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Background: Microvascular dysfunction, reflected by an inadequate increase in myocardial blood flow in response to dipyridamole infusion, is a recognized feature of hypertrophic cardiomyopathy. Its long-term effect on the prognosis is unknown. We prospectively evaluated a cohort of patients with hypertrophic cardiomyopathy after they had undergone quantitative assessment of myocardial blood flow by positron-emission tomography (PET). Methods: Fifty-one patients (New York Heart Association class I or II) were followed for a mean (+/-SD) of 8.1+/-2.1 years after PET. Twelve subjects with atypical chest pain served as controls. Measurement of flow was performed at base line and after the infusion of the coronary vasodilator dipyridamole, with the use of nitrogen-13-labeled ammonia. Patients were then divided into three equal groups with increasing values of myocardial blood flow. Results: The response of myocardial blood flow to dipyridamole was severely blunted in the patients, as compared with the controls (1.50+/-0.69 vs. 2.71+/-0.94 ml per minute per gram of tissue, P

We sought to test the response of the coronary microcirculation to alpha-adrenoceptor blockade in patients with syndrome X (angina, ischemia-like stress electrocardiogram, and a normal coronary arteriogram). The response of the microcirculation was assessed by quantification of coronary vasodilator reserve (the ratio of hyperemic to resting myocardial blood flow). We investigated 28 patients with syndrome X [18 women, age 54.4 (7.6) years]. Myocardial blood flow was measured at rest and after dipyridamole by using positron emission tomography with H(2)15O. The measurements were made before and after treatment for 10 days with doxazosin (1 mg o.d. for 3 days, followed by 2 mg o.d. for 7 days) or a matched placebo, similarly administered. Patients were randomized to alpha1-blockade or to placebo in double-blind fashion. No significant differences were demonstrable between syndrome X patients treated with doxazosin and those receiving placebo, with respect to resting myocardial blood flow, myocardial blood flow after dipyridamole, or coronary vasodilator reserve (the ratio of the latter two). In addition, no relations were demonstrable among myocardial blood flow, coronary vasodilator reserve, development of chest pain after dipyridamole, or development of ischemia-like ECG changes. Doxazosin had no effect on the perception of chest pain after dipyridamole. No differences were found between the effects of alpha1-blockade with doxazosin or those of placebo with respect to myocardial blood flow in syndrome X. The values obtained for myocardial blood flow and coronary vasodilator reserve for the patients were within the normal range. The data do not support the case for alpha1-mediated vasoconstriction having an etiologic role in the chest pain of syndrome X.

Non-sustained ventricular tachycardia on Holter and syncope have been considered risk factors for sudden death in hypertrophic cardiomyopathy. Aims In these patients the coronary vasodilator reserve is impaired despite normal coronaries, so we evaluated the correlation between the severity of coronary vasodilator reserve impairment and the occurrence of syncope and non-sustained ventricular tachycardia. Methods and Results Eighty-four patients with hypertrophic cardiomyopathy (62 males, age 43 +/- 12 years) had a two-dimensional echocardiographic study and a 48-h Holter. Myocardial blood flow was measured by positron emission tomography, at baseline and after dipyridamole, and the coronary vasodilator reserve was computed as dipyridamole myocardial blood flow/baseline myocardial blood flow. In 27 patients, subendocardial and subepicardial myocardial blood flow was measured in the septum and the subendocardial/subepicardial ratio was computed. Twenty of 84 patients had at least one syncopal episode, and 26 had at least one run of non-sustained ventricular tachycardia on Holter. Baseline and dipyridamole myocardial blood flow, coronary vasodilator reserve, and baseline and dipyridamole subendocardial/subepicardial myocardial blood flow ratio were similar in patients with and without syncope and with and without non-sustained ventricular tachycardia on Holter. However, patients with nonsustained- ventricular tachycardia had larger left ventricular end-diastolic (47+/-6 vs 44+/-5 mm, P

