Hemodynamics and ventricular function in dilated cardiomyopathies following administration of the new beta-blocker ridazolol

Recent reports in the literature indicate that beta-blockade may improve survival in patients with dilated cardiomyopathy (DCMP). This goal can obviously not be attained if the beta-blocker employed effects deleterious actions on the left ventricular function or hemodynamics. Accordingly, to assess the suitability of the new beta-blocker ridazolol for use in this regard, in nine patients with DCMP NYHA class II/III, studies were performed (by means of balloon-tipped pulmonary artery catheter and radionuclide ventriculography) at rest and during exercise prior to and one hour after oral administration of a 40 mg-dose of the agent. At rest, there was a decreasing tendency in systolic blood pressure from 123 +/- 18.5 mm Hg to 113 +/- 15.2 mm Hg and heart rate from 94 +/- 19 beats/min to 83 +/- 17 beats/min. Pulmonary capillary wedge pressure was not significantly altered at 16.2 +/- 7.9 mm Hg and 17.1 +/- 8.4 mm Hg, respectively. Ejection fraction remained unchanged with 29 +/- 14%. The slight decrease in cardiac output from 5.1 +/- 1.3 l/min to 4.5 +/- 1.3 l/min was not significant. During exercise, there were also decreasing tendencies in the heart rate from 128 +/- 21 beats/min to 102 +/- 22 beats/min and the systolic blood pressure from 148 +/- 20.5 mm Hg to 141 +/- 18.4 mm Hg. Essentially unchanged were the pulmonary capillary wedge pressure (26.1 +/- 7.2 mm Hg/27.8 +/- 5.0 mm Hg) and ejection fraction (30 +/- 10%/27 +/- 8%) during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reversal of exertional hypotension by prolonged exercise training in selected patients with ischemic heart disease

The effect of prolonged intense endurance exercise training on exertional hypotension was investigated in 16 patients with coronary artery disease who had a 10 mm Hg or greater fall in systolic blood pressure (SBP) during progressive exercise testing. Training consisted of walking, running, or cycling at 50% to 60% of peak oxygen uptake (peak VO2) for 30 min 3 days per week for an initial 3 months and was followed by an additional 9 months of similar exercise performed at 70% to 90% of peak VO2 for 50 to 60 min 5 days per week. The 1 year program resulted in a 41% increase in peak VO2 and lower heart rate and blood pressure responses to submaximal work. Before conditioning, SBP attained a maximal value of 162 +/- 5 mm Hg but fell 21 +/- 3 mm Hg, to 141 +/- 7 mm Hg, at peak effort (p less than .01). After training, maximal SBP was achieved at a faster heart rate (157 +/- 5 vs 132 +/- 6 beats/min; p less than .001) and was 7.4% higher (174 +/- 6 vs 162 +/- 5 mm Hg; p less than .005), while SBP at peak exercise had increased by 21% (171 +/- 6 vs 141 +/- 7 mm Hg; p less than .001) and ST segment depression was slightly reduced. Left ventricular ejection fraction (LVEF) before training declined from 56 +/- 4% at rest to 52 +/- 3% at peak exercise (p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of beta-blockade on heart rate variability in decompensated heart failure

BACKGROUND: One of the putative mechanisms for the salutary effects of beta-blockers in patients with congestive heart failure is their ability to improve autonomic dysfunction. However, patients with profound neurohumoral abnormalities derive little survival benefit from beta-blockers. The purpose of the current study was to evaluate the effect of beta-blockers on heart rate variability in decompensated heart failure. METHODS: Time and frequency domain heart rate variability indices were obtained from 24-h Holter recordings and compared to assess the role of beta-blockade in 199 patients (mean age 60+/-14 years [range 21 to 87]) with decompensated heart failure (New York Heart Association functional class III [66%] and IV [34%]). RESULTS: All heart rate variability indices were markedly suppressed but were substantially higher in patients who were on beta-blockers. Time domain measures of parasympathetic cardiac activity, the percentage of RR intervals with >50 ms variation (4.9+/-0.6 vs. 7.7+/-1.2%, P=0.006) and the square root of mean squared differences of successive RR intervals (22.7+/-2.0 vs. 31.6+/-4.1 ms, P=0.004), were higher in the beta-blocker group. Spectral analysis revealed that the total power and the ultra low frequency power were significantly higher in patients on beta-blockers (82% and 59%, respectively). The high frequency power, a spectral index of parasympathetic modulation, was 41% higher in the beta-blocker group (121+/-25 vs. 171+/-27 ms(2), P=0.02). Multiple linear regression, adjusted for clinical parameters and drug therapies, revealed a strong positive relationship between beta-blockade and higher values of time and frequency domain measures. The mean number of ventricular tachycardia episodes were significantly lower in patients on beta-blocker therapy (3.6+/-1.5 vs. 19.0+/-5.3, P=0.04). CONCLUSIONS: beta-blockers improve the impaired cardiac autonomic regulation during high sympathetic stress of decompensated heart failure.     

