Effects of verapamil on left ventricular diastolic filling in children with hypertrophic cardiomyopathy

The effects of oral verapamil on resting left ventricular (LV) diastolic filling were examined in 10 children and adolescents with hypertrophic cardiomyopathy. Measurements of diastolic filling were made from gated technetium-99m radionuclide angiograms with postbeat rejection of data outside a 5% RR-interval window. LV time-activity curves were generated and the rapid-filling phase fit with a 3 degrees polynomial to calculate the peak filling rate and the time from end-systole to the point of peak filling. All patients had a radionuclide angiogram performed before and after 0.25 to 3 years of oral verapamil therapy. Verapamil did not change the LV ejection fraction but increased the peak filling rate (3.24 +/- 0.15 to 4.62 +/- 1.05 end-diastolic volume/s,p less than 0.01) and reduced the time to peak filling (217 +/- 57 to 168 +/- 63 ms, p less than 0.01). An increase in exercise endurance as measured by exercise treadmill test and subjective symptomatic improvement were also seen after verapamil therapy. Thus, in children with hypertrophic cardiomyopathy, symptomatic improvement and LV diastolic filling parameters improved with long-term oral verapamil.     

Haemodynamic effects of nifedipine and propranolol in patients with hypertrophic obstructive cardiomyopathy.

The haemodynamic effects of nifedipine, propranolol, and the combined administration of the two drugs were studied in 12 patients with hypertrophic obstructive cardiomyopathy. The combined administration of nifedipine and propranolol appeared to be superior to that of nifedipine alone. The spontaneous heart rate was reduced in most cases after nifedipine plus propranolol, and at atrial pacing the following results were obtained: left ventricular peak systolic pressure was reduced from 200 +/- 39 to 157 +/- 30 mmHg; a positive correlation was found between the pre-drug left ventricular end-diastolic pressure and the magnitude of reduction in left ventricular end-diastolic pressure; systolic blood pressure was reduced from 125 +/- 31 to 111 +/- 27 mmHg, and total peripheral resistance was reduced from 1403 +/- 307 to 1160 +/- 209 dyne s-1 cm-5. The combined administration reduced the resting left ventricular outflow gradient from 76 +/- 19 to 45 +/- 26 mmHg, while cardiac index was left unchanged. The effects on mean pulmonary arteriolar resistance and mean pulmonary arteriolar resistance and mean pulmonary capillary venous pressure were in most cases slight and insignificant. The results indicate an improved haemodynamic condition in patients with hypertrophic obstructive cardiomyopathy after the combined administration of nifedipine and propranolol: a treatment that might provide a new and useful alternative to already existing medication.     

Verapamil-induced improvement in left ventricular diastolic filling and increased exercise tolerance in patients with hypertrophic cardiomyopathy: short- and long-term effects

Verapamil improves exercise tolerance and decreases symptoms in many patients with hypertrophic cardiomyopathy. The mechanisms responsible for these effects are not completely understood, although previous studies indicate that verapamil enhances left ventricular relaxation and diastolic filling in such patients. To investigate the association between changes in left ventricular filling and exercise tolerance after verapamil, we studied 55 patients with hypertrophic cardiomyopathy by radionuclide angiography and graded treadmill testing before and after 1 to 4 weeks of therapy with orally administered verapamil, 320 to 640 mg/d. The verapamil-induced increase in peak left ventricular filling rate at rest (from 3.1 +/- 1.3 to 3.7 +/- 1.3 end-diastolic volumes/sec; p less than .001) was associated with an increase in exercise tolerance (from 5.9 +/- 3.6 to 8.7 +/- 4.7 min; p less than .001); exercise capacity increased in 34 of 43 patients (79%) manifesting an increase in peak filling rate but only one of 12 patients (8%) with unchanged or decreased peak filling rate (p less than .001). This initial trend persisted in 25 patients studied after 1 year of therapy; 11 of 16 patients (69%) with a persistent increase in peak filling rate had persistent improvement in exercise tolerance relative to preverapamil values, compared with only one of nine patients (11%) in whom peak filling rate was unchanged or decreased relative to preverapamil levels (p less than .02). Verapamil withdrawal after 1 to 2 years in 24 patients resulted in reduction in peak filling rate (p less than .001) and was associated with deterioration in exercise tolerance in 17 patients (71%). Hence, verapamil-induced changes in left ventricular peak filling rate were associated significantly with objective symptomatic improvement. These data support the concept that enhanced left ventricular diastolic filling is an important mechanism contributing to the clinical improvement experienced by many patients with hypertrophic cardiomyopathy during therapy with verapamil.     

