Heart Failure Clinical Trials Research Articles

Nitroxyl donating and visualization with a coumarin-based fluorescence probe

Nitroxyl (HNO), the single-electron reduction product of nitric oxide (NO), has attracted great interest in the treatment of congestive heart failure in clinical trials. In this paper, we describe the first coumarin-based compound N-hydroxy-2-oxo-2H-chromene-6-sulfonamide (CD1) as a dualfunctional HNO donor, which can release both an HNO signaling molecule and a fluorescent reporter. Under physiological conditions (pH 7.4 and 37 °C), the CD1 HNO donor can readily decompose with a half-life of ∼90 min. The corresponding stoichiometry HNO from the CD1 donor was confirmed using both Vitamin B12 and phosphine compound traps. In addition to HNO releasing, specifically, the degradation product 2-oxo-2H-chromene-6-sulfinate (CS1) was generated as a fluorescent marker during the decomposition. Therefore, the HNO amount released in situ can be accurately monitored through fluorescence generation. As compared to the CD1 donor, the fluorescence intensity increased by about 4.9-fold. The concentration limit of detection of HNO releasing was determined to be ∼0.13 μM according to the fluorescence generation of CS1 at physiological conditions. Moreover, the bioimaging of the CD1 donor was demonstrated in the cell culture of HeLa cells, where the intracellular fluorescence signals were observed, inferring the site of HNO release. Finally, we anticipate that this novel coumarin-based CD1 donor opens a new platform for exploring the biology of HNO.

Real-world characteristics and use patterns of patients treated with vericiguat: A nationwide longitudinal cohort study in Germany.

Vericiguat reduced clinical endpoints in patients experiencing worsening heart failure in clinical trials, but its implementation outside trials is unclear. This retrospective analysis of longitudinally collected data was based on the IQVIA™ LRx database, which includes ~ 80% of the prescriptions of the 73 million people covered by the German statutory health insurance. Between September 2021 and December 2022, vericiguat was initiated in 2916 adult patients. Their mean age was 73 ± 13 years and 28% were women. While approximately 70% were uptitrated beyond 2.5 mg, only 36% reached 10 mg. Median time to up-titration from 2.5 mg to 5 mg was 17 (quartiles: 11-33) days, and from 2.5 to 10 mg 37 (25-64) days, respectively. In 87% of thepatients, adherence to vericiguat was high as indicated by a medication possession ratio of ≥ 80%, and 67% of thepatients persistently used vericiguat during the first year. Women and older patients reached the maximal dose of 10 mg vericiguat less often and received other substance classes of guideline-recommended therapy (GDMT) less frequently. The proportion of patients receiving four pillars of GDMT increased from 29% before vericiguat initiation to 44% afterwards. In a real-world setting, despite higher age than in clinical trials, adherence and persistence of vericiguat appeared satisfactory across age categories. Initiation of vericiguat was associated with intensification of concomitant GDMT. Nevertheless, barriers to vericiguat up-titration and implementation of other GDMT, applying in particular to women and elderly patients, need to be investigated further.

Trends in use of composite endpoints in clinical trials: A comparison between acute heart failure trials and COVID-19 trials.

Composite endpoints can encode multiple pieces of information and are increasingly adopted in clinical trials. Advocacy for using composite endpoints began decades ago in cardiovascular trials, leading to incorporation of patient-oriented outcomes and consideration of a hierarchical ranking system. The use of composite endpoints in coronavirus disease (COVID-19) trials has evolved similarly. We conducted a literature review to investigate the use of composite endpoints in acute heart failure and COVID-19 clinical trials. The results showed more frequent use of patient-oriented outcomes and ordinal composite endpoints in COVID-19 trials, which might be driven by global consensus on a set of common outcome measures.

Rewarding Site-Based Research: A Step Towards Improving The Ecosystem Of Heart Failure Clinical Trials

Rewarding Site-Based Research: A Step Towards Improving The Ecosystem Of Heart Failure Clinical Trials

Role of vericiguat in management of patients with heart failure with reduced ejection fraction after worsening episode.

