Myocardial Ischemia In Hypertrophic Cardiomyopathy Research Articles

Microvascular Dysfunction in Hypertrophic Cardiomyopathy.

Myocardial ischemia is an established pathophysiological feature of hypertrophic cardiomyopathy (HCM) that impacts various clinical features, including heart failure (HF) and sudden cardiac death (SCD). The major determinant of myocardial ischemia in HCM is coronary microvascular dysfunction (CMD) in the absence of epicardial coronary artery abnormalities. Despite the impossibility to directly visualize microcirculation in vivo, a multimodality approach can allow a detailed assessment of microvascular dysfunction and ischemia. Accordingly, the non-invasive assessment of CMD using transthoracic Doppler echocardiography, positron emission tomography, and cardiac magnetic resonance should now be considered mandatory in any HCM patient. Noteworthy, a complete diagnostic work-up for myocardial ischemia plays a major role in the approach of the patients with HCM and their risk stratification. Chronic and recurrent episodes of ischemia can contribute to fibrosis, culminating in LV remodeling and HF. Ischemia can potentially constitute an arrhythmic substrate and might prove to have an added value in risk stratification for SCD. Accordingly, strategies for the early diagnosis of CMD should now be considered an important challenge for the scientific community.

Examining the impact of inducible ischemia on myocardial fibrosis and exercise capacity in hypertrophic cardiomyopathy

Myocardial ischemia in hypertrophic cardiomyopathy (HCM) is associated with poor outcomes. Vasodilator stress cardiac magnetic resonance (CMR) can detect and quantitate inducible ischemia in HCM patients. We hypothesized that myocardial ischemia assessed by CMR is associated with myocardial fibrosis and reduced exercise capacity in HCM. In 105 consecutive HCM patients, we performed quantitative assessment of left ventricular volume and mass, wall thickness, segmental wall thickening percent, segmental late Gadolinium enhancement (LGE), and extracellular volume fraction (ECV). Time-signal intensity curves of first pass perfusion sequences were generated for each segment at stress and rest. A myocardial perfusion reserve index (MPRI) (stress/rest slope) was calculated. Patients who underwent an echocardiographic (n = 73) and cardiopulmonary exercise test (n = 37) within 30 days were included. The mean age was 53.2 ± 15.4 years; 60% were male, and 82 patients had asymmetric hypertrophy. Segments with end diastolic thickness ≥ 1.2 cm had a higher burden of LGE (4.1% vs 0.5% per segment), reduced MPRI (2.6 ± 1.5 vs 3.1 ± 1.8) and reduced thickening percent (48.9 ± 41.7% vs. 105.3 ± 59.5%), (P < 0.0001 for all comparisons). Patients with ischemia (any segment with MPRI < 2) were more likely to have dynamic left ventricular outflow tract (LVOT) obstruction (63.3% vs 36.7%, P = 0.01), to be smokers (17% vs 6.9%, P = 0.04), and had a higher ECV (30% vs 28%, P = 0.04). The total LGE burden was similar between the two groups (P = 0.47). Increasing ischemia burden (number of segments with MPRI < 2) was associated with worsened ventilatory efficiency (VE/VCO2) (P < 0.001) but not peak oxygen consumption or anerobic threshold (P > 0.2). In a patient-level multivariable logistic regression model, only LVOT obstruction remained a significant predictor of ischemia burden (P = 0.03). Myocardial ischemia by CMR is associated with myocardial segmental dysfunction and interstitial fibrosis, as assessed by ECV, in HCM patients, even in segments free of LGE. Conversely, quantitative ischemia burden was not associated with replacement fibrosis as assessed by total LGE burden. Patients with ischemia had greater prevalence of dynamic LVOT obstruction; and in a subset of patients with cardiopulmonary exercise testing, ischemia burden was associated with worsened ventilatory efficiency.

