Paradoxical pressor effects of beta-blockers in standing elderly patients with mild hypertension: a beneficial side effect.

BACKGROUND: Baroreflex sensitivity declines with age, creating a fall in systolic blood pressure and pulse pressure when standing. If, in addition, blood pressure is reduced as a result of antihypertensive medication, compensatory mechanisms may be inadequate and orthostatic problems may occur. This may be less true in patients on beta-blockers. beta-blockers cause pressor effects in standing patients with autonomic neuropathy, but their effects on standing pulse pressures in elderly subjects with mild hypertension have not been systematically studied. METHODS AND RESULTS: We studied 3741 patients with mild hypertension for 6 months who were being treated with the beta-blocker nebivolol 5 mg daily. Blood pressures were measured after 10 minutes in the supine position and after 1 minute in the standing position. Overall, systolic and diastolic blood pressures rose slightly while standing, whereas pulse pressures remained unchanged. When previously untreated patients (n=2085) >60 and <60 years of age were assessed separately, supine pulse pressures were consistently higher in the elderly group compared with those of the younger subjects by 6 to 11 mm Hg (P<0.001 to 0.0001). However, while standing, pulse pressures rose in the younger subjects, whereas they tended to fall in the elderly group. After 6 months of beta-blockade, this pattern was unchanged in the younger subjects but reversed into significant rise of pulse pressures in the elderly group by 4 (SD 1) mm Hg (P<0.001). In the patients previously treated with other classes of antihypertensive drugs (n=712), the effects were essentially the same. CONCLUSIONS: In elderly patients with mild hypertension, a depressor trend of pulse pressure while standing can be turned into a significant pressor response by treatment with a beta-blocker.

Assessment of quality of life in patients with angina pectoris: Progress made by the Dutch Mononitrate Quality-Of-Life (DUMQOL) Study Group.

BACKGROUND: Two major issues in quality of life (QOL) research are the patient's opinion as a contributing factor in QOL assessments, and the lack of sensitivity of QOL assessments. OBJECTIVES: To review results from recent research by the Dutch Mononitrate Quality Of Life (DUMQOL) Study Group relevant to these two issues. METHODS: Using a test battery including Stewart's Short Form (SF)-36 Questionnaire and the DUMQOL-50 questionnaire, the DUMQOL Study Group tested the hypothesis that the patient's opinion might be an independent determinant of QOL. To do this, a stepwise multiple regression analysis of data from 82 patients attending an outpatient clinic with stable angina pectoris was performed. Secondly, using an odds ratio approach to QOL scores in 1350 outpatients with stable angina pectoris who were attending a clinic, the DUMQOL Study Group assessed the question whether relative scores might provide increased precision in estimating the effects of patient characteristics on QOL data. RESULTS: Psychological distress was the most important contributor to QOL (beta 0.43, p<0.0001). Also, the patient's opinion on his/her QOL significantly contributed to QOL (beta 0.22, p=0.032). Physical health status according to the patient's judgement only made a borderline contribution (beta 0.19, p=0.71), while the physician's judgement was not associated with QOL at all (beta 0.11, p=0.87). Regarding the second issue, increased QOL difficulties were observed in New York Heart Association (NYHA) angina class III-IV patients, in patients with comorbidity, as well as in female and elderly patients. Odds ratios can be used in these categories to predict the benefit from treatments. CONCLUSIONS: Recent QOL research of the DUMQOL Study Group allows conclusions to be drawn that are relevant to clinical practice. QOL should be defined in a subjective rather than an objective method. The patient's opinion is an important independent contributor to QOL. The comparison of absolute QOL scores lacks the sensitivity to truly estimate QOL. The odds ratio approach of QOL scores provides increased precision in estimating QOL.

Independent determinants of the efficacy of nitrate therapy.

