Heart failure with preserved ejection fraction epidemiology, pathophysiology, diagnosis and treatment strategies.
International journal of cardiology
The prevalence of HF with preserved ejection raction (HFpEF, with EF ≥50%) is increasing across all populations with high rates of hospitalization and mortality, reaching up to 80% and 50%, respectively, within a 5-year timeframe. Comorbidity-driven systemic inflammation is thought to cause coronary microvascular dysfunction and increased epicardial adipose tissue, leading to downstream friborsis and molecular changes in the cardiomyocyte, leading to increased stiffness and diastolic dynsfunction. HFpEF poses unique challenges in terms of diagnosis due to its complex and diverse nature. The diagnosis of HFpEF relies on a combination of clinical assessment, imaging studies, and biomarkers. An additional important step in diagnosing HFpEF involves excluding certain cardiac diagnoses that may be specific underlying causes of HFpEF or may be masquerading as HFpEF and require specific alternative treatment approaches. In addition to administering sodium-glucose cotransporter 2 inhibitors to all patients, the most effective approach to enhance clinical outcomes may involve tailored therapy based on each patient's unique clinical profile. Exercise should be recommended for all patients to improve the quality of life. Glucagon-like peptide-1 1 agonists are a promising treatment option in obese HFpEF patients. Novel approaches targeting inflammation are also in early phase trials.
10.1016/j.ijcard.2024.132304
Heart Failure: Heart Failure With Preserved Ejection Fraction.
Kane Shawn F
FP essentials
The incidence and prevalence of heart failure (HF) in the United States are high, with an estimated 6.2 million cases, and these numbers are expected to increase. Age is a nonmodifiable risk factor for HF development. Hypertension, diabetes, and ischemic heart disease are modifiable risk factors that can be addressed to reduce the morbidity and mortality associated with HF. Improvements in understanding of the pathophysiology of HF have led to changes in terminology. Terms such as , , and should no longer be used. Currently, the ejection fraction (EF) is used to classify left-sided HF. Patients with classic HF symptoms and an EF of 50% or greater have HF with a preserved EF (HFpEF). Patients with an EF of 40% or less have HF with a reduced EF (HFrEF). Priorities in HFpEF management are symptom management and control of comorbid conditions. This includes avoidance of fluid overload, blood pressure control optimization, and atrial fibrillation management. The diagnosis of HFpEF is associated with a 22% to 65% 5-year mortality rate, with 51% to 60% of deaths due to cardiovascular causes.
The sympathetic/parasympathetic imbalance in heart failure with reduced ejection fraction.
Floras John S,Ponikowski Piotr
European heart journal
Cardiovascular autonomic imbalance, a cardinal phenotype of human heart failure, has adverse implications for symptoms during wakefulness and sleep; for cardiac, renal, and immune function; for exercise capacity; and for lifespan and mode of death. The objectives of this Clinical Review are to summarize current knowledge concerning mechanisms for disturbed parasympathetic and sympathetic circulatory control in heart failure with reduced ejection fraction and its clinical and prognostic implications; to demonstrate the patient-specific nature of abnormalities underlying this common phenotype; and to illustrate how such variation provides opportunities to improve or restore normal sympathetic/parasympathetic balance through personalized drug or device therapy.
10.1093/eurheartj/ehv087
Impact of exercise testing mode on exercise parameters in patients with chronic heart failure.
Beckers Paul J,Possemiers Nadine M,Van Craenenbroeck Emeline M,Van Berendoncks An M,Wuyts Kurt,Vrints Christiaan J,Conraads Viviane M
European journal of preventive cardiology
AIM:To verify the impact of testing mode on maximal, sub-maximal parameters and on cardiopulmonary exercise test (CPET) derived prognostic markers in patients with chronic heart failure (CHF). METHOD:55 patients (age 60.3 years ±11.1) with CHF (ejection fraction 26 %±8) underwent a maximal CPET on a bicycle and on a treadmill, in a random order, within one week. Maximal, sub-maximal parameters and CPET derived prognostic markers were compared. RESULTS:VO(2)peak and VO(2)peak corrected for lean body mass were significantly higher on treadmill compared to bicycle (+11%, p < 0.0001). This was also the case for the following sub-maximal parameters; heart rate, workload and VO(2) at ventilatory anaerobic threshold and VO(2) at the respiratory compensation point (RCP). In contrast, both VE/VCO(2) slopes (start to RCP and start to end test) were similar. Time to 1/2 VO(2)peak was longer and circulatory power was higher on the treadmill compared to exercise testing on the bicycle. CONCLUSION:The results of the present study suggest that the mode of exercise testing significantly affects absolute values for VO(2)peak but does not greatly impact the prognostic utility of the VE/VCO(2) slope in patients with moderate to severe CHF. Besides the consequences of these findings in terms of prognostication, testing mode should be taken into consideration when exercise prescription is based on VO(2)peak.
10.1177/1741826711400664
Characteristics of self-care interventions for patients with a chronic condition: A scoping review.
International journal of nursing studies
BACKGROUND:Self-care is a fundamental element of treatment for patients with a chronic condition and a major focus of many interventions. A large body of research exists describing different types of self-care interventions, but these studies have never been compared across conditions. Examination of heterogeneous interventions could provide insights into effective approaches that should be used in diverse patient populations. OBJECTIVES:To provide a comprehensive and standardized cross-condition overview of interventions to enhance self-care in patients with a chronic condition. Specific aims were to: 1) identify what self-care concepts and behaviors are evaluated in self-care interventions; 2) classify and quantify heterogeneity in mode and type of delivery; 3) quantify the behavior change techniques used to enhance self-care behavior; and 4) assess the dose of self-care interventions delivered. DESIGN:Scoping review DATA SOURCES: Four electronic databases - PubMed, EMBASE, PsychINFO and CINAHL - were searched from January 2008 through January 2019. ELIGIBILITY CRITERIA FOR STUDY SELECTION:Randomized controlled trials (RCTs) with concealed allocation to the intervention were included if they compared a behavioral or educational self- care intervention to usual care or another self-care intervention and were conducted in adults. Nine common chronic conditions were included: hypertension, coronary artery disease, arthritis, chronic kidney disease, heart failure, stroke, asthma, chronic obstructive lung disease, and type 2 diabetes mellitus. Diagnoses that are psychiatric (e.g. schizophrenia), acute rather than chronic, or benefitting little from self-care (e.g. dementia) were excluded. Studies had to be reported in English with full-text available. RESULTS:9309 citations were considered and 233 studies were included in the final review. Most studies addressed type 2 diabetes mellitus (n = 85; 36%), hypertension (n = 32; 14%) or heart failure (n = 27; 12%). The majority (97%) focused on healthy behaviors like physical activity (70%), dietary intake (59%), and medication management (52%). Major deficits found in self-care interventions included a lack of attention to the psychological consequences of chronic illness, technology and behavior change techniques were rarely used, few studies focused on helping patients manage signs and symptoms, and the interventions were rarely innovative. Research reporting was generally poor. CONCLUSIONS:Major gaps in targeted areas of self-care were identified. Opportunities exist to improve the quality and reporting of future self-care intervention research. Registration: The study was registered in the PROSPERO database (#123,719).
10.1016/j.ijnurstu.2020.103713
Exercise for Primary and Secondary Prevention of Cardiovascular Disease: JACC Focus Seminar 1/4.
