Outcomes and quality of life in patients receiving durable left ventricular assist device with biventricular support.

BACKGROUND: Patients requiring biventricular support (BIVAD) face higher morbidity than those undergoing durable left ventricular assist device (LVAD) implantation alone. The goal of the current study was to evaluate quality of life (QOL) of patients with LVAD therapy in the modern era, stratified by use of biventricular support. METHODS: All patients undergoing LVAD at our center were reviewed between October 2017 and September 2021. Patients were stratified by perioperative use of BIVAD. Patients were administered a telephone survey consisting of the Kansas City Cardiomyopathy Questionnaire (KCCQ-12) as well as free-responses regarding satisfaction surrounding their operation. Outcomes included survival, KCCQ-12 metrics, and thematic analysis of free response questions. RESULTS: 92 patients were identified, of whom 26 (28%) received BIVAD support. BIVAD patients had more preoperative ECMO use (54% vs. 12%, p < 0.001) and lower INTERMACS scores (Category 1: 46% vs. 14%, p = 0.001). Three-year survival was 73.8% among LVAD-alone patients and 50.1% among BIVAD patients (log-rank p = 0.022). Median composite KCCQ-12 score was 78 (57-88). No differences in composite or any component scores were noted between groups. 76% of patients report they would be moderately or extremely like to go through surgery again if given repeat choice. The most common themes expressed were overall gratitude (24%) and disappointment with device-related restrictions (20%). CONCLUSIONS: Patients requiring BIVAD therapy have more advanced shock, longer associated hospital courses, and lower long-term survival. However, those that survive enjoy similar overall quality of life, and many endorse positive outlooks on their surgical course. Continued assessments of quality of life are important in providing patient-centered LVAD care.

Vasohibin inhibition improves myocardial relaxation in a rat model of heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome associated with increased myocardial stiffness and cardiac filling abnormalities. Prior studies implicated increased α-tubulin detyrosination, which is catalyzed by the vasohibin enzymes, as a contributor to increased stabilization of the cardiomyocyte microtubule network (MTN) and stiffness in failing human hearts. We explored whether increased MTN detyrosination contributed to impaired diastolic function in the ZSF1 obese rat model of HFpEF and designed a small-molecule vasohibin inhibitor to ablate MTN detyrosination in vivo. Compared with ZSF1 lean and Wistar Kyoto rats, obese rats exhibited increased tubulin detyrosination concomitant with diastolic dysfunction, left atrial enlargement, and cardiac hypertrophy with a preserved left ventricle ejection fraction, consistent with an HFpEF phenotype. Ex vivo myocardial phenotyping assessed cardiomyocyte mechanics and contractility. Vasohibin inhibitor treatment of isolated cardiomyocytes from obese rats resulted in reduced stiffness and faster relaxation. Acute in vivo treatment with vasohibin inhibitor improved diastolic relaxation in ZSF1 obese rats compared with ZSF1 lean and Wistar Kyoto rats. Vasohibin inhibition also improved relaxation in isolated human cardiomyocytes from both failing and nonfailing hearts. Our data suggest the therapeutic potential for vasohibin inhibition to reduce myocardial stiffness and improve relaxation in HFpEF.

Re-repair for mitral insufficiency.

BACKGROUND: Mitral valve repair provides superior outcomes to replacement for primary MR. Whether this is true following previous repair is unknown. We present the results of a strategy of re-repair for failed mitral valve repair. We examine patients who were brought to the operating room for an intended mitral valve re-repair. METHODS: We reviewed the last one decade of our institutional mitral valve databases at The University of Pennsylvania and Plano Heart Hospital and identified patients undergoing repeat mitral valve repair, in whom the index operation was mitral valve repair. We analyzed their operative details, clinical and echocardiographic outcomes. RESULTS: Between 2008 and 2021, 71 patients (aged 61.5 ±10.7 years, 20% female) underwent mitral valve reoperation at an mean of 6.24 ±7.62 years following index mitral repair. 20% of patients presented with NYHA class III/IV symptoms. At index operation, 34 (47.9%) had repair through a right mini-thoracotomy. 15 patients (21.1%) required the reoperation within one year. There were 0 early and 8 late deaths. One patient who underwent mitral replacement instead of repair, required reoperation for paravalvular leak during the follow-up period. Three patients required mitral valve replacement at an average of 2.28 ±2.03 years following initial mitral valve re-repair. CONCLUSIONS: Mitral re-repair can be performed with acceptable results at a valve reference center. Durability and functional advantages of this approach remain to be proven.

