Cardiomyopathy
Effect of Diffuse Subendocardial Hypoperfusion on Left Ventricular Cavity Size by 13N-Ammonia Perfusion PET in Patients With Hypertrophic Cardiomyopathy

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Vasodilator-induced transient left ventricular (LV) cavity dilation by positron emission tomography (PET) is common in patients with hypertrophic cardiomyopathy (HC). Because most patients with PET-LV cavity dilation lack obstructive epicardial coronary artery disease, we hypothesized that vasodilator-induced subendocardial hypoperfusion resulting from microvascular dysfunction underlies this result. To test this hypothesis, we quantified myocardial blood flow (MBF) (subepicardial, subendocardial, and global MBF) and left ventricular ejection fraction (LVEF) in 104 patients with HC without significant coronary artery disease, using 13NH3-PET. Patients with HC were divided into 2 groups, based on the presence/absence of LV cavity dilation (LVvolumestress/LVvolumerest >1.13). Transient PET-LV cavity dilation was evident in 52% of patients with HC. LV mass, stress left ventricular outflow tract gradient, mitral E/E′, late gadolinium enhancement, and prevalence of ischemic ST-T changes after vasodilator were significantly higher in patients with HC with LV cavity dilation. Baseline LVEF was similar in the 2 groups, but LV cavity dilation+ patients had lower stress-LVEF (43 ± 11 vs 53 ± 10; p <0.001), lower stress-MBF in the subendocardial region (1.6 ± 0.7 vs 2.3 ± 1.0 ml/min/g; p <0.001), and greater regional perfusion abnormalities (summed difference score: 7.0 ± 6.1 vs 3.9 ± 4.3; p = 0.004). The transmural perfusion gradient, an indicator of subendocardial perfusion, was similar at rest in the 2 groups. Notably, LV cavity dilation+ patients had lower stress-transmural perfusion gradients (0.85 ± 0.22, LV cavity dilation+ vs 1.09 ± 0.39, LV cavity dilation; p <0.001), indicating vasodilator-induced subendocardial hypoperfusion. The stress-transmural perfusion gradient, global myocardial flow reserve, and stress-LVEF were associated with LV cavity dilation. In conclusion, diffuse subendocardial hypoperfusion and myocardial ischemia resulting from microvascular dysfunction contribute to development of transient LV cavity dilation in HC.

Section snippets

Methods

This study was approved by the Institutional Review Board at the Johns Hopkins University. We included patients with HC (n = 104) evaluated at the Johns Hopkins Hypertrophic Cardiomyopathy Clinic who underwent cardiac rest-stress 13N ammonia PET/computed tomography (CT) from 2009 to 2013. All patients fulfilled the standard diagnostic criteria of HC, namely presence of unexplained left ventricular hypertrophy with maximum wall thickness ≥15 mm and septal/posterior wall ratio >1.3 in the absence

Results

This study included 104 patients with a clinical diagnosis of HC. Patients with HC were divided into 2 groups, based on the presence or absence of transient PET-LV cavity dilation after vasodilator stress (Figure 1). Demographic characteristics, LVEF, and LV volumes were similar in the 2 groups, but patients with HC with PET-LV cavity dilation had greater degree of LV hypertrophy, diastolic dysfunction, higher stress-left ventricular outflow tract (LVOT) gradients, and greater amounts of

Discussion

The main result of our study is that vasodilator-induced subendocardial hypoperfusion and myocardial ischemia resulting from microvascular dysfunction contribute to development of transient PET-LV cavity dilation in patients with HC.

Transient LV cavity dilation and reduction in LVEF are frequently observed by nuclear imaging and echocardiography after vasodilator/dobutamine infusion and exercise,19 in patients with severe, extensive CAD. In contrast, most patients with HC lack obstructive

Acknowledgment

The authors would like to acknowledge help from Dr. Junaid Afzal, MS, Dr. Dhananjay Vaidya, PhD, and the Image Response Assessment Team (NIH P30CA006973).

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    This study was supported by the John Taylor Babbit (JTB) Foundation.

    See page 1914 for disclosure information.

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