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An abstract of the article "Anemia in diastolic heart failure is frequent and associated with worse outcome," by S. Brucks et al., is presented.

Background: Obesity combined with heart failure with preserved ejection fraction (HFpEF) is the dominant form of HF among older persons. In a randomized trial, we previously showed that a 5-month calorie restriction (CR) program, with or without aerobic exercise training (AT), resulted in significant weight and fat loss and improved exercise capacity. However, little is known regarding the long-term effects of these outcomes after a short-term (5-month) intervention of CR with or without AT in older patients with obesity and HFpEF., Methods: Sixteen participants from either the CR or CR+AT who experienced significant weight loss ≥ 2 kg were reexamined after a long-term follow-up endpoint (28.0 ± 10.8 months) without intervention. The follow-up assessment included body weight and composition via dual-energy X-ray absorptiometry and exhaustive cardiopulmonary treadmill exercise testing., Results: Compared to the 5-month time-point intervention endpoint, at the long-term follow-up endpoint, mean body weight increased +5.2 ± 4.0 kg (90.7 ± 11.2 kg vs 95.9 ± 11.9; P < 0.001) due to increased fat mass (38.9 ± 9.3 vs 43.8 ± 9.8; P < 0.001) with no change in lean mass (49.6 ± 7.1 vs 49.9±7.6; P = 0.67), resulting in worse body composition (decreased lean-to-fat mass). Change in total mass was strongly and significantly correlated with change in fat mass (r = 0.75; P < 0.001), whereas there appeared to be a weaker correlation with change in lean mass (r = 0.50; P = 0.051). Additionally, from the end of the 5-month time-point intervention endpoint to the long-term follow-up endpoint, there were large, significant decreases in VO 2 peak (-2.2 ± 2.1 mL/kg/min; P = 0.003) and exercise time (-2.4 ± 2.6 min; P = 0.006). There appeared to be an inverse correlation between the change in VO 2 peak and the change in fat mass (r = -0.52; P = 0.062)., Conclusion: Although CR and CR+AT in older patients with obesity and HFpEF can improve body composition and exercise capacity significantly, these positive changes diminish considerably during long-term follow-up endpoints, and regained weight is predominantly adipose, resulting in worsened overall body composition compared to baseline. This suggests a need for long-term adherence strategies to prevent weight regain and maintain improvements in body composition and exercise capacity following CR in older patients with obesity and HFpEF., Competing Interests: Disclosures BU has received research funding from Novartis and Corvia. PHB has received honoraria as a consultant for Boston Scientific, Boehringer Ingelheim, Corvia Medical, and Merck. DWK has received honoraria as a consultant for Bayer, Medtronic, Relypsa, Merck, Corvia Medical, Boehringer Ingelheim, Ketyo, Rivus, NovoNordisk, AstraZeneca‚ and Novartis, grant funding from Novartis, Bayer, NovoNordisk‚ and AstraZeneca‚ and has stock ownership in Gilead Sciences. All other authors report no disclosures. The manuscript is not under consideration elsewhere, nor have any of its contents been previously published. All authors have read and approved the manuscript. All authors contributed to the work by ICMJE guidelines. None of the other authors have any financial disclosures or conflicts of interest concerning this manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background The REHAB-HF (Rehabilitation Therapy in Older Acute Heart Failure Patients) randomized trial demonstrated that a 3-month transitional, tailored, progressive, multidomain physical rehabilitation intervention improves physical function, frailty, depression, and health-related quality of life among older adults with acute decompensated heart failure. Whether there is differential intervention efficacy by race is unknown. Methods and Results In this prespecified analysis, differential intervention effects by race were explored at 3 months for physical function (Short Physical Performance Battery [primary outcome], 6-Minute Walk Distance), cognition, depression, frailty, health-related quality of life (Kansas City Cardiomyopathy Questionnaire, EuroQoL 5-Dimension-5-Level Questionnaire) and at 6 months for hospitalizations and death. Significance level for interactions was P ≤0.1. Participants (N=337, 97% of trial population) self-identified in near equal proportions as either Black (48%) or White (52%). The Short Physical Performance Battery intervention effect size was large, with values of 1.3 (95% CI, 0.4-2.1; P =0.003]) and 1.6 (95% CI, 0.8-2.4; P <0.001) in Black and White participants, respectively, and without significant interaction by race ( P =0.56). Beneficial effects were also demonstrated in 6-Minute Walk Distance, gait speed, and health-related quality of life scores without significant interactions by race. There was an association between intervention and reduced all-cause rehospitalizations in White participants (rate ratio, 0.73 [95% CI, 0.55-0.98]; P =0.034) that appears attenuated in Black participants (rate ratio, 1.06 [95% CI, 0.81-1.41]; P =0.66; interaction P =0.067). Conclusions The intervention produced similarly large improvements in physical function and health-related quality of life in both older Black and White patients with acute decompensated heart failure. A future study powered to determine how the intervention impacts clinical events is required. REGISTRATION URL: https://www.clinicaltrials.gov. Identifier: NCT02196038.

Heart failure (HF) prevention is an urgent public health need with national and global implications. Stage A HF patients do not show HF symptoms or structural heart disease but are at risk of HF development. There are no unique recommendations on detecting Stage A patients. Patients in Stage A are heterogeneous; many patients have different combinations of risk factors and, therefore, have markedly different absolute risks for HF. Comprehensive strategies to prevent HF at Stage A include intensive blood pressure lowering, adequate glycemic and lipid management, and heart-healthy behaviors (adopting Life's Essential 8). First and foremost, it is imperative to improve public awareness of HF risk factors and implement healthy lifestyle choices very early. In addition, recognize the HF risk-enhancing factors, which are nontraditional cardiovascular (CV) risk factors that identify individuals at high risk for HF (genetic susceptibility for HF, atrial fibrillation, chronic kidney disease, chronic liver disease, chronic inflammatory disease, sleep-disordered breathing, adverse pregnancy outcomes, radiation therapy, a history of cardiotoxic chemotherapy exposure, and COVID-19). Early use of biomarkers, imaging markers, and echocardiography (noninvasive measures of subclinical systolic and diastolic dysfunction) may enhance risk prediction among individuals without established CV disease and prevent chemotherapy-induced cardiomyopathy. Efforts are needed to address social determinants of HF risk for primordial HF prevention.Central illustrationPolicies developed by organizations such as the American Heart Association, American College of Cardiology, and the American Diabetes Association to reduce CV disease events must go beyond secondary prevention and encompass primordial and primary prevention., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier B.V.)

