Publications by authors named "Ian Kulac"
Aims: The relationship between body mass index (BMI) and clinical outcomes in patients with cardiovascular disease, including acute heart failure (AHF) and acute myocardial infarction (AMI), remains debated. This study investigates the association between BMI and clinical outcomes within the PARADISE-MI cohort, while also evaluating the impact of angiotensin receptor-neprilysin inhibitor (ARNI) versus angiotensin-converting enzyme inhibitor (ACE-I) treatment on this relationship.
Methods And Results: The analysis included 5589 patients from the PARADISE-MI study with available baseline BMI data.
Background: Finerenone has kidney protective effects in patients with chronic kidney disease (CKD) with type 2 diabetes, but effects on kidney outcomes in patients with heart failure (HF) with and without diabetes and/or CKD are not known.
Objectives: Examine the effects of finerenone on kidney outcomes in FINEARTS-HF, a randomized trial of finerenone vs. placebo among patients with HF with mildly reduced or preserved ejection fraction.
Article Synopsis
- Patients with heart failure (HF) are at an increased risk of hospital readmission and mortality, particularly following a recent worsening heart failure (WHF) event.
- The FINEARTS-HF trial investigated the impact of the drug finerenone on cardiovascular events in HF patients, focusing on their WHF history and timing of treatment initiation.
- Results showed that those treated with finerenone shortly after a WHF event (within 7 days) had a significantly reduced risk of cardiovascular issues compared to the placebo group, indicating timeliness of treatment may influence effectiveness.
Background: Aficamten is a cardiac myosin inhibitor that mitigates left ventricular outflow gradients in obstructive hypertrophic cardiomyopathy (oHCM). The clinical efficacy of aficamten across multiple outcome domains in oHCM has not been fully defined.
Objectives: This responder analysis from the SEQUOIA-HCM (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM) trial characterizes the clinical impact of aficamten.
Article Synopsis
- Patients with heart failure (HF) experience increased risks of health complications, but medications like SGLT2 inhibitors (SGLT2i) and finerenone can help reduce cardiovascular events.
- A study called FINEARTS-HF examined the effects of finerenone in patients with HF and varying ejection fractions, especially looking at those already using SGLT2i.
- Results showed finerenone effectively lowered the primary health risks in patients regardless of whether they were on SGLT2i, indicating that these treatments can be beneficial together.
Article Synopsis
- The SEQUOIA-HCM trial examines the effectiveness of aficamten, a new cardiac myosin inhibitor, in improving exercise capacity in adults suffering from symptomatic obstructive hypertrophic cardiomyopathy (HCM).
- The study involves a double-blind, placebo-controlled design, with participants recruited from 101 sites across 14 countries, focusing on those with objectively measured exertional intolerance.
- The main goal is to assess changes in integrated exercise performance after 24 weeks of treatment using a combination of peak oxygen uptake and ventilation efficiency, along with monitoring clinical health outcomes.
Background: Obstructive hypertrophic cardiomyopathy (oHCM) is characterized by left ventricular (LV) hypertrophy, LV outflow tract obstruction, and left atrial dilation, which can be associated with progressive heart failure, atrial fibrillation, and stroke. Aficamten is a next-in-class cardiac myosin inhibitor that reduces outflow tract obstruction by modulating cardiac contractility, with the potential to reverse pathological remodeling and, in turn, reduce cardiovascular events.
Objectives: This study sought to investigate the effect of aficamten on cardiac remodeling compared with placebo using cardiovascular magnetic resonance (CMR) and its association with key clinical endpoints in the SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM) CMR substudy.
Article Synopsis
- The study analyzed the role of biomarkers NT-proBNP and hs-cTnI in managing obstructive hypertrophic cardiomyopathy (oHCM) and how they relate to treatment effects of aficamten.
- Baseline levels of NT-proBNP correlated with the left ventricular outflow tract gradient (LVOT-G) and diastolic function, while hs-cTnI correlated with left ventricular thickness.
- After 8 weeks of aficamten treatment, NT-proBNP decreased by 79% and hs-cTnI by 41%, with these reductions linked to improvements in heart function, health status, and exercise capacity, suggesting that these biomarkers are useful for tracking treatment response.
Aims: Type 2 diabetes (T2D) and heart failure (HF) frequently coexist, but whether clinical outcomes and treatment effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) vary in relation to background glucose-lowering therapy (GLT) in this population is uncertain.
Methods And Results: DELIVER randomized patients with HF and left ventricular ejection fraction (LVEF) >40% to dapagliflozin or placebo. The primary outcome was a composite of worsening HF (HF hospitalization or urgent HF visit) or cardiovascular death.
Aims: Patients with heart failure (HF) and history of myocardial infarction (MI) face a higher risk of disease progression and clinical events. Whether sodium-glucose cotransporter 2 inhibitors may modify clinical trajectory in such individuals remains incompletely understood.
Methods And Results: The DAPA-HF and DELIVER trials compared dapagliflozin with placebo in patients with symptomatic HF with left ventricular ejection fraction (LVEF) ≤40% and > 40%, respectively.
Article Synopsis
- Sodium glucose cotransporter-2 (SGLT2) inhibitors, like dapagliflozin, are recommended for heart failure treatment, but their economic impact when added to standard care hasn't been thoroughly evaluated.
