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[Display omitted] [ABSTRACT FROM AUTHOR]

Exercise intolerance (EI) is the primary manifestation of chronic heart failure with preserved ejection fraction (HFpEF), the most common form of heart failure among older individuals. The recent recognition that HFpEF is likely a systemic, multiorgan disorder that shares characteristics with other common, difficult-to-treat, aging-related disorders suggests that novel insights may be gained from combining knowledge and concepts from aging and cardiovascular disease disciplines. This state-of-the-art review is based on the outcomes of a National Institute of Aging-sponsored working group meeting on aging and EI in HFpEF. We discuss aging-related and extracardiac contributors to EI in HFpEF and provide the rationale for a transdisciplinary, "gero-centric" approach to advance our understanding of EI in HFpEF and identify promising new therapeutic targets. We also provide a framework for prioritizing future research, including developing a uniform, comprehensive approach to phenotypic characterization of HFpEF, elucidating key geroscience targets for treatment, and conducting proof-of-concept trials to modify these targets. [ABSTRACT FROM AUTHOR]

Both obesity and atrial fibrillation (AF) are increasing in epidemic proportions, and both increase the prevalence of cardiovascular disease events. Obesity has adverse effects on cardiovascular hemodynamics and cardiac structure and function, and increases the prevalence of AF, partly related to electroanatomic remodeling in obese patients. However, numerous studies, including in AF, have demonstrated an obesity paradox, where overweight and obese patients with these disorders have a better prognosis than do leaner patients with the same degree of severity of cardiovascular disease/AF. In this paper, the authors discuss special issues regarding AF in obesity, as well as the evidence that despite the presence of an obesity paradox, there are benefits of weight loss, physical activity/exercise training, and increases in cardiorespiratory fitness on the prognosis of obese patients with AF. [ABSTRACT FROM AUTHOR]

Background: Lower leisure-time physical activity (LTPA) and higher body mass index (BMI) are independently associated with risk of heart failure (HF). However, it is unclear if this relationship is consistent for both heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF).Objectives: This study sought to quantify dose-response associations between LTPA, BMI, and the risk of different HF subtypes.Methods: Individual-level data from 3 cohort studies (WHI [Women's Health Initiative], MESA [Multi-Ethnic Study of Atherosclerosis], and CHS [Cardiovascular Health Study]) were pooled and participants were stratified into guideline-recommended categories of LTPA and BMI. Associations between LTPA, BMI, and risk of overall HF, HFpEF (ejection fraction ≥45%), and HFrEF (ejection fraction <45%) were assessed by using multivariable adjusted Cox models and restricted cubic splines.Results: The study included 51,451 participants with 3,180 HF events (1,252 HFpEF, 914 HFrEF, and 1,014 unclassified HF). In the adjusted analysis, there was a dose-dependent association between higher LTPA levels, lower BMI, and overall HF risk. Among HF subtypes, LTPA in any dose range was not associated with HFrEF risk. In contrast, lower levels of LTPA (<500 MET-min/week) were not associated with HFpEF risk, and dose-dependent associations with lower HFpEF risk were observed at higher levels. Compared with no LTPA, higher than twice the guideline-recommended minimum LTPA levels (>1,000 MET-min/week) were associated with an 19% lower risk of HFpEF (hazard ratio: 0.81; 95% confidence interval: 0.68 to 0.97). The dose-response relationship for BMI with HFpEF risk was also more consistent than with HFrEF risk, such that increasing BMI above the normal range (≥25 kg/m2) was associated with a greater increase in risk of HFpEF than HFrEF.Conclusions: Our study findings show strong, dose-dependent associations between LTPA levels, BMI, and risk of overall HF. Among HF subtypes, higher LTPA levels and lower BMI were more consistently associated with lower risk of HFpEF compared with HFrEF. [ABSTRACT FROM AUTHOR]

