Collagen 18A1/Endostatin Expression in the Progression of Right Ventricular Remodeling and Dysfunction in Pulmonary Arterial Hypertension.

Numerous studies have demonstrated that endostatin (ES), a potent angiostatic peptide derived from collagen type XVIII α 1 chain and encoded by COL18A1, is elevated in pulmonary arterial hypertension (PAH). It is important to note that elevated ES has consistently been associated with altered hemodynamics, poor functional status, and adverse outcomes in adult and pediatric PAH. This study used serum samples from patients with Group I PAH and plasma and tissue samples derived from the Sugen/hypoxia rat pulmonary hypertension model to define associations between COL18A1/ES and disease development, including hemodynamics, right ventricle (RV) remodeling, and RV dysfunction. Using cardiac magnetic resonance imaging and advanced hemodynamic assessments with pressure-volume loops in patients with PAH to assess RV-pulmonary arterial coupling, we observed a strong relationship between circulating ES levels and metrics of RV structure and function. Specifically, RV mass and the ventricular mass index were positively associated with ES, whereas RV ejection fraction and RV-pulmonary arterial coupling were inversely associated with ES levels. Our animal data demonstrate that the development of pulmonary hypertension is associated with increased COL18A1/ES in the heart as well as the lungs. Disease-associated increases in COL18A1 mRNA and protein were most pronounced in the RV compared with the left ventricle and lung. COL18A1 expression in the RV was strongly associated with disease-associated changes in RV mass, fibrosis, and myocardial capillary density. These findings indicate that COL18A1/ES increases early in disease development in the RV and implicates COL18A1/ES in pathologic RV dysfunction in PAH.

Donor utilization in heart transplant with donation after circulatory death in the United States.

Heart transplantation using donation after circulatory death (DCD) was recently adopted in the United States. This study aimed to characterize organ yield from adult (≥18 years) DCD heart donors in the United States using the United Network for Organ Sharing registry. The registry does not identify potential donors who do not progress to circulatory death, and only those who progressed to death were included for analysis. Outcomes included organ recovery from the donor operating room and organ utilization for transplant. Multiple logistic regression was used to identify predictors of heart recovery and utilization. Among 558 DCD procurements, recovery occurred in 89.6%, and 92.5% of recovered hearts were utilized for transplant. Of 506 DCD procurements with available data, 65.0% were classified as direct procurement and perfusion and 35.0% were classified as normothermic regional perfusion (NRP). Logistic regression identified that NRP, shorter agonal time, younger donor age, and highest volume of organ procurement organizations were independently associated with increased odds for heart recovery. NRP independently predicted heart utilization after recovery. DCD heart utilization in the United States is satisfactory and consistent with international experience. NRP procurements have a higher yield for DCD heart transplantation compared with direct procurement and perfusion, which may reflect differences in donor assessment and acceptance criteria.

Pulmonary hypertension associated with left heart disease.

Left heart disease (LHD) is the most common cause of pulmonary hypertension (PH), which may be classified further as isolated post-capillary (ipcPH) or combined post- and pre-capillary PH (cpcPH). The 7th World Symposium on Pulmonary Hypertension PH-LHD task force reviewed newly reported randomised clinical trials and contemplated novel opportunities for improving outcome. Results from major randomised clinical trials reinforced prior recommendations against the use of pulmonary arterial hypertension therapy in PH-LHD outside of clinical trials, and suggested possible harm. Greater focus on phenotyping was viewed as one general strategy by which to ultimately improve clinical outcomes. This is potentially achievable by individualising ipcPH versus cpcPH diagnosis for patients with pulmonary arterial wedge pressure within a diagnostic grey zone (12-18 mmHg), and through a newly developed PH-LHD staging system. In this model, PH accompanies LHD across four stages (A=at risk, B=structural heart disease, C=symptomatic heart disease, D=advanced), with each stage characterised by progression in clinical characteristics, haemodynamics and potential therapeutic strategies. Along these lines, the task force proposed disaggregating PH-LHD to emphasise specific subtypes for which PH prevalence, pathophysiology and treatment are unique. This includes re-interpreting mitral and aortic valve stenosis through a contemporary lens, and focusing on PH within the hypertrophic cardiomyopathy and amyloid cardiomyopathy clinical spectra. Furthermore, appreciating LHD in the profile of PH patients with chronic lung disease and chronic thromboembolic pulmonary disease is essential. However, engaging LHD patients in clinical research more broadly is likely to require novel methodologies such as pragmatic trials and may benefit from next-generation analytics to interpret results.

