Skeletal Muscle Myopathy in Heart Failure: the Role of Ejection Fraction

Purpose of Review

This review summarizes: (1) the structural and functional features coupled with pathophysiological factors responsible of skeletal muscle myopathy (SMM) in both heart failure with reduced (HFrEF) and preserved (HFpEF) ejection fraction and (2) the role of exercise as treatment of SMM in these HF-related phenotypes.

Recent Findings

The recent literature showed two main phenotypes of heart failure (HF): (1) HFrEF primarily due to a systolic dysfunction of the left ventricle and (2) HFpEF, mainly related to a diastolic dysfunction. Exercise intolerance is one of most disabling symptoms of HF and it is shown that persists after the normalization of the central hemodynamic impairments by therapy and/or cardiac surgery including heart transplant. A specific skeletal muscle myopathy (SMM) has been defined as one of the main causes of exercise intolerance in HF.

Summary

The SMM has been well described in the last 20 years in the HFrEF; on the contrary, few studies are available in HFpEF. Recent evidences have revealed that exercise training counteracts HF-related SMM and in turn ameliorates exercise intolerance.

     

Impaired Exercise Tolerance in Heart Failure: Role of Skeletal Muscle Morphology and Function

Purpose of Review

To discuss the impact of deleterious changes in skeletal muscle morphology and function on exercise intolerance in patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), as well as the utility of exercise training and the potential of novel treatment strategies to preserve or improve skeletal muscle morphology and function.

Recent Findings

Both HFrEF and HFpEF patients exhibit a reduction in percent of type I (oxidative) muscle fibers and oxidative enzymes coupled with abnormal mitochondrial respiration. These skeletal muscle abnormalities contribute to impaired oxidative metabolism with an earlier shift towards glycolytic metabolism during exercise that is strongly associated with exercise intolerance. In both HFrEF and HFpEF patients, peripheral “non-cardiac” factors are important determinants of the improvement in exercise tolerance following aerobic exercise training. Adjunctive strategies that include nutritional supplementation with amino acids and/or anabolic drugs to stimulate anabolic molecular pathways in skeletal muscle show great promise for improving exercise tolerance and treating heart failure-associated sarcopenia, but these efforts remain early in their evolution, with no immediate clinical applications.

Summary

There is consistent evidence that heart failure is associated with multiple skeletal muscle abnormalities which impair oxygen uptake and utilization and contribute greatly to exercise intolerance. Exercise training induces favorable adaptations in skeletal muscle morphology and function that contribute to improvements in exercise tolerance in patients with HFrEF. The contribution of skeletal muscle adaptations to improved exercise tolerance following exercise training in HFpEF remains unknown and warrants further investigation.

     

The Evolving Role of Cardiorespiratory Fitness and Exercise in Prevention and Management of Heart Failure

Purpose of Review

This paper highlights the dynamic relationship between cardiorespiratory fitness (CRF) and heart failure (HF). As heart failure with preserved ejection fraction (HFpEF) surpasses heart failure with reduced ejection fraction (HFrEF) in prevalence, our void in understanding how to treat this syndrome becomes less justifiable. As such, significant attention has been given to the role that obesity and physical inactivity play, as both risk factors for heart failure, and therapeutic targets for its treatment.

Recent Findings

Previous findings have shown that low CRF, obesity, and physical inactivity are all risk factors for HF. More recently, it has been discovered that these factors are even more significant when applied to HFpEF, even after accounting for traditional cardiovascular risk factors. As such, new investigations have attempted to discover whether improvements in CRF could be utilized as a tool for prevention of HF. In addition, small studies have shown that interventions to improve CRF in patients with HF could improve both quality of life and fitness.

Summary

The role of CRF, PA, and obesity in the development of HF is now well established; however, our ability to attenuate that risk is yet to be determined. Observational data have signaled a correlation between improvements in PA, CRF and lower risk of HF however, large randomized controlled trials are still required to truly determine whether exercise training could be used in the prevention and treatment of HF, particularly HFpEF.

     

Heart Failure with Preserved Ejection Fraction Trials Have Heterogeneous Control Groups: a Comparison of Kaplan-Meier Curves

Purpose

Previous studies have evaluated intra-study heterogeneities of heart failure with preserved ejection fraction (HFpEF), but inter-study heterogeneities remain poorly understood. We investigate the heterogeneities of outcomes among control groups of HFpEF trials.