Background Current guidelines recommend cardiac rehabilitation (CR) in medically stable outpatients with heart failure (HF); however, temporal trends and factors associated with CR referral among these patients in real-world practice are not entirely known. Objectives The purpose of this study was to assess proportional use, temporal trends, and factors associated with CR referral at discharge among patients admitted with decompensated HF. Methods Using data from a national Get With the Guidelines–Heart Failure registry, we assessed the temporal trends in CR referral among eligible patients with HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF) at discharge after HF hospitalization between 2005 and 2014. On multivariable analysis, we also assessed patient- and hospital-level characteristics that are associated with CR referral. Results Among 105,619 HF patients (48% with HFrEF, 52% with HFpEF), 10.4% (12.2% with HFrEF, 8.8% with HFpEF) received CR referral at discharge. A significant increase in CR referral rates was observed among both HFpEF and HFrEF patients over the study period (p trend <0.0001 for HFrEF, HFpEF, and overall). Compared with patients discharged without CR referral, patients referred for CR were younger, predominantly men, and more likely to receive evidence-based HF therapies at discharge. On multivariable analysis, younger age, fewer comorbid conditions, and in-hospital procedures such as coronary artery bypass grafting, percutaneous coronary intervention, and cardiac valve surgery were most strongly associated with CR referral. Conclusions Only one-tenth of eligible HF patients received CR referral at discharge after hospitalization for HF. The proportional use of CR referral is increasing over time among both HFrEF and HFpEF patients. Further strategies to improve physician and patient awareness in regard to the benefit of CR should be used to increase CR referral among patients with HF. [ABSTRACT FROM AUTHOR]

Geroscience posits that cardiovascular disease (CVD) and other chronic diseases result from progressive erosion of the effectiveness of homeostatic mechanisms that oppose age-related accumulation of molecular damage. This hypothetical common root to chronic diseases explains why patients with CVD are often affected by multimorbidity and frailty and why older age negatively affects CVD prognosis and treatment response. Gerotherapeutics enhance resilience mechanisms that counter age-related molecular damage to prevent chronic diseases, frailty, and disability, thereby extending healthspan. Here, we describe the main resilience mechanisms of mammalian aging, with a focus on how they can affect CVD pathophysiology. We next present novel gerotherapeutic approaches, some of which are already used in management of CVD, and explore their potential to transform care and management of CVD. The geroscience paradigm is gaining traction broadly in medical specialties, with potential to mitigate premature aging, reduce health care disparities, and improve population healthspan. [Display omitted] • Reduced efficiency of mechanisms opposing age-related molecular damage increases susceptibility to cardiovascular disease. • Key resilience mechanisms associated with aging have been identified as potential therapeutic targets. • By targeting these mechanisms, geroscience could transform the diagnosis, prevention, treatment, and prognosis of cardiovascular disease in an aging population. [ABSTRACT FROM AUTHOR]

Background: Few data exist regarding the implementation of high-sensitivity cardiac troponin (hs-cTn) assays in the United States since their approval.Objectives: To explore trends in hs-cTn assay implementation over time and assess the association of their use with in-hospital cardiac testing and outcomes.Methods: We examined trends in implementation of hs-cTn assays among participating hospitals in the NCDR® Chest Pain-MI Registry from 1/1/2019 through 9/30/2021. Associations between hs-cTn use, use of in-hospital diagnostic imaging, and patient outcomes were assessed using generalized estimating equation models with logistic or Gamma distributions.Results: Among 550 participating hospitals (251,000 patients), implementation of hs-cTn assays increased from 3.3% in Q1, 2019 to 32.6% in Q3, 2021 (Ptrend<0.001). hs-cTn use was associated with more echocardiography among persons with NSTE-ACS (82.4% vs. 75.0%; aOR: 1.43, 95% CI, 1.19-1.73) but not among low-risk chest pain individuals. hs-cTn use was associated with less invasive coronary angiography among low-risk patients (3.7% vs. 4.5%; aOR: 0.73, 95% CI, 0.58-0.92) but similar use for NSTE-ACS. There was no association between hs-cTn use and non-invasive stress/CTCA testing. Among NSTE-ACS individuals, hs-cTn use was not associated with revascularization or in-hospital mortality. Use of hs-cTn was associated with shorter length of stay (LOS; median 47.6 hours vs. 48.0 hours; ratio: 0.94, 95% CI, 0.90-0.98).Conclusions: Implementation of hs-cTn among U.S. hospitals is increasing but most U.S hospitals continue to use less-sensitive assays. hs-cTn use was associated with modestly shorter LOS, greater use of echocardiography for NSTE-ACS, and less use of invasive angiography among low-risk patients. [ABSTRACT FROM AUTHOR]

