Microvascular Dysfunction In Hypertrophic Cardiomyopathy Research Articles

Coronary disorder is not necessarily caused exclusively by coronary microvascular dysfunction in hypertrophic cardiomyopathy.

Coronary disorder is not necessarily caused exclusively by coronary microvascular dysfunction in hypertrophic cardiomyopathy.

Microvascular dysfunction in hypertrophic cardiomyopathy: diagnostic role of noninvasive, fully automated quantitative perfusion cardiovascular magnetic resonance imaging.

Microvascular dysfunction in hypertrophic cardiomyopathy: diagnostic role of noninvasive, fully automated quantitative perfusion cardiovascular magnetic resonance imaging.

MDM2 Regulation of HIF Signaling Causes Microvascular Dysfunction in Hypertrophic Cardiomyopathy.

Microvasculature dysfunction is a common finding in pathologic remodeling of the heart and is thought to play an important role in the pathogenesis of hypertrophic cardiomyopathy (HCM), a disease caused by sarcomere gene mutations. We hypothesized that microvascular dysfunction in HCM was secondary to abnormal microvascular growth and could occur independent of ventricular hypertrophy. We used multimodality imaging methods to track the temporality of microvascular dysfunction in HCM mouse models harboring mutations in the sarcomere genes Mybpc3 (cardiac myosin binding protein C3) or Myh6 (myosin heavy chain 6). We performed complementary molecular methods to assess protein quantity, interactions, and post-translational modifications to identify mechanisms regulating this response. We manipulated select molecular pathways in vivo using both genetic and pharmacological methods to validate these mechanisms. We found that microvascular dysfunction in our HCM models occurred secondary to reduced myocardial capillary growth during the early postnatal time period and could occur before the onset of myocardial hypertrophy. We discovered that the E3 ubiquitin protein ligase MDM2 (murine double minute 2) dynamically regulates the protein stability of both HIF1α (hypoxia-inducible factor 1 alpha) and HIF2α (hypoxia-inducible factor 2 alpha)/EPAS1 (endothelial PAS domain protein 1) through canonical and noncanonical mechanisms. The resulting HIF imbalance leads to reduced proangiogenic gene expression during a key period of myocardial capillary growth. Reducing MDM2 protein levels by genetic or pharmacological methods normalized HIF protein levels and prevented the development of microvascular dysfunction in both HCM models. Our results show that sarcomere mutations induce cardiomyocyte MDM2 signaling during the earliest stages of disease, and this leads to long-term changes in the myocardial microenvironment.

Index of microcirculatory resistance in the assessment of coronary microvascular dysfunction in hypertrophic cardiomyopathy

Introduction and objectivesCoronary microvascular dysfunction (CMD) is one of the most important pathophysiological features in hypertrophic cardiomyopathy (HCM). The index of microcirculatory resistance (IMR) is an invasive method to assess the coronary microcirculation. The aim was to assess CMD in patients with HCM by IMR. MethodsAdult patients with HCM without epicardial coronary artery disease underwent cardiac catheterization for the assessment of CMD by IMR (normal cut-off value ≤22.0) and coronary flow reserve (CFR) (normal cut-off value ≥2). Cardiovascular magnetic resonance (CMR) was performed to assess the ischemic burden by perfusion imaging during regadenoson-induced hyperemia, and the extent of myocardial fibrosis was assessed by late gadolinium enhancement (LGE), native T1 mapping and extracellular volume (ECV). ResultsFourteen patients were enrolled with a mean age of 62.8±6.2years, 8 (57.1%) males, of whom 9 (64.3%) had obstructive HCM. Using IMR, CMD was detected in 4 (29%) patients. Among four patients with an IMR>22.0, all had non-obstructive HCM and two had angina. CFR<2 was reported in eight patients (57%). Concordance between IMR and CFR (both normal or both abnormal) was verified in 6 patients (43%). Among four patients with IMR>22.0, perfusion defects were found in two of the three patients who underwent stress CMR. Increased ECV (>28%) was documented in two of the patients with IMR>22 and in three of the patients with IMR≤22.0. LGE was >15% in 2 of the patients with IMR>22 and in 4 with IMR≤22.0. ConclusionsIMR assessment in HCM is feasible and safe. Patients with abnormal IMR seemed to have more significant tissue abnormalities on CMR.