Introduction: Observational studies have reported associations between cannabis use and coronary heart disease. Since diabetes is a coronary heart disease equivalent, we hypothesized that cannabis use would be associated with prevalent angina among individuals with diabetes. Methods: This analysis included 1314 participants with diabetes (age 47.4±9.0 years, 49.5% male, 28.3% Caucasians) from the National Health and Nutrition Examination Survey years 2011-2018. Cannabis use was self-reported. Prevalent angina was defined by self-reported physician diagnosis. Multivariable logistic regression models were used to examine the association between prevalent angina and cannabis use. Results: Approximately 3.3% ( n =43) of participants had prevalent angina and 45.7% ( n =601) were ever cannabis users. After adjustment, ever cannabis users did not have significantly increased odds of prevalent angina compared with never users (odds ratio: 3.29, 95% confidence interval [95% CI]: 0.88-12.22, p =0.08). However, those who had used cannabis at least once per month for at least 1 year had greater than fivefold increased odds of prevalent angina (odds ratio: 5.73, 95% CI: 1.26-26.04, p =0.03). Current cannabis users had greater than fivefold increased odds of prevalent angina (odds ratio: 5.35, 95% CI: 1.26-22.70, p =0.03), with a dose-response increase based on level of use. Effect modification was present among those with history of cocaine use (interaction p -value <0.001). Conclusion: Among individuals with diabetes, cannabis use is associated with prevalent angina with apparent dose response. This finding supports emerging evidence that cannabis may have negative cardiovascular (CV) health effects, and an individualized CV risk assessment should be pursued among those with diabetes.

Background: We have shown that combined caloric restriction (CR) and aerobic exercise training (AT) improve peak exercise O 2 consumption (VO 2peak ), and quality-of-life in older patients with obese heart failure with preserved ejection fraction. However, ≈35% of weight lost during CR+AT was skeletal muscle mass. We examined whether addition of resistance training (RT) to CR+AT would reduce skeletal muscle loss and further improve outcomes., Methods: This study is a randomized, controlled, single-blind, 20-week trial of RT+CR+AT versus CR+AT in 88 patients with chronic heart failure with preserved ejection fraction and body mass index (BMI) ≥28 kg/m 2 . Outcomes at 20 weeks included the primary outcome (VO 2peak ); MRI and dual X-ray absorptiometry; leg muscle strength and quality (leg strength ÷ leg skeletal muscle area); and Kansas City Cardiomyopathy Questionnaire., Results: Seventy-seven participants completed the trial. RT+CR+AT and CR+AT produced nonsignificant differences in weight loss: mean (95% CI): -8 (-9, -7) versus -9 (-11, -8; P =0.21). RT+CR+AT and CR+AT had non-significantly differences in the reduction of body fat [-6.5 (-7.2, -5.8) versus -7.4 (-8.1, -6.7) kg] and skeletal muscle [-2.1 (-2.7, -1.5) versus -2.1 (-2.7, -1.4) kg] ( P =0.20 and 0.23, respectively). RT+CR+AT produced significantly greater increases in leg muscle strength [4.9 (0.7, 9.0) versus -1.1 (-5.5, 3.2) Nm, P =0.05] and leg muscle quality [0.07 (0.03, 0.11) versus 0.02 (-0.02, 0.06) Nm/cm 2 , P =0.04]. Both RT+CR+AT and CR+AT produced significant improvements in VO 2peak [108 (958, 157) versus 80 (30, 130) mL/min; P =0.001 and 0.002, respectively], and Kansas City Cardiomyopathy Questionnaire score [17 (12, 22) versus 23 (17, 28); P =0.001 for both], with no significant between-group differences. Both RT+CR+AT and CR+AT significantly reduced LV mass and arterial stiffness. There were no study-related serious adverse events., Conclusions: In older obese heart failure with preserved ejection fraction patients, CR+AT produces large improvements in VO 2peak and quality-of-life. Adding RT to CR+AT increased leg strength and muscle quality without attenuating skeletal muscle loss or further increasing VO 2peak or quality-of-life., Registration: URL: https://ClincalTrials.gov; Unique identifier: NCT02636439.

Importance: Frailty is common among older patients with acute decompensated heart failure (ADHF) and is associated with worse quality of life (QOL) and a higher risk of clinical events. Frailty can also limit recovery and response to interventions. In the Rehabilitation Therapy in Older Acute Heart Failure Patients (REHAB-HF) trial, a 3-month innovative, early, transitional, tailored, multidomain physical rehabilitation intervention improved physical function and QOL (vs usual care) in older patients with ADHF., Objective: To evaluate whether baseline frailty modified the benefits of the physical rehabilitation intervention among patients with ADHF enrolled in the REHAB-HF trial and to assess the association between changes in frailty with the risk of adverse clinical outcomes on follow-up., Design, Setting, and Participants: This prespecified secondary analysis of the REHAB-HF trial, a multicenter randomized clinical trial, included 337 patients 60 years and older hospitalized for ADHF. Patients were enrolled from September 17, 2014, through September 19, 2019. Participants were stratified across baseline frailty strata as assessed using modified Fried criteria. Data were analyzed from July 2021 to September 2022., Interventions: Physical rehabilitation intervention or attention control., Main Outcomes and Measures: Primary outcome was the Short Physical Performance Battery (SPPB) score at 3 months. Clinical outcomes included all-cause hospitalization or mortality at 6 months., Results: This prespecified secondary analysis included 337 participants; 181 (53.7%) were female, 167 (49.6%) were Black, and the mean (SD) age was 72 (8) years. A total of 192 (57.0%) were frail and 145 (43.0%) were prefrail at baseline. A significant interaction was observed between baseline frailty status and the treatment arm for the primary trial end point of overall SPPB score, with a 2.6-fold larger improvement in SPPB with intervention among frail patients (2.1; 95% CI, 1.3-2.9) vs prefrail patients (0.8; 95% CI, -0.1 to 1.6; P for interaction = .03). Trends consistently favored a larger intervention effect size, with significant improvement among frail vs prefrail participants for 6-minute walk distance, QOL, and the geriatric depression score, but interactions did not achieve significance., Conclusions and Relevance: In this prespecified secondary analysis of the REHAB-HF trial, patients with ADHF with worse baseline frailty status had a more significant improvement in physical function in response to an innovative, early, transitional, tailored, multidomain physical rehabilitation intervention than those who were prefrail., Trial Registration: Clinical Trials.gov Identifier: NCT02196038.

Background: Most guidelines directing clinicians to manage valve disease are directed at single valve lesions. Limited data exists to direct our understanding of how concomitant valve disease impacts the left ventricle (LV)., Methods: We identified 2817 patients with aortic stenosis (AS) from the echocardiography laboratory database between September 2012 and June 2018 who had a LV ejection fraction (EF) ≥50%. LV mass, LV mass index, LV systolic pressure (systolic blood pressure + peak aortic gradient). Covariates were collected from the electronic medical record. Multi-variate analysis of covariance was used to generate adjusted comparisons., Results: Our population was 66% female, 17% African-American with a mean age of 65 years. Of note, 7.3% were noted to have significant (moderate/severe) aortic regurgitation (AR), and 11% had significant (moderate/severe) mitral regurgitation (MR). Adjusting for covariates at different levels, significant MR had a much stronger association with heart failure compared to those with significant AR (p < .001 vs. p = .313, respectively) at all levels of adjustment. Both significant mitral and AR exhibited an association with increasing left ventricular mass, even with adjustment for baseline demographics and clinical features (p < .001 vs. p = .007, respectively)., Conclusion: In patients with AS, 16% also experience at least moderate MR or AR. Further, significant MR has a stronger association with heart failure than significant AR, even though both increase left ventricular mass. Those with moderate AS and significant MR or AR experience similar or higher levels of heart failure compared to severe AS without regurgitation. Mixed valve disease merits further studies to direct longitudinal management., (© 2022 The Authors. Echocardiography published by Wiley Periodicals LLC.)