Beta-blocker use and outcomes among hospitalized heart failure patients.

OBJECTIVES: The purpose of this study was to determine the effect of beta-blocker therapy on outcomes of hospitalized heart failure (HF) patients enrolled in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization (ESCAPE). BACKGROUND: The effect of beta-blocker therapy on outcomes among hospitalized HF patients is not well documented. METHODS: We studied the association between beta-blocker therapy and outcomes among 432 hospitalized HF patients in the ESCAPE trial. RESULTS: A total of 268 patients (62%) were on beta-blockers before admission. These patients had a shorter length of stay (7.9 +/- 6.3 days vs. 9.4 +/- 6.7 days; p < 0.01) and a lower six-month mortality rate (16% vs. 24%; p = 0.03) compared with those who were not on beta-blockers. Of the patients who were on admission beta-blockers and were discharged alive (n = 263), beta-blockers were discontinued in 54 and significantly modified (>50% dose reduction or changed to alternative beta-blocker) in 28 patients during hospitalization. Factors associated with discontinuation of beta-blockers during hospitalization included respiratory rate >24 breaths/min (30.8% vs. 16.9%; p = 0.03), heart rate >100 beats/min (19.2% vs. 7.3%; p = 0.01), lower ejection fraction (17.9 +/- 5.4% vs. 20.2 +/- 7.1%; p = 0.04), diabetes (21.2% vs. 37.1%; p = 0.03), and systolic blood pressure <100 mm Hg during hospitalization (70.3% vs. 54.1%; p = 0.03). After adjusting for factors associated with beta-blocker use and those with outcomes, consistent beta-blocker use during hospitalization was associated with a significant reduction in the rate of rehospitalization or death within six months after discharge (odds ratio 0.27, 95% confidence interval 0.10 to 0.71; p < 0.01). CONCLUSIONS: Beta-blocker therapy before and during hospitalization for HF is associated with improved outcomes.     

Antianginal efficiency of nifedipine with and without a beta-blocker, studied with exercise test. A double-blind, randomized subacute study.

Twenty-one patients, mean age 60.3 years, with stable angina pectoris earlier treated with beta-blockers, were investigated with standardized exercise tests to evaluate the action of nifedipine alone and in combination with a beta-blocker. The first exercise test was performed 3 weeks after treatment with the patient's usual beta-blocker. Following this, the patients were tested twice after a double-blind cross-over 3-week trial with nifedipine and placebo. The patients were subsequently treated for 3 weeks with nifedipine 10 mg 3 times daily or placebo and then performed an exercise test. During the 4th period of 3 weeks the patients took a combination of nifedipine, 10 mg 3 times daily, and their usual beta-blocker and then performed the final exercise test. Nifedipine alone raised the heart rate by 5 beats/min at rest and diminished the systolic blood pressure at rest by 17 mm Hg. During exercise at comparable load the heart rate did not change significantly, but the systolic blood pressure decreased with 22 mm Hg. The exercise tolerance expressed as total work increased on a average by 20%, range-14 - + 194%. Nifedipine in combination with a beta-blocker gave a further decrease in the systolic blood pressure, totally 37 mm Hg at comparable load. The exercise tolerance increased more, totally by an average of 41%. There was a significant correlation between basal values for systolic blood pressure registered during the placebo period at rest and the percentage change in total work. The atrioventricular conduction time did not change significantly compared to placebo during treatment with nifedipine or the combination nifedipine + beta-blocker. No serious side-effects were observed during the study.     

