Prognostic Significance of Myocardial Ischemia Detected by Single-Photon Emission Computed Tomography in Children with Hypertrophic Cardiomyopathy

Abstract

Myocardial ischemia caused by microvascular dysfunction is an important pathophysiologic component of hypertrophic cardiomyopathy (HCM), promoting myocardial fibrosis, adverse left ventricular remodeling, and impacting on clinical course and outcome in HCM patients. The aim of study was to assess the prevalence and clinical significance of myocardial ischemia in children with HCM using 99mTc-MIBI single-photon emission computed tomography (SPECT). Ninety-one children with HCM, median age 13.6 years, underwent SPECT evaluation from 2006 to 2017. Imaging was performed at rest and after maximal exercise. Myocardial perfusion defects were identified in 70 children (76.9%; group I), median age 13.8 years. Fixed perfusion defects were evident in 22 of them, while reversible at rest in 48. In 21 children (23.1%; group II), median age 11 years, myocardial perfusion defects were not detected. Patient demographics, echocardiography, resting electrocardiogram (ECG), 24-h Holter ECG, myocardial fibrosis in cardiovascular magnetic resonance imaging, and cardiovascular events were analyzed and compared between the groups. During follow-up at a median of 8.3 years in children with myocardial ischemia, clinical endpoints occurred more often (47 vs. 5; p = 0.02) and more patients reached a clinical endpoint (28 [40%] vs. 3 [14.3%]; p = 0.036). In children with myocardial ischemia, myocardial fibrosis was observed with greater frequency. Myocardial perfusion defects may reflect an ischemic process which (1) affects the clinical manifestations and (2) is an important predictor of adverse clinical events and risk of death in children with HCM. Myocardial ischemia in HCM patients frequently correlates with myocardial fibrosis.

Mechanisms and prognostic impact of myocardial ischaemia in hypertrophic cardiomyopathy

“…Despite these reported associations, other studies have found no relationship between LVOT obstruction and ischaemia, and infarction has been reported in non-obstructive HCM [ 11 ], confirming the role of other mechanisms including microvascular dysfunction [ 4 , 10 , 27 , 32 , 44 ].…”

“…With perfusion defects often remote from coronary territories [ 37 ], and in young patients likely without coronary stenoses [ 10 ], myocardial ischaemia in HCM is multifactorial in origin. Numerous post-mortem, biopsy and imaging studies have investigated the micro-, macrostructural and metabolic mechanisms underlying ischaemia in HCM.…”

“…Furthermore, as the major cause of SCDs in the general population, the assessment of ischaemia in HCM may address some limitations of SCD risk stratification, which has suboptimal sensitivity [ 9 ]. This may be particularly true in young HCM patients [ 10 ], who carry significant SCD burden, and in whom acute myocardial infarction is possible [ 11 ], because a structural substrate for lethal arrhythmias is frequently absent in juvenile SCDs [ 12 ]. Although ischaemia is hypothesised to contribute to SCD events, the prognostic value of imaging for ischaemia in HCM is not yet well established.…”

Microvascular Rarefaction and Myocardial Fibrosis in Hypertrophic Obstructive Cardiomyopathy: A Histopathological Comparison of Pediatric and Adult Patients

“…Myocardial ischemia caused by microvascular dysfunction is an important pathophysiologic component of hypertrophic cardiomyopathy, promoting myocardial fibrosis, adverse left ventricular remodeling, and impacting clinical course and outcome in HOCM patients [Aguiar Rosa 2021;Raman 2019]. Analysis of patients with childhood hypertrophic cardiomyopathy using single-photon emission computed tomography (SPECT) myocardial perfusion studies have shown that myocardial perfusion deficit, myocardial ischemia leads to clinical symptoms, and predicted sudden death and adverse cardiac events in children hypertrophic cardiomyopathy patients [Ziolkowska 2021]. Left ventricular outflow tract pressure gradients, increased vascular impedance, and increased vessel wall tension can all contribute to ventricular diastolic dysfunction and abnormal myocardial perfusion [Knaapen 2008;Güçlü 2015].…”

Nuclear Imaging in Pediatric Cardiology: Principles and Applications

“…Microvascular ischemia is thought to be involved in the development of adverse ventricular remodeling, and diastolic and systolic dysfunction, impacting clinical outcomes in adults and children ( 60 – 64 ). NMPI can contribute as a reliable non-invasive methods for the detection of myocardial ischemia, adding to risk stratification and treatment ( 59 , 62 ). However, the current guidelines suggests that stress echocardiography should be preferred in these patients since it also allows to diagnose LV outflow tract obstruction which is a common concern in this population ( 65 ).…”