Methods

We included randomized controlled trials recruiting HFpEF patients with ejection fraction ≥?40% and reporting Kaplan-Meier curves for at least 36 months. The Kaplan-Meier curves of control groups were extracted and calculated for hazard ratios and 95% confidence intervals. Two virtual trials were developed to validate the reliability and accuracy of our method.

Results

Of 4161 studies, we included six trials containing 7682 HFpEF patients in control groups. The DIG trial had the highest all-cause mortality, cardiovascular mortality, heart failure mortality, and composite endpoints of cardiovascular mortality and heart failure hospitalization (all p?<?0.001). The TOPCAT trial had the lowest all-cause mortality, cardiovascular mortality, heart failure hospitalization, and composite of cardiovascular mortality and heart failure hospitalization (all p?<?0.001). Adoption of different ejection fraction cut-off values for HFpEF diagnosis did not significantly change the outcomes of control groups in the DIG trial (45% vs. 50%: hazard ratio, 1.05, 95% confidence interval, 0.97–1.13, p?=?0.271), or in the CHARM-Preserved trial (40% vs. 50%: hazard ratio, 1.01, 95% confidence interval, 0.93–1.09, p?=?0.864) during 36-month follow-up.

Conclusions

The control groups of HFpEF trials have heterogeneous outcomes. Future trials should consider these heterogeneities when designing protocols.

     

Prevalence of Prediabetes and Undiagnosed Diabetes in Patients with HFpEF and HFrEF and Associated Clinical Outcomes

Purpose

The prevalence and consequences of prediabetic dysglycemia and undiagnosed diabetes is unknown in patients with heart failure (HF) and preserved ejection fraction (HFpEF) and has not been compared to heart failure and reduced ejection fraction (HFrEF).

Methods

We examined the prevalence and outcomes associated with normoglycemia, prediabetic dysglycemia and diabetes (diagnosed and undiagnosed) among individuals with a baseline glycated hemoglobin (hemoglobin A1c, HbA1c) measurement stratified by HFrEF or HFpEF in the Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity programme (CHARM). We studied the primary outcome of HF hospitalization or cardiovascular (CV) death, and all-cause death, and estimated hazard ratios (HR) by use of multivariable Cox regression models.

Results

HbA1c was measured at baseline in CHARM patients enrolled in the USA and Canada and was available in 1072/3023 (35%) of patients with HFpEF and 1578/4576 (34%) patients with HFrEF. 18 and 16% had normoglycemia (HbA1c < 6.0), 20 and 22% had prediabetes (HbA1c 6.0–6.4), respectively. Finally among patients with HFpEF 22% had undiagnosed diabetes (HbA1c > 6.4), and 40% had known diabetes (any HbA1c), with corresponding prevalence among HFrEF patients being 26 and 35%. The rates of both clinical outcomes of interest were higher in patients with undiagnosed diabetes and prediabetes, compared to normoglycemic patients, irrespective of HF subtype, and in general higher among HFrEF patients. For the primary composite outcome among HFpEF patients, the HRs were 1.02 (95% CI 0.63–1.65) for prediabetes, HR 1.18 (0.75–1.86) for undiagnosed diabetes and 2.75 (1.83–4.11) for known diabetes, respectively, p value for trend across groups < 0.001. Dysglycemia was also associated with worse outcomes in HFrEF.

Conclusions

These findings confirm the remarkably high prevalence of dysglycemia in heart failure irrespective of ejection fraction phenotype, and demonstrate that dysglycemia is associated with a higher risk of adverse clinical outcomes, even before the diagnosis of diabetes and institution of glucose lowering therapy in patients with HFpEF as well as HFrEF.

     

The Future of Biomarker-Guided Therapy for Heart Failure After the Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) Study

Purpose of Review

Biomarker-guided management of patients with chronic heart failure with reduced ejection fraction (HFrEF) remains controversial.

Recent Findings

Biomarkers have established roles for diagnosis and prognostication in HF. Pilot data suggested that use of natriuretic peptides might be helpful to guide HF care. The recent Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) randomized–controlled trial did not find therapy guided by NT-proBNP to be more effective than usual care in improving the primary endpoint of HF hospitalization or cardiovascular mortality amongst patients with chronic HFrEF. Patients in GUIDE-IT received similar care and had similar NT-proBNP lowering regardless of treatment allocation.