Purpose of Review: We reviewed the effects of hypertension and the means to prevent and treat it across the spectrum of a woman's lifespan and identified gaps in sex-specific mechanisms contributing to hypertension in women that need to be addressed., Recent Findings: Hypertension continues to be an important public health problem for women across all life stages from adolescence through pregnancy, menopause, and older age. There remain racial, ethnic, and socioeconomic differences in hypertension rates not only overall but also between the sexes. Blood pressure cutoffs during pregnancy have not been updated to reflect the 2017 ACC/AHA changes due to a lack of data. Additionally, the mechanisms behind hypertension development in menopause, including sex hormones and genetic factors, are not well understood. In the setting of increasing inactivity and obesity, along with an aging population, hypertension rates are increasing in women. Screening and management of hypertension throughout a women's lifespan are necessary to reduce the burden of cardiovascular disease, and further research to understand sex-specific hypertension mechanisms is needed., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: In the REHAB-HF (Rehabilitation Therapy in Older Acute Heart Failure Patients) trial, a novel, early, transitional, multidomain rehabilitation intervention improved physical function, frailty, quality of life (QOL), and depression in older patients hospitalized for acute decompensated heart failure (ADHF), but the potential impact of baseline obesity on this intervention has not been studied., Objectives: This study assessed for treatment interactions by body mass index (BMI) subgroups for a novel rehabilitation intervention in ADHF., Methods: Three-month outcomes including Short Physical Performance Battery (SPPB) (primary outcome), 6-minute walk distance (6MWD), and Kansas City Cardiomyopathy Questionnaire (KCCQ) were assessed by baseline BMI (≥30 kg/m 2 vs <30 kg/m 2 ). Six-month end points included all-cause rehospitalization and death. All analyses were adjusted for age, sex, clinical site, and ejection fraction category, and 3-month outcomes were also adjusted for baseline measure. The prespecified significance level for treatment interaction by BMI category was P ≤ 0.10., Results: Of 349 trial participants, 204 (58%) had BMI ≥30 kg/m 2 and 145 (42%) <30 kg/m 2 . Compared with patients with BMI <30 kg/m 2 , participants with BMI ≥30 kg/m 2 were younger (age 71 ± 7 years vs 75 ± 9 years), more frequently women (57% vs 46%), and had significantly worse baseline physical function and QOL. Although interaction P values for 3-month outcomes by BMI were not significant (interaction P > 0.15 for overall measures), adjusted SPPB effect sizes were nominally larger for participants with BMI ≥30 kg/m 2 compared with those with BMI <30 kg/m 2 : +1.7 (95% CI: 0.8-2.7) vs +1.1 (95% CI: -0.1 to 2.2). This difference in SPPB effect size was due largely to improvements in the balance component of the SPPB for participants with BMI ≥30 kg/m 2 : +0.6 (95% CI: 0.2-1.0) vs 0.0 (-0.6 to 0.5) for those with BMI <30 kg/m 2 (interaction P = 0.02). In contrast, adjusted 6MWD and KCCQ effect sizes were smaller for participants with BMI ≥30 kg/m 2 compared with those with BMI <30 kg/m 2 : +21 meters (-17 to 59) vs +53 meters (6-100), and +5.0 (-4 to 14) vs +11 (-0.5 to 22), respectively. There was no significant interaction by BMI for 6-month clinical outcomes (all interaction P > 0.30)., Conclusions: Older patients with ADHF benefit from the rehabilitation therapy regardless of BMI. Benefits for patients with obesity may be more evident in the multidomain measure of physical function (SPPB), compared with the 6MWD or KCCQ, which may be driven, in part, by the unique aspects of the novel rehabilitation intervention. (A Trial of Rehabilitation Therapy in Older Acute Heart Failure Patients [REHAB-HF]; NCT02196038)., Competing Interests: Funding Support and Author Disclosures This study was supported by research grants from the National Institutes of Health (R01AG045551, R01AG18915, P30AG021332, P30AG028716, U24AG059624, and U01HL160272), the Kermit Glenn Phillips II Chair in Cardiovascular Medicine, and the Oristano Family Fund at Wake Forest School of Medicine. Dr Peters is supported by the National Heart Lung and Blood Institute (T32HL069749) and has stock ownership in Bristol Myers Squibb. Dr Kitzman has received honoraria outside the present study as a consultant for Bayer, Merck, Medtronic, Relypsa, Merck, Corvia Medical, Boehringer-Ingelheim, NovoNordisk, AstraZeneca, Rivus, Pfizer, and Novartis; has received grant funding outside the present study from Novartis, Bayer, NovoNordisk, and AstraZeneca; and has stock ownership in Gilead Sciences. Dr Upadhya has received research support from Novartis and Corvia. Dr Whellan has received research support and consulting fees from Amgen, CVRx, Cytokinetics, Fibrogen, Novartis, and NovoNordisk. Dr Mentz has received research support and honoraria from Abbott, American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim/Eli Lilly, Boston Scientific, Cytokinetics, Fast BioMedical, Gilead, Innolife, Medtronic, Merck, Novartis, Relypsa, Respicardia, Roche, Sanofi, Vifor, Windtree Therapeutics, and Zoll. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Older patients hospitalized with acute decompensated heart failure (ADHF) have marked functional impairments, which may contribute to their delayed and incomplete recovery and persistently poor outcomes. However, whether impairment severity differs by race and sex is unknown., Methods: REHAB-HF trial participants (≥60 years) were assessed just before discharge home from ADHF hospitalization. Physical function [Short Physical Performance Battery; 6-min walk distance (6MWD)], frailty (Fried criteria), cognition [Montreal Cognitive Assessment (MoCA)], quality-of-life [Kansas City Cardiomyopathy Questionnaire, Short-Form-12, EuroQol-5D-5L], and depression [Geriatric Depression Scale (GDS)] were examined by race and sex., Results: This prespecified subgroup cross-sectional analysis included 337 older adults (52% female, 50% Black). Black participants were on average younger than White participants (70.3 ± 7.2 vs. 74.7 ± 8.3 years). After age, body mass index, ejection fraction, comorbidity, and education adjustment, and impairments were similarly common and severe across groups except: Black male and Black and White female participants had more severely impaired walking function compared with White male participants [6MWD (m) 187 ± 12, 168 ± 9170 ± 11 vs. 239 ± 9, p < 0.001]; gait speed (m/s) (0.61 ± 0.03, 0.56 ± 0.02, 0.55 ± 0.02 vs. 0.69 ± 0.02, p < 0.001); White female participants had the highest frailty prevalence (72% vs. 47%-51%, p = 0.007); and Black participants had lower MoCA scores compared with White participants (20.9 ± 4.5 vs. 22.8 ± 3.9, p < 0.001). Depressive symptoms were common overall (43% GDS ≥5), yet underrecognized clinically (18%), especially in Black male participants compared with White male participants (7% vs. 20%)., Conclusion: Among older patients hospitalized for ADHF, frailty and functional impairments with high potential to jeopardize patient HF self-management, safety, and independence were common and severe across all race and sex groups. Impairment severity was often worse in Black participant and female participant groups. Formal screening across frailty and functional domains may identify those who may require greater support and more tailored care to reduce the risk of adverse events and excess hospitalizations and death., (© 2022 The American Geriatrics Society.)

