Aortic stenosis in cirrhosis: Pathophysiology and management in the context of liver transplantation

Abstract

Aortic stenosis (AS), a progressive disease affecting aortic valve function, is common among individuals with metabolic and degenerative conditions, and is notably challenging to manage in patients with cirrhosis. Patients with cirrhosis frequently experience exacerbated AS symptoms due to the hyperdynamic circulatory state induced by portal hypertension, which masks early AS signs, resulting in delayed diagnosis. The coexistence of AS and liver disease significantly complicates management, particularly for those awaiting liver transplantation (LT), where untreated AS can increase perioperative morbidity and mortality. This review examines the pathophysiology, clinical manifestations, and management of AS in cirrhotic patients, with a focus on implications for LT candidates. Available treatment options, including surgical aortic valve replacement and transcatheter aortic valve replacement (TAVR), are discussed, with TAVR emerging as a preferred approach due to favorable outcomes in high-risk patients. We also explore the potential role of TAVR as a bridge to LT, with case reports showing promising, albeit anecdotal, success in restoring LT candidacy. Limitations in current perioperative risk assessment tools, which inadequately address the unique risks faced by cirrhotic patients undergoing cardiac procedures, highlight the need for multi-disciplinary care and further research to improve outcomes of patients with concomitant end-stage liver disease and AS.

Key Words: Aortic stenosis; Liver transplant; Cardio-hepatology; End stage liver disease; Aortic valve replacement

Core Tip: Managing aortic stenosis in patients with cirrhosis presents unique challenges due to overlapping pathophysiology and high surgical risks, particularly for those undergoing liver transplantation. Transcatheter aortic valve replacement is emerging as the preferred intervention for high-risk cirrhotic patients, offering improved short-term outcomes and the potential to serve as a bridge to liver transplantation. Current perioperative risk scoring systems inadequately account for liver disease, highlighting the need for specialized guidelines and a multidisciplinary approach to optimize outcomes in this complex patient population.

INTRODUCTION

Aortic stenosis (AS) is the most prevalent valvular heart disease globally[1,2]. Characterized by progressive, degenerative restriction of aortic valve leaflet opening, AS can lead to exercise intolerance, angina, syncope, cardiomyopathy, heart failure, and ultimately death. Although pharmacologic interventions can temporarily alleviate symptoms and slow disease progression, definitive treatment requires either surgical or catheter-based aortic valve replacement[3]. It is estimated that approximately 5% of patients with severe AS have concomitant cirrhosis[4], with some studies showing a direct link between metabolic-dysfunction associated steatotic liver disease (MASLD) and AS[5,6]. The management of AS in patients with cirrhosis is challenging due to the complex pathophysiology associated with chronic liver disease (CLD). At the same time, untreated AS can exacerbate symptoms of liver disease, necessitating intervention when appropriate. Management of AS is particularly relevant in the context of liver transplantation (LT) as untreated AS influences perioperative morbidity and mortality. In this review, we discuss the pathophysiology, clinical manifestations, and management of AS in patients with cirrhosis, with a focus on those who are pursuing or have undergone LT.

PATHOPHYSIOLOGY OF AS

The pathophysiology of AS is categorized into three main groups: Degenerative, congenital, and rheumatic[7]. Degenerative (or calcific) AS accounts for up to 80% of cases of AS[8]. Risk factors for degenerative AS include smoking, hypertension, diabetes and elevated low-density lipoprotein[9]. Many these risk factors overlap with those for MASLD[10]. The pathogenesis of degenerative AS parallels the aging process, where prolonged mechanical stress and cellular senescence lead to endothelial damage, promoting lipid infiltration, oxidative stress, and a subsequent inflammatory response. This results in a pro-fibrotic environment, leading to calcific remodeling that progressively thickens and restricts the aortic valve[11]. In patients with cirrhosis, these pathophysiologic processes are further exacerbated by the physiological and biochemical derangements associated with portal hypertension. Splanchnic vasodilation leads to a hyperdynamic circulatory state, resulting in a compensatory increase in cardiac output to maintain perfusion[12,13]. This exacerbates shearing forces on the endocardium, potentially accelerating valvular injury. Additionally, the systemic inflammatory state associated with CLD impairs immune function and may enhance fibrosis and calcification of the valve (Figure 1)[14].