BACKGROUND: Asymmetric dosage regimens of isosorbide mononitrate provide better antianginal efficacy and quality of life in patients with stable angina pectoris than the daily administration of multiple small doses of the compound. It is not known whether certain patient characteristics contribute to this improved benefit. OBJECTIVE: To determine independent factors contributing to this improved benefit. Multiple linear regression analysis was performed with a self assessment study in 1350 patients with stable angina pectoris. Quality of life was assessed by the Marquis questionnaire for patients with angina and included the assessment of immobility, pain and psychological distress. Individual scores were calculated as the pooled sums of the assessment scores and were expressed on an ordinal scale of 10. RESULTS: Age did not influence the improvement in benefit. Gender, rhythmic disturbances, peripheral artery disease and the concomitant use of calcium channel blockers or beta-blockers were without effect. New York Heart Association angina classification was an independent variable: patients with a class I or II showed less benefit than did patients with class III or IV (p = 0.02). Obese patients as well as hypertensive patients (p = 0.04 and 0.02), and smokers also tended to benefit less (p = 0.08). In contrast, the presence of cholesterolemia and diabetes mellitus were associated with increase in the beneficial effect of nitrates on quality of life (p = 0.03 and 0.05). CONCLUSIONS: Patients with severe angina pectoris benefit better from nitrate therapy than do patients with New York Heart Association class I - II. Also, patients with coronary artery disease and concomitant diabetes mellitus or cholesterolemia may benefit better from nitric oxide donor therapy than patients without such condition. In contrast, patients with concomitant obesity, hypertension, or who are smokers may show less benefit.

Isosorbide mononitrate 30% immediate-release 70% sustained-release formulation: a review. DUMQOL (DUtch Mononitrate Quality of Life) Study Group.

Since the first publication of isosorbide mononitrate 30% immediate-release 70% sustained-release (IR-SR) formulation in 1985, a considerable body of literature concerning its clinical efficacy and safety has become available. Theoretically, the formulation has the advantage over conventional isosorbide mononitrate or dinitrate (ISMN/ISDN) that it has a simpler and more predictable pharmacokinetic profile. The objectives of this paper are to review published data so far and to see whether the theoretical advantages translate into better clinical effectiveness. 1. After oral administration, isosorbide mononitrate IR-SR has a rapid onset of action (30 minutes), and effects are evident for up to 17 hours. 2. The antianginal effects of once-daily isosorbide mononitrate IR-SR increased with increasing dosages, were generally larger than those of either placebo or equipotent doses of conventional ISMN/ISDN, and were somewhat larger than those of the beta blocker bupranolol. The effects were generally similar to those of sustained release nifedipine. 3. Patients showed significantly greater improvement in some quality-of-life indices with once-daily isosorbide mononitrate IR-SR than with twice or three times daily regimens of conventional ISMN/ISDN. This was particularly so with mobility, psychological distress, and life satisfaction indices. 4. Tolerance did not develop after 13 months of once daily isosorbide dinitrate IR-SR. No rebound increase in incidence of ischemic episodes was observed after discontinuation of treatment. 5. Long-term efficacy data both of isosorbide mononitrate IR-SR and of conventional ISMN/ISDN are limited so far. Large studies in patients with angina pectoris and patients with heart failure addressing long-term effects are ongoing, and some of the data will be completed within the next months. Isosorbide mononitrate IR-SR has a rapid onset of action and has been shown to be clinically efficient and, in addition, to be more so than conventional ISMN / ISDN. Nitrate tolerance with continued use of the formulation has not yet been reported. Long-term effects on morbidity and mortality are currently being assessed.

Factors influencing efficacy of nitrate therapy for stable angina pectoris: a multiple linear regression analysis.

In an open-label self-controlled study of 1,350 patients with stable angina pectoris (SAP), we previously demonstrated that 50 mg of isosorbide mononitrate (ISMN) slow release formulation once daily not only provided a better antianginal effect but also a better quality of life (QOL) than did the daily administration of multiple small doses of the compound. It is unknown whether certain patient characteristics contribute to this benefit. The objective of this article was to determine what independent factors contribute to this benefit. Multiple linear regression analysis was performed on the data from these 1,350 patients. Quality of life was assessed by the Marquis QOL-questionnaire for patients with angina and included the domains of immobility, pain, and psychological distress. For the purpose of this study, overall QOL was calculated as the pooled sums of the domain scores and expressed as mean scores on an ordinal scale of 10. Age did not influence the beneficial effect of nitrate therapy on QOL. Neither did gender, rhythmic disturbances, peripheral artery disease, or the concomitant use of calcium channel blockers or beta blockers. New York Heart Association (NYHA) angina classification was an independent variable: patients with a NYHA class I or II benefited less than did patients with NYHA III or IV (p = 0.02). Obese patients as well as hypertensive patients benefited less (p = 0.04 and 0.02), and smokers tended to benefit less also (p = 0.08). In contrast, hypercholesterolemia and diabetes mellitus improved the beneficial effect of nitrates on QOL (p = 0.03 and 0.05). The authors conclude that patients with coronary artery disease (CAD) and concomitant diabetes mellitus or hypercholesterolemia, a category particularly prone to early endothelial dysfunction and thus dysfunctional endogenous nitric oxide (NO) production, may benefit more from NO-donor therapy than patients without such concomitant conditions.

