Comprehensive Interventions in End-Stage Cardiomyopathy: Mechanical Circulatory Support and Heart Transplantation

Abstract

This chapter provides a comprehensive exploration of the primary indications for employing mechanical circulatory support and heart transplantation in the treatment of end-stage cardiomyopathy. It emphasizes the specific types of support, patient selection criteria, optimal timing for intervention, and the prevalent varieties of mechanical assistance devices currently utilized. The chapter delves into nuanced patient outcomes concerning both temporary and long-term support, while also offering a succinct overview of the evolving perspectives within this field. Heart transplantation serves as the ultimate resource for cardiomyopathy patients for whom conventional medical therapy has proven ineffective. This section centers on delineating the indications and contraindications for heart transplantation, emphasizing patient care protocols, early and late postoperative complications, and the future trajectories in this domain. A critical analysis scrutinizes and compares the efficacy and applicability of mechanical assistance against heart transplantation within this patient cohort. Given the intricacies of surgical interventions for cardiomyopathy, the chapter outlines prospects, encompassing advancements such as xenotransplantation and the integration of new mechanical assist devices into the evolving landscape of treatments.

1. Introduction

Cardiomyopathies (CMP) were initially characterized as myocardial diseases of unknown origin. Subsequently, the American Heart Association (AHA) redefined them as a diverse group of myocardial diseases linked to mechanical and or electrical dysfunction, which often manifest inappropriate ventricular hypertrophy or dilatation, and they are attributed to a variety of causes, frequently with a genetic basis [1]. Cardiomyopathies are commonly categorized into two groups: primary CMP which predominantly affects the heart and secondary cardiomyopathies which involve additional organ system complications. The primary CMP is subdivided in genetic, mixed, or acquired. The main genetic CMP is hypertrophic cardiomyopathy (HCM), arrhythmogenic CMP (ACM), left ventricular noncompaction, mitochondrial myopathies, etc. The acquired CMP is myocarditis, peripartum CMP, Taksubo, and tachycardia-induced CMP. Mixed CMP includes dilated and restrictive cardiomyopathies. Mechanical circulatory support (MCS) and heart transplantation (HT) serve as surgical interventions designed for cases of cardiomyopathies complicated by advanced heart failure (AHF). These procedures are typically pursued when sustainable medical or interventional treatments are not viable, and the affected individuals face a limited lifespan.

2. Mechanical circulatory support

Mechanical circulatory support (MCS) is used in the management of individuals experiencing advanced heart failure (AHF) or cardiogenic shock. These devices offer temporary hemodynamic assistance to patients facing severe heart failure with potential for recovery (bridge to recovery) as well as to those with irreversible heart failure where the goal is to extend the time available for transplant donor allocation (bridge to transplantation, BTT). Additionally, these devices may be utilized for providing permanent circulatory support to individuals who are not suitable candidates for HT (as destination therapy, DT) or as a bridge to decision. This final category encompasses patients who are hemodynamically unstable and require urgent MCS. However, the ultimate decision regarding MCS cannot be determined at the time of surgery [2].

2.1 Temporary mechanical circulatory support (TMCS)

TMCS may be employed for individuals experiencing acute heart failure or cardiogenic shock (CS). This includes extracorporeal membrane oxygenation (ECMO), extracorporeal life support (ECLS), and percutaneous cardiac support devices (Table 1) [3].

Stages of shock	Haemodynamics	Biochemical markers	Description
Stage A at risk	Normotensive; CI > _2.5 L/min/m^2; CVP < 10; PA sat > _65%	Normal renal function and lactate, elevated BNP	Patients not in Cardiogenic shock (CS) but at risk of developing CS (STEMI, or NSTEMI)
Stage B Beginning	SBP < 90 mm Hg, or MAP <60 or > 30 mm Hg drop from baseline; Pulse >_100/min; CI > _2.2 L/min/m2; PA sats >_ 65%	Normal renal function and lactate; elevated BNP	Clinical evidence of hypotension or tachycardia without hypoperfusion
Stage C Classic	SBP < 90; MAP <60 or > 30 mm Hg drop from baseline and drugs/device to maintain BP above these targets; CI < 2.2 L/min/m2; PCWP>15 mm Hg; RAP/PCWP >_0.8; CPO < _0.6 W/m2; PAPi<1.85	Lactate >_2 mmol/L: serum creatinine doubling or > 50% drop in GFR; elevated LFTs and BNP	Clinical evidence of hypoperfusion requiring medications/MCS beyond volume resuscitation to restore perfusion
Stage D deteriorating/doom	Stage C + requiring multiple pressors or MCS devices to maintain perfusion	Stage C and deteriorating	Similar to stage C, but getting worse and failing to respond to initial interventions
Stage E	Hypotensive despite maximal support	pH < −7.2; Lactate >_5 mmol/L	Cardiac arrest (PEA or refractory VT/VF) with ongoing CPR or ECLS placement

Table 1.

Stages of cardiogenic shock [3, 4].