Summary

Though biomarkers retain important standing for diagnosis and prognosis in HF, the GUIDE-IT trial results suggest carefully managed patients may not benefit from a biomarker-guided strategy. Future studies focusing this intervention on patients treated in a more real-world setting are needed.

     

Imaging and Management of Heart Failure and Preserved Ejection Fraction

Purpose of review

The prevalence of heart failure with preserved ejection fraction (HFpEF) is rising and in some places, it is already the most prevalent form of heart failure. The usual treatments of HF do not improve mortality or outcomes in HFpEF, suggesting a distinct pathophysiology that remains poorly characterized. The neutrality of clinical trial results is also attributable to the heterogeneity of patient profiles, and by poor characterization offered by classical echocardiography parameters. Emerging imaging modalities may overcome this problem. We therefore aimed to summarize recent advances offered by cardiovascular imaging in disease characterization, and the implication of findings to new phenotype-specific treatment options.

Recent findings

Novel cardiovascular imaging techniques such as LV global longitudinal strain, left atrial strain, tissue characterization by magnetic resonance T1 time, as well as incorporation of systolic and diastolic stress testing offer greatly improved characterization, diagnosis, and stratification of disease pathogenesis. These techniques offer insight into identification of HFpEF sub-phenotypes that are resistant to, or responsive to therapies.

Summary

There is a growing body of evidence that novel cardiovascular imaging modalities are able to characterize HFpEF patients with much greater accuracy than current guideline-driven parameters. Whether this information can be synthesized to adequately stratify patients into sub-phenotypes with clearer disease pathogenesis amenable to targeted intervention will be of particular future interest.

     

Role of Angiotensin Receptor-Neprilysin Inhibition in Heart Failure

Purpose of Review

Numerous evidence-based medical and device therapies proven to reduce morbidity and mortality have advanced care for heart failure with reduced ejection fraction (HFrEF). The primacy of this approach has now been superseded by striking new data resulting in the approval of the combination of valsartan and sacubitril, a neprilysin inhibitor (also known as LCZ696), in 2015 for the treatment of HFrEF. LCZ696 is a novel heart failure drug that simultaneously inhibits the renin-angiotensin system and potentiates the natriuretic peptide system.

Recent Findings

In the Prospective Comparison of ARNI with ACE-I to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial, LCZ696 significantly improved cardiovascular outcomes compared to current guideline-directed medical therapy. Compared to an angiotensin-converting enzyme (ACE) inhibitor, LCZ696 was associated with a 20 % reduction in cardiovascular mortality (number needed to treat [NNT] 32) and a similar reduction in total mortality (NNT 36). Morbidity benefits of the drug were seen within 1 month of initiation. However, hypotension due to enalapril or the LCZ696 regimen during a run-in phase eliminated 20 % of patients. Safety concerns included the risk of angioedema and the theoretical concern of neurocognitive dysfunction due to the protean effects of neprilysin inhibition. The role of LCZ696 in patients with asymptomatic left ventricular systolic dysfunction is uncertain. LCZ696 is currently being evaluated in patients with heart failure with preserved ejection fraction, with promising initial results.

Summary

LCZ696 represents a novel mechanistic approach to targeting heart failure with reduced ejection fraction, and ongoing studies will address its use in other cardiovascular populations.

     

Novel Insights and Treatment Strategies for Right Heart Failure

Purpose of Review

The function of the right ventricle (RV) is intimately linked to its preload (systemic volume status) and afterload (pulmonary vasculature). In this review, we explore current knowledge in RV physiology, RV function assessment, causes of right heart failure (RHF), and specific treatment strategies for RHF.

Recent Findings

We examine the evidence behind new pharmacological therapies available, such as macitentan and riociguat in the treatment of specific etiologies of RHF. We will also focus on RHF in the setting of heart failure with preserved ejection fraction (HFpEF) and in the presence of left ventricular assist devices (LVAD), looking at current treatment recommendations, including mechanical circulatory support. Lastly, we will look to the horizon for the latest research on RHF, including the molecular basis of RHF and potential novel treatment methods for this old yet poorly understood syndrome.

Summary

Disturbances in this complex relationship result in the clinical syndrome of RHF. Despite advances in the management of left heart diseases, much work remains to be done to understand and manage RHF.

