[Treatment of hypertrophic cardiomyopathy with nifedipine and propranolol in combination]. / Behandlung der hypertrophischen Kardiomyopathie mit Nifedipin und Propranolol in Kombination.

Fifteen patients (14 males and 1 female) with hypertrophic cardiomyopathy, ranging from 22 to 67 years of age (mean: 45.5 years) were treated with oral nifedipine and propranolol for 6 to 24 (mean: 18) months. Twelve of the patients had been pretreated with a mean oral dose of 560 mg verapamil for 60 to 93 (mean 78.5) months, showing slight subjective and objective improvement. Treatment with nifedipine and propranolol was terminated in five cases, due to deterioration or side effects after 6 and 12 months, respectively. During combined therapy, two patients reported improvement, whereas in five cases there was no change and eight patients reported deterioration. There was no change in the Sokolow index. The radiologically determined heart volume increased in 10 out of 15 patients and in the total group from 887 +/- 214 to 938 +/- 248 ml/1.73 m2. Echocardiographic measurements showed a significant increase in left atrial diameter from 40.0 +/- 9 to 44.0 +/- 11 mm, whereas ventricular wall thickness remained unchanged. Thus, high-dose verapamil therapy seems superior to nifedipine-propranolol therapy in patients with hypertrophic cardiomyopathy.

The Frankfurt experience in restenosis after coronary angioplasty.

Three hundred and thirty-three of 356 patients underwent angiographic follow-up from 1 to 18 months (mean 5.6 months) after percutaneous transluminal coronary angioplasty (PTCA). This is a reangiography rate of 94%. Recurrence rate after the first PTCA was 15% (n = 289). Restenosis rate was defined as an increase from immediate post-PTCA stenosis of more than 30%, or the loss of at least half of the initial gain in luminal diameter. Patients who needed a second angioplasty due to restenosis (n = 30) had a restenosis rate of 33%. Patients with angioplasty in the aortocoronary bypass (n = 14) had a restenosis rate of 45%. All patients were treated before, during and at least 4 to 6 months after the procedure with 60 to 100 mg of isosorbide dinitrate daily plus 160 to 360 mg of verapamil or 100 to 150 mg of gallopamil and 1.5 g of acetylsalicylic acid. In a second retrospective study 111 of 399 patients had the acetylsalicylic acid therapy discontinued or decreased. Forty-two of them developed restenosis (38%), whereas only 49 of 288 patients who continued to receive 1.5 g aspirin developed restenosis (17%). The restenosis rate was 32% in those who received the reduced dose of aspirin. Thus, a large dose of acetylsalicylic acid given before, during and 4 to 6 months after the procedure seems to be necessary to achieve a low rate of restenosis after PTCA.

Effects of nifedipine and propranolol combined therapy in patients with hypertrophic cardiomyopathy.

Fifteen (14 male and one female) patients with hypertrophic cardiomyopathy, ranging from 22 to 67 (mean: 45.5) years of age were treated with oral nifedipine and propranolol for 6 to 24 (mean:18) months. Twelve of the patients had been pretreated with a mean oral dose of 560 mg verapamil for 60 up to 93 (mean: 78.5) months, showing slight subjective and objective improvement. Treatment with nifedipine-propranolol was terminated in five cases due to deterioration or side effects after 6 and 12 months, respectively. During combined therapy, two patients reported subjective improvement, but in five cases there was no change and eight patients reported deterioration. The mean Sokolow-index showed no change. The radiologically determined heart volume increased in 11/15 patients and significantly in the mean of all patients from 887 +/- 239 to 947 +/- 246 ml/m2. In addition, echocardiographic measurements showed a significant increase in left atrial diameter from 40.0 +/- 9 to 42.1 +/- 9 mm, whereas ventricular wall thickness remained unchanged. Thus, high dose verapamil therapy seems superior to nifedipine-propranolol therapy in most patients with hypertrophic cardiomyopathy.

Treatment of hypertrophic cardiomyopathy: relation to pathological mechanisms.

In patients with hypertrophic cardiomyopathy, clinical symptoms such as exertional dyspnea, angina and collapse are considered to be rather the consequence of diastolic than of systolic dysfunction of the left ventricle. Beta-blocker therapy is aimed at reducing systolic overcontraction while calcium blockers predominantly therapy is aimed at reducing systolic overcontraction while calcium blockers predominantly improve diastolic filling characteristics. Therefore 61 consecutive patients with well defined hypertrophic cardiomyopathy were treated with calcium channel blockers: 60 patients with verapamil at average dose 530 mg (320 to 720 mg/d) and one patient received 30 mg nifedipine. All patients had clinical, noninvasive and cardiac catheterization evaluation at the time of entry into the study. Therapy was continued for an average of 54 months (10 to 96). Follow-up studies were performed at 6-month intervals. Subjective improvement was achieved in 47 of 55 symptomatic patients (85%). Heart size, judged as heart volume from tele-chest X-ray in supine position, showed a reduction in 36/61, no change in 15/61 and increase in 10/61. On average in all 61 patients, a significant reduction from 947 to 833 ml/1.73 m2 was seen. Twenty-six patients who had been followed for an average of 24 months prior to verapamil therapy on beta blockers or no treatment had heart volume increases averaging 12% in the pre-verapamil period. Electrocardiography (ECG) showed a significant reduction in QRS amplitude and a tendency towards normalization of ST/T segments. Serial echocardiography study showed small but significant reduction in left atrial diameter. Repeat catheterization was performed in 19 patients and a significant reduction in intraventricular pressure gradient, left ventricular muscle mass and coronary artery diameter was demonstrated. Three patients died during the study (256 patient-treatment-years) for an annual mortality rate of 1.3%. This mortality is considerably lower than reported for patients receiving no treatment, beta-blockade, or surgery. Of all 61 patients only one had surgery related to the hypertrophic cardiomyopathy. One patient had the dose of verapamil reduced because of the occurrence of heart block. No patient discontinued the drug because of side-effects. Utilizing serial noninvasive and invasive studies, we conclude that verapamil therapy in hypertrophic cardiomyopathy results in objective and subjective improvement, a low death rate and little need for operation as compared to standard therapy.

