.cat",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"346717",title:"Dr.",name:"Elena",middleName:null,surname:"Sandoval",fullName:"Elena Sandoval",slug:"elena-sandoval",email:"esandova@clinic.cat",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Hospital Clinic of Barcelona",institutionURL:null,country:{name:"Spain"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Short-term mechanical circulatory support (ST-MCS)",level:"1"},{id:"sec_2_2",title:"2.1 Indications",level:"2"},{id:"sec_3_2",title:"2.2 General management",level:"2"},{id:"sec_4_2",title:"2.3 Specialized management",level:"2"},{id:"sec_4_3",title:"2.3.1 Anticoagulation",level:"3"},{id:"sec_5_3",title:"2.3.2 Infections",level:"3"},{id:"sec_7_2",title:"2.4 Pretransplant assessment",level:"2"},{id:"sec_7_3",title:"2.4.1 ECMO or extracorporeal membrane oxygenator",level:"3"},{id:"sec_8_3",title:"2.4.2 IMPELLA®",level:"3"},{id:"sec_9_3",title:"2.4.3 Levitronix-centrimag®",level:"3"},{id:"sec_11_2",title:"2.5 Surgical considerations",level:"2"},{id:"sec_12_2",title:"2.6 Results",level:"2"},{id:"sec_14",title:"3. Long-term mechanical circulatory support (LT-MCS)",level:"1"},{id:"sec_14_2",title:"3.1 Indications",level:"2"},{id:"sec_15_2",title:"3.2 Specialized management",level:"2"},{id:"sec_15_3",title:"3.2.1 Anticoagulation",level:"3"},{id:"sec_16_3",title:"3.2.2 Infection",level:"3"},{id:"sec_17_3",title:"3.2.3 Blood pressure control",level:"3"},{id:"sec_19_2",title:"3.3 Surgical implant",level:"2"},{id:"sec_20_2",title:"3.4 Transplant surgery",level:"2"},{id:"sec_21_2",title:"3.5 Results",level:"2"},{id:"sec_22_2",title:"3.6 Bridge-to-bridge",level:"2"},{id:"sec_24",title:"4. Discussion",level:"1"},{id:"sec_25",title:"5. Conclusions",level:"1"},{id:"sec_29",title:"Conflict of interest",level:"1"}],chapterReferences:[{id:"B1",body:'Barnard CN. Human heart transplantation. Canadian Medical Association Journal. 1969;100:91-104'},{id:"B2",body:'Baumgartner WA, Reitz BA, Bieber CP, Oyer PE, Shumway NE, Stinson EB. Current expectations in cardiac transplantation. 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DOI: 10.1016/j.athoracsurg.2016.06.002'},{id:"B44",body:'Rose EA, Gelijns AC, Moskowitz AJ, Heitjan DF, Stevenson LW, Dembitsky W, et al. Randomized evaluation of mechanical assistance for the treatment of congestive heart failure (REMATCH) study group. The New England Journal of Medicine. 2001;345(20):1435-1443. DOI: 10.1056/NEJMoa.012175'},{id:"B45",body:'Cogswell R, John R, Estep JD, Duval S, Tedford RJ, Pagani FD, et al. An early investigation of outcomes with the new 2018 donor heart allocation system in the United States. The Journal of Heart and Lung Transplantation. 2020;39(1):1-4. DOI: doi.10.1016/j.healun.2019.11.002'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Elena Sandoval",address:"esandova@clinic.cat",affiliation:'
Cardiovascular Surgery Department, Hospital Clínic, Barcelona, Spain
Cardiovascular Surgery Department, Hospital Clínic, Barcelona, Spain
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1. Introduction
Following the survey carried out in Germany in 2017, the number of cases with temporomandibular joint dislocation as hypermobility movement accounts for 3% of all documented dislocation, which means at least 25 cases per 100,000 inhabitants each year [1]. Following European Commission rules, it could be classified as a rare disease – affecting fewer than 5 people in 10,000 are considered to be so. It is also reported to represent 3% of all dislocated joints cases in the human body. On the other hand, dislocation of temporomandibular joint occurs in up to 7% of people during their lifetime [2]. Shorey and Campbell [3] referred to Sir Astley Cooper’s research from the year 1832, who proposed principles for diagnosis and treatment of lower jaw dislocations and introduced nomenclature of joints hypermobility: ‘complete dislocation’ as luxation and ‘imperfect dislocation’ as subluxation. The incidences of subluxation are estimated to occur in about 70% of the population based on clinical and radiographic analysis [4]. In new classification proposed by Akinbami [5], three types of dislocation based on clinic-radiological evaluation were presented: type I – the head of condyle directly below the tip of the eminence; type II – the head of condyle in the front of the tip of the eminence; type III – the head of condyle located high up in the front of base of the eminence. Two types of dislocation with a possibility to self-reduce the hypermobility can be distinguished - subluxation – with, or luxation – without self-reducing.
From The Glossary of Prosthodontic Terms [6], the definition of temporomandibular joint condylar subluxation is: ‘self-reducing incomplete or partial dislocation of the condyle’, and of incomplete dislocation is: ‘a border position of the disk-condyle complex out of the physiological end of movement position in relation to articular eminence’. Partial dislocation is explained in the glossary [6] as a ‘displacement of the articular disk resulting in a seriously impaired disk-condyle complex function’. Condylar dislocation [6] is defined as ‘a non-self-reducing displacement of the mandibular condyle usually forward of the articular eminence’.