Vasculitic immune checkpoint inhibitor-related adverse events (irAEs) are rare, with limited data to guide their management. Here, we present a case of a 67-year-old female with stage IV cutaneous melanoma who received first-line pembrolizumab. She had completed 21 cycles of pembrolizumab dosed at 200 mg every 21 days over 15 months when she developed fatigue, chills, decreased appetite, night sweats, nausea, diarrhea, dry cough, and chest pain. A routine, staging positron emission tomography (PET) scan revealed aortitis of the transverse aortic arch. An extensive workup was unremarkable for other causes, so her condition was labeled a grade III immune-related vasculitis. Based on this diagnosis, we started high-dose prednisone and discontinued pembrolizumab. After two months of high-dose prednisone, she developed bothersome weight gain and insomnia, leading to a switch from prednisone to tocilizumab as a steroid-sparing agent. The selection of tocilizumab was based on its routine use for giant cell arteritis which can have extracranial symptoms including thoracic aortitis. Her symptoms resolved, and subsequent PET scans showed resolution of the aortitis and no evidence of metastatic melanoma. As the indications for immunotherapy expand, rare complications are becoming more prevalent, and more data will be needed to guide their management. While there is evidence for tocilizumab use as a steroid-sparing treatment for large-vessel vasculitides due to other conditions, this is the first case of its use to treat an aortitis irAE to our knowledge. In this case, it was an effective means of treating the patient while sparing them from prolonged corticosteroids., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Chance H. Bloomer et al.)

Background: Cannabis is associated with risk of acute coronary syndrome in observational studies. However, its association with prevalent coronary artery disease (CAD) remains unclear. We hypothesized that cannabis use is associated with prevalent CAD., Methods: This analysis included 12,543 participants (age 39.3 ± 11.6 years, 48.8% male, 35.3% Caucasians) from The National Health and Nutrition Examination Survey (NHANES). Cannabis use was self-reported. Prevalent CAD was defined by physician diagnosis. The association between cannabis use and CAD was tested for using multivariable logistic regression., Results: About 53.1% (n = 6,650) of participants were ever cannabis users and 1.1% (n = 137) had prevalent CAD. Ever (versus never) cannabis users had 90% increased odds of CAD [OR (95% CI): 1.90 (1.24 - 2.93), p = 0.003]. Those who had used cannabis at least once per month for at least one year had 68% increased odds of CAD [OR (95% CI): 1.68 (1.02-2.77), p = 0.04]. Current cannabis users had near 98% increased odds of CAD [OR (95% CI): 1.98 (1.11 - 3.54), p = 0.02]. Similar results were seen with heavy cannabis users [OR (95% CI): 1.99 (1.02 - 3.89), p = 0.045]. These results were consistent in subgroups stratified by race, gender, hypertension, obesity, COPD, hyperlipidemia, tobacco smoking status, and diabetes., Conclusions: Cannabis use is associated with prevalent CAD. This finding emphasizes the potential harmful effects of cannabis use on cardiovascular health and highlights the need for further research as it becomes more accepted at both a national and global level., Competing Interests: Declaration of Competing Interest The authors whose names are listed certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript., (Copyright © 2022 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Background: Catheter ablation for atrial fibrillation (CAAF) can result in stiff left atrial syndrome (SLAS) in up to 8% of patients. SLAS can be challenging to diagnose and difficult to distinguish from heart failure with preserved ejection fraction (HFpEF), presenting with similar signs and symptoms., Case Presentation: We report the first case of using an interatrial stent to maintain therapeutic benefit of atrial septostomy in a patient with symptomatic SLAS. While interatrial shunt devices have preliminarily been shown to be safe and efficacious for the treatment of HFpEF, their utilization in those with SLAS has not previously been described [1]., Conclusions: In patients with prior CAAF, SLAS should be considered to explain dyspnea when alternative processes have been excluded. Treatment of SLAS can be challenging with medical therapy alone, and septostomy may provide significant symptomatic benefit in these patients. Interatrial stenting can improve the patency of such interventions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Heart failure with preserved ejection fraction (HFpEF) is the fastest growing form of HF and is associated with high morbidity and mortality. The primary chronic symptom in HFpEF is exercise intolerance, associated with reduced quality of life. Emerging evidence implicates left atrial (LA) dysfunction as an important pathophysiologic mechanism. Here we extend prior observations by relating LA dysfunction to peak oxygen uptake (peak VO 2 ), physical function (distance walked in 6 minutes [6MWD]) and quality of life (Kansas City Cardiomyopathy Questionnaire)., Methods and Results: We compared 75 older, obese, patients with HFpEF with 53 healthy age-matched controls. LA strain was assessed by magnetic resonance cine imaging using feature tracking. LA function was defined according to its 3 distinct phases, with the LA serving as a reservoir during systole, as a conduit during early diastole, and as a booster pump at the end of diastole. The LA stiffness index was calculated as the ratio of early mitral inflow velocity-to-early annular tissue velocity (E/e', by Doppler ultrasound examination) and LA reservoir strain. HFpEF had a decreased reservoir strain (16.4 ± 4.4% vs 18.2 ± 3.5%, P = .018), lower conduit strain (7.7 ± 3.3% vs 9.1 ± 3.4%, P = .028), and increased stiffness index (0.86 ± 0.39 vs 0.53 ± 0.18, P < .001), as well as decreased peak VO 2 , 6MWD, and lower quality of life. Increased LA stiffness was independently associated with impaired peak VO 2 (β = 9.0 ± 1.6, P < .001), 6MWD (β = 117 ± 22, P = .003), and Kansas City Cardiomyopathy Questionnaire score (β = -23 ± 5, P = .001), even after adjusting for clinical covariates., Conclusions: LA stiffness is independently associated with impaired exercise tolerance and quality of life and may be an important therapeutic target in obese HFpEF., Registration: NCT00959660., (Copyright © 2021 Elsevier Inc. All rights reserved.)