Comparison of 50-mg and 100-mg sustained-release isosorbide mononitrate in the treatment of stable angina pectoris: effects on quality-of-life indices. Dutch Mononitrate Quality of Life (DUMQOL) Study Group.

High-dosage nitrates are more effective for the management of anginal symptoms but produce more adverse effects, including development of tolerance and the zero-hour effect (rebound angina at the end of the dosing interval). Such effects may reduce the beneficial effect of treatment on quality of life. In a self-controlled, 6-month study, the effects on symptoms and quality of life of 50 mg and 100 mg sustained-release isosorbide mononitrate (SR ISMN), administered once daily, on anginal symptoms and quality of life (QOL) were assessed in 453 patients with stable angina pectoris. QOL was assessed by means of a test battery based on the Medical Outcomes Short-Form 36 Health Survey and the Angina Pectoris Quality of Life Questionnaire. The internal consistency and reliability of the multiitem scales were estimated by use of Cronbach's alpha coefficient. Based on their improvements in New York Heart Association (NYHA) angina classification, patients who received 100 mg daily showed greater improvement than those who received 50 mgdaily; the mean difference between treatments was consistent with a significantly greater improvement of mobility and angina indices. Adverse effects, as estimated by side-effect index, including rebound angina at times of rest, and by patient compliance rating, differed slightly between the two treatment regimens and were even less problematic with the higher dosage than with the lower dosage. Psychological distress index and life satisfaction scores also were significantly higher with 100 mg than with 50 mg daily. The results of this study suggest that SR ISMN 100 mg once daily provided a better NYHA angina classification than SR ISMN 50 mg did and did not produce further adverse effects. In addition SR ISMN 100 mg improved various QOL indices more than SR ISMN 50 mg did, particularly the mobility index and certain life satisfaction scores, which are the most important indicators of QOL in this category of patients.

T-channel-selective calcium channel blockade: a promising therapeutic possibility, only preliminarily tested so far: a review of published data. T-Channel Calcium Channel Blocker Study Group.

Basic studies as well as short-term clinical trials of the T-channel-selective calcium channel blocker, mibefradil, are reviewed. The compound reduced afterload and was effective for the symptomatic treatment of hypertension and stable angina pectoris. It did not display any relevant negative inotropic or positive chronotropic effect. Mibefradil has been withdrawn by the manufacturer because of drug interaction at the cytochrome P-450 3A4 enzyme. It is hoped that new T-channel-selective calcium channel blockers will be developed to explore further this promising but so far only preliminarily tested therapeutic possibility.

A randomized, placebo-controlled study of loop diuretics in patients with essential hypertension: the bumetanide and furosemide on lipid profile (BUFUL) clinical study report.

This study was conducted to determine whether loop diuretics are more effective than placebo in reducing blood pressure without raising serum lipid levels, and whether bumetanide is more effective than furosemide in this respect. In a double-blind, 24-week placebo-controlled crossover study, 27 patients with essential hypertension were treated in four periods of 6 weeks each, including placebo twice, furosemide 40 mg daily, and bumetanide 1 mg daily. Several metabolic parameters, including serum lipid levels, and blood pressure were assessed. Overall levels of total cholesterol, triglycerides, and low-density lipoprotein (LDL) cholesterol were 5%, 12.4%, and 4.8% higher, respectively, during loop diuretic therapy than during placebo treatment. Overall systolic and diastolic blood pressure measurements were 12 mmHg and 4 mmHg lower, respectively, during loop diuretic therapy than during placebo treatment. Any added effect of bumetanide on serum lipid levels and blood pressure compared with furosemide, however, could not be confirmed. Our results indicate that the loop diuretics bumetanide and furosemide are effective in reducing blood pressure, and influence serum lipid levels markedly less than do thiazide diuretics or chlorthalidone. In addition, these results indicate that differences in blood pressure reduction and serum lipid levels between the two compounds were small and nonsignificant.

