Patterns, Prognostic Implications, and Rural-Urban Disparities in Optimal GDMT Following HFrEF Diagnosis Among Medicare Beneficiaries.

BACKGROUND: Patterns and disparities in guideline-directed medical therapy (GDMT) uptake for heart failure with reduced ejection fraction (HFrEF) across rural vs urban regions are not well described. OBJECTIVES: This study aims to evaluate patterns, prognostic implications, and rural-urban differences in GDMT use among Medicare beneficiaries following new-onset HFrEF. METHODS: Patients with a diagnosis of new-onset HFrEF in a 5% Medicare sample with available data for Part D medication use were identified from January 2015 through December 2020. The primary exposure was residence in rural vs urban zip codes. Optimal triple GDMT was defined as ≥50% of the target daily dose of beta-blockers, ≥50% of the target daily dose of angiotensin-converting enzyme inhibitors/angiotensin receptor blocker or any dose of sacubitril/valsartan, and any dose of mineralocorticoid receptor antagonist. The association between the achievement of optimal GDMT over time following new-onset HFrEF diagnosis and risk of all-cause mortality and subsequent HF hospitalization was also evaluated using adjusted Cox models. The association between living in rural vs urban location and time to optimal GDMT achievement over a 12-month follow-up was assessed using cumulative incidence curves and adjusted Fine-Gray subdistribution hazard models. RESULTS: A total of 41,296 patients (age: 76.7 years; 15.0% Black; 27.6% rural) were included. Optimal GDMT use over the 12-month follow-up was low, with 22.5% initiated on any dose of triple GDMT and 9.1% on optimal GDMT doses. Optimal GDMT on follow-up was significantly associated with a lower risk of death (HR: 0.89 [95% CI: 0.85-0.94]; P < 0.001) and subsequent HF hospitalization (HR: 0.93 [95% CI: 0.87-0.98]; P = 0.02). Optimal GDMT use at 12 months was significantly lower among patients living in rural (vs urban) areas (8.4% vs 9.3%; P = 0.02). In adjusted analysis, living in rural (vs urban) locations was associated with a significantly lower probability of achieving optimal GDMT (HR: 0.92 [95% CI: 0.86-0.98]; P = 0.01 Differences in optimal GDMT use following HFrEF diagnosis accounted for 16% of excess mortality risk among patients living in rural (vs urban) areas. CONCLUSIONS: Use of optimal GDMT following new-onset HFrEF diagnosis is low, with substantially lower use noted among patients living in rural vs urban locations. Suboptimal GDMT use following new-onset HFrEF was associated with an increased risk of mortality and subsequent HF hospitalization.

Sex disparities in the current era of pediatric heart transplantation in the United States.

BACKGROUND: While sex-related differences in transplant outcomes have been well characterized amongst adults, there are no sex-specific pediatric heart transplant studies over the last decade and none evaluating waitlist outcomes. In a contemporary cohort of children undergoing heart transplantation in the United States, this analysis was performed to determine if there were sex disparities in waitlist and/or post-transplant outcomes. METHODS: Retrospective review of Scientific Registry of Transplant Recipients database from December 16, 2011 to February 28, 2019 to compare male and female children after listing and after transplant. Demographic, clinical characteristics and outcomes were compared unadjusted and after 1:1 propensity matching for selected covariates. RESULTS: Of 4089 patients, 2299 (56%) were males. At listing, males were more likely to be older, have congenital heart disease (58% vs 48%), renal dysfunction (49% vs 44%) and implantable cardioverter defibrillator (9% vs 7%). At transplant, males were more likely to have renal (42 % vs 35%) and liver dysfunction (13% vs 10%), PRA >10% (29% vs 22%) and ischemic time >3.5 hours (p < 0.05 for all). There were no significant sex differences found in unadjusted rates of transplant or mortality. After propensity matching, females had increased waitlist mortality (HR 1.3, 95%CI 1.04-1.5; p =0.019) compared to males. There were no significant differences in post-transplant morbidity or mortality (HR 1.2, 95% CI 0.93-1.5; p = 0.18) between groups. CONCLUSION: In a contemporary pediatric cohort, females have inferior heart transplant waitlist survival compared to propensity-matched males despite lower acuity of illness at listing and similar rates of transplantation. There were no sex-disparities noted in post-transplant outcomes.