Worsening heart failure (HF) is a vulnerable period in which the patient has a markedly high risk of death or HF hospitalization (up to 10% and 30%, respectively, within the first weeks after episode). The prognosis of HF patients can be improved through a comprehensive approach that considers the different neurohormonal systems, with the early introduction and optimization of the quadruple therapy with sacubitril-valsartan, beta-blockers, mineralocorticoid receptor antagonists, and inhibitors. Despite that, there is a residual risk that is not targeted with these therapies. Currently, it is recognized that the cyclic guanosine monophosphate deficiency has a negative direct impact on the pathogenesis of HF, and vericiguat, an oral stimulator of soluble guanylate cyclase, can restore this pathway. The effect of vericiguat has been explored in the VICTORIA study, the largest chronic HF clinical trial that has mainly focused on patients with recent worsening HF, evidencing a significant 10% risk reduction of the primary composite endpoint of cardiovascular death or HF hospitalization (number needed to treat 24), after adding vericiguat to standard therapy. This benefit was independent of background HF therapy. Therefore, optimization of treatment should be performed as earlier as possible, particularly within vulnerable periods, considering also the use of vericiguat.

Novel Trial Designs in Heart Failure: Using Digital Health Tools to Increase Pragmatism.

Heart failure is an important clinical and public health issue. There is an urgent need to improve the efficiency of clinical trials in heart failure to rapidly identify new therapies and evidence-based implementation strategies for currently existing therapies. Electronic health (eHealth) platforms and digital health tools are being integrated into heart failure care. In this manuscript, we review opportunities to use these tools to potentially improve the design of and reduce the complexity of clinical trials in heart failure. The PRECIS-2 tool outlines clinical trial design domains that are targets for pragmatism. We believe incorporating pragmatic design elements with the aid of eHealth platforms and digital health tools into clinical trials may help address the current complexity of clinical trials in heart failure and improve efficiency. In the manuscript, we provide examples from recent clinical trials across clinical trial design domains. We believe the current adoption of eHealth platforms and digital health tools is an opportunity improve the design of heart failure clinical trials. We specifically believe these tools can enhance pragmatism in clinical trials and reduce delays in generating high-quality evidence for new heart failure therapeutics.

Underrepresentation of Women in Reduced Ejection Heart Failure Clinical Trials With Improved Mortality or Hospitalization

BackgroundThere are established sex-specific differences in heart failure with reduced ejection fraction (HFrEF) outcomes. Randomized clinical trials (RCTs) based on cardiovascular outcome benefits, typically either reduced cardiovascular mortality or hospitalization for heart failure (HHF), influence current guidelines for therapy. ObjectivesThe authors evaluate the representation of women in HFrEF RCTs that observed reduced all-cause or cardiovascular mortality or HHF. MethodsWe queried Cumulative Index to Nursing and Allied Health Literature, Excerpta Medica dataBASE, Medical Literature Analysis and Retrieval System Online, and PubMed for HFrEF RCTs that reported a statistically significant benefit of intervention resulting in improved mortality or HHF published from 1980 to 2021. We estimated representation using the participation-to-prevalence ratio (PPR). A PPR of 0.8 to 1.2 was considered representative. ResultsThe final analysis included 33 RCTs. Women represented only 23.2% of all enrolled participants (n = 24,366/104,972), ranging from 11.4% to 40.1% per trial. Overall PPR was 0.58, with per-trial PPR estimates ranging from 0.29 to 1.00. Only 5 trials (15.2%) had a PPR of women representative of the disease population. Representation did not change significantly over time. The proportion of women in North American trials was significantly greater than trials conducted in Europe (P = 0.03). The proportion of women was greater in industry trials compared to government-funded trials (P = 0.05). ConclusionsWomen are underrepresented in HFrEF RCTs that have demonstrated mortality or HHF benefits and influence current guidelines. Representation is key to further delineation of sex-specific differences in major trial results. Sustained efforts are warranted to ensure equitable and appropriate inclusion of women in HFrEF trials.