Verapamil improves the pacing-induced vasodilatation in symptomatic patients with hypertrophic cardiomyopathy

The purpose of the study was to assess the effect of verapamil on the response of diastolic coronary flow velocity and coronary vascular resistance to pacing in symptomatic patients with hypertrophic cardiomyopathy. In 14 patients with hypertrophic cardiomyopathy, the coronary flow velocity was detected in the left anterior descending coronary artery using transthoracic Doppler echocardiography. The peak diastolic coronary flow velocity and coronary vascular resistance was measured at baseline and during pacing. Changes of these parameters induced by the pacing (expressed as the percentage of baseline values) were compared on verapamil treatment and after verapamil withdrawal. The same measurements were obtained in ten control subjects. The results show that, in hypertrophic cardiomyopathy patients, increase in coronary flow velocity during pacing was significantly higher on than off verapamil therapy (64.8+/-32.5 vs. 41.1+/-21.3%, P<0.05). In control subjects, pacing-induced increase in coronary flow velocity was comparable to changes in coronary flow velocity in hypertrophic cardiomyopathy patients receiving verapamil (80.2+/-18.4 vs. 64.8+/-32.5%, P>0.05). After verapamil withdrawal in hypertrophic cardiomyopathy patients, coronary flow velocity increase during pacing was significantly lower than in control subjects (41.1+/-21.3 vs. 80.2+/-18.4%, P<0.05). During pacing the coronary vascular resistance decreased more on verapamil than after drug withdrawal (-34.7+/-11.7 vs. -24.6+/-12.9%, P<0.05). In control subjects the coronary vascular resistance decreased during pacing -38.6+/-6.3% to similar extent as in hypertrophic cardiomyopathy patients on verapamil. We can conclude that endothelium-dependent vasodilatation during pacing was impaired in symptomatic patients with hypertrophic cardiomyopathy. Verapamil treatment was able to restore adequate vasodilator response to pacing stress.     

Comparative study of the effects of verapamil and propranolol therapy in 16 cases of obstructive hypertrophic myocardiopathy

In a randomized, double-blind, cross-over study with plasma drug assays, 16 patients (11 men, 5 women; mean age 48.56 +/- 3.61 years) presenting with hypertrophic obstructive cardiomyopathy confirmed by echocardiography, left ventriculography and left intraventricular gradient measurement were treated with verapamil 480 mg/day or propranolol 320 mg/day. Both treatments produced functional improvement (p less than 0.01) which was more distinct with verapamil (NS). No changes in cardiothoracic index, echocardiographic parameters and Sokolow's index were observed. Mean total heart work during exercise, which was 1,197.27 +/- 135.89 watts before treatment, increased to 1,260.91 +/- 146.60 watts under propranolol (NS) and to 1,344.09 +/- 171.06 watts under verapamil (NS). Maximum heart rate during exercise, which was 162.3 +/- 3.46 beats/min before treatment, was reduced to a greater extent by propranolol (122.1 +/- 6.6 beats/min; p less than 0.001) than by verapamil (147.7 less than 5.08 beats/min; p +/- 0.01). The two treatments did not significantly modify ventricular arrhythmia, arterial and capillary pulmonary pressures, mean aortic pressure and left ventricular end-systolic pressure. Cardiac index, unchanged under verapamil, fell from 2.98 +/- 0.16 1 X min-1 X m-2 to 2.60 +/- 0.11 1 X min-1 X m-2 under propranolol (p less than 0.05). The left intraventricular gradient present in 5 patients at rest and during exercise, was reduced by both drugs. The gradient under isoprenaline (n = 16), which was 162.07 +/- 18.77 mmHg before treatment, fell to 93.86 +/- 24.48 mmHg with propranolol (p less than 0.05) and to 128.86 +/- 18.22 mmHg with verapamil (p less than 0.05). Left ventricular ejection fraction, mean circumferential fibre shortening speed and compliance coefficient remained unchanged under both drugs (NS). Left ventricular diastolic function, evaluated by radioisotope angiography in the last 9 patients, was most often improved by verapamil (NS). Verapamil was better tolerated generally and by the heart than propranolol. No correlation was observed between plasma verapamil levels and clinical results. Low plasma propranolol levels were often noted in non-responders, suggesting a need for treatment with high doses. It is concluded that at the dosage level used in this study propranolol and verapamil were equally effective, but there were individual variations in best response to one or the other of these two drugs.     

