Myocardial contrast echocardiography assessment of perfusion abnormalities in hypertrophic cardiomyopathy

Abstract

Background: Perfusion defects during stress can occur in hypertrophic cardiomyopathy (HCM) from either structural or functional abnormalities of the coronary microcirculation. In this study, vasodilator stress myocardial contrast echocardiography (MCE) was used to quantify and spatially characterize hyperemic myocardial blood flow (MBF) deficits in HCM.

Methods: Regadenoson stress MCE was performed in patients with septal-variant HCM (n = 17) and healthy control subjects (n = 15). The presence and spatial distribution (transmural diffuse, patchy, subendocardial) of perfusion defects was determined by semiquantitative analysis. Kinetic analysis of time-intensity data was used to quantify MBF, microvascular flux rate (β), and microvascular blood volume. In patients undergoing septal myectomy (n = 3), MCE was repeated > 1 years after surgery. RESULTS: In HCM subjects, perfusion defects during stress occurred in the septum in 80%, and in non-hypertrophied regions in 40%. The majority of septal defects (83%) were patchy or subendocardial, while 67% of non-hypertrophied defects were transmural and diffuse. On quantitative analysis, hyperemic MBF was approximately 50% lower (p < 0.001) in the hypertrophied and non-hypertrophied regions of those with HCM compared to controls, largely based on an inability to augment β, although hypertrophic regions also had blood volume deficits. There was no correlation between hyperemic MBF and either percent fibrosis on magnetic resonance imaging or outflow gradient, yet those with higher degrees of fibrosis (≥ 5%) or severe gradients all had low septal MBF during regadenoson. Substantial improvement in hyperemic MBF was observed in two of the three subjects undergoing myectomy, both of whom had severe pre-surgical outflow gradients at rest.

Conclusion: Perfusion defects on vasodilator MCE are common in HCM, particularly in those with extensive fibrosis, but have a different spatial pattern for the hypertrophied and non-hypertrophied segments, likely reflecting different contributions of functional and structural abnormalities. Improvement in hyperemic perfusion is possible in those undergoing septal myectomy to relieve obstruction. TRIAL REGISTRATION: ClinicalTrials.gov NCT02560467.

Keywords: Hypertrophic cardiomyopathy; Ischemia; Myocardial contrast echocardiography.

Conflict of interest statement

Material support was provided by Bracco Pharmaceuticals, Princeton, NJ (Lumason ultrasound contrast agent) and by Astellas Pharma, Tokyo, Japan (Lexiscan [regadenoson]). No other financial or non-financial competing interests exist for any of the authors.

© 2022. The Author(s).

Figures

Fig. 1

MCE detection of abnormal perfusion during vasodilator stress in HCM subjects. A Percentage of subjects with transmural diffuse, subendocardial or patchy, or normal perfusion during regadenoson for hypertrophied and non-hypertrophied control regions. B Example of end-systolic MCE images (apical 4-chamber) and corresponding time-intensity curves during vasodilator stress illustrating a patchy perfusion defect of the hypertrophied septum (arrows) and both reduced microvascular flux rate (β) and MBV (A-value). Images are shown immediately after microbubble destruction (T0) and at 3.2 s after refill (T3.2). C Vasodilator MCE (4-chamber view) illustrating delayed refill in all myocardial segments that was worse in the subendocardium. D Vasodilator MCE (4-chamber view) > 5 s after refill illustrating a transmural severe defect of the non-hypertrophied lateral wall (arrows)

Fig. 2

Quantitative MCE perfusion data (mean ± SEM) at rest and during vasodilator stress from normal control subjects and in the non-hypertrophied and hypertrophied regions from HCM subjects. Data include: (A) microvascular blood flow, (B) microvascular blood volume, and (C) Microvascular flux rate (β) derived from time-intensity data

Fig. 3

Quantitative MCE at rest (A-C) and during vasodilator stress (E–G) for microvascular blood flow (MBF), microvascular blood volume (MBV) and microvascular flux rate according to presence or absence of fibrosis > 2% by late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR). (D and H) Relation between percent fibrosis by LGE and MBF at rest or stress. (I-K) Quantitative MCE during vasodilator stress according to the presence or absence of a history of anginal chest pain (CP). (E–G) Relation between left ventricular outflow tract (LVOT) gradient at rest and MBF at rest or during vasodilator stress

Fig. 4

A Myocardial blood flow (MBF) in the hypertrophic and non-hypertrophic segments in patients with HCM during vasodilator stress showing individual data from the initial study (baseline), and after surgical myectomy (n = 3 subjects, data points in red). End-systolic images in the apical 4-chamber view during vasodilator MCE from a single for the study prior to myectomy B and more than one year after myectomy C. End-systolic images shown were acquired immediately after microbubble destruction (T0) and at approximately two seconds (T2) after replenishment and illustrate improvement in contrast enhancement in the hypertrophied and remote segments