Poor cardiac output reserve in pulmonary arterial hypertension is associated with right ventricular stiffness and impaired interventricular dependence.

BACKGROUND: Pulmonary arterial hypertension (PAH) is characterised by poor exercise tolerance. The contribution of right ventricular (RV) diastolic function to the augmentation of cardiac output during exercise is not known. This study leverages pressure-volume (P-V) loop analysis to characterise the impact of RV diastology on poor flow augmentation during exercise in PAH. METHODS: RV P-V loops were measured in 41 PAH patients at rest and during supine bike exercise. Patients were stratified by median change in cardiac index (CI) during exercise into two groups: high and low CI reserve. Indices of diastolic function (end-diastolic elastance (E ed)) and ventricular interdependence (left ventricular transmural pressure (LVTMP)) were compared at matched exercise stages. RESULTS: Compared to patients with high CI reserve, those with low reserve exhibited lower exercise stroke volume (36 versus 49 mL·m-2; p=0.0001), with higher associated exercise afterload (effective arterial elastance (E a) 1.76 versus 0.90 mmHg·mL-1; p<0.0001), RV stiffness (E ed 0.68 versus 0.26 mmHg·mL-1; p=0.003) and right-sided pressures (right atrial pressure 14 versus 8 mmHg; p=0.002). Higher right-sided pressures led to significantly lower LV filling among the low CI reserve subjects (LVTMP -4.6 versus 3.2 mmHg; p=0.0001). Interestingly, low exercise flow reserve correlated significantly with high afterload and RV stiffness, but not with RV contractility nor RV-PA coupling. CONCLUSIONS: Patients with poor exercise CI reserve exhibit poor exercise RV afterload, stiffness and right-sided filling pressures that depress LV filling and stroke work. High afterload and RV stiffness were the best correlates to low flow reserve in PAH. Exercise unmasked significant pathophysiological PAH differences unapparent at rest.

Guide to Lung-Protective Ventilation in Cardiac Patients.

The incidence of acute respiratory insufficiency has continued to increase among patients admitted to modern-day cardiovascular intensive care units. Positive pressure ventilation (PPV) remains the mainstay of treatment for these patients. Alterations in intrathoracic pressure during PPV has distinct effects on both the right and left ventricles, affecting cardiovascular performance. Lung-protective ventilation (LPV) minimizes the risk of further lung injury through ventilator-induced lung injury and, hence, an understanding of LPV and its cardiopulmonary interactions is beneficial for cardiologists.

Management of Pulmonary Hypertension in the Context of Heart Failure with Preserved Ejection Fraction.

PURPOSE OF REVIEW: To review the current evidence and modalities for treating pulmonary hypertension (PH) in heart failure with preserved ejection fraction (HFpEF). RECENT FINDINGS: In recent years, several therapies have been developed that improve morbidity in HFpEF, though these studies have not specifically studied patients with PF-HFpEF. Multiple trials of therapies specifically targeting the pulmonary vasculature such as phosphodiesterase (PDE) inhibitors, prostacyclin analogs, endothelin receptor antagonists (ERA), and soluble guanylate cyclase stimulators have also been conducted. However, these therapies demonstrated lack of consistency in improving hemodynamics or functional outcomes in PH-HFpEF. There is limited evidence to support the use of pulmonary vasculature-targeting therapies in PH-HFpEF. The mainstay of therapy remains the treatment of the underlying HFpEF condition. There is emerging evidence that newer HF therapies such as sodium-glucose transporter 2 inhibitors and angiotensin-receptor-neprilysin inhibitors are associated with improved hemodynamics and quality of life of patients with PH-HFpEF. There is also a growing realization that more robust phenotyping PH and right ventricular (RV) function may hold promise for therapeutic strategies for patients with PH-HFpEF.