Relation of antianginal efficacy of nifedipine to degree of coronary arterial narrowing and to presence of coronary collateral vessels.

Thirty-six patients with chronic stable angina pectoris or with stable and vasospastic components of angina pectoris were classified by coronary arteriographic findings into 4 groups. Patients in group A had a single stenotic coronary artery; patients in groups B, C and D had occluded arteries, but these arteries had been collateralized to varying degrees, and an epicardial coronary steal phenomenon was possible. All patients underwent multiple exercise tests before and after randomized, double-blind, crossover treatment with 20 mg of nifedipine, 20 mg of isosorbide dinitrate, a combination of both, and placebo. Maximal and mean ST-segment depression, occurrence of angina pectoris and heart rate were evaluated. After nifedipine treatment, mean ischemic ST-segment depression was reduced 21% in group A (p less than 0.05), but was not significantly altered in the other groups (group B, 2% decrease; group C, 10% increase; group D, 3% decrease). However, isosorbide dinitrate reduced ST-segment depression significantly in all groups (group A, 29%, p less than 0.001; group B, 18%, p less than 0.01; group C, 19%, p less than 0.05; group D, 33%, p less than 0.05). The combination with nifedipine did not further improve the effect of isosorbide dinitrate. Maximal ST-segment depression and angina pectoris paralleled the changes in mean ST depression during the different medications. Heart rate at rest was not significantly changed after nifedipine treatment in any group, but increased significantly after isosorbide dinitrate treatment in groups B and C (group B, 12%, p less than 0.01; group C, 9%, p less than 0.05); heart rate during exercise did not differ significantly in any group or after any form of medication from placebo.

[Anti-angina effect of gallopamil in comparison with another calcium antagonist and a placebo]. / Die antianginöse Wirkung von Gallopamil im Vergleich mit einem anderen Calciumantagonisten und Placebo.

UNLABELLED: In 12 male patients with angiographically confirmed coronary heart disease and stable angina the antianginal effects of 50 mg Gallopamil have been studied in comparison with 10 mg Nifedipine and placebo. The study has been carried out using a double-blind cross-over protocol with standardized exercise stress tests. Patients underwent 5 exercise step tests, without any medication and 120 minutes after randomized drug administration (placebo, placebo, Gallopamil, Nifedipine). Both Gallopamil and Nifedipine had good antianginal effects. Following 50 mg Gallopamil, ischemic ST-depression was reduced by 45% compared to placebo and by 50% compared to ergometry without any medication. The reduction of ST-depression after 10 mg Nifedipine was 26% compared to placebo and 31% compared to a drug-free exercise test. Due to the negative chronotropic effects, Gallopamil led to a slight but significant reduction of heart rate at rest and during exercise of about 5%. In contrast, after Nifedipine administration, a reflex-mediated increase in heart rate could be seen. In normotensive patients both channel-blocking agents showed a slight reduction of arterial blood pressure. CONCLUSIONS: The results indicate a considerable antianginal effect of a single oral dose of 50 mg Gallopamil. In comparison to 10 mg Nifedipine this effect is more pronounced.

[Anti-angina effectiveness of the calcium antagonist nifedipine in relation to coronary involvement]. / Antianginöse Wirksamkeit des Kalziumantagonisten Nifedipin in Abhängigkeit vom Koronarbefall.

36 patients with chronic stable or the variant form of angina pectoris were subdivided according to their coronary angiogram into 4 groups: Group A with a single highgrade stenosis in one coronary artery, Groups B, C and D with different patterns of occluded, but collateralized coronary arteries supplying noninfarcted myocardium. All patients underwent multiple exercise step tests before (K) and after randomly assigned crossover treatment with 20 mg nifedipine (N), 20 mg isosorbiddinitrate (I), the combination of both (I + N) and Placebo (P). Peak and mean ischemic ST-segment depression, the occurrence of angina pectoris and heart rate were evaluated. The mean ischemic ST-segment depression decreased significantly after N in group A by -28% (p less than 0.01), but was not significantly altered in the groups B, C and D (B: -12%, C: +7%, D: +2%). After I, mean ST-segment depression decreased significantly in all groups (A: -36%, p less than 0.001; B: -27%, p less than 0.001; C: -22%, p less than 0.01; D: -29%, p less than 0.05). The combination of I + N was not better than I alone. Peak ST-depression and angina pectoris paralleled the results of mean ST-depression. The resting heart rate increased significantly after N only in group A (+9%, p less than 0.01) and increased after I in the groups A, B and C (A: +11%, p less than 0.05; B: +12%, p less than 0.05; C: +12%, p less than 0.01). During exercise, heart rate was not significantly different in any group or after any type of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)