Figure 1 Pathophysiology of aortic stenosis in patients with chronic liver disease. This figure was created with BioRender.

CLINICAL MANIFESTATIONS OF AS

Early signs of worsening AS include fatigue and decreased exercise tolerance. As the disease progresses, patients may experience dyspnea on exertion, lightheadedness, and syncopal events[7]. The hallmark physical examination finding is a crescendo-decrescendo late peaking systolic murmur, best heard at the right upper sternal border and radiating to the carotids[15]. Additional findings may include a weak and delayed carotid pulse (“pulsus parvus et tardus”), narrow pulse pressure, soft and eventually single second heart sound (S2) and rarely a third heart sound (S3)[16]. Severe AS eventually leads to congestive heart failure (with or without left ventricular systolic dysfunction) with symptoms of volume overload including progressive dyspnea, orthopnea, and lower extremity edema. In advanced stages, structural changes to the heart associated with higher afterload can lead to pump failure, thereby creating a substrate for arrhythmias and increasing the risk of sudden cardiac death[17,18].

The clinical presentation of AS in patients with CLD and MASLD is more complex. Patients with cirrhosis experience hyperdynamic circulation as a compensatory response for splanchnic vasodilation before cardiac reserve exhaustion[19]. The compensatory increase in cardiac output delays the onset of dyspnea, syncope, and chest pain and potentially masking the early signs of AS and delaying diagnosis[20]. Over time, AS can also exacerbate the hemodynamic changes of cirrhosis. Coupled with the systemic vasodilation of CLD, the fixed obstruction and diminished cardiac output characteristic of severe AS creates adverse flow gradients and low perfusion state. The resultant passive congestion further aggravates volume leading to worsening ascites and third spacing[12,21]. In summary, AS presents with more insidious symptoms in patients with cirrhosis, but its effect on cardiac dysfunction may progress rather rapidly. This underscores the importance of prompt evaluation and management of AS in patients with CLD, however current literature provides limited and often anecdotal guidance on the optimal approach for evaluating and treating AS in the context of CLD, which will be addressed in subsequent sections.

MANAGEMENT OF AS IN CIRRHOSIS

There are no specific treatment guidelines for managing AS in patients with cirrhosis. The treatment for non-severe AS revolves around managing established cardiovascular risks including hypertension control and lipid management. Commonly used medications for non-severe AS include beta-blockers, angiotensin converting enzyme-inhibitors or angiotensin receptor blockers, and 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (e.g., statins)[22]. Some of these therapies may also be beneficial for managing portal hypertension in patients with CLD. However, medical management in decompensated patients and in those with end-stage liver disease (ESLD) is challenging and limited due to baseline hypotension, volume distribution; there are also historic concerns regarding statin hepatotoxicity though these are less salient in MASLD[21,23].

Patients with severe AS or those intolerant or refractory to medical therapy may be referred for valve replacement with either surgical or catheter-based valve replacement. This decision is complex in patients with CLD as both AS and cirrhosis are associated with elevated perioperative risk. For example, severe AS has been associated with high perioperative mortality (13% vs 1.6% in the original Cardiac Risk Index)[24]. Though advancements in surgical techniques have reduced these risks, perioperative morbidity persists due to altered hemodynamics, increased myocardial oxygen demand, and the risk of arrhythmias during surgery[25]. Likewise, perioperative mortality is estimated to be two to ten times higher in patients with cirrhosis compared to those without cirrhosis, with overall morbidity rates up to 30%[26,27]. Multiple physiological changes contribute to these risks including coagulopathy, malnutrition, and immune dysfunction that predispose patients to tissue hypoperfusion and bleeding[28,29]. Further, invasive procedures are known to precipitate hepatic decompensation, and thus the decision to pursue valve replacement and its timing requires careful assessment of the risks and benefits. Scoring tools to assist in this decision have been explored and will be addressed in a later section of this paper.