For the condylar displacement, the definition stands as follow – it is when the condyle stands out of the articular eminence in maximal jaw opening position. However, definitions confuse subluxation, luxation and disk displacement. From the clinical point of view, subluxation occurs when the opening of patient’s mandibular ends with disk-condyle complex position forward to the articular eminence, which is self-reducing [3]. It means that the patient can close the mandible without any assistance, only by repositioning the mandibular into the disk-condyle complex. It usually concerns joint on one side. With both sides affected it could be more difficult to close the mouth, but patients can usually manage with that on their own. This concerns especially patients with general joints hypermobility, like the Ehlers-Danlos syndrome [7]. They may be frightened or disoriented when it happens for the first time i.e. during yawning. If there is a problem with self-healing and the patient is looking for medical help it could be named as joint dislocation, complete dislocation or luxation. When the dislocation concerns both joints, it looks very dramatic, because patient is unable to speak, swallow and of course, close the mouth. Such cases require medical help, whereas in recurring cases surgical treatment should be considered. It is compatible with Cooper and other authors who followed him, that suggest calling it habitual or recurrent dislocation in cases with more frequent incidents of dislocation and when it is going progressively wrong [3, 8, 9].
As with the other temporomandibular disorders, joint dislocation is often reported by females, especially in recurrent cases. Tendency to dislocation is associated with the shape of anatomical elements like the condyle, glenoid fossa and articular eminence. The pathogenesis is multifactorial, however, for almost 60% of cases, a preceding trauma has been indicated. The mechanism of dislocation also contributes: age, dentition and neurological or neuromuscular diseases. The older the patient, the more he/she is exposed. Lack of posterior teeth support, correlated with advanced tooth loss or edentulous arches without the denture is regarded as favorable to develop joint dislocation. As a recurrent problem for older people with multimorbidity, it significantly reduces their quality of life.
2. Anatomy and physiology
The ‘displacement of the articular disk’ which is ‘non-self-reducing’ is usually understood as a pathological position of the disk in relation to the condyle. That pathology is explained as a forward movement of the disk in relation to the condyle (non-reducing), which results in limitations of condylar head movements, and it is often called ‘disk lock’ or ‘disk displacement without reduction’. The main symptoms of that pathology are sudden disappearance of joints sounds, limitation in jaw opening, and lateral jaw displacement during movement, and usually acute pain from the joint region. The above symptoms are opposite to suspected joint subluxation.
From the anatomy of the temporomandibular joints’ point of view, it is well known that these joints are extremely complex synovial articulations. In the distal part of the joints — which is in the backside of the disk — exists a bilaminar zone, named also retro-articular structure or hydrodynamic retral pad or retrodiscal tissue [10, 11]. It is a mass of loose, highly vascularized and innervated, connective tissue attached to the posterior edge of the articular disk which extends and fills the loose folds of the posterior capsule of the temporomandibular joint [6]. It changes its position simultaneously with all the disk moves and protects the joints against posteriorly oriented trauma [12]. Although the research of Schmolke [13] carried out on human cadavers has concluded, that it was not possible to distinguish the distal disk as a part of a separated structure, Merida-Velasco et al. [10] reported that after examination of 20 cadavers they have identified two separated laminae and retroarticular region filled with venous plexus. The authors confirmed the presence of discomalleolar ligaments in that region and agreed with suggestion about limitation of the range of opening function by those ligaments [14]. Apparently, that part of the joint capsule is still not fully explored.
During the jaw function, both left and right joints move and they are in mutual interdependence. Going again to the anatomy, joints are divided by the disk into two compartments — the upper and the lower. In that two compartments, different movements take place. The movement in the upper one is mostly translational. In the lower compartment movements are mostly rotational. One of the joint’s functions is to connect the mandibular condyle movements in relation to the articular fossa of the temporal bone with the temporomandibular disk interposed. The disk itself is connected with the joint capsule. The capsule is constructed from fibrous ligaments that enclose the joint and limit its motion [15]. It is lined with the synovial membrane.
In order for the movement to be smooth and free of any sound, each surface of the joints, the disks and condylar heads as well as the articular fossae should be sleek and moistened. The articular surfaces are covered by synovial membrane and moistened by synovial fluid. That fluid is produced by specialized endothelial cells capable of producing synovial fluid. It fills all joints’ cavities surrounded by the membrane. For proper joints movements, the capsules need to be flexible enough and tight to keep joints parts together during all joints positions [11].
The joints’ shifting results in opening, closing, forward, backward and lateral movements of the mandible. During the first four movements, both joints work simultaneously, in mirror reflection. Yet, in the lateral movements, the movement made by the side joint is smaller than the one made by the opposite joint. When one moves, it always results in the movement of the other. That relationship — where one bone (the mandible) moves between two joints, which are mutually dependent on each other — is specific in human skeleton and occurs only in that very specific joints.
Movements are related to joints disks position, capsules and ligaments tension and muscle function. Muscles that are involved in the temporomandibular joint functions are mainly the temporal, masseter, digastricus, medial and lateral pterygoid. From contemporary anatomy, we know that some fibers of temporal, masseter and upper head of lateral pterygoid muscle penetrate to the joint capsule and even to the joint disk [11, 16]. This can result in disk movements, but in the case of muscle hyperactivity could cause disk displacement.
The physiological joints opening movement starts with condyles located in the higher position in relation to the glenoid fossa with the disk between them in the uppermost position. Then, the condyle’s head makes a rotation movement in relation to the disk in the lower joint compartment, and the disk translates down and forward in relation to the glenoid fossa and the articular eminence, as a movement in the upper jaw compartment. At the end of the movement, the condyle head is covered by the disk and located on the top of the articular eminence in its lowest possible position. This movement is limited by the joint capsule tension and the ligaments. The bilaminar zone tissues are maximally stretched. In the physiological movement of the joints, the relation between the condyles and the eminences is expected to be the same during the entire action of the opening and closing of the lower jaw. That condyle head position in relation to the fossa and the eminence can be visualized by pantomographic x-ray examination [17].