The prognostic value of post-exercise blood pressure reduction in patients with hypertensive response during exercise stress test

BACKGROUND: Hypertensive response at peak-exercise and during the recovery phase of exercise stress test (ET) is associated with poor cardiovascular prognosis. We investigated whether decrease in blood pressure (BP) from peak to post-exercise would identify a subgroup at higher cardiovascular risk. METHODS: Eighty-six non-hypertensive patients (0-4 cardiovascular risk factors) with hypertensive reaction at peak-ET (systolic>180 mm Hg and/or diastolic>100 mm Hg) were divided based on BP 5 min after exercise termination into two groups: Normal response (NrmR) (<160/90 mm Hg), Hypertensive response (HypR) (>/=160/90 mm Hg). Five years later the prevalence of cardiovascular risk factors and cardiovascular morbidity and mortality was assessed for each group. RESULTS: Both groups had similar pre- and peak-exercise BP. However the HypR group had higher post-exercise BP (systolic: 163+/-13 vs. 125+/-14 mm Hg, respectively, p<0.01, and diastolic: 74+/-6 vs. 75+/-4 mm Hg, respectively, p<0.01), smaller decrease in BP after exercise (Delta systolic: 46.9+/-3.1 vs. 73.9+/-3.6 mm Hg, respectively, p<0.01, Delta diastolic: 12.4+/-1.5 vs. 26.5+/-2.2 mm Hg, respectively, p<0.01), and higher post- than pre-exercise BP (Delta systolic: 24.5+/-3.5 vs. -6+/-4.1 mm Hg, respectively, p<0.01, A diastolic: 19+/-2.1 vs. -13+/-2.3 mm Hg, respectively, p<0.01). Five years later, HypR group had higher prevalence of abnormal cholesterol serum level (p<0.01), hypertension (p<0.01) and combined ischemic heart disease and cerebrovascular disease (RR 1.32, 95% CI=1.13-1.54, p<0.01). CONCLUSION: During ET evaluation, it is important to evaluate the BP at 5 min after exercise because reduced BP drop, at this routinely measured point, identifies a subgroup with higher cardiovascular risk.     

Abrupt withdrawal of beta-blockade therapy in patients with myocardial infarction: effects on infarct size, left ventricular function, and hospital course

The effects of abrupt withdrawal or continuation of beta-blockade therapy during acute myocardial infarction were evaluated in 326 patients participating in the Multicenter Investigation of the Limitation of Infarct Size (MILIS). Thirty-nine patients previously receiving a beta-blocker and randomly selected for withdrawal of beta-blockers and placebo treatment during infarction (group 1) were compared with 272 patients previously untreated with beta-blockers who were also randomly assigned to placebo therapy (group 2). There were no significant differences between the two groups in MB creatine kinase isoenzyme (15.8 +/- 10.9 vs 18.2 +/- 14.4 g-eq/m2, respectively) estimates of infarct size, radionuclide-determined left ventricular ejection fractions within 18 hr of infarction (0.44 +/- 0.15 vs 0.47 +/- 0.16) or 10 days later (0.42 +/- 0.14 vs 0.47 +/- 0.16), creatine kinase-determined incidence of infarct extension (13% vs 6%), congestive heart failure (43% vs 37%), nonfatal ventricular fibrillation (5% vs 7%), or in-hospital mortality (13% vs 9%). Patients in group 1 had more recurrent ischemic chest pain (p = .002) within the first 24 hr after infarction, but not thereafter. However, this did not appear to be related to a rebound increase in systolic blood pressure, heart rate, or double product. In a separate analysis, 20 propranolol-eligible group 1 patients randomly selected for withdrawal of beta-blockade (group 3) were compared with 15 patients randomly selected for continuation of prior beta-blockade therapy (group 4). This comparison yielded similar results. These data indicate that the beta-blockade withdrawal phenomenon is not a major clinical problem in patients with acute myocardial infarction. beta-Blockade therapy can be discontinued abruptly during acute myocardial infarction if clinically indicated.     

Functional improvement in heart failure patients treated with beta-blockers is associated with a decline of cytokine levels