Tc-99m tetrofosmin myocardial SPECT perfusion imaging: comparison of rest-stress and stress-rest protocols.

AIM: The purpose of this study was to evaluate the diagnostic value of Tc-99m tetrofosmin SPECT myocardial perfusion scintigraphy rest/stress and stress/rest protocols for the assessment of coronary artery disease (CAD). METHODS: 65 patients underwent both rest and stress SPECT imaging in a one-day protocol and coronary angiography within 2 months before or after scintigraphy. Scintigraphic data was obtained according to two different protocols; 1) rest-stress (n = 18) and 2) stress-rest (n = 47). RESULTS: Scintigraphic evidence for myocardial ischaemia was found in 36 patients (55%). The overall sensitivity to detect CAD (> 50% luminal stenosis) was 94% (34/36), specificity 66% (19/24), positive predictive value 77%, negative predictive value 90%. The sensitivity to detect CAD for protocols 1 and 2 were 100% and 93%, specificity 56% and 70%, positive predictive value 69% and 81% and negative predictive value 100% and 88%, respectively. The left anterior descending coronary artery showed a sensitivity (overall, protocol 1 & 2) of 78%, 75% (3/4) and 79% (15/19) and a specificity of 71%, 64% (9/14) and 75% (21/28). The right coronary artery showed a sensitivity (overall, protocol 1 & 2) of 91%, 100% (6/6) and 88% (14/16) and a specificity of 70%, 92% (11/12) and 61% (19/31). The left circumflex coronary artery showed a sensitivity (overall, protocol 1 & 2) of 50%, 67% (2/3) and 46% (6/13) and a specificity of 94%, 100% (15/15) and 91% (31/34). CONCLUSION: Tc-99m tetrofosmin appears to be a valuable tool in predicting significant CAD. The sensitivity and the positive predictive value are high, making this test highly appropriate for the diagnosis of CAD. The diagnostic value of the individual coronary arteries is high to moderate. No significant differences were found between both protocols.

Comparison of thallium scintigraphy and positron emission tomography.

Assessment of tissue viability has become an important issue in recent years. Scintigraphic measurements have provided important diagnostic, therapeutic, and prognostic information in patients with myocardial dysfunction, who may improve in left ventricular function after revascularization. For detection of regional myocardial ischemia and viability, thallium 201 (201Tl) has been the most widely used tracer in single-photon scintigraphy. However, 201Tl scintigraphy may underestimate regional viability, especially after myocardial infarction. Positron emission tomography (PET) provides an advanced imaging technology that permits the accurate definition of regional tracer distribution. In combination with nitrogen (13N) ammonia, PET allows for the sensitive and specific detection of coronary artery disease. Several studies indicate the superiority of this approach in comparison with standard 201Tl tomographic (SPECT) imaging. In addition, regional blood flow can be accurately measured with 13N ammonia PET, and this approach can be employed in conjunction with pharmacologic stress imaging to quantify regional flow reserve. In combination with metabolic markers, such as fluorine 18 (18F) deoxyglucose, an indicator of glucose uptake, PET is capable of assessing myocardial viability. Furthermore, the PET approach may differentiate between various forms of cardiomyopathy. More studies are needed to define the cost-benefit ratio of both the 201Tl reinjection and the PET technique for the management of patients with coronary artery disease or cardiomyopathy.

Comparison of multiple-dose and once-daily nitrate therapy in 1212 patients with stable angina pectoris: effects on quality of life indices. Dutch Mononitrate Quality of Life (DUMQOL) Study Group.

BACKGROUND: Nitrates, although important for the management of anginal symptoms, produce significant side effects. Little is known about their net effects on health-related, quality-of-life indices. METHODS: In a self-controlled, 6-month study, the effects on symptoms and quality of life of multiple-dose and once-daily nitrate therapy were evaluated in 1212 patients with stable angina pectoris. Quality of life was assessed by a test battery based on the exercise-tolerance index of Wiklund, the psychological well-being index of Dupuy, and the Short Form 36 questionnaire of Stewart. The internal consistency and reliability of the multi-item scales were estimated by Cronbach's alpha coefficients. RESULTS: The effects of the two treatment regimens on pain index and number of additional sublingual nitrate tablets required were not different. However, based on the New York Heart Association (NYHA) angina classification, patients improved better on the once-daily than on the multiple-dose regimen: by > 1 category in 281 vs 62 of the patients (P < 0.0001); mobility and psychological distress indices also improved (P = 0.006, and P = 0.007). CONCLUSIONS: Once-daily nitrate therapy not only provides a better NYHA angina classification than multiple-dose therapy does, but also provides a better quality of life as estimated by improvement of mobility and distress indices, the most important indicators of quality of life in this category of patients.

