Circulation: Heart Failure最新文献

Background: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome that may emerge from overlapping systemic processes associated with comorbidities. We assessed whether unique clusters of circulating proteins are associated with specific clinical characteristics and functional status at baseline and follow-up in a well-phenotyped cohort of patients with HFpEF.

Methods: We evaluated 368 proteins associated with cardiovascular disease and inflammation in prerandomization blood samples from 763 VITALITY-HFpEF (Vericiguat to Improve Physical Functioning in Daily Living Activities of Patients With HFpEF) participants who had a left ventricular ejection fraction ≥45% and a heart failure decompensation event within 6 months. Proteins were clustered, and their associations with clinical characteristics, baseline, and 24-week functional outcomes (Kansas City Cardiomyopathy Questionnaire Physical Limitation Score, 6-minute walk distance [6MWD], and Fried frailty phenotype) were estimated with linear regression. Elastic net regression was used to derive a proteomic summary composite to predict changes in 24-week functional outcomes.

Results: Four unique protein clusters were identified, containing 24, 66, 197, and 81 proteins. At baseline, 2 protein clusters with the hub proteins caspase-3 and Dickkopf-related protein 1 were associated with increased frailty, whereas the cluster with tumor necrosis factor receptor 1 as a hub protein was associated with lower Kansas City Cardiomyopathy Questionnaire Physical Limitation Score and shorter 6MWD. By contrast, the cluster with protein C as a hub protein was associated with less frailty and longer a 6MWD. The 24-week increase in 6MWD was negatively correlated with the protein cluster with caspase-3; the protein C cluster was correlated with less frailty at 24 weeks. The baseline proteomic summary composite predicted observed changes in Kansas City Cardiomyopathy Questionnaire Physical Limitation Score and 6MWD at 24 weeks (r=0.42 and 0.30; P<0.001 for both).

Conclusions: Proteomics differentiate specific baseline functional traits associated with HFpEF and may facilitate phenotyping in a heterogeneous disease. These proteins also provide insights into the diverse pathophysiology of HFpEF and which patients may improve functional status during follow-up.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03547583.

Background: More women of childbearing age are surviving after heart transplantation (HT), many of whom have a desire to become pregnant. Limited data exist evaluating patients' perspectives, receipt of counseling, and knowledge surrounding contraception, pregnancy, breastfeeding, and medication safety after HT.

Methods: We conducted a voluntary, confidential, web-based cross-sectional survey of women who were childbearing age (defined as 18-45 years) at the time of HT. Transplants occurred between January 2005 and January 2020. Surveys were conducted across 6 high-volume HT centers in the United States.

Results: There were 64 responses from women who were of childbearing age at the time of HT. Twenty-five women (39.1%) were pregnant before HT, and 6 (9.4%) women reported at least 1 pregnancy post-transplant. Fifty-three percent (n=34) reported they did not receive enough information on post-HT pregnancy before listing for HT, and 26% (n=16) did not discuss their ability to become pregnant with their care team before proceeding with HT. Following HT, 44% (n=28) still felt that they had not received enough information regarding pregnancy. The majority of women (n=49, 77%) had discussed contraception to prevent unplanned pregnancy with their transplant team. Twenty percent (n=13) reported that pregnancy was never safe after transplantation based on the information they had received from their transplant providers.

Conclusions: Many women feel they are not receiving adequate counseling with regard to posttransplant reproductive health. This survey highlights an opportunity to improve both provider education and patient communication to better support women with HT desiring posttransplant pregnancy.

Background: Increased hsCRP (high-sensitivity C-reactive protein), a marker of inflammation, is associated with incident cardiovascular events. We aim to determine whether the baseline or trajectory of hsCRP levels over time predicts incident heart failure (HF) hospitalization.

Methods: JHS (Jackson Heart Study) participants' (n=3920 Black adults) hsCRP levels were measured over 3 visits (from 2000 to 2013). We assessed the association of hsCRP at baseline (visit 1) with incident HF hospitalization using Cox proportional hazards models. Furthermore, we assessed the association of the trajectory of hsCRP over repeated measurements (visits 1-3) with incident HF using joint models. Hazard ratios are reflective of an increase in hsCRP by 1 SD on a log2 scale. We also assessed the association of change in hsCRP between visit 1 and visit 3 with Cox proportional hazards models by grouping patients by low (<2 mg/L) and high (≥2 mg/L) hsCRP levels. The 4 groups were low-to-low (referent), low-to-high, high-to-low, and high-to-high.