Outcomes and quality of life in patients receiving mitral surgery for asymptomatic disease.

Objectives: We sought to characterize the demographics, outcomes, and quality of life of asymptomatic patients undergoing mitral valve surgery at our center over a 10-year period. Methods: Adults undergoing mitral surgery were retrospectively reviewed between 2010 and 2019. Patients were included if deemed asymptomatic by review of referring cardiologist and surgeon consultation. Patients were administered a telephone survey consisting of the Kansas City Cardiomyopathy Questionnaire as well as free-response regarding satisfaction surrounding their operation. Outcomes included survival, Kansas City Cardiomyopathy Questionnaire metrics, and thematic analysis of free response questions. Results: A total of 145 patients were identified who were deemed asymptomatic. Their average age was 60.3 ± 12.1 years, and 71% were male. No patients had endocarditis, and 34% had decreased ejection fraction (<60%). Repair was achieved in 95% of patients. Median length of stay was 6 (5-8) days. Ten-year survival was 91%, with no differences noted by ejection fraction. Composite Kansas City Cardiomyopathy Questionnaire score was 100 (96-100). The lowest component score was "Quality of Life," with 22% of patients reporting being "mostly satisfied" with present cardiac status. Most common themes expressed were gratitude with surgery results (58%), satisfaction with being able to stay active (23%), and happiness with early disease treatment (21%). Only 1 patient (0.7%) expressed regret with surgery choice. Conclusions: Mitral surgery for asymptomatic disease can be performed with good long-term outcomes in select patients, and the majority experience excellent quality of life and satisfaction with current health. Continued assessments of quality of life are important in evaluating outcomes of mitral surgery as indications grow.

Deactivation of LVAD support for myocardial recovery-surgical perspectives.

Left ventricular assist devices (LVADs) are excellent therapies for advanced heart failure patients either bridged to transplant or for lifetime use. LVADs also allow for reverse remodeling of the failing heart that is often associated with functional improvement. Indeed, growing enthusiasm exists to better understand this population of patients, whereby the LVAD is used as an adjunct to mediate myocardial recovery. When patients achieve benchmarks suggesting that they no longer need LVAD support, questions related to the discontinuation of LVAD therapy become front and center. The purpose of this review is to provide a surgical perspective on the practical and technical issues surrounding LVAD deactivation.

Mortality and morbidity after combined heart and liver transplantation in the failing Fontan: An updated dual center retrospective study.

INTRODUCTION: As the adult Fontan population with Fontan associated liver disease continues to increase, more patients are being referred for transplantation, including combined heart and liver transplantation. METHODS: We report updated mortality and morbidity outcomes after combined heart and liver transplant in a retrospective cohort series of 40 patients (age 14 to 49 years) with Fontan circulation across two centers from 2006-2022. RESULTS: The 30-day, 1-year, 5-year and 10-year survival rate was 90%, 80%, 73% and 73% respectively. Sixty percent of patients met a composite comorbidity of needing either post-transplant mechanical circulatory support, renal replacement therapy or tracheostomy. Cardiopulmonary bypass time > 283 min (4.7 h) and meeting the composite comorbidity were associated with mortality by Kaplan Meier analysis. CONCLUSION: Further study to mitigate early mortality and the above comorbidities as well as the high risk of bleeding and vasoplegia in this patient population is warranted.

A heart transplant center experience with basiliximab induction strategies: A double edged sword?