     

The Emerging Role of Cardiac Magnetic Resonance Imaging in the Evaluation of Patients with HFpEF

Purpose of Review

To give an update on the emerging role of cardiac magnetic resonance imaging in the evaluation of patients with heart failure with preserved ejection fraction (HFpEF). This is important as the diagnosis of HFpEF remains challenging and cardiac imaging is pivotal in establishing the function of the heart and whether there is evidence of structural heart disease or diastolic dysfunction. Echocardiography is widely available, although the gold standard in quantifying heart function is cardiac magnetic resonance (CMR) imaging.

Recent Findings

This review includes the recently updated 2016 European Society of Cardiology guidelines on diagnosing HFpEF that define the central role of imaging in identifying patients with HFpEF. Moreover, it includes the pathophysiology in HFpEF, how CMR works, and details current CMR techniques used to assess structural heart disease and diastolic function. Furthermore, it highlights promising research techniques that over the next few years may become more used in identifying these patients.

Summary

CMR has an emerging role in establishing the diagnosis of HFpEF by measuring the left ventricular ejection fraction (LVEF) and evidence of structural heart disease and diastolic dysfunction.

     

Barriers to Beta-Blocker Use and Up-Titration Among Patients with Heart Failure with Reduced Ejection Fraction

Purpose

For patients with heart failure with reduced ejection fraction (HFrEF), guidelines recommend use of beta-blockers with gradual up-titration. However, many patients with HFrEF do not use beta-blockers and up-titration is rare. Our purpose was to identify and rank barriers to beta-blocker use and up-titration from the perspective of primary care physicians.

Methods

We conducted 4 moderated, structured group discussions among 19 primary care physicians using the nominal group technique; 16 participants also completed a survey. Participants generated lists of barriers to beta-blocker use and up-titration among patients with HFrEF. Each participant had six votes with three votes assigned to the item ranked most important, two to the second most important item, and one to the third most important item. Investigators characterized items into themes. The percentage of available votes was calculated for each theme.

Results

Fifteen of 16 participating primary care physicians who completed the survey reported that management of beta-blockers was their responsibility. Treatment/side effects, particularly hypotension, were identified as the most important barrier for beta-blocker use (72% of available votes) followed by polypharmacy (11%), healthcare system barriers (10%), and comorbidities (6%). Barriers to up-titration included treatment/side effects (49% of available votes), patient communication/buy-in (21%), polypharmacy (13%), and healthcare system barriers (8%).

Conclusions

Many barriers to guideline concordant use of beta-blockers among patients with HFrEF identified by primary care providers are not readily modifiable. Addressing these barriers may require development, testing, and dissemination of protocols for beta-blocker initiation and up-titration that are safe and appropriate in primary care.

     

Associations With and Prognostic and Discriminatory Role of N-Terminal Pro–B-Type Natriuretic Peptide in Heart Failure With Preserved Versus Mid-range Versus Reduced Ejection Fraction

Background

The aim of this study was to characterize N-terminal pro–B-type natriuretic peptide (NT-proBNP) in terms of determinants of levels and of its prognostic and discriminatory role in heart failure with mid-range (HFmrEF) versus preserved (HFpEF) and reduced (HFrEF) ejection fraction.

Evolving Landscape of Clinical Trials in Heart Failure: Patient Populations,Endpoint Selection,and Regions of Enrollment

Purpose of Review

Clinical trial design and execution are evolving as increasingly important considerations with respect to the success of heart failure trials. The current review highlights temporal trends in characteristics of heart failure clinical trials.

Recent Findings

Recent trials in heart failure have required longer recruitment phases, displayed inefficient enrollment rates, increased use of composite and nonfatal endpoints, undergone rapid globalization, and gradually increased focus on heart failure with preserved ejection fraction.

Summary

Understanding patterns and trends in clinical trial design and execution may inform future planning and conduct of trials of heart failure therapeutics.

     

How Heart Rate Should Be Controlled in Patients with Atherosclerosis and Heart Failure

Purpose of Review

Resting heart rate is an independent risk factor for all-cause and cardiovascular mortality in patients with heart failure. The main objectives are to discuss the prognosis of heart rate, its association with coronary atherosclerosis, and the modalities of control of the heart rate in sinus rhythm and in the rhythm of atrial fibrillation in patients with chronic heart failure.

