搜索结果：Circulation. Heart failure

Long-term oxygen therapy (LTOT) is a cornerstone of management for chronic hypoxemic respiratory diseases, such as chronic obstructive pulmonary disease, yet its physiological impact as a potent modulator of cardiovascular function remains a subject of ongoing investigation. While oxygen is primarily prescribed to correct arterial desaturation, its role as a regulator of vascular tone and cellular metabolism suggests it can exert significant, and sometimes contrasting, effects on the heart and systemic circulation. This review evaluates the evidence for LTOT in heart failure and pulmonary hypertension, 2 conditions where oxygen is frequently utilized despite varying levels of baseline hypoxemia. In heart failure, LTOT has not been shown to improve key hemodynamic variables and relevant endpoints, such as exercise capacity, in normoxemic patients. Some studies suggest that supplemental oxygen may even impose hemodynamic strain in this population by increasing systemic vascular resistance and reducing cardiac output. On the other hand, LTOT shows promise in improving relevant hemodynamic variables in pulmonary hypertension, such as mean pulmonary arterial pressure, as well as exercise capacity and other clinical measures across various baseline oxygen saturation levels. These findings suggest that the cardiovascular response to LTOT is highly dependent on the specific underlying pathology.

Renal dysfunction (RD) is common at admission for acute heart failure (AHF), but there is limited evidence focusing on older adults and considering the influence of physical function. We evaluated the prognostic significance of admission RD severity as a risk factor for adverse outcomes in older patients with AHF, while considering the potential modifying effect of physical function. This multicenter prospective cohort study enrolled 710 patients aged &#x2265;65 years with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Admission RD was stratified into 4 severity classes: mild RD (eGFR 45-59), moderate RD (eGFR 30-44), severe RD (eGFR 15-29), and kidney failure (eGFR <15). The primary outcome was a composite of HF readmission and all-cause death within 1 year post-discharge. Subgroup analyses assessed potential effect modification by physical function and other variables. After multivariable adjustment, severe RD or kidney failure was significantly associated with a higher risk of the composite outcome compared with mild RD (adjusted hazard ratio: 1.529; 95% confidence interval: 1.005-2.326). A possible interaction was observed between moderate RD and the Short Physical Performance Battery score at discharge (P for interaction=0.093). Severe RD or kidney failure at admission independently predicted 1-year HF readmission and all-cause death. In moderate RD, physical function may modify RD prognostic impact.

Symptomatic hypotension can limit sacubitril/valsartan therapy. Neprilysin inhibition may augment vasodilators, such as bradykinin. We hypothesized that bradykinin contributes to blood pressure (BP) lowering with sacubitril/valsartan in stable ambulatory patients with heart failure and reduced ejection fraction <50%. In a randomized, double-blind crossover trial, participants received intravenous infusion of the bradykinin B2 receptor inhibitor icatibant and a matching placebo for 6 hours following sacubitril/valsartan dosing at acute initiation (n=36) and after 8 weeks of chronic therapy (n=30). The primary end point was maximal change in mean arterial pressure (MAP). Plasma natriuretic peptides, urine cyclic GMP, urine volume, sodium excretion, renal plasma flow, and renovascular resistance were measured. The first dose of sacubitril/valsartan (50 mg) significantly lowered MAP by a mean maximum of &#x2248;10 mm&#x2009;Hg, which was similar during icatibant and placebo. Within 6 hours after the first sacubitril/valsartan dose, plasma ANP (atrial natriuretic peptide [1-28]) and urine cGMP/creatinine increased significantly, whereas B-type NP (1-32) and NT-proBNP (N-terminal pro B-type natriuretic peptide) did not. Icatibant partially blunted the rise in urine cGMP/creatinine, but did not affect other parameters. After 8 weeks of sacubitril/valsartan titrated to maximally tolerated doses, baseline ANP (1-28) remained increased, and baseline MAP and NT-proBNP were decreased compared with before sacubitril/valsartan initiation. MAP decreased further after dose administration of sacubitril/valsartan, and the mean maximal reduction in MAP was significantly attenuated during icatibant compared with placebo (9 versus 12 mm&#x2009;Hg; P=0.013). Icatibant also decreased renal plasma flow and increased renal vascular resistance after chronic dosing, without affecting heart rate, urine volume, urine sodium, cGMP/creatinine, or natriuretic peptides. BP lowering with sacubitril/valsartan occurs with both acute and chronic dosing. ANP (1-28) appears to mediate the initial BP reduction, whereas bradykinin contributes to BP lowering after dosing during chronic therapy. Clarifying these mechanisms may inform clinical management to optimize the benefit of this important heart failure and reduced ejection fraction therapy. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04113109.