The diagnostic methods of temporomandibular joint hypermobility are various and there is a possibility to use non-invasive methods such as clinical examination, auscultation, ultrasonography (USG) or magnetic resonance imaging (MRI). It can be also diagnosed by some invasive methods such as X-ray or computed tomography (CT). Clinical examination, X-rays and auscultation are more convenient for the patients and they give enough medical data for proper diagnoses, so there is no need to buy advanced equipment.
Firstly, the clinical examination should be carried out in a repetitive way at every patient [18]. To realize the assumptions a way of examination was thoroughly described in the validated international protocol Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) [19]. It helps to make the examination in a repeatable way and find a proper diagnosis. The stethoscopes are the main instruments for joint auscultation, their advantage is their vast accessibility [20, 21]. The researchers used various modifications of stethoscopes for joints auscultation [22]. The use of a stethoscope, especially an electronic one for examination allows sending the signal via Bluetooth to the computer for further analysis. That tool was used in the research by Wiedmann et al. [23]. Such a method could also help an inexperienced dentist to consult the cases with a specialist. USG of joints region, especially made by an experienced person allows detecting the position of the disk-condyle complex in a dynamic, real way during the test [24]. It informs about the muscle tension, shape of joints compartments and the amount of synovial fluid. This method is non-invasive, repetitive and gives a satisfying amount of information. MRI, belonging also to the non-invasive examination methods, requires dedicated tools and an experienced person for proper interpretation of the results. It can help to detect disc position, the amount of joint fluid and present the bones structures, yet this technique is the most expensive of the non-invasive methods [25].
Computed tomography (CT) belongs to the invasive examination methods and the radiation dose is the biggest. The advantage of this examination is the very precise detection of the properties of the osseous components of the temporomandibular joints [26]. A much lower radiation dose and sufficient amount of clinical data are obtained from an x-ray examination from pantomographs. Currently, they are the very basic equipment of almost all dental offices so diagnostic technic seems to be very easy and common. As the result of that examination, we receive four pictures, two of each side of the face. Two of them present the mandible in the state of closing and the other two in the maximal opening position. The analysis of both sides is possible and easy. Not too many anatomical structures disturb the image. The example of that x-ray is presented in Figure 1.
Figure 1.
Right (two left pictures) and left temporomandibular joints in opening (outer images) and closing position with physiological relation of joints elements.
That examination informs us about condyle bone structure, shape and relation to the fossae in maximal intercuspal position and at the end of opening movement. The result of such an x-ray should be compared with patient’s clinical status. It is important to analyze the opening and closing jaw movements in relation to upper and lower incisor midline positions during all the movements. The range of openings should be measured between the incisal edges. Then palpation in temporomandibular joints region during mandibular movements and auscultation of that region would be crucial [27].
3.1 Symptoms and diagnosis
Signs and symptoms of acute or chronic dislocation as hypermobility are the same and include temporary inability to close the mouth, preauricular depression of the skin, excessive salivation, tense, spastic muscle of mastication and pain of temporomandibular joint. At the time of a wide opening, specific sounds may appear. It would happen during excessive mouth opening such as yawning, eating, singing or vomiting. The people who are most vulnerable are the ones who suffer from generalized joint hypermobility as Ehlers-Danlos syndrome or Marfan syndrome as well as neurodegenerative/neurodysfunctional diseases or muscle dystrophies [28, 29]. In the described groups of patients, that symptom could be physiological and often that joint hypermobility is painless. Very characteristic in that cases of hypermobility movement are self-reducing, but sometimes the patients are afraid about complications. The problem could also appear after intubation in general anesthesia too. Repeated episodes of subluxation may result in the lengthening of the capsule ligaments or cause damage to the joint capsule. To make the proper diagnosis clinical examination with joint auscultation and x-ray examination are required.
The clinical examination includes the measurement of jaw abduction, lateral movements and protrusion. The symmetry of movements and their straight direction inform us about their proper function. Then the palpation of jaw movement muscle is required. During the examination, muscles should be in the relaxed position. Before palpation, the stretch of the muscle should be investigated. We are expecting symmetrical contraction in the muscles on both sides during the opening and closing of the mandible. Similarly during forward and backward movement. At that moment the tendons and muscle bodies are palpated, especially temporalis, masseter and digastricus. Those muscles are suitable for direct palpation. Lateral pterygoid muscle can be examined using indirect movements. In such a case the examiner’s hands should block patient’s forward and lateral jaw movements and the doctor should ask the patients about the pain in the region of the joints. The appearance of pain informs about muscle dysfunction, hyperfunction or overactivity [30].
During physiological jaw movements, neither sound nor noises from joints region are expected. If they appear, some disturbances occur i.e. in relation between disk and condylar head or between disk-condyle complex and fossa to articular eminence. The joint dysfunction might be differentiated by sound and it requires auscultating them. Typical sound associated with joints dislocation correlated with hypermobile movement appears at the end of the movement, usually when the mouth is being opened. Subluxation sounds are very specific. Using two electronic stethoscopes the examination takes place during opening and closing movements. That examination is safe for the patient and is easy even for inexperienced doctors. The measured signals from electronic stethoscopes are sent to the computer and the signals are analyzed [31].