Medical treatment of hypertrophic myocardiopathy. Comparison of propranolol and verapamil

It remains difficult to make a reasoned choice between betablockers and calcium antagonists in the medical treatment of hypertrophic cardiomyopathy. In order to help in making this choice, we compared the effects of 320 mg of propranolol and 480 mg of verapamil, prescribed in a random order for an average period of 2.5 months in 24 patients. In 15 patients the two therapeutic sequences were preceded and followed by a clinical examination and an exercise stress test after withdrawal of all treatment. The overall functional status correlated to oxygen consumption was unchanged by the two drugs, but patients felt better more often with verapamil. These was no significant change in maximal power developed during exercise testing although verapamil increased it by 9 p. 100 throughout with a corresponding increase in oxygen consumption. Two parameters were significantly changed by both drugs: the maximal heart rate fell from 161 +/- 22 to 122 +/- 18 with propranolol, and to 145 +/- 28 with verapamil; the oxygen pulse (equivalent to the systolic index) increased from 10.9 +/- 2.2 to 14.8 +/- 3.9 with propranolol, and to 13.7 +/- 2.4 with verapamil. There were no changes in the blood pressure profiles during exercise. Side effects were observed with both drugs; muscular weakness was the biggest problem with propranolol and sinus node dysfunction with verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)     

Echocardiographic and electrocardiographic evaluation of the effects of propranolol and verapamil in obstructive hypertrophic cardiomyopathy

The purpose of this study is to compare M-mode echocardiographic and electrocardiographic modifications obtained by short-term therapy (6 weeks) with high doses (480 mg/day) of propranolol or verapamil in six patients with hypertrophic obstructive cardiomyopathy. Propranolol prevents heart rate acceleration and reduces significantly the echocardiographic obstruction index during provocative testing with isoprenaline, when verapamil doesn't. However verapamil seems to be more able than propranolol to suppress ventricular arrhythmias as demonstrated in Holter monitoring. Evaluation of each patient suffering from hypertrophic obstructive cardiomyopathy with echocardiography and 24-hours electrocardiography would permit to better define appropriate therapy.     

Hypertrophic obstructive cardiomyopathy. Effects of acute and chronic verapamil treatment on left ventricular systolic and diastolic function.

Changes in left ventricular systolic and diastolic function and outflow gradient were evaluated in patients with obstructive hypertrophic cardiomyopathy after intravenous acute treatment with verapamil (15 patients) and after six months of oral chronic treatment (11 patients). All patients had severe symptoms despite beta blockade, and the condition of all but two improved appreciably after chronic treatment with verapamil. Resting left ventricular outflow tract gradient decreased in six of 15 patients after intravenous verapamil, and in five of 11 patients after long term treatment, but there was no change in provocable gradients nor any correlation between changes in gradient and improvement in symptoms. Left ventricular ejection rate did not change after intravenous or oral treatment. End systolic pressure/end systolic volume index remained unchanged after oral verapamil treatment. Whereas left ventricular total stroke volume index and end diastolic volume index increased without any significant change in left ventricular end diastolic pressure, indicating improved left ventricular diastolic function. In some patients the left ventricular diastolic pressure-volume curve shifted downwards or to the right or both. These findings suggest that improvement in symptoms with verapamil in patients with obstructive hypertrophic cardiomyopathy is unlikely to be related to changes in left ventricular outflow gradient or in systolic function and may be related to improved diastolic function.     

Hypertrophic obstructive cardiomyopathy. Effects of acute and chronic verapamil treatment on left ventricular systolic and diastolic function

Changes in left ventricular systolic and diastolic function and outflow gradient were evaluated in patients with obstructive hypertrophic cardiomyopathy after intravenous acute treatment with verapamil (15 patients) and after six months of oral chronic treatment (11 patients). All patients had severe symptoms despite beta blockade, and the condition of all but two improved appreciably after chronic treatment with verapamil. Resting left ventricular outflow tract gradient decreased in six of 15 patients after intravenous verapamil, and in five of 11 patients after long term treatment, but there was no change in provocable gradients nor any correlation between changes in gradient and improvement in symptoms. Left ventricular ejection rate did not change after intravenous or oral treatment. End systolic pressure/end systolic volume index remained unchanged after oral verapamil treatment. Whereas left ventricular total stroke volume index and end diastolic volume index increased without any significant change in left ventricular end diastolic pressure, indicating improved left ventricular diastolic function. In some patients the left ventricular diastolic pressure-volume curve shifted downwards or to the right or both. These findings suggest that improvement in symptoms with verapamil in patients with obstructive hypertrophic cardiomyopathy is unlikely to be related to changes in left ventricular outflow gradient or in systolic function and may be related to improved diastolic function.     