AORTIC VALVE REPLACEMENT IN CIRRHOSIS

For patients in whom the benefits of aortic valve replacement outweigh the risks, determining the optimal intervention strategy and timing is complex. Two interventions are commonly used for managing severe AS in pre-transplant patients: Surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR).

SAVR

SAVR is an open-heart procedure involving midline thoracotomy, cardiopulmonary bypass, and direct valve excision and replacement[30]. Cardiopulmonary bypass poses significant risks for cirrhotic patients, as it can induce systemic inflammation and precipitate hepatic decompensation[31]. Studies have shown that patients with cirrhosis undergoing SAVR experience more complications, longer hospital stays, higher costs, and increased mortality[32,33], compared to non-cirrhotic patients. For instance, a systematic analysis by Lee et al[33] reported longer hospital stays (13.3 vs 11.3 days, P < 0.001), increased costs (273487 dollars vs 238097 dollars, P < 0.001), and higher rates of respiratory failure [9.02% vs 7.19%, odds ratio: 1.28, 95% confidence interval (CI): 1.03-1.59] and bleeding in cirrhotic patients (8.43% vs 6.33%, odds ratio: 1.36, 95%CI: 1.08-1.71). Multivariate analysis demonstrated a 2.6-fold increase in mortality associated with cirrhosis (95%CI: 2.00-3.38).

TAVR

TAVR is a less invasive procedure that involves arterial access, most commonly through the femoral artery, and catheter-assisted placement of a replacement valve, guided by echocardiography and/or fluoroscopy. TAVR use has increased by 250% over the past decade due to its advantages in high-risk patients. Several studies have demonstrated the TAVR procedure to be associated with improved outcomes in patients CLD and AS compared to medical therapy alone[34-36]. Despite this, concerns of safety have limited widespread use in patients with CLD, particularly with ESLD. While the American Heart Association cites CLD as a risk factor for poor outcomes with TAVR, patients with cirrhosis have not exhibited higher rates of short-term mortality or cardiac complications compared to the general population in several studies, though outcomes vary with liver disease severity[37-39]. The strongest data for this comes from a multi-centered, observational study assessing outcomes and prognostic factors of TAVR procedures in patients with and without liver disease[39]. Mild periprocedural kidney injury was more common in CLD patients however severe complications such as stroke, bleeding, and death events were similar. However, these data should be interpreted with caution, with favorable prognosis being less common in Child-Turcotte-Pugh (CTP) class C cirrhosis, particularly beyond 2 years where mortality may be higher even in patients who undergo LT[39,40]. In addition, a recent population-based cohort study reported that despite there being an increase in the number of TAVR procedures performed in patients with cirrhosis from 2011 to 2020, the gross number of complications and mortality was lower[41].

SAVR vs TAVR

Several retrospective studies that have directly compared SAVR and TAVR in patients with cirrhosis. In general, TAVR has been associated with shorter hospital length for stay and shorter healthcare costs[42], which is likely due lower rates of complications and improved tolerance of the TAVR procedure. Intraoperatively, TAVR is linked to lower rates of cardiogenic shock and decreased need for mechanical circulatory support compared to SAVR[43]. Postoperatively, TAVR has been associated with lower rates of bleeding[44], arrhythmias[42], vascular complications, hepatorenal syndrome[45], and 30-day readmissions[43] and mortality[46] compared to SAVR. Although long-term data on TAVR outcomes are limited by its recency, durability has emerged as a concern. A meta-analysis by Ler et al[47] showed that TAVR may be associated with higher rates of perivalvular regurgitation, aortic regurgitation, and reintervention at 1, 3, and 5 years when compared to SAVR. From our review, there have not been studies specifically comparing valve durability of SAVR compared to TAVR in patients with cirrhosis. Given the accelerated degeneration of native aortic valves in patients with cirrhosis as described previously, this may be an important area for further investigation.