BACKGROUND: In patients with severe heart failure (CHF), chronically elevated cytokine levels document a systemic inflammation. Experimental data suggest that activation of the beta-adrenergic system may participate in this inflammatory response. Herein, we studied as to whether beta-adrenergic blockade on top of standard CHF therapy affects plasma cytokine levels (interleukin-6 [IL-6] and tumor necrosis factor alpha [TNFalpha]). Moreover, we studied if beta-blocker related changes of these cytokines correspond to changes in left ventricular (LV) function and exercise capacity. METHODS: In a prospective study, 21 patients with stable CHF (NYHA functional class II-III, ejection fraction <40%, mean age 57.6+/-12.4 years) were treated with captopril (100-150 mg/day), furosemide (40-120 mg/day), and/or digoxin (0.1-0.2 mg/day) for at least 1 month before they entered a 4 week run-in period in which dosages were kept unchanged. Metoprololsuccinate was administered in increasing dosages (up to 190 mg/day) for the following 3 months. Clinical, echocardiographic, spiroergometric, and biochemical changes were assessed at the start and the end of the run-in period as well as after 3 month of beta-blockade. RESULTS: As compared to 210 healthy volunteers, CHF patients, prior to beta-blockade, presented with markedly elevated IL-6 (8.9+/-9.9 vs. 2.1+/-0.5 pg/ml; p<0.05) and TNFalpha levels (1.51+/-0.49 vs. 0.64+/-0.15 pg/ml; p<0.05) levels. In CHF patients, 3 month of beta-blockade lowered heart rate (84+/-14 vs. 68+/-12 bpm; p<0.01), systolic (131+/-7 vs. 118+/-6 mm Hg; p<0.01), and diastolic blood pressure (78+/-5 vs. 71+/-6 mm Hg; p<0.01). Spiroergometric determined VO2 max (17.8+/-4.5 vs. 19.8+/-4.3 ml/min kg; p=0.013) increased significantly during 3 month of beta-blockade. Moreover, LV functional parameters tended to improve but the interindividual response varied and changes were non-significant. Interestingly, IL-6 levels decreased markedly during beta-blockade (8.9+/-9.9 vs. 4.5+/-3.1 pg/ml; p=0.036), whereas TNFalpha levels remained unchanged. Moreover, significant positive correlations were found between decrease of IL-6 levels and left ventricular end diastolic diameters (r2=0.59; p=0.012), whereas an inverse correlation was found between the decrease of IL-6 and the increase of VO2 max (r2=0.54; p=0.037), respectively. CONCLUSION: In heart failure patients, beta-blockade may lower IL-6 but not TNFalpha levels. Changes of IL-6 during beta-blockade may be related to changes of LV function and geometry.     

Nonselective beta-adrenergic blocking agent, carvedilol, improves arterial baroflex gain and heart rate variability in patients with stable chronic heart failure

OBJECTIVES: The purpose of this study was to investigate in a case-controlled study whether carvedilol increased baroreflex sensitivity and heart rate variability (HRV). BACKGROUND: In chronic heart failure (CHF), beta-adrenergic blockade improves symptoms and ventricular function and may favorably affect prognosis. Although beta-blockade therapy is supposed to decrease myocardial adrenergic activity, data on restoration of autonomic balance to the heart and, particularly, on vagal reflexes are limited. METHODS: Nineteen consecutive patients with moderate, stable CHF (age 54 +/- 7 years, New York Heart Association [NYHA] class II to III, left ventricular ejection fraction [LVEF] 24 +/- 6%), treated with optimized conventional medical therapy, received carvedilol treatment. Controls with CHF were selected from our database on the basis of the following matching criteria: age +/- 3 years, same NYHA class, LVEF +/- 3%, pulmonary wedge pressure +/- 3 mm Hg, peak volume of oxygen +/- 3 ml/kg/min, same therapy. All patients underwent analysis of baroreflex sensitivity (phenylephrine method) and of HRV (24-h Holter recording) at baseline and after six months. RESULTS: Beta-blockade therapy was associated with a significant improvement in symptoms (NYHA class 2.1 +/- 0.4 vs. 1.8 +/- 0.5, p < 0.01), systolic and diastolic function (LVEF 23 +/- 7 vs. 28 +/- 9%, p < 0.01; pulmonary wedge pressure 17 +/- 8 vs. 14 +/- 7 mm Hg, p < 0.05) and mitral regurgitation area (7.0 +/- 5.1 vs. 3.6 +/- 3.0 cm2, p < 0.01). No significant differences were observed in either clinical or hemodynamic indexes in control patients. Phenylephrine method increased significantly after carvedilol (from 3.7 +/- 3.4 to 7.1 +/- 4.9 ms/mm Hg, p < 0.01) as well as RR interval (from 791 +/- 113 to 894 +/- 110 ms, p < 0.001), 24-h standard deviation of normal RR interval and root mean square of successive differences (from 56 +/- 17 to 80 +/- 28 ms and from 12 +/- 7 to 18 +/- 9 ms, all p < 0.05), while all parameters remained unmodified in controls. During a mean follow-up of 19 +/- 8 months a reduced number of cardiac events (death plus heart transplantation, 58% vs. 31%) occurred in those patients receiving beta-blockade. CONCLUSIONS: Besides the well-known effects on ventricular function, treatment with carvedilol in CHF restores both autonomic balance and the ability to increase reflex vagal activity. This protective mechanism may contribute to the beneficial effect of beta-blockade treatment on prognosis in CHF.     

