Supervised Exercise Training for Chronic Heart Failure With Preserved Ejection Fraction: A Scientific Statement From the American Heart Association and American College of Cardiology.

Heart failure with preserved ejection fraction (HFpEF) is one of the most common forms of heart failure; its prevalence is increasing, and outcomes are worsening. Affected patients often experience severe exertional dyspnea and debilitating fatigue, as well as poor quality of life, frequent hospitalizations, and a high mortality rate. Until recently, most pharmacological intervention trials for HFpEF yielded neutral primary outcomes. In contrast, trials of exercise-based interventions have consistently demonstrated large, significant, clinically meaningful improvements in symptoms, objectively determined exercise capacity, and usually quality of life. This success may be attributed, at least in part, to the pleiotropic effects of exercise, which may favorably affect the full range of abnormalities-peripheral vascular, skeletal muscle, and cardiovascular-that contribute to exercise intolerance in HFpEF. Accordingly, this scientific statement critically examines the currently available literature on the effects of exercise-based therapies for chronic stable HFpEF, potential mechanisms for improvement of exercise capacity and symptoms, and how these data compare with exercise therapy for other cardiovascular conditions. Specifically, data reviewed herein demonstrate a comparable or larger magnitude of improvement in exercise capacity from supervised exercise training in patients with chronic HFpEF compared with those with heart failure with reduced ejection fraction, although Medicare reimbursement is available only for the latter group. Finally, critical gaps in implementation of exercise-based therapies for patients with HFpEF, including exercise setting, training modalities, combinations with other strategies such as diet and medications, long-term adherence, incorporation of innovative and more accessible delivery methods, and management of recently hospitalized patients are highlighted to provide guidance for future research.

Targeting Parasympathetic Activity to Improve Autonomic Tone and Clinical Outcomes.

In this review we will briefly summarize the evidence that autonomic imbalance, more specifically reduced parasympathetic activity to the heart, generates and/or maintains many cardiorespiratory diseases and will discuss mechanisms and sites, from myocytes to the brain, that are potential translational targets for restoring parasympathetic activity and improving cardiorespiratory health.

Multidisciplinary Care in Heart Failure Services.

The American College of Cardiology/American Heart Association/Heart Failure Society of American 2022 guidelines for heart failure (HF) recommend a multidisciplinary team approach for patients with HF. The multidisciplinary HF team-based approach decreases the hospitalization rate for HF and health care costs and improves adherence to self-care and the use of guideline-directed medical therapy. This article proposes the optimal multidisciplinary team structure and each team member's delineated role to achieve institutional goals and metrics for HF care. The proposed HF-specific multidisciplinary team comprises cardiologists, surgeons, advanced practice providers, clinical pharmacists, specialty nurses, dieticians, physical therapists, psychologists, social workers, immunologists, and palliative care clinicians. A standardized multidisciplinary HF team-based approach should be incorporated to optimize the structure, minimize the redundancy of clinical responsibilities among team members, and improve clinical outcomes and patient satisfaction in their HF care.

Emerging Roles for Artificial Intelligence in Heart Failure Imaging.

Artificial intelligence (AI) applications are expanding in cardiac imaging. AI research has shown promise in workflow optimization, disease diagnosis, and integration of clinical and imaging data to predict patient outcomes. The diagnostic and prognostic paradigm of heart failure is heavily reliant on cardiac imaging. As AI becomes increasingly validated and integrated into clinical practice, AI influence on heart failure management will grow. This review discusses areas of current research and potential clinical applications in AI as applied to heart failure cardiac imaging.

The Degree of the Predischarge Pulmonary Congestion in Patients Hospitalized for Worsening Heart Failure Predicts Readmission and Mortality.