Disparities in heart and lung transplantation.

PURPOSE OF REVIEW: Cardiothoracic transplantation is the definitive therapy for end-stage heart and lung disease. In service to this population, disparities in access and care must be simultaneously understood and addressed. RECENT FINDINGS: There are sex, race, geographic, age, and underlying disease disparities in both heart and lung transplantation. Women have reduced waitlist survival but improved posttransplant survival when compared with men for both heart and lung transplantation. Black patients have worse outcome compared with other races postheart transplant. Geographic disparities impact the likelihood of receiving heart or lung transplant and the growing number of patients with advanced age seeking transplant complicates discussions on survival benefit. Finally, underlying disease has affected outcomes for both heart and lung transplant and now are incorporated into the allocation system. SUMMARY: Though heart and lung transplantation have several existing disparities, it remains to be seen how advancements in medical technology, changes in donor organ allocation policies, and growing experience in patient selection will impact these concerns.

Dynamic Assessment of Pulmonary Artery Pulsatility Index Provides Incremental Risk Assessment for Early Right Ventricular Failure After Left Ventricular Assist Device.

BACKGROUND: The pulmonary artery pulsatility index (PAPi) has been studied to predict right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation, but only as a single time point before LVAD implantation. Multiple clinical factors and therapies impact RV function in pre-LVAD patients. Thus, we hypothesized that serial PAPi measurements during cardiac intensive care unit (CICU) optimization before LVAD implantation would provide incremental risk stratification for early RVF after LVAD implantation. METHODS AND RESULTS: Consecutive patients who underwent sequential pulmonary artery catherization with cardiac intensive care optimization before durable LVAD implantation were included. Serial hemodynamics were reviewed retrospectively across the optimization period. The optimal PAPi was defined by the initial PAPi + the PAPi at optimized hemodynamics. RVF was defined as need for a right ventricular assist device or prolonged inotrope use (>14 days postoperatively). Patients with early RVF had significantly lower mean optimal PAPi (3.5 vs 7.5, P < .001) compared with those who did not develop RVF. After adjusting for established risk factors of early RVF after LVAD implantation, the optimal PAPi was independently and incrementally associated with early RVF after LVAD implantation (odds ratio 0.64, 95% confidence interval 0.532-0.765, P < .0001). CONCLUSIONS: Optimal PAPi achieved during medical optimization before LVAD implantation provides independent and incremental risk stratification for early RVF, likely identifying dynamic RV reserve.

Heart Transplantation: An In-Depth Survival Analysis.

OBJECTIVES: This study aims to understand the complex factors affecting heart transplant survival and to determine the importance of possible sex-specific risk factors. BACKGROUND: Heart transplant allocation is primarily focused on preventing waitlist mortality. To prevent organ wastage, future allocation must balance risk of waitlist mortality with post-transplantation mortality. However, more information regarding risk factors after heart transplantation is needed. METHODS: We included all adults (30,606) in the Scientific Registry of Transplant Recipients database who underwent isolated heart transplantation from January 1, 2004, to July 1, 2018. Mortality (8,278 deaths) was verified with the complete Social Security Death Index with a median follow-up of 3.9 years. Temporal decomposition was used to identify phases of survival and phase-specific risk factors. The random survival forests method was used to determine importance of mortality risk factors and their interactions. RESULTS: We identified 3 phases of mortality risk: early post-transplantation, constant, and late. Sex was not a significant risk factor. There were several interactions predicting early mortality such as pretransplantation mechanical ventilation with presence of end-organ function (bilirubin, renal function) and interactions predicting later mortality such as diabetes and older age (donor and recipient). More complex interactions predicting early-, mid-, and late-mortality existed and were identified with machine learning (i.e., elevated bilirubin, mechanical ventilation, and dialysis). CONCLUSIONS: Post-heart transplant mortality risk is complex and dynamic, changing with time and events. Sex is not an important mortality risk factor. To prevent organ wastage, end-organ dysfunction should be resolved before transplantation as much as possible.

Sex Differences in Advanced Heart Failure Therapies.