H2FPEF Scores Are Increased in Patients with NASH Cirrhosis and Are Associated with Post-liver Transplant Heart Failure.

INTRODUCTION: Patients with cirrhosis are at risk for cardiac complications such as heart failure, particularly heart failure with preserved ejection fraction (HFpEF) due to left ventricular diastolic dysfunction (LVDD). The H2FPEF score is a predictive model used to identify patients with HFpEF. Our primary aim was to assess the H2FPEF score in patients with cirrhosis and determine its potential to identify patients at risk for heart failure after liver transplant. METHODS: This was a cohort study of patients undergoing liver transplant for cirrhosis from January 2010 and October 2018 who had a pre-transplant transthoracic echocardiogram. RESULTS: 166 cirrhosis subjects were included in the study. The majority were men (65%) and Caucasian (85%); NASH was the most common cause of cirrhosis (41%) followed by alcohol (34%). The median H2FPEF score was 2.0 (1.0-4.0). Patients with NASH cirrhosis had higher H2FPEF scores (3.22, 2.79-3.64) than those with alcohol induced cirrhosis (1.89, 1.5-2.29, p < 0.001) and other causes of cirrhosis (1.73, 1.28-2.18, p < 0.001). All subjects with a H2FPEF score > 6 had NASH cirrhosis. There was no association between the H2FPEF scores and measures of severity of liver disease (bilirubin, INR, or MELD score). Patients with heart failure after liver transplant had higher H2FPEF scores than those without heart failure (4.0, 3.1-4.9 vs. 2.3, 2.1-2.6, respectively; p = 0.015), but the score did not predict post-transplant mortality. CONCLUSION: H2FPEF scores are higher in cirrhosis patients with NASH and appear to be associated with post-transplant heart failure, but not death.

Elevated Pulmonary Arterial Compliance Is Associated with Survival in Pulmonary Hypertension: Results from a Novel Network Medicine Analysis.

Rationale: Predictors of adverse outcome in pulmonary hypertension (PH) are well established; however, data that inform survival are lacking. Objectives: We aim to identify clinical markers and therapeutic targets that inform the survival in PH. Methods: We included data from patients with elevated mean pulmonary artery pressure (mPAP) diagnosed by right heart catheterization in the U.S. Veterans Affairs system (October 1, 2006-September 30, 2018). Network medicine framework was used to subgroup patients when considering an N of 79 variables per patient. The results informed outcome analyses in the discovery cohort and a sex-balanced validation right heart catheterization cohort from Vanderbilt University (September 24, 1998-December 20, 2013). Measurements and Main Results: From an N of 4,737 complete case patients with mPAP of 19-24 mm Hg, there were 21 distinct subgroups (network modules) (all-cause mortality range = 15.9-61.2% per module). Pulmonary arterial compliance (PAC) drove patient assignment to modules characterized by increased survival. When modeled continuously in patients with mPAP ⩾19 mm Hg (N = 37,744; age, 67.2 yr [range = 61.7-73.8 yr]; 96.7% male; median follow-up time, 1,236 d [range = 570-1,971 d]), the adjusted all-cause mortality hazard ratio was <1.0 beginning at PAC ⩾3.0 ml/mm Hg and decreased progressively to ∼7 ml/mm Hg. A protective association between PAC ⩾3.0 ml/mm Hg and mortality was also observed in the validation cohort (N = 1,514; age, 60.2 yr [range = 49.2-69.1 yr]; 48.0% male; median follow-up time, 2,485 d [range = 671-3,580 d]). The association was strongest in patients with precapillary PH at the time of catheterization, in whom 41% (95% confidence interval, 0.55-0.62; P < 0.001) and 49% (95% confidence interval, 0.38-0.69; P < 0.001) improvements in survival were observed for PAC ⩾3.0 versus <3.0 ml/mm Hg in the discovery and validation cohorts, respectively. Conclusions: These data identify elevated PAC as an important parameter associated with survival in PH. Prospective studies are warranted that consider PAC ⩾3.0 ml/mm Hg as a therapeutic target to achieve through proven interventions.

