Carvedilol in HF With Preserved EF

Study Overview
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Brief Summary
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Beta-blockers improve clinical outcomes in heart failure and reduced ejection fraction (HFrEF); but not in those with preserved EF. Global longitudinal strain (GLS) is a prognostic factor independent of left ventricular ejection fraction (LVEF). In a retrospective with 1969 patients with HF and LVEF of ≥40%, beta-blocker was associated with improved survival in those with low GLS (GLS <14%), but not in those with GLS ≥14%. In this prospective, randomized clinical study, the investigators will assess the effect of slow-release carvedilol in patients with HFpEF and hypertension. The primary endpoint is the time-averaged proportional changes in NT-proBNP level and GLS change from baseline to month 6.

Official Title
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Slow-release CArvedilol in Patients With REduced Strain and Preserved Ejection Fraction Heart Failure (CARE-preserved HF): A Prospective Randomized, Double-Blinded, Multicenter Study

Conditions
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Heart Failure With Preserved Ejection Fraction, Beta Blocker, Myocardial Strain

Intervention / Treatment
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* Drug: Carvedilol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age ≥20 yrs symptomatic HFpEF with LVEF≥50% NT-proBNP ≥220 pg/ml (sinus rhythm) or ≥660 pg/ml(AF) (BNP ≥80 pg/ml (sinus rhythm) or ≥240 pg/ml(AF) ) SBP≥140mmHg and/or DBP ≥90mmHg, or if taking anti-hypertensive medication, SBP ≥110mmHg. LAVI≥29(sinus rhythm)/34ml/m2 (AF) or LVMI≥115(male)/95(female) g/m2 meet one the following Average E/e'≥ 9 Septal e' < 7 cm/s Lateral e' <10 cm/s TR velocity > 2.8 m/s PASP > 35 mmHg GLS < 16% Exclusion Criteria: systolic blood pressure < 110 mmHg, or heart rate < 60 beats/min contra-indication to beta-blockers creatinine> 2.4mg/dL amyloidosis, hypertrophic cardiomyopathy with obstruction, severe aortic or mitral valve disease, acute coronary syndrome, Cerebrovascular event within 6 months, PCI within 3 months before AST/ALT >3 x normal upper range

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A prospective, randomized, double-blinded, placebo-controlled study
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Carvedilol-group<br>Patients receiving carvedilol | Drug: Carvedilol<br>* patients randomized to carvedilol group will receive carvedilol-SR.<br>* Other names: carvedilol slow-release (SR);|
| Placebo Comparator: Placebo-group<br>Patients receiving placebo | Drug: Placebo<br>* patients randomized to placebo group will receive placebo.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NT-proBNP change | Time averaged NT-proBNP change from baseline to 6 months | 6 months | 
| GLS change | Change of GLS from baselin to 6 months | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| off-level NT-proBNP | Decrease in NT-proBNP > 10% from baseline to 6 months | 6 months | 
| Mortality | All-cause mortality from baseline to 6 months | 6 months | 
| rehospitalization | rehospitalization from baseline to 6 months | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BNP, HFPEF, beta-blocker, reduced strain