Coronary microvascular dysfunction in hypertrophic cardiomyopathy – impact from tissue characteristics to clinical manifestations

Abstract Background Coronary microvascular dysfunction (CMD) is an important pathophysiological feature in hypertrophic cardiomyopathy (HCM). Purpose This study investigated the role of CMD in tissue characteristics, left ventricular (LV) systolic performance and clinical manifestations in HCM. Methods This prospective study enrolled patients with HCM without obstructive epicardial coronary artery disease. Each patient underwent cardiovascular magnetic resonance (CMR) including parametric mapping, perfusion imaging during regadenoson-induced hyperemia, late gadolinium enhancement (LGE) and three-dimensional longitudinal, circumferential and radial strains analysis. Electrocardiogram and 24 hours Holter recording were performed to assess arrhythmias. Results 75P were enrolled, 47 (63%) males, mean age 54.6 (14.8) years; 51 patients (68%) had non obstructive HCM, mean maximum wall thickness (MWT) was 20.2 (4.6)mm, LV ejection fraction 71.6 (8.3)%, ischemic burden 22.5 (16.9)% of LV. Greater MWT was associated the severity of ischemia (β-estimate: 1.809, 95% CI: 1.073; 2.545; p&amp;lt;0.001). Ischemic burden was strongly associated with higher values of native T1 (β-estimate: 9.018, 95% CI: 4.721, 13.315; p&amp;lt;0.001). An association between ischemia and the extent of LGE was found (β-estimate: 2.02, 95% CI: 0.93, 3.10; p&amp;lt;0.001). Ischemia in ≥21% of LV was associated with LGE &amp;gt;15% (AUC 0.766, sensitivity 0.724, specificity 0.659). In multivariable analysis, in the overall population, MWT and LGE were independently associated with ischemia, however the evidence of association between ischemia and extent of LGE became weaker (β-estimate: 1.070, 95% CI: −0.106; 2.245; p=0.074). In subgroup analysis, the association between ischemia and LGE remained significant in individuals with MWT 15–20mm, non-obstructive HCM, female and age &amp;lt;40 years. The severity of ischemia was not associated with markers of LV systolic function, namely LVEF, longitudinal, radial and circumferential strain A strong evidence of association was found between ischemia and atrial fibrillation/flutter (AF/AFL) (OR: 1.481, 95% CI: 1.020,2.152; p=0.039), but no association was verified with non-sustained ventricular tachycardia. Conclusion In HCM, CMD is related to the severity of LV hypertrophy. Ischemia secondary to CMD promotes fibrosis and is associated with an increase in the odds of AF/ALF. Funding Acknowledgement Type of funding sources: None.

Higher incidence of vasodilator-induced left ventricular cavity dilation by PET when compared to treadmill exercise-ECHO in hypertrophic cardiomyopathy

BackgroundVasodilator-induced transient left ventricular cavity dilation (LVCD) by positron emission tomography (PET) is associated with microvascular dysfunction in hypertrophic cardiomyopathy (HCM). Here we assessed whether HCM patients who develop LVCD by PET during vasodilator stress also develop LV cavity dilation by echocardiography (ECHO-LVCD) following exercise stress. MethodsA retrospective analysis of cardiac function and myocardial blood flow (MBF) was conducted in 108 HCM patients who underwent perfusion-PET and exercise-ECHO as part of their clinical evaluation. We performed a head-to-head comparison of LV volumes and ejection fraction (LVEF) at rest and stress (during vasodilator stress, post-exercise), in 108 HCM patients. A ratio > 1.13 of stress to rest LV volumes was used to define PET-LVCD, and a ratio > 1.17 of stress to rest LVESV was used to define ECHO-LVCD. Patients were divided into 2 groups based on the presence/absence of PET-LVCD. MBF and myocardial flow reserve were quantified by PET, and global longitudinal strain (GLS) was assessed by ECHO at rest/stress in the two groups. ResultsPET-LVCD was observed in 51% (n = 55) of HCM patients, but only one patient had evidence of ECHO-LVCD (ratio = 1.36)—this patient also had evidence of PET-LVCD (ratio = 1.20). The PET-LVCD group had lower PET-LVEF during vasodilator stress, but ECHO-LVEF increased in both groups post-exercise. The PET-LVCD group demonstrated higher LV mass, worse GLS at rest/stress, and lower myocardial flow reserve. Incidence of ischemic ST-T changes was higher in the PET-LVCD group during vasodilator stress (42 vs 17%), but similar (30%) in the two groups during exercise. ConclusionPET-LVCD reflects greater degree of myopathy and microvascular dysfunction in HCM. Differences in the cardiac effects of exercise and vasodilators and timing of stress-image acquisition could underlie discordance in ischemic EKG changes and LVCD by ECHO and PET, in HCM.