Differences in Donor Heart Acceptance by Race and Gender of Patients on the Transplant Waiting List.

Importance: Barriers to heart transplant must be overcome prior to listing. It is unclear why Black men and women remain less likely to receive a heart transplant after listing than White men and women. Objective: To evaluate whether race or gender of a heart transplant candidate (ie, patient on the transplant waiting list) is associated with the probability of a donor heart being accepted by the transplant center team with each offer. Design, Setting, and Participants: This cohort study used the United Network for Organ Sharing datasets to identify organ acceptance with each offer for US non-Hispanic Black (hereafter, Black) and non-Hispanic White (hereafter, White) adults listed for heart transplant from October 18, 2018, through March 31, 2023. Exposures: Black or White race and gender (men, women) of a heart transplant candidate. Main Outcomes and Measures: The main outcome was heart offer acceptance by the transplant center team. The number of offers to acceptance was assessed using discrete time-to-event analyses, nonparametrically (stratified by race and gender) and parametrically. The hazard probability of offer acceptance for each offer was modeled using generalized linear mixed models adjusted for candidate-, donor-, and offer-level variables. Results: Among 159 177 heart offers with 13 760 donors, there were 14 890 candidates listed for heart transplant; 30.9% were Black, 69.1% were White, 73.6% were men, and 26.4% were women. The cumulative incidence of offer acceptance was highest for White women followed by Black women, White men, and Black men (P < .001). Odds of acceptance were less for Black candidates than for White candidates for the first offer (odds ratio [OR], 0.76; 95% CI, 0.69-0.84) through the 16th offer. Odds of acceptance were higher for women than for men for the first offer (OR, 1.53; 95% CI, 1.39-1.68) through the sixth offer and were lower for the 10th through 31st offers. Conclusions and Relevance: The cumulative incidence of heart offer acceptance by a transplant center team was consistently lower for Black candidates than for White candidates of the same gender and higher for women than for men. These disparities persisted after adjusting for candidate-, donor-, and offer-level variables, possibly suggesting racial and gender bias in the decision-making process. Further investigation of site-level decision-making may reveal strategies for equitable donor heart acceptance.

Metabolic profiling of in vivo right ventricular function and exercise performance in pulmonary arterial hypertension.

Right ventricular (RV) adaptation is the principal determinant of outcomes in pulmonary arterial hypertension (PAH), however, RV function is challenging to assess. RV responses to hemodynamic stressors are particularly difficult to interrogate without invasive testing. This study sought to identify metabolomic markers of in vivo right ventricular function and exercise performance in PAH. Consecutive subjects with PAH (n = 23) underwent rest and exercise right heart catheterization with multibeat pressure volume loop analysis. Pulmonary arterial blood was collected at rest and during exercise. Mass spectrometry-based targeted metabolomics were performed, and metabolic associations with hemodynamics and comprehensive measures of RV function were determined using sparse partial least squares regression. Metabolite profiles were compared with N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) measurements for accuracy in modeling ventriculo-arterial parameters. Thirteen metabolites changed in abundance with exercise, including metabolites reflecting increased arginine bioavailability, precursors of catecholamine and nucleotide synthesis, and branched-chain amino acids. Higher resting arginine bioavailability predicted more favorable exercise hemodynamics and pressure-flow relationships. Subjects with more severe PAH augmented arginine bioavailability with exercise to a greater extent than subjects with less severe PAH. We identified relationships between kynurenine pathway metabolism and impaired ventriculo-arterial coupling, worse RV diastolic function, lower RV contractility, diminished RV contractility with exercise, and RV dilation with exercise. Metabolite profiles outperformed NT-proBNP in modeling RV contractility, diastolic function, and exercise performance. Specific metabolite profiles correspond to RV functional measurements only obtainable via invasive pressure-volume loop analysis and predict RV responses to exercise. Metabolic profiling may inform discovery of RV functional biomarkers.NEW & NOTEWORTHY In this cohort of patients with pulmonary arterial hypertension (PAH), we investigate metabolomic associations with comprehensive right ventricular (RV) functional measurements derived from multibeat RV pressure-volume loop analysis. Our results show that tryptophan metabolism, particularly the kynurenine pathway, is linked to intrinsic RV function and PAH pathobiology. Findings also highlight the importance of arginine bioavailability in the cardiopulmonary system's response to exercise stress. Metabolite profiles selected via unbiased analysis outperformed N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) in predicting load-independent measures of RV function at rest and cardiopulmonary system performance under stress. Overall, this work suggests the potential for select metabolites to function as disease-specific biomarkers, offers insights into PAH pathobiology, and informs discovery of potentially targetable RV-centric pathways.

