Sequential monotherapy of hypertension.

In most cases, the antihypertensive therapy for an individual patient is selected through a process of trial and error. This study determined if, by treating each hypertensive patient sequentially, with six antihypertensive drugs, one from each of the major classes, one could decide on the best possible drug for control of hypertension. In a randomized open-label crossover study, 19 patients (16 male and 3 female), 28-70 years of age with a sitting diastolic blood pressure of 95-110 mm Hg were given atenolol, captopril, clonidine, indapamide, prazosin, and verapamil in a sequential manner. Each drug was started at the minimum recommended or lower dose and titrated upwards every 2 weeks, if well tolerated, until blood pressure was controlled (diastolic BP < 90 mm Hg). If blood pressure was controlled, the drug was continued for another 2 weeks. A washout period of at least 2 weeks was allowed between drugs. Both systolic and diastolic blood pressures were reduced significantly with all of the six drugs. In 18 of the 19 patients, blood pressure was controlled with at least one of six drugs, frequently with the lowest dose. The authors conclude that if hypertension is not controlled with the lowest recommended dose of a drug, other antihypertensive drugs should be tried sequentially rather than increasing the dose or adding a second drug.

Detection of chronic coronary artery disease: value of pharmacologically stressed, dynamically enhanced turbo-fast low-angle shot MR images.

OBJECTIVE: The potential of MR imaging for evaluating myocardial perfusion and viability may make it the imaging procedure of choice for examining patients with ischemic heart disease. Accordingly, the purpose of this study is to determine the value of pharmacologically stressed, dynamically enhanced turbo-fast low-angle shot (FLASH) MR imaging in detecting chronic coronary artery disease. SUBJECTS AND METHODS: Five patients who had coronary angiography within the past 6-12 months were included in the study. After injection of 0.56 mg/kg of dipyridamole over 4 min, a bolus of 0.05 mg/kg of gadopentetate dimeglumine and subsequently 10 mCi (370 MBq) of 99mTc-sestamibi were injected. Short-axis turbo-FLASH images were obtained before injection and immediately, 1 min, 3 min, and 5 min after the injection of contrast material. Stress single-photon emission computed tomography (SPECT) images of the heart were obtained 60 min after the 99mTc-sestamibi injection. One and a half hours after an additional 30 mCi (1110 MBq) of 99mTc-sestamibi was injected, SPECT images were obtained with patients at rest. Prospective MR imaging evaluation of these five patients was performed by radiologists who did not know any of the imaging data. The MR imaging studies were compared with the near simultaneous 99mTc-sestamibi SPECT studies and with recent coronary angiograms. RESULTS: Thirteen myocardial segments were diagnosed as abnormal when 99mTc-sestamibi SPECT was used as the gold standard (12 reversible defects and one fixed defect). Twelve segments were normal on the 99mTc-sestamibi SPECT study. With SPECT as the gold standard, prospective MR imaging had a sensitivity of 77% and a specificity of 75%, whereas retrospectively it had a sensitivity of 92% and a specificity of 75%. With recent coronary angiography as the gold standard, prospective MR imaging had a sensitivity of 81% and a specificity of 100%. The quantitative data did not improve the accuracy of the qualitative analysis. CONCLUSION: Our results suggest that accurate prospective identification of chronic coronary artery disease may be possible with dynamically enhanced, pharmacologically stressed, turbo-FLASH MR imaging. Studies of additional patients to confirm this initial impression are warranted.

Diagnostic accuracy of seismocardiography compared with electrocardiography for the anatomic and physiologic diagnosis of coronary artery disease during exercise testing.

A multicenter study was performed to compare the diagnostic accuracy of a new technique, seismocardiography, with that of electrocardiography for physiologically and anatomically significant ischemic coronary artery disease (CAD) during exercise stress testing. Five participating centers enrolled 129 patients who had simultaneous seismocardiograms and 12-lead electrocardiograms at the time of their exercise treadmill stress tests. Two different definitions of CAD were used: anatomic and physiologically significant disease. The presence of anatomically significant CAD (> or = 50% diameter stenosis) was documented by coronary angiography. Physiologically significant CAD was defined as present in the same 129 patients when coronary arteriography (> or = 50% diameter stenosis) and thallium-201 scintigraphy (defect on initial postexercise images) were both abnormal. Seismocardiography had a significantly better sensitivity for detecting anatomic CAD than did electrocardiography (73 vs 48%; p < 0.001), without loss of specificity (78 vs 80%; p = NS). Exercise seismocardiography added significant incremental diagnostic information beyond that provided by exercise electrocardiography. Seismocardiography was more sensitive (without less specificity) in women and in patients who did not achieve maximal predicted heart rate. In patients with physiologically significant CAD, the seismocardiogram was also significantly more sensitive (78%) than was the electrocardiogram (55%) (p < 0.02), without loss of specificity (84 vs 74%). Seismocardiography significantly improved sensitivity for the detection of anatomic and physiologic CAD. It is easy to perform and may be a clinically useful adjunct in exercise stress testing.