BACKGROUND: Prediction of readmission and death after hospitalization for heart failure (HF) is an unmet need. AIM: We evaluated the ability of clinical parameters, NT-proBNP level and noninvasive lung impedance (LI), to predict time to readmission (TTR) and time to death (TTD). METHODS AND RESULTS: The present study is a post hoc analysis of the IMPEDANCE-HF extended trial comprising 290 patients with LVEF ≤45% and New York Heart Association functional class II-IV, randomized 1:1 to LI-guided or conventional therapy. Of all patients, 206 were admitted 766 times for HF during a follow-up of 57 ± 39 months. The normal LI (NLI), representing the "dry" lung status, was calculated for each patient at study entry. The current degree of pulmonary congestion (PC) compared with its dry status was represented by ΔLIR = ([measured LI/NLI] - 1) × 100%. Twenty-six parameters recorded during HF admission were used to predict TTR and TTD. To determine the parameter which mainly impacted TTR and TTD, variables were standardized, and effect size (ES) was calculated. Multivariate analysis by the Andersen-Gill model demonstrated that ΔLIRadmission (ES = 0.72), ΔLIRdischarge (ES = -3.14), group assignment (ES = 0.2), maximal troponin during HF admission (ES = 0.19), LVEF related to admission (ES = -0.22) and arterial hypertension (ES = 0.12) are independent predictors of TTR (p < 0.01, χ2 = 1,206). Analysis of ES showed that residual PC assessed by ∆LIRdischarge was the most prominent predictor of TTR. One percent improvement in predischarge PC, assessed by ∆LIRdischarge, was associated with a likelihood of TTR increase by 14% (hazard ratio [HR] 1.14, 95% confidence interval [CI] 1.13-1.15, p < 0.01) and TTD increase by 8% (HR 1.08, 95% CI 1.07-1.09, p < 0.01). CONCLUSION: The degree of predischarge PC assessed by ∆LIR is the most dominant predictor of TTR and TTD.

Menopausal Hormone Therapy and Risks of First Hospitalized Heart Failure and its Subtypes During the Intervention and Extended Postintervention Follow-up of the Women's Health Initiative Randomized Trials.

BACKGROUND: We assessed whether postmenopausal hormone therapy (HT) was associated with incident heart failure (HF) and its subtypes and examined whether there was a modifying effect of age on the associations. METHODS AND RESULTS: Postmenopausal women aged 50-79 enrolled in the Women's Health Initiative HT trials were analyzed. The 16,486 women with a uterus were randomized to receive conjugated equine estrogens (CEE 0.625 mg/day) plus medroxyprogesterone acetate (MPA 2.5 mg/day) or placebo, and 10,739 women with prior hysterectomy were randomized to receive CEE (0.625 mg/day) alone or placebo. Incident HF was defined as the first HF hospitalization. HF with reduced ejection fraction (HFrEF) or preserved EF (HFpEF) was defined as EF < 50% or ≥ 50%. During the intervention phase, median follow-up was 5.6 years in the CEE-plus-MPA trial and 7.2 years in the CEE-alone trial. During the cumulative follow-up of 18.9 years, women randomized to HT vs placebo in the 2 combined trials had incidence rates of 3.90 vs 3.89 per 1000 person-years for total HF; 1.25 vs 1.40 per 1000 person-years for HFrEF, and 1.88 vs 1.79 per 1000 person-years for HFpEF, respectively. There were no significant effects of HT on the risk of total incident HF or its subtypes in either trial, and age at randomization did not significantly modify the results. CONCLUSIONS: Postmenopausal HT did not alter the risk of hospitalization for HF or its subtypes during the intervention or cumulative 18.9 years of follow-up, and results did not vary significantly by age at randomization. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT0000611 https://clinicaltrials.gov/ct2/show/NCT00000611?cond=women%27s±health±initiative&rank=5.

Cardiac work is related to creatine kinase energy supply in human heart failure: a cardiovascular magnetic resonance spectroscopy study.