Decoupling of Hemodynamics and Congestive Symptoms in Obese Patients With Heart Failure.

BACKGROUND: Prior studies indicate significant physiological differences between obese and nonobese patients with heart failure (HF), but none have evaluated differences in hemodynamic patterns in these patient populations during treatment for acute decompensated HF (ADHF). OBJECTIVES: In this study, we assessed differences in hemodynamic trends between obese and nonobese patients during treatment for ADHF. METHODS: Obese (body mass index (BMI) >30, n = 63) and nonobese (BMI < 25, n = 69) patients with ADHF in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) study who had pulmonary artery catheterization data available through the duration of treatment were evaluated. Hemodynamics were analyzed at baseline and optimal day. Changes in BNP levels, weight, creatinine, BUN, 6MWT, orthopnea and dyspnea scores were assessed. RESULTS: Despite similar baseline hemodynamics, obese patients had significantly less absolute and relative pulmonary arterial wedge pressure (PAWP) reduction (-16 ± 28 vs -32 ± 29%; P = 0.03) during treatment. Obese patients also had higher PAWPs (19.9 + 8 vs 15.5 + 6.8 mmHg; P = 0.01) and PA pressures at optimization compared with nonobese patients. Obese and nonobese patients had similar relative improvements in weight, BNP, 6-minute walk test distance, dyspnea and orthopnea scores, and similar changes in creatinine and BUN levels. CONCLUSIONS: Obese patients treated for ADHF display less reduction in invasively measured left heart filling pressures, despite similar improvements in symptoms, weight loss, and noninvasive surrogates of congestion. Our findings suggest a degree of decoupling between left heart filling pressures and congestive symptoms in obese patients undergoing treatment for ADHF.

Standardization of the Right Heart Catheterization and the Emerging Role of Advanced Hemodynamics in Heart Failure.

The accurate assessment of hemodynamics is paramount to providing timely and efficacious care for patients presenting in cardiogenic shock. Recently, the regular use of the pulmonary artery catheter in cardiogenic shock has had a resurgence with emerging data indicating improved survival in the modern era. Optimal multidisciplinary management of advanced heart failure and cardiogenic shock relies on our ability to effectively communicate and understand the complete hemodynamic assessment. Standardization of data acquisition and a renewed focus on the physiological processes, and thresholds driving disease progression, including the coupling ratio and myocardial reserve, are needed to fully understand and interpret the hemodynamic assessment. This State-of-the-Art review discusses best practices in the cardiac catheterization laboratory as well as emerging data on the prognostic role of emerging advanced hemodynamic parameters.

Impact of Donor Hemodynamics on Recipient Survival in Heart Transplantation.