Hypertonie und Bewegung

Physical exercise is of paramount therapeutic importance in nonpharmacological interventions of arterial hypertension. The extent and the effects of exercise on blood pressure lowering are analyzed according to the actual literature. Suitable and nonsuitable activities are considered. Dynamic isotonic endurance training is more effective than static isometric exercise. A rather low or moderate extent of endurance training lowers the systolic and diastolic blood pressure by approximately 5-11 mmHg and 3-8 mmHg, respectively. This effect of exercise can be achieved besides the favorable effects on other cardiovascular risk factors. Intensity of exercise should be monitored by the heart rate. The mean intensity should not exceed 70% of the maximal heart rate. An initial ergometry might be suitable for the planning of training recommendations.     

Acute electrophysiologic, hemodynamic and left ventricular effects of nifedipine and beta-blocker interactions. Maintenance of global and regional left ventricular wall motion

To assess potential cardiac effects of nifedipine and beta-blocker interactions, 10 men receiving chronic beta-blocker therapy for angina underwent hemodynamic, electrophysiologic and left ventricular (LV) functional analyses at the time of cardiac catheterization before and after buccal administration of 10 mg of nifedipine. Although this combination is usually well tolerated, there have been occasional reports suggesting that the combination of nifedipine and beta-blocking agents may increase the likelihood of congestive heart failure, severe hypotension or exacerbation of angina. All patients had class II or III stable angina pectoris and were receiving at least 160 to 240 mg/day of propranolol or equivalent doses of beta-blocker therapy. Nifedipine produced no acute electrophysiologic changes, including heart rate, PR interval, AH interval, HV interval, sinus node recovery time or heart rate at which atrioventricular nodal block occurred. Hemodynamic effects included no significant change in mean right atrial pressure (7 +/- 1 vs 5 +/- 1 mm Hg), while mean pulmonary artery pressure decreased significantly (20 +/- 2 vs 17 +/- 1 mm Hg, p less than or equal to 0.05). In addition, LV end-diastolic pressure decreased significantly from 16 +/- 2 to 10 +/- 1 mm Hg (p less than or equal to 0.05), with a nonsignificant decrease in mean aortic pressure from 93 +/- 5 to 86 +/- 4 mm Hg. Likewise, no significant change occurred in cardiac index (3.2 +/- 0.4 vs 3.0 +/- 0.4 liters/min/m2) or systemic vascular resistance (1,157 +/- 247 vs 1,170 +/- 236 dynes/s/cm-5). Left ventricular ejection fraction (EF) was the same before and after nifedipine (73 +/- 2% vs 74 +/- 2%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Oxygen may improve dyspnea and endurance in patients with chronic obstructive pulmonary disease and only mild hypoxemia.

Oxygen (O2) has been reported to improve exercise tolerance in some patients with chronic obstructive pulmonary disease (COPD) despite only mild resting hypoxemia (PaO2 greater than 60 mm Hg). To confirm these prior studies and evaluate potential mechanisms of benefit, we measured dyspnea scores by numeric rating scale during cycle ergometry endurance testing and correlated the severity of dyspnea with right ventricular systolic pressure (RVSP) measured by Doppler echocardiography during a separate supine incremental exercise test. Both sets of exercise were performed according to a randomized double-blind crossover protocol in which patients breathed compressed air or 40% O2. We studied 12 patients with severe COPD (FEV1 0.89 +/- 0.09 L [mean +/- SEM], FEV1/FVC 37 +/- 2%, DLCO 9.8 +/- 1.5 ml/min/mm Hg[47% of predicted], PaO2 71 +/- 2.6 mm Hg). With endurance testing on compressed air, PaO2 did not change significantly in the group as whole (postexercise PaO2 63 +/- 5.1 mm Hg, p = NS), but did fall to less than 55 mm Hg in four patients from this group. Duration of exercise increased on 40% O2 from 10.3 +/- 1.6 to 14.2 +/- 1.5 min (p = 0.005), and the rise in dyspnea scores was delayed. Oxygen delayed the rise in RVSP with incremental exercise in all patients and lowered the mean RVSP at maximum exercise from 71 +/- 8 to 64 +/- 7 mm Hg (p less than 0.03). Improvement in duration of exercise correlated with decrease in dyspnea (r2 = 0.66, p = 0.001) but not with decreases in heart rate, minute ventilation, or RVSP.(ABSTRACT TRUNCATED AT 250 WORDS)     

