Perspective Chapter: Right Ventricular Free Wall – The Forgotten Territory for Revascularization

Abstract

Revascularization of the right ventricle free wall is not routinely addressed during coronary bypass surgery, yet the clinical impact is not well studied. Addressing right ventricular free wall ischemia is feasible via bypassing branches of the right coronary artery. In this article, we aim to examine the hypothesis that ignoring the right ventricular free wall ischemia during coronary artery bypass surgery could have an early, and possibly late, clinical impact, such as right ventricular dysfunction and functional tricuspid regurgitation, in patients with extended right coronary artery disease without adequate collateralization from the left coronary system. We present the current available evidence that is relevant to that hypothesis.

1. Introduction

One of the motivations for our hypothesis is a recent case of acute right ventricular (RV) dysfunction after coronary artery bypass grafting (CABG) that resolved after bypassing the right coronary artery (RCA) in the atrio-ventricular groove [1]. The patient was an 82-year-old woman who presented with coronary artery disease, including extended RCA disease, a tight mid-lesion, and another long, tight lesion in the distal part of the artery. There was one large, acute marginal branch in between the two lesions supplying the RV-free wall. There were no robust collaterals between the left and right coronary circulations. She underwent revascularization of the left coronary system lesions as well as the posterior descending artery (PDA). However, upon separation from the cardiopulmonary bypass, she developed new acute RV dysfunction that did not resolve with prolonged reperfusion on the pump and required an increased dosage of inotropes and pressors to support the hemodynamics. After excluding all other possible etiologies, we decided to add a bypass to the RCA in the atrio-ventricular groove between the mid and distal lesions, with the aim to provide blood flow to the RV-free wall through a large acute marginal branch. Only after adding the bypass to the mid-RCA, the RV dysfunction resolve, and the patient required minimal pharmacological support. The patient made a complete recovery with normal RV function at 3 months of follow-up [1].

In addition to this case, it’s our clinical observation that similar patients with extended RCA disease and no adequate collateral from the left coronary system, would require higher blood pressure to maintain RV-free wall perfusion, which can be achieved with pharmacological support or an intra-aortic balloon pump. Although this approach may not have a clinical impact in some patients, it could pose a complication risk in older patients with peripheral arterial or kidney disease. In a large cohort study from the Netherlands that included 1109 patients who underwent cardiac surgery, postoperative RV dysfunction (RV ejection fraction <20%) was associated with complicated intensive care unit courses, including prolonged stay, longer duration of mechanical ventilation, higher dosage of inotropes, and higher rates of acute kidney dysfunction [2]. In a similar study from France, out of 3826 patients who underwent cardiac surgery between 2016 and 2019, 3% developed postoperative RV failure with worse outcomes [3]. In addition to the early impact after surgery, not addressing RV-free wall ischemia in patients undergoing CABG could have a late effect. Several studies have reported the persistence of RV dysfunction later after CABG during follow-up [4, 5, 6, 7]. Moreover, other studies have shown that RV-free wall revascularization prevented postoperative RV dysfunction and peri-operative ischemic complications [8, 9, 10]. In this article, we aim to examine the available relevant evidence to address the question of how important RV-free wall revascularization during CABG is.