Relationship of Delayed Enhancement by Magnetic Resonance to Myocardial Perfusion by Positron Emission Tomography in Hypertrophic Cardiomyopathy

Presence of delayed enhancement (DE) on cardiac magnetic resonance (CMR) is associated with worse clinical outcomes in hypertrophic cardiomyopathy. We investigated the relationship between DE on CMR and myocardial ischemia in hypertrophic cardiomyopathy. Hypertrophic cardiomyopathy patients (n=47) underwent CMR for assessment of DE and vasodilator stress ammonia positron emission tomography to quantify myocardial blood flow and coronary flow reserve. The summed difference score for regional myocardial perfusion was also assessed. Patients in the DE group (n=35) had greater left ventricular wall thickness (2.09±0.44 versus 1.78±0.34 cm; P=0.03). Stress myocardial blood flow (2.25±0.46 versus 1.78±0.43 mL/min per gram; P=0.01) and coronary flow reserve (2.78±0.32 versus 2.01±0.52; P<0.001) were significantly lower in DE-positive patients. Summed difference score (7.3±6.6 versus 0.9±1.4; P<0.0001) was significantly higher in patients with DE. A coronary flow reserve <2.00 was seen in 18 patients (51%) with DE but in none of the DE-negative patients (P<0.0001). CMR and positron emission tomography showed visually concordant DE and regional myocardial perfusion abnormalities in 31 patients and absence of DE and perfusion defects in 9 patients. Four DE-positive patients demonstrated normal regional myocardial perfusion, and 3 DE-negative patients had (apical) regional myocardial perfusion abnormalities. We found a close relationship between DE by CMR and microvascular function in most of the patients studied. However, a small proportion of patients had DE in the absence of perfusion abnormalities, suggesting that microvascular dysfunction and ischemia are not the sole causes of DE in hypertrophic cardiomyopathy patients.

No-reflow pattern in penetrating intramyocardial coronary artery suggests myocardial ischemia in hypertrophic cardiomyopathy

No-reflow pattern in penetrating intramyocardial coronary artery suggests myocardial ischemia in hypertrophic cardiomyopathy

Increased plasma brain natriuretic peptide level as a guide for silent myocardial ischemia in patients with non-obstructive hypertrophic cardiomyopathy

ObjectivesWe measured plasma atrial/brain natriuretic peptide (ANP/BNP) levels at rest and during exercise and correlated the results with various clinical findings, particularly with myocardial ischemia, in asymptomatic hypertrophic cardiomyopathy (HCM). BackgroundIn patients with HCM, ANP and BNP levels are elevated and exercise-induced myocardial ischemia is common. However, it has not yet been elucidated how these levels at rest and their change with dynamic exercise are related to ischemia. MethodsLevels of ANP and BNP were measured at rest and at peak exercise during 99mTc-tetrofosmin scintigraphy in 31 asymptomatic patients with non-obstructive HCM and in 10 control subjects. ResultsLevels of ANP and BNP at rest and the change of ANP and BNP levels (pg/ml) from rest to exercise were significantly greater in HCM than in control subjects (ANP: rest, 53.2 ± 31.8 vs. 11.6 ± 6.1; exercise, 114.5 ± 74.8 vs. 28.3 ± 23.4. BNP: rest, 156.7 ± 104.1 vs. 9.8 ± 9.6; exercise, 201.6 ± 131.5 vs. 13.2 ± 14.5). Septal perforator compression (SPC) and exercise-induced ischemia were observed, respectively, in 20 (64.5%) and in 19 (61.3%) patients with HCM. The increment of ANP during exercise was similar between HCM subgroups with or without inducible ischemia. However, BNP levels at rest and BNP increments during exercise were significantly greater in the HCM subgroup with inducible ischemia than in the subgroup without (rest, 190.5 ± 116.2 vs. 103.1 ± 48.3; exercise, 250.5 ± 142.2 vs. 124.2 ± 58.6). Multiple logistic regression analysis revealed that SPC and BNP levels at rest were independently associated with exercise-induced ischemia. ConclusionsMeasurement of plasma BNP levels at rest may be useful in predicting silent myocardial ischemia in HCM.