BACKGROUND: The use of induction immunosuppression for heart transplantation (HT) is debated given the uncertain benefit and potential risks of infection and malignancy. METHODS: This is a retrospective single-center analysis of 475 consecutive HT recipients from 2003 to 2020 grouped by use of induction with basiliximab group (BG) and the no basiliximab group (NBG). Subgroup analysis by era compared pre-2016 standard-basiliximab (BX) induction and 2016-2020 with selective-BX use as part of a calcineurin-inhibitor-sparing regimen. RESULTS: When adjusted for confounders (sex, age, PRA, eGFR), the BG was less likely to have acute cellular rejection (ACR) (OR.42, p < .001), but had more antibody mediated rejection (AMR) (OR 11.7, p < .001) and more cardiac allograft vasculopathy (CAV) (OR 3.8, p = .04). There was no difference between BG and NBG in the incidence of malignancies or infections. When stratified by era (pre-2016 vs. 2016-2020), ACR remained less common in the BG than the NBG (36% vs. 50%, p = .045) groups, while AMR remained more common (9.7 vs. 0% p = .005). There was no significant difference in conditional survival comparing pre-and post-2016 NBG (HR 2.20 (95% CI.75-6.43); however, both pre-2016 BG and post-2016 BG have significantly higher mortality (HR 2.37 [95% CI 1.02-5.50) and HR 2.69 (95% CI 1.08-6.71), p = .045 and.03, respectively]. CONCLUSION: Basiliximab reduces the incidence of ACR but increases the risk of AMR, CAV, and may be associated with increased mortality. Mechanistic studies are needed to describe a potential T-cell-escape mechanism with enhanced humoral immunity.

The Tricuspid Valve: A Review of Pathology, Imaging, and Current Treatment Options: A Scientific Statement From the American Heart Association.

Tricuspid valve disease is an often underrecognized clinical problem that is associated with significant morbidity and mortality. Unfortunately, patients will often present late in their disease course with severe right-sided heart failure, pulmonary hypertension, and life-limiting symptoms that have few durable treatment options. Traditionally, the only treatment for tricuspid valve disease has been medical therapy or surgery; however, there have been increasing interest and success with the use of transcatheter tricuspid valve therapies over the past several years to treat patients with previously limited therapeutic options. The tricuspid valve is complex anatomically, lying adjacent to important anatomic structures such as the right coronary artery and the atrioventricular node, and is the passageway for permanent pacemaker leads into the right ventricle. In addition, the mechanism of tricuspid pathology varies widely between patients, which can be due to primary, secondary, or a combination of causes, meaning that it is not possible for 1 type of device to be suitable for treatment of all cases of tricuspid valve disease. To best visualize the pathology, several modalities of advanced cardiac imaging are often required, including transthoracic echocardiography, transesophageal echocardiography, cardiac computed tomography, and cardiac magnetic resonance imaging, to best visualize the pathology. This detailed imaging provides important information for choosing the ideal transcatheter treatment options for patients with tricuspid valve disease, taking into account the need for the lifetime management of the patient. This review highlights the important background, anatomic considerations, therapeutic options, and future directions with regard to treatment of tricuspid valve disease.

Transcatheter aortic valve replacement achieves similar predicted effective orifice area to surgical aortic valve replacement in bicuspid aortic stenosis.

BACKGROUND: Studies comparing transcatheter and surgical aortic valve replacement (TAVR and SAVR) for patients with trileaflet aortic stenosis (AS) have found similar or larger effective orifice area (EOA) for TAVR prostheses. To our knowledge, no studies have compared EOA in patients undergoing TAVR versus SAVR for bicuspid AS. METHODS: We retrospectively compared prosthetic valvular sizing and predicted EOA for patients with bicuspid AS undergoing TAVR or SAVR at our institution between January 1, 2016, and December 31, 2021. We excluded patients undergoing procedures for indications other than AS and those without a pre-procedural gated Chest CT. Comparisons included demographics, comorbidities, annular size, prosthetic valve size, predicted EOA and prosthesis-patient mismatch (PPM) for TAVR (N = 78) and SAVR (N = 74) cohorts. RESULTS: TAVR patients had smaller pre-procedural annular area (501.7 mm2 vs. 571.8 mm2, p < 0.05) and annular perimeter (80.6 mm vs. 86.5 mm, p < 0.05), but larger mean implanted prosthetic valve size (26.4 mm vs 24.2 mm, p < 0.001) compared to SAVR patients. No differences were observed in predicted EOA, predicted EOA indexed to patient body surface area (EOAi), or predicted PPM grade between TAVR and SAVR groups, including in cohorts sorted by pre-procedural annular size. CONCLUSIONS: For bicuspid AS patients undergoing aortic valve replacement, TAVR achieves similar predicted EOA to SAVR. These data support the use of TAVR in selected patients with bicuspid AS and can inform heart team discussions.