BACKGROUND: It has been hypothesized that the supply of chemical energy may be insufficient to fuel normal mechanical pump function in heart failure (HF). The creatine kinase (CK) reaction serves as the heart's primary energy reserve, and the supply of adenosine triphosphate (ATP flux) it provides is reduced in human HF. However, the relationship between the CK energy supply and the mechanical energy expended has never been quantified in the human heart. This study tests whether reduced CK energy supply is associated with reduced mechanical work in HF patients. METHODS: Cardiac mechanical work and CK flux in W/kg, and mechanical efficiency were measured noninvasively at rest using cardiac pressure-volume loops, magnetic resonance imaging and phosphorus spectroscopy in 14 healthy subjects and 27 patients with mild-to-moderate HF. RESULTS: In HF, the resting CK flux (126 ± 46 vs. 179 ± 50 W/kg, p < 0.002), the average (6.8 ± 3.1 vs. 10.1 ± 1.5 W/kg, p  <0.001) and the peak (32 ± 14 vs. 48 ± 8 W/kg, p < 0.001) cardiac mechanical work-rates, as well as the cardiac mechanical efficiency (53% ± 16 vs. 79% ± 3, p < 0.001), were all reduced by a third compared to healthy subjects. In addition, cardiac CK flux correlated with the resting peak and average mechanical power (p < 0.01), and with mechanical efficiency (p = 0.002). CONCLUSION: These first noninvasive findings showing that cardiac mechanical work and efficiency in mild-to-moderate human HF decrease proportionately with CK ATP energy supply, are consistent with the energy deprivation hypothesis of HF. CK energy supply exceeds mechanical work at rest but lies within a range that may be limiting with moderate activity, and thus presents a promising target for HF treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00181259 .

Cardiac Complications of Cancer Therapy: Pathophysiology, Identification, Prevention, Treatment, and Future Directions.

PURPOSE OF REVIEW: Cardiotoxicity is an important complication of cancer therapy. With a significant improvement in the overall survival and prognosis of patients undergoing cancer therapy, cardiovascular toxicity of cancer therapy has become an important public health issue. Several well-established as well as newer anticancer therapies such as anthracyclines, trastuzumab, and other HER2 receptor blockers, antimetabolites, alkylating agents, tyrosine kinase inhibitors, angiogenesis inhibitors, checkpoint inhibitors, and thoracic irradiation are associated with significant cardiotoxicity. RECENT FINDINGS: Cardiovascular imaging employing radionuclide imaging, echocardiography, and magnetic resonance imaging is helpful in early detection of the cardiotoxicity and prevention of overt heart failure. These techniques also provide important tools for understanding the mechanism of cardiotoxicity of these modalities, which would help develop strategies for the prevention of cardiac morbidity and mortality related to the use of these agents. An understanding of the mechanism of the cardiotoxicity of cancer therapies can help prevent and treat their adverse cardiovascular consequences. Clinical implementation of algorithms based upon cardiac imaging and several non-imaging biomarkers can prevent cardiac morbidity and mortality associated with the use of cardiotoxic cancer therapies.

Diagnosis and Management of Heart Failure in Older Adults.

Aging is characterized by heterogeneity, both in health and illness. Older adults with heart failure often have preserved ejection fraction and atypical and delayed clinical manifestations. After diagnosis of heart failure is established, a cause should be sought. The patient's comorbidities may provide clues. An elevated jugular venous pressure is the most reliable clinical sign of fluid volume overload and should be carefully evaluated. Left ventricular ejection fraction must be determined to assess prognosis and guide therapy. These 5 steps, namely, diagnosis, etiologic factor, fluid volume, ejection fraction, and therapy for heart failure may be memorized by mnemonic: DEFEAT-HF.

The lower the achieved blood pressure goal the better.

PURPOSE OF REVIEW: Hypertension is the eminent risk factor for renal and cardiovascular disease (CVD). Its management is a topic of public health priority. As either too high or too low blood pressure (BP) levels can have detrimental effects on health, optimal targets for BP continue to be controversial. The current manuscript will review relevant data published over the last year that add to this topic of controversy. RECENT FINDINGS: Recent studies confirm increased CVD-related risk with increasing SBP levels more than 140  mmHg among patients with hypertension and CVD as well as those over the age of 60 years. A SBP target less than 140  mmHg conveyed lessened risk of CVD-related events. There is some evidence suggesting that the ideal BP target lies between 120 and 140  mmHg. SUMMARY: Recent data support a target SBP of less than 140  mmHg among patients with hypertension or CVD, and achievement of this target might benefit those older than 60 years of age as well. Treating to SBPs below 120  mmHg may not result in further benefit. Data from randomized controlled trials specifically addressing the question whether lower BPs are associated with better outcomes are needed to further define ideal BP-target goals.