2. Coronary revascularization

CABG has been the standard surgical intervention for coronary artery disease for over 50 years [11, 12]. The practice of CABG has been dedicated primarily to address coronary artery pathology with respect to the left ventricular territories (anterior, lateral, and inferior walls), while less commonly to address RV ischemia. This is supported by the current guidelines that focus on the indications for revascularization and different approaches to address left main or multi-vessels disease, yet there are no specific recommendations regarding RV ischemic disease [13, 14]. The evolution in the practice of CABG has been directed toward the utilization of cardiopulmonary bypass versus off-pump, minimally invasive approaches, conduit selection, and harvesting [11, 12, 15]. Completeness of revascularization has been an important focus of CABG, as the outcomes of incomplete revascularization have been shown to be inferior to complete revascularization [13, 16, 17]. However, there is no established definition of complete revascularization, and it continues to be variable across different studies or guideline recommendations. In general, complete revascularization is reported as bypassing coronary vessels with >50% stenosis in the major territories and vessel diameter > 1.5 mm [13, 16, 17]. However, revascularization of the RV-free wall in cases with extended RCA disease has not been specifically considered in the definitions of complete revascularization. Thus, addressing RCA disease commonly includes bypassing the PDA or posterolateral ventricular (PLV) branch and less commonly includes bypassing acute marginal branches or main RCA for extended disease, which could include multi-stenotic lesions or complete occlusion.

3. The forgotten territory in CABG: the RV-free wall

Anatomically, the RV is composed of three components: (1) inflow through tricuspid valve and sub-valvular apparatus (2), trabecular apex, and (3) outflow or infundibulum [18, 19, 20]. In cross-section, the RV-free wall, which is part of the ventricular wall not in contact with the interventricular septum, appears as a crescent over the left ventricle (LV) and is composed of anterior, lateral, and inferior walls [19, 20]. The RCA provides the primary blood supply to the RV wall through marginal branches to the lateral wall, and PDA to the inferior wall and posterior one-third of the interventricular septum. The RV anterior wall is supplied by the left anterior descending artery while the infundibulum is supplied by the conal artery [18, 19]. Bowers et al. studied the flow in RCA branches in 125 patients presenting with inferior myocardial infarction secondary to RCA disease [21]. They reported that RCA branch perfusion was critical for RV global performance as proximal lesions resulted in significant RV dysfunction. Spontaneous reperfusion or presence in collaterals maintained the flow in the RV branches which resulted in the preservation of RV function [21]. On echocardiographic imaging of the RV, one of the standard views used for assessment of the RV function is the apical four chambers view, in which the RV-free wall is the anatomical lateral wall supplied by RCA marginal branches [19, 20]. The ejection performance of the RV is based on three mechanisms: inward movement of the free wall (bellows effect), longitudinal shortening that brings tricuspid annulus toward the apex, and stretching of the free wall over the septum secondary to left ventricular contraction [18]. The contribution of each mechanism to RV pump function may vary in different pathological conditions [22]. Recent studies are suggesting for equal contribution of longitudinal and radial movements to global RV performance [23].

4. RV-free wall revascularization

In a pioneer work by Dr. Vineberg in 1968, he reported implanting the right internal mammary artery in the RV myocardium to treat RCA disease in 15 patients [24]. The authors reported no operative mortality or late death during 7 to 22 months of follow-up. In 1988, Drs. Rich, Akins, and Daggett from Massachusetts General Hospital wrote an editorial discussing the possible etiologies for RV dysfunction after cardiopulmonary bypass, ignoring RV revascularization as a possible important etiology [25]. The authors followed a complete RV revascularization approach that includes bypassing disease RCA branches and reported no early or late RV failure in two different cohorts regardless of the technique of the myocardial protection. However, this approach was not widely adopted among cardiac surgeons in the current practice. This could be related to the development of collaterals between the right and left coronary arteries in patients with chronic occlusive disease of the RCA which reduces the incidence of significant RV dysfunction after CABG. Cho et al. reported a case of ischemic tricuspid regurgitation (TR) that improved after revascularization of the left anterior descending artery that provided collateral blood supply to the ischemic region of the RV-free wall [26]. Conversely, if ischemic TR developed in the absence of collaterals between right and left coronary arteries, revascularization of RCA has been shown to improve the TR [27].

