(A) Native heart of a patient with end-stage HCM who underwent transplantation. Large areas of gross macroscopic scarring are evident throughout the LV myocardium (white arrows). (B) Intramural coronary artery in cross-section showing thickened intimal and medial layers of the vessel wall associated with small luminal area. (C) Area of myocardium with numerous abnormal intramural coronary arteries within a region of scarring, adjacent to an area of normal myocardium. Original magnification x55. Reprinted, with permission, from Maron et al. (38). HCM = hypertrophic cardiomyopathy; LV = left ventricular.

Abnormal microvascular remodeling promotes blunted myocardial blood flow leading to myocardial ischemia, fibrosis, and adverse LV remodeling in HCM. Abbreviations as in Figure 1.

(A and B) A 23-year-old patient with HCM and massive asymmetric ventricular septal hypertrophy (wall thickness 39 mm). At baseline (A), an area of reduced ¹³N-ammonia uptake by PET can be seen at the base of the anterior papillary muscle (11 o'clock position; arrow). (B) PET after dipyridamole stress, in which myocardial blood flow increases more substantially in the subepicardial than in the subendocardial ventricular septum (VS) as well as the contiguous anterior LV wall (Ant. FW). (C and D) Relationship of abnormal myocardial blood flow by PET and areas of myocardial fibrosis by contrast-enhanced CMR. (C) A PET short-axis slice at the basal LV level in a patient with HCM, with color scale showing highest myocardial blood flow in red and lowest in green. (D) In the same patient, after intravenous infusion of gadolinium, a corresponding short-axis contrast-enhanced CMR image showing areas of late gadolinium enhancement (bright) that match closely to the identical areas of abnormal myocardial blood flow by PET. Reprinted, with permission, from Sotgia et al. (65). CMR = cardiovascular magnetic resonance; PET = positron emission tomography; other abbreviations as in Figure 1.

(A) Comparison of LV end-diastolic dimension and ejection fraction at the time of PET study and at final evaluation expressed as tertiles of myocardial blood flow after dipyridamole infusion. Those patients with a dipyridamole myocardial blood flow value in the lowest tertile showed the greatest change in cavity size and ejection fraction. Vertical bars indicate mean ± SD for each group. *p < 0.05 versus same group at the time of PET scan; p < 0.05 versus patients in the highest tertile; p < 0.05 versus patients in other tertiles. Reprinted, with permission, from Olivotto et al. (72). (B) Evidence that myocardial blood flow by PET predicts adverse disease outcome in patients with HCM. Cardiovascular mortality was highest in those HCM patients with a dipyridamole myocardial blood flow value in the lowest tertile of myocardial blood flow. Reprinted, with permission, from Cecchi et al. (12). PET = positron emission tomography; other abbreviations as in Figure 1.

*Consideration could be given to assessing myocardial ischemia in select HCM patients if concern persists with regard to prognosis after conventional risk assessment. **If suspicion is sufficiently high for epicardial coronary artery disease, coronary angiography (or alternatively computed tomographic angiography) may be indicated to exclude obstructive coronary artery disease or other anatomic causes of chest pain (e.g., myocardial bridging or congenital coronary artery anomalies). Although there are presently insufficient clinical data to support a firm recommendation for angiotensin-converting enzyme inhibitors or aldosterone inhibitors in patients with HCM, these drugs may be considered based on studies in HCM transgenic mouse models of HCM. The assessment of active ischemia using stress CMR is an evolving area, and at present there are no data with this technique relating ischemia to clinical outcome. ACE = angiotensin-converting enzyme; CMR = cardiovascular magnetic resonance; ICD = implantable cardioverter-defibrillator; LGE = late gadolinium enhancement; LV = left ventricle; MBF = myocardial blood flow; PET = positron emission tomography; SCD = sudden cardiac death; SPECT = single-photon emission computed tomography; other abbreviations as in Figure 1.