We hypothesized that cannabis use is associated with cardiovascular disease (CVD) risk factors. This could explain the reported link between cannabis and cardiovascular events including stroke and myocardial infarction. This analysis included 7,159 participants (age 37.8 ± 12.4 years, 48.6% men, and 61.5% Caucasian) from the National Health and Nutrition Examination Survey years 2011 to 2018. Cannabis use was defined by self-report. Participants with a history of stroke or myocardial infarction were excluded. Composite CVD risk was assessed using the American College of Cardiology/American Heart Association 10-year atherosclerotic cardiovascular risk (ASCVD) score. Participants were classified based on their ASCVD risk levels as low (<5.0%), borderline (5.0% to 7.4%), intermediate (7.5% to 19.9%), and high (≥20.0%). Multinomial logistic regression was used to examine the association between cannabis use and ASCVD risk category using low-risk ASCVD category as the reference level. About 63.9% (n = 4,573) of participants had ever used cannabis. Ever cannabis use was associated with 60% increased odds of high-risk ASCVD score (odds ratio [OR] 95% confidence interval [CI] 1.60 [1.04 to 2.45], p = 0.03). We also observed a dose-response relation between increased use of cannabis and a higher risk of ASCVD. Those reporting ≥2 uses per month had 79% increased odds of high-risk ASCVD score (OR [95% CI] 1.79 [1.10 to 2.92], p = 0.02) and those reporting ≥1 use per day had 87% increased odds of high-risk ASCVD score (OR [95% CI] 1.87 [1.16 to 3.01], p <0.001]. In conclusion, cannabis use is associated with elevated CVD risk. Individuals using cannabis should be screened for CVD risk, and appropriate risk reduction strategies should be implemented., Competing Interests: Disclosures The authors have no conflict of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose of Review: This review aims to investigate the blood pressure (BP)-lowering effects of emerging drugs developed to treat diabetic kidney disease and heart failure (HF). We summarize the potential pathophysiological mechanisms responsible for mitigating hypertensive target organ damage and evaluating the available clinical data on these newer drugs., Recent Findings: Nonsteroidal dihydropyridine-based mineralocorticoid receptor antagonists (MRAs), dual angiotensin II receptor-neprilysin inhibitors (valsartan with sacubitril), sodium-glucose cotransporter 2 inhibitors (SGLT2i), and soluble guanylate cyclase stimulators are new classes of chemical agents that have distinct mechanisms of action and have been shown to be effective for the treatment of cardiovascular (CV) disease (CVD), HF, and type 2 diabetes mellitus (T2D). These drugs can be used either alone or in combination with other antihypertensive and CV drugs. Among these, SGLT2i and valsartan with sacubitril offer new avenues to reduce CVD mortality. SGLT2i have a mild-to-moderate effect on BP lowering with a favorable effect on CV and renal hemodynamics and have been shown to produce a significant reduction in the incidence of major adverse CVD events (as monotherapy or add-on therapy) compared with controls (placebo or non-SGLT2i treatment). Most of the participants in these studies had hypertension (HTN) at baseline and were receiving antihypertensive therapy, including renin-angiotensin system blockers. The combination of valsartan with sacubitril also lowers BP in the short term and has demonstrated a striking reduction in CVD mortality and morbidity in HF patients with a reduced left ventricular ejection fraction. If widely adopted, these novel therapeutic agents hold significant promise for reducing the public health burden posed by HTN and CVD. Based on the results of several clinical trials and considering the high prevalence of HTN and T2D, these new classes of agents have emerged as powerful therapeutic tools in managing and lowering the BP of patients with diabetic kidney disease and HF., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: In the SPRINT (Systolic Blood Pressure Intervention Trial), intensive BP treatment reduced acute decompensated heart failure (ADHF) events. Here, we report the effect on HF with preserved ejection fraction (HFpEF) and HF with reduced EF (HFrEF) and their subsequent outcomes., Methods: Incident ADHF was defined as hospitalization or emergency department visit, confirmed, and formally adjudicated by a blinded events committee using standardized protocols. HFpEF was defined as EF ≥45%, and HFrEF was EF <45%., Results: Among the 133 participants with incident ADHF who had EF assessment, 69 (52%) had HFpEF and 64 (48%) had HFrEF ( P value: 0.73). During average 3.3 years follow-up in those who developed incident ADHF, rates of subsequent all-cause and HF hospital readmission and mortality were high, but there were no significant differences between those who developed HFpEF versus HFrEF. Randomization to the intensive arm had no effect on subsequent mortality or readmissions after the initial ADHF event, irrespective of EF subtype. During follow-up among participants who developed HFpEF, although relatively modest number of events limited statistical power, age was an independent predictor of all-cause mortality, and Black race independently predicted all-cause and HF hospital readmission., Conclusions: In SPRINT, intensive BP reduction decreased both acute decompensated HFpEF and HFrEF events. After initial incident ADHF, rates of subsequent hospital admission and mortality were high and were similar for those who developed HFpEF or HFrEF. Randomization to the intensive arm did not alter the risks for subsequent all-cause, or HF events in either HFpEF or HFrEF. Among those who developed HFpEF, age and Black race were independent predictors of clinical outcomes. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01206062.

Heart failure (HF) with preserved ejection fraction (HFpEF) is the most rapidly increasing form of HF, occurs primarily in older women, and is associated with high rates of morbidity, mortality, and health care expenditures. In the highest age decile (≥90 years old), nearly all patients with HFpEF. As our understanding of the disease has grown in the last few years, we now know that HFpEF is a systemic disorder influenced by aging processes. The involvement of this broad collection of abnormalities in HFpEF, the recognition of the high frequency and impact of noncardiac comorbidities, and systemic, multiorgan involvement, and its nearly exclusive existence in older persons, has led to the recognition of HFpEF as a true geriatric syndrome. Most of the conventional therapeutics used in other cardiac diseases have failed to improve HFpEF patient outcomes significantly. Several recent studies have evaluated exercise training (ET) as a therapeutic management strategy in patients with HFpEF. Although these studies were not designed to address clinical endpoints, such as HF hospitalizations and mortality, they have shown that ET is a safe and effective intervention to improve peak oxygen consumption, physical function, and quality of life in clinically stable HF patients. Recently, a progressive, multidomain physical rehabilitation study among older adults showed that it is feasible in older patients with acute decompensated HF who have high frailty and comorbidities and showed improvement in physical function. However, the lack of Centers for Medicare and Medicaid Services coverage can be a major barrier to formal cardiac rehabilitation in older HFpEF patients. Unfortunately, insistence upon demonstration of mortality improvement before approving reimbursement overlooks the valuable and demonstrated benefits of physical function and life quality., (Copyright © 2021. Published by Elsevier Inc.)