SBP = systolic blood pressure, BNP=B-type natriuretic peptide, CI = cardiac index, CVP = central venous pressure, PA = pulmonary artery, MAP = mean arterial pressure, GFR = glomerular filtration rate, LFT = liver function test, MCS = mechanical circulatory support, BP = blood pressure, bpm = beats per minute, RAP = right atrial pressure, PCWP = pulmonary capillary wedge pressure, CHF = congestive heart failure, CPO = cardiac power output, PAPi = pulmonary artery pulsatility index, PEA = pulseless electrical activity, CPR = cardiopulmonary resuscitation, CS = cardiogenic shock; ECLS = extracorporeal life support, sat = saturation, VF = ventricular fibrillation, VT = ventricular tachycardia.

Criteria for CS are low cardiac index (<1.8 L/min/m2), systolic blood pressure < 90 mm Hg, and general signs of systemic hypoperfusion, such as elevated lactic acid in the absence of hypovolemia [4].

In a review article Atti [4] highlighted the stages of cardiogenic shock as per the Society of Cardiovascular Angiography and Interventions.

The objectives of MCS in CS include enhancing overall perfusion, optimizing coronary artery perfusion, and alleviating stress on the left ventricle.

Indications for mechanical circulatory support use are presented in Table 2 [4].

Mechanical complications in acute myocardial infarction

Acute heart failure/acute or chronic heart failure

Post-cardiotomy shock

Acute cardiac allograft failure

Post-transplant RV failure

Refractory arrhythmias

Difficulty weaning from cardiopulmonary bypass

Prophylactic use for high-risk complex PCI

High-risk or complex ablation of VT

High-risk percutaneous interventions

Table 2.

Indications for mechanical circulatory support device use after [4].

2.2 Short-term MCS devices are intra-aortic balloon pump (IABP), Impella device, tandem-heart, and Veno-arterial ECMO

2.2.1 Intra-aortic balloon pump (IABP)

IABP is a left ventricle support device that augments the diastolic flow and secondary increases coronary perfusion by counter-pulsating balloon deployed in the descending aorta by femoral or axillary approach. The cardiac output (CO) is increased by 0.5 L/min, or after other data there is no improvement in CO [4]. It contains a double-lumen catheter and a pump console that controls the balloon. The triggers for balloon inflation are ECG or blood pressure. The balloon starts inflating at the end of aortic valve closure, or when diastole starts and rapidly deflating during the onset of systole increasing by this mechanism the coronary artery perfusion. This process involves generating a vacuum force that moves the blood into the aorta, thereby reducing the left ventricle afterload. With this mechanism of inflation-deflation, the coronary perfusion is increased, and LV afterload is decreased consecutively. The best outcome is attained when the balloon is correctly positioned into the aorta, and the inflation commences at the end of systole (correlates with T wave on ECG) and deflation starts at the end of diastole (R wave of ECG) [5]. Complications of IABP are vascular and nonvascular. Vascular complications are limb ischemia, arterial thrombosis, and retroperitoneal hematoma by abdominal aortic injury, which usually needs IABP removal and vascular repair of the artery. Arterial dissection, spinal cord ischemia, cholesterol embolization, and stroke, are less encountered. Balloon rupture with helium embolization is a rare complication and can cause ischemia or stroke [4].

2.2.2 Left ventricle to aorta support devices

Impella devices are widely utilized in contemporary medical practices, with approximately 40% of these being implanted in cases of cardiogenic shock [5]. These devices feature a rotary-flow axial pump, which comes in various capacities as 2.5, 3.5, 5.0 L, and most recently 5.5 liters. Notably, the 5.5 liter has a maximum flow of 6.2 liters, and this version eliminates the need for a pigtail catheter, thereby preventing potential issues like mitral valve entrapment [6]. The Impella devices are inserted either percutaneously or by surgical approach (impella 5.0 and 5.5) on femoral or axillary/subclavian arteries. The axillary approach provides the benefit of enabling patients to mobilize and walk. Each device consists of a pump motor and a flexible catheter, which is inserted into the aorta through the aortic valve [7]. An external console regulates the speed and flow, where increased speeds will lead to elevated blood circulation. The appropriate placement of the Impella device is monitored by radiography and echocardiography and by the pressure waveform generated by a sensor at the distal end of the pump. The pump may be positioned with the inlet in the ventricle and the output in the ascending aorta giving a pulsatile waveform because of the pressure differential between the two cavities. Complications arising from the insertion of the Impella device include hemolysis, aortic valve injury, arrhythmias, bleeding, vascular issues, such as leg or arm ischemia, and arterial bleeding or thrombosis. Apparently, Impella use has a higher risk of bleeding and vascular complications as IABP [7].

2.2.3 Left atrium to aorta support devices: tandemheart

The TandemHeart device is positioned between the left atrium and aorta consisting of a transeptal cannula terminating in the left atrium [5], which brings the blood to the iliofemoral arterial system. It comprises four components: the left atrial cannula (LA), a centrifugal pump, a femoral arterial line, and a control console [5]. The femoral cannula, with a diameter of 21 Fr, connects the femoral vein to the right atrium and traverses the septum into the left atrium. Blood from the left atrium is directed through the arterial cannula (15–19 Fr), entering the right common femoral artery. The extracorporeal centrifugal pump, equipped with a spinning impeller, propels the blood, generating a rotation speed between 3000 to 7500 RPM. The TandemHeart reduces PCWP and CVP and secondarily lowers LV and RV pressures, thereby diminishing the workload on the ventricles and oxygen demand. Contraindications of use include severe peripheral artery disease, left atrial thrombosis, and complications are related to insertion point (bleeding, arterial thrombosis, hematoma), limb ischemia, thromboembolism, or hemolysis [5].

