Physical Rehabilitation for Older Patients Hospitalized for Heart Failure.

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.).

Prevalence and clinical associations of mitral and aortic regurgitation in patients with aortic stenosis.

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.

Left Atrial Stiffness Index Independently Predicts Exercise Intolerance and Quality of Life in Older, Obese Patients With Heart Failure With Preserved Ejection Fraction.

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 VO2), 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 VO2, 6MWD, and lower quality of life. Increased LA stiffness was independently associated with impaired peak VO2 (ß = 9.0 ± 1.6, P < .001), 6MWD (ß = 117 ± 22, P = .003), and Kansas City Cardiomyopathy Questionnaire score (ß = -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.

Newer Drugs to Reduce High Blood Pressure and Mitigate Hypertensive Target Organ Damage.

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.

Hypertension Across a Woman's Life Cycle.

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.

Left ventricular diastolic dysfunction and exercise intolerance in obese heart failure with preserved ejection fraction.

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 V̇o2). 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/m2) 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 V̇o2. 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 V̇o2 (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 V̇o2, 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 V̇o2. In contrast, the data show a much stronger relationship between elevated LV filling pressures and exercise intolerance, refocusing future therapeutic priorities.

Optimizing The Management of Obese HFpEF Phenotype: Can We Mind Both The Heart and The Kidney?

The adverse prognostic implications of significant renal dysfunction during treatment of acute decompensated heart failure (HF) in patients with obese HF and preserved ejection fraction (HFpEF) provide strong rationale for development of therapeutic strategies that enhance decongestion while preserving renal function in this cohort. The combination of preload sensitivity, intrinsic renal dysfunction related to obesity, glomerular hyperfiltration, reversible renal hypoperfusion (poor renal arterial perfusion and renal venous congestion), and decreased systemic vascular resistance in obesity may predispose patients to renal hemodynamic compromise during diuresis. Thus, serum creatinine increase should not be evaluated in isolation but rather considered in the context of the entire clinical picture in patients with obese HFpEF.

Hypertension as a Road to Treatment of Heart Failure with Preserved Ejection Fraction.

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.

Anticoagulation for coexisting bioprosthetic aortic valve thrombosis and anticoagulant-related bleeding: "A double edge sword".

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.

P-wave axis is associated with all-cause mortality in diabetes: The ACCORD trial.

Abnormal P-wave axis (PWA) has emerged as a novel marker of risk for both cardiovascular disease (CVD) and all-cause mortality (ACM) in the general population, though this relationship has not been adequately explored among those with type 2 diabetes (DM2). We aimed to explore the association between abnormal PWA and ACM among a large, well-phenotyped group of participants with DM2 from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. This analysis included 8899 ACCORD participants with available PWA data on baseline electrocardiogram. Cox proportional hazards models were used to examine the association between PWA and ACM in models adjusted for demographics, ACCORD trial treatment assignment, and potential confounders. PWA was modeled as either normal (0° -75°) or abnormal (<0° or >75°). Over 44,000 person-years of follow up, there were 609 deaths. Participants with abnormal PWA had increased risk of ACM (HR 1.61, 95% CI 1.25-2.08). After multivariable adjustment, the association remained significant (HR 1.33, 95% CI 1.03-1.72). This relationship was similar in subgroups stratified by age, race, sex, and history of CVD. Among ACCORD trial participants, abnormal PWA was associated with an increased risk of mortality. Abnormal PWA may have added value beyond traditional risk factors in prediction models.

Is Left Ventricular Hypertrophy a Valid Therapeutic Target?