Background We tested the hypothesis that a reduced delivery of blood to the myocardium is involved in the develop ment of systolic dysfunction of patients with hypertrophic cardiomyopathy (HCM). Methods and Results Eighty-four patients with HCM (62 men, age 43 +/- 12 years) were studied. Left ventricular dimensions and function (fractional shortening) were evaluated by 2-dimensional echocordiography. Myocardial blood flow (MBF) was measured by N-13-ammonia or O-15-water and positron emission tomography at baseline and after dipyridamole; coronary vasodilator reserve (CVR) was calculated as dipyridamole/baseline MBF. Patients with HCM in advanced New York Heart Association (NYHA) classes had lower dipyridamole MBF (NYHA class I = 1.57 +/- 0.64 vs class II = 1.52 +/- 0.58 vs class III = 0.96 +/- 0.32 mL/min per gram; analysis of variance, P < .05) and CVR (NYHA class I = 1.93 +/- 0.64 vs class II = 1.69 +/- 0.54 vs class III = 1.40 +/- 0.43; analysis of variance, P < .05). A positive linear correlation between fractional shortening and dipyridamole MBF was demonstrated (R = 0.23, P < .05), and patients with abnormal fractional shortening had lower dipyridamole MBF (1.07 +/-: 0.43 vs 1.58 +/- 0.62 mL/min per gram, P < .01). Conclusions systolic dysfunction in HCM may be caused by a more severe alteration of the coronary vasodilator capacity.

Objective—To compare the predictive value of dobutamine echocardiography (DE) and positron emission tomography (PET) in identifying reversible chronic left ventricular (LV) dysfunction (hibernating myocardium) in patients with coronary artery disease (CAD) and overt heart failure. Patients—30 patients (four women) with CAD and heart failure undergoing coronary artery bypass grafting (CABG). Methods—Myocardial viability was assessed with DE (5 and 10 µg/kg/min) and PET with [18F] 2-fluoro-2-deoxy-D-glucose (FDG) under hyperinsulinaemic euglycaemic clamp. Regional (echo) and global LV function (MUGA) were assessed at baseline and six months after CABG. Results—192 of the 336 (57%) dysfunctional LV segments improved function following CABG (hibernating) and the LV ejection fraction (EF) increased from 23(7) to 32(9)% (p 5%). DE and PET had similar positive predictive values (68% and 66%) in the identification of hibernating myocardium, but DE had a significantly lower negative predictive value than PET (54% v 96%; p 5%, whereas the number of DE viable segments, the baseline LVEF, and wall motion were not. Conclusions—DE has a higher false negative rate than PET in identifying recoverable LV dysfunction in patients with severe postischaemic heart failure. The amount of PET viable myocardium correlates with the functional outcome following CABG. Keywords: dobutamine echocardiography; positron emission tomography; coronary artery disease; heart failure; hibernating myocardium

In the present study we aimed to assess the effect of alpha(1)-adrenoceptor blockade on resting and hyperemic myocardial blood flow in normal humans. Myocardial blood flow, at baseline and after dipyridamole, was measured with positron emission tomography and O-15-labeled water in 11 normal volunteers at control and during alpha(1)-blockade with doxazosin. Baseline myocardial blood flow during alpha(1)-blockade was not different from control, whereas coronary resistance was significantly lower (73.48 +/- 18.31 vs. 89.84 +/- 27.96 mmHg . min . ml(-1). g(-1); P < 0.05). After dipyridamole, myocardial blood flow during alpha(1)-blockade was significantly higher (3.50 +/- 0.75 vs. 2.58 +/- 0.54 ml . min(-1). g(-1); P < 0.01) and coronary resistance lower (25.30 +/- 7.37 vs. 33.89 +/- 7.04 mmHg . min . ml(-1). g(-1); P < 0.01) compared with control. In conclusion, in normal humans, dipylidamole-induced increase in myocardial blood flow is limited by alpha(1)-mediated coronary vasoconstriction.

BACKGROUND Coronary vasodilator reserve is reduced in some patients with a history of chest pain and angiographically normal coronary arteries. ECG changes suggestive of myocardial ischemia during exercise also can be demonstrated in a subset of these patients. METHODS AND RESULTS We have investigated the correlation between coronary vasodilator reserve, assessed with 13N-labeled ammonia and positron emission tomography, and the ECG during exercise stress in 45 patients with a history of chest pain, angiographically normal coronary arteries, and a negative ergonovine test. ST segment depression on the ECG during exercise was present in 29 of 45 patients. Mean resting left ventricular blood flow was 1.04 +/- 0.22 ml.min-1.g-1; it increased to 1.32 +/- 0.47 ml.min-1.g-1 (p less than 0.01 versus baseline value) during atrial pacing and to 2.52 +/- 0.96 ml.min-1.g-1 (p less than 0.01 versus baseline value) after dipyridamole (0.56 mg/kg i.v.). No regional flow defects could be demonstrated in any patient during pacing or after dipyridamole. Myocardial flows after dipyridamole, however, did not show a normal frequency distribution (Kolmogorov-Smirnov test), and two patient populations could be identified. Twenty-nine (67%) patients had a mean left ventricular flow of 3.02 +/- 0.33 ml.min-1.g-1 after dipyridamole (range, 2.13-5.46 ml.min-1.g-1), and 14 (33%) patients had a mean flow of 1.48 +/- 0.29 ml.min-1.g-1 (range, 1.06-2.04 ml.min-1.g-1, p less than 0.01 versus the "high-flow group"). CONCLUSIONS Approximately one third of patients in our series showed a reduced coronary vasodilator reserve. Although 12 of 14 patients in the "low-flow group" had ST segment depression during exercise stress, 16 of 29 patients in the high-flow group also had ST segment depression during exercise stress. Therefore, despite a good sensitivity (86%) in identifying patients with a blunted increment of coronary flow, the ECG response during exercise stress appears to have a rather low specificity (45%). This suggests that factors other than reduced coronary reserve and myocardial ischemia may play a role in the genesis of the ST segment depression in these patients.

