Most patients with advanced systolic dysfunction who are assessed for a left ventricular assist device (LVAD) also have some degree of right ventricular (RV) dysfunction. Hence, RV failure (RVF) remains a common complication of LVAD placement. Severe RVF after LVAD implantation is associated with increased peri-operative mortality and length of stay and can lead to coagulopathy, altered drug metabolism, worsening nutritional status, diuretic resistance, and poor quality of life. However, current medical and surgical treatment options for RVF are limited and often result in significant impairments in quality of life. There has been continuing interest in developing risk models for RVF before LVAD implantation. This report reviews the anatomy and physiology of the RV and how it changes in the setting of LVAD support. We will discuss proposed mechanisms and describe biochemical, echocardiographic, and hemodynamic predictors of RVF in LVAD patients. We will describe management strategies for reducing and managing RVF. Finally, we will discuss the increasingly recognized and difficult to manage entity of chronic RVF after LVAD placement and describe opportunities for future research.

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Background: Sodium glucose cotransporter 2 inhibitors (SGLT2i) prevent heart failure (HF) hospitalizations in patients with Type 2 Diabetes (T2D), and improve outcomes in those with HF and reduced ejection fraction (EF), regardless of T2D. Mechanisms of HF benefits remain unclear, and effects of SGLT2i on hemodynamics (filling pressures) are not known. EMBRACE-HF Trial was designed to address this knowledge gap. Methods: EMBRACE-HF is an investigator-initiated, randomized, multi-center, double-blind, placebo-controlled trial. From July 2017 to November 2019, patients with HF (regardless of EF, with or without T2D) and previously implanted pulmonary artery (PA) pressure sensor (CardioMEMS) were randomized across 10 US centers to empagliflozin 10 mg daily or placebo and treated for 12 weeks. The primary endpoint was change in PA diastolic pressure (PADP) from baseline to end of treatment (average PADP weeks 8-12). Secondary endpoints included health status (Kansas City Cardiomyopathy Questionnaire (KCCQ)), natriuretic peptides and 6-minute walking distance. Results: Overall, 93 patients were screened, and 65 were randomized (33 empagliflozin, 32 placebo). Mean age was 66 years, 63% were male, 52% had T2D, 54% NYHA class III/IV; mean EF 44%, median NT-proBNP 637 pg/mL and mean PADP 22 mmHg. Empagliflozin significantly reduced PADP, with effects beginning at week 1, and amplified over time; average PADP (weeks 8-12) was 1.5 mmHg lower (95% CI (0.2, 2.8); p = 0.02); and at week 12, PADP was 1.7 mmHg lower (95% CI (0.3, 3.2); p = 0.02) with empagliflozin vs placebo. Results were consistent for PA systolic and PA mean pressures. There was no difference in mean loop diuretic management (daily furosemide equivalents) between treatment groups. No significant differences between treatment groups were observed in KCCQ, natriuretic peptide levels and 6-minute walking distance. Conclusions: In patients with HF and CardioMEMS PA pressure sensor, empagliflozin produced rapid reductions in PA pressures that were amplified over time and appeared to be independent of loop diuretic management. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03030222.

BACKGROUNDThe appropriate dose of aspirin to lower the risk of death, myocardial infarction, and stroke and to minimize major bleeding in patients with established atherosclerotic cardiovascular disease is a subject of controversy. METHODSUsing an open-label, pragmatic design, we randomly assigned patients with established atherosclerotic cardiovascular disease to a strategy of 81 mg or 325 mg of aspirin per day. The primary effectiveness outcome was a composite of death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke, assessed in a time-to-event analysis. The primary safety outcome was hospitalization for major bleeding, also assessed in a time-to-event analysis. RESULTSA total of 15,076 patients were followed for a median of 26.2 months (interquartile range [IQR], 19.0 to 34.9). Before randomization, 13,537 (96.0% of those with available information on previous aspirin use) were already taking aspirin, and 85.3% of these patients were previously taking 81 mg of daily aspirin. Death, hospitalization for myocardial infarction, or hospitalization for stroke occurred in 590 patients (estimated percentage, 7.28%) in the 81-mg group and 569 patients (estimated percentage, 7.51%) in the 325-mg group (hazard ratio, 1.02; 95% confidence interval [CI], 0.91 to 1.14). Hospitalization for major bleeding occurred in 53 patients (estimated percentage, 0.63%) in the 81-mg group and 44 patients (estimated percentage, 0.60%) in the 325-mg group (hazard ratio, 1.18; 95% CI, 0.79 to 1.77). Patients assigned to 325 mg had a higher incidence of dose switching than those assigned to 81 mg (41.6% vs. 7.1%) and fewer median days of exposure to the assigned dose (434 days [IQR, 139 to 737] vs. 650 days [IQR, 415 to 922]). CONCLUSIONSIn this pragmatic trial involving patients with established cardiovascular disease, there was substantial dose switching to 81 mg of daily aspirin and no significant differences in cardiovascular events or major bleeding between patients assigned to 81 mg and those assigned to 325 mg of aspirin daily. (Funded by the Patient-Centered Outcomes Research Institute; ADAPTABLE ClinicalTrials.gov number, NCT02697916.