Journal of the American College of Cardiology
Regular exercise that meets or exceeds the current physical activity guidelines is associated with a reduced risk of cardiovascular disease (CVD) and mortality. Therefore, exercise training plays an important role in primary and secondary prevention of CVD. In this part 1 of a 4-part focus seminar series, we highlight the mechanisms and physiological adaptations responsible for the cardioprotective effects of exercise. This includes an increase in cardiorespiratory fitness secondary to cardiac, vascular, and skeletal muscle adaptations and an improvement in traditional and nontraditional CVD risk factors by exercise training. This extends to the role of exercise and its prescription in patients with CVDs (eg, coronary artery disease, chronic heart failure, peripheral artery disease, or atrial fibrillation) with special focus on the optimal mode, dosage, duration, and intensity of exercise to reduce CVD risk and improve clinical outcomes in these patients.
10.1016/j.jacc.2022.07.004
Exercise-based cardiac rehabilitation for adults with heart failure - 2023 Cochrane systematic review and meta-analysis.
European journal of heart failure
AIMS:Despite strong evidence, access to exercise-based cardiac rehabilitation (ExCR) remains low across global healthcare systems. We provide a contemporary update of the Cochrane review randomized trial evidence for ExCR for adults with heart failure (HF) and compare different delivery modes: centre-based, home-based (including digital support), and both (hybrid). METHODS AND RESULTS:Databases, bibliographies of previous systematic reviews and included trials, and trials registers were searched with no language restrictions. Randomized controlled trials, recruiting adults with HF, assigned to either ExCR or a no-exercise control group, with follow-up of ≥6 months were included. Two review authors independently screened titles for inclusion, extracted trial and patient characteristics, outcome data, and assessed risk of bias. Outcomes of mortality, hospitalization, and health-related quality of life (HRQoL) were pooled across trials using meta-analysis at short-term (≤12 months) and long-term follow-up (>12 months) and stratified by delivery mode. Sixty trials (8728 participants) were included. In the short term, compared to control, ExCR did not impact all-cause mortality (relative risk [RR] 0.93; 95% confidence interval [CI] 0.71-1.21), reduced all-cause hospitalization (RR 0.69; 95% CI 0.56-0.86, number needed to treat: 13, 95% CI 9-22), and was associated with a clinically important improvement in HRQoL measured by the Minnesota Living with Heart Failure Questionnaire (MLWHF) overall score (mean difference: -7.39; 95% CI -10.30 to -4.47). Improvements in outcomes with ExCR was seen across centre, home (including digitally supported), and hybrid settings. A similar pattern of results was seen in the long term (mortality: RR 0.87, 95% CI 0.72-1.04; all-cause hospitalization: RR 0.84, 95% CI 0.70-1.01, MLWHF: -9.59, 95% CI -17.48 to -1.50). CONCLUSIONS:To improve global suboptimal levels of uptake for HF patients, global healthcare systems need to routinely recommend ExCR and offer a choice of mode of delivery, dependent on an individual patient's level of risk and complexity.
10.1002/ejhf.3046
Cardiac resynchronization therapy: Current status and near-future prospects.
Journal of cardiology
Cardiac resynchronization therapy (CRT) has been established as a standard treatment for heart failure. The effectiveness of CRT has been shown in many clinical trials and realized in actual clinical practice. Nevertheless, underutilization of CRT is a major problem in the treatment of heart failure. One factor leading to underutilization is the existence of CRT non-responders. CRT non-response has been discussed for approximately 20 years, since CRT was introduced. Since the beginning, the CRT non-response rate has been reported to be 30%. However, we are now undergoing a major transformation in the thinking about CRT response. First, heart failure is a progressive disease. Like many medications for heart failure, CRT does not cure the underlying disease of heart failure. Considering the natural course of heart failure, it is easy to understand that there will definitely be non-responders. There might have been misunderstandings about how to determine CRT response. Although CRT is a treatment for heart failure, it does not cure heart failure or myocardial tissue damage. Instead, by correcting conduction disorders and dyssynchrony, it modifies factors that exacerbate heart failure, which contributes to improvement. In addition, it is important to realize that pacing is the only treatment for correcting conduction disorders. Thus, in theory, CRT is an essential treatment for heart failure at any stage, regardless of severity, when it is accompanied by conduction disorder. Here, we consider the current state of CRT and the causes of underutilization. Returning to the origin of CRT, reconsidering the effects of CRT and the thinking about response, and spreading a new way of thinking will lead to the proper utilization of CRT.
10.1016/j.jjcc.2021.10.021
Various aspects of inflammation in heart failure.
Dutka Mieczysław,Bobiński Rafał,Ulman-Włodarz Izabela,Hajduga Maciej,Bujok Jan,Pająk Celina,Ćwiertnia Michał
Heart failure reviews
Despite significant advances in the prevention and treatment of heart failure (HF), the prognosis in patients who have been hospitalised on at least one occasion due to exacerbation of HF is still poor. Therefore, a better understanding of the underlying pathophysiological mechanisms of HF is crucial in order to achieve better results in the treatment of this clinical syndrome. One of the areas that, for years, has aroused the interest of researchers is the activation of the immune system and the elevated levels of biomarkers of inflammation in patients with both ischaemic and non-ischaemic HF. Additionally, it is intriguing that the level of circulating pro-inflammatory biomarkers correlates with the severity of the disease and prognosis in this group of patients. Unfortunately, clinical trials aimed at assessing interventions to modulate the inflammatory response in HF have been disappointing, and the modulation of the inflammatory response has had either no effect or even a negative effect on the HF prognosis. The article presents a summary of current knowledge on the role of immune system activation and inflammation in the pathogenesis of HF. Understanding the immunological mechanisms pathogenetically associated with left ventricular remodelling and progression of HF may open up new therapeutic possibilities for HF.
10.1007/s10741-019-09875-1
Chronic Heart Failure and Exercise Rehabilitation: A Systematic Review and Meta-Analysis.
Palmer Katie,Bowles Kelly-Ann,Paton Michelle,Jepson Megan,Lane Rebecca
Archives of physical medicine and rehabilitation
OBJECTIVE:The aim of this systematic review was to identify the effect of specific exercise parameters on physical function and quality of life (QOL) in people with chronic heart failure living in the community. DATA SOURCES:A total of 5 electronic databases were searched for relevant studies published after 1994. STUDY SELECTION:The screening process was completed by 2 independent researchers, with a third independent reviewer for conflict resolution. Studies were selected if they included only chronic hHart failure participants, and the sole intervention was a structured exercise training program in an outpatient or community setting. DATA EXTRACTION:Two independent researchers completed the data extraction and qualiy assessment. Quality was assessed using the Physiotherapy Evidence Database and Grading of Recommendations Assessment, Development and Evaluation scales. DATA SYNTHESIS:In total, 40 articles (n=5411) were included in the review for meta-analysis and meta-regression, including 27 randomized control trials and 13 cohort studies. Exercise was shown to have a positive effect on QOL outcomes (standardized mean difference 1.16; 95% confidence interval [CI], 0.76-1.56) with the most commonly used measure, the Minnesota Living with Heart Failure Questionnaire, showing a clinically significant change of 8.5 points. Physical function was improved postexercise intervention in the 23 included studies (standardized mean difference 0.89; 95% CI, 0.40-1.38), with a clinically significant change of 49.8 m seen in studies using the 6-minute walk test (95% CI, 26.52-73.13). These improvements were independent of study design, study quality, participant demographics, disease severity, and exercise prescription variables. CONCLUSION:Exercise significantly improves QOL and physical function. Current evidence suggests that engagement with exercise is a more important factor in achieving improvement than how the exercise is performed. Future research should aim to identify and address barriers to engagement in exercise rehabilitation in this population.
10.1016/j.apmr.2018.03.015
Neuropsychiatric disorders in patients with heart failure: not to be ignored.