3.2 Material and method
In our examination the patients with temporomandibular disorders were included based on our national version of The Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) as well as a group of patients without diagnoses but with symptoms and sounds from the joints region [32, 33]. After clinical examination, the auscultation procedure takes place. Patients with diagnoses based on RDC/TMD with sounds from temporomandibular joints and that those with joints sounds who did not receive the diagnoses were taken to the analyzes. All patients with other diagnoses without joints sounds were excluded from the study. After sound differentiation, the group suspected hypermobile joints were selected and an x-ray as confirmation was recommended.
3.2.1 Auscultation technic
Two electronic stethoscopes (Littmann Model 3200 Manufacturer 3 M Health Care, St. Paul, MN, USA) were used for the examination. Patients were asked to open and close the mouth 5 to 8 times. The auscultation of the temporomandibular joints region was carried out on both sides simultaneously. Electronic stethoscopes convert analogue signals to digital domains and make it possible to analyze about 15 s sounds. Stethoscopes provide a 4000 Hz sampling rate that ensures possibilities to reproduce sound components up to 2000 Hz. The measured sounds were sent to the computer to analyses the recorded signals. The representation of the signal in the frequency domain was computed with the use of the Numpy library and the fast Fourier transform algorithm. In order to achieve local spectral representation, we split the signal into atomic sections with the Blackman window of 512 samples length and 256 samples overlapping. The frequencies below 80 Hz were removed from spectrograms to emphasize higher harmonics that were responsible for the effect of clicking [31]. Usage of two independent stethoscopes is beneficial in terms of capability of identification which joint generates sounds but on the other hand, makes difficulties in interpretation. Vibrations are conducted by bone and tissues therefore to differentiate where the origin of sound is located signals recorded by stethoscopes have to be synchronized. This feature is based on an external synchronization system. Small actuators placed on stethoscopes generate synchro beep sound and are triggered by physician during auscultation using a footswitch [34]. Promising results were achieved by signal analysis in time-frequency domain. This representation provides both information, when acoustic event occurred and which frequency components are present. Artificial intelligence-based approach seems to be the most appropriate in terms of mentioned signal analysis. Dedicated algorithms are still being developed. One of the main challenges is signal identification and segmentation [35]. Only when the auscultation signals will be split into parts corresponding to each jaw movement there will be possible to provide comprehensive automatic signals recognition algorithms.
3.3 Results
Totally 120 patients participated in the study. For sounds analyses were qualified 40 persons, in that group 32 were women. Hypermobile sounds were recognized in 4 patients (2 men and 2 women) based on lack of RDC/TMD diagnoses, sound analyses and x-ray confirmation.
From our research, we have very characteristic results for hypermobile joints in relation to the healthy one and with disk displacement with reduction, which is presented in Figures 2–4.
Figure 2.
The signal traces recorded on both sides in time domain in healthy joints.
Figure 3.
The signal traces recorded on both sides in time domain from patients with disk displacement with reduction in both joints.
Figure 4.
The signal traces recorded on both sides in time domain from patients with hypermobile joints as subluxation.
The sound record from a healthy temporomandibular joint presented in Figure 2 concerns the time representation. The record representation is obtained from the serving program from electronic stethoscope Littmann 3200. It is worth mentioning that both joints do not present pathological sounds. Graphs represent a sound that indicates the correct movement of the structures of the temporomandibular joints during opening and closing.
In Figure 3, there is the signal representation from software Littmann 3200 from patient with disk displacement with reduction in both joints.
The signal time representation in Figure 4 is characteristic for a person with subluxation in both joints.
Another helpful auscultation result is presented as time-frequency domain in the form of spectrograms (Figures 5–7).
Figure 5.
The signal traces recorded on the short-time Fourier transform (STFT) representation of healthy joints.
Figure 6.
The signal traces are recorded on the STFT representation of a disk displacement with reduction in both joints.
Figure 7.
Signal traces were recorded on the STFT representation of a hypermobile joints as subluxation.
As a complementary examination x-ray of the joints was required. The results are very characteristic in hypermobile jaw movements patients with a subluxation in one or both joints. For example, in Figure 8 the position of the condyles in the front of the articular eminence was visible.
Figure 8.
An example of both sides subluxation x-ray. From left to right: Right side joint in wide jaw open position (the condyle head in the front of articular eminence), right side joint in maximal intercuspation position (the condyle head in glenoid fossa), left side joint in maximal intercuspation position (the condyle head in glenoid fossa) and left side joint in wide jaw open position (the condyle head in the front of articular eminence).
3.4 Discussion
The presented method of examination in the group of patients with temporomandibular joints region sounds is easy, inexpensive and gives possibility for future development. It takes the way for telemedicine as remote consultation. It allows enlargement of patients’ medical data for monitoring present status and progress of treatment. Hypermobile jaw sounds are rare problem in a group of patients with temporomandibular disorders. In our group, it was 3.3% of examined patients which was correlated with the literature [2]. Although the problem affects a relatively small group of patients, it should not be underestimated. It is worth searching for simple solutions for diagnosis. It is possible that the lack of diagnosis is associated with the difficulty and no additional equipment. There is an alternative tool- BioJVA (BioResearch Associates, Inc. Milwaukee WI USA) that can be used to diagnose patients with temporomandibular disorders and for joints sounds analysis [36, 37, 38]. It is non-invasive diagnostic equipment, supplementing the basic clinical examination that can help to observe the present status and the effectiveness of the therapy. The use of this device is not common, it usually occurs in research medical centres due to very high prices and lack of knowledge of how to interpret diagnostic results. The use of a stethoscope could be a common examining method performed by every practising dentist.