Impact of worsening renal function in patients with incident heart failure across the spectrum of ejection fraction: a population-based longitudinal study

Abstract Background Renal dysfunction is a common occurrence in patients with heart failure (HF) and may impact on HF treatment and outcomes. HF clinical trial data suggest that worsening renal function (WRF) is associated with worse prognosis, however many of the medications used in HF cause a short-term decline in renal function that may improve in the longer-term. The real-world incidence and implications of WRF following an initial diagnosis of HF across the spectrum of ejection have not been well-characterised. Purpose The present study was designed to establish the incidence and outcomes associated with WRF in patients with incident HF on the risk of mortality and HF hospitalisation (hHF) in a real-world setting. Methods Electronic health records were linked to echocardiography data between 2016 to 2021 to define incident HF with reduced/mildly reduced/preserved EF (HFrEF/HFmrEF/HFpEF). Incidence of WRF at 6 months was determined as a composite endpoint of (i) having two consecutive eGFR declined by 40% or greater; (ii) having an eGFR <15 mL/min/1.73m^2; (iii) on sustained dialysis; or (iv) receiving kidney transplantation. Incidence of hHF and all-cause mortality were compared in HF patients with versus without WRF. We performed a stratified analysis according to baseline renal function (eGFR: >60, 45-59, 30-44, 15-29, or <15 mL/min/1.73m2). Results 4254 individuals were identified, 1100 HFrEF, 650 HFmrEF, 1252 HFpEF, and 1252 HF with unknown EF. Within 6 months of HF diagnosis, 592 patients died and 349 had WRF. Baseline eGFR <60 was present in 32% of individuals with HFrEF, 32% in HFpEF, 27% in HFmrEF, and 37% in HF with unknown EF. The incidence of WRF was similar in HFrEF (20.7 [95% CI: 16.9 – 25.1] per 100 person-years) and in HF with unknown EF (20.9 [17.1 – 25.3]), but was significantly lower in HFmrEF (13.6 [9.8 – 18.4]) and HFpEF (16.8 [13.7 – 20.5]). Patients with WRF were more likely to be female (adjusted hazard ratio [aHR]: 1.32 [1.06 – 1.64], p=0.014), having diabetes (1.34 [1.07 – 1.69], p = 0.012), and with lower baseline renal function (eGFR categories 45-59, 30-44, 15-29, or <15 compared with >60: aHR 1.75 [1.29 – 2.38], p<0.001; 1.64 [1.12 – 2.42], p=0.012; 5.65 [4.06 – 7.87], p<0.001; 90.74 [63.2 – 130.28], p<0.001). Individuals with WRF had significantly higher incidence of subsequent hHF (HR adjusted for age, sex, baseline renal function, and diabetes: 1.79 [1.35 – 2.39], p<0.001) and all-cause death (2.18 [1.66 – 2.88], p<0.001), compared to those without WRF. This was driven by patients diagnosed with HFrEF (2.46 [1.45 – 4.18], p<0.001) or HFpEF (3.45 [2.21 – 5.40], p<0.001), but was not seen in HFmrEF (1.91 [0.91 – 3.99], p=0.086) or HF within unknown EF (1.28 [0.65 – 2.52], p=0.484). Conclusion WRF is an important and common consequence following initial diagnosis of HF across the spectrum of EF with associated severe clinical outcomes in HF. Priority should be given to prevention of WRF in patients with incident HF.Impact of WRF on Clinical Outcomes

Abstract 12936: Quality of Life Assessments as Inclusion Criteria in Heart Failure Clinical Trials