Coronary microvascular dysfunction in hypertrophic cardiomyopathy: Pathophysiology, assessment, and clinical impact.

Myocardial ischemia constitutes one of the most important pathophysiological features in hypertrophic cardiomyopathy. Chronic and recurrent myocardial ischemia leads to fibrosis, which may culminate in myocardial dysfunction. Since the direct visualization of coronary microcirculation in vivo is not possible, its function must be studied indirectly. Invasive and noninvasive techniques allow microcirculatory dysfunction to be evaluated, including echocardiography, magnetic resonance, positron emission tomography, and cardiac catheterization. Blunted myocardial blood flow and coronary flow reserve have been suggested to associate with unfavorable prognosis. Microcirculatory dysfunction may be one additional important parameter to take into account for risk stratification beyond the conventional risk factors.

Coronary microvascular dysfunction in hypertrophic cardiomyopathy detected by Rubidium-82 positron emission tomography and cardiac magnetic resonance imaging

Coronary microvascular dysfunction in hypertrophic cardiomyopathy detected by Rubidium-82 positron emission tomography and cardiac magnetic resonance imaging

Microvascular Dysfunction in Hypertrophic Cardiomyopathy

In hypertrophic cardiomyopathy (HCM), the presence of vessel abnormalities with microvascular dysfunction is a well-known feature. The aim of this review is to present the evidences that support this notion and to describe the physiopathologic and clinical consequences of microvascular dysfunction. After having demonstrated the presence and significance of microvascular dysfunction in HCM, the myocardial blood flow (MBF) measurement by positron emission tomography (PET) is ready to develop into a clinical tool for disease evaluation, in particular for patient prognostication. Alternative methods are becoming available, but they are not yet equally reliable. By means of MBF measurement using quantitative PET, the importance of microvascular dysfunction in HCM has been clearly demonstrated, explaining the chest pain and the ischemic abnormalities frequently registered in this disease. The physiopathologic implications of microvascular dysfunction have been established, and an increasing number of reports indicate that the assessment of microvascular dysfunction is as well important for patient characterization and prognostication. Most recently, perfusion measurements using magnetic resonance imaging have been used, but their role is still under debate.

3.0 T MR myocardial perfusion imaging for quantitative evaluation on coronary microvascular dysfunction in hypertrophic cardiomyopathy