Acute kidney injury (AKI) occurs in up to 40% of hospitalizations for acute decompensated heart failure (ADHF) and is associated with higher morbidity, longer hospital stays, and increased mortality. Despite its prevalence, current management remains largely supportive, with limited impact on kidney recovery or survival. This article proposes a novel, catheter-based extracorporeal system designed to preserve renal function in ADHF by directly addressing the underlying hemodynamic disturbances. The concept integrates venous decompression with direct renal arterial perfusion of oxygenated blood, thereby relieving renal congestion and improving oxygen delivery during systemic hypoperfusion. Drawing on principles of extracorporeal membrane oxygenation, the system would extract venous blood, oxygenate it externally, and reintroduce it into the renal circulation via percutaneous access. The physiologic rationale, technical feasibility, and potential clinical applications are discussed, along with pathways for preclinical validation and translation. Targeted renal perfusion with oxygenated blood represents a novel and potentially transformative approach to preventing AKI in ADHF. By addressing venous congestion, impaired perfusion, and renal hypoxia simultaneously, this strategy may redefine organ-specific protection in heart failure.

Heart failure (HF) is a major cause of morbidity and mortality in patients with congenital heart disease (CHD), driven by residual lesions and progressive ventricular dysfunction. The heterogeneity of CHD anatomy and physiology often limits the applicability of standard HF therapies. This review aims to summarize contemporary catheter-based strategies used to diagnose, stabilize, and treat HF in patients with CHD across both acute and chronic clinical settings, and to evaluate their role in improving outcomes and delaying surgical or transplant-based therapies. Recent advances in transcatheter technology have expanded therapeutic options for HF in CHD. Invasive hemodynamic monitoring and implantable sensors enable more precise assessment and remote management of complex circulations. Short-term mechanical circulatory support systems, including extracorporeal membrane oxygenation and percutaneous ventricular assist devices, are increasingly used as bridges to recovery or transplantation. Catheter-based closure of shunts (e.g., atrial or ventricular septal defects and patent ductus arteriosus) and creation of controlled shunts using devices such as atrial flow regulators provide strategies to optimize hemodynamics. Transcatheter valve therapies, including pulmonary valve implantation and atrioventricular valve repair, have become important alternatives to repeat surgery. In patients with failing Fontan circulation, interventions such as fenestration creation, pathway stenting, collateral embolization, and emerging lymphatic procedures have demonstrated promising clinical benefits. Percutaneous interventions have become central to the management of HF in CHD, offering minimally invasive, anatomy-specific approaches that can stabilize acute decompensation, address residual lesions, and palliate chronic circulatory failure. These strategies enable individualized treatment pathways and may delay or reduce the need for surgical reintervention or transplantation. Continued technological innovation, improved patient selection, and multidisciplinary expertise will be essential to further refine these approaches.

The residential environment may influence access to care and prognosis in patients with heart failure (HF). Evidence on the impact of geographic factors in Japan is limited. We investigated the association of home-to-hospital distance and residential population density with 1-year clinical outcomes in patients hospitalized for acute decompensated HF. We used the Kyoto Congestive Heart Failure registry to analyze 3,616 patients who were discharged alive after their first hospitalization. Home-to-hospital distance was calculated using road travel distance and dichotomized by the median (8.0 km). Residential density was classified as urban (densely inhabited districts [DID]) or suburban (non-DID). The primary outcome was all-cause death at 1 year, assessed using hospital-stratified Cox proportional hazards models. The median home-to-hospital distance was 8.0 km (interquartile range 4.1-14.5 km); 1,797 (49.7%) patients were in the long-distance group. The long-distance group had a higher risk of all-cause death than the short-distance group (adjusted hazard ratio [HR] 1.19; 95% confidence interval [CI] 1.02, 1.39; P=0.02). As a continuous variable, each doubling of distance was associated with increased all-cause death (HR 1.06; 95% CI 1.02, 1.10). Suburban residence was not significantly associated with the primary outcome compared with urban residence (adjusted HR 1.18; 95% CI 0.99, 1.44; P=0.06). In Japanese patients hospitalized for acute decompensated HF, longer home-to-hospital distance, but not residential population density, was associated with a higher risk of 1-year all-cause death.