4. Conclusion
As the summary about hypermobile temporomandibular jaw movements, it is important to know, that in all cases with subluxation the appearing sounds are frightening, and sometimes the doctors are more surprised than the accustomed patient. The associated unexpected jaw movements which are correlated with the thud sound in relation to inexperienced dentists would lead to a patient becoming sick. On the other hand, subluxation in some cases would lead to luxation and the patients may require surgery which is at risk of multiple complications. So the necessary recommendations for patients with hypermobile joints with the subluxation are to avoid wide mouth opening during yawning, eating or singing. The most difficult is to control jaw opening during yawning. Our recommendation is to bend your head to the chest and protect jaw opening by neck spine. Another possibility is to suction the tongue to the palate during yawning and protect wide opening by tongue frenulum. In addition, physiotherapeutic procedures are required, to strengthen the muscle for joints protection.
\n',keywords:"temporomandibular joint, hypermobility, joint auscultation",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/81080.pdf",chapterXML:"https://mts.intechopen.com/source/xml/81080.xml",downloadPdfUrl:"/chapter/pdf-download/81080",previewPdfUrl:"/chapter/pdf-preview/81080",totalDownloads:12,totalViews:0,totalCrossrefCites:0,dateSubmitted:"February 11th 2022",dateReviewed:"February 25th 2022",datePrePublished:"May 5th 2022",datePublished:null,dateFinished:"April 2nd 2022",readingETA:"0",abstract:"The temporomandibular joint (TMJ), being an almost well-known anatomical structure but its diagnosis may become difficult due to sounds accompanying joint movement. One example is temporomandibular joint hypermobility (TMJH), which still requires comprehensive study. TMJH is a rare disorder; however, its prevalence at the level of around 4% is still significant. We propose a diagnostic method of TMJH based on the digital time-frequency analysis of sounds generated by TMJ. The volunteers were diagnosed using the RDC/TMD questionnaire and auscultated with the Littmann 3200 electronic stethoscopes on both sides of the head simultaneously. Recorded TMJ sounds were transferred to the computer via Bluetooth® for numerical analysis. The research reveals characteristic time-frequency features in acoustic signals which can be used to detect TMJH. This can help differentiate other disc displacements from joint hypermobility.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/81080",risUrl:"/chapter/ris/81080",signatures:"Jolanta E. Loster and Justyna Grochala",book:{id:"11240",type:"book",title:"Temporomandibular Joint - Surgical Reconstruction and Managements",subtitle:null,fullTitle:"Temporomandibular Joint - Surgical Reconstruction and Managements",slug:null,publishedDate:null,bookSignature:"Prof. Raja K Kummoona",coverURL:"https://cdn.intechopen.com/books/images_new/11240.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-80355-964-3",printIsbn:"978-1-80355-963-6",pdfIsbn:"978-1-80355-965-0",isAvailableForWebshopOrdering:!0,editors:[{id:"93854",title:"Prof.",name:"Raja",middleName:"K",surname:"Kummoona",slug:"raja-kummoona",fullName:"Raja Kummoona"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Anatomy and physiology",level:"1"},{id:"sec_3",title:"3. Temporomandibular joint examination opportunities",level:"1"},{id:"sec_3_2",title:"3.1 Symptoms and diagnosis",level:"2"},{id:"sec_4_2",title:"3.2 Material and method",level:"2"},{id:"sec_4_3",title:"3.2.1 Auscultation technic",level:"3"},{id:"sec_6_2",title:"3.3 Results",level:"2"},{id:"sec_7_2",title:"3.4 Discussion",level:"2"},{id:"sec_9",title:"4. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'Prechel U, Ottl P, Ahlers OM, Neff A. The treatment of temporomandibular joint dislocation. Deutsches Arzteblatt International. 2018;115:59-64'},{id:"B2",body:'Marques-Mateo M, Puche-Torres M, Iglesias-Gimilio ME. Temporomandibular chronic dislocation: The long-standing condition. Medicina Oral, Patología Oral y Cirugía Bucal. 2016;21:e776-ee83'},{id:"B3",body:'Shorey CW, Campbell JH. Dislocation of the temporomandibular joint. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2000;89:662-668'},{id:"B4",body:'Pogrel MA. Articular eminectomy for recurrent dislocation. The British Journal of Oral & Maxillofacial Surgery. 1987;25:237-243'},{id:"B5",body:'Akinbami BO. Evaluation of the mechanism and principles of management of temporomandibular joint dislocation. Systematic review of literature and a proposed new classification of temporomandibular joint dislocation. Head & Face Medicine. 2011;7:10'},{id:"B6",body:'The Glossary of Prosthodontic Terms Ninth Edition GPT-9. In: Ferro KJ, editor. The Journal of Prosthetic Dentistry. 2017;117:C1, e1-e105'},{id:"B7",body:'Beighton P, Horan F. Orthopaedic aspects of the Ehlers-Danlos syndrome. The Journal of Bone and Joint Surgery. British Volume. 1969;51:444-453'},{id:"B8",body:'Caminiti MF, Weinberg S. Chronic mandibular dislocation: The role of non-surgical and surgical treatment. Journal of the Canadian Dental Association. 1998;64:484-491'},{id:"B9",body:'Kai S, Kai H, Nakayama E, Tabata O, Tashiro H, Miyajima T, et al. Clinical symptoms of open lock position of the condyle. Relation to anterior dislocation of the temporomandibular joint. Oral Surgery, Oral Medicine, and Oral Pathology. 1992;74:143-148'},{id:"B10",body:'Merida-Velasco JR, Rodriguez JF, de la Cuadra C, Peces MD, Merida JA, Sanchez I. The posterior segment of the temporomandibular joint capsule and its anatomic relationship. Journal of Oral and Maxillofacial Surgery. 