Coronary vasodilator reserve is impaired in patients with hypertrophic cardiomyopathy and left ventricular dysfunction.

BACKGROUND: We tested the hypothesis that a reduced delivery of blood to the myocardium is involved in the development 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 echocardiography. Myocardial blood flow (MBF) was measured by N13 -ammonia or O15 -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.

[Clinical course of hypertrophic cardiomyopathy in a non selected population. The Experience of the Italian Multicenter Cardiomyopathy Study]. / Decorso clinico della cardiomiopatia ipertrofica in una popolazione non selezionata. Lésperienza dello Studio Policentrico Italiano Cardiomiopatie (SPIC).

BACKGROUND: Most of the information available on the clinical course and prognosis of hypertrophic cardiomyopathy (HCM) is based on data generated from international referral centres and as a result, it constitutes a potentially biased perspective of the disease process in this complex and diverse condition. A multicentric study was therefore set up with the aim of providing information on unselected patient populations with HCM. METHODS: The study group comprised 330 patients from 5 non-referral hospitals (mean age 42 +/- 16 years, M/F 226/104, 74-22%-obstructive, 299-91%-in NYHA class I-II) who were followed up regularly for 9.5 +/- 5.6 years. RESULTS: The vast majority of patients (n = 272, 82%) remained asymptomatic or mildly symptomatic during the follow-up period, whereas the remaining patients (n = 58, 18%) experienced clinical deterioration or died. Of the 18 patients (5%) who died of cardiovascular causes related to hypertrophic cardiomyopathy, 14 had progressive congestive heart failure and only 4 died suddenly. The annual mortality rate for cardiovascular disease was 0.57%, while the mortality rate due to sudden cardiac death was only 0.1%. The cumulative survival rate was 98, 95 and 93%, at 5, 10 and 15 years of follow-up respectively. Atrial fibrillation proved to be a relatively common (n = 81, 24%) and particularly unfavourable clinical feature, with higher mortality rate for cardiovascular causes related to hypertrophic cardiomyopathy. Syncope occurred in 47 patients (14%) but did not appear to have prognostic significance. CONCLUSIONS: In an unselected population, hypertrophic cardiomyopathy had a relatively benign prognosis that was inconsistent with its prior characterization as a generally progressive disorder, based primarily on the experience of selected referral institutions. Sudden unexpected cardiac death was distinctly uncommon, although a sizable proportion of patients, particularly the subset prone to atrial fibrillation, did experience clinical deterioration.

Syncope and ventricular arrhythmias in hypertrophic cardiomyopathy are not related to the derangement of coronary microvascular function.

UNLABELLED: 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 non-sustained ventricular tachycardia had larger left ventricular end-diastolic (47 +/- 6 vs 44 +/- 5 mm, P < 0.05) and end-systolic diameters (30 +/- 6 vs 27 +/- 4 mm, P < 0.05). CONCLUSIONS: (1) Coronary vasodilation is not more severely impaired in patients with hypertrophic cardiomyopathy and syncope or non-sustained ventricular tachycardia. (2) The left ventricle is more dilated in hypertrophic cardiomyopathy with non-sustained ventricular tachycardia.

Dipyridamole echocardiography for diagnosis of coexistent coronary artery disease in hypertrophic cardiomyopathy. Echo-Persantine International Cooperative (EPIC) Study Group--Subproject Hypertrophic Cardiomyopathy.

The recognition of coexistent coronary artery disease (CAD) in patients with hypertrophic cardiomyopathy may be difficult by noninvasive testing based upon electrocardiographic changes or perfusion defects. Dipyridamole-stress echocardiography has proved a sensitive and highly specific test for noninvasive diagnosis of CAD in various patient subsets. To establish the feasibility, safety, and diagnostic accuracy of dipyridamole-stress echocardiography in patients with hypertrophic cardiomyopathy, we performed high-dose dipyridamole testing (up to 0.84 mg/kg over 10 minutes) in 88 patients with hypertrophic cardiomyopathy (63 men; mean age +/- SD, 46 +/- 17 years). A subset of 60 patients was referred for coronary angiography independently of test results; CAD was defined as > or = 50% diameter narrowing in at least 1 major coronary vessel. Dipyridamole echocardiography/electrocardiography testing was completed in all patients, with no limiting side effects or adverse reactions. In the subgroup of 60 patients with coronary angiography (14 with and 46 without CAD), chest pain occurred in 18 patients (8 with and 10 without CAD, p = NS); ST-segment depression > or = 2 mm from baseline in 28 (7 with and 21 without CAD, p = NS); and transient dyssynergy in 10 patients (10 with and none without CAD, p < 0.0001). Assuming the transient regional dyssynergy to be the only criterion of positivity, the dipyridamole echocardiography test showed 71% sensitivity, 100% specificity, 100% positive predictive value, and 93% diagnostic accuracy for diagnosis of angiographically assessed CAD. We conclude that high-dose dipyridamole echocardiography testing may be considered a feasible and accurate tool for the noninvasive diagnosis of CAD in patients with hypertrophic cardiomyopathy.

Evidence for a systemic defect of resistance-sized arterioles in hypertrophic cardiomyopathy.