Verapamil therapy: A new approach to the pharmacologic treatment of hypertrophic cardiomyopathy: III. Effects of long-term administration

To determine the efficacy of long-term therapy with verapamil in patients with hypertrophic cardiomyopathy, 78 patients began treatment with the drug in the hospital. Sixty-two patients (79 percent) were in New York Heart Association functional class III or IV despite treatment with beta receptor blocking drugs. Fifty-four percent of all patients evaluated (42 of 78) and 63 percent of those discharged from the hospital (42 of 68) experienced sustained symptomatic improvement 6 to 30 months (median 14 months) after initiation of verapamil therapy. Of these 42 patients in improved condition, 25 had improvement by at least one New York Heart Association functional class, 14 improved by less than one functional class, two felt better taking verapamil than propranolol, and in one patient verapamil controlled asymptomatic ventricular tachycardia. Of the 53 patients who had the obstructive form of the disorder and were considered operative candidates, 25 (47 percent) experienced sufficient improvement so as to forgo operation. In patients remaining on verapamil therapy, the duration of treadmill exercise performed 5 days after the start of verapamil therapy increased by 3.1 ± 0.6 minutes (53 ± 10 percent, p < 0.001) from the value obtained with no medication before verapamil. A further increase of 2.3 ± 0.6 minutes (25 ± 7 percent, p < 0.0025) over the initial value with verapamil was recorded on the patients' last vistt (median 12 months after the start of therapy). Echocardiographic measurements of wall thicknesses and left atrial dimension demonstrated no significant changes during 1 year of verapamil treatment in 31 patients. Administration of verapamil was associated with adverse hemodynamic effects in 9 patients (12 percent) and adverse electrophysiologic effects In 10 (13 percent): Three patients died (with pulmonary edema) and 6 had to have treatment terminated. These results indicate an important role for long-term verapamil therapy in the treatment of hypertrophic cardiomyopathy, but patients must be carefully selected and followed up closely for the development of important adverse hemodynamic or electrophysiologic effects.     

Acute left ventricular filling time and rate changes in hypertrophic cardiomyopathy after verapamil and propranolol evaluated by nuclear stethoscope

We have undertaken the present study to evaluate the acute effects of propranolol and verapamil on the diastolic function in patients with hypertrophic cardiomyopathy. We used a non imaging isotope device, the nuclear stethoscope, that has been so far mainly employed for assessment of systolic function, although fitted for detecting diastolic filling rates and times as well. Relative cardiac output, ejection fraction, rapid and slow filling times and rates were measured in five patients suffering from hypertrophic cardiomyopathy in basal conditions and 10.20 and 30 minutes after i.v. administration for either propranolol or verapamil, with a time interval of at least 24 hours between the two acute drug studies. With respect to the baseline values only verapamil showed a significant improvement in rapid and maximum filling rates, suggesting that diastolic function is more beneficially affected by Ca-entry blockers rather than beta-blockers in hypertrophic cardiomyopathy.     

Sustained-release verapamil and nifedipine in exercise-induced angina pectoris.