Center Volume Predicts Improved Early Outcomes in Multiorgan Heart Transplantation.

PURPOSE: Center volume is associated with improved survival after isolated heart transplant, but its impact on multiorgan heart transplant (MHT) outcomes is unknown. This study examines the impact of institutional MHT volume on MHT outcomes. METHODS: Adult patients undergoing first time MHT from 2011 to 2021 were identified in the United Network for Organ Sharing database. Transplant centers were annually classified as low-, medium-, or high-volume if they performed <3, 3 to 5, or ≥6 MHTs that year, respectively. Graft failure was defined as death, failure, or re-transplantation of any allograft. RESULTS: A total of 1860 MHTs were performed at 104 centers, including 482 (26%) at low-, 601 (32%) at medium-, and 777 (42%) at high-MHT volume centers. Noncardiac allografts included kidney (83%), liver (16%), and lung (2%). The proportion of MHTs performed at high-volume centers increased from 10% in 2011 to 62% in 2021. Recipient age, race, and body mass index did not vary by center volume (all P > .05). Patients at high-volume centers were more likely to be in the intensive care unit pre-transplant (58% vs 44%, P < .001) and have shorter waitlist times (47 vs 92 days, P < .001) than those at low-volume centers. 30-day graft survival was higher in combined medium- and high-volume compared with low-volume centers (95% vs 92%, P = .004). Increasing center MHT volume was protective against 30-day graft failure (adjusted hazard ratio 0.93 [0.88-0.98]) on multivariate Cox regression. CONCLUSIONS: Higher MHT volume is associated with improved early graft survival after MHT, which may justify centralizing the performance of MHTs to high-volume centers.

Heart Retransplantation Under the 2018 Adult Heart Allocation Policy.

BACKGROUND: The purpose of the present study was to characterize the impact of the 2018 adult heart allocation policy change on waiting list and posttransplant outcomes of heart retransplantation in the United States. METHODS: All adults listed for heart retransplantation from May 2015 to June 2022 were identified using the United Network for Organ Sharing database. Patients were stratified into eras (era 1 and era 2) based on the heart allocation change on October 18, 2018. Competing risks regressions and Cox proportional hazards models were used to assess differences across eras in waiting list outcomes and 1-year posttransplant survival, respectively. RESULTS: The analysis included 356 repeat heart transplant recipients, with 207 (58%) receiving retransplantation during era 2. Patients who received a retransplant in era 2 were more commonly bridged with extracorporeal membrane oxygenation (21% vs 8%, P < .01) and intra-aortic balloon pump (29% vs 13%, P < .001) and had a lower likelihood of death/deterioration on the waiting list (subdistribution hazard ratio, 0.52; 95% CI, 0.33-0.82) compared with those in era 1. Rates of 30-day mortality (7% vs 7%, P = .99) and 1-year survival (82% vs 87%, P = .27) were not significantly different among retransplantation recipients across eras. After adjustment, retransplantation in era 2 was not associated with an increased hazard of mortality (adjusted hazard ratio, 1.13; 95% CI, 0.55-2.30). The gap in 1-year mortality between primary transplant and retransplant recipients increased from era 1 to 2. CONCLUSIONS: Heart retransplantation candidates have experienced improved waiting list outcomes after the 2018 adult heart allocation policy, without significant changes to posttransplant survival.

A multicenter evaluation of the HeartMate 3 risk score.