Background: Patient-reported quality of life (QoL) assessments, such as the Kansas City Cardiomyopathy Questionnaire (KCCQ) or Minnesota Living with Heart Failure Questionnaire (MLHFQ), reflect an individual’s health status and symptom severity at a given timepoint, and may have utility as inclusion criteria in heart failure (HF) clinical trials. Method: The Heart Failure Collaboratory-Academic Research Consortium, a group of stakeholders including patients, investigators, and representatives from government and industry, convened to review data from multiple HF clinical trials discuss the use of patient reported QoL-based inclusion criteria in clinical trials of HF. Result: Patient-reported QoL assessments, such as the KCCQ, have high test-retest reliability and, in contrast with the physician-assigned New York Heart Association (NYHA) class, are not subject to clinician bias or influenced by knowledge of prognostic variables such as Left Ventricular Ejection Fraction (LVEF) or N-terminal pro B-type Natriuretic Peptide (NT-proBNP). The U.S. FDA has qualified KCCQ as an effective clinical outcomes assessment for HF, and recent clinical trials that demonstrated substantial reductions in morbidity and mortality also showed improvements in KCCQ scores, provided patients had a decrement at baseline. However, KCCQ use is limited by both complicated clinical interpretability, with total symptom score consisting of aggregate scores from different physical and symptomatic domains and uncertainty around the threshold of clinically important difference, and by its length, with average completion time of 5 to 8 minutes. Conclusion: Patient-reported functional assessments have potential as inclusion criteria in clinical trials of HF by ensuring the enrollment of patients with a diminished QoL who have the potential to improve in response to therapeutic intervention, especially in clinical trials with QoL-based endpoints.

Abstract 18005: Underrepresentation of Women in Clinical Trials of Heart Failure With Reduced Ejection Fraction

Background: There are established sex-specific differences in heart failure with reduced ejection fraction (HFrEF) outcomes. Randomized clinical trials (RCTs) based on cardiovascular outcome benefits, typically either reduced cardiovascular mortality or hospitalization for heart failure (HHF), and influence current guidelines for therapy. Objectives: To evaluate the representation of women in HFrEF RCTs that observed reduced all-cause or cardiovascular mortality or HHF. Methods: We queried Excerpta Medica dataBASE, Medical Literature Analysis and Retrieval System Online, Cumulative Index to Nursing and Allied Health Literature, and PubMed for HFrEF RCTs that reported a statistically significant benefit of intervention resulting in improved mortality or HHF published from 1980 to 2021. We estimated representation using the participation-to-prevalence ratio (PPR). PPR was calculated based on the proportion of women with HFrEF in the Framingham cohort (40%). A PPR of 0.8 to 1.2 was considered representative. Results: The final analysis included 33 RCTs. All trials except two were mentioned in the 2022 American College of Cardiology/American Heart Association/Heart Failure Society of America Guidelines for the Management of Heart Failure. Women represented 23.2% of enrolled participants (n = 24,363/ 104,972), ranging from 11.4% to 40.1% per-trial. Overall PPR was 0.58, with per-trial estimates ranging from 0.29 - 1.00. Five trials (15.2%) had a PPR of women representative of the disease population. Representation didn’t change significantly by the decade examined. The proportion of women in North American and Multiregional trials was significantly greater than in trials conducted in Europe (p = 0.04). The proportion of women was greater in industry trials compared to government-funded trials (p = 0.05). Conclusions: Women are underrepresented in HFrEF RCTs that have demonstrated mortality or HHF benefits, which may affect the sex-specific generalizability of major trial results. Sustained efforts are warranted to ensure equitable and appropriate inclusion of women in HFrEF trials.

Abstract 17493: Racial/Ethnic Under-Representation in Early Phase Clinical Trials