In a randomised, double-blind, crossover study of oral sustained-release verapamil 360 mg o.d. ('SR-verapamil') and oral nifedipine 20 mg t.d.s. in 19 patients with chronic stable angina pectoris, significantly greater improvement from baseline was seen with SR-verapamil than with nifedipine. Mean exercise duration was 380 +/- 108 s with SR-verapamil and 343 +/- 130 s with nifedipine (P less than 0.05); mean time to onset of angina was 326 +/- 79 s with SR-verapamil and 239 +/- 79 s with nifedipine (P less than 0.01); median time to 1 mm ST depression was 252 s (range 114-579) with SR-verapamil and 182 s (range 84-582) with nifedipine (P less than 0.01); mean ST depression at maximum exercise was 1.65 +/- 0.56 mm with SR-verapamil and 2.17 +/- 0.98 mm with nifedipine (P less than 0.05). Ambulatory ECG recordings indicated a trend in favour of SR-verapamil (median ST-time integral 0.00 [range 0-24.16] mm h-1 with SR-verapamil, 1.15 [range 0-12.50] mm h-1 with nifedipine, not significant). Median glyceryl trinitrate consumption was significantly lower (P less than 0.05) with SR-verapamil (0.21; range 0-1.25 per day) than with nifedipine (0.31; range 0-1.32 per day), but there was no significant difference between angina attack frequency. Adverse events were reported by two patients with SR-verapamil and nine with nifedipine. Once-daily sustained-release verapamil 360 mg has a significantly better effect on exercise tolerance than nifedipine 20 mg t.d.s. and also appears to be better-tolerated.     

Verapamil prevents silent myocardial perfusion abnormalities during exercise in asymptomatic patients with hypertrophic cardiomyopathy

Recent studies indicate that reversible 201Tl perfusion defects, compatible with silent myocardial ischemia, commonly develop during exercise in asymptomatic or mildly symptomatic patients with hypertrophic cardiomyopathy (HCM). To determine whether this represents a dynamic process that may be modified favorably by medical therapy, we studied 29 asymptomatic or minimally symptomatic patients with HCM, aged 12-55 years (mean, 28), with exercise 201Tl emission computed tomography under control conditions and again after 1 week of oral verapamil (mean dosage, 453 mg/day). Treadmill time increased slightly during verapamil (21.0 +/- 3.6 to 21.9 +/- 2.7 minutes, p less than 0.005), but peak heart rate-blood pressure product was unchanged (26.3 +/- 6.0 X 10(3) compared with 25.0 +/- 6.4 X 10(3). Two midventricular short-axis images per study were divided into five regions each, and each of these 10 regions was then analyzed on a 0-2 scale by three observers blinded with regard to the patients' therapy. Average regional scores of 1.5 or less were considered to represent perfusion defects, and a change in regional score of 0.5 or more was considered to constitute a significant change. During control studies, 15 patients (52%) developed perfusion defects with exercise (average, 3.7 regions per patient). In 14 of these patients, all perfusion defects completely reversed after 3 hours of rest; one patient had fixed defects. After administration of verapamil, exercise perfusion scores improved in 10 of the 14 patients (71%) with reversible defects; there was overall improvement in 34 of 50 (68%) regions with initially reversible perfusion defects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of the effects of nitroprusside and nifedipine on diastolic properties in patients with hypertrophic cardiomyopathy: Altered left ventricular loading or improved muscle inactivation?

The calcium channel blocking agent, nifedipine, has been shown to improve indexes of left ventricular relaxation, diastolic filling and compliance in patients with hypertrophic cardiomyopathy. The mechanism of action of nifedipine on diastolic properties in patients with hypertrophic cardiomyopathy is unclear and could result from an improvement in myocardial inactivation or from systemic vasodilation and left ventricular unloading. To distinguish between these mechanisms, the effects of nifedipine and the vasodilator nitroprusside on left ventricular diastolic properties were compared in 10 patients with nonobstructive hypertrophic cardiomyopathy using simultaneous micromanometer left ventricular pressure and echocardiographic measurements. Left ventricular peak systolic pressure was comparable during nitroprusside infusion (132 +/- 38 mm Hg) and after nifedipine (132 +/- 32 mm Hg). During nitroprusside infusion, the decrease in left ventricular end-diastolic pressure (22 +/- 11 to 17 +/- 11 mm Hg, p less than 0.05) was associated with a decrease in left ventricular end-diastolic dimension. In contrast, the decrease in left ventricular end-diastolic pressure after nifedipine (22 +/- 11 to 18 +/- 10 mm Hg, p less than 0.05) was associated with no reduction of left ventricular end-diastolic dimensions, suggesting an increase in left ventricular distensibility. Compared with nitroprusside, nifedipine was associated with less prolongation of the left ventricular isovolumic relaxation time and less depression of the peak left ventricular posterior wall thinning rate and peak left ventricular internal dimension filling rate. These data suggest that the effects of the calcium channel blocker, nifedipine, on diastolic mechanics in hypertrophic cardiomyopathy result not only from systemic vasodilation but also from improved cardiac muscle inactivation.     