Immunohistochemical Analysis of Platelet-derived Growth Factor-B Expression in Myocardial Tissues In Hypertrophic Cardiomyopathy

Intimal and/or medial hyperplasia of intramyocardial small vessels is thought to be one of the causes of myocardial ischemia in hypertrophic cardiomyopathy (HCM). However, the pathogenesis of such vascular lesions in HCM is not yet known. To evaluate the pathogenic role of platelet-derived growth factor (PDGF-B) and basic fibroblast growth factor (b-FGF), which have a potential to induce cellular and molecular changes observed in the vessels in HCM, we examined the expression of these molecules and PDGF receptors in cardiac tissues from six patients with HCM and seven controls using immunohistochemistry. The percentage of PDGF-B positive cells in the myocyte population in HCM was significantly higher than that in controls (52.6 ± 16.2 (mean ± SD) vs. 21.6 ± 9.6, p < 0.01). PDGF-B was also observed in vascular regions in HCM (61.1 ± 25.5% of arterioles) but not in controls. There were no significant differences in the expression of b-FGF and PDGF receptors in the myocyte and non-myocyte populations and the vascular regions between the HCM and control groups. Our study revealed that the expression of PDGF-B protein was up-regulated in HCM, suggesting the contribution of this molecule to the development of intramyocardial vasculopathy.

Abnormal coronary flow profiles at rest and during rapid atrial pacing in patients with hypertrophic cardiomyopathy.

To examine the mechanism of myocardial ischemia in hypertrophic cardiomyopathy (HCM), coronary flow velocity was measured in the left anterior descending coronary artery (LAD) using a Doppler guide wire in 11 patients with HCM and in 8 normal controls. The average peak velocity (APV), percent increase of APV (%APV), and APV during systole (Vs) and diastole (Vd) were calculated at rest and during rapid atrial pacing. The APV in HCM reached a peak value at a heart rate of 90 beats/min, while in the controls the APV increased continuously until the heart rate reached 130 beats/min [%APV (130 beats/min); 103+/-30% in HCM vs 139+/-23% in controls, p<0.04]. During rapid atrial pacing, Vs in the controls increased, whereas Vs in HCM decreased further. During high-rate pacing, Vd in HCM reached a peak value at a heart rate of 90 beats/min, whereas in the controls, Vd increased continuously until the heart rate reached 130 beats/min. The acceleration rate of early diastolic flow was significantly lower in HCM than in the controls (1.85+/-0.66 vs 3.18+/-1.62 m/s2, p<0.03). This abnormal response might be due to an increase in the reverse systolic flow and a decrease in the diastolic flow, probably caused by a slow acceleration of early diastolic flow velocity in the LAD.

Myocardial metabolic abnormalities in hypertrophic cardiomyopathy assessed by iodine-123-labeled beta-methyl-branched fatty acid myocardial scintigraphy and its relation to exercise-induced ischemia.

Reversible thallium-201 (201Tl) abnormalities during exercise stress have been used as markers of myocardial ischemia in hypertrophic cardiomyopathy (HCM) and are most likely to identify relatively underperfused myocardium. Although metabolic abnormalities in HCM were reported, the relationship between impaired energy metabolism and exercise-induced ischemia has not been fully elucidated as yet. To assess the relationship between myocardial perfusion abnormalities and fatty acid metabolic abnormalities, 28 patients with HCM underwent exercise 201Tl and rest 123I-15-(p-iodophenyl)-3-methyl pentadecanoic acid (BMIPP) scintigraphy. Perfusion abnormalities were observed by exercise 201Tl in 19/28 patients with HCM. 123I-BMIPP uptake was decreased compared with delayed 201Tl in 106/364 (29%) of the total myocardial segments (p<0.01, McNemar symmetry test). Such disparity between 123I-BMIPP and 201Tl was observed more often in the 49/75 (65%) segments with reversible exercise 201Tl defects (p<0.001). Our results indicate that exercise-induced myocardial ischemia exists in HCM, resulting in metabolic abnormalities. The combination of 123I BMIPP and 201Tl suggests that myocardial ischemia may play an important role in metabolic abnormalities in HCM.

901-103 Effects of Dual Chamber Pacing on Myocardial Ischemia in Hypertrophic Cardiomyopathy Studied with 13-N Ammonia and 18-FDG Positron Emission Tomography