There are limited data about the role of cardiac resynchronization therapy (CRT) in adults with congenital heart disease (CHD) and heart failure with reduced ejection fraction (HFrEF). (i) Assess the relationship between CRT and clinical outcomes (all-cause mortality and cardiovascular events). (ii) Assess temporal changes in clinical indices of disease severity (NYHA class, peak oxygen consumption, NT-proBNP, and LVEF) post-CRT. Retrospective study of adults with CHD, biventricular circulation and systemic LV and HFrEF who received CRT at Mayo Clinic (2003-203). Clinical indices of disease severity were assessed pre-CRT and 1-year post-CRT. We defined a CRT responder as a patient with absolute increase in LVEF &#x2265;10% and improvement in NYHA class by &#x2265;1 unit post-CRT. Intensity of HF therapy was assessed using the guideline-directed medical therapy (GDMT) score. Of 327 CHD patients with HFrEF, 105 (32%) received CRT (age 51&#xb1;15 years, 68% males). CRT was associated with 24% decrease in mortality (adjusted hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.51, 0.97), and 21% decrease in cardiovascular events (adjusted HR 0.79, 95%CI 0.63, 0.94). Of the 105 patients, 71 (68%) were CRT responders. Higher GDMT score was associated with greater odds of CRT response (adjusted odds ratio 1.28, 95% CI 1.04, 1.47). CRT responders had greater temporal improvement in NYHA class, peak oxygen consumption, NT-proBNP levels, and lower risk of cardiovascular events (unadjusted HR 0.73, 95% CI 0.47, 0.99). These data highlight the clinical benefits of CRT and GDMT for management of HFrEF in CHD and support the use of these therapies in this population.

Heart failure with preserved ejection fraction (HFpEF) constitutes a considerable global health burden and a major clinical challenge due to the absence of effective therapies, and the underlying pathophysiology remains elusive. Coronary microvascular dysfunction (CMD), which is highly prevalent in patients with HFpEF, triggers myocardial ischemia that impairs both left ventricular diastolic and systolic function. Given that microvascular dysfunction is a central feature of HFpEF, CMD is now considered an important factor in its pathogenesis. Coronary flow reserve (CFR), defined as the ratio of maximal hyperemic to resting blood flow velocity, is a highly valuable marker of myocardial ischemia. Furthermore, it serves as a comprehensive indicator of coronary vasomotor dysfunction, measuring the combined hemodynamic effects of both epicardial and microvascular coronary arteries on myocardial perfusion. This protocol focused on assessing the changes in CFR in a mouse model of HFpEF using Doppler echocardiography. In this study, control mice&#xa0;showed&#xa0;a&#xa0;greater than twofold&#xa0;increase in peak coronary blood flow velocity with isoflurane-induced vasodilation compared to resting values, whereas this response was significantly attenuated in HFpEF mice. In HFpEF, a reduced CFR predicts adverse outcomes and reflects underlying microvascular dysfunction, positioning it as a key tool for studying disease progression and guiding patient selection.

Heart failure with reduced ejection fraction (HFrEF) affects millions worldwide and is characterized by chronic cardiac dysfunction, impaired perfusion, altered skeletal muscle energetics, and, thus, exercise intolerance. Efficient therapeutic strategies reducing the burden of the impaired muscle metabolism in HFrEF are currently lacking. Hence, in the present study, we sought to determine whether myosin dynamics and its important role in ATP consumption can constitute a potent biochemical target to optimize skeletal muscle energy usage in HFrEF. We used skeletal muscle tissue from 11 human patients with HFrEF and 10 controls with comparable age, sex, and body mass index. We isolated individual myofibres and incubated them ex vivo with varying concentrations of a myosin inhibitor, mavacamten. We then performed 2'-(or-3')-O-(N-Methylanthraniloyl) adenosine 5'-triphosphate chase experiments, together with LC/MS-based proteomics profiling. We observed a distinct regulation of acetyl-lysine sites and higher myosin energy consumption in resting muscle fibers from patients with HFrEF than in controls. When exposed to mavacamten, we found a dose-dependent reduction in myosin ATP consumption in myofibres of patients with HFrEF, reversing the pathological over-consumption. Skeletal muscle myosin becomes inefficient in HFrEF. Pharmacological inhibition of myosin ATPase activity offers an inventive strategy to lower muscle energy demand and potentially address metabolic disturbances in HFrEF.

Heart failure (HF) remains a leading cause of morbidity and mortality worldwide despite major advances in pharmacological and device-based therapies. A central limitation of current treatments is their predominant focus on neurohumoral modulation rather than the intrinsic biological processes driving cardiac remodeling. Recent progress in genetics, single-cell and spatial omics, and systems biology has fundamentally reshaped our understanding of HF, revealing it as a heterogeneous, multicellular syndrome characterized by disrupted intercellular communication within the cardiac cellular ecosystem. Endothelial cells, fibroblasts, immune cells, and cardiomyocytes engage in dynamic signaling networks that coordinate myocardial structure, metabolism, and function; pathological remodeling emerges when these networks become maladaptive. Circulating biomarkers increasingly serve as readouts of these intercellular interactions, reflecting senescence, inflammation, fibrosis, and metabolic stress. Among them, insulin-like growth factor-binding protein 7 has emerged as a key mediator linking endothelial cell senescence to cardiomyocyte metabolic dysfunction. In parallel, stress-activated fibroblast subpopulations drive HF progression through paracrine signaling pathways such as the MYC-CXCL1-CXCR2 axis. These insights open new therapeutic opportunities beyond conventional pharmacology. Immunization-based strategies targeting pathological intercellular communication represent a novel paradigm for disease-modifying HF therapy. Peptide-based vaccines that neutralize circulating mediators or eliminate pathogenic cell populations have demonstrated efficacy in preclinical models and early clinical studies. In this review, we integrate emerging trends in HF research with recent advances in multicellular biology and therapeutic vaccination, proposing immunization as a unifying strategy to target cardiac remodeling at its roots.