Chronic verapamil therapy in pediatric and young adult patients with hypertrophic cardiomyopathy

Oral verapamil, 5.2 +/- 1.1 mg/kg/day (range 2.8 to 7), was administered to 13 pediatric patients with hypertrophic cardiomyopathy for 13 +/- 6 months (range 2 to 20). The patients had significant symptomatic improvement on verapamil therapy. Murmur intensity diminished in 6 patients during therapy and left ventricular (LV) electromotive forces on the electrocardiogram diminished in 4, increased in 5 and did not change in 4. Exercise endurance increased from 8.4 +/- 3.9 to 10.9 +/- 2.8 minutes (p less than 0.01). Seven patients had ST-segment depression (0.38 +/- 0.28 mV) before verapamil therapy, which improved after verapamil therapy in 5 (0.24 +/- 0.17 mV, p less than 0.02). Of 4 patients with exercise-induced ventricular ectopic activity, 3 had diminution or abolishment of ectopy following verapamil. By echocardiography, the patients had an increase in LV end-diastolic dimension from 3.4 +/- 0.7 to 3.9 +/- 0.8 cm (p less than 0.01), with no significant change in shortening fraction (46.1 +/- 8.0% vs 44.6 +/- 8.0%). When adjusted for body size and age there was a significant decrease in LV septal thickness (from 106 +/- 70 to 45 +/- 52% of predicted normal values, p less than 0.05) and LV posterior wall thickness (from 40 +/- 45 to 5 +/- 26% of predicted normal values p = 0.05) after verapamil. Isovolumic relaxation time decreased from 69 +/- 26 to 42 +/- 19 ms after verapamil (p less than 0.01). Systolic anterior motion of the anterior mitral leaflet disappeared in 5 of 8 patients and midsystolic closure of the aortic valve was no longer present in 4 of 8.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes of the degree of hypertrophy in hypertrophic obstructive cardiomyopathy under medical and surgical treatment

The aim of our study was to establish the extent to which therapy of hypertrophic obstructive cardiomyopathy (HOCM) can influence the degree of hypertrophy. By means of two-dimensionally guided M-mode echocardiography, 120 patients with HOCM (age range 4-72 years, mean age 41 years) were observed over an average period of 49 +/- 41 months. Depending on the respective therapy, we formed four patient groups: group 1: 13 patients without any therapy (follow-up period 31 +/- 30 months); group 2: 27 patients receiving propranolol (follow-up period 47 +/- 34 months); group 3: 50 patients receiving verapamil (follow-up period 39 +/- 27 months), and group 4: 30 patients with myectomy (follow-up period 34 +/- 32 months). In group 4, as expected, the thickness of the interventricular septum (IVS) decreased postoperatively (from 24.2 +/- 4.5 to 19.8 +/- 6.7 mm, p less than 0.05), and the left ventricular posterior wall (LVPW) thickness also decreased later postoperatively (from 13.0 +/- 2.6 to 11.9 +/- 2.3 mm, p less than 0.05). The left ventricular diameters increased. In groups 2 and 3 treated with pharmacotherapy as in the untreated patients of group 1, on average there was no change in IVS and LVPW thickness nor in the left ventricular diameters (with the exception of increasing left ventricular end-diastolic diameter in the propranolol-treated group). In contrast to group 1, in occasional cases there were substantial decreases of IVS thickness (11% of the patients in group 2, 13% in group 3) or LVPW thickness (13% of the patients in group 2, 12% in group 3).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of propranolol and disopyramide on left ventricular function at rest and during exercise in hypertrophic cardiomyopathy.

In 19 patients with hypertrophic cardiomyopathy (15 males, 4 females, mean age 49.2 +/- 10.8 years) left ventricular function was studied with radionuclide ventriculography at rest and during exercise in a crossover design without intervention and after disopyramide and propranolol treatment. 15 of the 19 patients had a resting or latent intraventricular gradient of more than 30 mm Hg. Left ventricular function at rest and during exercise was evaluated before medication, 90 min after oral administration of 200 mg disopyramide or 160 mg propranolol and after 3 weeks of oral therapy with disopyramide 200 mg 2 times a day or propranolol 80 mg 4 times a day. After long-term treatment with disopyramide, resting ejection fraction decreased from 72 +/- 12 to 69 +/- 14% (p less than 0.01) and peak ejection rate (PER) decreased from 3.46 +/- 135 to 3.24 +/- 65 end-diastolic volume (EDV).s-1 (p less than 0.01). Peak filling rate (PFR) at rest decreased from 3.01 +/- 0.8 to 2.77 +/- 0.63 EDV.s-1 (p less than 0.05). Time to peak filling rate (TPFR) at rest and during exercise after acute and chronic therapy did not change compared to control values. Acute and long-term administration of propranolol lead to a significant reduction in heart rate at rest and during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of verapamil, diltiazem, nifedipine and propranolol on metabolic control in hypertensives with non-insulin dependent diabetes mellitus