This in-depth review of sex differences in advanced heart failure therapy summarizes the existing literature on implantable cardioverter defibrillators, biventricular pacemakers, mechanical circulatory support, and transplantation with a focus on utilization, efficacy/clinical effectiveness, adverse events, and controversies. One will learn about the controversies regarding efficacy/clinical effectiveness of implantable cardioverter defibrillators and understand why these devices should be implanted in women even if there are sex differences in appropriate shocks. Individuals will learn about the sex differences with biventricular pacemakers with respect to ventricular remodeling and reduction in heart failure hospitalizations/mortality, as well as, possible mechanisms. We will demonstrate sex differences in heart transplantation and waitlist survival. Despite similar survival for women and men with left ventricular assist devices, there are sex differences in adverse events. These devices do successfully bridge women and men to transplant, yet women are less likely than men to have a left ventricular assist at time of listing and time of transplantation. Finally, one will learn about the concerns regarding poor outcome for men who receive female donor hearts and discover this may not be due to sex, but rather size. More research is needed to better understand sex differences and further improve advanced heart failure therapy for both women and men.

Variables of importance in the Scientific Registry of Transplant Recipients database predictive of heart transplant waitlist mortality.

The prelisting variables essential for creating an accurate heart transplant allocation score based on survival are unknown. To identify these we studied mortality of adults on the active heart transplant waiting list in the Scientific Registry of Transplant Recipients database from January 1, 2004 to August 31, 2015. There were 33 069 candidates awaiting heart transplantation: 7681 UNOS Status 1A, 13 027 Status 1B, and 12 361 Status 2. During a median waitlist follow-up of 4.3 months, 5514 candidates died. Variables of importance for waitlist mortality were identified by machine learning using Random Survival Forests. Strong correlates predicting survival were estimated glomerular filtration rate (eGFR), serum albumin, extracorporeal membrane oxygenation, ventricular assist device, mechanical ventilation, peak oxygen capacity, hemodynamics, inotrope support, and type of heart disease with less predictive variables including antiarrhythmic agents, history of stroke, vascular disease, prior malignancy, and prior tobacco use. Complex interactions were identified such as an additive risk in mortality based on renal function and serum albumin, and sex-differences in mortality when eGFR >40 mL/min/1.73 m. Most predictive variables for waitlist mortality are in the current tiered allocation system except for eGFR and serum albumin which have an additive risk and complex interactions.

Advances in Cardiovascular Health in Women over the Past Decade: Guideline Recommendations for Practice.

Cardiovascular disease (CVD) remains the number one cause of death in women. It is estimated that 44 million women in the United States are either living with or at risk for heart disease. This article highlights the recent significant progress made in improving care, clinical decision-making, and policy implications for women with CVD. We provide our perspective supported by evidence-based advances in cardiovascular research and clinical care guidelines in seven areas: (1) primary CVD prevention and community heart care, (2) secondary prevention of CVD, (3) stroke, (4) heart failure and cardiomyopathies, (5) ischemia with nonobstructive coronary artery disease, (6) spontaneous coronary artery dissection, and (7) arrhythmias and device therapies. Advances in these fields have improved the lives of women living with and at risk for heart disease. With increase awareness, partnership with national organizations, sex-specific research, and changes in policy, the morbidity and mortality of CVD in women can be further reduced.

Verification of Heart Disease: Implications for a New Heart Transplantation Allocation System.

OBJECTIVES: This study sought to determine the accuracy of the pre-transplantation clinical diagnosis of heart disease in the United Network for Organ Sharing (UNOS) database. BACKGROUND: Because survival on the heart transplantation waitlist depends on underlying heart disease, a new allocation system will include the type of heart disease. Accuracy of the pre-transplantation clinical diagnosis and the effect of misclassification are unknown. METHODS: We included all adults who received transplants at our center between January 2009 to December 2015. We compared the pre-transplantation clinical diagnosis at listing with pathology of the explanted heart and determined the potential effect of misclassification with the proposed allocation system. RESULTS: A total of 334 patients had the following clinical cardiac diagnoses at listing: 148 had dilated cardiomyopathy, 19 had restrictive cardiomyopathy, 103 had ischemic cardiomyopathy, 24 had hypertrophic cardiomyopathy, 11 had valvular disease, 16 had congenital heart disease (CHD), and 13 patients had a diagnosis of "other." Pathology of the explanted hearts revealed 82% concordance and 18% discordance (10% coding errors and 8% incorrect diagnosis). The most common incorrect diagnoses were sarcoidosis (66%), arrhythmogenic right ventricular dysplasia (60%), and other causes of predominately right-sided heart failure (33%). Among the misclassified diagnoses, 40% were listed as UNOS status 2, 8% remained at status 2 at transplantation, and only sarcoidosis and CHD were potentially at a disadvantage with the new allocation. CONCLUSIONS: There is high concordance between clinical and pathologic diagnosis, except for sarcoidosis and genetic diseases. Few misclassifications result in disadvantages to patients based on the new allocation system, but rare diseases like sarcoidosis remain problematic. To improve the UNOS database and enhance outcome research, pathology of the explanted hearts should be required post-transplantation.