Cardiovascular Disease and Mortality in Black Women Carrying the Amyloidogenic V122I Transthyretin Gene Variant.

BACKGROUND: Long-term data on cardiovascular disease (CVD) and mortality in female carriers of the transthyretin (TTR) V122I (pV142I) variant, one of the most common variants of hereditary transthyretin cardiac amyloidosis, are sparse and the effects of blood pressure, heart rate, body mass index, and physical activity on CVD outcomes remain largely unknown. OBJECTIVES: The aim was to first examine the relationship of TTR V122I (pV142I) carrier status with CVD and mortality and second to investigate the effects of blood pressure, heart rate, body mass index, and physical activity in a large cohort of postmenopausal women. METHODS: The study population consisted of 9,862 non-Hispanic Black/African American women, 9,529 noncarriers and 333 TTR V122I carriers, enrolled in the Women's Health Initiative at 40 centers in the United States. Women were generally healthy and postmenopausal at the time of enrollment (1993-1998). CVD was defined as a composite endpoint consisting of coronary heart disease, stroke, acute heart failure or CVD death, and all-cause mortality. CVD cases were based on self-reported annual mailed health updates. All information was centrally adjudicated by trained physicians. HRs and 95% CIs were obtained from adjusted Cox proportional hazards models. RESULTS: Among 9,862 Black female participants (mean age: 62 years [IQR: 56-67 years]), the population frequency of the TTR V122I variant was 3.4% (333 variant carriers and 9,529 noncarriers). During a mean follow-up of 16.1 years (IQR: 9.7-22.2 years), incident CVD occurred in 2,229 noncarriers and 96 carriers, whereas 2,689 noncarriers and 108 carriers died. In adjusted models including demographic, lifestyle, and medical history covariates, TTR V122I carriers were at higher risk of the composite endpoint CVD (HR: 1.52; 95% CI: 1.22-1.88), acute heart failure (HR: 2.21; 95% CI: 1.53-3.18), coronary heart disease (HR: 1.80; 95% CI: 1.30-2.47), CVD death (HR: 1.70; 95% CI: 1.26-2.30), and all-cause mortality (HR: 1.28; 95% CI: 1.04-1.56). The authors found a significant interaction by age but not by blood pressure, heart rate, body mass index, or physical activity. CONCLUSIONS: Black female TTR V122I (pV142I) carriers have a higher CVD and all-cause mortality risk compared to noncarriers. In case of clinical suspicion of amyloidosis, they should be screened for TTR V122I (pV142I) carrier status to ensure early treatment onset.

Supervised Exercise Training for Chronic Heart Failure With Preserved Ejection Fraction: A Scientific Statement From the American Heart Association and American College of Cardiology.

Heart failure with preserved ejection fraction (HFpEF) is one of the most common forms of heart failure; its prevalence is increasing, and outcomes are worsening. Affected patients often experience severe exertional dyspnea and debilitating fatigue, as well as poor quality of life, frequent hospitalizations, and a high mortality rate. Until recently, most pharmacological intervention trials for HFpEF yielded neutral primary outcomes. In contrast, trials of exercise-based interventions have consistently demonstrated large, significant, clinically meaningful improvements in symptoms, objectively determined exercise capacity, and usually quality of life. This success may be attributed, at least in part, to the pleiotropic effects of exercise, which may favorably affect the full range of abnormalities-peripheral vascular, skeletal muscle, and cardiovascular-that contribute to exercise intolerance in HFpEF. Accordingly, this scientific statement critically examines the currently available literature on the effects of exercise-based therapies for chronic stable HFpEF, potential mechanisms for improvement of exercise capacity and symptoms, and how these data compare with exercise therapy for other cardiovascular conditions. Specifically, data reviewed herein demonstrate a comparable or larger magnitude of improvement in exercise capacity from supervised exercise training in patients with chronic HFpEF compared with those with heart failure with reduced ejection fraction, although Medicare reimbursement is available only for the latter group. Finally, critical gaps in implementation of exercise-based therapies for patients with HFpEF, including exercise setting, training modalities, combinations with other strategies such as diet and medications, long-term adherence, incorporation of innovative and more accessible delivery methods, and management of recently hospitalized patients are highlighted to provide guidance for future research.

