scholarly journals Study Design and Rationale of EXPLORER-HCM

2020 ◽  
Vol 13 (6) ◽  
Author(s):  
Carolyn Y. Ho ◽  
Iacopo Olivotto ◽  
Daniel Jacoby ◽  
Steven J. Lester ◽  
Matthew Roe ◽  
...  
Keyword(s):  
New York ◽  
Oxygen Consumption ◽  
Exercise Capacity ◽  
Heart Association ◽  
Outflow Tract ◽  
Peak Oxygen Consumption ◽  
York Heart Association Class ◽  
Phase 3 ◽  
Association Class ◽  
New York Heart Association

Background: Obstructive hypertrophic cardiomyopathy (oHCM) is characterized by unexplained left ventricular (LV) hypertrophy associated with dynamic LV outflow tract obstruction. Current medical therapies are nonspecific and have limited efficacy in relieving symptoms. Mavacamten is a first-in-class targeted inhibitor of cardiac myosin, which has been shown to reduce LV outflow tract obstruction, improve exercise capacity, and relieve symptoms of oHCM in the PIONEER-HCM phase 2 study. Methods: EXPLORER-HCM is a multicenter, phase 3, randomized, double-blind, placebo-controlled trial to investigate the efficacy and safety of mavacamten in treating symptomatic oHCM. Eligible adults with oHCM and New York Heart Association Functional Class II or III are randomized 1:1 to receive once-daily, oral mavacamten, or matching placebo for 30 weeks. The primary composite functional end point is clinical response at week 30 compared to baseline defined as either (1) an increase in peak oxygen consumption ≥1.5 mL/kg/min and reduction of at least one New York Heart Association class; or (2) an improvement of ≥3.0 mL/kg/min in peak oxygen consumption with no worsening of New York Heart Association class. Secondary end points include change in postexercise LV outflow tract gradient, New York Heart Association class, peak oxygen consumption, and patient-reported outcomes assessed by the Kansas City Cardiomyopathy Questionnaire and a novel HCM-specific instrument. Exploratory end points aim to characterize the effect of mavacamten on multiple aspects of oHCM pathophysiology. Conclusions: EXPLORER-HCM is a phase 3 trial in oHCM testing a first-in-class, targeted strategy of myosin inhibition to improve symptom burden and exercise capacity through reducing LV outflow tract obstruction. Results of this trial will provide evidence to support the first disease-specific treatment for HCM. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03470545.

Transcatheter Aortic Valve Replacement for Degenerated Transcatheter Aortic Valves: The TRANSIT International Project

2021 ◽  
Author(s):  
Luca Testa ◽  
Mauro Agnifili ◽  
Nicolas M. Van Mieghem ◽  
Didier Tchétché ◽  
Anita W. Asgar ◽  
...  
Keyword(s):  
New York ◽  
Transcatheter Aortic Valve Replacement ◽  
Heart Association ◽  
York Heart Association Class ◽  
Class Iii ◽  
Transcatheter Aortic Valve ◽  
Significant Difference ◽  
Association Class ◽  
New York Heart Association ◽  
Overall Mortality

Background: Transcatheter aortic valve replacement (TAVR) has determined a paradigm shift in the treatment of patients with severe aortic stenosis. However, the durability of bioprostheses is still a matter of concern, and little is known about the management of degenerated TAV. We sought to evaluate the outcomes of patients with a degenerated TAV treated by means of a second TAVR. Methods: The TRANSIT is an international registry that included cases of degenerated TAVR from 28 centers. Among around 40 000 patients treated with TAVR in the participating centers, 172 underwent a second TAVR: 57 (33%) for a mainly stenotic degenerated TAV, 97 (56%) for a mainly regurgitant TAV, and 18 (11%) for a combined degeneration. Overall, the rate of New York Heart Association class III/IV at presentation was 73.5%. Results: Valve Academic Research Consortium 2 device success rate was 79%, as a consequence of residual gradient (14%) or regurgitation (7%). At 1 month, the overall mortality rate was 2.9%, while rates of new hospitalization and New York Heart Association class III/IV were 3.6% and 7%, respectively, without significant difference across the groups. At 1 year, the overall mortality rate was 10%, while rates of new hospitalization and New York Heart Association class III/IV were 7.6% and 5.8%, respectively, without significant difference across the groups. No cases of valve thrombosis were recorded. Conclusions: Selected patients with a degenerated TAV may be safely and successfully treated by means of a second TAVR. This finding is of crucial importance for the adoption of the TAVR technology in a lower risk and younger population. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04500964.

scholarly journals Impact of Left Ventricular Function and Heart Failure Symptoms on Outcomes Post Ablation of Atrial Fibrillation in Heart Failure

2020 ◽  
Vol 13 (10) ◽  
Author(s):  
Christian Sohns ◽  
Konstantin Zintl ◽  
Yan Zhao ◽  
Lilas Dagher ◽  
Dietrich Andresen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
New York ◽  
Ventricular Dysfunction ◽  
Heart Association ◽  
Left Ventricular ◽  
Pharmacological Therapy ◽  
York Heart Association Class ◽  
Association Class ◽  
New York Heart Association

Background: Recent data demonstrate promising effects on left ventricular dysfunction and left ventricular ejection fraction (LVEF) improvement following ablation for atrial fibrillation (AF) in patients with heart failure. We sought to study the relationship between LVEF, New York Heart Association class on presentation, and the end points of mortality and heart failure admissions in the CASTLE-AF study (Catheter Ablation for Atrial Fibrillation With Heart Failure) population. Furthermore, predictors for LVEF improvement were examined. Methods: The CASTLE-AF patients with coexisting heart failure and AF (n=363) were randomized in a multicenter prospective controlled fashion to ablation (n=179) versus pharmacological therapy (n=184). Left ventricular function and New York Heart Association class were assessed at baseline (after randomization) and at each follow-up visit. Results: In the ablation arm, a significantly higher number of patients experienced an improvement in their LVEF to >35% at the end of the study (odds ratio, 2.17; P <0.001). Compared with the pharmacological therapy arm, both ablation patient groups with severe (<20%) or moderate/severe (≥20% and <35%) baseline LVEF had a significantly lower number of composite end points (hazard ratio [HR], 0.60; P =0.006), all-cause mortality (HR, 0.54; P =0.019), and cardiovascular hospitalizations (HR, 0.66; P =0.017). In the ablation group, New York Heart Association I/II patients at the time of treatment had the strongest improvement in clinical outcomes (primary end point: HR, 0.43; P <0.001; mortality: HR, 0.30; P =0.001). Conclusions: Compared with pharmacological treatment, AF ablation was associated with a significant improvement in LVEF, independent from the severity of left ventricular dysfunction. AF ablation should be performed at early stages of the patient’s heart failure symptoms.

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