PURPOSE OF REVIEW: The purpose of this review is to answer the question whether left ventricular hypertrophy (LVH) could be considered a therapeutic target in patients with hypertension. To fulfill this purpose, we briefly outline different methods of measuring LVH, then discuss the current evidence and unresolved controversies regarding the relationships among LVH, blood pressure (BP), and cardiovascular disease (CVD) outcomes. RECENT FINDINGS: The methods and criteria used for defining LVH in clinical studies lack consistency and are inherently different. Electrocardiogram (ECG) has been the most common method, but some studies used echocardiography, and recently, the cardiac magnetic resonance imaging was used by some studies as well. Regardless of the method, studies have shown that higher BP is a risk factor for LVH, regression of LVH is possible by successful BP lowering, and LVH is associated with CVD outcomes. Nevertheless, recent trials revealed that although intensive BP lowering (systolic BP target of < 120 mm of Hg) resulted in lower rates of developing new ECG-LVH and higher rates of regression of existing LVH, the benefit of intensive BP lowering on the risk of CV events was not meaningfully influenced by its favorable effect on ECG-LVH. These findings raise several critical questions about the mechanistic links between hypertension treatment, LVH regression, and reduction in CV events. Given these questions and findings, LVH improvement cannot yet be considered a reliable surrogate outcome measure for use in the context of hypertensive heart disease. LVH is a modifiable risk factor related to systolic BP and regression of LVH may reduce subsequent CV events. However, LVH may not be the "holy grail" in regard to therapeutic targets in hypertensive heart disease, but it could be considered one of the markers in the successful management of hypertension.

Preventing Heart Failure by Treating Systolic Hypertension: What Does the SPRINT Add?

PURPOSE OF REVIEW: Previous trials definitively established that lowering systolic blood pressure (BP) to 140 mmHg prevented heart failure (HF) exacerbations, but the potential benefits and risks of further BP reduction remain unclear due to a paucity of trial-based data. RECENT FINDINGS: A recent secondary analysis of the Systolic Blood Pressure Intervention Trial (SPRINT) found that in older, high-risk, non-diabetic participants with systolic hypertension, a BP treatment target < 120 mmHg resulted in a 36% lower rate of acute decompensated HF as compared with a BP target < 140 mmHg. Those participants with incident HF had a 26-fold increased risk of subsequent cardiovascular events and death. Based in part on the SPRINT results, the 2017 American Heart Association/American College of Cardiology/HF Society Guideline for the Management of HF acknowledged that targeting a significant reduction in BP in those at increased risk for cardiovascular disease is a novel risk-based strategy to prevent HF. SPRINT redefines systolic BP target goals in older, high-risk patients and provides a key opportunity for preventing HF in this patient group.

The effect of Aliskiren on exercise capacity in older patients with heart failure and preserved ejection fraction: A randomized, placebo-controlled, double-blind trial.

In older patients (70 ± 7 years) with chronic well-compensated heart failure with preserved ejection and controlled blood pressure, 6 months treatment with aliskiren (direct renin inhibitor) showed non-significant trends for modest improvements in peak exercise oxygen consumption (14.9 ± 0.2 mL kg-1 min-1 versus 14.4 ± 0.2 mL kg-1 min-1; P = .10, trend) and ventilatory anaerobic threshold (888 ± 19 mL/min versus 841 ± 18 mL/min; P = .08).

Therapy for heart failure with preserved ejection fraction: current status, unique challenges, and future directions.

Heart failure (HF) with preserved ejection fraction (HFpEF) is the most common form of HF. Among elderly women, HFpEF comprises more than 80% of incident HF cases. Adverse outcomes-exercise intolerance, poor quality of life, frequent hospitalizations, and reduced survival-approach those of classic HF with reduced EF (HFrEF). However, despite its importance, our understanding of the pathophysiology of HFpEF is incomplete, and despite intensive efforts, optimal therapy remains uncertain, as most trials to date have been negative. This is in stark contrast to management of HFrEF, where dozens of positive trials have established a broad array of effective, guidelines-based therapies that definitively improve a range of clinically meaningful outcomes. In addition to providing an overview of current management status, we examine evolving data that may help explain this paradox, overcome past challenges, provide a roadmap for future success, and that underpin a wave of new trials that will test novel approaches based on these insights.

