Coronary flow reserve in hypertrophic cardiomyopathy: relation with microvascular dysfunction and pathophysiological characteristics

Kofflard, Marcel; Michels, Michelle; Krams, Rob; Kliffen, Mike; Geleijnse, Marcel L.; Cate, Folkert J. ten; Serruys, Patrick W.

doi:10.1007/bf03085982

Cited by 38 publications

(29 citation statements)

References 30 publications

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“…Finally, in the presence of resting or provocable dynamic LV outflow obstruction, observed in more than two thirds of HCM patients [31], the pathological increase in intracavitary pressures may substantially contribute to myocar- [20,27,28]. Such consequences appear to be particularly adverse in patients with midventricular obstruction, in whom progressive apical dilatation may occur with scar formation, which may further progress to LV dilatation, dysfunction, and heart failure [10,16].…”

Section: The Triggers: Exercise Sinus Tachycardia Supraventricular mentioning

confidence: 89%

“…In addition to the intrinsic structural remodeling of the microcirculation, other potential relevant factors include reduced capillary density, myocyte disarray, interstitial fibrosis, and increased oxygen demand of the hypertrophied cardiomyocytes [19][20][21]. Such abnormalities constitute the anatomical basis for microvascular dysfunction and represent the substrate for ischemia in HCM patients.…”

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confidence: 97%

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Microvascular Dysfunction, Myocardial Ischemia, and Progression to Heart Failure in Patients with Hypertrophic Cardiomyopathy

Cecchi

Sgalambro

Baldi

et al. 2009

J. of Cardiovasc. Trans. Res.

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Microvascular dysfunction can be demonstrated in most patients with hypertrophic cardiomyopathy (HCM), both in the hypertrophied and nonhypertrophied myocardial walls, mostly due to intimal and medial hyperplasia of the intramural coronary arteries and subsequent lumen reduction. As a consequence, regional myocardial ischemia may be triggered by exercise, increased heart rate, or arrhythmias, in areas which are unable to increase myocardial blood flow. In patients with HCM, microvascular dysfunction leading to severe myocardial hypoperfusion during maximal hyperemia represents a strong predictor of unfavorable outcome, left ventricular remodeling with progressive wall thinning, left ventricular dysfunction, and heart failure. Accurate quantitative assessment of microvascular dysfunction and myocardial ischemia is not easily feasible in clinical practice. Although signs of inducible myocardial ischemia may be detected by electrocardiogram, echocardiography, or myocardial scintigraphy, the vasodilator response to dipyridamole by positron emission tomography is considered the method of choice for the assessment of maximal regional and global flow. Cardiac magnetic resonance provides further information, by late gadolinium enhancement (LGE), which may show areas where replacement fibrosis has occurred following microvascular ischemia and focal necrosis. LGE areas colocalize with severe regional microvascular dysfunction, are associated with increased prevalence of ventricular arrhythmias, and show more extensive distribution in the late stages of the disease, when heart failure is the dominant feature. The present review aims to provide a concise overview of the available evidence of microvascular dysfunction and ischemia eventually leading to disease progression and heart failure in HCM patients.

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Section: The Triggers: Exercise Sinus Tachycardia Supraventricular mentioning

confidence: 89%

mentioning

confidence: 97%

Microvascular Dysfunction, Myocardial Ischemia, and Progression to Heart Failure in Patients with Hypertrophic Cardiomyopathy

Cecchi

Sgalambro

Baldi

et al. 2009

J. of Cardiovasc. Trans. Res.

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“…(18) Microvascular dysfunction in these diseases may be mechanistically related to coronary microvascular remodeling, rarefaction and interstitial fibrosis (hypertensive heart disease), small vessel disease, relatively reduced capillary density, increased LV end-diastolic pressures and systolic compression of the septal coronary arteries (19) or increased LV mass. (20) Some or all of these mechanisms may explain the coronary vasomotor dysfunction in cardiac amyloidosis.…”

Section: Discussionmentioning

confidence: 99%

Coronary Microvascular Dysfunction Is Related to Abnormalities in Myocardial Structure and Function in Cardiac Amyloidosis