Interval resistance exercise in comparison with bicycle ergometry stress. Studies with resistance endurance training in coronary patients]

In the rehabilitation of coronary patients there is an increased interest in using complementary resistance exercise training. Therefore, we studied nine patients (males; age: 51 +/- 7 years) with chronic stable coronary heart disease during extensive resistance exercise (ex RE) (legpress, abduction, adduction) (60-s work: 60-s rest; contraction intensity: 65% of 1 RM) and during intensive resistance exercise (int. RE) (legpress) (30-s work: 45-s rest) with 85% of 1 RM. Non-invasive continuously measured blood pressure, heart rate, norepinephrine, epinephrine, lactic acid, and glucose were compared with values from maximal bicycle ergometry (3-min steps, each 25 w; max. performance: mean 156 w; range 125-200 w). Results: 1) Comparing ex RE and int RE with bicycle ergometry there were no differences in blood pressure (systolic: 206 and 204 vs. 210 mm Hg; ns; diastolic: 98 and 104 vs. 92 mm Hg; ns). Heart rates (104 and 103 vs. 125/min; p < .01), norepinephrine (3.8 and 3.3 vs. 8.8 nmol/l; p < .01) and epinephrine (0.7 and 0.6 vs. 1.4 nmol/l; p < .01) were considerably lower. 2) The most significant increase and decrease of blood pressure and heart rate occurred within 15-30 s after the beginning and end, respectively, of isometric exercise. Conclusions: 1) ex RE is suitable for patients with stable CHD and cardiac exercise tolerances of 1.5-2 W/kg = 125-150 watts. 2) Blood pressure monitoring by the cuff method (RR) immediately after RE did not reflect blood pressure during RE. 3) Controlling RE by the training heart rate prescribed for endurance exercise is not possible.     

Predictors of controlled ambulatory blood pressure in treated hypertensive patients with uncontrolled office blood pressure.

Although some treated hypertensive patients have controlled 24-h ambulatory blood pressure (ABP) despite their uncontrolled office blood pressure (BP), the factors relating to the control of 24-h ABP remain unknown. We conducted a study to assess 24-h ABP and its association with other cardiovascular risk factors, including echocardiographic left ventricular hypertrophy (LVH), in elderly hypertensive patients (n =41) with uncontrolled office BP (>140/90 mmHg) during long-term medication. Although a majority of the patients had isolated elevation of office systolic BP (SBP), there was no significant relationship between office SBP and 24-h SBP, and about half of the patients had controlled 24-h ABP (125+/-8/69+/-6 mmHg). Patients with controlled 24-h ABP (125+/-8/69+/-6 mmHg) had similar office BP (150+/-6/77+/-5 vs. 150+/-7/79+/-7 mmHg), but lower left ventricular mass index (LVMI) (123+/-34 vs. 156+/-34 g/m(2)) and body mass index (BMI) (24.4+/-2.1 vs. 26.4+/-3.6 kg/m(2)) compared with those with uncontrolled 24-h ABP (149+/-13/78+/-7 mmHg). Multivariate analysis showed that LVMI and BMI were independently associated with controlled 24-h ABP, and the control status of 24-h ABP was highly dependent on the presence of LVH and obesity. Therefore, absence of LVH and obesity may be useful for predicting the level of control of 24-h ABP in treated patients whose office BP is uncontrolled without ABP measurements.     