2.2.4 Extracorporeal membrane oxygenation (ECMO)

ECMO is an adapted technique stemming from cardiopulmonary bypass and involves a blood pump, oxygenator, conduit tubing, and heat exchanger [4]. There are two types of ECMO, Veno-Arterial (VA) ECMO and Veno-Venous (VV) ECMO. The first aids the heart and lungs and the second supports primary the lungs. In VA-ECMO, the inflow cannula receives deoxygenated blood through a centrifugal pump in a membrane oxygenator and sent by an outflow cannula into an artery (VA) or venous (VV) system [8]. ECMO maintains cardiac output, is used in hypoxemic cardiogenic shock, and increases coronary blood flow. VA-ECMO increases LV afterload, LV end-diastolic pressure, and volume, and there is decreased coronary flow in diastole. That’s the reason for adding another device as Impella or IABP to reduce afterload and preload [8]. Emergency indications for VA-ECMO are massive pulmonary embolism with right ventricular failure, sepsis-associated cardiomyopathy which ends with myocardial depression secondary to severe sepsis, and circulatory support in high-risk invasive procedures (TAVI, PCA, ventricular tachycardia) [9].

Complications of ECMO are vascular, neurological, hematological, and infections. Vascular issues in ECMO may manifest as limb ischemia linked to factors such as obesity, association with IABP, or arterial thrombosis, requiring surgical intervention [9]. Neurological complications are ischemic stroke and intracranial bleeding, coma, encephalopathy, and anoxic brain injury all with high mortality. Hematologic complications are bleeding which is the most common with 27 to 50% [4] due to low hemoglobin, anticoagulation, or acquired von Willebrand syndrome. Infections are very common and include cannula-site infections, or mediastinitis, pneumonia, sepsis [9]. A very common complication is thrombus on the circuit special in patients on ECMO for many days. Other complications are pulmonary edema, heparin-induced thrombocytopenia, air embolism, or acute kidney failure [4].

2.2.5 CentriMag and Rotaflow

CentriMag is a type of extracorporeal blood pump designed to assist or replace the heart function. Is completely magnetically levitated with no bearings with a very small prime volume of 31–32 ml. It can be used to assist one ventricle (RV or LV) or both ventricles [10]. The pump works by drawing blood from the patient body through a cannula, which is inserted into a large vein or artery. The blood is pumped through the centrifugal pump into the circulation. The system consists of centrifugal pump, console, and flow probe and can provide flows up to 10 L/min. An oxygenator can be attached to the tubing system for blood oxygenation. CentriMag pump offers comprehensive blood support, ensures effective decompression of both ventricles, enables potential patient mobilization, and can provide support for weeks or months. However, drawbacks include the requirement for surgical procedures during both implantation and removal. The device can be inserted by a median sternotomy or lateral thoracotomy [11]. Rotaflow pump is magnetically suspended on a sapphire bearing with no shafts. CentriMag pump has the best hemolytic performances [12] comparatively with other centrifugal magnetically pumps as Rotaflow and Revolution. The outcome of using CentriMg device in Intermacs 1 critical cardiogenic shock is showing very good outcomes with 65% overall survivors after total explant [13].

2.3 Long-term mechanical circulatory support (LTMCS)

Long-term VAD can be categorized into intracorporeal, paracorporeal, and total artificial heart (TAH) types. In the intracorporeal category, devices as Heart Mate II, Heart Mate 3, EvaHeart 2, Jarvik 2000, and Heart Assist 5 are included. The paracorporeal group comprises devices like Excor Berlin Heart, while total artificial hearts include Syncardia TAH, first implanted in 1986 and the Carmat TAH, with its initial implantation occurring in 2013 [3]. We are introducing the Heart Mate 3 VAD as a prototype within the category of long-term VADs.

2.3.1 Indications for long-term VAD implantation

Durable mechanical circulatory support in the United States is primary utilized for two main purposes: serving as bridge to cardiac transplantation (BT) or as a permanent therapeutic solution for end-stage heart failure, commonly referred to as destination therapy (DT) [14]. The short-term mechanical circulatory support (MCS) group comprises MCS employed as a bridge to recovery and bridge to transplant, as well as long-term MCS for destination therapy (DT). Various clinical conditions, such as nonischemic cardiomyopathy, and myocarditis have the potential for reversing myocardial damage, making the weaning process from MCS feasible [14].

ISHLT Selection Guidelines for Durable left ventricular assist devices were detailed by Pagani [6] and are presented in Table 3.

Inclusion criteria

AHA Stage D Heart Failure

VO2 max <14 ml/kg/min, or > 50% predicted attainment of respiratory anaerobic threshold

NYHA functional class III/IV for at least 45 of the last 60 days, despite the use of maximally tolerated doses of drugs. The inability to tolerate neurohormonal antagonist medications (e.g., beta-adrenergic blockers) may lead to earlier consideration.

Exclusion criteria

Reversible cardiac dysfunction

Active uncontrolled coagulopathy

Inability to tolerate anticoagulation mandated for the LVAD

Renal disease that would significantly shorten life expectancy.

