There are currently no therapies that can improve prognosis in cases of heart failure (HF) with preserved ejection fraction (EF). We hypothesized that there is a point of no return after which no response to treatment is noted and that for the prevention of hypertensive HF this point may be determined by left ventricle (LV) strain, in the prevention of hypertensive HF. Here an angiotensin-converting enzyme inhibitor (ACE-I) was initiated based on myocardial strain imaging and its effects were determined in an animal model. Thirty-two male Dahl salt-sensitive rats, age 6weeks, were divided into six experimental groups and compared with low-salt (n=8) and high-salt control groups (n=8). In the early treatment group, ACE-I was administered from the age of 6weeks (n=4); in the longitudinal strain (LS) group, at 10-12weeks when LS impairment was >-21% (n=4); in the circumferential strain (CS) group, at 16-18weeks when CS impairment was >-18% (n=4); and in the EF group, at 20weeks when EF was <55% (n=4). Subsequently, all rats were sacrificed at 23weeks age, the LV and lung weight were measured, and pathologic analyses were performed. At 23weeks of age, the lung and LV weights increased in the high-salt control, EF, and CS groups, whereas the lung and LV weights in the LS and early groups were similar to those in the low-salt control group. The percentage of area of subendocardial fibrosis was >6% in the high-salt control, EF, and CS groups and <3% in the LS, early, and low-salt groups. Serial echocardiography demonstrated LS improvement in the LS group; however, the CS and EF groups showed no differences. Heart failure-related lung congestion was prevented when ACE-I was administered soon after LS impairment, accompanied by suppression of cardiac hypertrophy and fibrosis, thereby suggesting that the point of no return of myocardial remodeling due to hypertension was present after LS but before CS impairment.