The effects of one month's treatment with each of nifedipine, verapamil, diltiazem, propranolol and placebo, given in random order, on fasting plasma glucose, haemoglobin Alc, serum fructosamine, immunoreactive insulin, cholesterol, and triglyceride were studied in a group of 19 patients with hypertension and non-insulin dependent diabetes mellitus. The metabolic effects of the active drugs were generally small but fasting plasma glucose was increased by propranolol from 9.3 +/- 3.0 to 10.4 +/- 3.4 mmol/l (P less than 0.01) (mean +/- SD) and to 10.1 +/- 3.2 mmol/l (P less than 0.05) by nifedipine. Serum fructosamine was increased from 2.75 +/- 0.53 to 2.89 +/- 0.62 mmol/l (P less than 0.05) by diltiazem and to 2.91 +/- 0.65 (P less than 0.05) by propranolol. Verapamil increased fasting serum immunoreactive insulin: diltiazem and propranolol tended to reduce it. Propranolol but not the other drugs significantly increased serum triglyceride. Calcium antagonists may be preferable to beta adrenoceptor blockers for the treatment of hypertensive diabetics. Of the three calcium antagonists we studied, verapamil may have advantages over nifedipine and diltiazem.     

"Maximal" drug therapy is not necessarily optimal in chronic angina pectoris

Beta-adrenergic blocking agents, nitrates and calcium channel antagonists are effective in treating angina pectoris, but much remains unknown about how they act in combination. Consequently, treadmill exercise was used to assess the relative efficacy of nifedipine or isosorbide dinitrate, or both, in 19 patients with stable angina receiving propranolol. Propranolol therapy was continued and either placebo, nifedipine (20 mg), isosorbide dinitrate (20 mg) or both drugs were given randomly 1 1/2 hours before exercise in a double-blind trial. In 16 patients who completed the protocol, heart rate at rest during propranolol therapy was 53.7 +/- 1.9 beats/min (mean +/- standard error of the mean); it increased 4.6 +/- 1.2 beats/min with the addition of nifedipine (p less than 0.01), but was unchanged with isosorbide dinitrate or both combined. Compared with values during treatment with propranolol alone, systolic blood pressure at rest decreased with each vasodilator individually and when combined. Rate-pressure product at maximal exercise was the same with all combinations. Exercise duration was 467 +/- 50 seconds with propranolol, increased to 556 +/- 47 seconds with isosorbide dinitrate (p less than 0.05) and to 636 +/- 50 seconds with nifedipine (p less than 0.001). Exercise duration with all three drugs was 597 +/- 47 seconds (p less than 0.01 compared with propranolol alone). The improvement with nifedipine was greater than with isosorbide dinitrate (p less than 0.05) but exercise duration was not significantly different with the combination of these drugs than when either drug was used alone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of propranolol on left ventricular relaxation in hypertrophic cardiomyopathy: an echographic study

Many authors have shown that hypertrophic cardiomyopathy (HCM) is often associated with diastolic abnormalities. The purpose of this study was to determine the effect of propranolol on left ventricular isovolumic relaxation time (IVRT) measured by echocardiography in 20 patients with hypertrophic cardiomyopathy under basal conditions and under increasing doses of propranolol (160 mg, 320 mg, and 480 mg per day) and in two control groups, 10 patients with aortic stenosis, and 10 normal subjects. IVRT was less than 50 msec in all normal subjects, while it was always above this limit in aortic stenosis (77 msec +/- 8, p less than 0.001), and in hypertrophic cardiomyopathy (94 msec +/- 19, p less than 0.001), with also a significant difference between these two last groups (p less than 0.01). Under increasing doses of propranolol, relaxation time often shortens gradually until 50 msec or less. These results show an improvement in left ventricular relaxation dependent on the propranolol dosage and often a normalization at high dosages.