Patients with HCM with sarcomere myofilament mutations are characterized by more severe impairment of microvascular function and increased prevalence of myocardial fibrosis, compared with genotype-negative individuals. These findings suggest a direct link between sarcomere gene mutations and adverse remodeling of the microcirculation in HCM, accounting for the increased long-term prevalence of ventricular dysfunction and heart failure in genotype-positive patients.

Whether treatment with β blockers (BBs) is of benefit to patients with hypertrophic cardiomyopathy (HC) and provocable outflow obstruction (with none or with only mild heart failure symptoms) is largely unresolved. Thus, we prospectively studied 27 patients with HC (age 36 ± 15 years; 81% men) with New York Heart Association class I or II, without obstruction at rest, but with exercise-induced left ventricular outflow tract (LVOT) gradient of ≥ 30 mm Hg. Patients underwent exercise echocardiography at baseline and after treatment with nadolol (n = 18; 40 to 80 mg/day) or bisoprolol (n = 9; 5 to 10 mg/day), according to a prespecified protocol. Without the BBs, the postexercise LVOT gradient was 87 ± 29 mm Hg and >50 mm Hg in 25 patients (93%). After a 12 ± 4-month period of BB treatment, the postexercise LVOT gradient had decreased to 36 ± 22 mm Hg (p <0.001) and was virtually abolished (to 0 or <30 mm Hg) in 14 patients (52%), substantially blunted (≥ 20 mm Hg reduction) in 9 (33%), and unchanged in only 4 (15%). Severe postexercise obstruction (range 58 to 80 mm Hg) persisted in 6 patients (22% compared to 93% without BBs; p <0.001). Nonresponders (residual postexercise gradient of ≥ 30 mm Hg with BBs) were characterized by an increased body mass index (hazard ratio 2.03/1 kg/m(2), 95% confidence interval 1.2 to 3.4; p <0.05). In conclusion, in patients with HC with mild or no symptoms, treatment with BBs can prevent the development of LVOT obstruction triggered by physiologic exercise. These findings provide a rationale for the novel strategy of early prophylactic pharmacologic treatment with standard, well-tolerated doses of BBs in physically active patients with provocable gradients, aimed at effective prevention of the hemodynamic burden associated with dynamic obstruction.

Microvascular dysfunction can be demonstrated in most patients with hypertrophic cardiomyopathy (HCM), both in the hypertrophied and nonhypertrophied myocardial walls, mostly due to intimal and medial hyperplasia of the intramural coronary arteries and subsequent lumen reduction. As a consequence, regional myocardial ischemia may be triggered by exercise, increased heart rate, or arrhythmias, in areas which are unable to increase myocardial blood flow. In patients with HCM, microvascular dysfunction leading to severe myocardial hypoperfusion during maximal hyperemia represents a strong predictor of unfavorable outcome, left ventricular remodeling with progressive wall thinning, left ventricular dysfunction, and heart failure. Accurate quantitative assessment of microvascular dysfunction and myocardial ischemia is not easily feasible in clinical practice. Although signs of inducible myocardial ischemia may be detected by electrocardiogram, echocardiography, or myocardial scintigraphy, the vasodilator response to dipyridamole by positron emission tomography is considered the method of choice for the assessment of maximal regional and global flow. Cardiac magnetic resonance provides further information, by late gadolinium enhancement (LGE), which may show areas where replacement fibrosis has occurred following microvascular ischemia and focal necrosis. LGE areas colocalize with severe regional microvascular dysfunction, are associated with increased prevalence of ventricular arrhythmias, and show more extensive distribution in the late stages of the disease, when heart failure is the dominant feature. The present review aims to provide a concise overview of the available evidence of microvascular dysfunction and ischemia eventually leading to disease progression and heart failure in HCM patients.

When applying echo-Doppler imaging for either clinical or research purposes it is very important to select the most adequate modality/technology and choose the most reliable and reproducible measurements. Quality control is a mainstay to reduce variability among institutions and operators and must be obtained by using appropriate procedures for data acquisition, storage and interpretation of echo-Doppler data. This goal can be achieved by employing an echo core laboratory (ECL), with the responsibility for standardizing image acquisition processes (performed at the peripheral echo-labs) and analysis (by monitoring and optimizing the internal intra- and inter-reader variability of measurements). Accordingly, the Working Group of Echocardiography of the Italian Society of Cardiology decided to design standardized procedures for imaging acquisition in peripheral laboratories and reading procedures and to propose a methodological approach to assess the reproducibility of echo-Doppler parameters of cardiac structure and function by using both standard and advanced technologies. A number of cardiologists experienced in cardiac ultrasound was involved to set up an ECL available for future studies involving complex imaging or including echo-Doppler measures as primary or secondary efficacy or safety end-points. The present manuscript describes the methodology of the procedures (imaging acquisition and measurement reading) and provides the documentation of the work done so far to test the reproducibility of the different echo-Doppler modalities (standard and advanced). These procedures can be suggested for utilization also in non referall echocardiographic laboratories as an "inside" quality check, with the aim at optimizing clinical consistency of echo-Doppler data.

The relation of exercise-induced left ventricular (LV) outflow tract obstruction to functional capacity in hypertrophic cardiomyopathy (HC) is incompletely defined. Thus, we assessed the patterns of onset of physiologically provoked LV outflow gradients and exercise performance in 74 consecutive patients with HC (age 45 ± 16 years; 74% men) without LV outflow obstruction at rest. The subaortic gradients were measured serially using echocardiography in these 74 patients during maximum, symptom-limited, upright bicycle exercise testing. The time course of the provoked gradients and the relation to exercise performance were assessed. Of the 74 patients, 30 (41%) developed a dynamic LV outflow gradient of ≥30 mm Hg (mean 78 ± 37 mm Hg) during upright exercise testing that correlated highly with the gradients measured with the patients supine during the immediate recovery period (R² = 0.97). The 16 patients in whom outflow obstruction developed rapidly at low exercise levels (≤5 METs) had a significantly reduced exercise capacity (6.1 ± 1.3 vs 8.0 ± 1.6 METs; p <0.01) compared to the other 14 patients in whom obstruction appeared later at greater exercise levels of >5 METs. The timing of the gradient onset was not predictable from the baseline clinical and echocardiographic features, peak exercise LV outflow tract gradient, or symptoms. In conclusion, in patients with HC without outflow obstruction at rest, the earlier onset of LV outflow tract gradients during physiologic exercise was associated with impaired exercise performance. These findings have provided insights into the determinants of functional impairment in HC and support the potential value of exercise echocardiography in the clinical assessment of patients with HC.