BACKGROUND: The Heartmate 3 (HM3) risk score (HM3RS) was derived and validated internally from within the Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3 (MOMENTUM 3) trial population and provides 1- and 2-year mortality risk prediction for patients in those before HM3 left ventricular assist device (LVAD) implantation. We aimed to evaluate the HM3RS in nontrial unselected patients, including those not meeting inclusion criteria for MOMENTUM 3 trial enrollment. METHODS: Patients who underwent HM3 LVAD implant at 1 of 7 US centers between 2017 and 2021, with at least 1-year follow-up, were included in this analysis. Patients were retrospectively assessed for their eligibility for the MOMENTUM 3 trial based on study inclusion and exclusion criteria. HM3RS risk discrimination was evaluated using time-dependent receiver operating characteristic curve analysis for 1-year mortality for all patients and further stratified by MOMENTUM 3 trial eligibility. Kaplan-Meier curves were constructed using the HM3RS-based risk categories. RESULTS: Of 521 patients included in the analysis, 266 (51.1%) would have met enrollment criteria for MOMENTUM 3. The 1- and 2-year survival for the total cohort was 85% and 81%, respectively. There was no statistically significant difference in survival between those who met and did not meet enrollment criteria at 1 (87% vs 83%; p = 0.21) and 2 years postimplant (80% vs 78%; p = 0.39). For the total cohort, HM3RS predicted 1-year survival with an area under the curve (AUC) of 0.63 (95% confidence interval [CI]: 0.57-0.69, p < 0.001). HM3RS performed better in the subset of patients meeting enrollment criteria: AUC 0.69 (95% CI:0.61-0.77, p < 0.001) compared to the subset that did not: AUC 0.58 (95% CI: 0.49-0.66, p = 0.078). CONCLUSIONS: In this real-world evidence, multicenter cohort, 1- and 2-year survival after commercial HM3 LVAD implant was excellent, regardless of trial eligibility. The HM3RS provided adequate risk discrimination in "trial-like" patients, but predictive value was reduced in patients who did not meet trial criteria.

Prospective Study of Risk Factors for Postoperative Atrial Fibrillation After Cardiac Surgery.

INTRODUCTION: To examine risk factors for new-onset postoperative atrial fibrillation (POAF) after cardiac surgery. METHODS: Patients enrolled in the Cardiothoracic Surgical Trials Network multicenter, randomized trial of rate control versus rhythm control for POAF were included. Predictors of POAF were determined using multivariable logistic regression. RESULTS: Among the 2104 patients who were enrolled preoperatively, 695 developed POAF (33.0%). Rates of POAF were 28.1% after isolated coronary artery bypass grafting (CABG), 33.7% after isolated valve repair or replacement, and 47.3% after CABG plus valve repair or replacement. Baseline characteristics associated with an increased risk of POAF identified on multivariable analysis included older age (odds ratio [OR] 1.57; 95% confidence interval [CI] 1.42-1.73, per 10 y), White race or non-Hispanic ethnicity (OR 1.52; CI: 1.11-2.07), history of heart failure (OR 1.55; CI: 1.16-2.08), and history of hypothyroidism (OR 1.42; CI 1.04-1.94). The type of cardiac procedure was associated with an increased risk of POAF with both isolated valve repair or replacement (OR 1.33, CI 1.08-1.64) and combined CABG plus valve repair or replacement (OR 1.64, CI 1.24-2.17) having increased risk of POAF compared to isolated CABG. No preoperative cardiac medication was associated with POAF. CONCLUSIONS: In this prospective cohort of patients, older age, a history of hypothyroidism, a history of heart failure, and valve repair or replacement, with or without CABG, and White non-Hispanic race were associated with an increased risk of POAF.

Short stature is a risk factor for heart transplant morbidity and mortality.

BACKGROUND: Short stature is associated with mortality after cardiac surgery and may increase size mismatch risk among transplant recipients. Yet, stature's impact on heart transplant outcomes is not well-characterized. METHODS: The Scientific Registry of Transplant Recipients was queried for data on all adult heart transplants in the United States from 2000 to 2022. Recipients were stratified into five cohorts by sex-corrected stature. Morbidity was assessed with Kruskal-Wallis and chi-squared tests. Mortality was analyzed using Kaplan-Meier estimation. Risk factors for mortality were assessed with multivariable Cox regression. RESULTS: Among 43,420 transplant recipients, 5321 (12.2%) had short stature (females >4'11″ & ≤5'1″; males >5'4″ & ≤5'7″) and 765 (1.8%) had very short stature (females ≤4'11″; males ≤5'4″). Very short stature patients had higher waitlist status (1A and 1), more congenital heart disease, and received more oversized donor hearts than other cohorts (all p < 0.05). Very short stature patients had decreased 30-day, 1-, 5-, and 10-year survival (94.6%, 84.3%, 69.3% and 52.5%, respectively, all p < 0.001), but less acute rejection (p = 0.005) and comparable stroke rates (p = 0.107). On multivariable regression adjusting for congenital heart disease and oversized donor hearts, very short and short stature were associated with 10-year mortality (hazard ratios: 1.40 and 1.12, respectively, both p < 0.005). CONCLUSIONS: Short stature confers increased mortality risk for heart transplant recipients and merits inclusion in prognostic models.

