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Stress Myocardial Blood Flow Heterogeneity Is a Positron Emission Tomography Biomarker of Ventricular Arrhythmias in Patients With Hypertrophic Cardiomyopathy.

ABSTRACT: Patients with hypertrophic cardiomyopathy (HC) are at increased risk of sudden cardiac death. Abnormalities in myocardial blood flow (MBF) detected by positron emission tomography (PET) are common in HC, but a PET marker that identifies patients at risk of sudden cardiac death is lacking. We hypothesized that disparities in regional myocardial perfusion detected by PET would identify patients with HC at risk of ventricular arrhythmias. To test this hypothesis, we quantified global and regional MBFs by 13NH3-PET at rest and at stress, and developed a heterogeneity index to assess MBF heterogeneity in 133 symptomatic patients with HC. The MBF heterogeneity index was computed by dividing the highest by the lowest regional MBF value, at rest and after vasodilator stress, in each patient. High stress MBF heterogeneity was defined as an index of ?1.85. Patients with HC were stratified by the presence or the absence of ventricular arrhythmias, defined as sustained ventricular tachycardia (VT) and/or nonsustained VT, during follow-up. We found that global and regional MBFs at rest and stress were similar in patients with HC with or without ventricular arrhythmias. Variability in regional stress MBF was observed in both groups, but the stress MBF heterogeneity index was significantly higher in patients with HC who developed ventricular arrhythmias (1.82?±?0.77 vs 1.49?±?0.25, p?<0.001). A stress MBF heterogeneity index of ?1.85 was an independent predictor of both sustained VT (hazard ratio 16.1, 95% confidence interval 3.2 to 80.3) and all-VT (sustained-VT?+?nonsustained VT: hazard ratio 3.7, 95% confidence interval 1.4 to 9.7). High heterogeneity of stress MBF, reflected by an MBF heterogeneity index of ?1.85, is a PET biomarker for ventricular arrhythmias in symptomatic patients with HC.

SUBMITTER: Lu DY

PROVIDER: S-EPMC5966031 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Stress Myocardial Blood Flow Heterogeneity Is a Positron Emission Tomography Biomarker of Ventricular Arrhythmias in Patients With Hypertrophic Cardiomyopathy.

Lu Dai-Yin DY Yalçin Hulya H Yalçin Fatih F Zhao Min M Sivalokanathan Sanjay S Valenta Ines I Tahari Abdel A Pomper Martin G MG Abraham Theodore P TP Schindler Thomas H TH Abraham M Roselle MR

The American journal of cardiology 20180206 9

Patients with hypertrophic cardiomyopathy (HC) are at increased risk of sudden cardiac death. Abnormalities in myocardial blood flow (MBF) detected by positron emission tomography (PET) are common in HC, but a PET marker that identifies patients at risk of sudden cardiac death is lacking. We hypothesized that disparities in regional myocardial perfusion detected by PET would identify patients with HC at risk of ventricular arrhythmias. To test this hypothesis, we quantified global and regional M ...[more]