Background: The long-term effect of bariatric surgery on cardiovascular outcomes in the elderly population is not well studied.Objectives: The aim of this study was to evaluate the association between bariatric surgery and long-term cardiovascular outcomes in the Medicare population.Methods: Medicare beneficiaries who underwent bariatric surgery from 2013 to 2019 were matched to a control group of patients with obesity with a 1:1 exact matching based on age, sex, body mass index, and propensity score matching on 87 clinical variables. The study outcomes included all-cause mortality, new-onset heart failure (HF), myocardial infarction (MI), and ischemic stroke. An instrumental variable analysis was performed as a sensitivity analysis.Results: The study cohort included 189,770 patients (94,885 matched patients in each group). By study design, the 2 groups had similar age (mean: 62.33 ± 10.62 years), sex (70% female), and degree of obesity (mean body mass index: 44.7 ± 7.3 kg/m2) and were well balanced on all clinical variables. After a median follow-up of 4.0 years (IQR: 2.4-5.7 years), bariatric surgery was associated with a lower risk of mortality (9.2 vs 14.7 per 1,000 person-years; HR: 0.63; 95% CI: 0.60-0.66), new-onset HF (HR: 0.46; 95% CI: 0.44-0.49), MI (HR: 0.63; 95% CI: 0.59-0.68), and stroke (HR: 0.71; 95%: CI: 0.65-0.79) (P < 0.001). The benefit of bariatric surgery was evident in patients who were 65 years and older. Using instrumental variable analysis, bariatric surgery was associated with a lower risk of mortality, HF, and MI.Conclusions: Among Medicare beneficiaries with obesity, bariatric surgery is associated with lower risk of mortality, new-onset HF, and MI. [ABSTRACT FROM AUTHOR]

Background: Patient-centric measures of hospital performance for transcatheter aortic valve replacement (TAVR) are needed.Objectives: This study evaluated 30-day, risk-adjusted home time as a hospital performance metric for patients who underwent TAVR.Methods: This study identified 160,792 Medicare beneficiaries who underwent elective TAVR from 2015 to 2019. Home time was calculated for each patient as the number of days alive and spent outside the hospital, skilled nursing facility (SNF), and long-term acute care facility for 30 days after the TAVR procedure date. Correlations between risk-adjusted, 30-day home time and other metrics (30-day, risk-adjusted readmission rate [RSRR], 30-day, risk-adjusted mortality rate [RSMR], and annual TAVR volume) were estimated using Pearson's correlation. Meaningful upward or downward reclassification (≥2 quartile ranks) in hospital performance based on quartiles of risk-adjusted, 30-day home time compared with quartiles of other measures were assessed.Results: Median risk-adjusted, 30-day home time was 27.4 days (interquartile range [IQR]: 26.3-28.5 days). The largest proportion of days lost from 30-day home time was hospital stay after TAVR and SNF stay. An inverse correlation was observed between hospital-level, risk-adjusted, 30-day home time and 30-day RSRR (r = -0.465; P < 0.001) and 30-day RSMR (r = -0.3996; P < 0.001). The use of the 30-day, risk-adjusted home time was associated with reclassification in hospital performance rank hospitals compared with other metrics (9.1% up-classified, 11.2% down-classified vs RSRR; 9.1% up-classified, 10.3% down-classified vs RSMR; and 20.1% up-classified, 19.3% down-classified vs annual TAVR volume).Conclusions: Risk-adjusted, 30-day home time represents a novel patient-centered performance metric for TAVR hospitals that may provide a complimentary assessment to currently used metrics. [ABSTRACT FROM AUTHOR]