Heart failure reviews
Among various neuropsychiatric disorders, depression and anxiety are commonly encountered in patients with heart failure (HF), reported in ≥ 50% of patients attending a HF clinic, but may frequently elude clinician's attention. Both disorders are associated with the development and progression of HF, incurring higher rates of morbidity/mortality, probably via physiologic and behavioral mechanisms. Patients with devices and/or advanced HF are more severely affected, especially early following device receipt. In addition, various other neuropsychiatric and neuropsychological disorders and symptoms of these and other disorders occur in and impact HF patients, including sleep disorders and cognitive impairment, which further interact with and amplify depression and anxiety. Mechanisms involved in the link between neuropsychiatric/neuropsychological disorders and HF may relate to pathophysiological processes, lifestyle factors, and behavioral patterns. Among the pathophysiological factors, inflammation, autonomic dysfunction, endothelial dysfunction, thrombotic mechanisms, and dysregulation of the hypothalamic-pituitary-adrenal axis may play a significant role as they are implicated in the pathogenesis, progression, and prognosis of HF. Multimodal psychiatric management strategies with flexible approaches, using antidepressants/anxiolytics/atypical antipsychotics and various psychotherapies such as cognitive behavioral therapy combined with exercise adjusted to patients' care and needs, appear promising in this patient group. Choosing agents with a higher efficacy/safety profile is a prudent strategy. Although depression and anxiety are risk factors for mortality in HF patients, indiscriminate use of psychiatric medications may not improve or even worsen survival when one neglects to closely monitor for potential proarrhythmic and other side effects. Newer meta-analytic data in HF patients indicate no increase in mortality for newer antidepressants, while secondary analyses show improved survival in patients who achieved remission of depressive symptoms.
10.1007/s10741-022-10290-2
Stress management interventions for adults with heart failure: Systematic review and meta-analysis.
Health psychology : official journal of the Division of Health Psychology, American Psychological Association
OBJECTIVE:Stress management interventions (SMIs) targeting psychological stress and other psychosocial factors associated with heart failure (HF) morbidity and mortality are increasingly recommended for adults with HF. SMI content and delivery varies widely and meta-analyses are needed to synthesize current findings to identify gaps in the literature. The purpose of this meta-analysis is to examine the efficacy of SMIs for improving anxiety, depressive symptoms, exercise capacity, and disease-specific quality of life in adults with HF. METHOD:Comprehensive searches of 10 electronic bibliographic databases identified peer-reviewed, published, randomized controlled trials (RCTs) of SMIs for adults with HF. RESULTS:Twenty-three RCTs were included (N = 2,294; Mage = 63.09 ± 7.27 years; 40% women, 56% White). Pooled effects indicated greater improvements in anxiety (d+ = .49, 95% confidence interval [CI] = [.09-.89], k = 10), depressive symptoms (d+ = .39, 95% CI [.03, .75], k = 13), disease-specific quality of life (d+ = .82, 95% CI [.40, 1.24], k = 16), and exercise capacity (d+ = .57, 95% CI [.20, .95], k = 14) among SMI recipients relative to controls at the first postintervention assessment. The benefits were not maintained at follow-up. Participant characteristics (e.g., proportion women, HF severity), but not intervention type, moderated the findings. CONCLUSIONS:SMIs for adults with HF demonstrated short-term improvements in anxiety, depressive symptoms, quality of life, and exercise capacity. Future research sampling patients who are psychologically distressed with more thorough assessment of stress and longer follow-ups can elucidate the benefits of SMIs among adults with HF. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
10.1037/hea0001084
The prognostic impact of symptom clusters in patients with heart failure: A systematic review and meta-analysis.
Journal of advanced nursing
AIM:To determine the impact of symptom clusters on clinical outcomes among heart failure patients. DESIGN:Systematic review and meta-analysis. DATA SOURCES:Peer-reviewed articles were searched from 12 English and Chinese language databases from inception to August 2021. REVIEW METHODS:Narrative syntheses were first conducted to integrate symptom clusters reported in the identified studies. This was followed by meta-analysis to synthesize the evidence on the association or predictive effects of symptom clusters on clinical outcomes. RESULTS:Twelve studies were identified. Among studies which identified highly correlated symptoms as in a cluster, meta-analysis indicated that severe congestive (r = .45, 95% CI = 0.38-0.52), weary (r = .41, 95% CI = 0.33-0.50), ischaemic (r = .29, 95% CI = 0.04-0.51) and stress-related (r = .62, 95% CI = 0.31-0.81) symptom clusters were correlated with a poorer health-related quality of life. As for studies used latent class to identified patient cohorts of similar symptom pattern, high symptom cohorts (hazard ratio = 1.86, 95% CI = 1.39-2.48) and incongruent physical and psycho-cognitive symptom cohorts was associated with a significantly higher risk (hazard ratio = 2.10, 95% CI = 1.44-3.07) of combined event rate relative to low symptom presentation. CONCLUSIONS:This review has identified the impact of symptom clusters on clinical outcomes in heart failure patients. In addition to the classical physical symptoms highlighted in the clinical management guidelines, our findings suggested the important predictive role of psycho-cognitive and weary symptoms in determining the clinical outcomes of HF patients. IMPACT:This review concluded the promising prospect of symptom clusters in shaping clinical outcomes of heart failure. The findings highlighted the importance of integrating care to minimize the disease impact on psycho-cognitive function and weary symptoms among this clinical cohort. The review also inform the direction on how to advance the knowledge on symptom clusters among this clinical cohort.
10.1111/jan.15302
Long-term management of end-stage heart failure.
Habal Marlena V,Garan A Reshad
Best practice & research. Clinical anaesthesiology
End-stage heart failure manifests as severe and often relentless symptoms that define the clinical syndrome of heart failure, namely congestion and hypoperfusion. These patients suffer from dyspnea, fatigue, abdominal discomfort, and ultimately cardiac cachexia. Renal and hepatic dysfunction frequently further complicates the process. Recurrent hospitalizations, cardiac arrhythmias, and intolerance to standard heart failure therapies are common as the disease progresses. Management focuses on controlling symptoms, correcting precipitants, avoiding triggers, and maximizing therapies with demonstrable survival benefit. Among appropriate candidates, advanced therapies such as orthotopic heart transplant (OHT) can significantly extend survival and improve the quality of life. Left ventricular assist devices have been used with increasing frequency as a bridge to OHT or as a destination therapy in appropriately selected candidates where they have a demonstrable mortality benefit over medical therapy. Importantly, a multidisciplinary patient-centered approach is crucial when considering these advanced therapies.
10.1016/j.bpa.2017.07.003
Interventional heart failure therapy: A new concept fighting against heart failure.
Journal of cardiology
Heart failure is a progressive disease that is associated with repeated exacerbations and hospitalizations. The rapid increase in the number of heart failure patients is a global health problem known as the 'heart failure pandemic'. To control the pandemic, multifaceted approaches are essential, ranging from prevention of onset to long-term disease management. Especially in patients with moderate to severe heart failure (stages C and D), surgical and catheter-based interventions are prerequisites for saving lives, preserving cardiac function, improving quality of life (QOL), and prognosis. In addition, various new medical technologies for these interventions have been clinically applied and have been shown to be effective against symptoms and improve the QOL and prognosis of patients with heart failure. Furthermore, the concept of interventional heart failure (IHF) therapy, which considers heart recovery and prevention of worsening of heart failure via multidisciplinary treatment using surgical, catheter interventions, and mechanical circulatory support devices, has been proposed worldwide. This review discusses the importance of IHF therapy in heart failure management, recent changes in interventional technologies and strategies for patients with heart failure, and worldwide education attempts for IHF specialists.
10.1016/j.jjcc.2021.11.018
Hyperkalemia in heart failure: Foe or friend?