Hepatic disease that would shorten life expectancy

Lung disease that would negatively impact post implantation survival.

Diabetes, Severe peripheral vascular disease, moderate to severe aortic insufficiency, mechanical aortic valve that will not be converted to bio-prosthesis at the time of implantation, severe right ventricular dysfunction, severe cognitive impairment, advanced age with frailty, etc.

Table 3.

Inclusion and exclusion criteria for durable left ventricular assist device selection after [6].

2.3.2 Technique of implantation of heart mate 3 assist device

The conventional method for Heart Mate 3 left ventricular assist device (LVAD) implantation involves median sternotomy, utilizing the left ventricular apex for inflow cannula insertion and ascending aorta for outflow tract placement. This approach provides an improved view of the heart, but it comes with drawbacks, including increased risk of bleeding, potential right ventricular dysfunction due to full pericardial opening, and the likelihood of later adhesions if a second surgery for transplant is required. The procedure is done on cardiopulmonary bypass and beating heart but can be done off pump as minimally invasive procedure [15]. The inflow cannula is positioned at the left ventricle apex, 2 cm lateral from the left anterior descending coronary artery, and aligned parallel to the interventricular septum. The placement of the sewing ring is determined by placing a finger on the left ventricular wall, as identified by transesophageal echocardiography. Subsequently, the sewing ring is secured with interrupted Prolene sutures, and coring is performed while inspecting the ventricle for thrombi or residual muscular tissue, which may be removed.

The inflow cannula is then inserted into the left ventricle within the sewing ring and rotated to achieve the correct position at the outflow anastomotic site. An alternative cannulation site is the “Frazier point” on the inferior wall, situated laterally and posteriorly from the posterior descending coronary artery. The outflow graft is positioned parallel to the right ventricular margin within the pericardium, avoiding passage in front of the right ventricular outflow tract. The graft is then anastomosed to the ascending aorta using continuous Prolene sutures, with additional stitches applied for optimal hemostasis. In special circumstances, alternative courses for the outflow graft may be considered, such as through the transverse sinus or other arterial sites like the innominate artery descending aorta, supra-celiac artery, or axillary artery. The descending aorta is particularly utilized in lateral placement of the left ventricular assist device (LAVD) through lateral thoracotomy or in redo surgeries to avoid sternal reentry [15].

2.3.2.1 Complications of LVADS implantation

The main complications are bleeding, infection, thrombosis emboli, neurologic events, right heart failure, and aortic insufficiency. Bleeding is most common in the early postoperative period. Early bleeding is correlated with surgery, which is complex and with increased risk, and late is due especially to gastrointestinal bleeding (almost 60%) [16].

The occurrence of bleeding is influenced by various factors, such as antiplatelet and anticoagulation therapies, acquired Von Willebrand syndrome, and the angiogenesis cascade. Several treatment options, including arterial embolization, cauterization, and surgical procedures, are available to manage bleeding. Substances like somatostatin, omega-3 fatty acids, and digoxin are effective in reducing bleeding in patients with LVAD. Pump thrombosis, more common in Heart Ware and less in HM 3 devices due to reduced friction and shear stress, is addressed with antithrombotic therapies, antiplatelets, LVAD exchange, or urgent transplant. Neurological events, including hemorrhagic and ischemic strokes with an incidence of 5 to 30%, are associated with elevated blood pressure and anticoagulation. Right heart failure can occur early (within 30 days post-LAVD implant, proximately 5%) or late (after 30 days), requiring temporary right ventricular assist device implantation for early acute RHF or medical therapy for late RHF. Aortic insufficiency typically manifests in around 30% of cases within the first 2 years [17].

2.3.3 Outcomes

The results following implantation of left ventricular assist device (LVAD) generally show improvement, with a 1-year survival rate of 82.3% and a 2-year survival rate of 73.1% during 2015–2019 period in USA. However, it is crucial to note that adverse events remain significant, with infections (41%) and major bleeding (33%) being notable in the first-year post-implantation. In the Momentum 3 trial, the Heart Mate 3 LVAD did not demonstrate an enhancement in overall survival when compared to the Heart Mate 2. However, it did exhibit fewer instances of reoperation and bleeding complications, or aortic insufficiency [18].

3. Heart transplantation (HT)

Heart transplantation stands as the primary therapeutic approach for end-stage heart failure considered a gold standard treatment. The inaugural human heart transplant was conducted by Christiaan Barnard in Cape Town in 1967, marking the beginning of a procedure that has since been successfully performed worldwide [19].

3.1 Indications of heart transplantation

The ISHLT indications for HT are advanced heart failure, a VO2</=12 mL/Kg/min at maximal cardiopulmonary exercise test (or </=14 if the patient is intolerant to B blockers) or VO2 < 50% of the predicted. After the European Society of Cardiology HT is indicated in advanced HF refractory to medical/device therapy in absence of the contraindications [19].

3.2 Contraindications of HT

Contraindications of HT are absolute or relative. Absolute contraindications are age > 70 years old, Severe pulmonary hypertension (PAP > 50 mm Hg, PVR > 3 UI Wood irreversible with milrinone or levosimendan), Multisystem disease, severe lung disease, history of cancer, severe systemic infection, active smokers or drugs users, viral infection with severe organ damage. Relative contraindications are diabetes mellitus with organ damage or poorly controlled, irreversible renal dysfunction or liver dysfunction (cirrhosis), and severe obesity [19].