Objective To evaluate the coronary microvascular dysfunction in patients with hypertrophic cardiomyopathy(HCM) by MR first-pass perfusion and late gadolinium enhancement. Methods From January 2011 to May 2015, 47 cases with HCM (HCM group) from the second affiliated hospital of Nanchang University were retrospectively analyzed. Additionally, 21 healthy volunteers were recruited as the control group. HCM group and control group underwent cardiac MR examinations at rest, including short axial cine, first-pass myocardial perfusion and late gadolinium enhancement scanning. Time to peak(tpeak), maximal upslope of time-intensity curve(Slopemax), peak signal intensity(SIpeak), myocardial thickening, and late myocardial gadolinium enhancement(LGE) were assessed for each myocardial segment. HCM group were divided into LGE segments group and non-LGE segments group. LGE segments group were divided into mild, moderate and severe LGE segments group. The SIpeak, Slopemax and tpeak in multiple groups were compared by one-way ANOVA and Kruskal-Wallis test. Spearman correlation tests were used to determine the relationships between perfusion parameter and LGE. Results The average values of tpeak in non-LGE segments group (527 segments), LGE segments group (225 segments) and control group (336 segments) were (67.0±27.4), (79.4±27.4), (59.7±21.6)s, respectively. The average values of Slopemax in the three groups were 17.2±7.0, 16.4±7.4, 20.4±6.3, respectively. The average values of SIpeak in the three groups were 442.7±143.2, 465.1±138.4, 521.9±146.7, respectively. Compared to the control group, tpeak increased and Slopemax, SIpeak decreased in non-LGE segments group and LGE segments group (P 0.05). There were significant differences among LGE segments groups, as the tpeak and SIpeak increased with increasing degrees of myocardial LGE (P 0.05). The degree of LGE were positively correlated with tpeak (r=0.237, P<0.01). Conclusions 3.0 T magnetic resonance myocardial perfusion imaging can show microvascular dysfunction accurately and reliably in non-LGE segments. It may be helpful in the early diagnosis of coronary microvascular dysfunction for HCM. Key words: Cardiomyopathy, hypertrophic; Myocardial perfusion imaging; Microcirculation

3.0T magnetic resonance myocardial perfusion imaging for semi-quantitative evaluation of coronary microvascular dysfunction in hypertrophic cardiomyopathy.

This study aimed to assess coronary microvascular dysfunction (CMD) differences in hypertrophic cardiomyopathy (HCM) patients using cardiac magnetic resonance (CMR) first-pass perfusion and late gadolinium enhancement imaging. Forty-seven patients with HCM and twenty-one healthy volunteers underwent CMR at rest. Imaging protocols included short axis cine, first-pass myocardial perfusion, and late gadolinium enhancement (LGE). Left ventricular end-diastolic wall thickness (EDTH), LGE, time to peak (Tpeak), maximal up-slope (Slopemax), and peak signal intensity (SIpeak) were assessed for each myocardial segment. The HCM myocardial segments were grouped by the degree of LGE and hypertrophy. Tpeak, SIpeak, Slopemax and EDTH in multiple groups were assessed and compared by ANOVA test/Kruskal-Wallis test. The Spearman correlation test was used to determine the relationships between EDTH, LGE and perfusion parameters (Tpeak, Slopemax and SIpeak). Compared to control group segments, Tpeak increased while Slopemax and SIpeak decreased in non-LGE/non-hypertrophic segments and LGE/hypertrophic segments in the HCM group, while Tpeak increased more significantly in LGE/hypertrophic segments (all p < 0.05). Tpeak statistically increased with increasing degrees of myocardial LGE (p < 0.01). Differences in Tpeak, SIpeak and EDTH were observed between segments with and without hypertrophy (p < 0.05). EDTH and LGE were positively correlated with Tpeak (r = 0.279, p = 0.031 and r = 0.237, p < 0.001). 3.0T magnetic resonance myocardial perfusion imaging identifies abnormal perfusion in non-LGE and non-hypertrophic segments of HCM patients, and it may be helpful in the early diagnosis of coronary microvascular dysfunction in HCM. This abnormal perfusion is associated with the severity of myocardial fibrosis and the degree of hypertrophy.

Hypertrophic cardiomyopathy: Cardiac structural and microvascular abnormalities as evaluated with multi-parametric MRI