Recent Findings

As a therapeutic option for control heart rate, medications such as beta-blockers, digoxin, and finally ivabradine have been studied. Non-dihydropyridine calcium channel blockers are contraindicated in patients with heart failure and reduced ejection fraction. The influence of the magnitude of heart rate reduction and beta-blocker dose on morbidity and mortality will be discussed. Regarding the patients with heart failure and atrial fibrillation, there are different findings in heart rate control with the use of a beta-blocker. Patients eligible for ivabradine have clinical benefits and increased ejection fraction. Vagal nerve stimulation has low efficacy for the control of heart rate. Complementary therapies such as tai chi and yoga showed no effect on heart rate.

Summary

In this review, we discuss the main therapeutic options for the control of heart rate in patients with atherosclerosis and heart failure. More research is needed to examine the effects of therapeutic options for heart rate control in different population types, as well as their effects on clinical outcomes and impact on morbidity and mortality.

     

Clinical Phenotyping of Transthyretin Cardiac Amyloidosis with Bone-Seeking Radiotracers in Heart Failure with Preserved Ejection Fraction

Purpose of Review

The two most common types of cardiac amyloidosis are caused by fibril deposits of immunoglobulin light chains (AL) and transthyretin (TTR), each with distinct prognosis and clinical management. Cardiac amyloidosis is under-recognized among heart failure patients with preserved ejection fraction (HFpEF). Bone-seeking tracers like ^99mTc-PYP and ^99mTc-DPD have long been used to identify cardiac amyloidosis, and more recently, to differentiate TTR from AL cardiac amyloidosis in symptomatic patients. However, results are mainly derived from single-center retrospective studies, with comparable but not standardized imaging protocols and interpretation criteria.

Recent Findings

The clinical scope of cardiac amyloidosis among HFpEF patients and current literature supporting the use of bone-seeking tracers for TTR cardiac amyloidosis are presented. The differences of imaging techniques for cardiac amyloid and bone disease evaluation, bone tracer pharmacodynamics, and imaging interpretation criteria for cardiac amyloidosis diagnosis are discussed. Finally, a diagnostic algorithm to use bone scintigraphy in cardiac amyloidosis diagnosis among HFpEF patients is proposed.

Summary

Bone scintigraphy with ^99mTc-PYP or ^99mTc-DPD can be a useful tool with high sensitivity and specificity for detecting TTR-related cardiac amyloidosis in patients with HFpEF. It is needed to standardize the imaging protocol and interpretation criteria and to perform prospective clinical studies.

     

Amiodarone plus Ranolazine for Conversion of Post-Cardiac Surgery Atrial Fibrillation: Enhanced Effectiveness in Reduced Versus Preserved Ejection Fraction Patients

Purpose

Ranolazine (RAN) added to amiodarone (AMIO) has been shown to accelerate termination of postoperative atrial fibrillation (POAF) following coronary artery bypass surgery in patients without heart failure (HF). This study aimed to investigate if treatment efficacy with AMIO or AMIO + RAN differs between patients with concomitant HF with reduced or preserved ejection fraction (HFrEF or HFpEF).

Methods

Patients with POAF and HFrEF (n?=?511, 446 males; 65?±?9 years) and with HFpEF (n?=?301, 257 males; 66?±?10 years) were enrolled. Onset of AF occurred 2.15?±?1.0 days after cardiac surgery, and patients within each group were randomly assigned to receive either AMIO monotherapy (300 mg in 30 min?+?1125 mg in 36 h iv) or AMIO+RAN combination (500 mg po?+?375 mg, after 6 h and 375 mg twice daily thereafter). Primary endpoint was the time to conversion of POAF within 36 h after initiation of treatment.

Results

AMIO restored sinus rhythm earlier in HFrEF vs. in HFpEF patients (24.3?±?4.6 vs. 26.8?±?2.8 h, p?<?0.0001). AMIO + RAN converted POAF faster than AMIO alone in both HFrEF and HFpEF groups, with conversion times 10.4?±?4.5 h in HFrEF and 12.2?±?1.1 h in HFpEF patients (p?<?0.0001). Left atrial diameter was significantly greater in HFrEF vs. HFpEF patients (48.2?±?2.6 vs. 35.2?±?2.9 mm, p?<?0.0001). No serious adverse drug effects were observed during AF or after restoration to sinus rhythm in any of the patients enrolled.

Conclusion

AMIO alone or in combination with RAN converted POAF faster in patients with reduced EF than in those with preserved EF. Thus, AMIO + RAN seems to be a valuable alternative treatment for terminating POAF in HFrEF patients.