BACKGROUND: To investigate whether the abnormalities of coronary arterioles observed in association with hypertrophic cardiomyopathy represent a generalized phenomenon, both forearm and coronary vasodilator reserve were measured in 12 patients with hypertrophic cardiomyopathy. METHODS: Forearm vasodilator reserve was evaluated by measuring minimal forearm vascular resistance (Rmin, the ratio of mean intra-arterial pressure to peak forearm blood flow measured by venous plethysmography) under conditions of maximal postocclusive reactive hyperemia. RESULTS: In a subgroup (n = 5) of patients, the intra-arterial infusion of sodium nitroprusside combined with arterial occlusion did not produce additional vasodilation, indicating that the ischemic stimulus was indeed maximal. Coronary reserve was quantitated by measuring left ventricular blood flow (13N-ammonia and positron emission tomography) and coronary resistance at baseline and after intravenous dipyridamole (0.56 mg/kg). Rmin was significantly greater in patients than in a group of age- and sex-matched controls. The percentage change in coronary resistance after dipyridamole was significantly related to Rmin, whereas no correlation was found between change in coronary resistance and individual septal thickness values. CONCLUSIONS: Independent of cardiac hypertrophy, systemic and coronary arterioles of patients with hypertrophic cardiomyopathy are affected by an abnormality that may contribute to the clinical evolution of this syndrome.

Safety of intravenous high-dose dipyridamole echocardiography. The Echo-Persantine International Cooperative Study Group.

Clinical data on 10,451 high-dose (up to 0.84 mg/kg over 10 minutes) dipyridamole-echocardiography tests (DET) performed in 9,122 patients were prospectively collected from 33 echocardiographic laboratories, each contributing greater than 100 tests. All patients were studied for documented or suspected coronary artery disease (1,117 early [less than 18 days] after acute myocardial infarction and 293 had unstable angina). Significant side effects including major adverse reactions and minor but limiting side effects occurred in 113 patients (1.2%). Major adverse reactions occurred in 7 cases (0.07%). In 6 of these cases, adverse reactions were associated with echocardiographically assessed ischemia and included 1 prolonged cardiac asystole (complicated by acute myocardial infarction and coma, with death after 23 days), 1 short-lasting cardiac asystole, 2 myocardial infarctions, 1 pulmonary edema and 1 sustained ventricular tachycardia. In all 6 cases, the cardiologist-echocardiographer performing the study had a limited experience (less than 100 tests) with DET, and at off-line reading in 5 cases, the obvious echo-positivity preceded the onset of complications by 1 to 5 minutes. The only ischemia-independent major side effect was a short-lasting cardiac asystole that was reversed by aminophylline and atropine. Significant side effects associated with echocardiographically assessed ischemia occurred in 89 additional cases (21 with and 68 without concomitant echocardiographically assessed myocardial ischemia). The most frequent of these side effects was hypotension or bradycardia, or both, which occurred in 40 patients with negative and 6 with positive DET. In all cases, side effects promptly subsided after aminophylline. In 1,857 cases, the high dose was not given for echo-positivity before the eighth minute.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary vasodilation is impaired in both hypertrophied and nonhypertrophied myocardium of patients with hypertrophic cardiomyopathy: a study with nitrogen-13 ammonia and positron emission tomography.

To assess regional coronary reserve in hypertrophic cardiomyopathy, regional myocardial blood flow was measured in 23 patients with hypertrophic cardiomyopathy and 12 control subjects by means of nitrogen-13 ammonia and dynamic positron emission tomography. In patients with hypertrophic cardiomyopathy at baseline study, regional myocardial blood flow was 1.14 +/- 0.43 ml/min per g in the hypertrophied (20 +/- 3 mm) interventricular septum and 0.90 +/- 0.35 ml/min per g (p less than 0.05 versus septal flow) in the nonhypertrophied (10 +/- 2 mm) left ventricular free wall. These were not statistically different from the corresponding values in control subjects (1.04 +/- 0.25 and 0.91 +/- 0.21 ml/min per g, respectively, p = NS). After pharmacologically induced coronary vasodilation (dipyridamole, 0.56 mg/kg intravenously over 4 min), regional myocardial blood flow in patients with hypertrophic cardiomyopathy increased significantly less than in control subjects both in the septum (1.63 +/- 0.58 versus 2.99 +/- 1.06 ml/min per g, p less than 0.001) and in the free wall (1.47 +/- 0.58 versus 2.44 +/- 0.82 ml/min per g, p less than 0.001). In addition, patients with hypertrophic cardiomyopathy who had a history of chest pain had more pronounced impairment of coronary vasodilator reserve than did those without a history of chest pain. After dipyridamole, coronary resistance in the septum decreased by 38% in patients without a history of chest pain, but decreased by only 14% in those with such a history (p less than 0.05). Coronary resistance in the free wall decreased by 45% in patients without and by 27% in those with a history of chest pain (p = 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)

Reliability of cerebral radioisotopic angiography and of directional Doppler C.W. in the diagnosis of cerebrovascular insufficiency.

The diagnostic value of radioisotopic cerebral angioscintigraphy (R.A.) and of Doppler CW (D.C.W.) techniques to identify stenosis of the internal carotid artery in its extracranial course was studied in 97 patients with ischaemic lesions (50 T.I.A. and 47 Complete Stroke). The results of R.A. and D.C.W. were compared with those of contrast carotid-angiography (C.A.). C.A. revealed stenosis above 50% or complete occlusion in 22% of cases, whereas D.C.W. and R.A. showed flow reduction in 27% and 48% of the cases respectively. In T.I.A., C.A. positivity went down to 8%; D.C.W. to 16%; and R.A. to 34%. In "Complete Stroke" positivity was 36% for C.A.; 41% for D.C.W.; and 62% for R.A. There was a high number of false positive findings with D.C.W. (8) but even more with R.A. (27). False negative findings occurred only in two cases with R.A. These data confirm the diagnostic value of these two noninvasive techniques to identify haemodynamically carotid stenosis. The use of both methods can reduce error due to false negativity. The rather marked frequency of false positivity, particularly with reference to R.A. doesn't affect the diagnostic value of the two methods.