Multiple surgical groups from Turkey have adopted the concept of RV-free wall revascularization and studied the impact on clinical outcomes [8, 9, 10]. In a prospective randomized study, Güney and Eren compared complete RV revascularization with multiple bypasses to RCA branches (n = 32 patients) to a single conventional bypass to RCA (n = 32 patients) [9]. The authors have demonstrated that complete RV revascularization had a protective effect against peri-operative ischemic events in the RCA territory in patients with ejection fraction <50%. In another study of 35 patients with diffuse atherosclerotic disease of the RCA who underwent CABG; RV diastolic function by echocardiography improved in 20 patients with sequential bypass to RCA compared to 15 patients with single bypass to RCA [10]. In another comparative analysis conducted by Sahin et al., 100 patients with multi-segments disease of the RCA underwent off-pump CABG, in which 50 patients had single bypass to distal RCA and 50 patients had additional bypass to marginal branch of RCA [8]. Patients who had additional bypass to the RV branch experienced faster recovery of RV function, less inotropic support, and shorter hospitalization than the group with single distal RCA bypass.

5. RV dysfunction after CABG

Several properties may render RV less susceptible to ischemia compared to LV, including smaller muscle mass and milder workload resulting in less oxygen requirements [26, 28]. More importantly, in patients with chronic coronary artery disease, rich collaterals develop between the left and right coronary systems and disease of the left coronary system may contribute to RV infarction [26]. This could explain in part the reason that early RV dysfunction is not common after CABG and did not receive increased attention over the evolution of CABG techniques. It could occur in cases with extended RCA disease (complete occlusion, diffuse disease, multi-segment stenosis) without adequate collaterals from the left coronary system while the patient underwent only conventional bypass of distal RCA or PDA [1]. On the other hand, little data is available about the fate of RV recovery after CABG in cases with extended RCA disease.

Roshanali et al. studied RV function after CABG in 240 patients using an echocardiographic assessment of the RV-free wall [4]. In their cohort, 60% had proximal RCA stenosis and 40% had distal RCA stenosis, but they did not elaborate on the details of the proximal RCA disease if it was complete occlusion or multi-segment disease. They reported depressed RV function on echocardiographic assessment up to 1 year after CABG, regardless of the status of RCA bypass which included only bypass to PDA or PLV branch [4]. In a two-part study, Yadav et al. have shown selective RV dysfunction following CABG compared to LV function using Myocardial tissue Doppler velocities to assess ventricular function [5]. The first part was a prospective study of 20 patients undergoing CABG with preoperative and 3-month postoperative echocardiograms. The second part was a retrospective analysis of 101 patients with established heart failure diagnosis, out of which 40 patients had previous CABG. In both parts of the study, the echocardiographic assessment of ventricular function showed a lower RV: left ventricular ratio. Interestingly, they reported the same observation even when CABG patients compared to patients with ischemic pathology of heart failure [5]. In another recent prospective study, Chinikar et al. studied RV function in 61 patients before and after CABG using echocardiographic assessment as well as functional capacity [6]. They found a high frequency of RV dysfunction at 1 week and 6 months after CABG as well as impaired exercise capacity. In that study cohort, 88.5% had RCA disease, 23% had RV branch disease, and 73% received RCA graft but the report did not indicate which part of the RCA or which branch was bypassed or the status of the bypass grafts [6].

6. Ischemic tricuspid regurgitation

Our group has studied the concept of “ischemic TR” in a cohort of ischemic MR patients (n = 568) undergoing mitral valve surgery and CABG +/− tricuspid valve repair [29]. The characteristics of TR in this cohort of patients mimic the characteristics of ischemic MR with dilated annulus, tethered leaflets, and RV dysfunction. However, in longitudinal analysis of left- versus right-sided heart remodeling in the same cohort of patients, we observed an important difference; the LV underwent reverse remodeling with regression in size and recovery of ejection fraction with stable MR over time after surgery [7]. Conversely, the RV continued to dilate with worsening RV function and increased recurrence of TR over time up to 5 years after surgery, even in patients who underwent TV repair. In this cohort, 83% of patients had >50% stenosis of the RCA system, 48% had total occlusion, and 73% of patients underwent bypass of RCA lesion [29]. However, there was no available granular data regarding the extent of the RCA disease (proximal, distal, multi-segment, presence of collaterals with left system) nor the location of the bypass graft to the RCA. Given the common practice of CABG among the surgeons, it is expected that most of the bypass graft to RCA in this cohort was to distal RCA branches such as PDA or PLV branches, and to a lesser extent to include bypass to acute marginal branches. In that sense, even though it is speculation, ignoring the RV-free wall revascularization in some of these patients could have contributed to progressive RV remodeling secondary to chronic ischemia. This could provide an explanation for the difference in recovery between the left ventricle and right ventricle after addressing the mitral valve disease and the coronary artery disease that commonly is dedicated to address the ischemia of the LV territories and to a lesser extent the RV-free wall ischemia.

