Relationship between baseline electrocardiographic measurements and outcomes in patients with high‐risk heart failure: Insights from the <scp>VerICiguaT</scp> Global Study in Subjects with Heart Failure with Reduced Ejection Fraction (<scp>VICTORIA</scp>) trial

Yogasundaram, Haran; Zheng, Yinggan; Ly, Eric; Ezekowitz, Justin; Ponikowski, Piotr; Lam, Carolyn S.P.; O'Connor, Christopher; Blaustein, Robert O.; Roessig, Lothar; Temple, Tracy; Westerhout, Cynthia M.; Armstrong, Paul W.; Sandhu, Roopinder K.; ,

doi:10.1002/ejhf.3021

Cited by 3 publications

(1 citation statement)

References 57 publications

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“…The human equivalent dose was 96 mg/day and 97.2 mg/day, respectively. The clinical dose of vericiguat for treating heart failure (heart failure with reduced ejection fraction and heart failure with preserved ejection fraction) is 10–15 mg/day ( Yogasundaram et al, 2023 ). The clinically effective dose of riociguat in PAH indications is 3.0 mg/day–7.5 mg/day ( Rosenkranz et al, 2015 ).…”

Section: Methodsmentioning

confidence: 99%

Safety, tolerability, pharmacokinetics, and pharmacodynamics of a soluble guanylate cyclase stimulator, HEC95468, in healthy volunteers: a randomized, double-blinded, placebo-controlled phase 1 trial

Gui,

Wang,

et al. 2024

Front. Pharmacol.

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Heart failure is the most costly cardiovascular disorder. New treatments are urgently needed. This study aims to evaluate the safety, pharmacokinetics, and pharmacodynamic profile of HEC95468, a soluble guanylate cyclase (sGC) stimulator, in healthy volunteers. Sixty-two, eighteen, and forty-eight participants were enrolled in the single ascending dose (SAD) study, the food effect (FE) study, and the multiple ascending dose (MAD) study, respectively. The study conforms to good clinical practice and the Declaration of Helsinki. Overall, HEC95468 was safe and tolerable; a higher proportion of HEC95468-treated participants reported mild headaches, dizziness, decreased blood pressure, increased heart rate, and gastrointestinal-related treatment-emergent adverse events (TEAEs), similar to the sGC stimulators riociguat and vericiguat. In terms of pharmacokinetic parameters, the maximum observed plasma concentration (Cmax) and the area under the concentration-time curve (AUC0-t) were dose-proportional over the dose range. Moderate accumulation was observed after multiple administrations of HEC95468. Systolic blood pressure (SBP) and diastolic blood pressure decreased, while 3′,5′-cyclic guanosine monophosphate (cGMP) concentration in plasma increased and heart rate was induced. Vasoactive hormones (renin, angiotensin II, and norepinephrine) in plasma were compensatorily elevated after oral administration. These data supported further clinical trials of HEC95468 in the treatment of heart failure and pulmonary arterial hypertension.Systematic Review Registration:http://www.chinadrugtrials.org.cn, identifier CTR20210064.

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Section: Methodsmentioning

confidence: 99%

Safety, tolerability, pharmacokinetics, and pharmacodynamics of a soluble guanylate cyclase stimulator, HEC95468, in healthy volunteers: a randomized, double-blinded, placebo-controlled phase 1 trial

Gui,

Wang,

et al. 2024

Front. Pharmacol.

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October 2023 at a glance: From prevention to diagnosis, prognosis and treatment of acute decompensation and comorbidities

