Table 2.

Inclusion and exclusion criteria

Inclusion criteria

1.Adults ≥18 years of age

2.Confirmed diagnosis of hypertrophic cardiomyopathy

3.Agreement to be a participant in the study protocol and willing/able to return for follow‐up

4.Able to provide written informed consent

5.In women of childbearing age: Willingness to use a highly effective contraceptive method (failure rate per year <1%)

Exclusion criteria

1.Less than 3 months postseptal reduction therapy (surgery or catheter‐based intervention)

2.Clinical cardiac decompensation in the previous 3 months, defined as New York Heart Association class IV congestive heart failure symptoms

3.Resting blood pressure >180/100 mmHg or systolic blood pressure <100 mmHg

4.Hypotensive response to exercise testing (≥20 mmHg decrease of systolic blood pressure from baseline blood pressure or an initial increase in systolic blood pressure followed by a decrease of systolic blood pressure ≥20 mmHg)

5.Concomitant use of angiotensin converting inhibitors or angiotensin receptor blockers; patients previously receiving angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker therapy will require a 36‐hour washout period before initiation of Sacubitril/Valsartan

6.Resting left ventricular outflow tract gradient >50 mmHg

7.Left ventricular ejection fraction <50% by echocardiography

8.Implanted pacemaker or cardio‐defibrillator in the last 3 months or scheduled

9.History of hyperkalemia (serum potassium >5.2 mmol/L)

10.Renal insufficiency with a glomerular filtration rate <30 mL/min per 1.73 m2

11.Present or planned pregnancy

12.Life expectancy less than 12 months

13.Patients with severe adipositas (adipositas permagna, body mass index >40 kg/m2)

14.History of exercise induced syncope or sustained ventricular arrhythmias

15.Inability to exercise due to orthopedic or other noncardiovascular limitations

16.Use of other investigational drugs at the time of enrolment

17.Concomitant treatment with aliskiren‐containing drugs; discontinuation of treatment with aliskiren‐containing drugs is required before initiation of Sacubitril/Valsartan

18.History of angiotensin converting inhibitors‐ or angiotensin receptor blockers‐induced angioedema or history of hereditary or idiopathic angioedema

19.Evidence of hepatic disease as determined by any one of the following: AST or ALT values exceeding 2× ULN, severe hepatic insufficiency (classification Child Pugh C), biliary cirrhosis, cholestasis (current or anamnesic evidence), history of hepatic encephalopathy, history of esophageal varices, or history of portocaval shunt

20.Any surgical or medical condition that in the opinion of the investigator may place the patient at higher risk from his/her participation in the study or is likely to prevent the patient from complying with the requirements of the study or completing the study

21.History of noncompliance to medical regimens and patients who are considered potentially unreliable

22.History or evidence of drug or alcohol abuse within the past 12 months

23.History of malignancy of any organ system (other than localized basal or squamous cell carcinoma of the skin or localized prostate cancer), treated or untreated, within the past 2 years, regardless of whether there is evidence of local recurrence or metastases

24.Life‐threatening or uncontrolled dysrhythmia, including symptomatic or sustained ventricular tachycardia and AF or atrial flutter with a resting ventricular rate >110 beats per minute