Heart failure is a global disease with significant morbidity. Heart transplant (HT) can be a lifesaving therapy for select patients with end-stage heart failure. In 2020, over 7000 HTs were performed globally; 90% of HTs were performed in the United States and Western Europe, with only 10% throughout the rest of the world. In this article, we offer an overview of the global landscape of HT, exploring challenges and prospects worldwide. We review HT practices, rates and post-HT outcomes, underscoring the differences between countries within each region. We review limitations hindering HT expansion, such as sociocultural factors, as seen in Japan and Israel; health care funding, in countries like India and South Africa; socioeconomic disparities in access, like the United States; and shortage in organ supply, as seen in China and Saudi Arabia. This review underscores the need to address limitations and highlights opportunities to enhance global HT accessibility, especially in lower- and middle-income countries.

Hypertrophic cardiomyopathy is the most common genetic cardiac disease and is characterized by left ventricular hypertrophy. Although this hypertrophy often associates with sarcomeric gene mutations, nongenetic factors also contribute to the disease, leading to diastolic dysfunction. Notably, this dysfunction manifests before hypertrophy and is linked to hypercontractility, as well as nonuniform contraction and relaxation (myofibril asynchrony) of the myocardium. Although the distribution of hypertrophy in hypertrophic cardiomyopathy can vary both between and within individuals, in most cases, it is primarily confined to the interventricular septum. The reasons for septal thickening remain largely unknown. In this article, we propose that alterations in muscle fiber geometry, present from birth, dictate the septal shape. When combined with hypercontractility and exacerbated by left ventricular outflow tract obstruction, these factors predispose the septum to an isometric type of contraction during systole, consequently constraining its mobility. This contraction, or more accurately, this focal increase in biomechanical stress, prompts the septum to adapt and undergo remodeling. Drawing a parallel, this is reminiscent of how earthquake-resistant buildings are retrofitted with vibration dampers to absorb the majority of the shock motion and load. Similarly, the heart adapts by synthesizing viscoelastic elements such as microtubules, titin, desmin, collagen, and intercalated disc components. This pronounced remodeling in the cytoskeletal structure leads to noticeable septal hypertrophy. This structural adaptation acts as a protective measure against damage by attenuating myofibril shortening while reducing cavity tension according to Laplace Law. By examining these events, we provide a coherent explanation for the septum's predisposition toward hypertrophy.

The development of tools to support shared decision-making should be informed by patients' decisional needs and treatment preferences, which are largely unknown for heart failure (HF) with reduced ejection fraction (HFrEF) pharmacotherapy decisions. We aimed to identify patients' decisional needs when considering HFrEF medication options. This was a qualitative study using semi-structured interviews. We recruited patients with HFrEF from 2 Canadian ambulatory HF clinics and clinicians from Canadian HF guideline panels, HF clinics, and Canadian HF Society membership. We identified themes through inductive thematic analysis. Participants included 15 patients and 12 clinicians. Six themes and associated subthemes emerged related to HFrEF pharmacotherapy decision-making: (1) patient decisional needs included lack of awareness of a choice or options, difficult decision timing and stage, information overload, and inadequate motivation, support and resources; (2) patients' decisional conflict varied substantially, driven by unclear trade-offs; (3) treatment attribute preferences-patients focused on both benefits and downsides of treatment, whereas clinicians centered discussion on benefits; (4) quality of life-patients' definition of quality of life depended on pre-HF activity, though most patients demonstrated adaptability in adjusting their daily activities to manage HF; (5) shared decision-making process-clinicians' described a process more akin to informed consent; (6) decision support-multimedia decision aids, virtual appointments, and primary-care comanagement emerged as potential enablers of shared decision-making. Patients with HFrEF have several decisional needs, which are consistent with those that may respond to decision aids. These findings can inform the development of HFrEF pharmacotherapy decision aids to address these decisional needs and facilitate shared decision-making.

Mutations in LMNA encoding nuclear envelope proteins lamin A/C cause dilated cardiomyopathy. Activation of the AKT/mTOR (RAC-α serine/threonine-protein kinase/mammalian target of rapamycin) pathway is implicated as a potential pathophysiologic mechanism. The aim of this study was to assess whether pharmacological inhibition of mTOR signaling has beneficial effects on heart function and prolongs survival in a mouse model of the disease, after onset of heart failure. We treated male LmnaH222P/H222P mice, after the onset of heart failure, with placebo or either of 2 orally bioavailable mTOR inhibitors: everolimus or NV-20494, a rapamycin analog highly selective against mTORC1. We examined left ventricular remodeling, and the cell biological, biochemical, and histopathologic features of cardiomyopathy, potential drug toxicity, and survival. Everolimus treatment (n=17) significantly reduced left ventricular dilatation and increased contractility on echocardiography, with a 7% (P=0.018) reduction in left ventricular end-diastolic diameter and a 39% (P=0.0159) increase fractional shortening compared with placebo (n=17) after 6 weeks of treatment. NV-20494 treatment (n=15) yielded similar but more modest and nonsignificant changes. Neither drug prevented the development of cardiac fibrosis. Drug treatment reactivated suppressed autophagy and inhibited mTORC1 signaling in the heart, although everolimus was more potent. With regards to drug toxicity, everolimus alone led to a modest degree of glucose intolerance during glucose challenge. Everolimus (n=20) and NV-20494 (n=20) significantly prolonged median survival in LmnaH222P/H222P mice, by 9% (P=0.0348) and 11% (P=0.0206), respectively, compared with placebo (n=20). These results suggest that mTOR inhibitors may be beneficial in patients with cardiomyopathy caused by LMNA mutations and that further study is warranted.