Amlodipine combined with beta blockade for chronic angina: results of a multicenter, placebo-controlled, randomized double-blind study.

Amlodipine, a potent long-acting dihydropyridine calcium antagonist, was compared with placebo in a parallel, randomized, double-blind study in 134 patients with chronic stable angina pectoris maintained on beta-adrenergic blocking agents. After a single-blind, two-week placebo period, patients were randomized to receive either amlodipine (2.5, 5, and 10 mg) or placebo once daily for four weeks. The effects of amlodipine on maximal exercise time, work, time to angina onset, and subjective indices including angina frequency, nitroglycerin tablet consumption, and patient and investigator ratings were assessed. Each dose of amlodipine produced increases in exercise time and calculated total work accomplished compared to baseline. Improvements at 5 and 10 mg were significantly greater than placebo which produced no significant change (p less than 0.05). Qualitative improvements in the severity of angina were produced by amlodipine at 5 and 10 mg daily assessed by patient-rating questionnaires (p less than 0.05). Reductions in angina frequency attacks per week and weekly nitroglycerin tablet consumption occurred but were not statistically significant when compared with placebo. Adverse effects observed during amlodipine treatment prompted discontinuation of treatment in only 2 out of 100 patients. Three patients discontinued treatment for reported lack of efficacy. No laboratory abnormalities prompted treatment discontinuation and minor side effects of dizziness, nausea, headache, and fatigue were observed infrequently. The results of this controlled, large-scale multicenter trial suggest that amlodipine significantly increased exercise capacity and was well tolerated when added to the antianginal regimen of patients remaining symptomatic while receiving beta-blocking agents.

Static versus dynamic exercise: effects on Doppler echocardiographic indices of left ventricular performance.

In order to compare the effects of static exercise with those of dynamic exercise on the Doppler echocardiographic measurements of ascending aortic blood flow velocity and acceleration, Doppler echocardiography was performed with sustained handgrip exercise and with supine bicycle exercise in 12 normal subjects, 12 patients with coronary artery disease, and 7 patients with heart failure. In normal subjects: peak velocity decreased by 16 +/- 11% with handgrip from the resting value and increased by 49 +/- 19% with bicycle exercise (p less than 0.01); mean acceleration decreased by 6 +/- 30% with handgrip and increased by 162 +/- 83% with bicycle exercise (p less than 0.01). In patients with coronary artery disease: peak velocity declined by 9 +/- 14% with handgrip and increased by 19 +/- 18% with bicycle exercise (p less than 0.01); mean acceleration increased by 13 +/- 27% with handgrip and by 41 +/- 33% with bicycle exercise (NS). In patients with congestive heart failure: peak velocity decreased by 19 +/- 13% with handgrip and increased by 5 +/- 17% with bicycle exercise (p less than 0.01); mean acceleration decreased by 12 +/- 23% with handgrip and by 4 +/- 37% with bicycle exercise. A marked increase in afterload stress induced by static exercise presumably offsets the moderately increased contractility and accounts for the decline of peak velocity and mean acceleration with static exercise both in normals and cardiac patients. In contrast, marked increase in contractile state along with little change in afterload with dynamic exercise results in markedly increased peak velocity and mean acceleration in normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular ochronosis: a case report and review of the medical literature.

Ochronosis is a rare disorder of tyrosine metabolism due to a deficiency of the enzyme homogentisic acid oxidase. The most common clinical manifestations include alkaptonuria, spondyloarthropathy, large joint arthritides and pigmentation of cartilage. Cardiac involvement may occur due to the deposition of polymerized homogentisic acid in the aortic, mitral and pulmonic valves. Usually, this leads to increasing rigidity and calcification. The only functionally significant valve lesion reported appears to be aortic stenosis. A possible link between ochronosis and coronary artery disease has been postulated. Further, a link between peripheral vascular disease and ochronosis may be present. We describe a case of ochronotic cardiovascular disease and review the literature on the subject.

Spontaneous recovery of left ventricular function following acute anterior myocardial infarction.