Tomasoni,

Adamo,

Metra

2023

European J of Heart Fail

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Prevention of heart failure (HF) has a key role in our health care. 1,2 Multivariable prediction models are frequently used to estimate the risk of incident HF. A systematic Bayesian meta-analysis, including 36 studies and 59 models for the prediction of HF, showed their predictive accuracy. However, 77% of model results were at high risk of bias, certainty of evidence was low, and no model had a clinical impact assessment. 3 Monzo et al. 4 investigated the association of aldosterone concentrations with left ventricular (LV) remodelling after acute myocardial infarction (MI) in patients successfully treated by primary percutaneous coronary angioplasty for a first acute ST-elevation MI. LV volumes were measured within 4 days after acute MI using cardiac magnetic resonance and transthoracic echocardiography, 6 months later and, in a subset of cases, 3-9 years later. Aldosterone concentrations were associated with LV remodelling at 6 months, even in patients with an initial LV ejection fraction (LVEF) >40%, but not in the long term follow-up. Heart failure with preserved ejection fractionRecent data are showing the prognostic significance of LV global longitudinal strain (GLS) for the prediction of HF events. 5,6 Brann et al. 7 assessed GLS in patients with HF and preserved ejection fraction (HFpEF). Among the 311 patients studied, 128 (41%) had normal GLS (>-15.8%) and 183 (59%) had reduced GLS (<-15.8%). After a median follow-up of 4.6 years, patients with reduced GLS had a greater rate of the primary composite endpoint of cardiovascular (CV) mortality or HF hospitalization (hazard ratio 1.74, 95% confidence interval 1.3-2.4) and were more likely to develop LV ejection fraction (LVEF) deterioration.The diagnosis of HFpEF remains challenging. 2,[8][9][10] The detection of a pulmonary capillary wedge pressure (PAWP) ≥25 mmHg during exercise is a diagnostic criterion of HFpEF. 2,11,12 The diagnostic value of other diagnostic procedures is unknown. Wernhart et al.

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The electrocardiogram in heart failure trials: Missing in action

Anderson

2024

European J of Heart Fail

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This article refers to 'Effects of dapagliflozin according to QRS duration across the spectrum of left ventricular ejection fraction: An analysis of DAPA-HF and DELIVER' by A. Abdin et al., published in this issue on pages 1952-1963.Abnormally long QRS duration (QRSd) on 12-lead electrocardiogram (ECG) portends poor heart failure (HF) outcomes as discovered decades ago. 1 Recent studies suggest that guideline-directed medical therapy (GDMT) is less effective or ineffective in patients with increased QRSd or a left bundle branch block (LBBB) morphology. 2,3 A retrospective, exploratory analysis from the randomized clinical trial (RCT) Eplerenone in Mild Patients: Hospitalization and SurvIval Study in Heart Failure (EMPHASIS-HF) reported treatment outcomes for patients grouped by QRSd: <120 ms, 120-149 ms and ≥150 ms and QRS morphology: normal, LBBB, and right bundle branch block (RBBB) or intraventricular conduction defect. 4 The investigators concluded that eplerenone consistently reduced the primary endpoint across QRSd and morphology subgroups. However, for the outcome of hospitalization for HF the interaction values bordered on significance (p = 0.06 and p = 0.03, respectively). The hazard ratio (HR) for QRSd ≥150 ms was 1.03 (95% confidence interval [CI] 0.65-1.62) suggesting no benefit and possible harm. For LBBB, the HR was 0.86, substantially higher than for normal (HR 0.58), and the 95% CI encompassed 1.00, suggesting a non-significant benefit of eplerenone compared to placebo for this subgroup. There were similar irregularities among the HRs for other outcomes suggesting uncertain benefit of eplerenone treatment in these subgroups. Reil et al. 5 analysed data from 6505 subjects enrolled in the Systolic Heart failure treatment with the I f inhibitor ivabradine Trial (SHIFT) grouped by presence (n = 912) or absence (n = 5593) of LBBB. Tests for interaction for presence/absence of LBBB and ivabradine/placebo were not significantly different, consistent with homogeneous benefit. However, the HRs for the primary endpoint and HF hospitalizations were highly significant for treatment with ivabradine in patients without LBBB (0.80, p < 0.001 and 0.71, p < 0.001, respectively), but weaker and not significant for patients with LBBB (0.92, p = 0.430

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Relationship between baseline electrocardiographic measurements and outcomes in patients with high‐risk heart failure: Insights from the VerICiguaT Global Study in Subjects with Heart Failure with Reduced Ejection Fraction (VICTORIA) trial

Cited by 3 publications

References 57 publications

Safety, tolerability, pharmacokinetics, and pharmacodynamics of a soluble guanylate cyclase stimulator, HEC95468, in healthy volunteers: a randomized, double-blinded, placebo-controlled phase 1 trial

Safety, tolerability, pharmacokinetics, and pharmacodynamics of a soluble guanylate cyclase stimulator, HEC95468, in healthy volunteers: a randomized, double-blinded, placebo-controlled phase 1 trial

October 2023 at a glance: From prevention to diagnosis, prognosis and treatment of acute decompensation and comorbidities

The electrocardiogram in heart failure trials: Missing in action

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