Introduction: There is severe underrepresentation of racial and ethnic groups in many cardiovascular clinical trials. Early-phase clinical trials examine the action and safety limits of treatment and thus, underrepresentation may have particularly deleterious effects. Hypothesis: Ethnic and Racial groups are underrepresented in early-phase trials. Methods: Using the clinicaltrials.gov database, we examined the racial and ethnic representation in Phases 1, 2, 3, and 4 in completed heart failure clinical trials (N=89) with reported results from 2016-2021. We examined the proportion of trials with a representation equal or greater than % U.S. Census population (12% for African American (AA), 19% for Hispanic/Latino (HL), and 7% for Asian (AN)) and determined the median trial representation percentage for AA, HL, and AN groups. Using Chi-square analysis we compared the percent representation across the trial phases. Results: We found that 49%, 91%, and 87% Phase 1 and 2 trials have a lower AA, HL, and AN representation, respectively, compared to that in the U.S. Population (Table 1). HL and AN representation in Phase 1 and 2 trials is particularly low. There is significant variation in AA, HL, and AN representation across all trial phases(p<0.001). Conclusions: Significant underrepresentation of racial and ethnic groups persist in contemporary Phase 1 and 2 trials. Efforts to create a standard for collecting and reporting demographics along with increasing racial and ethnic group representation closer to US population may reduce the risk of future adverse events.

Abstract 14640: Community Socioeconomic Distress is Associated With Poor Access to Heart Failure Clinical Trials in the United States

Introduction: Clinical trials have historically lacked representation from minorities and individuals from lower socioeconomic backgrounds. Little is known about the role geographic access plays in recruiting diverse populations for clinical trials. Objectives: Given disparities in clinical trial enrollment, we sought to analyze how access to heart failure trials varies across demographic groups. Methods: We queried clinicaltrials.gov for trials classified under “heart failure” that are recruiting and enrolling adult patients. Trial site addresses were obtained using Google Maps. We calculated drive times from each US census tract to the closest trial site using ArcGIS Pro v3.1. Demographic information and urban / rural statuses for census tracts were obtained from the US Census Bureau. Distressed Community Index (DCI) scores (0 = no distress, 100 = severe distress) based on metrics including education level, poverty, and unemployment were collected. Data were analyzed using Python v3.8. Results: We identified 954 heart failure trials with 644 unique sites in the US. About 54% of the rural population lives more than 30 minutes from a trial site compared to 22% of the urban population (OR 0.23; p < 0.001). Analysis of DCI scores covering 328 million people revealed that drive times increase with higher socioeconomic distress ( p < 0.001; Figure). In both urban and rural settings, median drive times for individuals in the top 10% of distressed communities (56 min urban and 79 rural) are more than three times those of individuals in the lowest 10% of distressed communities (18 min urban and 23 rural). A larger proportion of non-white minorities live less than 30 minutes from a trial site compared to the white population (77% vs. 60%; OR 2.23; p < 0.001). Conclusions: Increased socioeconomic distress is associated with worse access to heart failure trial sites for both urban and rural populations. Geographic barriers should be addressed to improve diversity in trials.

Istaroxime: A Novel Therapeutic Agent for Acute Heart Failure.

Acute decompensated heart failure (ADHF) is a multifactorial process that is associated with high morbidity and mortality. Treatment with inotropes can rapidly improve hemodynamic status; however, their use has been associated with increased mortality and incidence of arrhythmias. Istaroxime is a first-in-class intravenous agent currently undergoing clinical trials for acute heart failure. It has the unique mechanism of action of both Na+/K+ ATPase inhibition and sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a stimulation. Notably, its action on sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a improves calcium handling, which is known to be abnormal in heart failure. Clinical trials have shown that istaroxime has beneficial hemodynamic effects; in particular, its ability to increase systolic blood pressure without causing significant increases in heart rate or clinically significant arrhythmias differentiates it from inotropes currently utilized for ADHF treatment, such as milrinone. While initial studies are encouraging, additional trials are needed to assess outcomes and to compare their performance to standard inotropes in patients hospitalized with ADHF. This article will review the relevant preclinical and clinical trials for istaroxime, as well as the relevant pharmacology.

Examining the Landscape of Surrogate Outcomes in Clinical Trials of Heart Failure With Preserved Ejection Fraction (HFpEF) Patients: A Narrative Review

Examining the Landscape of Surrogate Outcomes in Clinical Trials of Heart Failure With Preserved Ejection Fraction (HFpEF) Patients: A Narrative Review

Improving cardiovascular outcomes for patients with heart failure in sub-Saharan Africa: conference proceedings of the 2022 Nigerian Cardiovascular Symposium.