2007;65:30-33'},{id:"B11",body:'Slavicek R. The Masticatory Organ. Klosterneuburg: Gamma Medizinisch-wissenschaftliche Fortbildungs-GmbH; 2006'},{id:"B12",body:'Fernández Rubio EM, Radlanski RJ. Hypothesis for the lack of a muscular antagonist to the lateral pterygoid. Annals of Anatomy. Jan 2022;239:151841'},{id:"B13",body:'Schmolke C. The relationship between the temporomandibular joint capsule, articular disc and jaw muscles. Journal of Anatomy. 1994;184(Pt 2):335-345'},{id:"B14",body:'Cheynet F, Guyot L, Richard O, Layoun W, Gola R. Discomallear and malleomandibular ligaments: Anatomical study and clinical applications. Surgical and Radiologic Anatomy: SRA. 2003;25:152-157'},{id:"B15",body:'Woodford SC, Robinson DL, Mehl A, Lee PVS, Ackland DC. Measurement of normal and pathological mandibular and temporomandibular joint kinematics: A systematic review. Journal of Biomechanics. 2020;111:109994'},{id:"B16",body:'Gross A, Bumann A, Hoffmeister B. Elastic fibers in the human temporo-mandibular joint disc. International Journal of Oral and Maxillofacial Surgery. 1999;28:464-468'},{id:"B17",body:'Loster JE, Groch M, Wieczorek A, Muzalewska M, Skarka W. An evaluation of the relationship between the range of mandibular opening and the condyle positions in functional panoramic radiographs. Dental and Medical Problems. 2017;54:347-351'},{id:"B18",body:'Serrano-Hernanz G, Futarmal Kothari S, Castrillon E, Alvarez-Mendez AM, Ardizone-Garcia I, Svensson P. Importance of standardized palpation of the human temporomandibular joint. Journal of Oral & Facial Pain and Headache. 2019;33:220-226'},{id:"B19",body:'Schiffman E, Ohrbach R, Truelove E, Look J, Anderson G, Goulet JP, et al. Diagnostic criteria for temporomandibular disorders (DC/TMD) for clinical and research applications: Recommendations of the international RDC/TMD consortium network* and orofacial pain special interest Groupdagger. Journal of Oral & Facial Pain and Headache. 2014;28:6-27'},{id:"B20",body:'Mishutin EA, Geletin PN, Morozov VG. Audiodiagnostics in examination of patients with internal TMJ derangement. Stomatologiia. 2014;93:32-34'},{id:"B21",body:'Westling L, Helkimo E, Mattiasson A. Observer variation in functional examination of the temporomandibular joint. Journal of Craniomandibular Disorders: Facial & Oral Pain. 1992;6:202-207'},{id:"B22",body:'Dagar SR, Turakiya V, Pakhan AJ, Jaggi N, Kalra A, Vaidya V. Modified stethoscope for auscultation of temporomandibular joint sounds. Journal of International Oral Health: JIOH. 2014;6:40-44'},{id:"B23",body:'Widmalm SE, Williams WJ, Adams BS. The wave forms of temporomandibular joint sound clicking and crepitation. Journal of Oral Rehabilitation. 1996;23:44-49'},{id:"B24",body:'Emshoff R, Bertram S, Rudisch A, Gassner R. The diagnostic value of ultrasonography to determine the temporomandibular joint disk position. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 1997;84:688-696'},{id:"B25",body:'Limchaichana N, Nilsson H, Ekberg EC, Nilner M, Petersson A. Clinical diagnoses and MRI findings in patients with TMD pain. Journal of Oral Rehabilitation. 2007;34:237-245'},{id:"B26",body:'Westesson PL, Katzberg RW, Tallents RH, Sanchez-Woodworth RE, Svensson SA. CT and MR of the temporomandibular joint: Comparison with autopsy specimens. AJR. American Journal of Roentgenology. 1987;148:1165-1171'},{id:"B27",body:'Loster JE, Groch M, Ryniewicz WI, Osiewicz MA, Wieczorek A. Assessment of the range of mandibular movements as related to gender in polish young adult non-patients. Journal of Stomatology. 2016;69:146-152'},{id:"B28",body:'Bauss O, Sadat-Khonsari R, Fenske C, Engelke W, Schwestka-Polly R. Temporomandibular joint dysfunction in Marfan syndrome. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2004;97:592-598'},{id:"B29",body:'Thexton A. A case of Ehlers-Danlos syndrome presenting with recurrent dislocation of the temporomandibular joint. The British Journal of Oral Surgery. 1965;3:190-193'},{id:"B30",body:'Osiewicz MA, Manfredini D, Loster BW, van Selms MKA, Lobbezoo F. Comparison of the outcomes of dynamic/static tests and palpation tests in TMD-pain patients. Journal of Oral Rehabilitation. 2018;45:185-190'},{id:"B31",body:'Grochala J, Grochala D, Kajor M, Iwaniec J, Loster JE, Iwaniec M. A novel method of temporomandibular joint hypermobility diagnosis based on signal analysis. Journal of Clinical Medicine. 2021;10'},{id:"B32",body:'Osiewicz MA, Lobbezoo F, Loster BW, Wilkosz M, Naeije M, Ohrbach R. Research diagnostic criteria for temporomandibular disorders (RDC/TMD) - the polish version of a dual-axis system for the diagnosis of TMD. RDC/TMD form. Journal of Stomalogy. 2013;66:576-649'},{id:"B33",body:'Dworkin SF, LeResche L. Research diagnostic criteria for temporomandibular disorders: Review, criteria, examinations and specifications, critique. Journal of Craniomandibular Disorders: Facial & Oral Pain. 1992;6:301-355'},{id:"B34",body:'Lemejda J, Kajor M, Grochala D, Iwaniec M, Loster JE. Synchronous auscultation of temporomandibular joints using electronic stethoscopes. International Conference on Perspective Technologies and Methods in MEMS Design. 2020:146-149'},{id:"B35",body:'Djurdjanovic D, Widmalm SE, Williams WJ, Koh CK, Yang KP. Computerized classification of temporomandibular joint sounds. IEEE Transactions on Biomedical Engineering. 2000;47:977-984'},{id:"B36",body:'Radke J, Garcia R Jr, Ketcham R. Wavelet transforms of TM joint vibrations: A feature extraction tool for detecting reducing displaced disks. Cranio. 2001;19:84-90'},{id:"B37",body:'Kondrat W, Sierpińska T, Gołębiewska M. Vibration analysis of temporomandibular joints – BioJVA device description and its clinical application in dental diagnostics – Review of literature. Journal of Stomatology. 2012;65:207-215'},{id:"B38",body:'Kondrat W, Sierpinska T, Radke J. Assessment of the temporomandibular joint function in young adults without complaints from the masticatory system. International Journal of Medical Sciences. 2018;15:161-169'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Jolanta E. Loster",address:"jolanta.loster@uj.edu.pl",affiliation:'