Does the UNOS heart transplant allocation system favor men over women?

OBJECTIVES: The aim of this paper was to identify sex differences in survival of patients awaiting orthotopic heart transplantation (OHT). BACKGROUND: Women have a higher mortality rate while awaiting OHT than men, and the reason has not been fully determined. METHODS: We included all adult patients in the Scientific Registry of Transplant Recipients (SRTR) placed on the OHT waiting list from 2000 to 2010. The primary endpoint was all-cause mortality before receiving OHT, analyzed using time-to-event analysis. Multivariate Cox proportional hazards models were used to evaluate sex differences in survival, with data stratified by United Network for Organ Sharing (UNOS) status at time of listing. RESULTS: There were 28,852 patients (24% women) awaiting OHT. This cohort included 6,163 UNOS status 1A (25% women), 9,168 UNOS status 1B (25% women), and 13,521 UNOS status 2 (24% women) patients. During a median follow-up of 3.7 years, 1,290 women and 4,286 men died. Female sex was associated with a significant risk of death among UNOS status 1A (adjusted hazard ratio [HR]: 1.20; 95% confidence interval [CI]: 1.05 to 1.37, p = 0.01) after adjusting for more than 30 baseline variables. In contrast, female sex was significantly protective for time to death among UNOS status 2 patients (adjusted HR: 0.75; 95% CI: 0.67 to 0.84, p < 0.001). No sex differences were noted among UNOS status 1B patients. CONCLUSIONS: There are sex differences in survival between women and men awaiting heart transplantation, and the current UNOS transplant criteria do not account for this disparity.

The impact of left ventricular size on response to cardiac resynchronization therapy.

UNLABELLED: Patients with nondilated (NDCM) or severely dilated cardiomyopathies (SDCM) have been underrepresented in clinical trials of cardiac resynchronization therapy (CRT). We examined changes in left ventricular ejection fraction (LVEF) and survival in patients with NDCM or SDCM compared with those with traditionally studied moderately dilated cardiomyopathy. METHODS: We evaluated 800 consecutive patients undergoing the original implantation of a biventricular pacemaker between January 2004 and August 2007. For inclusion, patients had a baseline and pre-CRT echocardiogram, an LVEF ≤40%, a US social security number, and New York Heart Association class II to IV symptoms on standard medical therapy. Patients with a follow-up echocardiogram >2 months after device implantation were included in an analysis of remodeling. Using multivariate models, the impact of baseline left ventricular end-diastolic diameter (LVEDD) on change in LVEF and all-cause mortality was assessed. RESULTS: A total of 668 patients met inclusion criteria and were included in the assessment of mortality. Four hundred seventy-one had an appropriately timed follow-up echocardiogram and were included in the analysis of remodeling. Patients in all 3 groups realized improvements in LVEF (%) after CRT as follows: NDCM (n = 137; LVEDD ≤5.5 cm) 10.0 ± 12.7, P < .001; moderately dilated cardiomyopathy (n = 233; LVEDD 5.6-6.9 cm) 8.2 ± 11.3, P < .001; and SDCM (n = 101; LVEDD ≥7.0 cm) 5.4 ± 9.4, P < .001. In multivariate analysis, baseline LVEDD was inversely associated with change in LVEF (parameter estimate -3.13 ± 0.56, P < .001) and directly associated with increased all-cause mortality (hazard ratio 1.25 [1.05-1.47] P = .01). CONCLUSION: Patients with NDCM and SDCM experience significant improvements in LVEF after CRT. The degree of baseline left ventricular dilatation before CRT is an important predictor of subsequent changes in LVEF and survival.