BACKGROUND: Heart transplantation is the gold-standard therapy for end-stage heart failure, but rates of donor-heart use remain low due to various factors that are often not evidence based. The impact of donor hemodynamics obtained via right-heart catheterization on recipient survival remains unclear. METHODS: The United Network for Organ Sharing registry was used to identify donors and recipients from September 1999-December 2019. Donor hemodynamics data were obtained and analyzed using univariate and multivariable logistical regression, with the primary endpoints being 1- and 5-year post-transplant survival. RESULTS: Of the 85,333 donors who consented to heart transplantation during the study period, 6573 (7.7%) underwent right-heart catheterization, of whom 5531 eventually underwent procurement and transplantation. Donors were more likely to undergo right-heart catheterization if they had high-risk criteria. Recipients who had donor hemodynamic assessment had 1- and 5-year survival rates similar to those without donor hemodynamic assessment (87% vs 86%, 1 year). Abnormal hemodynamics were common in donor hearts but did not impact recipient survival rates, even when risk-adjusted in multivariable analysis. CONCLUSIONS: Donors with abnormal hemodynamics may represent an opportunity to expand the pool of viable donor hearts.

Outcomes in Patients With Chronic Kidney Disease and End-stage Renal Disease and Durable Left Ventricular Assist Device: Insights From the United States Renal Data System Database.

BACKGROUND: There is paucity of data regarding durable left ventricular assist device (LVAD) outcomes in patients with chronic kidney disease (CKD) stages 3-5 and CKD stage 5 on dialysis (end-stage renal disease [ESRD]). METHODS AND RESULTS: We conducted a retrospective study of Medicare beneficiaries with ESRD and a 5% sample of patients with CKD with an LVAD (2006-2018) to determine 1-year outcomes using the United States Renal Data System database. The LVAD implantation, comorbidities, and outcomes were identified using appropriate International Classification of Diseases, 9th and 10th edition codes. We identified 496 patients with CKD and 95 patients with ESRD who underwent LVAD implantation. The patients with ESRD were younger (59 years vs 66 years; P < .001), had more Blacks (40% vs 24.6%, P = .009), compared with the CKD group. The 1-year mortality (49.5% vs 30.9%, P < .001) and index mortality (27.4% vs 16.7%, P = .014) rates were higher for patients with ESRD. A subgroup analysis showed significantly higher mortality in ESRD vs CKD 3 (49.5% vs 30.2%, adjusted P = .009), but no significant difference in mortality between stage 3 vs 4/5 (30.2% vs 30.8%, adjusted P = .941). There was no significant difference in secondary outcomes (bleeding, stroke, and sepsis/infection) during follow-up between the 2 groups. CONCLUSIONS: Patients with ESRD undergoing LVAD implantation had significantly higher index and 1-year mortality rates compared with patients with CKD.

Outcomes in Patients With LVADs Undergoing Simultaneous Heart-Kidney Transplantation.

BACKGROUND: Multiple studies have shown better outcomes for simultaneous heart-kidney transplant (sHKT) than for isolated orthotopic heart transplant (iOHT) in recipients with chronic kidney disease (CKD). However, outcomes in patients supported by durable left ventricular assist devices (LVADs) have not been well studied. METHODS: Patients with durable LVADs and stage 3 or higher CKD (eGFR < 60 mL/min/1.73 m2) undergoing iOHT or sHKT between 2008 and 2020 were identified from the United Network for Organ Sharing registry. A Kaplan-Meier survival analysis with associated log-rank test was conducted to compare post-transplant survival rates. Multivariable modeling was used to identify risk-adjusted predictors of 1 year post-transplant mortality. RESULTS: We identified 4375 patients; 366 underwent sHKT, and 4009 underwent iOHT. The frequency of sHKT increased during the study period. The 1-year post-transplant survival rate was worse in patients after sHKT than in patients after iOHT (80.3% vs 88.3%; P < 0.001) and persisted up to 5 years post-transplant (P = 0.001). sHKT recipients were more likely to require dialysis after transplantation and had longer hospital lengths of stay (P < 0.001). Multivariable analysis showed that sHKT remained an independent risk factor for mortality at 1 year (OR 1.58; P = 0.002). CONCLUSIONS: sHKT is becoming more common in patients with durable LVADs. Compared with iOHT, patients with sHKTs have worse short- and long-term survival rates and are more likely to require post-transplant dialysis.