3.3 Donor selection

3.3.1 Donation after brain death (DBD)

In DBD donation organs are retrieved for transplantation from individuals who have been declared brain death. The evaluation of donors is initiated by confirmation of brain death and family agreed with donation the donor may be analyzed according to the guidelines [20]. The main parameters taken into account are age < 45 years, size, hemodynamic status and inotropic support, metabolism status, systolic function documented by echocardiography repeated daily, blood group and Anti-Human Leukocyte Antigen Compatibility, drug use or comorbidities as hypertension, dyslipidemia, or diabetes [19]. Coronary artery status is analyzed by the surgeon and or on angiography whenever possible.

3.3.2 Donors after circulatory death (DCD)

DCD donation can be performed in three ways: direct procurement followed by normothermic machine perfusion (DP-NMP) for storage and transportation, normothermic regional perfusion followed by procurement and storage in normothermic machine perfusion (NRP-NMP), and normothermic regional perfusion followed by procurement and static cold storage (NRP-SCS) [21]. Direct procurement with normothermic machine perfusion (DP-NMP) was initiated for the first time in Sydney in 2014, this approach involves pharmacological postconditioning of the organ. It includes the addition of erythropoietin and glyceryl trinitrate (GTN) to the preservation solution, combined with normothermic machine perfusion for transportation to the implanting hospital.Normothermic regional perfusion with normothermic machine perfusion (NRP-NMP) was developed in Papworth by Messer and after the circulatory death is confirmed extracorporeal membrane oxygenation is used to resuscitate the organs in situ but with the exclusion of the brain by clamping the cerebral arteries. After in situ heart revival, the cardiac function is assessed as in DBD donation, the heart is harvested in the usual way and placed on the normothermic machine perfusion device for transportation to the hospital. Normothermic regional perfusion-static cold storage (NRP-SCS) consists of ECMO perfusion after declaration of death and after heart function assessment, the heart is retrieved and preserved in cold storage if a short ischemic time is anticipated [21].

3.4 Heart assessment and retrieval technique on the donor

The contractility of the heart is judged by focusing on the right ventricle first then on the left ventricle. The whole heart needs to be inspected and the contractility assessed with very gentle maneuvers. The coronary arteries are inspected and palpated in all territories making sure they are free from coronary disease or malformations. During handling the heart attention is paid to the development of arrhythmias and drops in blood pressure. If the blood pressure, heart rate, and rhythm remain stable and in normal parameters, during the handling, this indicates a good-quality graft. Next, the pressures are measured directly in the right atrium, pulmonary artery, and left atrium. The filling of the heart is weighed to interpret these results correctly. The pressures must be in normal ranges to consider that the graft has a good function. All these information gathered during direct surgical assessment of the heart are analyzed together with the number of inotropes and vasopressors requirements, Echocardiogram, Electrocardiogram, and clinical history to reach a definite conclusion about using the heart for transplantation or not. All these data shall point towards a normal heart anatomically and functionally to accept the heart for transplantation. After the heart has been accepted for transplant the cardioplegia solution and preservation solutions are prepared. In our center, we use St Thomas cardioplegia to arrest the heart for explant and cold Ringer’s for preservation during transfer to the implant center.