Objectives: This study assessed for treatment interactions by ejection fraction (EF) subgroup (≥45% [heart failure with preserved ejection fraction (HFpEF); vs <45% [heart failure with reduced ejection fraction (HFrEF)])., Background: The REHAB-HF trial showed that an early multidomain rehabilitation intervention improved physical function, frailty, quality-of-life, and depression in older patients hospitalized with acute decompensated heart failure (ADHF)., Methods: Three-month outcomes were: Short Physical Performance Battery (SPPB), 6-min walk distance (6MWD), and Kansas City Cardiomyopathy Questionnaire (KCCQ). Six-month end points included all-cause rehospitalization and death and a global rank of death, all-cause rehospitalization, and SPPB. Prespecified significance level for interaction was P ≤ 0.1., Results: Among 349 total participants, 185 (53%) had HFpEF and 164 (47%) had HFrEF. Compared with HFrEF, HFpEF participants were more often women (61% vs 43%) and had significantly worse baseline physical function, frailty, quality of life, and depression. Although interaction P values for 3-month outcomes were not significant, effect sizes were larger for HFpEF vs HFrEF: SPPB +1.9 (95% CI: 1.1-2.6) vs +1.1 (95% CI: 0.3-1.9); 6MWD +40 meters (95% CI: 9 meters-72 meters) vs +27 (95% CI: -6 meters to 59 meters); KCCQ +9 (2-16) vs +6 (-2 to 14). All-cause rehospitalization rate was nominally lower with intervention in HFpEF but not HFrEF [effect size 0.83 (95% CI: 0.64-1.09) vs 0.99 (95% CI: 0.74-1.33); interaction P = 0.40]. There were significantly greater treatment benefits in HFpEF vs HFrEF for all-cause death [interaction P = 0.08; intervention rate ratio 0.63 (95% CI: 0.25-1.61) vs 2.21 (95% CI: 0.78-6.25)], and the global rank end point (interaction P = 0.098) with benefit seen in HFpEF [probability index 0.59 (95% CI: 0.50-0.68)] but not HFrEF., Conclusions: Among older patients hospitalized with ADHF, compared with HFrEF those with HFpEF had significantly worse impairments at baseline and may derive greater benefit from the intervention. (A Trial of Rehabilitation Therapy in Older Acute Heart Failure Patients [REHAB-HF]; NCT02196038)., Competing Interests: Funding Support and Author Disclosures This study was supported in part by the National Institutes of Health (research grants R01AG045551, R01AG18915, P30AG021332, P30AG028716, and U24AG059624). Support was also provided in part by the Kermit Glenn Phillips II Chair in Cardiovascular Medicine and the Oristano Family Fund at Wake Forest School of Medicine. Dr Mentz received research support and honoraria from Abbott, American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Medtronic, Merck, Novartis, Roche, Sanofi, and Vifor. Dr Whellan received research support and consulting fees from Amgen, CVRx, Cytokinetics, Fibrogen, Novartis, and NovoNordisk. Dr Upadhya received research support from Novartis and Corvia. Dr Reed received research support from Abbott, AstraZeneca, Janssen Research and Development, Lundbeck, Monteris, and Merck; and received consulting with Minomic International, SVC Systems, and Regeneron Pharmaceuticals. Dr Kitzman received honoraria outside the present study as a consultant for Bayer, Merck, Medtronic, Relypsa, Merck, Corvia Medical, Boehringer-Ingelheim, NovoNordisk, AstraZeneca, and Novartis; grant funding outside the present study from Novartis, Bayer, NovoNordisk, and AstraZeneca; and has stock ownership in Gilead Sciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Obesity is common in heart failure with preserved ejection fraction (HFpEF), and a hypocaloric diet can improve functional capacity. Malnutrition, sarcopenia, and frailty are also frequently present, and calorie restriction could harm some patients. Resting metabolic rate (RMR) is an essential determinant of caloric needs; however, it is rarely measured in clinical practice. The accuracy of commonly used predictive equations in HFpEF is unknown., Methods: RMR was measured with indirect calorimetry in 43 patients with HFpEF undergoing right heart catheterization at the University of Michigan, and among 49 participants in the SECRET trial (Study of the Effects of Caloric Restriction and Exercise Training in Patients With Heart Failure and a Normal Ejection Fraction); SECRET patients also had dual-energy X-ray absorptiometry body composition measures. Measured RMR was compared with RMR estimated using the Harris Benedict, Mifflin-St Jeor, World Health Organization, and Academy for Nutrition and Dietetics equations., Results: All predictive equations overestimated RMR (by >10%, P <0.001 for all), with mean (95% CI) differences Harris Benedict equation +250 (186-313), Mifflin-St. Jeor equation +169 (110-229), World Health Organization equation +300 (239-361), and Academy for Nutrition and Dietetics equation +794 (890-697) kcal/day. Results were similar across both patient groups, and the discrepancy between measured and estimated RMR tended to increase with body mass index. In SECRET, measured RMR was closely associated with lean body mass (ρ=0.74; by linear regression adjusted for age and sex: β=27 [95% CI, 18-36] kcal/day per kg, P <0.001; r 2 =0.56)., Conclusions: Commonly used predictive equations systematically overestimate measured RMR in patients with HFpEF. Direct measurement of RMR may be needed to effectively tailor dietary guidance in this population. Registration: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT00959660.

Background: Older patients who are hospitalized for acute decompensated heart failure have high rates of physical frailty, poor quality of life, delayed recovery, and frequent rehospitalizations. Interventions to address physical frailty in this population are not well established., Methods: We conducted a multicenter, randomized, controlled trial to evaluate a transitional, tailored, progressive rehabilitation intervention that included four physical-function domains (strength, balance, mobility, and endurance). The intervention was initiated during, or early after, hospitalization for heart failure and was continued after discharge for 36 outpatient sessions. The primary outcome was the score on the Short Physical Performance Battery (total scores range from 0 to 12, with lower scores indicating more severe physical dysfunction) at 3 months. The secondary outcome was the 6-month rate of rehospitalization for any cause., Results: A total of 349 patients underwent randomization; 175 were assigned to the rehabilitation intervention and 174 to usual care (control). At baseline, patients in each group had markedly impaired physical function, and 97% were frail or prefrail; the mean number of coexisting conditions was five in each group. Patient retention in the intervention group was 82%, and adherence to the intervention sessions was 67%. After adjustment for baseline Short Physical Performance Battery score and other baseline characteristics, the least-squares mean (±SE) score on the Short Physical Performance Battery at 3 months was 8.3±0.2 in the intervention group and 6.9±0.2 in the control group (mean between-group difference, 1.5; 95% confidence interval [CI], 0.9 to 2.0; P<0.001). At 6 months, the rates of rehospitalization for any cause were 1.18 in the intervention group and 1.28 in the control group (rate ratio, 0.93; 95% CI, 0.66 to 1.19). There were 21 deaths (15 from cardiovascular causes) in the intervention group and 16 deaths (8 from cardiovascular causes) in the control group. The rates of death from any cause were 0.13 and 0.10, respectively (rate ratio, 1.17; 95% CI, 0.61 to 2.27)., Conclusions: In a diverse population of older patients who were hospitalized for acute decompensated heart failure, an early, transitional, tailored, progressive rehabilitation intervention that included multiple physical-function domains resulted in greater improvement in physical function than usual care. (Funded by the National Institutes of Health and others; REHAB-HF ClinicalTrials.gov number, NCT02196038.)., (Copyright © 2021 Massachusetts Medical Society.)