Angiotensin-converting enzyme inhibitor therapy after heart transplant: From molecular basis to clinical effects.

The use of angiotensin-converting enzyme inhibitors is an important therapy for various cardiovascular diseases, such as hypertension, ischemic heart disease and heart failure (HF). In heart transplant recipients, angiotensin-converting enzyme inhibitors have been demonstrated to be a keystone for the treatment of hypertension with a wide spectrum of pleiotropic molecular effects ranging from improvement of the peripheral vascular system to regulation of the fluid and sodium balance. In addition, angiotensin-converting enzyme inhibitors may be also useful in the prevention of graft failure, cardiac allograft vasculopathy (CAV) and chronic kidney disease (CKD) progression. Further tailored multicenter and randomized studies are warranted to confirm the pleiotropic clinical effects of ACEi therapy in HTRs and to support more extended use in daily clinical practice. Finally in the near future, the use of novel pharmacological agents that inhibit the renin-angiotensin-aldosterone system (RAAS) such as the neprilysin inhibitor sacubitril should be investigated in heart transplant recipients.

HVAD versus heartmate III bridge to heart transplantation: Waitlist and posttransplant outcomes.

BACKGROUND: This study compared outcomes of patients bridged with either the Heartware HVAD or Heartmate 3 (HM3) device to orthotopic heart transplantation (OHT). METHODS: The United Network of Organ Sharing registry was queried to perform two separate analyses of adult, isolated OHT candidates bridged with HVAD or HM3. First, waitlist outcomes were compared among patients waitlisted 1/1/2015-3/20/2020. Second, posttransplant survival was compared among those transplanted 1/1/2015-3/20/2020. RESULTS: Two thousand two hundred fifty-five candidates were waitlisted within the study period, 1587 (70.4%) bridged with HVAD and 668 (29.6%) with HM3. At 1 year from waitlisting, cumulative incidence of OHT higher in the HVAD cohort (p < .001). During the same time period, 2643 patients underwent OHT, 2154 (81.5%) with prior HVAD and 489 (18.5%) with HM3. Yearly proportions of patients bridged with HM3 increased across the study period and decreased for HVAD (p < .001). HM3-bridged recipients had shorter waitlist times, longer graft cold ischemic times, and experienced a higher rate of posttransplant dialysis requirement. Unadjusted and risk-adjusted posttransplant mortality rates were similar between both groups. CONCLUSIONS: Posttransplant survival is equivalent regardless of device type used for bridging. However, HM3 patients had lower likelihood of reaching transplantation, which may be a reflection of the recent heart allocation policy changes.

The HeartMate 3 left ventricular assist device as a strategy to bridge to transplant.

PURPOSE: Recent changes in the market for left ventricular assist devices have resulted in the HeartMate 3 (HM3) being the only commercially-available device. This study evaluates the outcomes of patients with a HM3 waitlisted for and undergoing orthotopic heart transplantation (OHT). METHODS: Patients waitlisted for isolated OHT with a HM3 or undergoing OHT after bridge-to-transplant (BTT) with a HM3 between 2015 and 2021 were identified from the UNOS registry and included in this study. Propensity matching was used to compare outcomes of BTT-HM3 versus primary OHT. RESULTS: A total of 1321 patients supported with a HM3 underwent OHT during our study period. Unadjusted 30-day, 90-day, and 1-year survival following OHT in the BTT-HM3 cohort was 96.5%, 94.4%, and 90.7%, respectively. In propensity-matched analysis, 1103 BTT-HM3 patients were compared with 1103 primary OHT patients. Rates of post-OHT stroke were higher in the BTT-HM3 group (4.4% vs. 2.0%, p = .001). The BTT-HM3 group had lower 30-day survival (96.2% vs. 97.4%, p = .033) although 90-day (94.2% vs. 95.3%, p = .103) and 1-year survival (90.4% vs. 91.7%, p = .216) were comparable. A total of 1251 patients were supported with a HM3 at the time of OHT listing during the study period. At the time of this analysis, 60 (4.5%) remained on the waitlist, 991 (75.0%) underwent OHT, and 119 (9.0%) died or clinically deteriorated with waitlist removal. CONCLUSIONS: The HM3 is a viable method for BTT with acceptable waitlist outcomes. Although 1-year survival is comparable to primary OHT, early outcomes are worse, suggesting that refinement of patient selection and perioperative management is prudent to optimizing outcomes.