Dorbala

Vangala

Bruyere

et al. 2014

JACC: Heart Failure

177

118

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Objectives We sought to test the hypothesis that coronary microvascular function is impaired in subjects with cardiac amyloidosis. Background Effort angina is common in subjects with cardiac amyloidosis even in the absence of epicardial coronary artery disease (CAD). Methods Thirty one subjects were prospectively enrolled in this study including 21 subjects with definite cardiac amyloidosis without epicardial CAD and 10 subjects with hypertensive left ventricular hypertrophy (LVH). All subjects underwent rest and vasodilator stress N-13 ammonia positron emission tomography and 2D echocardiography. Global LV myocardial blood flow (MBF) was quantified at rest and during peak hyperemia, and coronary flow reserve (CFR) was computed (peak stress MBF / rest MBF) adjusting for rest rate pressure product. Results Compared to the LVH group, the amyloid group showed lower rest MBF (0.59 ± 0.15 vs. 0.88 ± 0.23 ml/g/min, P = 0.004), stress MBF (0.85 ± 0.29 vs. 1.85 ± 0.45 vs. ml/min/g, P < 0.0001), CFR (1.19 ± 0.38 vs. 2.23 ± 0.88, P < 0.0001), and higher minimal coronary vascular resistance (111 ± 40 vs. 70 ± 19 mm Hg/mL/g/min, P = 0.004). Of note, almost all amyloid subjects (> 95%) demonstrated significantly reduced peak stress MBF (< 1.3 mL/g/min). In multivariable linear regression analyses, a diagnosis of amyloidosis, increased LV mass and age were the only independent predictors of impaired coronary vasodilator function. Conclusions Coronary microvascular dysfunction is highly prevalent in subjects with cardiac amyloidosis even in the absence of epicardial CAD, and may explain their anginal symptoms. Further study is required to understand whether specific therapy directed at amyloidosis may improve coronary vasomotion in amyloidosis.

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“…An important biologic response to the increase in myocardial mass is the induction of angiogenesis to increase myocardial perfusion and oxygen delivery. Frequently, the angiogenic response is inadequate as seen in some HCM cases as a reduction in coronary flow reserve and reduced capillary density and luminal diameter (2)(3)(4)(5). Resulting regional perfusion abnormalities probably contribute to cell injury and myocardial fibrosis, an important predictor of adverse outcomes in HCM (6,7).…”

mentioning

confidence: 99%

“…In an adult series, 71% of patients with HCM had myocardial fibrosis when assessed by magnetic resonance imaging and serum markers of fibrosis (8). Together, impaired angiogenesis and fibrosis can predispose to arrhythmias and sudden death (2,3). Given the low sensitivity of current imaging methods to identify fibrosis in the early stages, better predictors of impaired angiogenesis and fibrosis are needed.…”

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confidence: 99%

Genetic variations in hypoxia response genes influence hypertrophic cardiomyopathy phenotype

et al. 2012

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Background: Risk factors for diastolic dysfunction in hypertrophic cardiomyopathy (hcM) are poorly understood. We investigated the association of variants in hypoxia-response genes with phenotype severity in pediatric hcM. Methods: a total of 80 unrelated patients <21 y and 14 related members from eight families with hcM were genotyped for six variants associated with vascular endothelial growth factor a (VEGFA) downregulation, or hypoxia-inducible factor a (HIF1A) upregulation. associations between risk genotypes and leftventricular (LV) hypertrophy, LV dysfunction, and freedom from myectomy were assessed. Tissue expression was measured in myocardial samples from 17 patients with hcM and 20 patients without hcM. results: age at enrollment was 9 ± 5 y (follow-up, 3.1 ± 3.6 y). Risk allele frequency was 67% VEGFA and 92% HIF1A. Risk genotypes were associated with younger age at diagnosis (P < 0.001), septal hypertrophy (P < 0.01), prolonged e-wave deceleration time (eWDT) (P < 0.0001) and isovolumic relaxation time (IVRT) (P < 0.0001), and lower freedom from myectomy (P < 0.05). These associations were seen in sporadic and familial hcM independent of the disease-causing mutation. Risk genotypes were associated with higher myocardial hIF1a and transforming growth factor B1 (TGFB1) expression and increased endothelialfibroblast transformation (P < 0.05). conclusion: HIF1A-upregulation and/or VEGFA-downregulation genotypes were associated with more severe septal hypertrophy and diastolic dysfunction and may provide genetic markers to improve risk prediction in hcM.

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Coronary flow reserve in hypertrophic cardiomyopathy: relation with microvascular dysfunction and pathophysiological characteristics

Cited by 38 publications

References 30 publications

Microvascular Dysfunction, Myocardial Ischemia, and Progression to Heart Failure in Patients with Hypertrophic Cardiomyopathy

Microvascular Dysfunction, Myocardial Ischemia, and Progression to Heart Failure in Patients with Hypertrophic Cardiomyopathy

Coronary Microvascular Dysfunction Is Related to Abnormalities in Myocardial Structure and Function in Cardiac Amyloidosis

Genetic variations in hypoxia response genes influence hypertrophic cardiomyopathy phenotype

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