Usefulness of exercise electrocardiography and thallium scintigraphy in unstable angina pectoris in predicting the extent and severity of coronary artery disease

The safety and efficacy of exercise electrocardiography and thallium scintigraphy early in the course of unstable angina pectoris were assessed 4.6 +/- 1.6 days after admission in 67 patients with unstable angina that stabilized after medical therapy. Coronary arteriography was performed in all patients 5.4 +/- 2.4 days after admission. There was no difference in clinical, exercise or scintigraphic variables between patients with stenoses less than 50% and patients with 1-vessel coronary artery disease (CAD) defined as a diameter stenosis greater than or equal to 50%. Patients with 3-vessel CAD had a significantly shorter exercise duration than patients with less than 50%-diameter narrowing (5.5 +/- 2.2 vs 8.3 +/- 3.3 minutes, respectively), lower exercise heart rate (119 +/- 20 vs 149 +/- 22 beats/min) and systolic blood pressure (156 +/- 29 vs 166 +/- 33 mm Hg), more frequent chest pain (76 vs 20%) and more pronounced ST depression (-1.48 +/- 1.37 vs -0.33 +/- 0.72 mm). In addition, thallium defect size on exercise was greater in the patients with 2-vessel CAD (159 +/- 132 degrees) and 3-vessel CAD (255 +/- 132 degrees) than in patients with no CAD (28 +/- 319 degrees) or 1-vessel CAD (73 +/- 78 degrees), p greater than or equal to 0.05. Multiple regression analysis demonstrated that thallium defect size was the best predictor of extent of CAD, with exercise heart rate and presence of chest pain during exercise also predictive of extent of CAD.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute effect of systemic versus intracoronary dipyridamole on coronary circulation

Dipyridamole has been proposed as an ideal agent to evaluate coronary vascular reserve because it produces selective coronary vasodilation without systemic hemodynamic effect. The actions of intracoronary (IC) and intravenous (IV) dipyridamole on coronary blood flow and systemic hemodynamics were compared in 15 patients with chest pain syndrome and normal coronary arteries. They received IC dipyridamole, followed 10 minutes later by 0.5 mg/kg of IV dipyridamole. IC dipyridamole produced a 73% increase in coronary sinus flow without hemodynamic changes, except for a slight increase in pulmonary systolic and diastolic pressures. IV dipyridamole administration produced an additional 88% increase in coronary sinus flow, reaching 172% over baseline; it was also associated with a significant (p less than 0.01) increase in heart rate (78 +/- 14 vs 102 +/- 19 beats/min), cardiac index (4 +/- 0.7 vs 6.3 +/- 1.7 liters/min/m2), and pulmonary artery systolic (27 +/- 5 vs 34 +/- 7 mm Hg) and diastolic pressures (12 +/- 4 vs 19 +/- 7 mm Hg). These data suggest that the coronary vasodilatory effect seen after IV dipyridamole administration is related to mechanisms other than direct coronary vasodilation.     

Comparison in young and elderly patients of pharmacodynamics and disposition of labetalol in systemic hypertension

Pharmacodynamics and pharmacokinetics of labetalol, a combined alpha- and beta-adrenoceptor antagonist drug, were studied in elderly and young hypertensive patients. After receiving intravenous labetalol, elderly patients had a greater maximal mean decrease in systolic blood pressure (BP) (39 +/- 8 vs 25 +/- 13 mm Hg, p less than 0.02); however, maximal decrease in diastolic BP was similar in elderly (18 +/- 10 mm Hg) and young (17 +/- 6 mm Hg) patients. After receiving oral labetalol, elderly patients had a greater maximal decrease in standing systolic BP (41 +/- 16 vs 16 +/- 14 mm Hg, p less than 0.001) and similar decreases in standing diastolic BP (21 +/- 7 vs 17 +/- 9 mm Hg). Sitting maximal BP decreases after oral labetalol treatment were similar in elderly and young patients (12 +/- 16 vs 17 +/- 7 mm Hg systolic and 24 +/- 6 vs 12 +/- 7 diastolic). The decrease in heart rate was greater in young patients after intravenous labetalol administration. To evaluate labetalol pharmacodynamics, a linear model was used. Slope of labetalol concentration vs systolic BP for elderly vs young patients was 0.928 +/- 1.05 vs 0.326 +/- 0.490 ng/ml X mm Hg-1 (difference not significant). The slope of labetalol concentration vs heart rate for elderly vs young patients was 0.176 +/- 0.063 vs 0.406 +/- 0.303 ng/ml X beats/min-1 (p less than 0.05), with 2 elderly patients showing no decrease in heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)     

Blunted hemodynamic response and reduced oxygen delivery with exercise in anemic heart failure patients with systolic dysfunction

