Calcium channel blockers as antihypertensive agents.

Because of their unique action on the cardiovascular system, the calcium channel blockers have generated a great deal of excitement among pharmacologists, physiologists, and clinicians. One obvious potential application for these drugs is in antihypertensive therapy and, although experience with these agents for this indication is limited in the United States, it is considerable in Europe and Japan. These agents' ultimate role in antihypertensive therapy, however, has not been established. Since the available calcium channel blockers are structurally diverse, it is uncertain whether they will have comparable effects in hypertension. The rationale for the use of calcium channel blockers in treating hypertension and the relevant pharmacologic actions of these agents is discussed, along with a summary of some of the clinical trials, observations from our own experience with these drugs, and speculation about their future role in antihypertensive therapy.

Antihypertensive therapy with diltiazem and comparison with hydrochlorothiazide.

Fourteen hypertensive patients with a mean sitting systolic and diastolic blood pressure (BP) of 153 +/- 16/100 +/- 4 mm Hg were treated successively with hydrochlorothiazide and diltiazem for 8 weeks each. The BP response and changes in heart rate, left ventricular size and function, and plasma catecholamine concentrations and renin activity were monitored. The 2 drugs had comparable antihypertensive effects, with mean decreases of 14, 9 and 11 mm Hg for the sitting, standing and supine diastolic BP, respectively, during hydrochlorothiazide treatment and mean decreases of 16, 18 and 12 mm Hg during diltiazem treatment. Heart rate was unchanged, although plasma norepinephrine concentrations increased significantly during diltiazem treatment. Plasma renin activity increased slightly, from 0.6 to 0.9 ng/ml/hour during diltiazem treatment, but the change was not significant (p less than 0.10). Left ventricular ejection fraction and end-diastolic volume were not affected by either agent. In conclusion, diltiazem is an effective antihypertensive agent, which because of its benign side effect profile, may be useful as a step 1 agent.

Failure of antihypertensive therapy with diuretic, beta-blocking and calcium channel-blocking drugs to consistently reverse left ventricular diastolic filling abnormalities.

The present protocol was designed to determine whether antihypertensive therapy with hydrochlorothiazide, propranolol or diltiazem, 3 agents with different mechanisms of action and potentially different effects on myocardial function, reverses left ventricular filling abnormalities. Twelve patients with essential hypertension and no evidence of associated cardiovascular disease, either clinically or with noninvasive testing, were evaluated while taking no medication and after 2 months of treatment with these agents. All 3 drugs produced equivalent control of blood pressure (BP), reducing sitting systolic BP by a mean of 20 to 24 mm Hg and diastolic BP by 14 to 16 mm Hg. LV ejection fraction and end-diastolic volume were normal in all but 1 subject (who was excluded from the analyses of LV diastolic filling) and were not altered by drug therapy. The peak LV filling rate and the first-third filling fraction were reduced in the patients with hypertension, but neither of these indexes nor the time to peak filling rate were significantly improved for the group as a whole by any of these medications. Nine of 10 patients whose BP was controlled by diltiazem had increases in their first-third filling fraction, but this change did not reach statistical significance. Our findings suggest that abnormalities of LV diastolic filling are not consistently affected by short-term therapy in patients with chronic, previously treated systemic hypertension.

Detection and quantification of previous myocardial infarction by exercise-redistribution tomographic thallium-201 scintigraphy.

Although myocardial perfusion scintigraphy at rest accurately diagnoses myocardial infarction (MI), the prevalence and size of previous MI is overestimated by exercise-redistribution thallium-201 studies. A new, quantitative approach to the analysis of tomographic thallium-201 scintigrams was developed in order to determine whether the presence and extent of MI could be determined. Sixty patients undergoing cardiac catheterization for chest pain syndromes, including 28 with previous MI, were studied by exercise and 3-hour delayed thallium-201 scintigraphy, with use of the 7-pinhole tomographic technique. Circumferential profiles of the postexercise and 3-hour radiotracer distribution were generated from apical, midventricular and basal left ventricular slices. The 3-hour profile fell below normal limits in 24 of 28 patients (86%) with remote MI, but was also abnormal in 9 of 22 patients (41%) with coronary disease but no MI. All missed MIs were either inferior or subendocardial and were associated with normal ejection fractions. To distinguish between MI and slowly resolving ischemic defects, a quantitative approach was used. MI area was calculated as the area in which the 3-hour profile fell below the 3-hour normal limits, and a redistribution area in the MI zone was determined as the area between the postexercise and 3-hour profiles in the region where the 3-hour profile was abnormal. The MI area was 1,000 +/- 980 units in patients with MI, vs 79 +/- 120 units in patients without MI (p less than 0.001), whereas the redistribution area was higher in patients without MI (1,240 +/- 810 vs 430 +/- 400 units, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of left ventricular diastolic filling: comparison of fixed and varying region of interest approaches.