Although much attention has been paid to admission and transfer patterns for cardiogenic shock, contemporary data are lacking on decompensated heart failure (HF) admissions and transfers and the impact of advanced therapy centers (ATCs) on outcomes. HF hospitalizations were obtained from the Nationwide Readmissions Database 2016 to 2019. Centers performing at least 1 heart transplant or left ventricular assist device were classified as ATCs. Patient characteristics, outcomes, and procedural volume were compared among 3 cohorts: admissions to non-ATCs, admissions to ATCs, and transfers to ATCs. A secondary analysis evaluated outcomes for severe HF hospitalizations (cardiogenic shock, cardiac arrest, and mechanical ventilation). Multivariable logistic regression was performed to adjust for the presence of HF decompensations and significant clinical variables during univariate analysis. A total of 2 331 690 hospitalizations (81.2%) were admissions to non-ATCs (94.5% of centers), 525 037 (18.3%) were admissions to ATCs (5.5% of centers), and 15 541 (0.5%) were transferred to ATCs. Patients treated at ATCs (especially those transferred) had higher rates of HF decompensations, procedural frequency, lengths of stay, and costs. Unadjusted mortality was 2.6% at non-ATCs and was higher at ATCs, both for directly admitted (2.9%, P<0.001) and transferred (11.2%, P<0.001) patients. However, multivariable-adjusted mortality was significantly lower at ATCs, both for directly admitted (odds ratio, 0.82 [95% CI, 0.78-0.87]; P<0.001) and transferred (odds ratio, 0.66 [95% CI, 0.57-0.78]; P<0.001) patients. For severe HF admissions, unadjusted mortality was 37.2% at non-ATCs and was lower at ATCs, both for directly admitted (25.3%, P<0.001) and transferred (25.2%, P<0.001) patients, with similarly lower multivariable-adjusted mortality. Patients with HF treated at ATCs were sicker but associated with higher procedural volume and lower adjusted mortality.

Individuals with heart failure (HF) and diabetes generally have more severe HF and more comorbidities than those with HF and no diabetes, and the former may therefore have an increased risk of competing causes of death to arrhythmic death.<br/><br/>In the DANISH trial (The Danish Study to Assess the Efficacy of Implantable Cardioverter Defibrillators [ICDs] in Patients With Nonischemic Systolic Heart Failure on Mortality), primary prophylactic ICD implantation, compared with usual care, significantly reduced the rate of sudden cardiovascular death, but not all-cause mortality.1 We have previously examined the effect of ICD implantation according to diabetes status in the DANISH trial and found no statistically significant interaction between diabetes and the effect of ICD implantation.2 However, given that diabetes is a chronic disease, which can cause various systemic adverse effects over the long term, we conducted an extended follow-up study of the DANISH trial, adding 4 years of additional follow-up, to examine the long-term effects of primary prophylactic ICD implantation, according to diabetes status.<br/><br/>The data that support the findings of this study are available from the corresponding author on reasonable request. The design of the DANISH trial has been published and described previously.1,3 In brief, 1116 patients with nonischemic HF with reduced ejection fraction (HFrEF) were enrolled from 5 ICD-implanting centers in Denmark and randomized in a 1:1 ratio to ICD implantation or usual care. In the present analysis with extended follow-up, patients were followed from randomization until death or May 18, 2020, whichever came first, and no patients were lost to follow-up. The primary outcome was death from any cause, and secondary outcomes were cardiovascular death and sudden cardiovascular death. The protocol was approved by the ethics committee in the Capital Region of Denmark (H-D-2007-0101), and all participants gave written informed consent.<br/><br/>The effect of ICD implantation versus usual care was evaluated using the Kaplan-Meier estimator, Aalen-Johansen estimator, and Cox proportional hazards regression models, stratified according to center and status with respect to cardiac resynchronization therapy implantation. Data were analyzed according to the intention-to-treat principle. A P-value of 0.05 was considered statistically significant.