Effect of Anesthesia Induction on Cardiac Hemodynamics in Patients Undergoing Durable Left Ventricular Assist Device Implantation: The EACH-LVAD Study.

Right ventricular (RV) dysfunction is common after left ventricular assist device (LVAD) implantation leading to clinical right heart failure (RHF) associated with worsened survival and quality of life. It is likely that intraoperative events such as anesthesia induction play a role in the development or unmasking of RV dysfunction in addition to known effects from hemodynamic changes that occur after LVAD implantation. The EACH-LVAD Study is a prospective, single-center, single-arm, observational cohort study of adult patients with advanced heart failure undergoing durable LVAD implantation with standard anesthesia induction. Intraoperative RV hemodynamics via central venous pressure, mean pulmonary artery pressure, pulmonary artery pulsatility index, and vasoactive-inotropic score (a simple weighted summation of standardized drug doses) and echocardiographic parameters (RV fractional area change, RV area in diastole, RV basal diameter, septum position, RV function, tricuspid regurgitation) were measured and compared at prespecified timepoints, including postinduction. Postoperative clinical RHF was determined based on published definitions. Forty-two patients receiving a first-time LVAD were included between September 2017 and March 2019. Propofol-based induction was used in 31 patients and etomidate-based induction in eight patients. A significant increase in central venous pressure (CVP; p < 0.001), mean pulmonary artery pressure (mPAP; p < 0.001), and vasoactive inotropic score (VIS; p < 0.001) with associated decrease in pulmonary artery pulsatility index (PAPi; p < 0.001) was observed. Right ventricular function worsened throughout. Right heart failure occurred in 70% of patients. Propofol-based induction was not associated with a higher risk of RHF (relative risk [RR], 1.01 [95% confidence interval {CI}, 0.64-1.61]). The EACH-LVAD study demonstrates an effect of anesthesia induction on worsened RV hemodynamics and echocardiographic changes which may have an effect on the development of RHF.

Emerging Racial Differences in Heart Transplant Waitlist Outcomes for Patients on Temporary Mechanical Circulatory Support.

Temporary mechanical circulatory support (tMCS) is increasingly used for patients awaiting heart transplantation. Although examples of systemic inequity in cardiac care have been described, biases in tMCS use are not well characterized. This study explores the racial disparities in tMCS use and waitlist outcomes. The United Network for Organ Sharing database was used to identify adults listed for first-time heart transplantation from 2015 to 2021. White and non-White patients on extracorporeal membrane oxygenation, intra-aortic balloon pump, or temporary left ventricular assist device were identified. Waitlist outcomes of mortality, transplantation, and delisting were analyzed by race using competing risks regression. The effect of the new heart allocation system was also assessed. A total of 16,811 patients were included in this study, with 10,377 self-identifying as White and 6,434 as non-White. White patients were more often male, privately ensured, and had less co-morbidities (p <0.05). tMCS use was found to be significantly higher in non-White patients (p <0.001). Among those on tMCS, non-White patients were more likely to be delisted because of illness (subhazard ratio 1.34 [1.09 to 1.63]) and less likely to die while on the waitlist (subhazard ratio 0.76 [0.61 to 0.93]). This disparity was not present before the implementation of the new heart allocation system. tMCS use was proportional to the risk factors identified in the non-White cohort. After the implementation of the new heart allocation system, White patients were more likely to die, whereas non-White patients were more likely to be delisted. Further work is needed to determine the causes of and potential solutions for disparities in the waitlist outcomes.