Dual chamber (DDD) pacing improves symptoms of angina in most patients with hypertrophic cardiomyopathy (HCM). Besides reduction of outflow tract obstruction, other factors may be operative, since symptoms also improve in HCM without severe obstruction. We studied with positron emission tomography (PET) whether permanent DDD pacing would influence myocardial perfusion (MP) and myocardial perfusion reserve (MPR). Six patients (age 52 ± 7 yrs) were treated with DDD pacing for HCM with angina refractory to medication. Before and 3 months after DDD insertion MP and MPR (ratio of dipyridamole and resting perfusion) were studied with 13-NH3 PET at rest and during a dipyridamole stress test. Myocardial glucose uptake was studied with 18-fluoro-deoxy-glucose PET (FDG). All studies were performed off medication. Results were compared to 18 normals.Empty CellMP (ml/l00 g/min)MPRSeptal-FDG (ml/l00 g/min)Baseline173 ± 27*1.40 ± 0.27*665 ± 9.0*DDD102 ± 23*1.70 ± 0.18*48.8 ± 8.5*Normals96 ± 191.96 ± 0.3454.8 ± 14.7*P &lt; 0.05 P &lt; 0.05 Thus DDD pacing decreased baseline myocardial perfusion and increased perfusion reserve in HCM. The decrease in septal FDG uptake suggests a reduction of septal ischemia. This is probably due to a reduction in outflow tract obstruction in combination with early septal activation resulting in reduced septal fiber strain and a redistribution in blood flow.

925-41 Coronary Sinus pH During Dipyridamole Infusion in Patients with Angina and Hypertrophic Cardiomyopathy

Typical angina pectoris and myocardial scarring suggestive of ischemia are common in patients with hypertrophic cardiomyopathy (HCM). However, the clinical evaluation of myocardial ischemia in HCM remains problematic as baseline ECG abnormalities are frequent and thallium-201 perfusion abnormalities correlate poorly with anginal symptoms. Similarly, coronary sinus lactate studies are subject to sampling errors. Coronary sinus pH measurement using a catheter mounted pH electrode is a validated, sensitive technique for the detection of myocardial ischemia. The change in coronary sinus pH during i.v. dipyridamole was determined in 10 patients with HCM and typical exertional chest pain (7 male, mean age 35 ± 11 years, range 19–53). Eight patients had ST segment depression of ≥ 1 mm in 2 or more leads of the baseline ECG at rest and 4 had reversible perfusion defects during stress thallium-201 scintigraphy. The pH electrode was introduced into the coronary sinus via the subclavian vein and dipyridamole (0.5 mg/kg) administered by slow i.v. injection. All patients experienced typical chest pain associated with a fall in coronary sinus pH (mean 0.08 ± 0.04, range: 0.020.15 units). Eight patients had changes ≥ 0.04 units. ST depression ( ≥ 1 mm from baseline) occurred in 3 patients. Peak heart rate Imean 95.5 ± 12 bpm, range 80 – 115) correlated with the maximal pH change (r = 0.7, P = 0.02). There was no association between maximum pH change and left ventricular dimensions or outflow tract gradient. Chest pain during dipyridamole infusion in patients with HCM is caused by myocardial ischemia. Coronary sinus pH electrodes can be used successfully in the evaluation of myocardial ischemia risk in patients with HCM.

Myocardial metabolic, hemodynamic, and electrocardiographic significance of reversible thallium-201 abnormalities in hypertrophic cardiomyopathy.

Exercise-induced abnormalities during thallium-201 scintigraphy that normalize at rest frequently occur in patients with hypertrophic cardiomyopathy. However, it is not known whether these abnormalities are indicative of myocardial ischemia. Fifty patients with hypertrophic cardiomyopathy underwent exercise 201Tl scintigraphy and, during the same week, measurement of myocardial lactate metabolism and hemodynamics during pacing stress. Thirty-seven patients (74%) had one or more 201Tl abnormalities that completely normalized after 3 hours of rest; 26 had regional myocardial 201Tl defects, and 26 had apparent left ventricular cavity dilatation with exercise, with 15 having coexistence of these abnormal findings. Of the 37 patients with reversible 201Tl abnormalities, 27 (73%) had metabolic evidence of myocardial ischemia during rapid atrial pacing (myocardial lactate extraction of 0 mmol/l or less) compared with four of 13 patients (31%) with normal 201Tl scans (p less than 0.01). Eleven patients had apparent cavity dilatation as their only 201Tl abnormality; their mean postpacing left ventricular end-diastolic pressure was significantly higher than that of the 13 patients with normal 201Tl studies (33 +/- 5 versus 21 +/- 10 mm Hg, p less than 0.001). There was no correlation between the angiographic presence of systolic septal or epicardial coronary arterial compression and the presence or distribution of 201Tl abnormalities. Patients with ischemic ST segment responses to exercise had an 80% prevalence rate of reversible 201Tl abnormalities and a 70% prevalence rate of pacing-induced ischemia. However, 69% of patients with nonischemic ST segment responses had reversible 201Tl abnormalities, and 55% had pacing-induced ischemia. Reversible 201Tl abnormalities during exercise stress are markers of myocardial ischemia in hypertrophic cardiomyopathy and most likely identify relatively underperfused myocardium. In contrast, ST segment changes with exercise and systolic compression of coronary arteries on angiography are unreliable markers of inducible myocardial ischemia in hypertrophic cardiomyopathy. Apparent cavity dilatation during 201Tl scintigraphy may indicate ischemia-related changes in left ventricular filling, with elevation in diastolic pressures and endocardial compression.