Rakisheva Amina,Marketou Maria,Klimenko Anna,Troyanova-Shchutskaia Tatyana,Vardas Panos
Clinical cardiology
Hyperkalemia is a frequent and sometimes life-threatening condition that may be associated with arrhythmia and cardiac dysfunction in patients with heart failure (HF). High potassium levels in HF represent both a direct risk for cardiovascular complication and an indirect biomarker of the severity of the underlying disease, reflecting neurohormonal activation and renal dysfunction. Evaluating the prevalence and significance of hyperkalemia in HF patients is essential for optimizing the use of potassium sparing agents, such the renin-angiotensin-aldosterone system inhibitors (RAASi) or angiotensin receptor-neprilysin inhibitors and mineralocorticoid receptor antagonists, which represent a well-established cornerstone and life-saving therapy. In this review we discuss recent findings and current concepts related to the epidemiology, pathological mechanisms and implications of hyperkalemia, as well as novel therapeutic approaches to counteract it in patients with HF. The balance between optimizing life-saving potassium sparing medication and minimizing hyperkalemia-associated risk is much needed in patients with HF. Although older potassium-binding agents are associated with serious adverse events, novel potassium-binding drugs are effective in lowering potassium levels and are generally well tolerated. Novel potassium-binding drugs, such as patiromer and sodium zirconium cyclosilicate, may help to optimize therapy in HF and achieve guideline-recommended doses. Hyperkalemia is common in HF patients and is associated with a poorer prognosis and an increased risk of cardiovascular complications: Contrariwise, "moderate" potassium levels go with a better prognosis, while the emergence of new drugs, potassium binders, could allow target doses of RAASi to be achieved.
10.1002/clc.23392
Advanced Heart Failure Therapies for Hypertrophic Cardiomyopathy: State-of-the-Art Review and an Updated Analysis From UNOS.
JACC. Heart failure
Hypertrophic cardiomyopathy (HCM) is most commonly associated with obstructive symptoms and sudden cardiac death; however, predominantly nonobstructive advanced heart failure in HCM, marked by medically refractory disease with severe functional impairment, occurs in 5% to 7% of patients with HCM. The diagnosis relies on the integration of imaging (echocardiography/cardiac magnetic resonance), hemodynamic data, and cardiopulmonary exercise testing to identify the patients who will benefit from advanced heart failure therapies. Most advanced heart failure therapies focus on systolic dysfunction and are not always applicable to this patient population. Left ventricular assist devices may be an option in a highly selected population with left ventricular dilation. Heart transplantation is often the best option for patients with advanced heart failure in HCM with excellent post-transplantation survival.
10.1016/j.jchf.2023.07.004
Advances in congestive heart failure biomarkers.
Advances in clinical chemistry
Congestive heart failure (CHF) is the leading cause of morbidity and mortality in the elderly worldwide. Although many biomarkers associated with in heart failure, these are generally prognostic and identify patients with moderate and severe disease. Unfortunately, the role of biomarkers in decision making for early and advanced heart failure remains largely unexplored. Previous studies suggest the natriuretic peptides have the potential to improve the diagnosis of heart failure, but they still have significant limitations related to cut-off values. Although some promising cardiac biomarkers have emerged, comprehensive data from large cohort studies is lacking. The utility of multiple biomarkers that reflect various pathophysiologic pathways are increasingly being explored in heart failure risk stratification and to diagnose disease conditions promptly and accurately. MicroRNAs serve as mediators and/or regulators of renin-angiotensin-induced cardiac remodeling by directly targeting enzymes, receptors and signaling molecules. The role of miRNA in HF diagnosis is a promising area of research and further exploration may offer both diagnostic and prognostic applications and phenotype-specific targets. In this review, we provide insight into the classification of different biochemical and molecular markers associated with CHF, examine clinical usefulness in CHF and highlight the most clinically relevant.
10.1016/bs.acc.2022.09.005
Thyroid Abnormalities in Heart Failure.
Danzi Sara,Klein Irwin
Heart failure clinics
The effects of hyperthyroidism and hypothyroidism on the heart and cardiovascular system are well documented. It has also been shown that various forms of heart disease including but not limited to congenital, hypertensive, ischemic, cardiac surgery, and heart transplantation cause an alteration in thyroid function tests including a decrease in serum liothyronine (T). This article discusses the basic science and clinical data that support the hypothesis that these changes pose pathophysiologic and potential novel therapeutic challenges.
10.1016/j.hfc.2019.08.002
Global Prevalence of Depression among Heart Failure Patients: A Systematic Review and Meta-Analysis.
Current problems in cardiology
The present study aimed to evaluate the prevalence of depression among heart failure (HF) patients. Depression is one of the main risk factors of mortality and reduction in quality of life in patients with HR. Despite individual studies, there is no comprehensive study on depression in HF patients. In the present systematic review and meta-analysis, databases (Web of Science, Scopus, and PubMed) were searched from January 1, 2000, to December 15, 2020. The keywords used included: depression and heart failure. The research stages including search, screening, quality evaluation, and extraction of study data were performed separately by two researchers. A total of 149 studies performed on 305,407 HF patients entered the final stage. The global prevalence of any severity and moderate to severe severity of depression was 41.9% and 28.1%, respectively. The results of the subgroup analysis showed that the prevalence of depression was higher in women (45.5%) than in men. Also, according to the NHYA classification, the prevalence of depression in patients in stages three and four (54.7%) was higher than stages 1 and 2. The prevalence of depression was higher in the EMRO region (70.1%) and lower economic status countries (56.7%).The high prevalence of depression among HF patients indicates the importance of paying more attention and providing the necessary training for patients to reduce depression.
10.1016/j.cpcardiol.2021.100848
Outpatient Emergencies: Acute Heart Failure.
Mysliwiec Malgorzata,Bonita Raphael E
The Medical clinics of North America
Heart failure is an epidemic in the United States and a major health problem worldwide. The syndrome of acute heart failure is marked by a recent onset of symptoms usually in terms of days to a few weeks of worsening fatigue, shortness of breath, orthopnea, swelling, and sudden onset of weight gain. Physicians caring for patients with heart failure must know the risk factors for this disease, pathophysiology, symptomatology, important examination findings, key diagnostic tests, and management approach so as to improve symptoms and reduce mortality.
10.1016/j.mcna.2016.12.010
Immune mechanisms in heart failure.
Zhang Yingying,Bauersachs Johann,Langer Harald F
European journal of heart failure
Elevated levels of circulating pro-inflammatory biomarkers in patients with both ischaemic and non-ischaemic heart failure (HF) correlate with disease severity and prognosis. Experimental studies have shown activation of immune response mechanisms in the heart to provoke cardiac adverse remodelling and cause left ventricular dysfunction. Consequently, most of the clinical trials targeting elements of the immune response in HF attempted to modulate the inflammatory response. Surprisingly, clinical studies targeting immune effectors were either neutral or even increased pre-specified clinical endpoints, and some studies resulted in worsening of HF. This review discusses immune mediators involved in the pathogenesis and progression of HF and potential therapeutic applications targeting inflammation in HF. Besides more obvious settings featuring immune activation such as inflammatory or ischaemic cardiomyopathy, the relevance of immune activation in acute or chronic HF of other origins, including volume overload or valvular heart disease, is highlighted. Understanding how cell-specific and molecular mechanisms of the immune response interfere with cardiac remodelling in HF may open new avenues to design biomarkers or druggable targets.
10.1002/ejhf.942
The Cardiovascular Manifestations of COVID-19.
Heart failure clinics
The Coronavirus 2019 (COVID-19) pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) virus, has resulted in unprecedented morbidity and mortality worldwide. While COVID-19 typically presents as viral pneumonia, cardiovascular manifestations such as acute coronary syndromes, arterial and venous thrombosis, acutely decompensated heart failure (HF), and arrhythmia are frequently observed. Many of these complications are associated with poorer outcomes, including death. Herein we review the relationship between cardiovascular risk factors and outcomes among patients with COVID-19, cardiovascular manifestations of COVID-19, and cardiovascular complications associated with COVID-19 vaccination.