Abnormalities in scintigraphic measurements of diastolic filling were assessed with respect to detection, reproducibility and sensitivity by means of fixed and varying left ventricular region-of-interest (ROI) approaches. Equilibrium blood pool scintigraphy was carried out in 11 control subjects, 15 patients with coronary artery disease (CAD), and 13 patients with hypertension. Results of these studies were analyzed for ejection fraction (EF), peak filling rate (PFR), time to PFR (TPFR), and filling fraction in the first third of diastole corrected for cycle length (FF1/3). With the fixed ROI technique, patients with CAD differed from the control subjects because they had lower EF (p less than 0.05), PFR (p less than 0.001), and FF1/3 (p less than 0.05) levels; patients with hypertension showed only a reduced FF1/3 (p less than 0.01). When the varying ROI method was employed, patients with CAD differed from normal subjects in their PFR (p less than 0.05) results; patients with hypertension and normal subjects differed in their FF1/3 (p less than 0.001) results. Although the ability to discriminate between patients and normal subjects was similar with the two techniques, interobserver variability was smaller and single observer reproducibility was greater with the fixed ROI method. We conclude that the fixed and varying ROI techniques are comparable in detecting diastolic filling abnormalities but that the fixed ROI method is superior in reducing measurement variability and may be the preferable method for analyzing serial studies and the response to therapeutic interventions.

Left ventricular filling is usually normal in uncomplicated coronary disease.

Abnormalities in left ventricular filling have been described as an early finding in coronary artery disease (CAD) and more recently, in hypertension (HTN). The present study was undertaken to compare the prevalence and pattern of diastolic dysfunction in these two entities. Three groups of patients were studied: 10 normal volunteers (NLS), 39 HTN patients, and 30 CAD patients. The CAD patients were divided into two subgroups--one with normal ejection fraction (mean 0.60 +/- 0.06) and the second with either a depressed ejection fraction (EF) or a history of HTN (mean EF 0.44 +/- 0.15). The diastolic indices examined were peak filling rate (PFR, in end-diastolic volume [EDV]/sec), time to peak filling rate (TPFR, in msec), and first-third filling fraction (FF 1/3, in sec-1). The PFR in CAD and HTN was significantly reduced (1.86 +/- 0.63 and 2.29 +/- 0.49 vs 2.70 +/- 0.35 EDV/sec in NLS, p less than 0.025 and p less than 0.001, respectively), with the CAD group also being significantly lower than the HTN group (p less than 0.005). TPFR was prolonged in HTN, but not in CAD. FF 1/3 was reduced in both HTN and CAD (0.38 +/- 0.11 and 0.50 +/- 0.14 vs 0.61 +/- 0.06 sec-1 in NLS, p less than 0.001 and p less than 0.025, respectively), but it was significantly lower in HTN than in CAD (p less than 0.001). However, when the subgroup of CAD patients with normal global systolic function was examined separately, diastolic indices were only slightly depressed. More importantly, only one, two, and five patients had PFR, TPFR, and FF 1/3, respectively, which were below the normal values of our laboratory.

Emergency defibrillation using a temporary pacing electrode catheter.

Direct application of electrical current to the heart utilizing special equipment such as implantable defibrillators or specially designed catheters has been useful in patients with recurrent ventricular tachyarrhythmias. We describe a patient who developed intractable ventricular fibrillation (VF) during the course of electrophysiologic testing. VF continued for 50 minutes, during which time multiple transthoracic shocks of 360 joules failed to convert the arrhythmia. Intracardiac shocks were then delivered via a transvenous 6 French standard quadripolar pacing catheter positioned in the right ventricular apex by direct application of the defibrillator paddle to the catheter, with the patient lying on the posterior paddle. Energy of up to 300 joules failed to defibrillate the patient, but use of 360 joules delivered in this fashion defibrillated the patient twice. Despite the protracted time of cardiac arrest, the patient recovered without sequelae. We report this case to demonstrate that VF refractory to transthoracic defibrillation may be converted by intracardiac shocks using a temporary pacing catheter without special equipment.