Onorati et al. had similar findings in a smaller cohort of patients (n = 64) who underwent CABG and mitral valve repair for ischemic MR during a shorter follow-up period of 6 months after surgery [30]. They suggested that patients who needed tricuspid repair had already advanced stage of RV cardiomyopathy as the reason for the failure of RV reverse remodeling compared to the LV. Another group has shown progression of functional TR in patients with dilated cardiomyopathy (the majority were ischemic) after repair of functional MR +/− CABG [31, 32]. In a recent study that included data from two prospective randomized ischemic MR trials, progression of non-severe TR was found to be infrequent while patients with > moderate TR at 2-year follow-up had significant clinical events [33]. This study included 492 patients, with 59% undergoing CABG, while 41% did not require CABG at the time of mitral valve surgery, and 66% of patients having echocardiographic data analysis at a 2-year follow-up. Only 15% of patients required bypass to the RCA [33]. However, these former reports did not indicate details about the extent of the RCA disease or the location and patency of the bypass to the RCA system.

In another longitudinal analysis study, but after percutaneous coronary intervention (PCI), Koren et al. followed the evolution of functional TR in 134 patients presented with ischemic MR after myocardial infarction for a median follow-up of 5 years [34]. They excluded all other etiologies of TR such as primary tricuspid valve pathology, pulmonary hypertension, or RV leads. At the time of the index event of myocardial infarction, 30% of patients developed functional TR, and failed revascularization was an independent predictor for the development and severity of functional TR. In their analysis, there was no association between the development of functional TR and infarct-related arteries or the existence of multi-vessel coronary artery disease. In their cohort, 36% had RCA disease but no available data about the extent of the disease or status of acute marginal branches or collaterals from the left coronary system. During follow-up, functional TR continues to progress in 97.5% of the patients with newly developed functional TR after the index event. The functional TR progression rate was highest in patients with moderate to severe RV dysfunction, > moderate MR, pulmonary hypertension, and LV dysfunction [34].

7. Reoperation for isolated tricuspid regurgitation

One critical question we aim to highlight in this article is: could ignoring the RV-free wall revascularization at the time of CABG have a late clinical impacts, such as RV dysfunction and functional TR in patients with extended RCA disease? Patients presenting for surgery for isolated tricuspid regurgitation, especially in the setting of reoperation after previous CABG, are often considered high-risk and likely will not be offered another surgery. This could be related to the high mortality rates reported among different groups [35]. These patients commonly present with clinical right heart failure manifestations secondary to RV dysfunction, including liver congestion, renal dysfunction, thrombocytopenia, and volume overload, which adds to the risk of the operation in addition to the technical aspects of re-operation after CABG with patent grafts. In that sense, there might be a group of patients developing right heart failure late after a CABG procedure who will not be referred to the surgeons by the cardiologists, knowing they are high-risk patients. In the current era of evolving trans-catheter therapies, a number of high-risk surgical patients could be referred to tricuspid valve catheter therapies [36]. History of coronary artery disease, PCI, and/or CABG with RV dysfunction can be observed in the reports of trans-catheter tricuspid valve intervention along with common etiologies of functional TR such as pulmonary hypertension, atrial fibrillation, and pacemaker leads (Table 1). In these reports, approximately one-third of patients had a history of CAD, PCI, and CABG, however no granular data was available about the extent of RCA disease or the status of revascularization. Additionally, trans-catheter intervention reports do not include all patients developed TR after CABG as some of these patients may not be candidates for available trans-catheter trials. Thus, it would be difficult to estimate how many patients present with significant TR after CABG as this is not a common long-term outcome to study, which is primarily focused on survival and graft patency [12, 15, 16, 46, 47].