The Nigerian Cardiovascular Symposium is an annual conference held in partnership with cardiologists in Nigeria and the diaspora to provide updates in cardiovascular medicine and cardiothoracic surgery with the aim of optimising cardiovascular care for the Nigerian population. This virtual conference (due to the COVID-19 pandemic) has created an opportunity for effective capacity building of the Nigerian cardiology workforce. The objective of the conference was for experts to provide updates on current trends, clinical trials and innovations in heart failure, selected cardiomyopathies such as hypertrophic cardiomyopathy and cardiac amyloidosis, pulmonary hypertension, cardiogenic shock, left ventricular assist devices and heart transplantation. Furthermore, the conference aimed to equip the Nigerian cardiovascular workforce with skills and knowledge to optimise the delivery of effective cardiovascular care, with the hope of curbing 'medical tourism' and the current 'brain drain' in Nigeria. Challenges to optimal cardiovascular care in Nigeria include workforce shortage, limited capacity of intensive care units, and availability of medications. This partnership represents a key first step in addressing these challenges. Future action items include enhanced collaboration between cardiologists in Nigeria and the diaspora, advancing participation and enrollment of African patients in global heart failure clinical trials, and the urgent need to develop heart failure clinical practice guidelines for Nigerian patients.

Sex Differences in the Generalizability of Randomized Clinical Trials in Heart Failure with Reduced Ejection Fraction.

To understand how sex differences impact the generalizability of randomized controlled trials (RCTs) in patients with heart failure and reduced ejection fraction (HFrEF, we sought to compare clinical characteristics and clinical outcomes between RCTs and HF observational registries stratified by sex. Data from 2 HF registries and 5 HFrEF RCTs were used to create three subpopulations: one RCT population (n=16,917; 21.7% females), registry patients eligible for RCT inclusion (n=26,104; 31.8% females), and registry patients ineligible for RCT inclusion (n=20,910; 30.2% females). Clinical endpoints included all-cause mortality, CV mortality, and first HF hospitalization at one-year. Males and females were equally eligible for trial enrollment (56.9% of females and 55.1% of males in the registries). One-year mortality rates were 5.6%, 14.0%, and 28.6% for females and 6.9%, 10.7%, and 24.6% for males in the RCT, RCT-eligible, and RCT-ineligible groups. After adjusting for 11 HF prognostic variables, RCT females showed higher survival compared to RCT-eligible females (Standardized mortality ratio (SMR) 0.72; 95% CI 0.62 - 0.83), while RCT males showed higher adjusted mortality rates compared to RCT-eligible males (SMR 1.16; 95% CI 1.09-1.24). Similar results were also found for cardiovascular mortality (SMR 0.89; 95%CI 0.76-1.03 for females, SMR 1.43; 95%CI 1.33-1.53 for males). Generalizability of HFrEF RCTs differed substantially between the sexes, with females having lower trial participation and females trial participants having lower mortality rates compared to similar females in the registries, while males had higher than expected cardiovascular mortality rates in RCTs compared to similar males in registries. This article is protected by copyright. All rights reserved.

Characteristics of United States Counties in Which Heart Failure Clinical Trials of Pharmacotherapy Were Conducted.