Background: Diabetes is associated with abnormalities in cardiac remodeling and high risk of heart failure (HF).Objectives: The purpose of this study was to evaluate the prevalence and prognostic implications of diabetes with cardiomyopathy (DbCM) among community-dwelling individuals.Methods: Adults without prevalent cardiovascular disease or HF were pooled from 3 cohort studies (ARIC [Atherosclerosis Risk In Communities], CHS [Cardiovascular Health Study], CRIC [Chronic Renal Insufficiency Cohort]). Among participants with diabetes, DbCM was defined using different definitions: 1) least restrictive: ≥1 echocardiographic abnormality (left atrial enlargement, left ventricle hypertrophy, diastolic dysfunction); 2) intermediate restrictive: ≥2 echocardiographic abnormalities; and 3) most restrictive: elevated N-terminal pro-B-type natriuretic peptide levels (>125 in normal/overweight or >100 pg/mL in obese) plus ≥2 echocardiographic abnormalities. Adjusted Fine-Gray models were used to evaluate the risk of HF.Results: Among individuals with diabetes (2,900 of 10,208 included), the prevalence of DbCM ranged from 67.0% to 11.7% in the least and most restrictive criteria, respectively. Higher fasting glucose, body mass index, and age as well as worse kidney function were associated with higher risk of DbCM. The 5-year incidence of HF among participants with DbCM ranged from 8.4%-12.8% in the least and most restrictive definitions, respectively. Compared with euglycemia, DbCM was significantly associated with higher risk of incident HF with the highest risk observed for the most restrictive definition of DbCM (HR: 2.55 [95% CI: 1.69-3.86]; least restrictive criteria HR: 1.99 [95% CI: 1.50-2.65]). A similar pattern of results was observed across cohort studies, across sex and race subgroups, and among participants without hypertension or obesity.Conclusions: Regardless of the criteria used to define cardiomyopathy, DbCM identifies a high-risk subgroup for developing HF. [ABSTRACT FROM AUTHOR]

Background: International Classification of Disease (ICD)-10 coding of type 1 myocardial infarction (MI) is used for reimbursement, value-based programs, and clinical research.Objectives: This study sought to determine whether the introduction of ICD-10 codes for type 2 and types 3-5 MI was associated with changes in hospitalizations for ICD-10 codes now attributed to type 1 MI.Methods: Using the Nationwide Readmissions Database, we identified patients with ICD-10 codes now attributed to type 1 MI between January 2016 and December 2018. Patients were stratified according to the timing of their event in relation to the introduction of the type 2 and types 3-5 MI codes on October 1, 2017.Results: There were 2,680,323 hospitalizations for ICD-10 codes now attributed to type 1 MI; after adjustment for seasonality, there was a 13.7% decline in hospitalizations after the introduction of the new subtype codes. Patients with ICD-10 codes now attributed to type 1 MI after the coding change were less likely to be female, had lower prevalence of several cardiovascular and noncardiovascular comorbidities, and had higher rates of coronary angiography and revascularization. After introduction of the new codes, there was a positive deflection in the slope of risk-adjusted in-hospital mortality (0.007%; P <0.001) and a negative deflection in risk-adjusted 30-day readmission (-0.002%; P = 0.05) for patients with ICD-10 codes now attributed to type 1 MI.Conclusions: The introduction of ICD-10 codes for type 2 and types 3-5 MI was associated with a decrease in hospitalizations for ICD-10 codes now attributed to type 1 MI and changes in the observed characteristics and treatment patterns of these patients. [ABSTRACT FROM AUTHOR]

Ticagrelor is a cornerstone of modern antithrombotic therapy alongside aspirin in patients with acute coronary syndrome and after percutaneous coronary intervention. Adverse effects such as bleeding and dyspnea have been associated with premature ticagrelor discontinuation, which may limit any potential advantage of ticagrelor over clopidogrel. The randomized trials of ticagrelor captured adverse events, offering the opportunity to more precisely quantify these effects across studies. Therefore, a meta-analysis of 4 randomized clinical trials of ticagrelor conducted between January 2007 and June 2017 was performed to quantify the incidence and causes of premature ticagrelor discontinuation. Among 66,870 patients followed for a median 18 months, premature ticagrelor discontinuation was seen in 25%; bleeding was the most common cause of discontinuation followed by dyspnea. Versus the comparators, the relative risk of dyspnea-related discontinuation during follow-up was 6.4-fold higher, the relative risk of bleeding was 3.2-fold higher, and the relative risk of discontinuation due to any adverse event was 59% higher for patients receiving ticagrelor. Understanding these potential barriers to adherence to ticagrelor is crucial for informed patient-physician decision making and can inform future efforts to improve ticagrelor adherence. This review discusses the incidence, causes, and biological mechanisms of ticagrelor-related adverse effects and offers strategies to improve adherence to ticagrelor. [ABSTRACT FROM AUTHOR]