PurposeTo determine the relationship between myocardial structural and microvascular abnormality in hypertrophic cardiomyopathy (HCM) by multi-parametric cardiac MRI. Materials and methodsTwenty-four HCM and eighteen controls were retrospectively included. Left ventricle mass (LVM), LV end-systolic and end-diastolic volume (LVESV, LVEDV), LV ejection fraction (LVEF), and 16-segment wall thickness at ES and ED (SESWT, SEDWT) were assessed with a 2D cine-MRI. Myocardial perfusion (reflected by Ktrans), interstitial volume (Ve) and mean transmit time (MTT) were evaluated with a model-dependent dynamic contrast-enhanced MRI. Myocardial fibrosis was assessed with late gadolinium enhancement (LGE) imaging. ResultsKtrans was significantly decreased in LGE-present (0.74±0.15mL/g/min) against LGE-absent (0.55±0.14mL/g/min, p=0.030) and normal group (0.81±0.32mL/g/min, p<0.001), but was unchanged in LGE-absent against normal group (p>0.05). Ve and MTT were significantly increased in LGE-present (Ve: 26.7±15.7%; MTT: 28.6±21.3s) against LGE-absent (37.6±18.3%; 49.8±30.5s) and normal group (19.7±6.9%; 15.1±3.9s; all p<0.001), and were significantly increased in LGE-absent against normal group (p<0.001). LGE significantly correlated to Ktrans, Ve, MTT, and SESWT (ρ=0.232, −0.247, −0.443, and −0.207, respectively). Ktrans negatively correlated to SEDWT and SESWT (ρ=−0.224 and −0.231). Ve and MTT positively correlated to SEDWT (Ve: ρ=0.223; MTT: ρ=0.239) and SESWT (Ve: ρ=0.248; MTT: ρ=0.254). ConclusionsConsistent relationship was determined between myocardial structural abnormality and microvascular dysfunction in HCM.

A COMBINATION OF 123I-BMIPP SPECT AND STRESS 201TL MYOCARDIAL PERFUSION SPECT AS A USEFUL PROGNOSTIC MARKER OF ASYMPTOMATIC PATIENTS WITH NON-OBSTRUCTIVE HYPERTROPHIC CARDIOMYOPATHY

Reduced coronary flow reserve (CFR) indicates adverse clinical outcome in hypertrophic cardiomyopathy (HCM). 123I-BMIPP (BMIPP) SPECT and stress 201Tl (TL) SPECT has been used to evaluate coronary microvascular dysfunction in HCM. We investigated the long-term prognostic value of BMIPP and stress TL

Coronary microvascular ischemia in hypertrophic cardiomyopathy - a pixel-wise quantitative cardiovascular magnetic resonance perfusion study.

BackgroundMicrovascular dysfunction in HCM has been associated with adverse clinical outcomes. Advances in quantitative cardiovascular magnetic resonance (CMR) perfusion imaging now allow myocardial blood flow to be quantified at the pixel level. We applied these techniques to investigate the spectrum of microvascular dysfunction in hypertrophic cardiomyopathy (HCM) and to explore its relationship with fibrosis and wall thickness.MethodsCMR perfusion imaging was undertaken during adenosine-induced hyperemia and again at rest in 35 patients together with late gadolinium enhancement (LGE) imaging. Myocardial blood flow (MBF) was quantified on a pixel-by-pixel basis from CMR perfusion images using a Fermi-constrained deconvolution algorithm. Regions-of-interest (ROI) in hypoperfused and hyperemic myocardium were identified from the MBF pixel maps. The myocardium was also divided into 16 AHA segments.ResultsResting MBF was significantly higher in the endocardium than in the epicardium (mean ± SD: 1.25 ± 0.35 ml/g/min versus 1.20 ± 0.35 ml/g/min, P < 0.001), a pattern that reversed with stress (2.00 ± 0.76 ml/g/min versus 2.36 ± 0.83 ml/g/min, P < 0.001). ROI analysis revealed 11 (31%) patients with stress MBF lower than resting values (1.05 ± 0.39 ml/g/min versus 1.22 ± 0.36 ml/g/min, P = 0.021). There was a significant negative association between hyperemic MBF and wall thickness (β = −0.047 ml/g/min per mm, 95% CI: −0.057 to −0.038, P < 0.001) and a significantly lower probability of fibrosis in a segment with increasing hyperemic MBF (odds ratio per ml/g/min: 0.086, 95% CI: 0.078 to 0.095, P = 0.003).ConclusionsPixel-wise quantitative CMR perfusion imaging identifies a subgroup of patients with HCM that have localised severe microvascular dysfunction which may give rise to myocardial ischemia.