3.5 Donor heart explant surgery

Once the abdominal surgical team has completed the dissection of the organs that they are planning to retrieve. The full dissection of the heart including the great vessels is rendered. The SVC shall be dissected fully, including the azygos and right brachiocephalic vein. The aorta is dissected along the arch vessels. The IVC is also dissected circumferentially to warrant a clear view of the transection point of this vessel without risk of injury to the coronary sinus. Silk ties are passed under the innominate vein, left brachiocephalic vein, and azygos vein. Heparin is given at a dose of 300 IU/kg and waits for 3 minutes before cannulation. An antegrade cannula is placed in the ascending aorta, as high as possible. The interatrial groove of Waterston’s Sonnengaard’s is dissected to expose as much left atrial wall as possible in this area. For a correct explant first tie the silk ties placed under the veins structures mentioned above. This reduces the blood flowing into the heart. The next step depends on whether the lungs are being explanted for transplant or not. If the lungs are being used for transplant, we open the left atrial appendage, and a suction device is inserted to empty the left heart. If the lungs are not being used, then open the left atrium through the interatrial groove of Waterston or Sonnegaard’s. Place a suction through this opening to empty the left heart. The following step is complete transection of IVC making sure not to injure the coronary sinus and preserve at least 5 mm of IVC with the heart. Once the heart is fully decompressed, apply the aorta cross-clamp as high as possible and start delivery of 1.2 liters of St Thomas cardioplegia. The heart shall arrest quickly and symmetrically, once the cardioplegia start to be delivered. This indicates good protection and patent coronary arteries. While administering cardioplegia there is forbidden to manipulate the heart. We may be sure that the heart is fully decompressed. Cold Ringer solution is applied on the heart surface but not ice to prevent thermal injury. After completion of the cardioplegia, the excision of the heart starts by dividing the right and left brachiocephalic veins. The SVC may be fully preserved with right brachiocephalic vein. The azygos vein is tied and divided below. The SVC is separated from the surrounding tissues until a clear view of the roof of left atrium is attained. Then the left atrium is cut close to pulmonary veins, if retrieving the lungs for transplant, it will be preserved 1 cm of tissue around the veins cuff. First, the cut goes to the roof of the left atrium until the level of aorta. Then, the IVC is completely divided preserving 5 mm at least and exposes the inferior pulmonary vein. Once this is achieved, the left atrial wall towards the IVC is cut. When doing this division, it may be to avoid inferior pulmonary vein damage and aim towards an inferior point located 1 cm from the lower margin of IVC to avoid penetrating the right atrium, which can happen sometimes. The above steps complete the excision of the right side of the heart. Now the remaining wall of the left atrium is divided, for achieving that we may lift gently the heart exposing the inferior and left lateral wall of the LA. Left atrium is divided by scissors preserving a small cuff of at least 1 cm attached to the pulmonary veins as well, for the use of lungs for transplant. The midpoint between left atrial appendage and the beginning of the left pulmonary veins is a good landmark to achieve this goal safely, the incision of the left side of the LA shall commence at this point. Once the inferior and lateral wall of the LA has been cut the only remaining attaching the left split is a few centimeters of atrial roof. This is accomplished very easily from the left side. Caution when dividing the LA always keep in mind to preserve no less than 2 cm of free wall around to facilitate the heart implant. The completion of the preceding steps means that the heart now is only attached to the mediastinum by the aorta and pulmonary artery. Proceed as follows, by dividing the ascending aorta at the level of the arch, to ensure to preserve all length. Consecutively aorta is separated from pulmonary artery until the bifurcation is clearly seen. If the lungs are being retrieved for transplant, then the PA is divided at the bifurcation level; differently, if the lungs are not being used, dividing the right and left PA branches will secure the PA whole length. Once the PA is divided, gentle traction to the heart up and downwards helps to divide the remaining tissue behind the aorta and PA to fully free the heart. The heart is then placed in cold Ringer’s solution on a back table and inspected for injuries or eventual congenital anomalies. Double check for the great vessels integrity and quality. Cardioplegia 300 ml are administered at this point and packing the heart and transportation are the final steps of the process.

3.6 Heart preservation

To preserve the heart during transportation, we use cold Ringer’s solution. These are other solutions used by different centers: University of Wisconsin (UW), Celsior and Histidine-Tryptofan-ketoglutarate (HTK). According to Yognan Li et al. [22], the University of Wisconsin solution shows improved survival results at 30 and 90 days. In our experience, Ringer’s solution works very well. There are diverse means of transportation for the heart: the classical is 3 bags system, where the heart is placed in a plastic bag surrounded by the preservation solution and this bag is placed in another one with cold Ringer’s, which is in turn placed in a third plastic bag with cold Ringer’s too. Then it is placed in ice cooler. This method was tested and gave good outcomes. The recent innovation has been the introduction of the Sherpa pack Cardiac Transport system by Paragonix Technologies and Transmedics OCS (Organ Care System). In the case of the Sherpa pack, the heart is placed in a plastic container with the preservation solution; the container then is placed in a type of ice cooler. It has a probe that allows to know the temperature of the preservation solution around the heart. In the case of OCS Transmedics, the heart is placed in machine that perfuses the heart with oxygenated blood and a solution developed by Transmedics. This allows the heart to be transported on normothermic conditions and pumping. Both techniques are in progress and time will tell, which will add a definitive advantage.

3.7 Heart transplantation bicaval technique

3.7.1 Cardiectomy

The heart cannulation is done with the aortic cannula placed as high as possible in the ascending aorta, one metal tip venous cannula is placed as high as possible in SVC and another metal tip cannula in IVC. An antegrade vent cannula is placed in the ascending aorta for cardioplegia delivery and drainage. The patient is on cardiopulmonary bypass as soon as the new heart arrives at the transplant center. While cardioplegia is being given to arrest the heart of the recipient, the new heart is brought into the surgical field. The heart is inspected the LA appendage is sutured and 300 ml of cardioplegia are delivered. The recipient cardiectomy starts by transecting the SVC and dividing any remnant tissue by diathermy until the roof of LA is exposed. Then the aorta is transected and dissected free from the PA by diathermy taking care to injure the right and left PA branches. Then the PA is divided just above the pulmonary valve. When transecting these vessels, the length is very important for a comfortable anastomosis. On completion of these steps, proceeds the disconnect the heart from IVC. This maneuver involves cutting through the right atrium keeping a cuff of RA connected to IVC of about 2 cm. This will facilitate the IVC anastomosis during the graft implant. Finally, it is the turn to excise the heart preserving the LA only. Usually, the LA is very large in the recipient. If LA is small, the dissection of the interatrial groove is mandatory. The RA is opened fully and access the LA through it. The LA wall is cut just below the coronary sinus to make sure that we are preserving the whole LA.