Results: Mean baseline age of participants was 54±13 years, and 63.8% were women. Over a median follow-up of 12 years, 308 (7.9%) participants were hospitalized with incident HF. Baseline hsCRP was not associated with incident HF (adjusted hazard ratio, 1.08 [95% CI, 0.96-1.22]). However, increasing hsCRP levels over repeated measures were associated with a higher risk of incident HF overall (adjusted hazard ratio, 1.22 [95% CI, 1.03-1.44]) and HF with preserved ejection fraction (adjusted hazard ratio, 1.30 [95% CI, 1.02-1.65]) but not HF with reduced ejection fraction (P>0.05). Furthermore, changes in hsCRP from low-to-high and high-to-low levels were associated with incident HF (P<0.05).

Conclusions: While baseline hsCRP was not associated with incident HF, an increasing trajectory of hsCRP over time was associated with increased risk for incident HF (particularly HF with preserved ejection fraction). Temporal change in hsCRP may be an important marker of risk for incident HF with preserved ejection fraction in Black adults.

Background: We identified peripherally limited patients using cardiopulmonary exercise testing and measured skeletal muscle oxygen transport and utilization during invasive single leg exercise testing to identify the mechanisms of the peripheral limitation.

Methods: Forty-five patients with heart failure with preserved ejection fraction (70±7 years, 27 females) completed seated upright cardiopulmonary exercise testing and were defined as having a (1) peripheral limitation to exercise if cardiac output/oxygen consumption (VO₂) was elevated (≥6) or 5 to 6 with a stroke volume reserve >50% (n=31) or (2) a central limitation to exercise if cardiac output/VO₂ slope was ≤5 or 5 to 6 with stroke volume reserve <50% (n=14). Single leg knee extension exercise was used to quantify peak leg blood flow (Doppler ultrasound), arterial-to-venous oxygen content difference (femoral venous catheter), leg VO₂, and muscle oxygen diffusive conductance. In a subset of participants (n=36), phosphocreatine recovery time was measured by magnetic resonance spectroscopy to determine skeletal muscle oxidative capacity.

Results: Peak VO₂ during cardiopulmonary exercise testing was not different between groups (central: 13.9±5.7 versus peripheral: 12.0±3.1 mL/min per kg; P=0.135); however, the peripheral group had a lower peak arterial-to-venous oxygen content difference (central: 13.5±2.0 versus peripheral: 11.1±1.6 mLO₂/dL blood; P<0.001). During single leg knee extension, there was no difference in peak leg VO₂ (P=0.306), but the peripherally limited group had greater blood flow/VO₂ ratio (P=0.024), lower arterial-to-venous oxygen content difference (central: 12.3±2.5 versus peripheral: 10.3±2.2 mLO₂/dL blood; P=0.013), and lower muscle oxygen diffusive conductance (P=0.021). A difference in magnetic resonance spectroscopy-derived phosphocreatine recovery time was not detected (P=0.199).

Conclusions: Peripherally limited patients with heart failure with preserved ejection fraction identified by cardiopulmonary exercise testing have impairments in oxygen transport and utilization at the level of the skeletal muscle quantified by invasive knee extension exercise testing, which includes an increased blood flow/V̇O₂ ratio and poor muscle diffusive capacity.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04068844.

Heart failure with preserved ejection fraction (HFpEF) is a common subtype of heart failure marked by impaired left ventricular diastolic function and decreased myocardial compliance. Given the limited availability of evidence-based pharmacological treatments for HFpEF, there is a growing interest in nonpharmacological interventions as viable therapeutic alternatives. This review aims to explore the pathophysiology of HFpEF and present recent advancements in nonpharmacological management approaches, encompassing noninvasive therapies, invasive procedures and targeted treatments for comorbidities. An extensive literature review was undertaken to identify and synthesize emerging nonpharmacological treatment options for HFpEF, assessing their potential to enhance patient outcomes. Nonpharmacological strategies, such as vagus nerve stimulation, percutaneous pulmonary artery denervation, renal denervation, transcatheter insertion of atrial shunts and pericardial resection, demonstrate promising potential for alleviating HFpEF symptoms and improving patient prognosis. Moreover, addressing comorbidities, such as hypertension and diabetes, may offer additional therapeutic benefits. These cutting-edge techniques, in conjunction with well-established exercise therapies, pave the way for future research and clinical applications in the field. Nonpharmacological interventions hold promise for advancing HFpEF patient care and fostering a deeper understanding of these treatment approaches, which will facilitate new clinical applications and contribute to the development of more targeted therapies.