Myocardial stunning in hypertrophic cardiomyopathy: Recovery predicted by single photon emission computed tomographic thallium-201 scintigraphy

A young woman with hypertrophic cardiomyopathy confirmed by echocardiography and cardiac catheterization presented with chest pain and features of a large left ventricular aneurysm. The initial diagnosis was myocardial ischemia with either an evolving or an ancient myocardial infarction. Subsequently, verapamil therapy was associated with complete resolution of the extensive left ventricular wall motion abnormalities, normalization of left ventricular ejection fraction and a minimal myocardial infarction. Normal thallium uptake on single photon emission computed tomographic scintigraphy early in the hospital course predicted myocardial viability in the region of the aneurysm. Thus, orally administered verapamil may reverse spontaneous extensive myocardial ischemia in hypertrophic cardiomyopathy and possibly limit the extent of myocardial infarction in such circumstances.

Myocardial ischemia in patients with hypertrophic cardiomyopathy: contribution of inadequate vasodilator reserve and elevated left ventricular filling pressures.

To study the mechanism and hemodynamic significance of myocardial ischemia in hypertrophic cardiomyopathy, 20 patients (nine with resting left ventricular outflow tract obstruction greater than or equal to 30 mm Hg) with a history of angina pectoris and angiographically normal coronary arteries underwent a pacing study with measurement of great cardiac vein flow, lactate and oxygen content, and left ventricular filling pressure. Compared with 28 control subjects without hypertrophic cardiomyopathy, their resting coronary blood flow was higher (91 +/- 27 vs 66 +/- 17 ml/min; p less than .001) and their coronary resistance was lower (1.13 +/- 0.38 vs 1.55 +/- 0.45 mm Hg/ml/min; p less than .001). Left ventricular end-diastolic pressure (16 +/- 6 vs 11 +/- 3 mm Hg; p less than .001) and pulmonary arterial wedge pressure (13 +/- 5 vs 7 +/- 3 mm Hg; p less than .001) were significantly higher in patients with hypertrophic cardiomyopathy. During pacing, coronary flow rose in both groups, although coronary and myocardial hemodynamics differed greatly. In contrast to the linear increase in flow in control subjects up to heart rate of 150 beats/min (66 +/- 17 to 125 +/- 28 ml/min), patients with hypertrophic cardiomyopathy demonstrated an initial rise in flow to 133 +/- 31 ml/min at an intermediate heart rate of 130 beats/min. At this point, 12 of 20 patients developed their typical chest pain. With continued pacing to a heart rate of 150 beats/min, mean coronary flow fell to 114 +/- 29 ml/min (p less than .002), with 18 of 20 patients experiencing their typical chest pain and metabolic evidence of myocardial ischemia. This fall in coronary flow was associated with a substantial rise in left ventricular end-diastolic pressure (30 +/- 9 mm Hg immediately after peak pacing). In the 14 patients whose coronary flow actually fell from intermediate to peak pacing, the rise in left ventricular end-diastolic pressure in the same interval was greater than that of the six patients whose flow remained unchanged or increased (11 +/- 8 vs 2 +/- 2 mm Hg; p less than .01). In addition, despite metabolic and hemodynamic evidence of myocardial ischemia, the arteriovenous O2 difference actually narrowed at peak pacing. Thus most patients with hypertrophic cardiomyopathy achieved maximum coronary vasodilation and flow at modest increases in heart rate. Elevation in left ventricular filling pressure, probably related to ischemia-induced changes in ventricular compliance, was associated with a decline in coronary flow.(ABSTRACT TRUNCATED AT 400 WORDS)