Multiple observational studies have demonstrated an association with cannabis use and acute myocardial infarction, especially among young adults. However, little is known about the connection with subclinical or electrocardiographic myocardial injury. We hypothesized that cannabis use would be associated with an increased risk of myocardial injury as defined by the cardiac infarction and/or injury score (CIIS). This analysis included 3,634 (age 48.0 ± 5.9 years, 47.1% male, 68.7% Caucasians) participants from the Third National Health and Examination Survey. Cannabis use was defined by self-report. Those with history of cardiovascular disease were excluded. Myocardial injury was defined as electrocardiographic CIIS ≥ 10. Multivariable logistic regression was used to examine the association between cannabis use and myocardial injury. The consistency of this association was tested among subgroups stratified by race, gender, tobacco smoking status, and comorbidities. About 26.0% (n = 900) of participants were ever-cannabis users and 15.5% (n = 538) had myocardial injury. In a model adjusted for potential confounders, ever-cannabis users had 43% increased odds of myocardial injury compared to never users (Odds ratio (95% confidence interval): 1.43 (1.14, 1.80); p = 0.002). This association was stronger among participants with a history of hypertension versus those without (Odds ratio (95% confidence interval): 1.83 (1.36, 2.47) vs 1.17 (0.83, 1.64), respectively; interaction p value 0.04). Cannabis use is associated with an increased risk of myocardial injury among those without cardiovascular disease with effect modification by co-existent hypertension. These novel findings underscore the harmful effects of cannabis use on cardiovascular health and also merit a personalized risk assessment when counseling patients with hypertension on its use., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: The cross-sectional association between accelerometer-measured physical activity (PA), sedentary behaviour (SB) and cardiac structure and function is less well described. This study's primary aim was to compare echocardiographic measures of cardiac structure and function with accelerometer measured PA and SB., Methods: Participants included 1206 self-identified Hispanic/Latino men and women, age 45-74 years, from the Echocardiographic Study of Latinos. Standard echocardiographic measures included M-mode, two-dimensional, spectral, tissue Doppler and myocardial strain. Participants wore an Actical accelerometer at the hip for 1 week., Results: The mean±SE age for the cohort was 56±0.4 years, 57% were women. Average moderate to vigorous PA (MVPA) was 21±1.1 min/day, light PA was 217±4.2 min/day and SB was 737±8.1 min/day. Both higher levels of light PA and MVPA (min/day) were associated with lower left ventricular (LV) mass index (LVMI)/end-diastolic volume and a lower E/e' ratio. Higher levels of MVPA (min/day) were associated with better right ventricular systolic function. Higher levels of SB were associated with increased LVMI. In a multivariable linear regression model adjusted for demographics and cardiovascular disease modifiable factors, every 10 additional min/day of light PA was associated with a 0.03 mL/m 2 increase in left atrial volume index (LAVI) (p<0.01) and a 0.004 cm increase in tricuspid annular plane systolic excursion (p<0.01); every 10 additional min/day of MVPA was associated with a 0.18 mL/m 2 increase in LAVI (p<0.01) and a 0.24% improvement in global circumferential strain (p<0.01)., Conclusions: Our findings highlight the potential positive association between the MVPA and light PA on cardiac structure and function., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Chronic hypertension is associated with left ventricular hypertrophy. Recent evidence suggests that secondhand smoke (SHS) exposure is associated with chronic hypertension, so we sought to examine the relationship between secondhand smoke exposure and electrocardiographic left ventricular (LV) mass among non-smokers., Methods: This analysis included 4982 non-smoker participants from the Third National Health and Nutrition Examination (NHANES-III). Non-smoking was defined by self-report and serum cotinine ≤10 ng/mL, a biomarker for tobacco exposure. SHS exposure was defined as serum cotinine level ≥1 ng/mL. LV mass was estimated using an electrocardiographic model developed and applied in NHANES-III then validated in the Cardiovascular Health Study. Multivariable linear regression was used to examine the cross-sectional association between SHS exposure (vs no exposure) with estimated LV mass index. In similar models, we also examined the associations of LV mass index across quartiles of serum cotinine (reference group, 1st quartile) and in subgroups stratified by age, race, sex, hypertension, and obesity., Results: About 9.8% (n=489) of the participants were exposed to SHS. Exposure to SHS was associated with an estimated 2.9 g/m 2 increase in LV mass index, with a dose-response relationship between higher serum cotinine and LV mass index. These results were consistent in men and women, Whites and non-Whites, elderly and non-elderly, and those with and without hypertension. Significant effect modification was present among obese individuals with an estimated 4.8 g/m 2 increase in LV mass index (interaction p=0.01)., Conclusions: In a racially diverse sample of non-smokers, SHS is associated with increased LV mass with a dose-response relationship between level of exposure and LV mass. Effect modification was present among obese individuals. These findings underscore the harmful effect of passive smoking on the cardiovascular system and highlight the need for more restrictions on smoking in public areas, especially in countries or regions with less-stringent public health policies., Competing Interests: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none was reported., (© 2021 Skipina T.M. et al.)

Hypertension is the most prevalent modifiable factor for the development of heart failure. However, the optimal blood pressure (BP) target for preventing heart failure remains uncertain. The SPRINT (Systolic BP Intervention Trial) was a large, randomized open-label trial (n=9361 participants) that showed the superiority of a systolic BP target of <120 mm Hg compared with <140 mm Hg, with a 36% lower rate of acute decompensated heart failure (ADHF) events. This beneficial effect was consistent across all the key prespecified subgroups, including advanced age, chronic kidney disease, and prior cardiovascular disease. Participants who had an ADHF event had a markedly increased risk of subsequent cardiovascular disease events, including recurrent ADHF. Randomization to the intensive arm did not affect the recurrence of ADHF after the initial ADHF event (hazard ratio, 0.93 [95% CI, 0.50-1.67]; P =0.81). A separate analysis demonstrated that the reduction in ADHF events in the intensive treatment group in SPRINT was not due to the differential use of diuretics between the 2 treatment groups. Although intensive BP treatment resulted in a lower cardiovascular disease event rate, this was not significantly associated with changes in left ventricular mass, function, or fibrosis, as assessed in SPRINT HEART, an ancillary study to SPRINT. Intensive BP treatment, however, significantly attenuated increases in carotid-femoral pulse wave velocity. Overall, these data highlight the importance of preventing ADHF in high cardiovascular risk hypertensive patients by optimal BP reduction as tested in SPRINT.

[Figure: see text].