3.7.2 Heart implant technique

The Prolene 3–0 extra long suture is used for left atrium anastomosis. Taking the new heart off cardiopulmonary bypass position the graft in the surgical field may be correct with LA appendage as a landmark on the left side. The anastomosis starts at the level of LA appendage with running sutures advancing towards the level of IVC. The bites shall include a good amount of tissue, the needle entry point about a minimum of 5 mm from the edge and no more than 3 mm apart to secure water tightness. After reaching the level of IVC, change direction and bring the other limb of the suture from the level of LA appendage and run towards the roof of the LA and tie. Now the next to anastomose is IVC and Prolene 4–0 is usually used. Here the cuff of RA that was preserved on the recipient IVC simplifies the anastomosis significantly. The wise advice is to anastomose the PA next with Prolene 4–0. The rationale for doing this anastomosis before the aorta is the fact that the wide surgical field allows a very comfortable PA anastomosis without having to push the aorta, which averts possible tear on the fresh aortic anastomosis line in the case that this was done first. It also grants a perfect view to adjust the length of the PA to prevent kinks and undue tension. Once the PA is done the aorta anastomosis is performed with Prolene 4–0. At this point, the heart is deaired and cross clamp removed. This is recorded as the time of graft reperfusion and end of the ischemic time. The target is to reperfusion the new heart in a time window of 4 hours from the moment of aorta cross clamp in the donor.

3.7.3 Taking the new heart off cardiopulmonary bypass

The rewarming phase of the new heart shall take at least 30 minutes. Then, very gradually start filling the heart and let it work harder bit by bit. Place atrial and ventricular pacing wires and pace at 110 or 110 beats per minute. Start inotropic support or vasodilators as required. And very slow wean from cardiopulmonary bypass. If distension of the heart occurs at any moment, stop the weaning process, go back to full cardiopulmonary bypass, wait another 15 or 20 minutes, and repeat the procedure. If there is left or right ventricular dysfunction, consider mechanical circulatory support starting with IABP first. In case of 3 attempts of unsuccessful weaning from CPB after correction of the electrolytes, column temperature, pH and optimizing inotropic support we can confirm the diagnosis of primary graft failure and place the patient on central Venous Arterial ECMO support. The patient is transferred to the ICU to wait for graft function recovery, which usually happens in the first 7 days post-transplant. The inotropic support reduction and echocardiography will inform about graft recovery to plan ECMO decannulation. Before closing the chest, hemostasis check is mandatory and to avoid pulling the heart and suture lines are very important because of the vulnerability of the heart.

3.8 Heart transplantation with bi-atrial anastomosis

Left atrial anastomosis is done as in the previous bicaval technique. The right atrial anastomosis is started at the superior part of atrial incision, and a continuous Prolene suture is carried inferiorly and superiorly to anastomose the septum and the lateral wall of the septum. The PA and aorta are sutured in the same manner as described on bicaval HT.

3.9 Heart transplantation with modified bicaval technique

The “modified” bicaval anastomosis involves performing left atrial anastomosis, inferior vena cava connection, and aortic anastomosis all while the aorta is clamped on cardiac arrest. Subsequently, the anastomoses of the superior vena cava and pulmonary artery are made on beating heart, after aortic clamp is removed. The method has the goal of shortening the warm ischemic time and secondarily to reduce the cardiopulmonary bypass time [23, 24].

4. Heart transplantation with LVAD explant

Performing heart transplantation in a patient with a prior LVAD implant is technically more challenging, necessitating the mandatory use of peripheral femoral cannulation and cardiopulmonary bypass to avoid catastrophic bleeding. Given that LVAD patients are typically on warfarin, it is common to administer vitamin K and fresh frozen plasma before surgery to reverse the anticoagulation effects. During LVAD implantation, the use of Gore-Tex membrane helps prevent adhesions between the sternum and the heart, facilitating easier explantation of the device [24].

4.1 Complications of HT

Complications following heart transplantation (HT) are associated with immunosuppressive therapy and can manifest either shortly after or long after surgery. Early complications encompass acute cardiac rejection, manifest as either cellular rejection or antibody-mediated rejection, primary graft dysfunction, cardiac tamponade, and right ventricular dysfunction. In some cases, temporary circulatory support may be required to facilitate heart recovery. Late complications include persistent graft rejection, coronary artery vasculopathy (CAV), and adverse effects of immunosuppressive medications, such as malignancy, chronic kidney disease, diabetes, hypertension, or infection. For early detection of acute rejection, frequent endomyocardial biopsies are essential, typically performed every week in the first month, or every second week for the second month, followed by intervals or every 3 months until the first-year post HT [25]. Long-term complications following HT include rejection, which can be present as heart failure or may even be asymptomatic, and coronary allograft vasculopathy (CAV). While coronary angiography has traditionally been the primary method for detecting CAV, the use of coronary computed tomography has been on the rise in recent times [25]. There is a significant risk of cancer in heart transplant patients, skin cancer being the most common [25]. Particular types of lymphoma or lymphoproliferative disease may also arise following HT. Additionally, other enduring complications include hypertension, diabetes, arrhythmias, and chronic kidney failure.