10.1016/j.hfc.2022.08.001
Supervised Exercise Training for Chronic Heart Failure With Preserved Ejection Fraction: A Scientific Statement From the American Heart Association and American College of Cardiology.
Circulation
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.
10.1161/CIR.0000000000001122
From Systemic Inflammation to Myocardial Fibrosis: The Heart Failure With Preserved Ejection Fraction Paradigm Revisited.
Circulation research
In accordance with the comorbidity-inflammation paradigm, comorbidities and especially metabolic comorbidities are presumed to drive development and severity of heart failure with preserved ejection fraction through a cascade of events ranging from systemic inflammation to myocardial fibrosis. Recently, novel experimental and clinical evidence emerged, which strengthens the validity of the inflammatory/profibrotic paradigm. This evidence consists among others of (1) myocardial infiltration by immunocompetent cells not only because of an obesity-induced metabolic load but also because of an arterial hypertension-induced hemodynamic load. The latter is sensed by components of the extracellular matrix like basal laminin, which also interact with cardiomyocyte titin; (2) expression in cardiomyocytes of inducible nitric oxide synthase because of circulating proinflammatory cytokines. This results in myocardial accumulation of degraded proteins because of a failing unfolded protein response; (3) definition by machine learning algorithms of phenogroups of patients with heart failure with preserved ejection fraction with a distinct inflammatory/profibrotic signature; (4) direct coupling in mediation analysis between comorbidities, inflammatory biomarkers, and deranged myocardial structure/function with endothelial expression of adhesion molecules already apparent in early preclinical heart failure with preserved ejection fraction (HF stage A, B). This new evidence paves the road for future heart failure with preserved ejection fraction treatments such as biologicals directed against inflammatory cytokines, stimulation of protein ubiquitylation with phosphodiesterase 1 inhibitors, correction of titin stiffness through natriuretic peptide-particulate guanylyl cyclase-PDE9 (phosphodiesterase 9) signaling and molecular/cellular regulatory mechanisms that control myocardial fibrosis.
10.1161/CIRCRESAHA.121.318159
Management of low blood pressure in ambulatory heart failure with reduced ejection fraction patients.
European journal of heart failure
Low blood pressure is common in patients with heart failure and reduced ejection fraction (HFrEF). While spontaneous hypotension predicts risk in HFrEF, there is only limited evidence regarding the relationship between hypotension observed during heart failure (HF) drug titration and outcome. Nevertheless, hypotension (especially orthostatic hypotension) is an important factor limiting the titration of HFrEF treatments in routine practice. In patients with signs of shock and/or severe congestion, hospitalization is advised. However, in the very frequent cases of non-severe and asymptomatic hypotension observed while taking drugs with a class I indication in HFrEF, European and US guidelines recommend maintaining the same drug dosage. In instances of symptomatic or severe persistent hypotension (systolic blood pressure < 90 mmHg), it is recommended to first decrease blood pressure reducing drugs not indicated in HFrEF as well as the loop diuretic dose in the absence of associated signs of congestion. Unless the management of hypotension appears urgent, a HF specialist should then be sought rather than stopping or decreasing drugs with a class I indication in HFrEF. If symptoms or severe hypotension persist, no recommendations exist. Our HF group reviewed available evidence and proposes certain steps to follow in such situations in order to improve the pharmacological management of these patients.
10.1002/ejhf.1835
Evidence and Current Use of Levosimendan in the Treatment of Heart Failure: Filling the Gap.
Conti Nicolina,Gatti Milo,Raschi Emanuel,Diemberger Igor,Potena Luciano
Drug design, development and therapy
Levosimendan is a distinctive inodilator combing calcium sensitization, phosphodiesterase inhibition and vasodilating properties through the opening of adenosine triphosphate-dependent potassium channels. It was first approved in Sweden in 2000 for the short-term treatment of acutely decompensated severe chronic heart failure when conventional therapy is not sufficient, and in cases where inotropic support is considered appropriate. After more than 20 years, clinical applications have considerably expanded across critical care and emergency medicine, and levosimendan is now under investigation in different cardiac settings (eg, septic shock, pulmonary hypertension) and for non-cardiac applications (eg, amyotrophic lateral sclerosis). This narrative review outlines key milestones in levosimendan history, by addressing regulatory issues, pharmacological peculiarities and clinical aspects (efficacy and safety) of a drug that did not receive great attention in the heart failure guidelines. A brief outlook to the ongoing clinical trials is also offered.
10.2147/DDDT.S295214
Classification of Heart Failure According to Ejection Fraction: JACC Review Topic of the Week.
Lam Carolyn S P,Solomon Scott D
Journal of the American College of Cardiology
The recent U.S. Food and Drug Administration expanded indication for sacubitril/valsartan introduces a new potential taxonomy for heart failure, with no reference to "preserved" ejection fraction but referring to "below normal" ejection fraction as those most likely to benefit. This review summarizes the evolution of nomenclature in heart failure and examines evidence showing that patients with ejection fraction in the "mid range" may benefit from neurohormonal blockade similar to those with more severely reduced (<40%) ejection fraction. Furthermore, prominent sex differences have been observed wherein the benefit of neurohormonal blockade appears to extend to a higher ejection fraction range in women compared to men. Based on emerging evidence, revised nomenclature is proposed defining heart failure with "reduced" (<40%), "mildly reduced," and "normal" (≥55% in men, ≥60% in women) ejection fraction. Such nomenclature signals consideration of potentially beneficial therapies in the largest group of patients with reduced or mildly reduced ejection fraction.
10.1016/j.jacc.2021.04.070
Assessment of filling pressures and fluid overload in heart failure: an updated perspective.
Revista espanola de cardiologia (English ed.)
Congestion plays a major role in the pathogenesis, presentation, and prognosis of heart failure and is an important therapeutic target. However, its severity and organ and compartment distribution vary widely among patients, illustrating the complexity of this phenomenon. Although clinical symptoms and signs are useful to assess congestion and manage volume status in individual patients, they have limited sensitivity and do not allow identification of congestion phenotype. This leads to diagnostic uncertainty and hampers therapeutic decision-making. The present article provides an updated overview of circulating biomarkers, imaging modalities (ie, cardiac and extracardiac ultrasound), and invasive techniques that might help clinicians to identify different congestion profiles and guide the management strategy in this diverse population of high-risk patients with heart failure.
10.1016/j.rec.2022.07.009
Heart failure with preserved ejection fraction: New approaches to diagnosis and management.
Upadhya Bharathi,Kitzman Dalane W
Clinical cardiology
The majority of older patients who develop heart failure (HF), particularly older women, have a preserved left ventricular ejection fraction (HFpEF). Patients with HFpEF have severe symptoms of exercise intolerance, poor quality-of-life, frequent hospitalizations, and increased mortality. The prevalence of HFpEF is increasing and its prognosis is worsening. However, despite its importance, our understanding of the pathophysiology of HFpEF is incomplete, and drug development has proved immensely challenging. Currently, there are no universally accepted therapies that alter the clinical course of HFpEF. Originally viewed as a disorder due solely to abnormalities in left ventricular (LV) diastolic function, our understanding has evolved such that HFpEF is now understood as a systemic syndrome, involving multiple organ systems, likely triggered by inflammation and with an important contribution of aging, lifestyle factors, genetic predisposition, and multiple-comorbidities, features that are typical of a geriatric syndrome. HFpEF is usually progressive due to complex mechanisms of systemic and cardiac adaptation that vary over time, particularly with aging. In this review, we examine evolving data regarding HFpEF that may help explain past challenges and provide future directions to care patients with this highly prevalent, heterogeneous clinical syndrome.