Normal values and reproducibility of left ventricular filling parameters by radionuclide angiography.

BACKGROUND: In physiologic situations age, heart rate (HR) and left ventricular ejection fraction (EF) may influence left ventricular filling rate. In this study, we determined normal values for radionuclide angiography (RNA) derived diastolic filling parameters, the correlations with age, HR and EF and their reproducibility. METHODS: The study was performed in 20 patients, 40-76 years old (mean 57), with normal findings at coronary angiography and left ventriculography. The first RNA was performed at rest (RNA1). Then, five minutes bicycle ergometry was performed and the patients were allowed five minutes rest before RNA was repeated (RNA2). From the left ventricular time activity curve we determined peak filling rate (PFR), time to peak filling rate (TPFR) and atrial contribution (AC) to ventricular filling. RESULTS: Values for PFR1 were 2.2 +/- 0.6 EDV/sec (PFR2 2.4 +/- 0.7 EDV/sec, r = 0.82), for TPFR1 198 +/- 22 msec (TPFR2 203 +/- 24 msec, r = 0.45) and for AC1 31 +/- 11% (AC2 31 +/- 10%, r = 0.72). The correlations of PFR and TPFR with age were statistically significant (respectively r = -0.68 and r = 0.48, P < 0.05). PFR was also influenced by HR and EF (resp. r = 0.51 and r = 0.50, P < 0.05). TPFR however was not influenced by HR and EF, whereas AC was positively correlated with HR (r = 0.79, P < 0.01). CONCLUSIONS: Radionuclide angiography is a reliable and reproducible method to assess parameters of diastolic left ventricular filling in individual patients. It may therefore be used to serially follow diastolic function. When used for interindividual comparison the dependency of RNA derived left ventricular filling parameters on age, HR and EF should however be considered.

Quality of life before and during antihypertensive treatment: a comparative study of celiprolol and atenolol.

Hypertensive patients may be adversely affected by complications and other concomitant processes such as anxiety, sedation, and drug side effects. It has been suggested that some recently developed antihypertensive agents do not affect quality of life by causing adverse effects. We compared the effects of two antihypertensive drugs on quality of life: atenolol, a standard cardioselective beta-blocker, and celiprolol, one of a new class of selective beta-blockers with vasodilatory properties. One hundred thirty-two patients with mild-to-moderate hypertension were eligible to enter a 28-week, double-blind, parallel-group study. The study protocol consisted of a 4-week period on placebo and a 24-week period of dosage-adjusted treatment with either atenolol or celiprolol. We assessed both systolic and diastolic blood pressure and quality of life perception by a selected test battery that included the Bulpitt and Fletcher Quality of Life Questionnaire. Supine blood pressure fell from 167/101 (range 120/95 to 200/116) to 150/92 mm Hg (p < 0. 0001) during celiprolol treatment. This antihypertensive effect was at least as good with celiprolol as with atenolol. Quality of life perception was comparable for the two drugs although adverse effects were seen more frequently with atenolol than with celiprolol, particularly after prolonged treatment. Patient compliance was better for celiprolol than for atenolol. Our results show that the selective beta-blocker with vasodilatory property celiprolol is at least as effective as atenolol and that it is more advantageous in terms of some quality of life variables.

SPECT versus planar 99mTc-sestamibi myocardial scintigraphy: comparison of accuracy and impact on patient management in chronic ischemic heart disease.

