The Role of Cardiovascular Magnetic Resonance in Sudden Death Risk Stratification in Hypertrophic Cardiomyopathy

Myocardial fibrosis, as diagnosed on cardiac magnetic resonance imaging (cMRI) by late gadolinium enhancement (LGE), is associated with adverse outcomes in adults with hypertrophic cardiomyopathy (HCM), but its prevalence and magnitude in children with HCM have not been established. We investigated: (1) the prevalence and extent of myocardial fibrosis as detected by LGE cMRI; (2) the agreement between echocardiographic and cMRI measurements of cardiac structure; and (3) whether serum concentrations of N-terminal pro hormone B-type natriuretic peptide (NT-proBNP) and cardiac troponin-T are associated with cMRI measurements.

A cross-section of children with HCM from 9 tertiary-care pediatric heart centers in the U.S. and Canada were enrolled in this prospective NHLBI study of cardiac biomarkers in pediatric cardiomyopathy (ClinicalTrials.gov Identifier: NCT01873976). The median age of the 67 participants was 13.8 years (range 1-18 years). Core laboratories analyzed echocardiographic and cMRI measurements, and serum biomarker concentrations.

In 52 children with non-obstructive HCM undergoing cMRI, overall low levels of myocardial fibrosis with LGE >2% of left ventricular (LV) mass were detected in 37 (71%) (median %LGE, 9.0%; IQR: 6.0%, 13.0%; range, 0% to 57%). Echocardiographic and cMRI measurements of LV dimensions, LV mass, and interventricular septal thickness showed good agreement using the Bland-Altman method. NT-proBNP concentrations were strongly and positively associated with LV mass and interventricular septal thickness (P < .001), but not LGE.

Low levels of myocardial fibrosis are common in pediatric patients with HCM seen at referral centers. Longitudinal studies of myocardial fibrosis and serum biomarkers are warranted to determine their predictive value for adverse outcomes in pediatric patients with HCM.

Cardiovascular magnetic resonance (CMR) late gadolinium enhancement (LGE) requires identification of the normal myocardial nulling time using inversion time (TI)-scout imaging sequence. Although TI-scout images are not primarily used for myocardial assessment, they provide information regarding different signal recovery patterns of normal and abnormal myocardium facilitating identification of LGE in instances where standard LGE images alone are not diagnostic. We aimed to assess the diagnostic performance of TI-scout as compared to that of standard LGE images.

CMR studies with LGE imaging in 519 patients (345 males, 1–17 years) were reviewed to assess the diagnostic performance of LGE imaging in terms of the location of LGE and the pathologic entities. The diagnostic performance of the TI-scout and standard LGE imaging was classified into four categories: (1) equally diagnostic, (2) TI-scout superior to standard LGE, (3) standard LGE superior to TI-scout, and (4) complementary, by the consensus of the two observers.

The study cohort consisted of 440 patients with negative LGE and 79 with evidence for LGE. For a negative diagnosis of LGE, TI-scout and standard LGE images were equally diagnostic in 75% of the cases and were complementary in 12%. For patients with LGE, TI-scout images were superior to standard LGE images in 52% of the cases and were complementary in 19%. The diagnostic performance of TI-scout images was superior to that of standard LGE images in all locations. TI-scout images were superior to standard LGE images in 11 of 12 (92%) cases with LGE involving the papillary muscles, in 7 /12 (58%) cases with subendocardial LGE, and in 4/7 (57%) cases with transmural LGE. TI-scout images were particularly useful assessing the presence and extent of LGE in hypertrophic cardiomyopathy (HCM). TI-scout was superior to standard LGE in 6/10 (60%) and was complementary in 3/10 (30%) of the positive cases with HCM.

TI-scout images enhance the diagnostic performance of LGE imaging in children.

Nonischemic cardiomyopathies encompass a broad spectrum of myocardial disorders with mechanical or electrical dysfunction without evidence of ischemia. There are five broad variants of nonischemic cardiomyopathies; hypertrophic cardiomyopathy (Variant 1), restrictive or infiltrative cardiomyopathy (Variant 2), dilated or unclassified cardiomyopathy (Variant 3), arrhythmogenic cardiomyopathy (Variant 4), and inflammatory cardiomyopathy (Variant 5). For variants 1, 3, and 4, resting transthoracic echocardiography, MRI heart function and morphology without and with contrast, and MRI heart function and morphology without contrast are the usually appropriate imaging modalities. For variants 2 and 5, resting transthoracic echocardiography and MRI heart function and morphology without and with contrast are the usually appropriate imaging modalities.

The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

The first operation for apical hypertrophic cardiomyopathy (ApHCM) was performed on September 7, 1972 by Dr Dwight McGoon at Mayo Clinic on a 16-year-old boy who was thought to have a cardiac neoplasm.

Hypertrophic cardiomyopathy (HCM) is frequently associated with exercise-related sudden death. One possible contributor to arrhythmias is pathologic hypertrophy, which can lead to QTc prolongation. Since β-adrenergic stimulation increases inward ionic currents and can increase spatial repolarization heterogeneity, we hypothesized that exercise would prolong QTc and predispose to arrhythmias in HCM patients. We tested this hypothesis by measuring QTc at rest and peak exercise, and examining ECGs for arrhythmias during exercise/recovery in 163 patients with a clinical diagnosis of HCM. Since hypertrophy and fibrosis are risk factors for arrhythmias in HCM, left ventricular (LV) mass and cardiac fibrosis were quantified using cardiac magnetic resonance imaging. Exercise led to an increase in QTc interval (436 ± 37 to 482 ± 45, p < 0.001), QRS duration (100 ± 9 to 109 ± 12, p < 0.001) and ST-T abnormalities. The proportion of patients with QTc prolongation (>470 ms) increased from 28% at rest, to 58% at peak exercise. An inverse correlation was detected between the approximated T1 relaxation time (using the Look–Locker sequence) and rest-QTc (r = −0.68, p < 0.001); this association was increased during exercise (r = −0.81, p < 0.001). Late gadolinium enhancement (LGE) and LV mass were weakly associated with exercise-QTc. A weak inverse correlation was also observed between approximated T1 relaxation time and rest/exercise-QRS duration. A trend for association with arrhythmia (non-sustained ventricular tachycardia on Holter) was observed for rest-QTc >470 ms (OR = 3.0; p = 0.06). We conclude that exercise leads to QTc prolongation in a subset of HCM patients. The association between the approximated T1 relaxation time and QTc interval may reflect concomitant electrical and structural remodeling in HCM.