BLOCKade of Calcium Channels and Beta Adrenergic Receptors for the Treatment of Hypertension in HFpEF

Inclusion Criteria:

1. Adults age 18-90 years

2. Diagnosis of hypertension defined by at least two of the following: A) ICD-9 (401.0-404.91) or ICD-10 (I10-I13) codes signifying hypertension; B) Treatment withantihypertensive medication other than a loop diuretic for at least two months; C)History of previous blood pressure readings ≥130/80 mmHg at two separate officevisits

3. Stable antihypertensive therapy; defined as no changes in antihypertensivemedications in the preceding 30 days

4. A diagnosis of heart failure

5. LV ejection fraction >50%

6. Elevated filling pressures defined by at least one of the following criteria: A)Mitral E/e' ratio (lateral or septal) >8 with low e' velocity (septal e' <7 cm/s orlateral e' <10 cm/s) and at least one of the following: a. Enlarged left atrium (LAvolume index >34 ml/m2); b. Chronic loop diuretic use for management of symptoms; c.Elevated natriuretic peptides (BNP levels >100 ng/L or NT-proBNP levels >300 ng/L);B) Mitral E/e' ratio (lateral or septal) >14; C) Previously elevated invasivelydetermined filling pressures based on one of the following criteria: a. RestingLVEDP >16 mmHg; b. Mean PCWP >12 mmHg; c. PCWP or LVEDP ≥25 mmHg with exercise; D)Previous acutely decompensated heart failure requiring IV diuretics;

Exclusion Criteria:

1. Systolic BP meeting any of the following criteria: A) Current office systolic BP <100 mmHg; B) Current office systolic BP 100-119 mmHg if not receiving treatmentwith an antihypertensive agent or if holding antihypertensive medication prior torandomization would be clinically contraindicated, as per the investigator'sclinical judgement; C) Current office systolic BP ≥180 mmHg if not receivingtreatment with a CCB or β-blocker, or ≥160 mmHg if already receiving a CCB and/or β-blocker prior to the pre-randomization wash-out period; D) Orthostatic hypotensiondefined as >20 mmHg decline in office systolic BP 3-5 minutes following thetransition from sitting to standing position

2. Resting heart rate <50 or >100 bpm

3. Contraindication to withholding CCB or β-blocker therapy (e.g. use ofnon-dihydropyridine CCB [diltiazem or verapamil] or β-blocker for rate control foratrial fibrillation) as per the investigator's clinical judgement

4. Children, fetuses, neonates, prisoners, and pregnant women (women of childbearingage will undergo a pregnancy test during the screening visit) are not included inthis research study.

5. Inability/unwillingness to exercise

6. Any the following echocardiographic findings: A) LV ejection fraction <45% on anyprior echocardiogram, unless it was in the setting of uncontrolled atrialfibrillation; B) Hypertrophic, infiltrative, or inflammatory cardiomyopathy; C)Clinically significant pericardial disease, as per investigator judgment; D)Moderate or greater left-sided valvular disease, any degree of mitral stenosis, orprosthetic mitral valve; E) Severe right-sided valvular disease; F) Severe rightventricular dysfunction

7. Active coronary artery disease, defined as any of the following: A) Acute coronarysyndrome or coronary intervention in the past 2 months; B) Ischemia on stresstesting without either subsequent revascularization or a subsequent angiogramdemonstrating the absence of clinically significant epicardial coronary arterydisease, as per investigator judgement

8. Clinically significant lung disease, defined as any of the following: A) ChronicObstructive Pulmonary Disease meeting GOLD criteria stage III or greater; B)Treatment with oral steroids within the past 6 months for an exacerbation ofobstructive lung disease; C) The use of daytime supplemental oxygen

9. Primary pulmonary arteriopathy

10. eGFR <30 mL/min/1.73m2

11. Any medical condition that, under the investigator's discretion, will interfere withsafe completion of the study or validity of the endpoint assessments

12. Known history of an allergy or clinically significant sensitivity (as determined bythe investigator) to either amlodipine besylate or metoprolol succinate