     

Multiple Avenues of Modulating the Nitric Oxide Pathway in Heart Failure Clinical Trials

Purpose of review

This review discusses the integral role of the nitric oxide (NO) pathway in the pathophysiology of heart failure (HF). We emphasize potential therapeutic targets in the NO pathway and review contemporary clinical trials evaluating these novel therapeutic options.

Recent findings

Nitrates, neprilysin inhibitors, and phosphodiesterase (PDE) inhibitors have all proven to be efficacious in HF patients with systolic dysfunction, with the former two classes of medications producing a net mortality benefit. However, neither PDE inhibitors nor nitrates have demonstrated significant clinical benefit in patients with HF with preserved ejection fraction (HFpEF), and neprilysin inhibitors have yet to be evaluated in this population. Soluble guanylate cyclase (sGC) stimulators have shown significant promise in all HF patients, leading to improvements in both quality of life scores and exercise capacity. Conversely, sGC activators have limited clinical utility in HF, owing largely to safety concerns of hypotension. Inorganic nitrates and nitrites, meanwhile, may be emerging as potential therapies for the HFpEF population.

Summary

The advent of novel therapies targeting the NO pathway is beginning to create a paradigm shift in the treatment of the HF patient. These therapies offer a promising outlook for the future, with hopes of reducing HF-associated morbidity and mortality.

     

Right Ventricular Dysfunction and Its Contribution to Morbidity and Mortality in Left Ventricular Heart Failure

Purpose

In patients with left-sided HF, there has been less emphasis on the pathophysiology of the RV in terms of diagnostic evaluation and treatment, versus focus on structural abnormalities of the LV. This review seeks to delineate the importance of RV dysfunction in terms of its contribution to symptomatic limitations and cardiovascular outcomes in patients with left-sided HF.

Recent Findings

Recent studies have demonstrated that RV dysfunction is common in both HFpEF and HFrEF, but more pronounced in HFrEF. LV dysfunction and atrial fibrillation are most commonly associated with RV dysfunction in left-sided HF. RV dysfunction may develop due to afterload-dependent and afterload-independent pathways. Regardless, RV dysfunction is strongly associated with functional limitations and worsened survival in patients with left-sided HF. In patients with HFpEF, a recent study showed that RV failure was the most common cause of overall mortality. Among LVAD patients and patients post-cardiac transplantation, RV dysfunction is also strongly associated with survival. Despite a number of previous and ongoing clinical trials that target the RV directly or decrease RV afterload in left-sided HF, there are no definitive therapies specifically targeting RV dysfunction in left-sided HF patients

Conclusions

RV dysfunction is an important determinant of symptomatic limitations and cardiovascular outcomes in patients with left-sided HF. Further research is needed to developed pharmacotherapy that may target the RV specifically in left-sided HF patients.

     

Rationale and Design of the Multicenter Trial on Japan Working Group on the Effects of Angiotensin Receptor Blockers Selection (Azilsartan vs. Candesartan) on Diastolic Function in the Patients Suffering from Heart Failure with Preserved Ejection Fraction: J-TASTE Trial

Background

Previous studies suggest that the pathophysiology of heart failure with preserved ejection fraction (HFpEF) is characterized not only by high ventricular stiffness, but also by vascular stiffness. Azilsartan has higher vascular affinity compared with other angiotensin II receptor blockers (ARBs), which were proven to have no beneficial effects on clinical outcomes in patients with HFpEF in earlier clinical trials. We aimed to test the hypothesis that azilsartan may improve left ventricular diastolic function in HFpEF patients with hypertension in this trial.

Methods

The Effects of Angiotensin Receptor Blockers on Diastolic Function in Patients Suffering from Heart Failure with Preserved Ejection Fraction: J-TASTE trial is a multicenter, randomized, open-labeled, and assessor(s)-blinded, active controlled using candesartan, parallel-group clinical trial, to compare changes in left ventricular (LV) diastolic dysfunction between HFpEF patients with hypertension who have received candesartan or azilsartan for 48 weeks. The primary endpoint is the change in early diastolic wave height/early diastolic mitral annulus velocity (E/e’) assessed by echocardiography from the baseline to the end of the study (48 weeks). A total of 190 patients will be recruited into the study.

Conclusions

The design of the J-TASTE trial will provide data on whether differences between the effects of the two tested drugs on LV diastolic function exist in HFpEF patients with hypertension and will improve understanding of the pathophysiological role of vascular stiffness on diastolic function.