Background: The health-related quality of life (HRQOL) and cardiopulmonary exercise testing (CPET) performance of individuals with subclinical and early stage hypertrophic cardiomyopathy (HCM) have not been systematically studied. Improved understanding will inform the natural history of HCM and factors influencing well-being.

Methods: VANISH trial (Valsartan for Attenuating Disease Evolution in Early Sarcomeric HCM) participants with early stage sarcomeric HCM (primary analysis cohort) and subclinical HCM (sarcomere variant without left ventricular hypertrophy comprising the exploratory cohort) who completed baseline and year 2 HRQOL assessment via the pediatric quality of life inventory and CPET were studied. Metrics correlating with baseline HRQOL and CPET performance were identified. The impact of valsartan treatment on these measures was analyzed in the early stage cohort.

Results: Two hundred participants were included: 166 with early stage HCM (mean age, 23±10 years; 40% female; 97% White; and 92% New York Heart Association class I) and 34 subclinical sarcomere variant carriers (mean age, 16±5 years; 50% female; and 100% White). Baseline HRQOL was good in both cohorts, although slightly better in subclinical HCM (composite pediatric quality of life score 84.6±10.6 versus 90.2±9.8; P=0.005). Both cohorts demonstrated mildly reduced functional status (mean percent predicted peak oxygen uptake 73±16 versus 78±12 mL/kg per minute; P=0.18). Percent predicted peak oxygen uptake and peak oxygen pulse correlated with HRQOL. Valsartan improved physical HRQOL in early stage HCM (adjusted mean change in pediatric quality of life score +4.1 versus placebo; P=0.01) but did not significantly impact CPET performance.

Conclusions: Functional capacity can be impaired in young, healthy people with early stage HCM, despite New York Heart Association class I status and good HRQOL. Peak oxygen uptake was similarly decreased in subclinical HCM despite normal left ventricular wall thickness and excellent HRQOL. Valsartan improved physical pediatric quality of life scores but did not significantly impact CPET performance. Further studies are needed for validation and to understand how to improve patient experience.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01912534.

Background: Growing evidence indicates that trimethylamine N-oxide, a gut microbial metabolite of dietary choline and carnitine, promotes both cardiovascular disease and chronic kidney disease risk. It remains unclear how circulating concentrations of trimethylamine N-oxide and its related dietary and gut microbe-derived metabolites (choline, betaine, carnitine, γ-butyrobetaine, and crotonobetaine) affect incident heart failure (HF).

Methods: We evaluated 11 768 participants from the Cardiovascular Health Study and the Multi-Ethnic Study of Atherosclerosis with serial measures of metabolites. Cox proportional hazard models were used to examine the associations between metabolites and incident HF, adjusted for cardiovascular disease risk factors.

Results: In all, 2102 cases of HF occurred over a median follow-up of 15.9 years. After adjusting for traditional risk factors, higher concentrations of trimethylamine N-oxide (hazard ratio, 1.15 [95% CI, 1.09-1.20]; P<0.001), choline (hazard ratio, 1.44 [95% CI, 1.26-1.64]; P<0.001), and crotonobetaine (hazard ratio, 1.24 [95% CI, 1.16-1.32]; P<0.001) were associated with increased risk for incident HF. After further adjustment for renal function (potential confounder or mediator), these associations did not reach Bonferroni-corrected statistical significance (P=0.01, 0.049, and 0.006, respectively). Betaine and carnitine were nominally associated with a higher incidence of HF (P<0.05). In exploratory analyses, results were similar for subtypes of HF based on left ventricular ejection fraction, and associations appeared generally stronger among Black and Hispanic/Latino versus White adults, although there were no interactions for any metabolites with race.

Conclusions: In this pooled analysis of 2 well-phenotyped, diverse, community-based cohorts, circulating concentrations of gut microbe-derived metabolites such as trimethylamine N-oxide, choline, and crotonobetaine were independently associated with a higher risk of developing HF.

Registration: URL: https://www.clinicaltrials.gov/; Unique identifiers: NCT00005133 and NCT00005487.