HomeCirculation: Heart FailureAhead of PrintCharacteristics of United States Counties in Which Heart Failure Clinical Trials of Pharmacotherapy Were Conducted No AccessResearch ArticleRequest AccessAboutView PDFSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toNo AccessResearch ArticleRequest AccessCharacteristics of United States Counties in Which Heart Failure Clinical Trials of Pharmacotherapy Were Conducted Elisabeth Cox, Muath A. Alsalloum, Marin Vander Schaaf, Abdulaziz S. Alfehaid, Marwah E. Alnewais and Erin R. Weeda Elisabeth CoxElisabeth Cox Medical University of South Carolina College of Pharmacy, Charleston (E.C., M.A.A., M.V.S., A.S.A., M.E.A., E.R.W.). Search for more papers by this author , Muath A. AlsalloumMuath A. Alsalloum Medical University of South Carolina College of Pharmacy, Charleston (E.C., M.A.A., M.V.S., A.S.A., M.E.A., E.R.W.). Department of Pharmacy Practice, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia (M.A.A.). Search for more papers by this author , Marin Vander SchaafMarin Vander Schaaf Medical University of South Carolina College of Pharmacy, Charleston (E.C., M.A.A., M.V.S., A.S.A., M.E.A., E.R.W.). Search for more papers by this author , Abdulaziz S. AlfehaidAbdulaziz S. Alfehaid Medical University of South Carolina College of Pharmacy, Charleston (E.C., M.A.A., M.V.S., A.S.A., M.E.A., E.R.W.). Pharmaceutical Care Services, King Faisal General Hospital, Alahsa Health Cluster, Ministry of Health, Saudi Arabia (A.S.A.). Search for more papers by this author , Marwah E. AlnewaisMarwah E. Alnewais Medical University of South Carolina College of Pharmacy, Charleston (E.C., M.A.A., M.V.S., A.S.A., M.E.A., E.R.W.). College of Clinical Pharmacy, King Faisal University, Alahsa, Saudi Arabia (M.E.A.). Search for more papers by this author and Erin R. WeedaErin R. Weeda Correspondence to: Erin R. Weeda, PharmD, Medical University of South Carolina, Department of Clinical Pharmacy and Outcomes Sciences, 280 Calhoun St, QE213C MSC140, Charleston, SC 29425. Email E-mail Address: [email protected] https://orcid.org/0000-0001-7876-5802 Medical University of South Carolina College of Pharmacy, Charleston (E.C., M.A.A., M.V.S., A.S.A., M.E.A., E.R.W.). Search for more papers by this author Originally published16 May 2023Circulation: Heart Failure. 2023;0:e010449FootnotesThis work was conducted at the Medical University of South Carolina.For Sources of Funding and Disclosures, see page XXX.Correspondence to: Erin R. Weeda, PharmD, Medical University of South Carolina, Department of Clinical Pharmacy and Outcomes Sciences, 280 Calhoun St, QE213C MSC140, Charleston, SC 29425. Email [email protected]edu Previous Back to top Next FiguresReferencesRelatedDetails Advertisement Article InformationMetrics © 2023 American Heart Association, Inc.PMID: 37191025 Originally publishedMay 16, 2023 Keywordsapplicabilitysocial determinants of healthdiversitygeneralizableruralclinical trialsexternal validityPDF download Advertisement SubjectsHeart Failure

Editorial introductions.