10.1002/clc.23321
Inotropic therapy in patients with advanced heart failure. A clinical consensus statement from the Heart Failure Association of the European Society of Cardiology.
European journal of heart failure
This clinical consensus statement reviews the use of inotropic support in patients with advanced heart failure. The current guidelines only support use of inotropes in the setting of acute decompensated heart failure with evidence of organ malperfusion or shock. However, inotropic support may be reasonable in other patients with advanced heart failure without acute severe decompensation. The clinical evidence supporting use of inotropes in these situations is reviewed. Particularly, patients with persistent congestion, systemic hypoperfusion, or advanced heart failure with need for palliation, and specific situations relevant to implantation of left ventricular assist devices or heart transplantation are discussed. Traditional and novel drugs with inotropic effects are discussed and use of guideline-directed therapy during inotropic support is reviewed. Finally, home inotropic therapy is described, and palliative care and end-of-life aspects are reviewed in relation to management of ongoing inotropic support (including guidance for maintenance and weaning of chronic inotropic therapy support).
10.1002/ejhf.2814
Anaemia, iron deficiency and heart failure in 2020: facts and numbers.
ESC heart failure
Anaemia is defined by WHO as Hb < 13.0 g/dL in male adults and <12.0 g/dL in female adults. It is a common comorbidity in patients of heart failure with both HFrEF and HFpEF. The incidence ranges between 30% and 50%, though in certain communities, it is likely to be higher still. Elderly age, severe heart failure, poor nutrition, and elevation of inflammatory markers are associated with a higher incidence of anaemia. However, the commonest contributing factor to anaemia in HF is iron deficiency. In a Canadian study of 12 065 patients, the incidence of absolute ID was 21% in anaemic patients. Many other western studies have also quoted incidences varying between 35% and 43%. The earlier attempts to improve outcomes by supplementation with Erythropoietic-stimulating factors were unsuccessful and resulted in a higher incidence of thrombotic events. Iron deficiency (ID) has emerged as an important factor in patients of HF, even in those without anaemia and worsens outcomes. It is defined as Ferritin levels below 100 mcg/L or 100-299 μg/L with transferrin saturation of <20%. Attempts to correct ID by oral supplementation have been unsuccessful as seen in IRON-HF and IRONOUT-HF trials. FAIR-HF and CONFIRM-HF conclusively established the role of IV Iron in improving exercise capacity and quality of life in patients with HFrEF. ESC guidelines have given a class IC indication for testing all heart failure patients for ID, and an IIaA recommendation for its correction by IV ferric carboxymaltose was found to be deficient. Ongoing trials will establish the role of IV iron in improving mortality and in HFpEF patients and in patients with acute heart failure.
10.1002/ehf2.12797
Improving Quality of Life in Heart Failure.
Freedland Kenneth E,Rich Michael W,Carney Robert M
Current cardiology reports
PURPOSE OF REVIEW:Heart failure has substantial effects on health-related quality of life. Maintaining or improving quality of life is an important goal of heart failure therapy, and many patients value better quality of life over greater longevity. RECENT FINDINGS:The symptoms and functional severity of heart failure, medical comorbidities, and depression are the strongest predictors of poor quality of life. Guideline-recommended medical and behavioral interventions for HF, including exercise training and cardiac rehabilitation, self-care interventions, and treatment of depression, can help to improve quality of life. Heart failure is, in most cases, a progressive condition with a poor prognosis. However, poor quality of life is not inevitable, and a variety of medical, surgical, and nonpharmacological interventions can help to maintain or improve quality of life in patients with heart failure.
10.1007/s11886-021-01588-y
'Time is prognosis' in heart failure: time-to-treatment initiation as a modifiable risk factor.
ESC heart failure
In heart failure (HF), acute decompensation can occur quickly and unexpectedly because of worsening of chronic HF or to new-onset HF diagnosed for the first time ('de novo'). Patients presenting with acute HF (AHF) have a poor prognosis comparable with those with acute myocardial infarction, and any delay of treatment initiation is associated with worse outcomes. Recent HF guidelines and recommendations have highlighted the importance of a timely diagnosis and immediate treatment for patients presenting with AHF to decrease disease progression and improve prognosis. However, based on the available data, there is still uncertainty regarding the optimal 'time-to-treatment' effect in AHF. Furthermore, the immediate post-worsening HF period plays an important role in clinical outcomes in HF patients after hospitalization and is known as the 'vulnerable phase' characterized by high risk of readmission and early death. Early and intensive treatment for HF patients in the 'vulnerable phase' might be associated with lower rates of early readmission and mortality. Additionally, in the chronic stable HF outpatient, treatments are often delayed or not initiated when symptoms are stable, ignoring the risk for adverse outcomes such as sudden death. Consequently, there is a dire need to better identify HF patients during hospitalization and after discharge and treating them adequately to improve their prognosis. HF is an urgent clinical scenario along all its stages and disease conditions. Therefore, time plays a significant role throughout the entire patient's journey. Therapy should be optimized as soon as possible, because this is beneficial regardless of severity or duration of HF. Time lavished before treatment initiation is recognized as important modifiable risk factor in HF.
10.1002/ehf2.13646
Diabetes, heart failure, and renal dysfunction: The vicious circles.
Braunwald Eugene
Progress in cardiovascular diseases
The prevalence of Type 2 diabetes mellitus (T2DM) has reached pandemic proportions. T2DM frequently causes macrovascular and/or microvascular pathologic changes and thereby increases the risks for the development of myocardial infarction, heart failure, stroke, renal failure, and reduced survival. This article describes the important interactions between T2DM, heart failure, and renal dysfunction, forming vicious circles. The interruption of these circles represents important therapeutic goals.
10.1016/j.pcad.2019.07.003
Tricuspid Regurgitation Management for Heart Failure.
JACC. Heart failure
There is growing evidence that severe tricuspid regurgitation (TR) impacts clinical outcomes in a variety of cardiovascular disease states. The late presentation of patients with advanced TR highlights the underappreciation of the disease, as well as the pitfalls of current guideline-directed medical management. Given the high in-hospital mortality associated with isolated tricuspid valve surgery, transcatheter options continue to be explored with the hope of improved survival and reduced heart failure hospitalizations. In this review, we explore the physiology of TR, discuss the etiologic classes of TR, and explore the transcatheter options for treatment and who might benefit from device therapy.
10.1016/j.jchf.2023.07.020
Pathophysiology of Diuretic Resistance and Its Implications for the Management of Chronic Heart Failure.
Hypertension (Dallas, Tex. : 1979)
Diuretic resistance implies a failure to increase fluid and sodium (Na) output sufficiently to relieve volume overload, edema, or congestion, despite escalating doses of a loop diuretic to a ceiling level (80 mg of furosemide once or twice daily or greater in those with reduced glomerular filtration rate or heart failure). It is a major cause of recurrent hospitalizations in patients with chronic heart failure and predicts death but is difficult to diagnose unequivocally. Pharmacokinetic mechanisms include the low and variable bioavailability of furosemide and the short duration of all loop diuretics that provides time for the kidneys to restore diuretic-induced Na losses between doses. Pathophysiological mechanisms of diuretic resistance include an inappropriately high daily salt intake that exceeds the acute diuretic-induced salt loss, hyponatremia or hypokalemic, hypochloremic metabolic alkalosis, and reflex activation of the renal nerves. Nephron mechanisms include tubular tolerance that can develop even during the time that the renal tubules are exposed to a single dose of diuretic, or enhanced reabsorption in the proximal tubule that limits delivery to the loop, or an adaptive increase in reabsorption in the downstream distal tubule and collecting ducts that offsets ongoing blockade of Na reabsorption in the loop of Henle. These provide rationales for novel strategies including the concurrent use of diuretics that block these nephron segments and even sequential nephron blockade with multiple diuretics and aquaretics combined in severely diuretic-resistant patients with heart failure.