This study tested the hypothesis that early left ventricular (LV) relaxation is impaired in older obese patients with heart failure with preserved ejection fraction (HFpEF), and related to decreased peak exercise oxygen uptake (peak V̇o 2 ). LV strain and strain rate were measured by feature tracking of magnetic resonance cine images in 79 older obese patients with HFpEF (mean age: 66 yr; mean body mass index: 38 kg/m 2 ) and 54 healthy control participants. LV diastolic strain rates were indexed to cardiac preload as estimated by echocardiography derived diastolic filling pressures ( E/e' ), and correlated to peak V̇o 2 . LV circumferential early diastolic strain rate was impaired in HFpEF compared with controls (0.93 ± 0.05/s vs. 1.20 ± 0.07/s, P = 0.014); however, we observed no group differences in early LV radial or longitudinal diastolic strain rates. Isolating myocardial relaxation by indexing all three early LV diastolic strain rates (i.e. circumferential, radial, and longitudinal) to E/e' amplified the group difference in early LV diastolic circumferential strain rate (0.08 ± 0.03 vs. 0.13 ± 0.05, P < 0.0001), and unmasked differences in early radial and longitudinal diastolic strain rate. Moreover, when indexing to E/e' , early LV diastolic strain rates from all three principal strains, were modestly related with peak V̇o 2 ( R  = 0.36, -0.27, and 0.35, respectively, all P < 0.01); this response, however, was almost entirely driven by E/e' itself, ( R = -0.52, P < 0.001). Taken together, we found that although LV relaxation is impaired in older obese patients with HFpEF, and modestly correlates with their severely reduced peak exercise V̇o 2 , LV filling pressures appear to play a much more important role in determining exercise intolerance. NEW & NOTEWORTHY Using a multimodal imaging approach to uncouple tissue deformation from atrial pressure, we found that left ventricular (LV) relaxation is impaired in older obese patients with HFpEF, but only modestly correlates with their severely reduced peak V̇o 2 . In contrast, the data show a much stronger relationship between elevated LV filling pressures and exercise intolerance, refocusing future therapeutic priorities.

The choice of anticoagulant agents for newly implanted bioprosthetic valve varies significantly, particularly in the presence of postoperative atrial fibrillation with increasing use of nonvitamin K oral anticoagulation (NOACs) in recent years. We reported a challenging case with a coexisting bioprosthetic aortic valve thrombosis and significant anticoagulant-related bleeding. Clinical management strategy and brief literature review were presented., (© 2020 Wiley Periodicals LLC.)

: Active smoking is a widely accepted risk factor for cardiovascular disease and is recognized as a major public health problem. Passive smoking, also known as secondhand smoke exposure (SHSE), is thought to have similar cardiovascular consequences and the risk has been postulated to be equivalent to that of active smoking. A major component of this risk involves the connection with chronic hypertension. There are several population-based observational studies investigating the relationship between SHSE and chronic hypertension, all of which demonstrate a positive association. Given that SHSE appears to be a risk factor for chronic hypertension, SHSE should also be a risk factor for hypertensive end-organ disease. Many studies have sought to investigate this relationship, but this has yet to be fully elucidated. In this review, we focus on the current evidence regarding the association between SHSE and hypertension as well as exploration of the links between SHSE and hypertensive end-organ damage.

Background Heavy alcohol consumption has a well-established association with hypertension. However, doubt persists whether moderate alcohol consumption has a similar link. This relationship is not well-studied in patients with diabetes mellitus. We aimed to describe the association of alcohol consumption with prevalent hypertension in participants in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial. Methods and Results Alcohol consumption was categorized as none, light (1-7 drinks/week), moderate (8-14 drinks/week), and heavy (≥15 drinks/week). Blood pressure was categorized using American College of Cardiology/American Heart Association guidelines as normal, elevated blood pressure, stage 1 hypertension, and stage 2 hypertension. Multivariable logistic regression was used to explore the association between alcohol consumption and prevalent hypertension. A total of 10 200 eligible participants were analyzed. Light alcohol consumption was not associated with elevated blood pressure or any stage hypertension. Moderate alcohol consumption was associated with elevated blood pressure, stage 1, and stage 2 hypertension (odds ratio [OR], 1.79; 95% CI, 1.04-3.11, P =0.03; OR, 1.66; 95% CI, 1.05-2.60, P =0.03; and OR, 1.62; 95% CI, 1.03-2.54, P =0.03, respectively). Heavy alcohol consumption was associated with elevated blood pressure, stage 1, and stage 2 hypertension (OR, 1.91; 95% CI, 1.17-3.12, P =0.01; OR, 2.49; 95% CI, 1.03-6.17, P =0.03; and OR, 3.04; 95% CI, 1.28-7.22, P =0.01, respectively). Conclusions Despite prior research, our findings show moderate alcohol consumption is associated with hypertension in patients with type 2 diabetes mellitus and elevated cardiovascular risk. We also note a dose-risk relationship with the amount of alcohol consumed and the degree of hypertension.

Purpose of Review: Hypertension heralds the diagnosis of heart failure (HF) with preserved ejection fraction (HFpEF) in 75-85% of cases and shares many of its adverse outcomes as well as its acute and chronic symptoms. This review provides important new data about the pathophysiology and mechanisms that connect hypertension and HFpEF as well as therapy used in both conditions., Recent Findings: The traditional model of HFpEF pathophysiology emphasizes the role of hypertension causing increased afterload on the left ventricle (LV), leading to LV hypertrophy (LVH) and subsequent LV diastolic dysfunction. Recent work has provided valuable insights into the mechanisms underlying the transition from hypertension to HFpEF, showing that the pathophysiology extends beyond LVH and diastolic dysfunction. An evolving paradigm suggests that HFpEF is inflammatory in nature with multifactorial pathophysiology, affected by age-related changes and comorbidities. Hypertension shares many of the proinflammatory mechanisms of HFpEF. Furthermore, hypertension precedes HFpEF in the majority of cases. Because of its clinically heterogeneous nature, development of standardized therapies for HFpEF has been challenging. As there are standardized approaches to hypertension, we suggest that similar approaches be used for the treatment of HFpEF, including medical and non-medical therapies. With medical therapies, a treat-to-target blood pressure (BP) strategy could be employed, such as systolic BP < 130 mmHg. With non-medical therapies, approaches to deal with physical inactivity, obesity, and sleep apnea could be used. Due to its heterogeneity, delineation of standardized therapies for HFpEF has been challenging. Focusing on the tremendous overlap of hypertensive heart disease with HFpEF, it is proposed that approaches currently used to guide therapies for hypertension be applied to the treatment of HFpEF.

Abnormal P-wave axis may reflect preclinical atrial dysfunction and has been associated with an increased risk of incident atrial fibrillation (AF) in the general population. Patients with diabetes mellitus (DM) have a higher prevalence of AF, but the association of abnormal P-wave axis and the risk of incident AF in those with diabetes has not been previously explored. For this analysis, we included 8,965 eligible participants from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. P-wave axis was automatically measured on study electrocardiogram and visually confirmed, with the normal range being between 0° and 75°. At baseline, 8% of the study population had an abnormal P-wave axis. During 43,856 person-years of follow-up, there were 145 cases of incident AF. Using multivariable-adjusted Cox proportional hazards models, participants with abnormal P-wave axis had an increased risk of incident AF (hazard ratio 2.65, 95% confidence interval 1.76 to 3.99, p < 0.0001). Findings were similar in prespecified subgroups, without evidence of effect modification. Both left- and right-axis deviation of the P-wave were associated with incident AF. Our results suggest that abnormal P-wave axis is associated with incident AF in those with DM and that this relation is conserved in prespecified subgroups. There may be utility in considering P-wave axis values from routine ECGs in these patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)