Heart Failure with Preserved Ejection Fraction in Older Adults.

Most elderly patients, particularly women, who have heart failure, have a preserved ejection fraction. Patients with this syndrome have severe symptoms of exercise intolerance, frequent hospitalizations, and increased mortality. Despite the importance of heart failure with preserved ejection fraction (HFpEF), the understanding of its pathophysiology is incomplete, and optimal treatment remains largely undefined. Unlike the management of HFrEF, there is a paucity of large evidence-based trials demonstrating morbidity and mortality benefit for the treatment of HFpEF. An update is presented on information regarding pathophysiology, diagnosis, management, and future directions in this important and growing disorder.

Clinical Outcomes in Different Types of Aortic Stenosis as Assessed by Doppler Echocardiography.

BACKGROUND AND AIM OF THE STUDY: Cardiologists continue to struggle with the prognosis and significance of low-gradient, severe aortic stenosis (AS) with preserved ejection fraction (EF). Conflicting data makes more substantive decisions challenging. The study aim was to determine the prognosis and significance of severe AS by reviewing index cases from the authors' echocardiography laboratory. METHODS: The study included 302 patients with AS and with aortic valve area (AVA) ≤1.0 cm2 who were identified from the echocardiography database between 2010 and 2011. AS was subdivided into four types based on AVA and mean pressure gradient (PG): (i) PG-matched, severe AS (AVA ≤1.0 cm2 and mean PG ≥40 mmHg; n = 143); (ii) low-PG, severe AS (AVA ≤1.0 cm2, mean PG <40 mmHg, and reduced EF <50%; n = 52); (iii) low-PG, severe AS (AVA ≤1.0 cm2, mean PG <40 mmHg, preserved EF ≥50%; n = 107); and patients with moderate AS (mean PG >25 mmHg and AVA ≥1.0 cm2; n = 104). RESULTS: Among patients medically managed, those with low-PG severe AS and a reduced EF had the worst outcome. Compared to low-PG severe AS with EF ≥50%, patients with a low-PG and severe AS with EF <50%, and with matched-PG severe AS, had an increased risk of death (p <0.001 and p = 0.052, respectively). For gradient-matched severe AS, those patients who were unoperated had a more than five-fold mortality risk compared to those who underwent surgery [Hazard Ratio (HR): 5; p <0.001]. Similarly, among patients with low-PG severe AS with EF ≥50%, those medically managed had a threefold greater mortality risk compared to those who underwent surgery (HR: 3.3; p = 0.002). CONCLUSIONS: Patients with low-PG severe AS and a preserved EF have a worse survival than those with moderate AS, but survived better than those with gradient-matched severe AS.

Heart failure with preserved ejection fraction in the elderly: scope of the problem.

Heart failure with preserved ejection fraction (HFpEF) is the most common form of heart failure (HF) in older adults, particularly women, and is increasing in prevalence as the population ages. With morbidity and mortality on par with HF with reduced ejection fraction, it remains a most challenging clinical syndrome for the practicing clinician and basic research scientist. Originally considered to be predominantly caused by diastolic dysfunction, more recent insights indicate that HFpEF in older persons is typified by a broad range of cardiac and non-cardiac abnormalities and reduced reserve capacity in multiple organ systems. The globally reduced reserve capacity is driven by: 1) inherent age-related changes; 2) multiple, concomitant co-morbidities; 3) HFpEF itself, which is likely a systemic disorder. These insights help explain why: 1) co-morbidities are among the strongest predictors of outcomes; 2) approximately 50% of clinical events in HFpEF patients are non-cardiovascular; 3) clinical drug trials in HFpEF have been negative on their primary outcomes. Embracing HFpEF as a true geriatric syndrome, with complex, multi-factorial pathophysiology and clinical heterogeneity could provide new mechanistic insights and opportunities for progress in management. This article is part of a Special Issue entitled CV Aging.