Assessment of coronary microvascular dysfunction in hypertrophic cardiomyopathy: First-pass myocardial perfusion cardiovascular magnetic resonance imaging at 1.5 T

To evaluate the integrity of the coronary microvasculature in patients with hypertrophic cardiomyopathy (HCM) using first-pass magnetic resonance perfusion imaging. Twenty-two patients with HCM and 13 healthy volunteers underwent cardiac magnetic resonance imaging (CMR) at rest. Imaging protocols included short axis cine, first-pass myocardial perfusion, and late-phase contrast-enhanced imaging. Left ventricular end-diastolic wall thickness (EDTH), myocardial thickening, maximal upslope of time-intensity curve (slopemax), and late myocardial gadolinium enhancement (LGE) were assessed for each myocardial segment. The differences in slopemax, myocardial thickening, and EDTH between healthy volunteers and HCM patients were evaluated as were differences among hypertrophic segments of different severities (mild, moderate, and severe hypertrophy) in a one-way analysis of variance analysis. The differences in slopemax, myocardial thickening, and EDTH between the segments with and without LGE were compared by independent-sample t-test. A Pearson correlation test was used to determine the relationships between slopemax, EDTH, and myocardial thickening. Slopemax was statistically significantly less in HCM patients; the degree of myocardial thickening was also significantly reduced (p < 0.001). Slopemax and the degree of thickening statistically significantly decreased with increasing degrees of myocardial hypertrophy (p < 0.05). Differences in slopemax, myocardial thickening, and EDTH were observed between segments with and without LGE (p < 0.05). Slopemax and myocardial thickening were negatively correlated with EDTH. First-pass myocardial perfusion CMR with slopemax measurements demonstrates microvascular coronary dysfunction in patients with HCM, a determination that may aid in risk stratification, therapeutic planning, and determination of prognosis for HCM.

Relation of Coronary Microvascular Dysfunction in Hypertrophic Cardiomyopathy to Contractile Dysfunction Independent from Myocardial Injury

We studied the spatial relations among hyperemic myocardial blood flow (hMBF), contractile function, and morphologic tissue alterations in 19 patients with hypertrophic cardiomyopathy (HC). All patients were studied with oxygen-15 water positron emission tomography during rest and adenosine administration to assess myocardial perfusion. Cardiovascular magnetic resonance was performed to derive delayed contrast-enhanced images and to calculate contractile function (E(cc)) with tissue tagging. Eleven healthy subjects underwent similar positron emission tomographic and cardiovascular magnetic resonance scanning protocols and served as a control group. In the HC group, hMBF averaged 2.46 ± 0.91 ml/min/g and mean E(cc) was -14.7 ± 3.4%, which were decreased compared to the control group (3.97 ± 1.48 ml/min/g and -17.7 ± 3.2%, respectively, p <0.001 for the 2 comparisons). Delayed contrast enhancement (DCE) was present only in patients with HC, averaging 6.2 ± 10.3% of left ventricular mass. In the HC group, E(cc) and DCE in the septum (-13.7 ± 3.6% and 10.2 ± 13.6%) significantly differed from the lateral wall (-16.0 ± 2.8% and 2.4 ± 5.9%, p <0.001 for the 2 comparisons). In general, hMBF and E(cc) were decreased in segments displaying DCE compared to nonenhanced segments (p <0.001 for the comparisons). In the HC group, univariate analysis revealed relations of hMBF to E(cc) (r = -0.45, p <0.001) and DCE (r = -0.31, p <0.001). Multivariate analysis revealed that E(cc) was independently related to hMBF (beta -0.37, p <0.001) and DCE (beta 0.28, p <0.001). In conclusion, in HC hMBF is impaired and related to contractile function independent from presence of DCE. When present, DCE reflected a progressed disease state as characterized by an increased perfusion deficit and contractile dysfunction.

Microvascular dysfunction in hypertrophic cardiomyopathy evaluated by cardiac magnetic resonance and computed tomography

A 36-year-old woman with hypertrophic cardiomyopathy (HCM) was referred for the evaluation of chest pain.A stress cardiac magnetic resonance showed severe hypertrophy of the anteroseptal wall with severe ischaemia induced after adenosine infusion. LV size and function were normal. On delayed enhancement imaging, extensive, patchy areas of hyperenhancement in the hypertrophic segments were observed. A 64-slice computed tomography scan showed no evidence of significant coronary disease. Microvascular dysfunction in HCM may be a predisposing factor for myocardial ischaemia, leading to an increased risk of sudden death. However, the pathophysiological mechanisms remain largely unknown as well as whether the extension of the hypertrophy is associated with poor perfusion reserve. Non-invasive imaging modalities may be helpful in the identification of the underlying substrate determining the risk in these patients.