PMID: 29678336

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Project description:BackgroundMyocardial disarray is a likely focus for fatal arrhythmia in hypertrophic cardiomyopathy (HCM). This microstructural abnormality can be inferred by mapping the preferential diffusion of water along cardiac muscle fibers using diffusion tensor cardiac magnetic resonance (DT-CMR) imaging. Fractional anisotropy (FA) quantifies directionality of diffusion in 3 dimensions. The authors hypothesized that FA would be reduced in HCM due to disarray and fibrosis that may represent the anatomic substrate for ventricular arrhythmia.ObjectivesThis study sought to assess FA as a noninvasive in vivo biomarker of HCM myoarchitecture and its association with ventricular arrhythmia.MethodsA total of 50 HCM patients (47 ± 15 years of age, 77% male) and 30 healthy control subjects (46 ± 16 years of age, 70% male) underwent DT-CMR in diastole, cine, late gadolinium enhancement (LGE), and extracellular volume (ECV) imaging at 3-T.ResultsDiastolic FA was reduced in HCM compared with control subjects (0.49 ± 0.05 vs. 0.52 ± 0.03; p = 0.0005). Control subjects had a mid-wall ring of high FA. In HCM, this ring was disrupted by reduced FA, consistent with published histology demonstrating that disarray and fibrosis invade circumferentially aligned mid-wall myocytes. LGE and ECV were significant predictors of FA, in line with fibrosis contributing to low FA. Yet FA adjusted for LGE and ECV remained reduced in HCM (p = 0.028). FA in the hypertrophied segment was reduced in HCM patients with ventricular arrhythmia compared to patients without (n = 15; 0.41 ± 0.03 vs. 0.46 ± 0.06; p = 0.007). A decrease in FA of 0.05 increased odds of ventricular arrhythmia by 2.5 (95% confidence interval: 1.2 to 5.3; p = 0.015) in HCM and remained significant even after correcting for LGE, ECV, and wall thickness (p = 0.036).ConclusionsDT-CMR assessment of left ventricular myoarchitecture matched patterns reported previously on histology. Low diastolic FA in HCM was associated with ventricular arrhythmia and is likely to represent disarray after accounting for fibrosis. The authors propose that diastolic FA could be the first in vivo marker of disarray in HCM and a potential independent risk factor.

Project description:BackgroundGray zone, a measure of tissue heterogeneity on late gadolinium enhanced-cardiac magnetic resonance (LGE-CMR) imaging, has been shown to predict ventricular arrhythmias (VAs) in ischemic cardiomyopathy (ICM) patients. However, no studies have described whether left ventricular (LV) tissue heterogeneity and intramyocardial fat mass on contrast-enhanced computed tomography (CE-CT), which provides greater spatial resolution, is useful for assessing the risk of VAs in ICM patients with LV systolic dysfunction and no previous VAs.ObjectiveThe purpose of this proof-of-concept study was to determine the feasibility of measuring global LV tissue heterogeneity and intramyocardial fat mass by CE-CT for predicting the risk of VAs in ICM patients with LV systolic dysfunction and no previous history of VAs.MethodsPatients with left ventricular ejection fraction ≤35% and no previous VAs were enrolled in a prospective, observational registry and underwent LGE-CMR. From this cohort, patients with ICM who additionally received CE-CT were included in the present analysis. Gray zone on LGE-CMR was defined as myocardium with signal intensity (SI) > peak SI of healthy myocardium but <50% maximal SI. Tissue heterogeneity on CE-CT was defined as the standard deviation of the Hounsfield unit image gradients (HU/mm) within the myocardium. Intramyocardial fat on CE-CT was identified as regions of image pixels between -180 and -5 HU. The primary outcome was VAs, defined as appropriate implantable cardioverter-defibrillator shock or sudden arrhythmic death.ResultsThe study consisted of 47 ICM patients, 13 (27.7%) of whom experienced VA events during mean follow-up of 5.6 ± 3.4 years. Increasing tissue heterogeneity (per HU/mm) was significantly associated with VAs after multivariable adjustment, including for gray zone (odds ratio [OR] 1.22; P = .019). Consistently, patients with tissue heterogeneity values greater than or equal to the median (≥22.2 HU/mm) had >13-fold significantly increased risk of VA events, relative to patients with values lower than the median, after multivariable adjustment that included gray zone (OR 13.13; P = .028). The addition of tissue heterogeneity to gray zone improved prediction of VAs (area under receiver operating characteristic curve increased from 0.815 to 0.876). No association was found between intramyocardial fat mass on CE-CT and VAs (OR 1.00; P = .989).ConclusionIn ICM patients, CE-CT-derived LV tissue heterogeneity was independently associated with VAs and may represent a novel marker useful for risk stratification.

Dataset Information

Stress Myocardial Blood Flow Heterogeneity Is a Positron Emission Tomography Biomarker of Ventricular Arrhythmias in Patients With Hypertrophic Cardiomyopathy.

Publications

Stress Myocardial Blood Flow Heterogeneity Is a Positron Emission Tomography Biomarker of Ventricular Arrhythmias in Patients With Hypertrophic Cardiomyopathy.

Similar Datasets

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