Four patients with acute anterior wall myocardial infarction showing spontaneous and marked improvement in systolic left ventricular function are described. All 4 patients showed abnormal Q waves and severe wall motion abnormalities soon after acute infarction. In all 4 patients, at least some regeneration of R-wave forces occurred and the regional wall motion in the involved area of the left ventricle improved dramatically without coronary angioplasty or surgical revascularization during the intervening period. The improvement in left ventricular function was attributed to spontaneous increase in nutrient flow to the involved area. It is concluded that Q waves and severe wall motion abnormalities do not necessarily indicate irreversible scar formation.

Effect of maintenance oral theophylline on dipyridamole-thallium-201 myocardial imaging using SPECT and dipyridamole-induced hemodynamic changes.

To evaluate the effect of maintenance oral theophylline therapy on the diagnostic efficacy of dipyridamole-thallium-201 single photon emission computed tomography (SPECT) imaging for coronary artery disease, dipyridamole-thallium-201 SPECT imaging was performed in eight men with documented coronary artery disease before initiation of theophylline treatment and repeated while these patients were receiving therapeutic doses of oral theophylline. Before theophylline treatment, intravenous dipyridamole caused a significant increase in heart rate, decrease in blood pressure, angina in seven of eight patients, and ST segment depression in four of eight patients. While they were being treated with theophylline, none of the patients had angina or ST segment depression, and there were no hemodynamic changes with intravenous dipyridamole. Before theophylline treatment, dipyridamole-thallium-201 SPECT imaging showed reversible perfusion defects in myocardial segments supplied by stenotic coronary arteries. With theophylline treatment, dipyridamole-thallium-201 SPECT showed total absence of reversible perfusion defects. Treatment with theophylline markedly reduced the diagnostic accuracy of dipyridamole-thallium-201 imaging for coronary artery disease.

Comparison of ST segment depression in upright treadmill and supine bicycle exercise testing.

Significant differences in the hemodynamic response to upright and supine exercise have been reported in patients with coronary artery disease. The purpose of the present study was to compare the degree of myocardial ischemia as assessed by ST segment depression during upright treadmill and supine bicycle exercise in 98 patients with coronary artery disease and in 34 patients with normal coronary arteries. The amount of ST segment depression at maximal exercise in patients with coronary artery disease was 0.90 +/- 0.80 mm for treadmill and 1.34 +/- 1.09 mm for supine bicycle (p less than 0.001). The amount of ST segment depression during treadmill and supine bicycle exercise tests was also compared at highest similar heart rates (0.68 +/- 0.77 versus 1.17 +/- 1.01, p less than 0.001), at highest similar rate-pressure products (0.71 +/- 0.77 versus 1.08 +/- 1.04, p less than 0.001), at highest similar metabolic equivalents of oxygen consumption (MET) levels (0.69 +/- 0.75 versus 1.20 +/- 1.05 mm, p less than 0.001) and at the onset of angina (0.84 +/- 0.73 versus 1.18 +/- 0.88 mm, p less than 0.001). The rate-pressure product achieved at maximal exercise was similar in both tests (18.74 +/- 5.80 x 10(3) versus 18.81 +/- 5.17 x 10(3), p = NS). The occurrence of angina during treadmill and supine bicycle exercise tests was similar (47 of 98 versus 48 of 98, respectively, p = NS). For the detection of coronary artery disease, the sensitivity was 50.0% for treadmill and 63.3% for supine bicycle (p less than 0.05) and the specificity was 73.5 versus 70.6%, respectively (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes mellitus and arteriographically-documented coronary artery disease.

Diabetics are at increased risk for coronary heart disease even after accounting for other risk factors, and the impact of diabetes mellitus may be particularly strong among females and at adverse levels of other risk factors. Therefore, the independent relation of diabetes to arteriographically-documented coronary artery disease (CAD) was examined in 5620 patients (18% female) referred to two Milwaukee hospitals from 1972 to 1986. As assessed by questionnaire, the prevalence of diabetes mellitus among these patients was 8% (n = 466). Diabetics had increased CAD (assessed by the number and severity of stenoses) even after accounting for levels of total and high-density lipoprotein cholesterol, triglycerides, hypertension, obesity, smoking, and alcohol consumption. In addition, regression analyses indicated that as compared with nondiabetics, female diabetics tended to have a greater increase in CAD than did male diabetics (p = 0.06 for sex x diabetes interaction). Although adverse levels of other risk factors did not increase the association between diabetes and CAD, female diabetics who were using oral hypoglycemics or insulin showed almost a two-fold increase in CAD severity (p less than 0.01). Results suggest that the higher relative risk of coronary heart disease among female (vs male) diabetics may be due to a proportionately greater increase in atherosclerosis.

Ochronotic cardiovascular disease.

