Hypertensive Heart Disease
Conditions
Brief summary
In Singapore, hypertension is very common in the adult population. Hypertensive heart disease is a leading cause of heart failure and cardiovascular death. Current management relies primarily on achieving blood pressure targets. However, the optimal blood pressure goals are controversial and there are inherent difficulties in measuring blood pressure using external devices applied to peripheral arteries. As a result of (usually longstanding) hypertension, the heart thickens (i.e. hypertrophies) to maintain function. Ultimately, HF may occur due to long standing energy deficits, muscle injury/death and diffuse interstitial fibrosis (heart muscle scarring). In an ongoing study (REMODEL, ClinicalTrial.gov Identifier NCT02670031), we have been able to undertake preliminary analyses with respect to factors associated with the development of fibrosis. In this randomize controlled trial, we will be examining a novel therapy that has the potential to induce regression cardiac hypertrophy and fibrosis.
Interventions
DRUGEntresto
Entresto (Valsartan/sacubitril) 100mg once a day, up-titrating to 200mg or maximum 400mg to achieve target systolic blood pressure below 140 mmHg, over a duration of 52 weeks. If necessary, amlodipine and/or hydrochlorothiazide may be added to achieve target systolic blood pressure.
DRUGValsartan
Valsartan 40mg once a day, up-titrating to 80 or maximum 160 mg to achieve target systolic blood pressure below 140mmHg, over a duration of 52 weeks. If necessary, amlodipine and/or hydrochlorothiazide may be added to achieve target systolic blood pressure.
Sponsors
National Medical Research Council (NMRC), Singapore
National Heart Centre Singapore
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Increased left ventricular mass on cardiovascular magnetic resonance (based on established local age- and sex-specific CMR ranges) * Essential hypertension
Exclusion criteria
* Known secondary causes of hypertension * Previous intolerance to angiotensin receptor blockers * History of heart failure * Stage IV/V chronic renal disease (eGFR \< 30ml/min/1.73m2) * Patients with serum potassium \> 5.2 mmol/L (mEg/L) at Visit 1 * History of cardiovascular events (myocardial infarction, strokes and transient ischemic attacks) * Known atrial fibrillation * Being unable to understand or comply with study procedures (including CMR) * History or presence of any other disease with a life expectancy of \< 3 years * Pregnant or nursing (lactating) women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fibrosis volume | 52 weeks | A difference in terms of change in interstitial volume from baseline following 52 weeks of treatment. Extracellular volume fraction (ECV) will be quantified from native and post-contrast myocardial T1. Fibrosis volume is defined as ECV x myocardial volume and indexed to body surface area (ml/m2) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Left ventricular mass measured on CMR | 52 weeks | Changes from baseline in left ventricular mass, indexed to body surface area (g/m2). |
| Biomarker/biochemistry | 52 weeks | Identify potential markers as indicators of cardiac structural effects of ARNi and ARB |
Countries
Singapore
Outcome results
None listed