10.1161/HYPERTENSIONAHA.120.15205
Cardiac rehabilitation for heart transplant patients: Considerations for exercise training.
Progress in cardiovascular diseases
Heart transplantation (HT) is the treatment of choice for eligible patients with end-stage chronic heart failure (HF). One-year survival world-wide is >85%. Many patients experience a reasonable functional ability post-HT, but episodes of acute rejection, as well as multiple co-morbidities such as hypertension, diabetes, chronic kidney disease and cardiac allograft vasculopathy are common. Immunosuppression with prednisone frequently results in increased body fat and skeletal muscle atrophy. Exercise capacity is below normal for most patients with a mean peak oxygen uptake (VO) of approximately 60% of expected. HT recipients have abnormal exercise physiology findings related to surgical cardiac denervation, diastolic dysfunction, and the legacy of reduced skeletal muscle oxidative capacity and impaired vasodilatory ability resulting from pre-HT chronic HF. The heart rate response to exercise is blunted. Cardiac reinnervation resulting in partial normalization of the heart rate response to exercise occurs in approximately 40% of HT recipients months to years after HT. Supervised exercise training in cardiac rehabilitation (CR) programs is safe and is recommended by professional societies both before (pre-habilitation) and after HT. Exercise training does not require alteration in immunosuppressants. Exercise training in adults after HT improves peak VO and skeletal muscle strength. It has also been demonstrated to reduce the severity of cardiac allograft vasculopathy. In addition, CR exercise training is associated with reduced stroke risk, percutaneous coronary intervention, hospitalization for either acute rejection or HF, and death. There are only limited data for exercise training in the pediatric population.
10.1016/j.pcad.2021.12.003
Inflammation in Heart Failure: JACC State-of-the-Art Review.
Murphy Sean P,Kakkar Rahul,McCarthy Cian P,Januzzi James L
Journal of the American College of Cardiology
It has long been observed that heart failure (HF) is associated with measures of systemic inflammation. In recent years, there have been significant advancements in our understanding of how inflammation contributes to the pathogenesis and progression of HF. However, although numerous studies have validated the association between measures of inflammation and HF severity and prognosis, clinical trials of anti-inflammatory therapies have proven mostly unsuccessful. On this backdrop emerges the yet unmet goal of targeting precise phenotypes within the syndrome of HF; if such precise definitions can be realized, and with better understanding of the roles played by specific inflammatory mediators, the expectation is that targeted anti-inflammatory therapies may improve prognosis in patients whose HF is driven by inflammatory pathobiology. Here, the authors describe mechanistic links between inflammation and HF, discuss traditional and novel inflammatory biomarkers, and summarize the latest evidence from clinical trials of anti-inflammatory therapies.
10.1016/j.jacc.2020.01.014
Exercise-based cardiac rehabilitation for chronic heart failure: the EXTRAMATCH II individual participant data meta-analysis.
Taylor Rod S,Walker Sarah,Ciani Oriana,Warren Fiona,Smart Neil A,Piepoli Massimo,Davos Constantinos H
Health technology assessment (Winchester, England)
BACKGROUND:Current national and international guidelines on the management of heart failure (HF) recommend exercise-based cardiac rehabilitation (ExCR), but do not differentiate this recommendation according to patient subgroups. OBJECTIVES:(1) To obtain definitive estimates of the impact of ExCR interventions compared with no exercise intervention (control) on mortality, hospitalisation, exercise capacity and health-related quality of life (HRQoL) in HF patients; (2) to determine the differential (subgroup) effects of ExCR in HF patients according to their age, sex, left ventricular ejection fraction, HF aetiology, New York Heart Association class and baseline exercise capacity; and (3) to assess whether or not the change in exercise capacity mediates for the impact of the ExCR on final outcomes (mortality, hospitalisation and HRQoL), and determine if this is an acceptable surrogate end point. DESIGN:This was an individual participant data (IPD) meta-analysis. SETTING:An international literature review. PARTICIPANTS:HF patients in randomised controlled trials (RCTs) of ExCR. INTERVENTIONS:ExCR for at least 3 weeks compared with a no-exercise control, with 6 months' follow-up. MAIN OUTCOME MEASURES:All-cause and HF-specific mortality, all-cause and HF-specific hospitalisation, exercise capacity and HRQoL. DATA SOURCES:IPD from eligible RCTs. REVIEW METHODS:RCTs from the Exercise Training Meta-Analysis of Trials for Chronic Heart Failure (ExTraMATCH/ExTraMATCH II) IPD meta-analysis and a 2014 Cochrane systematic review of ExCR (Taylor RS, Sagar VA, Davies EJ, Briscoe S, Coats AJ, Dalal H, . Exercise-based rehabilitation for heart failure. 2014;:CD003331). RESULTS:Out of the 23 eligible RCTs (4398 patients), 19 RCTs (3990 patients) contributed data to this IPD meta-analysis. There was a wide variation in exercise programme prescriptions across included studies. Compared with control, there was no statistically significant difference in pooled time-to-event estimates in favour of ExCR, although confidence intervals (CIs) were wide: all-cause mortality had a hazard ratio (HR) of 0.83 (95% CI 0.67 to 1.04); HF-related mortality had a HR of 0.84 (95% CI 0.49 to 1.46); all-cause hospitalisation had a HR of 0.90 (95% CI 0.76 to 1.06); and HF-related hospitalisation had a HR of 0.98 (95% CI 0.72 to 1.35). There was a statistically significant difference in favour of ExCR for exercise capacity and HRQoL. Compared with the control, improvements were seen in the 6-minute walk test (6MWT) (mean 21.0 m, 95% CI 1.57 to 40.4 m) and Minnesota Living with Heart Failure Questionnaire score (mean -5.94, 95% CI -1.0 to -10.9; lower scores indicate improved HRQoL) at 12 months' follow-up. No strong evidence for differential intervention effects across patient characteristics was found for any outcomes. Moderate to good levels of correlation ( > 50% and > 0.50) between peak oxygen uptake (Opeak) or the 6MWT with mortality and HRQoL were seen. The estimated surrogate threshold effect was an increase of 1.6 to 4.6 ml/kg/minute for Opeak. LIMITATIONS:There was a lack of consistency in how included RCTs defined and collected the outcomes: it was not possible to obtain IPD from all includable trials for all outcomes and patient-level data on exercise adherence was not sought. CONCLUSIONS:In comparison with the no-exercise control, participation in ExCR improved the exercise and HRQoL in HF patients, but appeared to have no effect on their mortality or hospitalisation. No strong evidence was found of differential intervention effects of ExCR across patient characteristics. Opeak and 6MWT may be suitable surrogate end points for the treatment effect of ExCR on mortality and HRQoL in HF. Future studies should aim to achieve a consensus on the definition of outcomes and promote reporting of a core set of HF data. The research team also seeks to extend current policies to encourage study authors to allow access to RCT data for the purpose of meta-analysis. STUDY REGISTRATION:This study is registered as PROSPERO CRD42014007170. FUNDING:The National Institute for Health Research Health Technology Assessment programme.
10.3310/hta23250
Evidence-Based Medical Therapy in Patients With Heart Failure With Reduced Ejection Fraction and Chronic Kidney Disease.