Anemic heart failure patients with systolic dysfunction are known to have reduced exercise capacity. Whether this is related to poor hemodynamic adaptation to anemia is not known. Peak exercise oxygen consumption (VO2) and hemodynamics at rest and peak exercise were assessed among 209 patients and compared among those who were (n=90) and were not (n=119) anemic. Peak VO2 was significantly lower among anemic patients (11.7+/-3.3 mL/min/kg vs 13.4+/-3.1 mL/min/kg; P=.01). At rest, right atrial pressure was higher (10+/-5 mm Hg vs 8+/-4 mm Hg; P=.02) and venous oxygen saturation lower (62%+/-8% vs 58%+/-10%; P<.01) among anemic patients. At peak exercise, anemic patients had a higher wedge pressure (27+/-9 mm Hg vs 24+/-10 mm Hg; P=.04). No significant differences in stroke volume, cardiac index, systemic vascular resistance, or oxygen saturation were noted between the 2 groups. In conclusion, the relative hemodynamic response to exercise among anemic heart failure patients appears blunted and may contribute to worse exercise tolerance.     

The effects of long-term beta-blockade on the ventilatory responses to exercise in chronic heart failure

AIMS: Chronic heart failure (CHF) patients complain of breathlessness and fatigue. Beta-blockers improve symptoms, echocardiograpahic variables and prognosis in CHF, but their effect on exercise capacity remains unclear. The aim of this study was to describe the effects of long-term beta-blocker therapy on metabolic gas exchange variables and ventilation during exercise in CHF patients. METHODS: 42 patients with symptomatic heart failure due to left ventricular systolic dysfunction (ejection fraction 33.2 (8.2)) on loop diuretics and angiotensin-converting enzyme inhibitors or angiotensin II antagonists, underwent exercise testing with metabolic gas exchange. They were then initiated onto and uptitrated to the maximum tolerated dose of beta-blockers. After 1 year of follow-up, patients were invited back for repeat testing. RESULTS: 35 patients attended for repeat exercise testing. Four patients had died, and three had not tolerated beta-blockade. After 1 year, exercise time was increased (487 (221) vs. 500 (217), p<0.05), and peak oxygen consumption and V(E)/V(CO(2)) slope were unchanged (20.9 (5.0) vs. 20.0 (5.4), p=0.15 and 36.7 (8.3) vs. 37.3 (7.8), p=0.70). Peak ventilation, (61.5 (12.9) vs. 57.1 (13.4), p<0.05), peak carbon dioxide production (1629 (404) vs. 1496 (375), p<0.02) and hence respiratory exchange ratio (1.02 (0.08) vs. 0.98 (0.06) p<0.02) and p<0.05) were reduced. Submaximal oxygen consumption and carbon dioxide production were lower at matched workloads. The slope relating symptoms to ventilation (Borg/V(E) slope) was less steep following beta-blockade (0.18 (0.09) vs. 0.15 (0.06), p<0.05). CONCLUSION: Long term beta-blocker therapy increases exercise time but not peak oxygen consumption, and reduces peak carbon dioxide production. CHF patients are less symptomatic for a given ventilation during exercise following beta-blocker treatment.     

Normalization of upright exercise hemodynamics and improved exercise capacity one year after orthotopic cardiac transplantation.

The mechanisms of improved functional capacity over the first year after cardiac transplantation are not well studied. To assess the contribution of cardiac changes to this improvement, the serial evolution of upright rest and exercise hemodynamics during graded upright bicycle exercise was studied in 17 patients at 3 and 12 months after heart transplantation. Heart rate responsiveness, reflected by rapid heart rate acceleration on sitting and rapid deceleration after exercise, developed in the first year. Pulmonary capillary wedge pressure was lower at 1 year, both at rest and at peak exercise (10 +/- 3 vs 13 +/- 5 mm Hg at rest supine and 14 +/- 6 vs 18 +/- 8 mm Hg at peak exercise, p less than 0.05). Similarly, right atrial pressures were also significantly lower at 1 year (4 +/- 2 vs 6 +/- 3 mm Hg at rest supine and 6 +/- 5 vs 11 +/- 5 mm Hg at peak exercise, p less than 0.05). Cardiac index at peak exercise was greater at 12 months (6.4 +/- 1.3 vs 5.8 +/- 0.8 liters/min/m2, p less than 0.05), mediated primarily by higher exercise heart rate (135 +/- 16 vs 125 +/- 12 beats/min, p less than 0.05). In the first year after heart transplantation, improved rest and exercise hemodynamics and heart rate responsiveness contribute significantly to the improved functional capacity observed in these patients.