Coverage for cardiac rehabilitation (CR) for patients with heart failure with reduced ejection fraction was expanded in 2014, but contemporary referral and participation rates remain unknown. Patients hospitalized for heart failure with reduced ejection fraction (≤35%) in the American Heart Association Get With The Guidelines-Heart Failure registry from 2010 to 2020 were included, and CR referral status was described as yes, no, or not captured. Temporal trends in CR referral were assessed in the overall cohort. Patient and hospital-level predictors of CR referral were assessed using multivariable-adjusted logistic regression models. Additionally, CR referral and proportional utilization of CR within 1-year of referral were evaluated among patients aged >65 years with available Medicare administrative claims data who were clinically stable for 6-weeks postdischarge. Finally, the association of CR referral with the risk of 1-year death and readmission was evaluated using multivariable-adjusted Cox models. Of 69,441 patients with heart failure with reduced ejection fraction who were eligible for CR (median age 67 years; 33% women; 30% Black), 17,076 (24.6%) were referred to CR, and referral rates increased from 8.1% in 2010 to 24.1% in 2020 (Ptrend<0.001). Of 8310 patients with Medicare who remained clinically stable 6-weeks after discharge, the CR referral rate was 25.8%, and utilization of CR among referred patients was 4.1% (mean sessions attended: 6.7). Patients not referred were more likely to be older, of Black race, and with a higher burden of comorbidities. In adjusted analysis, eligible patients with heart failure with reduced ejection fraction who were referred to CR (versus not referred) had a lower risk of 1-year death (hazard ratio, 0.84 [95% CI, 0.70-1.00]; P=0.049) without significant differences in 1-year readmission. CR referral rates have increased from 2010 to 2020. However, only 1 in 4 patients are referred to CR. Among eligible patients who received CR referral, participation was low, with <1 of 20 participating in CR.

HomeCirculation: Heart FailureAhead of PrintPredicting Stroke in Heart Failure With Preserved Ejection Fraction Without Atrial Fibrillation No AccessEditorialRequest AccessAboutView PDFSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toNo AccessEditorialRequest AccessPredicting Stroke in Heart Failure With Preserved Ejection Fraction Without Atrial Fibrillation Phillip H. Lam and Anwar Chahal Phillip H. LamPhillip H. Lam Correspondence to: Phillip H. Lam, MD, MedStar Washington Hospital Center, 110 Irving St NW, Washington, DC 20010. Email E-mail Address: [email protected] Department of Cardiology, MedStar Heart and Vascular Institute, Washington, DC (P.H.L.). Georgetown University, Washington, DC (P.H.L.). Search for more papers by this author and Anwar ChahalAnwar Chahal https://orcid.org/0000-0001-7825-8827 Department of Cardiology, WellSpan Heart and Vascular Center, York, PA (A.C.). Barts Heart Centre, London, United Kingdom (A.C.). Search for more papers by this author Originally published23 Jun 2023https://doi.org/10.1161/CIRCHEARTFAILURE.123.010762Circulation: Heart Failure. 2023;0:e010762FootnotesFor Disclosures, see page xxx.The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.Correspondence to: Phillip H. Lam, MD, MedStar Washington Hospital Center, 110 Irving St NW, Washington, DC 20010. Email phillip.h.[email protected]net Previous Back to top Next FiguresReferencesRelatedDetails Advertisement Article InformationMetrics © 2023 American Heart Association, Inc.https://doi.org/10.1161/CIRCHEARTFAILURE.123.010762PMID: 37350258 Originally publishedJune 23, 2023 KeywordsHFpEFstrokeEditorialsatrial fibrillationPDF download Advertisement SubjectsBiomarkersClinical Studies

Following treatment for acute decompensated heart failure, in-hospital observation on oral diuretics (OOD) is recommended, assuming it provides actionable information on discharge diuretic dosing and thus reduces readmissions. In the Mechanisms of Diuretic Resistance (MDR) cohort, we analyzed in-hospital measures of diuretic response, provider's decisions, and diuretic response ≈30 days postdischarge. In a Yale multicenter cohort, we assessed if in-hospital OOD was associated with 30-day readmission risk. The main objective of this study was to evaluate the utility of in-hospital OOD. Of the 468 patients in the MDR cohort, 57% (N=265) underwent in-hospital OOD. During the OOD, weight change and net fluid balance correlated poorly with each other (r=0.36). Discharge diuretic dosing was similar between patients who had increased, stable, or decreased weight (decreased discharge dose from OOD dose in 77% versus 72% versus 70%, respectively), net fluid status (decreased discharge dose from OOD dose in 100% versus 69% versus 74%, respectively), and urine output (decreased discharge dose from OOD dose in 69% versus 79% versus 72%, respectively) during the 24-hour OOD period (P>0.27 for all). In participants returning at 30 days for formal quantification of outpatient diuretic response (n=98), outpatient and inpatient OOD natriuresis was poorly correlated (r=0.26). In the Yale multicenter cohort (n=18 454 hospitalizations), OOD occurred in 55% and was not associated with 30-day hospital readmission (hazard ratio, 0.98 [95% CI, 0.93-1.05]; P=0.51). In-hospital OOD did not provide actionable information on diuretic response, was not associated with outpatient dose selection, did not predict subsequent outpatient diuretic response, and was not associated with lower readmission rate. Additional research is needed to replicate these findings and understand if these resources could be better allocated elsewhere. URL: https://www. gov; Unique identifier: NCT02546583.