A head-to-head comparison between 99mTc-sestamibi SPECT and planar myocardial imaging using dipyridamole low-level exercise stress was performed for the assessment of coronary artery disease (CAD) and for the impact on patient management in 78 patients (pts) who underwent coronary arteriography. Overall sensitivity and specificity for detection of CAD were 82% and 82% for SPECT, and 78% and 73% for planar imaging, respectively (both NS). Compared to planar imaging the sensitivity of SPECT imaging was significantly higher for detecting left anterior descending (p = 0.02) and left circumflex (p = 0.03) coronary artery disease. In predicting distally located stenoses, SPECT was significantly superior to planar imaging for the left circumflex artery (p = 0.025). Concordance analysis of perfusion status showed agreement in 308 of 390 (79%) of coronary flow regions both with respect to the presence or absence of perfusion and to the reversibility or irreversibility of defects (kappa = 0.60, SE 0.04). Stress-induced perfusion defects were significantly more detected by SPECT than by planar imaging (p < 0.001). Based on SPECT findings 31 pts were proposed for revascularization compared to 30 pts based on planar imaging (NS). Overall there was agreement in 65 (83%) pts regarding treatment strategy. We conclude that in a head-to-head comparison SPECT provided improved diagnostic value compared with planar imaging. However, with respect to patient treatment, the superiority of SPECT was not always translated into improved patient management.

Detection of coronary artery disease: comparison between technetium 99m-labeled sestamibi single-photon emission computed tomography and two-dimensional echocardiography with dipyridamole low-level exercise-stress.

BACKGROUND: Myocardial perfusion imaging in conjunction with dipyridamole low-level exercise stress has proved its value in the evaluation of patients with coronary artery disease (CAD). Simultaneous wall motion analysis by two-dimensional (2D) echocardiography may provide additional information beyond that obtained by myocardial perfusion imaging alone. The purpose of this study was to compare 99mTc-labeled sestamibi single-photon emission computed tomography (SPECT) and 2D echocardiography for the evaluation of CAD according to a dipyridamole low-level bicycle exercise stress protocol. METHODS AND RESULTS: We studied 35 consecutive patients referred for the evaluation of chest pain who had undergone coronary arteriography. 99mTc-labeled sestamibi SPECT and 2D echocardiography agreed in 27 patients (80%) studied for overall detection of CAD. On a segmental basis, agreement was found between SPECT and 2D echocardiography in 124 (73%) of 170 segments (Cohen's kappa = 0.43). The accuracy of the combined assessment of myocardial perfusion and echocardiographic wall motion in detecting CAD was 86%, which was not different from the accuracy of SPECT alone (80%; difference not significant) but significantly higher than for 2D echocardiography alone (71%; p = 0.03). In the detection of individual coronary artery stenoses, SPECT had a significantly higher accuracy for detecting left anterior descending coronary artery lesions than had 2D echocardiography (80% vs 60%; p < 0.01); combining the two method did not improve the accuracy (80%). The combined assessment slightly improved the accuracy for detecting left circumflex coronary artery stenoses from 71% to 83% (p = 0.05). CONCLUSION: The combined simultaneous assessment of myocardial perfusion by 99mTc-labeled sestamibi SPECT and wall motion by 2D echocardiography did not significantly improve overall accuracy over that obtained by 99mTc-labeled sestamibi SPECT alone. Therefore 99mTc-labeled sestamibi SPECT with dipyridamole low-level exercise stress appears the preferred imaging modality for the evaluation of patients with CAD.

Stress-reinjection 201Tl scintigraphy without redistribution imaging: prediction of the effect of coronary artery bypass grafting on regional myocardial 201Tl uptake.

Reinjection of thallium-201 (201Tl) improves the detection of myocardial ischaemia in approximately 50% of irreversible defects present on 3 h redistribution images. Additional reinjection studies, however, may limit the capacity of the nuclear laboratory and they are not patient-friendly Previous studies have suggested that only severe persistent defects with less than 50% of maximal 201Tl uptake are irreversibly damaged, with little chance of recovery following coronary artery bypass grafting (CABG). We examined the ability of a modified stress-reinjection protocol without redistribution imaging to predict subsequent improvement in myocardial perfusion post-CABG. Thirty-seven patients underwent quantitative planar stress/3 h reinjection 201Tl scintigraphy before and after uncomplicated CABG. After stress, segments were classified as normal (> or = 75% maximum 201Tl uptake), moderate defect (50-75%) or severe defect (< 50%). After reinjection, they were classified as completely normalizing (> or = 75%), partially improving moderate defect (increase > or = 10% but < 75%), partially improving severe defect (increase > or = 10% but < 50%), persistent moderate defect (< 10% increase) or persistent severe defect (< 50% initial uptake with < 10% increase). Scintigraphic classification was compared with left ventricular wall motion and post-operative classification. Of 336 initial stress defects, 264 (79%) were moderate defects and 72 (21%) were severe defects. After reinjection, 146 (55%) moderate defects normalized, 25 (9%) improved partially and 93 (35%) persisted. Nineteen (26%) severe defects normalized, 33 (46%) improved to become moderate defects, 7 (10%) improved only slightly and 13 (18%) persisted. Post-CABG, 201T1 uptake was normal in 123 of 146 (84%) completely normalizing moderate defects, 15 of 25 (60%) partially improving moderate defects, 53 of 93 (57%) persistent moderate defects, 11 of 19 (58%) completely normalizing severe defects and 13 of 33 (39%) partially improving moderate defects. None of the partially improving severe defects or persistent severe defects normalized. The sensitivity and specificity of detection of viability with pre-CABG stress-injection scintigraphy were 66% and 72% respectively, with pre-CABG wall motion 80% and 40% respectively, whereas in combination they resulted in a sensitivity and specificity of 94% and 70% respectively. We conclude that stress/3 h reinjection without redistribution imaging is a clinically feasible method for predicting myocardial 201T1 uptake post-CABG. The severity of defects and the pattern of change of uptake after stress-injection are related to the likelihood of normal 201T1 uptake post-CABG. Severe defects after reinjection are very unlikely to recover.