- A cost-effectiveness analysis was conducted using data from key trials showing that adding dapagliflozin can improve patient quality of life by 0.53 QALYs, with varying cost-effectiveness ratios depending on the price of the drug.
- The results suggest that dapagliflozin can be valuable in treating heart failure, with its cost-effectiveness sensitive to its price and impact on cardiovascular mortality, indicating it remains a beneficial option for patients under certain cost conditions.
Article Synopsis
- Hereditary transthyretin amyloidosis (ATTRv) can lead to complications like polyneuropathy and cardiomyopathy, with eplontersen being investigated for its effects on heart health.
- A study (NEURO-TTRansform) involved 144 participants with ATTRv, some of whom had cardiomyopathy, and found that eplontersen led to significant improvements in heart function compared to a historical placebo group.
- The results showed better left ventricular ejection fraction and stroke volume in the eplontersen group, prompting further research in the ongoing CARDIO-TTRansform trial.
Background: Although beta-blockers are not recommended for the treatment of heart failure with preserved ejection fraction (HFpEF) according to the latest European Society of Cardiology and American Heart Association/American College of Cardiology/Heart Failure Society of America guidelines, these therapies remain commonly used for comorbidity management. There has been concern that beta-blockers may adversely influence clinical outcomes by limiting chronotropic response in HFpEF.
Objectives: This study sought to examine the contemporary use and implications of beta-blockers in patients with heart failure with mildly reduced ejection fraction (HFmrEF) or HFpEF.
Aims: Adrenomedullin is a vasodilatory peptide with a role in microcirculatory and endothelial homeostasis. Adrenomedullin is a substrate for neprilysin and may therefore play a role in beneficial effects of sacubitril/valsartan (Sac/Val) treatment.
Methods And Results: Mid-regional pro-adrenomedullin (MR-proADM) was measured in 156 patients with heart failure with reduced ejection fraction (HFrEF) treated with Sac/Val and 264 patients with heart failure with preserved ejection fraction (HFpEF) randomized to treatment with Sac/Val or valsartan.
Background: Patients with heart failure (HF) have a high burden of multimorbidity, often necessitating numerous medications. There may be clinical concern about introducing another medication, especially among individuals with polypharmacy.
Objectives: This study examined the efficacy and safety of addition of dapagliflozin according to the number of concomitant medications in HF with mildly reduced or preserved ejection fraction.
Aims: Patients with heart failure experience a high burden of symptoms and physical limitations, and poor quality of life. Dapagliflozin reduces heart failure hospitalization and cardiovascular death in patients with reduced, mildly reduced, and preserved ejection fractions. We examined the effects of dapagliflozin on health status, measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ), across the full spectrum of left ventricular ejection fraction (LVEF).
View Article and Find Full Text PDFAims: The PARAGLIDE-HF trial demonstrated reductions in natriuretic peptides with sacubitril/valsartan compared with valsartan in patients with heart failure (HF) with mildly reduced or preserved ejection fraction who had a recent worsening HF event, but was not adequately powered to examine clinical outcomes. PARAGON-HF included a subset of PARAGLIDE-HF-like patients who were recently hospitalized for HF. Participant-level data from PARAGLIDE-HF and PARAGON-HF were pooled to better estimate the efficacy and safety of sacubitril/valsartan in reducing cardiovascular and renal events in HF with mildly reduced or preserved ejection fraction.
View Article and Find Full Text PDFBackground: Patients with heart failure with mildly reduced ejection fraction (HFmrEF) and heart failure with preserved ejection fraction (HFpEF) experience a high burden of symptoms, physical limitations, and poor quality of life; improving health status is a key goal of management.
Objectives: In a prespecified analysis of the DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) trial, we examine effects of dapagliflozin on health status using the Kansas City Cardiomyopathy Questionnaire (KCCQ).
Methods: The DELIVER trial randomized patients with symptomatic HFmrEF/HFpEF to dapagliflozin 10 mg or placebo.
Background: Sodium-glucose cotransporter-2 inhibitors have emerged as a key pharmacotherapy in heart failure (HF) with both reduced and preserved ejection fraction. The benefit of other HF therapies may be modified by sex, but whether sex modifies the treatment effect and safety profile of sodium-glucose cotransporter-2 inhibitors remains unclear. Our analyses aim to assess the effect of sex on the efficacy and safety of dapagliflozin.
View Article and Find Full Text PDFBackground: Patients recently hospitalized for heart failure (HF) are at high risk for rehospitalization and death.
Objectives: The purpose of this study was to investigate clinical outcomes and response to dapagliflozin in patients with HF with mildly reduced or preserved left ventricular ejection fraction (LVEF) who were enrolled during or following hospitalization.
Methods: The DELIVER (Dapagliflozin Evaluation to Improve the LIVES of Patients With PReserved Ejection Fraction Heart Failure) trial randomized patients with HF and LVEF >40% to dapagliflozin or placebo.
Background: The prevalence of heart failure with mildly reduced or preserved ejection fraction markedly increases with age, with older individuals disproportionately facing excess risk for mortality and hospitalization.
Methods: The DELIVER trial (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) randomized patients with New York Heart Association functional class II-IV and left ventricular ejection fraction >40% to either dapagliflozin or placebo for a median follow-up period of 2.3 years.