Study	Trans-catheter Intervention	History of CAD, PCI, CABG
Besler et al. [37] (n = 117)	MitraClip	Previous PCI 32%; Previous CABG 16%
Fam et al. [38] (n = 28)	PASCAL	CAD 46%; PreviousPCI 18%; Previous CABG 18%
Kodali et al. [39] (n = 34)	PASCAL	CAD 32%; Previous PCI 21%; Previous CABG 29%
Nickenig et al. [40] (n = 30)	Cardioband	CAD 37%; Previous PCI 20%; Previous CABG 23%
Davidson et al. [41] (n = 30)	Cardioband	CAD 13%; Previous PCI 27%; Previous CABG 3%
Nickenig et al. [42] (n = 61)	Cardioband	CAD 12%; Previous PCI 23%; Previous CABG 8%
Hahn et al. [43] (n = 15)	Trialign	Previous PCI 7%; Previous CABG 27%
Hahn et al. [44] (n = 30)	Navigate	Previous MI 27%; Previous PCI 17%; Previous CABG 33%
Fam et al. [45] (n = 25)	Evoque	CAD 28%; Previous PCI 8%; Previous CABG 20%

Table 1.

Prevalence of coronary artery disease in patients undergoing transcatheter intervention for tricuspid regurgitation.

8. Conclusions

RV-free wall ischemic disease is not routinely addressed during the current CABG practice. The impact of ignoring the RV-free wall revascularization is not well examined in dedicated studies. In the early era of CABG evolution, there was more attention to RV-free wall ischemic disease; however, less attention continued toward RV revascularization. Due to the nature of the RV tolerance to ischemia and the presence of collateralization between the RCA and the left coronary system, the majority of patients with extended RCA disease may not have a prominent early impact of RV dysfunction if they underwent standard distal bypass. Perhaps this is the rationale for surgeons deviating away from RV-free wall revascularization in modern CABG practice, as they may not observe an early impact. However, the available data in the literature that we presented in this review suggests late RV dysfunction after CABG with worsening functional TR in some patients. This in part could be related to pulmonary hypertension or left-sided cardiac pathology, but it could also be very well related to ongoing RV-free wall ischemia that results in RV cardiomyopathy and functional TR, mimicking ischemic MR. At this point, further dedicated studies focusing on the long-term impact of ignoring RV-free wall ischemia are needed to develop a consensus, if proven significant. Addressing RV-free wall ischemic disease does not require additional complex procedures, but simply adding a bypass to an acute marginal branch or mid-RCA in patients with extended RCA disease (Figure 1). This may avoid the development of late RV dysfunction and functional TR in certain groups of patients with extended RCA disease without robust collateralization.

Figure 1.

A: Preoperative coronary angiogram showing significant in-stent stenosis lesion (arrow) of the proximal right coronary artery (RCA), significant lesion (arrow) in the proximal posterior descending artery (PDA), and a medium sized marginal artery branch (AMB) originating between the two lesions. B: Operative photo of bypass grafting to acute marginal branch (AMB, dashed line) using side-to-side sequential anastomosis technique (arrow) of the bypass graft to posterior descending artery (SVG to PDA). RA: Right atrium, RV: Right ventricle.

Conflict of interest

HE has financial relationship with Edwards Lifesciences, Artivion, and LifeNet Health. Rest of authors have nothing to disclose.