Quality of life before and during antihypertensive treatment: a comparative study of celiprolol and atenolol.

BACKGROUND: The well-being of hypertensive patients may be adversely affected by the disease itself, its complications, and other concomitant processes such as anxiety, sedation, and side effects of the prescribed drugs. Some recently developed antihypertensive agents have been suggested to be devoid of these deleterious effects on well-being expressed as quality of life. OBJECT: We compared the effect on quality of life of a standard cardioselective beta-blocker atenolol to the effect of celiprolol as a representative of a new class of selective beta-blockers with vasodilatory properties. One-hundred-thirty-two patients with mild to moderate hypertension were eligible to enter a 28-week double-blind parallel-group study, consisting of a 4-week run-in period on placebo and a 24-week period on dosage-adjusted treatment with either atenolol or celiprolol. RESULTS: Both systolic and diastolic blood pressure were assessed, as was quality of life perception by a selected test battery including the Quality of Life Questionnaire of Bulpitt and Fletcher [1990]. During celiprolol treatment, supine blood pressure fell from 167/101 (range 120-200/95-116) to 150/92 mm Hg (p < 0.0001). This antihypertensive effect was at least as good with celiprolol as with atenolol. Quality of life perception was comparable for the 2 drugs, although some adverse effects were more frequent during atenolol than during celiprolol, particularly after prolonged treatment. Also patient compliance was better for celiprolol than for atenolol. CONCLUSIONS: Our results show that the selective beta-blocker with vasodilatory property celiprolol is at least as effective as atenolol and that it has additional advantage in terms of enhancement of some quality of life variables.

Effect of mibefradil on left ventricular diastolic function in patients with congestive heart failure.

Calcium antagonists have antihypertensive and antianginal properties. In heart failure, however, their use can be hazardous, as systolic function can deteriorate. This may not be true of the new calcium antagonist mibefradil, which has a new chemical structure. Calcium antagonists may also be beneficial for diastolic left ventricular function in coronary artery disease. To investigate the possible effects of mibefradil on diastolic left ventricular function, we performed the present study as a multicenter, double-blind,placebo-controlled, multiple-dose safety trial. Fifteen patients with New York Heart Association (NYHA) class II or III for dyspnea and depressed ejection fraction (<40%) due to a previous myocardial infarction were investigated. The measured nuclear angiographic parameters included ejection fraction (EF), peak ejection rate (PER), and peak filling rate (PFR). Systolic and diastolic blood pressure (SBP, DBP) and heart rate (HR) were also obtained. Group I (5 patients) received placebo medication; group IIA (6 patients) received mibefradil 6.25, 12.5, or 25 mg/day; and group IIB (4 patients) received mibefradil 50 or 100 mg/day. Measurements were made before and after the first dose and after 1 week of treatment before and after the final dose. Mibefradil clearly decreased HR (repeated-measures analysis of variance p < 0.05). No statistically significant effects of mibefradil were noted on SBP or DBP or on systolic and diastolic left ventricular function. In our study conditions, mibefradil caused no worsening of systolic function and preserved diastolic function in short-term treatment of patients with decreased EF and heart failure.