While studies report lower risk of death after TAVR compared to SAVR[46], this may depend on disease severity. One small prospective study found that among patients with a Model for End Stage Liver Disease (MELD) score < 12, survival was lower following TAVR compared to SAVR (median survival of 2.8 years vs 4.4 years, P = 0.047)[37]. In patients with a MELD score ≥ 12, survival rates after TAVR, SAVR, and medical therapy alone were similar (1.3 years vs 2.1 years vs 1.6 years, respectively, P = 0.53). Prospective studies evaluating mortality are limited. The PARTNER trial, a randomized controlled study comparing TAVR with medical therapy in inoperable AS, found that liver disease was predictive of mortality in SAVR but not TAVR patients[48]. The findings of the PARTNER trials support the use of TAVR over SAVR, especially in those with compensated liver disease.

In summary, AVR can be a viable option for patients with CLD and severe AS, with TAVR being the generally preferred modality due to more favorable outcomes. The available prospective data support short mortality benefit for patients with cirrhosis, but long-term data is limited. Unsurprisingly, AVR-related mortality following LT cohort is higher. However, for patients with ESLD, the procedure may not prolong life in patients in the absence of LT, and a case-by-case risk-benefit analysis is warranted with a multidisciplinary team before considering definitive options for such a high-risk cohort. This analysis should ideally be performed by a multidisciplinary team, comprising cardiac surgeons, transplant surgeons, hepatologists, and structural cardiologists- those who are best equipped to prognosticate procedural outcomes for CLD and AS patients.

SEVERE AS PRIOR TO LIVER TRANSPLANT: TAVR AS BRIDGE

There are several additional factors to consider when managing AS in the pre-LT patient. The hemodynamic strain of LT in those with AS is associated with an increased risk of acute cardiac decompensation and perioperative death. For this reason, advanced valvular pathology has historically been a barrier to LT. In recent years, there has been increasing evidence to support the use of TAVR to mitigate the perioperative cardiovascular risk of solid organ transplantation and potentially restore transplant candidacy[49,50]. Beyond perioperative mortality risk for effectively managing AS in patients pending LT has potential benefits of alleviating symptoms of dyspnea and fatigue which can optimize their functional status prior to surgery.

Evidence to support this practice is limited to around a dozen case reports (Table 1)[49]. For example, Silvestre et al[51] reported the case of a patient with severe AS considered too high-risk for cardiac surgery due to cirrhosis and thrombocytopenia who underwent successful TAVR and was eligible for LT six months later . Similar cases were reported by Cabasa et al[52] and Kaafarani et al[53], where patients with hepatic decompensations underwent TAVR with minimal complications, and subsequently received LT. This strategy has employed in a patients with severe hepatic dysfunction and high-short term mortality risks (MELD > 20) who, despite post-TAVR complications (bacteremia, hepatorenal syndrome) ,were successfully bridges to LT with an uncomplicated post-LT course[54-57]. Several cases have been reported in patients with bicuspid vales as well, including a patients who required pre-and post LT valve procedures[58,59]. Table 2 summarizes case reports with their unique clinical features, complications, and LT outcomes.

Table 1 Transcatheter aortic valve replacement as a bridge to liver transplant: Summary of published cases.

Ref.	Case description	Outcome
Silvestre et al[51], 2014	66-year-old male; mean/peak gradient 48/71; MELD 16	No post-TAVR complications; underwent LT 6 months later; no cardiovascular complications at time of LT
Kaafarani et al[53], 2023	63-year-old male; mean/peal gradient: 38.3/67.7; decompensations: Varices, ascites	Post-TAVR stroke like symptoms that self-resolved; successful LT post-TAVR; graft survival > 2 years
Wilkey et al[54], 2016	Severe AS and moderate aortic insufficiency; MELD 29; CTP Class C	Post TAVR complications: Bacteremia and hepato-renal syndrome; still underwent uncomplicated LT one month later
Nemati et al[55], 2008	39-year-old-male with viral hepatitis; decompensations: Severe coagulopathy; CTP Class C	No Post TAVR complications: Successful LT months 2 later
Rejjal et al[56], 2017	56-year-old female; decompensations: Ascites, hepato-renal syndrome; MELD-Na 21	Post-TAVR complications: None; successful LT months 6 later
Kaliamoorthy et al[58], 2020	Patient with bicuspid aortic stenosis; MELD 21	Kiving donors LT 6 months later; no documented complications
Pocar et al[59], 2007	39-year-old male with hydatids liver disease with acute endocarditis; CTP Class C; MELD 26	Post-TAVR complications: Wound infection; successful valve re-replacement following LT
Levy et al[57], 2020	60-year-old male; CTP A, MELD 11; no decompensations	Successful, uncomplicated TAVR; successful LT 6 months later
Levy et al[57], 2020	50-year-old female; CTP B, MELD 19; decompensations: Ascites, hepatic encephalopathy, spontaneous bacterial peritonitis	Successful LT 6 months later