Circulation
Chronic kidney disease (CKD) as identified by a reduced estimated glomerular filtration rate (eGFR) is a common comorbidity in patients with heart failure with reduced ejection fraction (HFrEF). The presence of CKD is associated with more severe heart failure, and CKD itself is a strong independent risk factor of poor cardiovascular outcome. Furthermore, the presence of CKD often influences the decision to start, uptitrate, or discontinue possible life-saving HFrEF therapies. Because pivotal HFrEF randomized clinical trials have historically excluded patients with stage 4 and 5 CKD (eGFR <30 mL/min/1.73 m), information on the efficacy and tolerability of HFrEF therapies in these patients is limited. However, more recent HFrEF trials with novel classes of drugs included patients with more severe CKD. In this review on medical therapy in patients with HFrEF and CKD, we show that for both all-cause mortality and the combined end point of cardiovascular death or heart failure hospitalization, most drug classes are safe and effective up to CKD stage 3B (eGFR minimum 30 mL/min/1.73 m). For more severe CKD (stage 4), there is evidence of safety and efficacy of sodium glucose cotransporter 2 inhibitors, and to a lesser extent, angiotensin-converting enzyme inhibitors, vericiguat, digoxin and omecamtiv mecarbil, although this evidence is restricted to improvement of cardiovascular death/heart failure hospitalization. Data are lacking on the safety and efficacy for any HFrEF therapies in CKD stage 5 (eGFR < 15 mL/min/1.73 m or dialysis) for either end point. Last, although an initial decline in eGFR is observed on initiation of several HFrEF drug classes (angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers/mineralocorticoid receptor antagonists/angiotensin receptor blocker neprilysin inhibitors/sodium glucose cotransporter 2 inhibitors), renal function often stabilizes over time, and the drugs maintain their clinical efficacy. A decline in eGFR in the context of a stable or improving clinical condition should therefore not be cause for concern and should not lead to discontinuation of life-saving HFrEF therapies.
10.1161/CIRCULATIONAHA.121.052792
Advanced heart failure: guideline-directed medical therapy, diuretics, inotropes, and palliative care.
ESC heart failure
Heart failure (HF) is a major cause of mortality, hospitalizations, and reduced quality of life and a major burden for the healthcare system. The number of patients that progress to an advanced stage of HF is growing. Only a limited proportion of these patients can undergo heart transplantation or mechanical circulatory support. The purpose of this review is to summarize medical management of patients with advanced HF. First, evidence-based oral treatment must be implemented although it is often not tolerated. New therapeutic options may soon become possible for these patients. The second goal is to lessen the symptomatic burden through both decongestion and haemodynamic improvement. Some new treatments acting on cardiac function may fulfil both these needs. Inotropic agents acting through an increase in intracellular calcium have often increased risk of death. However, in the recent Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF) trial, omecamtiv mecarbil was safe and effective in the reduction of the primary outcome of cardiovascular death or HF event compared with placebo (hazard ratio, 0.92; 95% confidence interval, 0.86-0.99; P = 0.03) and its effects were larger in those patients with more severe left ventricular dysfunction. Patients with severe HF who received omecamtiv mecarbil experienced a significant treatment benefit, whereas patients without severe HF did not (P = 0.005 for interaction). Lastly, clinicians should take care of the end of life with an appropriate multidisciplinary approach. Medical treatment of advanced HF therefore remains a major challenge and a wide open area for further research.
10.1002/ehf2.13859
Artificial intelligence and heart failure: A state-of-the-art review.
European journal of heart failure
Heart failure (HF) is a heterogeneous syndrome affecting more than 60 million individuals globally. Despite recent advancements in understanding of the pathophysiology of HF, many issues remain including residual risk despite therapy, understanding the pathophysiology and phenotypes of patients with HF and preserved ejection fraction, and the challenges related to integrating a large amount of disparate information available for risk stratification and management of these patients. Risk prediction algorithms based on artificial intelligence (AI) may have superior predictive ability compared to traditional methods in certain instances. AI algorithms can play a pivotal role in the evolution of HF care by facilitating clinical decision making to overcome various challenges such as allocation of treatment to patients who are at highest risk or are more likely to benefit from therapies, prediction of adverse outcomes, and early identification of patients with subclinical disease or worsening HF. With the ability to integrate and synthesize large amounts of data with multidimensional interactions, AI algorithms can supply information with which physicians can improve their ability to make timely and better decisions. In this review, we provide an overview of the AI algorithms that have been developed for establishing early diagnosis of HF, phenotyping HF with preserved ejection fraction, and stratifying HF disease severity. This review also discusses the challenges in clinical deployment of AI algorithms in HF, and the potential path forward for developing future novel learning-based algorithms to improve HF care.
10.1002/ejhf.2994
Heart Failure with Preserved Ejection Fraction: Mechanisms and Treatment Strategies.
Annual review of medicine
Approximately half of all patients with heart failure (HF) have a preserved ejection fraction, and the prevalence is growing rapidly given the aging population in many countries and the rising prevalence of obesity, diabetes, and hypertension. Functional capacity and quality of life are severely impaired in heart failure with preserved ejection fraction (HFpEF), and morbidity and mortality are high. In striking contrast to HF with reduced ejection fraction, there are few effective treatments currently identified for HFpEF, and these are limited to decongestion by diuretics, promotion of a healthy active lifestyle, and management of comorbidities. Improved phenotyping of subgroups within the overall HFpEF population might enhance individualization of treatment. This review focuses on the current understanding of the pathophysiologic mechanisms underlying HFpEF and treatment strategies for this complex syndrome.
10.1146/annurev-med-042220-022745
Heart Failure With Reduced Ejection Fraction: A Review.
JAMA
IMPORTANCE:Worldwide, the burden of heart failure has increased to an estimated 23 million people, and approximately 50% of cases are HF with reduced ejection fraction (HFrEF). OBSERVATIONS:Heart failure is a clinical syndrome characterized by dyspnea or exertional limitation due to impairment of ventricular filling or ejection of blood or both. HFrEF occurs when the left ventricular ejection fraction (LVEF) is 40% or less and is accompanied by progressive left ventricular dilatation and adverse cardiac remodeling. Assessment for heart failure begins with obtaining a medical history and physical examination. Also central to diagnosis are elevated natriuretic peptides above age- and context-specific thresholds and identification of left ventricular systolic dysfunction with LVEF of 40% or less as measured by echocardiography. Treatment strategies include the use of diuretics to relieve symptoms and application of an expanding armamentarium of disease-modifying drug and device therapies. Unless there are specific contraindications, patients with HFrEF should be treated with a β-blocker and one of an angiotensin receptor-neprilysin inhibitor, angiotensin-converting enzyme inhibitor, or angiotensin receptor blocker as foundational therapy, with addition of a mineralocorticoid receptor antagonist in patients with persistent symptoms. Ivabradine and hydralazine/isosorbide dinitrate also have a role in the care of certain patients with HFrEF. More recently, sodium-glucose cotransporter 2 (SGLT2) inhibitors have further improved disease outcomes, significantly reducing cardiovascular and all-cause mortality irrespective of diabetes status, and vericiguat, a soluble guanylate cyclase stimulator, reduces heart failure hospitalization in high-risk patients with HFrEF. Device therapies may be beneficial in specific subpopulations, such as cardiac resynchronization therapy in patients with interventricular dyssynchrony, transcatheter mitral valve repair in patients with severe secondary mitral regurgitation, and implantable cardiac defibrillators in patients with more severe left ventricular dysfunction particularly of ischemic etiology. CONCLUSIONS AND RELEVANCE:HFrEF is a major public health concern with substantial morbidity and mortality. The management of HFrEF has seen significant scientific breakthrough in recent decades, and the ability to alter the natural history of the disease has never been better. Recent developments include SGLT2 inhibitors, vericiguat, and transcatheter mitral valve repair, all of which incrementally improve prognosis beyond foundational neurohormonal therapies. Disease morbidity and mortality remain high, with a 5-year survival rate of 25% after hospitalization for HFrEF.
10.1001/jama.2020.10262