Current Opinion in Cardiology was launched in 1985. It is part of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of cardiology is divided into 14 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Editor and Section Editors for this issue. SECTION EDITORS Ali J MarianAli J MarianDr Marian received his training in clinical cardiology and human molecular genetics at Baylor College of Medicine, Houston, USA. He was appointed as a faculty at the Section of Cardiology at Baylor College of Medicine, Houston, USA in 1992. He joined the Institute of Molecular Medicine in 2006 to lead the Center for Cardiovascular Genetics. Dr Marian is recognized for his research achievements in molecular genetics and clinical aspects of cardiomyopathies. He has published over 200 articles in peer-reviewed journals, which collectively have garnered over 12,000 citations and an H index of 60. He received the Young Investigator Award from the American College of Cardiology, the Established Investigator Award from the American Heart Association, the Clinician-Scientist Award in Translational Research from Burroughs Wellcome Fund, Distinguished Scientist Award from Baylor St Luke's Medical Center, and the Best Editor Award from the American Heart Association Circulation Research. Dr Marian is currently a Deputy Editor for Cardiovascular Research, Section Editor on Genetics for Current Opinion in Cardiology, and the Editor-in-Chief of The Journal of Cardiovascular Aging. He is a former Deputy Editor for Circulation Research, Associate Editor for Circulation and European Journal of Clinical Investigation. Dr Marian's research is supported by R01 grants from the NHLBI-NIH, Leducq Foundation Trans-Atlantic Network of Excellence, and local foundations. Gene KimGene KimDr Kim is a cardiologist with the Advanced heart failure, Cardiac transplant, and Mechanical Circulatory Support Program at the University of Chicago Medicine, USA. He is an Associate Professor of Medicine and the Advanced Heart Failure Fellowship Program Director. His medical school, residency, and fellowship training were completed at the University of Chicago, USA. Dr Kim also directs the Genetic Cardiomyopathy and Hypertrophic Cardiomyopathy Clinics at University of Chicago, USA. Dr Kim's research interests include the genetic and epigenetic regulation of heart failure and arrhythmogenesis with publications on the role of microRNAs in cardiomyopathy. His interests also include myocardial recovery, extracellular matrix in failing myocardium. He has published over 100 articles and book chapters and is an investigator in numerous clinical trials. Bhavadharini RamuBhavadharini RamuDr Bhavadharini (Dharini) Ramu is an Advanced Heart Failure & Transplant Cardiologist, Director of the Cardio-Obstetrics Program and an Associate Professor of Medicine at the University of Minnesota, USA. She completed her internal medicine residency and cardiology fellowship at the University of Connecticut, USA followed by Advanced Heart Failure Fellowship at the University of Minnesota, USA in 2016. She previously served on the faculty at the Medical University of South Carolina, USA from 2016 to 2023. Dr Ramu has been an invited faculty lecturer at scientific meetings of the American College of Cardiology (ACC), Heart Failure Society of America, American Society of Transplantation, and International Society of Heart & Lung Transplantation. She is a member of the ACC's Heart Failure & Transplant Section Leadership Council, the program planning committee for the ACC's Scientific Sessions, and serves on the leadership council of the Women in Heart Transplantation & MCS Network. Dr Ramu's research interests include increasing the understanding of and reducing the impact of health-related disparities in patients with advanced heart failure, with a goal of reducing health inequities and improving the health of disadvantaged and vulnerable populations. She has served as a peer reviewer for many journals and is an investigator in heart failure clinical trials.

Soluble Guanylate Cyclase Activators and Stimulators in Patients with Heart Failure

This review sought to summarize the current emerging soluble guanylate cyclase activators and stimulators in patients with heart failure, both heart failure with reduced and preserved ejection fraction, to provide a reference for soluble guanylate cyclase activators and stimulators discovery. Heart failure is a common disease with considerable morbidity, hospitalization, and mortality Soluble guanylate cyclase is a key enzyme in the nitric oxide signaling pathway and has attracted rapidly growing interest as a therapeutic target in heart failure. Currently, several soluble guanylate cyclase agonists are in clinical development. Cinaciguat and praliciguat have shown no clear clinical benefit in patients with heart failure in clinical trials. Riociguat increased the 6-min walk distance, cardiac index, and stroke volume index as well as decreased N-terminal pro-B-type natriuretic peptide. Although these populations cover nearly every range of ejection fractions, these were not clinical trials directly in patients with heart failure but were designed in patients with pulmonary hypertension. Vericiguat is recommended in the latest American guideline for patients with heart failure with reduced ejection fraction; however, it gets mixed results in patients with heart failure with preserved ejection fraction. To date, only vericiguat reduces the composite of death from cardiovascular causes or first hospitalization for heart failure in patients with heart failure with reduced ejection fraction and riociguat might improve clinical symptoms and quality of life in patients with heart failure, both heart failure with reduced and preserved ejection fraction. We need more exploration about soluble guanylate cyclase activators and stimulators in patients with heart failure.

Characteristics Of Heart Failure Clinical Trials Registered In Clinicaltrials.gov- A Cross Sectional Analysis

Characteristics Of Heart Failure Clinical Trials Registered In Clinicaltrials.gov- A Cross Sectional Analysis