The impact of changes in renal function during waitlist time on outcomes after heart transplantation.

BACKGROUND AND AIM: This study evaluated the impact of changes in renal function during the waitlist period on posttransplant outcomes of orthotopic heart transplantation (OHT). METHODS: The United Network for Organ Sharing registry was used to identify adult patients undergoing isolated OHT from 2010 to 2020. Patients were stratified by whether their National Kidney Foundation chronic kidney disease (CKD) stage improved, worsened, or remained unchanged between listing and transplantation. Univariate analysis and multivariable Cox regression were conducted to determine whether a change in estimated glomerular filtration rate (eGFR) or change in CKD stage predicted 1-year mortality after OHT. RESULTS: Of 22,746 patients, the majority of patients remained in the same CKD stage (59.6%), and the frequencies of patients progressing to improved (19.3%) and worsened (21.1%) CKD stages were similar. Temporary mechanical circulatory support (MCS) was associated with improved CKD stage and durable MCS with worsened CKD stage (p < .001). Post-OHT dialysis was most common in patients with worsened CKD stage (13.2%) and least common in the improved cohort (9.4%) (p < .001). Kaplan-Meier unadjusted 1-year survival rates after OHT were similar between CKD change groups (log-rank p = .197). Multivariable analysis demonstrated no risk-adjusted effect of change in eGFR (p = .113) or change in CKD stage (p = .076) on 1-year mortality after OHT. CONCLUSIONS: Approximately 20% of patients improve CKD stage and 20% worsen CKD stage between listing and OHT, with the remaining 60% having unchanged CKD stage. Worsening CKD stage predicts increased likelihood of post-OHT dialysis, but CKD stage change does not predict 1-year survival following OHT.

Right ventricular pressure-volume loop shape and systolic pressure change in pulmonary hypertension.

Right ventricular (RV) function determines outcome in pulmonary arterial hypertension (PAH). RV pressure-volume loops, the gold standard for measuring RV function, are difficult to analyze. Our aim was to investigate whether simple assessments of RV pressure-volume loop morphology and RV systolic pressure differential reflect PAH severity and RV function. We analyzed multibeat RV pressure-volume loops (obtained by conductance catheterization with preload reduction) in 77 patients with PAH and 15 patients without pulmonary hypertension in two centers. Patients were categorized according to their pressure-volume loop shape (triangular, quadratic, trapezoid, or notched). RV systolic pressure differential was defined as end-systolic minus beginning-systolic pressure (ESP - BSP), augmentation index as ESP - BSP/pulse pressure, pulmonary arterial capacitance (PAC) as stroke volume/pulse pressure, and RV-arterial coupling as end-systolic/arterial elastance (Ees/Ea). Trapezoid and notched pressure-volume loops were associated with the highest afterload (Ea), augmentation index, pulmonary vascular resistance (PVR), mean pulmonary arterial pressure, stroke work, B-type natriuretic peptide, and the lowest Ees/Ea and PAC. Multivariate linear regression identified Ea, PVR, and stroke work as the main determinants of ESP - BSP. ESP - BSP also significantly correlated with multibeat Ees/Ea (Spearman's ρ: -0.518, P < 0.001). A separate retrospective analysis of 113 patients with PAH showed that ESP - BSP obtained by routine right heart catheterization significantly correlated with a noninvasive surrogate of RV-arterial coupling (tricuspid annular plane systolic excursion/pulmonary arterial systolic pressure ratio; ρ: -0.376, P < 0.001). In conclusion, pressure-volume loop shape and RV systolic pressure differential predominately depend on afterload and PAH severity and reflect RV-arterial coupling in PAH.