Ochronosis is a disease of tyrosine metabolism. Although most commonly associated with alcaptonuria and spondyloarthropathy, cardiovascular abnormalities have been associated. We describe a case which exemplifies the cardiovascular findings in this entity.

Value of exercise electrocardiography to predict additional jeopardized myocardial regions remote from site of previous myocardial infarction.

In order to evaluate the efficacy of exercise electrocardiography (ECG) to identify jeopardized myocardial regions remote from the site of previous infarction, exercise ECG, left ventriculography, and coronary arteriography were performed in 90 patients with previous transmural myocardial infarction (MI). Of the 90 patients, angiographic studies revealed jeopardized myocardial regions in 47 patients. Exercise ECG correctly identified 32 of these 47 patients for a sensitivity value of 68%. There were 43 patients without any additional jeopardized myocardial regions. Exercise ECG correctly identified only 24 of these 43 patients for a specificity value of 56%. The sensitivity and specificity values were similar in patients with prior anterior and inferior wall MI. It is concluded that relatively low sensitivity and specificity values preclude the ability of exercise ECG to accurately identify patients with jeopardized myocardial regions distant from the site of previous MI. Moreover, when such patients were correctly detected, exercise ECG was rather poor in localizing these additional jeopardized myocardial areas.

Refractory coronary artery spasm.

A patient with an episode of refractory myocardial ischemia induced by ergonovine is described. The patient underwent cardiac catheterization 2 weeks after an inferior wall myocardial infarction for evaluation of recurrent rest angina. He developed severe spasm of the proximal right coronary artery in response to ergonovine which was partially relieved with nitrates and calcium channel antagonists. However, myocardial ischemia persisted, culminating in a new inferior wall infarction. The possible mechanism of continuing intense ischemia despite partial relief of the proximal right coronary spasm is discussed. It is suggested that ergonovine testing should perhaps be avoided during the early postinfarction period. Furthermore, if an ergonovine test is anticipated, beta-adrenergic blocking agents should be withheld.

The Valsalva maneuver: mechanisms and clinical implications.

The previous discussion has focused on the mechanisms, both respiratory and circulatory, that occur during the Valsalva maneuver. The increase in intrathoracic pressure that occurs during the Valsalva maneuver incites a sequence of rapid changes in preload and afterload stress. During the strain, venous return to the heart is decreased and peripheral venous pressures become increased. Within the next few beats, systolic and pulse pressures begin to fall while mean arterial pressure remains near (or is elevated above) control levels owing to the transmission of airway pressure. Thus it would appear that the benefits to cardiac contractility derived from a decrease in systolic and pulse pressure are counterbalanced by an increase in mean arterial pressure. Increases in total peripheral resistance that begin after about 7 seconds of strain produce further increases in afterload. Recruitment of autonomically mediated increases in heart rate and cardiac contractility assists the heart to maintain its cardiac output in the presence of diminished venous return. With the increased venous return that accompanies termination of Valsalva strain, there is an increase in diastolic filling and stroke volume output by means of the Frank-Starling mechanism. Heart rate and total peripheral resistance continue to be increased during the immediate poststrain period, and the ejection of an increased stroke volume into a constricted arterial system produces a rapid and marked increase in arterial pressure--the phase IV overshoot with its subsequent slowing of heart rate.

Digital processing of contrast echocardiograms: a new technique for measuring right ventricular ejection fraction.

Imaging of the right ventricle with 2-dimensional echocardiography (2-D echo) is hampered by trabeculation of the right ventricular (RV) endocardial surface and by limited echocardiographic resolution. Determination of RV ejection fraction (EF) is thus often an inconsistent and tedious procedure. The process of digital subtraction contrast echocardiography was developed to maximize echocardiographic definition of the right ventricle and to assess RVEF with minimal operator interaction. Videotaped 2-D echocardiograms recorded during i.v. injection of agitated saline were digitized. Masks were constructed from end-systolic and end-diastolic apical 4-chamber and parasternal RV short-axis images. Masks were subtracted from corresponding images recorded with contrast in the right ventricle; images of the contrast alone were extracted and their areas determined. EF was calculated from raw area measurements and after conversion to volume. Comparison with RVEF measured by first-pass radionuclide angiography yielded the following correlation coefficients: 4-chamber RV area, r = 0.79; parasternal short-axis RV area, r = 0.59; ellipsoid approximation RV volume, r = 0.84; pyramidal RV volume, r = 0.79; and Simpson's rule triangular cylinder RV volume, r = 0.62. Digital subtraction contrast echocardiography is a new method that can be used for semiautomated determination of RVEF. Further studies to assess the clinical values of digital image processing of 2-D echocardiograms to measure RV function appear warranted.