MELD: Model for end stage liver disease; TAVR: Transcatheter aortic valve replacement; LT: Liver transplantation; CTP: Child-Turcotte-Pugh.

Table 2 Scoring systems used in aortic valve replacement.

System	Description	Strengths	Limitations
Child-Turcotte Pugh	Developed for surgical risk stratification; assesses risk using five parameters: Ascites, encephalopathy, bilirubin, albumin, and INR	Incorporates clinical factors like ascites and encephalopathy	Subjectivity in grading ascites and encephalopathy
Model for End-Stage Liver Disease	Developed for short-term mortality prediction and organ allocation; calculates score from bilirubin, creatinine, sodium, INR; recently incorporated sex + albumin (3.0)	Objective lab values reduce subjectivity; new version incorporates gender	Does not directly assess cardiac risk; limited predictive accuracy for perioperative outcomes; historic gender vias; several iterations
Model for End-Stage Liver Disease- excluding INR	Modified MELD score that excludes INR	More accurate in predicting 6-month mortality post-TAVR; May not confound bleeding risk with INR	Not routinely used in adult patients
European System for Cardiac Operative Risk Evaluation	Assesses risk of mortality after cardiac surgery based on comorbidities	Widely used for preoperative cardiac risk assessment; considers type of cardiac surgery performed	Does not incorporate liver function; underpredicts mortality in cirrhotic patients
Society of Thoracic Surgeons Risk Score	Assesses risk of mortality after cardiac surgery based on anthropometric profile, comorbidities, medications, labs, and socioeconomic factors	Broader assessment of clinical status; commonly used for valve replacement; includes history of liver disease	May under-estimate risk in cirrhosis; poorly associated with outcomes in patients with cirrhosis in present studies
Veterans Outcomes and Costs Associated with Liver Disease Model	Developed to predict post-operative mortality in patients with cirrhosis, for any surgical procedures	Demonstrated superior discrimination than other surgical risk calculators	Lack of prospective data; data predominantly in men

INR: International normalized ratio; MELD: Model for end stage liver disease; TAVR: Transcatheter aortic valve replacement.

While these cases highlight promising outcomes, there is potential for publication bias with use of case reports. To date, no prospective studies or randomized trials have evaluated TAVR as a bridge to LT compared to alternative strategies. Currently there are no established absolute contraindications to TAVR as a bridge to LT. However, in many clinical scenarios, its practicality may be limited. Notably, severe pulmonary hypertension is associated with increased mortality risk in both TAVR patients and LT candidates and thus would likely not be a good candidate for this sequential intervention[60,61]. Concurrent end stage non-cardiac, non-liver organ failure, the presence of CTP class C cirrhosis, and active infection are other factors that may limit the feasibility of this approach. The lack of strong scientific evidence to support or oppose TAVR as a bridge in this context highlights a critical gap in the literature and an area of future investigation.