Department of Prosthodontics and Orthodontics, Jagiellonian University in Kraków, Medical College, Dental Institute, Kraków, Poland
Department of Prosthodontics and Orthodontics, Jagiellonian University in Kraków, Medical College, Dental Institute, Kraków, Poland
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Saxena",hash:"d92a4085627bab25ddc7942fbf44cf05",volumeInSeries:2,fullTitle:"Current Perspectives in Human Papillomavirus",editors:[{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Bacterial Infectious Diseases",value:3,count:2},{group:"subseries",caption:"Parasitic Infectious Diseases",value:5,count:4},{group:"subseries",caption:"Viral Infectious Diseases",value:6,count:7}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:2},{group:"publicationYear",caption:"2021",value:2021,count:4},{group:"publicationYear",caption:"2020",value:2020,count:3},{group:"publicationYear",caption:"2019",value:2019,count:3},{group:"publicationYear",caption:"2018",value:2018,count:1}],authors:{paginationCount:148,paginationItems:[{id:"165328",title:"Dr.",name:"Vahid",middleName:null,surname:"Asadpour",slug:"vahid-asadpour",fullName:"Vahid Asadpour",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/165328/images/system/165328.jpg",biography:"Vahid Asadpour, MS, Ph.D., is currently with the Department of Research and Evaluation, Kaiser Permanente Southern California. He has both an MS and Ph.D. in Biomedical Engineering. He was previously a research scientist at the University of California Los Angeles (UCLA) and visiting professor and researcher at the University of North Dakota. He is currently working in artificial intelligence and its applications in medical signal processing. In addition, he is using digital signal processing in medical imaging and speech processing. Dr. Asadpour has developed brain-computer interfacing algorithms and has published books, book chapters, and several journal and conference papers in this field and other areas of intelligent signal processing. He has also designed medical devices, including a laser Doppler monitoring system.",institutionString:"Kaiser Permanente Southern California",institution:null},{id:"169608",title:"Prof.",name:"Marian",middleName:null,surname:"Găiceanu",slug:"marian-gaiceanu",fullName:"Marian Găiceanu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/169608/images/system/169608.png",biography:"Prof. Dr. Marian Gaiceanu graduated from the Naval and Electrical Engineering Faculty, Dunarea de Jos University of Galati, Romania, in 1997. He received a Ph.D. (Magna Cum Laude) in Electrical Engineering in 2002. Since 2017, Dr. Gaiceanu has been a Ph.D. supervisor for students in Electrical Engineering. He has been employed at Dunarea de Jos University of Galati since 1996, where he is currently a professor. Dr. Gaiceanu is a member of the National Council for Attesting Titles, Diplomas and Certificates, an expert of the Executive Agency for Higher Education, Research Funding, and a member of the Senate of the Dunarea de Jos University of Galati. He has been the head of the Integrated Energy Conversion Systems and Advanced Control of Complex Processes Research Center, Romania, since 2016. He has conducted several projects in power converter systems for electrical drives, power quality, PEM and SOFC fuel cell power converters for utilities, electric vehicles, and marine applications with the Department of Regulation and Control, SIEI S.pA. (2002–2004) and the Polytechnic University of Turin, Italy (2002–2004, 2006–2007). He is a member of the Institute of Electrical and Electronics Engineers (IEEE) and cofounder-member of the IEEE Power Electronics Romanian Chapter. He is a guest editor at Energies and an academic book editor for IntechOpen. He is also a member of the editorial boards of the Journal of Electrical Engineering, Electronics, Control and Computer Science and Sustainability. Dr. Gaiceanu has been General Chairman of the IEEE International Symposium on Electrical and Electronics Engineering in the last six editions.",institutionString:'"Dunarea de Jos" University of Galati',institution:{name:'"Dunarea de Jos" University of Galati',country:{name:"Romania"}}},{id:"4519",title:"Prof.",name:"Jaydip",middleName:null,surname:"Sen",slug:"jaydip-sen",fullName:"Jaydip Sen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/4519/images/system/4519.jpeg",biography:"Jaydip Sen is associated with Praxis Business School, Kolkata, India, as a professor in the Department of Data Science. His research areas include security and privacy issues in computing and communication, intrusion detection systems, machine learning, deep learning, and artificial intelligence in the financial domain. He has more than 200 publications in reputed international journals, refereed conference proceedings, and 20 book chapters in books published by internationally renowned publishing houses, such as Springer, CRC press, IGI Global, etc. Currently, he is serving on the editorial board of the prestigious journal Frontiers in Communications and Networks and in the technical program committees of a number of high-ranked international conferences organized by the IEEE, USA, and the ACM, USA. He has been listed among the top 2% of scientists in the world for the last three consecutive years, 2019 to 2021 as per studies conducted by the Stanford University, USA.",institutionString:"Praxis Business School",institution:null},{id:"320071",title:"Dr.",name:"Sidra",middleName:null,surname:"Mehtab",slug:"sidra-mehtab",fullName:"Sidra Mehtab",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00002v6KHoQAM/Profile_Picture_1584512086360",biography:"Sidra Mehtab has completed her BS with honors in Physics from Calcutta University, India in 2018. She has done MS in Data Science and Analytics from Maulana Abul Kalam Azad University of Technology (MAKAUT), Kolkata, India in 2020. Her research areas include Econometrics, Time Series Analysis, Machine Learning, Deep Learning, Artificial Intelligence, and Computer and Network Security with a particular focus on Cyber Security Analytics. Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. Currently, she is working as a Data Scientist with an MNC in Delhi, India.",institutionString:"NSHM College of Management and Technology",institution:null},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:"Polytechnic University of Timişoara",institution:{name:"Polytechnic University of Timişoara",country:{name:"Romania"}}},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:null},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. Science CV available at: https://www.cienciavitae.pt//pt/8E1C-A8B3-78C5 and ORCID: https://orcid.org/0000-0002-0298-3974',institutionString:"University of Lisbon",institution:{name:"Universidade Lusófona",country:{name:"Portugal"}}},{id:"241400",title:"Prof.",name:"Mohammed",middleName:null,surname:"Bsiss",slug:"mohammed-bsiss",fullName:"Mohammed Bsiss",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241400/images/8062_n.jpg",biography:null,institutionString:null,institution:null},{id:"276128",title:"Dr.",name:"Hira",middleName:null,surname:"Fatima",slug:"hira-fatima",fullName:"Hira Fatima",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/276128/images/14420_n.jpg",biography:"Dr. Hira Fatima\nAssistant Professor\nDepartment of Mathematics\nInstitute of Applied Science\nMangalayatan University, Aligarh\nMobile: no : 8532041179\nhirafatima2014@gmal.com\n\nDr. Hira Fatima has received his Ph.D. degree in pure Mathematics from Aligarh Muslim University, Aligarh India. Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. 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It will provide significant opportunities and support for scientists, clinical doctors, mycologists, antifungal drug researchers, public health practitioners, and epidemiologists from all over the world to share new research, ideas and solutions to promote the development and progress of medical mycology.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/4.jpg",keywords:"Emerging Fungal Pathogens, Invasive Infections, Epidemiology, Cell Membrane, Fungal Virulence, Diagnosis, Treatment"},{id:"5",title:"Parasitic Infectious Diseases",scope:"Parasitic diseases have evolved alongside their human hosts. In many cases, these diseases have adapted so well that they have developed efficient resilience methods in the human host and can live in the host for years. Others, particularly some blood parasites, can cause very acute diseases and are responsible for millions of deaths yearly. Many parasitic diseases are classified as neglected tropical diseases because they have received minimal funding over recent years and, in many cases, are under-reported despite the critical role they play in morbidity and mortality among human and animal hosts. The current topic, Parasitic Infectious Diseases, in the Infectious Diseases Series aims to publish studies on the systematics, epidemiology, molecular biology, genomics, pathogenesis, genetics, and clinical significance of parasitic diseases from blood borne to intestinal parasites as well as zoonotic parasites. We hope to cover all aspects of parasitic diseases to provide current and relevant research data on these very important diseases. In the current atmosphere of the Coronavirus pandemic, communities around the world, particularly those in different underdeveloped areas, are faced with the growing challenges of the high burden of parasitic diseases. At the same time, they are faced with the Covid-19 pandemic leading to what some authors have called potential syndemics that might worsen the outcome of such infections. Therefore, it is important to conduct studies that examine parasitic infections in the context of the coronavirus pandemic for the benefit of all communities to help foster more informed decisions for the betterment of human and animal health.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/5.jpg",keywords:"Blood Borne Parasites, Intestinal Parasites, Protozoa, Helminths, Arthropods, Water Born Parasites, Epidemiology, Molecular Biology, Systematics, Genomics, Proteomics, Ecology"},{id:"6",title:"Viral Infectious Diseases",scope:"The Viral Infectious Diseases Book Series aims to provide a comprehensive overview of recent research trends and discoveries in various viral infectious diseases emerging around the globe. The emergence of any viral disease is hard to anticipate, which often contributes to death. A viral disease can be defined as an infectious disease that has recently appeared within a population or exists in nature with the rapid expansion of incident or geographic range. This series will focus on various crucial factors related to emerging viral infectious diseases, including epidemiology, pathogenesis, host immune response, clinical manifestations, diagnosis, treatment, and clinical recommendations for managing viral infectious diseases, highlighting the recent issues with future directions for effective therapeutic strategies.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/6.jpg",keywords:"Novel Viruses, Virus Transmission, Virus Evolution, Molecular Virology, Control and Prevention, Virus-host Interaction"}],annualVolumeBook:{},thematicCollection:[],selectedSeries:null,selectedSubseries:null},seriesLanding:{item:null},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"onlineFirst.detail",path:"/online-first/81080",hash:"",query:{},params:{id:"81080"},fullPath:"/online-first/81080",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()