Determinants of coronary microvascular dysfunction in symptomatic hypertrophic cardiomyopathy

Impaired hyperemic myocardial blood flow (MBF) in hypertrophic cardiomyopathy (HCM), despite normal epicardial coronary arteries, results in microvascular dysfunction. The aim of the present study was to determine the relative contribution of extravascular compressive forces to microvascular dysfunction in HCM. Eighteen patients with symptomatic HCM and normal coronary arteries and 10 age-matched healthy volunteers were studied with PET to quantify resting and hyperemic MBF at a subendocardial and subepicardial level. In HCM patients, MRI was performed to determine left ventricular (LV) mass index (LVMI) and volumes, echocardiography to assess diastolic perfusion time, heart catheterization to measure LV outflow tract gradient (LVOTG) and LV pressures, and serum NH(2)-terminal pro-brain natriuretic peptide (NT-proBNP) as a biochemical marker of LV wall stress. Hyperemic MBF was blunted in HCM vs. controls (2.26 +/- 0.97 vs. 2.93 +/- 0.64 ml min(-1) g(-1), P < 0.05). In contrast to controls (1.38 +/- 0.15 to 1.25 +/- 0.19, P = not significant), the endocardial-to-epicardial MBF ratio decreased significantly in HCM during hyperemia (1.20 +/- 0.11 to 0.88 +/- 0.18, P < 0.01). This pattern was similar for hypertrophied septum and lateral wall. Hyperemic MBF was inversely correlated with LVOTG, NT-proBNP, left atrial volume index, and LVMI (all P < 0.01). Multivariate regression analysis, however, revealed that only LVMI and NT-proBNP were independently related to hyperemic MBF, with greater impact at the subendocardial myocardial layer. Hyperemic MBF is more severely impaired at the subendocardial level in HCM patients. The level of impairment is related to markers of increased hemodynamic LV loading conditions and LV mass. These observations suggest that, in addition to reduced capillary density caused by hypertrophy, extravascular compressive forces contribute to microvascular dysfunction in HCM patients.

Evidence for Microvascular Dysfunction in Hypertrophic Cardiomyopathy

Microvascular dysfunction in hypertrophic cardiomyopathy (HCM) may create an ischemic substrate conducive to sudden death, but it remains unknown whether the extent of hypertrophy is associated with proportionally poorer perfusion reserve. Comparisons between magnitude of hypertrophy, impairment of perfusion reserve, and extent of fibrosis may offer new insights for future clinical risk stratification in HCM but require multiparametric imaging with high spatial and temporal resolution. Degree of hypertrophy, myocardial blood flow at rest and during hyperemia (hMBF), and myocardial fibrosis were assessed with magnetic resonance imaging in 35 HCM patients (9 [26%] male/26 female) and 14 healthy controls (4 [29%] male/10 female), aged 18 to 78 years (mean+/-SD, 42+/-14 years) with the use of the American Heart Association left ventricular 16-segment model. Resting MBF was similar in HCM patients and controls. hMBF was lower in HCM patients (1.84+/-0.89 mL/min per gram) than in healthy controls (3.42+/-1.76 mL/min per gram, with a difference of -0.95+/-0.30 [SE] mL/min per gram; P<0.001) after adjustment for multiple variables, including end-diastolic segmental wall thickness (P<0.001). In HCM patients, hMBF decreased with increasing end-diastolic wall thickness (P<0.005) and preferentially in the endocardial layer. The frequency of endocardial hMBF falling below epicardial hMBF rose with wall thickness (P=0.045), as did the incidence of fibrosis (P<0.001). In HCM the vasodilator response is reduced, particularly in the endocardium, and in proportion to the magnitude of hypertrophy. Microvascular dysfunction and subsequent ischemia may be important components of the risk attributable to HCM.

554 Coronary microvascular dysfunction in hypertrophic cardiomyopathy: Doppler echocardiography study

554 Coronary microvascular dysfunction in hypertrophic cardiomyopathy: Doppler echocardiography study