A SPECIAL SCENARIO: CONCURRENT LT AND AVR

There are certain cases in which LT and AVR (LT-AVR or AVR-LT) have been performed concurrently (i.e., the same hospital admission or procedure). This scenario arises when patients with advanced valvular pathology and ESLD are deemed unsafe to undergo LT due to the risk of cardiac decompensation and also deemed unsafe to undergo AVR due to risk of hepatic decompensation[62]. Specifically, these surgeries are reserved for patients with structural heart disease, multivessel coronary disease or severe valvular disease with heart failure, in the setting of end stage liver disease, such that the untreated organ is at high risk of decompensation[63]. The first simultaneous AVR with LT was reported by Parker et al[64] in 2001, when a 56-year-old male with ESLD was admitted to the hospital for congestive heart failure in the setting of progressive AS. The patient was previously delisted for LT when a transthoracic echocardiogram revealed a narrow valve, with a peak valvular gradient of 64 mmHg, consistent with moderate-to-severe AS. He was declined for valvuloplasty prompting the multi-disciplinary team to consider a combined procedure. After being admitted to the hospital for a heart failure exacerbation and renal failure, he successfully underwent a combined LT-SAVR and was discharged from the hospital with improved renal function on day 30. A second case reported in 2003 was of a 49-year-old patient who received LT-AVR and whose post-operative course was complicated by pulmonary embolism originating in the graft liver[65].

Combined AVR-LT procedures pose significant operative risks for patients who already present with end-stage multi-system disease. The most common complication of AVR-LT appears to be bleeding in the setting of fibrinolysis[62]. In a series of seven patients, two patients suffered subsequent hemorrhagic complications (abdominal and mediastinal)[66]. Suggested steps to combating this complication have been suggested aprotinin administration throughout the procedure, the use of a bioprosthetic valve to avoid increased anticoagulation requirements, and the administration of conjugated estrogen[64,66]. Thus far, a majority of combined AVR-LT have been SAVR, and though data on this unique population of patients is limited, retrospective analyses and reviews have cited modest success in outcomes. A single-center study including seven patients that underwent combined AVR-LT concluded that survival was modestly improved relative to that of heart operations without LT or LT without cardiac operation[67]. In a retrospective cohort including eight patients (MELD 20-27, CTP A) who underwent AVR-LT, the short-term mortality was 25%. The causes of death included myocardial infarction (n = 1) and a hemorrhagic stroke (n = 1). Of the six surviving patients, all but one was transferred out of the intensive care unit within one week and all were discharged from the hospital within one month[68]. Compared to bride or staged procedures, available evidence suggests combined LT-AVR is associated with similar in-hospital mortality but slightly longer hospital stays[69].

SCORING SYSTEMS FOR AVR AND THEIR LIMITATIONS

Several scoring systems exist to assist decision-making related to cardiac surgery, including American College of Rheumatology. Two commonly referenced scoring systems are the European System for Cardiac Operative Risk Evaluation and the Society of Thoracic Surgery (STS) Risk Score (Table 2)[70]. While they carry predictive power in the general population, these scoring systems do not account for the physiological derangements seen in liver disease, leading to inaccuracies in assessing surgical risk for cirrhotic patients[50,71]. For example, in a study 218 cirrhotic patients undergoing cardiac surgery, the European System for Cardiac Operative Risk Evaluation II significantly underpredicted mortality mortality[72]. Likewise, the STS score has been shown to be a poor predictor of long-term survival compared to cirrhosis-related risk models that were not developed for cardiac surgery[37].

In most cases, non-specific risk stratification tools for cirrhosis are used, including the CTP score and the MELD score[73,74]. The CTP score was developed in the 1960’s as a means to risk stratify patients undergoing surgery for portal decompression, and was used thereafter for general surgical evaluation[73]. The MELD score was originally developed as a tool to prognosticate short term mortality and improve organ allocation in ESLD, and now serves as a surrogate for the severity of liver disease in many contexts[75]. The CTP score has been critiqued for its subjectivity in grading ascites and hepatic encephalopathy compared to the objective lab values used in the MELD score. On the other hand, the has undergone several variations including the more recent MELD-sodium (MELD-Na) score and the MELD-3.0. Studies have evaluated the potential for both CTP and MELD predict outcomes after cardiac surgery, with a CTP score > 7 points and a MELD-Na score > 13 points to signify high-risk[76]. While both scores demonstrate discriminative ability, CTP score > 7 has exhibited higher sensitivity and specificity than MELD-Na > 13 for cardiac risk. Individual laboratory parameters, such as bilirubin, albumin, and international normalized ratio (INR), were also associated with poorer prognosis, but do not outperform CTP or MELD scores.