The Multidisciplinary Heart Team in Cardiovascular Medicine: Current Role and Future Challenges.

Cardiovascular multidisciplinary heart teams (MDHTs) have evolved significantly over the past decade. These teams play a central role in the treatment of a wide array of cardiovascular diseases affecting interventional cardiology, cardiac surgery, interventional imaging, advanced heart failure, adult congenital heart disease, cardio-oncology, and cardio-obstetrics. To meet the specific needs of both patients and heart programs, the composition and function of cardiovascular MDHTs have had to adapt and evolve. Although lessons have been learned from multidisciplinary cancer care, best practices for the operation of cardiovascular MDHTs have yet to be defined, and the evidence base supporting their effectiveness is limited. This expert panel review discusses the history and evolution of cardiovascular MDHTs, their composition and role in treating patients across a broad spectrum of disciplines, basic tenets for successful operation, and the future challenges facing them.

The j-point phenomenon in aggressive therapy of hypertension: new insights.

In the era of aggressive control of cardiovascular risk factors such as hypertension, the mantra of "lower is better" has taken a strong foothold. Although there is clear epidemiologic evidence that lower blood pressure improves specific organ-related outcomes, this rule does not apply to all patients and definitely not all target organs. The concept of J-curve or adverse outcomes at lower blood pressure has been proposed for more than three decades but has recently come under increasing scrutiny. Specifically, a relationship between adverse cardiovascular outcomes and low diastolic blood pressure has been observed in multiple clinical trials. In this article we review the advances in understanding of the J-curve phenomenon and include a discussion on specific populations that might be at higher risk due to the J-curve relationship.

Primary Graft Dysfunction after Heart Transplantation - Unravelling the Enigma.

Primary graft dysfunction (PGD) remains the main cause of early mortality following heart transplantation despite several advances in donor preservation techniques and therapeutic strategies for PGD. With that aim of establishing the aetiopathogenesis of PGD and the preferred management strategies, the new consensus definition has paved the way for multiple contemporaneous studies to be undertaken and accurately compared. This review aims to provide a broad-based understanding of the pathophysiology, clinical presentation and management of PGD.

The association of walking pace and incident heart failure and subtypes among postmenopausal women.

BACKGROUND: To investigate the association between walking pace and the risk of heart failure (HF) and HF sub-types. METHODS: We examined associations of self-reported walking pace with risk of incident HF and HF subtypes of preserved (HFpEF) and reduced (HFrEF) ejection fractions, among 25,183 postmenopausal women, ages 50-79 years. At enrollment into the Women's Health Initiative cohort in 1993-1998, this subset of women was free of HF, cancer, or the inability to walk one block, with self-reported information on walking pace and walking duration. Multivariable Cox regression was used to examine associations of walking pace (casual <2 mph [referent], average 2-3 mph, and fast >3 mph) with incident HF. We also examined the joint association of walking pace and duration with incident HF. RESULTS: There were 1455 incident adjudicated acute decompensated HF hospitalization cases during a median of 16.9 years of follow-up. There was a strong inverse association between walking pace and overall risk of HF (HR = 0.73, 95% CI [0.65, 0.83] for average vs. casual walking; HR = 0.66, 95%CI [0.56, 0.78] for fast vs. casual walking). There were similar associations of walking pace with HFpEF (HR = 0.73, 95%CI [0.62, 0.86] average vs. casual; HR = 0.63, 95%CI [0.50, 0.80] for fast vs. casual) and with HFrEF (HR = 0.72, 95%CI [0.57, 0.91] for average vs. casual; HR = 0.74, 95%CI [0.54, 0.99] for fast vs. casual). The risk of HF associated with fast walking with less than 1 h/week walking duration was comparable with the risk of HF among casual and average walkers with more than 2 h/week walking duration. CONCLUSION: Walking pace was inversely associated with risks of overall HF, HFpEF, and HFrEF in postmenopausal women. Whether interventions to increase the walking pace in older adults will reduce HF risk and whether fast pace will compensate for the short duration of walking warrants further study.