Background The etiology of idiopathic dilated cardiomyopathy (DCM) is unknown by definition, but its familial subtype is considered to have a genetic component. We hypothesize that most idiopathic DCM, whether familial or non-familial, has a genetic basis, in which case a genetics-driven approach to identifying at-risk family members for clinical screening and early intervention could reduce morbidity and mortality. Methods Based on this hypothesis, we have launched the NHLBI- and NHGRI-funded DCM Precision Medicine Study, which aims to enroll 1,300 individuals (600 non-Hispanic African ancestry, 600 non-Hispanic European ancestry, and 100 Hispanic) who meet rigorous clinical criteria for idiopathic DCM along with 2,600 of their relatives. Enrolled relatives will undergo clinical cardiovascular screening to identify asymptomatic disease, and all individuals with idiopathic DCM will undergo exome sequencing to identify relevant variants in genes previously implicated in DCM. Results will be returned by genetic counselors 12-14 months after enrollment. The data obtained will be used to describe the prevalence of familial DCM among idiopathic DCM cases and the genetic architecture of idiopathic DCM in multiple ethnicity-ancestry groups. We will also conduct a randomized controlled trial to test the effectiveness of Family Heart Talk, an intervention to aid family communication, for improving uptake of preventive screening and surveillance in at-risk first-degree relatives. Conclusions We anticipate this study will demonstrate that idiopathic DCM has a genetic basis and guide best practices for a genetics-driven approach to early intervention in at-risk relatives.

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Background: The hypothesis of the Dilated Cardiomyopathy Precision Medicine Study is that most dilated cardiomyopathy has a genetic basis. The study returns results to probands and, when indicated, to relatives. While both the American College of Medical Genetics and Genomics/Association for Molecular Pathology and ClinGen’s MYH7 -cardiomyopathy specifications provide relevant guidance for variant interpretation, further gene- and disease-specific considerations were required for dilated cardiomyopathy. To this end, we tailored the ClinGen MYH7 -cardiomyopathy variant interpretation framework; the specifications implemented for the study are presented here. Methods: Modifications were created and approved by an external Variant Adjudication Oversight Committee. After a pilot using 81 probands, further adjustments were made, resulting in 27 criteria (9 modifications of the ClinGen MYH7 framework and reintroduction of 2 American College of Medical Genetics and Genomics/Association of Molecular Pathology criteria that were deemed not applicable by the ClinGen MYH7 working group). Results: These criteria were applied to 2059 variants in a test set of 97 probands. Variants were classified as benign (n=1702), likely benign (n=33), uncertain significance (n=71), likely pathogenic (likely pathogenic; n=12), and pathogenic (P; n=3). Only 2/15 likely pathogenic/P variants were identified in Non-Hispanic African ancestry probands. Conclusions: We tailored the ClinGen MYH7 criteria for our study. Our preliminary data show that 15/97 (15.5%) probands have likely pathogenic/P variants, most of which were identified in probands of Non-Hispanic European ancestry. We anticipate continued evolution of our approach, one that will be informed by new insights on variant interpretation and a greater understanding of the genetic architecture of dilated cardiomyopathy. Clinical Trial Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03037632

NP education plus tablet use was not associated with significantly lower 30-day readmission rates in comparison with NP alone, but a positive trend was seen. Patient satisfaction trended higher and heart failure explanations were better with NP education plus tablet. A larger study is needed to determine if NP education plus tablet reduces readmission rates following heart failure admission.