Several variations of the MELD score have been studied in CLD patients undergoing TAVR specifically. The MELD-XI is a modified calculation of the MELD excluding the INR that was developed as a risk stratification tool for patients with CLD on chronic anti-coagulation. In a study of > 700 patients with cirrhosis, MELD-XI (MELD excluding INR) more accurately predicted 6 -month mortality after TAVR in patients with liver disease than other risk prediction tools[77]. In this study, a MELD-XI > 10 points was identified as a predictor of increased risk of stroke, bleeding, acute kidney injury, and 30-day mortality. In a comparative analysis of TAVR and SAVR in 105 patients with cirrhosis, Peeraphatdit et al[37] concluded that MELD scores independently predicted long-term survival while STS score did not. When interpreting these studies, it must be cautioned that the MELD scoring system has historically instilled gender disparity in the evaluation of ESLD patients prior to the introduction MELD-3.0, potentially influencing risk stratification of women in these studies[78].

The Veterans Outcomes and Costs Associated with Liver Disease Model developed at the University of Pennsylvania is a relatively newer risk assessment tool specifically designed to predict postoperative mortality in patients with cirrhosis undergoing surgery[79]. In a large retrospective study, the Veterans Outcomes and Costs Associated with Liver Disease Model developed at the University of Pennsylvania demonstrated superior performance with respect to predicting mortality after surgery compared to MELD, MELD-Na and CTP scores in retrospective analyses, though this study was comprised near completely of men (> 97%) and < 10% of patients underwent a cardiac procedure. Both prospective and gender inclusive data are needed prior to routine implementation of this model for high-risk cardiac procedures.

FUTURE AREAS OF STUDY

To date, the American Gastroenterological Association, American College of Gastroenterology, American Heart Association, the American Thoracic Society and the American College of Cardiology, do not provide specific guidelines for risk stratification or management of cirrhotic patients undergoing cardiac procedures[80]. As such, modernized models or adaptations to current models are needed to better assess patients with cirrhosis undergoing cardiac procedures. Incorporation of liver disease severity to cardiac models, as well as malnutrition screening and frailty assessment scores[81], have all been suggested as additional factors to further enhance risk stratification, which are areas of opportunity in the coming years[72].

In addition, novel technologies for AVR to improve durability, reduce complications, and limit time under anesthesia or cardiac bypass are emerging and may influence approach to AVR in patients with cirrhosis. For example the use of novel bioprosthetic tissues aimed at improving durability and reducing calcification have been approved in both TAVR and SAVR[82]. There have also been advances in self-expanding and re-sheathable valves to reduce complications such as perivalvular leakage[83]. Additionally suture-less valves in SAVR are being employed which can reduce time under cardiac bypass[84]. As these and other technologies become available, it will be prudent to have an understanding of present risk stratification to safely plan prospective studies in this high-risk cohort.

CONCLUSION

AS and CLD independently confer significantly increased morbidity and mortality. Patients with co-existing disease are exceptionally high risk, especially when advanced, posing major interdisciplinary challenges for healthcare providers. Patient with AS initially present with symptoms of reduced cardiac output, such as dyspnea and syncope, which may progress to signs of decompensated heart failure. Because these symptoms are frequently masked in patients with CLD, diagnosis can be delayed allowing the combination of valvular disease and circulatory changes with cirrhosis to accelerate decompensation and cardiac dysfunction. Current evidence favors TAVR as the preferred option in patients with CLD who require. In addition, promising anecdotal evidence supports the use of TAVR as a bridge to LT a potential role for combined LT-AVR, though prospective studies in this area are limited. Designing randomized controlled trials for bridging procedures may not be feasible given the very sick patient population and high risks associated with both treated and untreated disease. The current scoring systems used to evaluate perioperative risk for cardiac procedure have not yet been meaningfully adjusted to account for the increased risk of intervention in patients with liver disease. The development of a tool to risk-stratify patients with liver disease who require cardiac intervention is an area that requires further research.