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As transcatheter aortic valve replacement (TAVR) expands to patients with longer life expectancy, the impact of failure mechanisms on outcomes of TAVR-explant and redo-TAVR remains uncertain. We sought to evaluate outcomes of TAVR reintervention based on the failure mechanism of the index transcatheter aortic valve. From 2009 to 2022, 553 patients from 29 centers in the EXPLANTORREDO-TAVR registry underwent TAVR-explant or redo-TAVR for transcatheter aortic valve failure. Patients with endocarditis were excluded. Patients with structural valve deterioration (SVD, N=224 [64.9%]) were compared with those with nonstructural valve dysfunction (NSVD, N=121 [35.1%]), comprising paravalvular leak (86.0%) and prosthesis-patient mismatch (14.0%). Outcomes were assessed at 30 days and 1 year. Mean age was 75.6&#xb1;9.3 years, with 42% women. There were no differences in reintervention type between groups (redo-TAVR in 58.0% SVD versus 49.6% NSVD; TAVR-explant: 42.0% versus 50.4%; P=0.14). Compared with NSVD, SVD was the predominant mode of failure in balloon-expandable valves (50.7% versus 24.8%; P<0.001), had a longer time to reintervention (50.7 versus 5.5 months; P<0.001), and favored non-balloon-expandable valves at redo-TAVR (56.9% versus 33.3%; P=0.003). Mortality at 30 days and 1 year did not differ significantly between SVD and NSVD for either redo-TAVR (30 days: 3.2% versus 1.7%, P=1.00; 1 year: 18.0% versus 12.0%; P=0.47) or TAVR-explant (30 days: 16.3% versus 12.1%, P=0.63; 1 year: 40.0% versus 29.5%; P=0.39). There were also no differences in risk-adjusted 3-year cumulative mortality between groups (redo-TAVR: HR, 1.30 [95% CI, 0.68-2.46], P=0.43 [ref=NSVD]; TAVR-explant: HR, 1.24 [95% CI, 0.64-2.41]; P=0.53). SVD and NSVD failures had distinct valve types and reintervention timing, with SVD having a longer time to TAVR reintervention, but the failure mechanism did not impact reintervention type or clinical outcomes.

Among accepted US heart organs, listing centers accept organ offers earliest for White women, followed by Black women, White men, and Black men. Understanding the relationships of center- and geographic-level decisions is necessary to understand waitlist disparities. We sought to determine whether listing center and geography are associated with the first heart organ acceptance by candidate race, since race demographics vary regionally across the United States. Using the United Network for Organ Sharing data sets, we identified first organ offers for Black and White candidates listed for heart transplant (October 18, 2018 to September 30, 2024) and compared models with and without listing center effects adjusted for candidate-, donor-, and offer-level variables. Among 20&#x2009;668 candidates (31.6% Black, 68.4% White, 26.5% women), the adjusted odds of first offer acceptance were lower for Black candidates compared with White candidates (odds ratio, 0.84 [95% CI, 0.76-0.94]; P=0.001) when listing center was not included in the model; but after adjusting for listing center effects, odds were similar by race (odds ratio, 0.98 [95% CI, 0.88-1.10]; P=0.78). There were no clear geographic patterns by center, but centers with lower proportions of Black candidates had higher acceptance rates. Variability in overall acceptance rate among listing centers explains the lower first offer acceptance for Black compared with White heart candidates. Baseline acceptance rates were linked to the center-level proportion of Black candidates but not geography. Investigation of strategies to systemically improve early acceptance of good heart organs may reduce Black and White disparities in wait time duration.

For much of the 20th century, cardiovascular disease (CVD) was viewed as a predominantly male condition, contributing to under-recognition and undertreatment in women. The Framingham Heart Study (FHS) fundamentally changed this paradigm by establishing that women experience a high lifetime burden of CVD and that traditional risk factors may have sex-specific effects. During nearly 8 decades of follow-up, FHS has demonstrated that women develop CVD later in life, but experience accelerated midlife accumulation of risk factors and substantial late-life morbidity, particularly from stroke and heart failure with preserved ejection fraction. FHS investigations further revealed that blood pressure, diabetes, adiposity, and lipid-related risk occur at lower biological thresholds in women and that ischemic heart disease is frequently different in presentation. Collectively, these findings define women's CVD as biologically distinct rather than a delayed manifestation of male disease, with important implications for sex-informed risk assessment, prevention, and clinical care.