4.2 Outcomes after HT

The outcomes after HT depend on many factors as donor characteristics, donation process, type of donation (donation after cardiac death or donation after brain death), recipient history, indications for HT, surgical procedure, and postoperative early and late complications. Miklin et al. showed [26] in an analysis of the last three decades that there were no differences in HT survival between restrictive cardiomyopathy (RCM) and non-RCM but if are compared RCM, only radiation/chemotherapy patients are worse than all other RCM subtypes and notably amyloid RCM short-term survival has improved but long-term survival is still worse. Median survival post-transplantation increased from 8.6 years in decade 1982–1991 to 12.5 years in 2002–2009 [27]. Donor heart allocation system was revised in 2018 by the United Network for Organ Sharing. This new system has modified the approach of candidates on ECMO support have a shorter waiting list from 10 to 5 days and survival at 30 days has increased from 76.4 to 94.2% [26]. Recipient risk factors with worse survival were BMI > =30 kg/m², under-sizing the donor hearts <=20% does not affect survival but older patients had worse survival post-transplant. Recipients with idiopathic DCM had a better 1-year survival than ischemic cardiomyopathy. Donation after circulatory death has increased the donor pool by 48% [27] and the outcomes were similar to DBD donation. They had similar rates of rejection DCD group vs. DBD group 25 vs. 23% in the UK experience. Primary graft dysfunction (PGD) occurring in the first 24 hours after surgery rates are between 7.4 and 31% [26]. Recipients with PGD had a higher 30-day mortality 6.1 vs. 0.9% and lower 5 years survival compared with non PGD group [27]. Graft rejection can be cellular, or antibody-mediated and acute or chronic and cellular rejection (ACR) generally decreased over time. Cardiac allograft vasculopathy is the most important cause of death after 1 year from HT and represents a coronary occlusive disease of the heart due to inflammatory-immune mechanism, which affects predominantly the medium and distal part of coronary arteries. The proximal coronary artery lesions are related to donor-derived coronary artery disease. Surgical revascularization or PCI has both high mortality and is difficult. Other complications, which are limiting long-term survival, are malignancies especially skin cancer is the most common, with a rate of 1.7% at 1-year and 18.5% at 10-year survivors [27]. Renal failure is another long-term complication related to nephrotoxic effect of tacrolimus and despite recent improvements is worsening the 1-year survival [27]. Renal dialysis or kidney transplantation is necessary for long-term survival. Twenty-year survival following heart transplantation was presented by Hess et al. [28]. On more than 20,000 patients the greatest 10-year survival with no risk factors was 59.7% and 20-year survival was 26.2% [28].

4.3 Heterotransplantation and xenotransplantation

Heterotransplantation purpose is to provide therapeutic solutions for organ failure when human-to-human transplantation is not feasible because of the shortage of organs. The main challenges of heterotransplantation are immune rejection and the risk of transmitting infection from donor species to the recipient. Advances in immunosuppressive therapies, genetic engineering, and organ preservation techniques are being investigated to improve the success rates and safety of hetero-transplantation procedures. Xenotransplantation, is a type of heterotransplantation when organs are transplanted from animals to humans, has a historical connection due to the perceived suitability of pigs as donors. Pigs are favored for their rapid growth, widespread availability, quick maturity, similar heart size to humans, low risk of infection transmission, and positive track record in genetic engineering. However, challenges arise from disparities in anatomy and physiology between pigs and humans, along with a significant divergence in the immune system relationship. The history of xenotransplanted hearts traces back to 1964 when James Hardy [28] performed the first attempt, transplanting a chimpanzee heart into a human who unfortunately succumbed within 90 minutes. Fast forward to 2022, when Dr. Bartley Griffith and his team [29] achieved a significant milestone by conducting the first successful pig heart transplant, which endured for 2 months. This groundbreaking procedure involved the use of a genetically modified heart, wherein 10 genes were either altered or knocked out. To enhance the compatibility and reduce the risk of complications like thrombosis, or complement activation, the researchers incorporated various human regulatory proteins [29]. Furthermore, a sophisticated immunosuppressive medication was added to prevent acute rejection and T-cell-mediated rejection. Despite these advancements, challenges persist, including religious barriers and potential risks, such as transmission of viral infections from pigs to humans [29]. While the likelihood of generating a new virus through mutations is low, it cannot be dismissed. Preserving solutions play a crucial role in enhancing survival rates by minimizing ischemic graft injury. In experimental studies, the preservation of pig hearts using oxygenated, 8-degree Celsius cold cardioplegia solution containing erythrocytes and hormones has significantly extended the preservation time [30]. In summary, xenotransplantation is a procedure that can offer a major reduction of the waiting list for heart transplants but there are still many questions and problems to be answered.

5. Conclusions

Mechanical circulatory support (MCS) and heart transplantation (HT) are complementary surgical interventions employed in cases of advanced heart failure. Despite existing guidelines and protocols, the decision to opt for MCS or HT is influenced by numerous factors. In the context of temporary mechanical circulatory support, the choice of devices is often determined by the expertise of the medical team, with VA-ECMO gaining popularity due to increasing use and improved outcomes. In the realm of long-term MCS, Heart Mate 3 has emerged as a dominant choice. Its popularity can be attributed to its smaller pump size, reduced thrombosis risk, and ease of implantation, even via thoracotomy. While heart transplantation is widely regarded as the optimal approach, its implementation is constrained by a limited pool of donors. Yet, progress in donations after circulatory death and encouraging strides in xenotransplantation hint at prospective solutions for surgical therapy, presenting a promising outlook for addressing the substantial rise in patients grappling with heart failure.