ObjectivesThis study sought to evaluate whether the entity of microvascular dysfunction, assessed by positron emission tomography (PET), predicts the long-term development of left ventricular (LV) remodeling and systolic dysfunction in hypertrophic cardiomyopathy (HCM).BackgroundA subgroup of patients with HCM developed LV dilation and systolic impairment. A causal role of coronary microvascular dysfunction has been suggested as the underlying pathophysiological mechanism.MethodsFifty-one patients (New York Heart Association functional class I to II) were followed up for 8.1 ± 2.1 years after measurement of resting and dipyridamole (Dip) myocardial blood flow (MBF). Left ventricular systolic dysfunction was defined as an ejection fraction (LVEF) 5 mm) during follow-up. These 11 patients showed lower Dip-MBF than the 40 with preserved LV function (1.04 ± 0.38 ml/min/g vs. 1.63 ± 0.71 ml/min/g, respectively; p = 0.001); Dip-MBF was particularly blunted in five patients with clinical progression to severe heart failure symptoms or death (Dip-MBF 0.89 ± 0.15 ml/min/g). At multivariate analysis, the two independent predictors of systolic dysfunction were Dip-MBF in the lowest tertile (45 mm; relative hazard, 12.3; p = 0.031).ConclusionsSevere microvascular dysfunction is a potent long-term predictor of adverse LV remodeling and systolic dysfunction in HCM. Our findings indicate microvascular dysfunction as a potential target for prevention of disease progression and heart failure in HCM.

Minimal forearm vascular resistances during maximal postischaemic vasodilation were measured in normotensive subjects with syndrome X, a condition characterized by angina and normal coronary arteries, in which a reduced coronary and systemic vasodilatory capacity has been reported. Age- and sex-matched normals and essential hypertensives constituted the control groups. The syndrome X patients had a significantly higher minimal forearm vascular resistance than the normals, indicating that arteriolar alterations may occur in the normotensive state and therefore cannot be considered solely as a consequence of hypertension.

Background: Exercise stress testing and dipyridamole infusion induce ischemic-like ST-segment depression in some of the patients with hypertrophic cardiomyopathy. The precise pathophysiologic meaning of these stress-induced ECG changes still appears elusive. The aim of this study was to assess the pathophysiologic meaning of these ECG changes. Methods: A high-dose dipyridamole test (two-dimensional echocardiographic and 12-lead ECG monitoring during dipyridamole infusion up to 0.84 mg/kg over 10 minutes) was performed in 22 patients with hypertrophic cardiomyopathy. In addition, regional myocardial blood flow was measured by means of N-13-ammonia and dynamic positron emission tomography in all patients at baseline and after intravenous dipyridamole (0.56 mg over 4 minutes). Results: After high-dose dipyridamole testing, seven of 22 patients (responders) had ST-segment depression over 0.2 mV from baseline while 15 of 22 (nonresponders) did not. However, echocardiographic monitoring during dipyridamole testing did not show regional or global dysfunction in any patient. Responders and nonresponders showed comparable values of septal thickness (19+/-1.6 vs 20+/-0.9 mm, P is not significant), posterior free wall thickness (10+/-0.6 vs 10+/-0.2 mm, P is not significant) and left ventricular end-diastolic diameter (45+/-2 vs 46+/-1.6 mm, P is not significant). Coronary vasodilator reserve (dipyridamole/baseline) was lower in responders than in nonresponders both in the septum (1.11+/-0.30 vs 1.72+/-0.53, P