Cardiovascular Outcomes in Patients With Mitochondrial Disease in the United States: A Propensity Score Analysis.

Mitochondrial disease comprises a wide range of genetic disorders caused by mitochondrial dysfunction. Its rarity, however, has limited the ability to assess its effects on clinical outcomes. To evaluate this relationship, we collected data from the 2016 National Inpatient Sample, which includes data from >7 million hospital stays. We identified 705 patients (mean age, 22 ± 20.7 yr; 54.2% female; 67.4% white) whose records included the ICD-10-CM code E88.4. We also identified a propensity-matched cohort of 705 patients without mitochondrial disease to examine the effect of mitochondrial disease on major adverse cardiovascular events, including all-cause in-hospital death, cardiac arrest, and acute congestive heart failure. Patients with mitochondrial disease were at significantly greater risk of major adverse cardiovascular events (odds ratio [OR]=2.42; 95% CI, 1.29-4.57; P=0.005), systolic heart failure (OR=2.37; 95% CI, 1.08-5.22; P=0.027), and all-cause in-hospital death (OR=14.22; 95% CI, 1.87-108.45; P<0.001). These findings suggest that mitochondrial disease significantly increases the risk of inpatient major adverse cardiovascular events.

Relation of Bariatric Surgery to Inpatient Cardiovascular Outcomes (from the National Inpatient Sample).

Approximately one in 3 patients in the United States are obese. There is a strong association between obesity and an increased rate of cardiovascular disease (CVD)-related mortality. Bariatric surgery (BS) has emerged as an effective strategy to achieve reduction of excess weight. Our study aims to explore the relationship between BS and major adverse cardiovascular events (MACE) among obese hospitalized patients in the United States. This is a retrospective study of all obese adult patients with BMI ≥35 kg/m2 (n= 1,700,943) in the National Inpatient Sample between 2012 and 2016. Differences in the clinical characteristics of obese patients with a history of BS versus obese patients without a history of BS were analyzed as well as the association between BS and MACE after adjusting for CVD risk factors. Among 50,296 obese patients with a history of BS (2.96%), the mean age was 53 ± 12 years with the majority being female (75.32%) and Caucasian (71.85%). Multivariate analysis revealed that obese patients with a history of BS had a1.6-fold decrease odds of MACE compared with patients without BS (OR 0.62; 95% CI, 0.60 to 0.65; p <0.001). In conclusion, this study illustrates that among obese patients with BMI ≥35 kg/m2, history of BS was associated with a significantly lower odds of inpatient MACE, after adjusting for CVD risk factors.

Cardiac Rehabilitation for Patients With Heart Failure: JACC Expert Panel.

Cardiac rehabilitation is defined as a multidisciplinary program that includes exercise training, cardiac risk factor modification, psychosocial assessment, and outcomes assessment. Exercise training and other components of cardiac rehabilitation (CR) are safe and beneficial and result in significant improvements in quality of life, functional capacity, exercise performance, and heart failure (HF)-related hospitalizations in patients with HF. Despite outcome benefits, cost-effectiveness, and strong practice guideline recommendations, CR remains underused. Clinicians, health care leaders, and payers should prioritize incorporating CR as part of the standard of care for patients with HF.

Evaluation for Heart Transplantation and LVAD Implantation: JACC Council Perspectives.

Timely referrals for transplantation and left ventricular assist device implantation play a key role in favorable outcomes in patients with advanced heart failure. Nonetheless, evaluation usually occurs at advanced heart failure centers and is obscured from referring physicians. The purposes of this review are to explain the decision-making process for candidacy for advanced therapies and to describe the potential impact of the new organ allocation algorithm on center decision making. The document first addresses the signs of advanced heart failure, specifically focusing on the importance of the syndrome of low cardiac output as a key feature of advanced heart failure, and then summarizes the evaluation as a 3-step process addressing the following questions: 1) Is transplantation or durable assist device placement indicated? 2) Are there contraindications to either intervention? 3) How can one choose between transplantation and left ventricular assist device implantation if advanced therapies are indicated and not contraindicated?