Comparison of safety and efficacy of the early injection of atropine during dobutamine stress echocardiography with the conventional protocol

Although dobutamine-atropine stress echocardiography (DASE) is an established method for evaluating patients who have coronary artery disease (CAD), it can increase test duration and a patient's exposure to large doses of dobutamine. New protocols, including the early injection of atropine during dobutamine stress echocardiography (EA-DSE), have been proposed to decrease test duration. This study compared the safety, efficacy, and accuracy of EA-DSE with those of DASE. We retrospectively evaluated 3,163 patients who underwent DASE and 1,664 patients who underwent EA-DSE over a period of 12 years. In EA-DSE, atropine at a dose 50% stenosis) was assessed in patients who underwent quantitative angiography 相似文献   

Enhanced sensitivity for detection of coronary artery disease by addition of atropine to dobutamine stress echocardiography.

Patients undergoing dobutamine stress echocardiography often take beta antagonists which limit heart rate response and sensitivity in the test for detection of coronary artery disease. The aim of this study was to assess the effect of the addition of atropine to dobutamine stress echocardiography on clinical, electrocardiographic and echocardiographic outcomes. Dobutamine stress echocardiography was performed starting at and increasing every 3 minutes with 10 micrograms/kg/min to a maximum of 40 micrograms/kg/min (stage 4), which was continued for 6 minutes. In patients not achieving 85% predicted maximal exercise heart rate and in whom the test was not judged positive on echocardiographic or electrocardiographic criteria, atropine (0.25 mg intravenously, repeated up to a maximum of 1 mg if necessary) was added and dobutamine continued for up to a further 5 minutes, or until an adequate heart rate was achieved or the test was stopped because of chest pain or electrocardiographic changes. Of 80 consecutive patients undergoing dobutamine stress echocardiography within 2 weeks of coronary angiography, 49 required atropine (group A) and 31 required only dobutamine (group B). After dobutamine alone, heart rate (mean +/- SD) was higher in group B than in group A: 129 +/- 20 vs 90 +/- 18 beats/min, p less than 0.0001; but after the addition of atropine, heart rate in group A increased to 120 +/- 20 beats/min. Overall sensitivity for the detection of coronary disease was 70%, 95% confidence interval (CI) 55 to 83%; after the addition of atropine, sensitivity for group A was 65%, 95% CI 45 to 81%; in group B, sensitivity was 81%, 95% CI 54 to 96%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Accelerated dobutamine stress testing: safety and feasibility in patients with known or suspected coronary artery disease

BACKGROUND: Dobutamine pharmodynamics require approximately 10 min to reach steady state. Despite this, standard dobutamine stress echo typically uses 3-min stages of advancing dobutamine doses because of safety concerns. HYPOTHESIS: In patients with a high pretest probability of coronary artery disease (CAD), a continuous infusion of high-dose dobutamine is a feasible and safe method for performing a dobutamine stress test. METHODS: Forty-seven consecutive patients (mean age 64 +/- 11 years) with 3.0 +/- 1.4 cardiac risk factors underwent dobutamine stress testing utilizing a single, high-dose (40 mcg/kg/min), continuous dobutamine infusion. The 40 mcg/kg/min infusion was continued for up to 10 min or until a test endpoint had been reached. If a test endpoint was not achieved, atropine (up to 1.0 mg) was added. RESULTS: Heart rate rose from 71 +/- 12 to 137 +/- 18 beats/min at peak (p<0.0001) with a concomitant change in systolic blood pressure (143 +/- 35 vs. 167 +/- 38 mmHg; p = 0.001) but no change in diastolic blood pressure (74 +/- 19 vs. 75 +/- 18 mmHg; p = NS). Target heart rate was achieved in 20 of 47 (43%) patients with accelerated dobutamine alone and in 34 of 47 (72%) with the addition of atropine. An average of 11.6 +/- 3.7 min was required to obtain target heart rate. Subjective sensations from the dobutamine occurred in 49% of patients (palpitations 21%, nausea 6%, chest pain 6%, headache 6%, dizziness 13%), mild arrhythmia in 48% of patients (ventricular premature beats 38%, supraventricular tachycardia 10%), and one patient had nonsustained ventricular tachycardia. CONCLUSION: A single, high-dose (40 mcg/kg/min) dobutamine-atropine protocol provides an efficient means of performing dobutamine stress echocardiography with a similar symptom profile as conventional dobutamine infusion protocols in patients with a high pretest probability of CAD. Randomized, controlled studies will be necessary to assess the sensitivity and specificity of this accelerated dobutamine echo protocol.     

Safety and efficacy of an accelerated dobutamine stress echocardiography protocol in the evaluation of coronary artery disease

Although dobutamine requires up to 10 minutes to achieve steady state, dobutamine stress echocardiography is routinely performed using stepwise increments at 3-minute intervals. Consequently, the full effect of any infusion rate is not attained before the dobutamine dose is advanced to the next level. This study sought to test the safety and efficiency of high-dose continuous dobutamine infusion. One hundred consecutive patients underwent an accelerated protocol using a constant infusion of 50 microg/kg/min. In the absence of a stress echocardiographic end point (>/=85% of maximal predicted heart rate, new wall motion abnormalities, hypotension, arrhythmia, or intolerable symptoms), dobutamine infusion was discontinued at 10 minutes. Hemodynamic responses and adverse effect profile were compared with 100 patients who underwent a standard stepwise dobutamine stress protocol. Peak heart rate (140 +/- 16 vs 140 +/- 19 beats/min, p = 0.95) and systolic blood pressure (169 +/- 32 vs 162 +/- 31 mm Hg, p = 0.08) were similar in both protocols. Accelerated dobutamine administration produced a rapid increase in heart rate (12.5 +/- 6.2 vs 5.7 +/- 2.6 beats/min, p <0.001), and a substantial reduction in test duration (6.4 +/- 2.4 vs 12.9 +/- 3.0 minutes, p <0.001). The mean weight-adjusted cumulative dobutamine dose was lower in the accelerated protocol group (320 +/- 111 vs 353 +/- 133 microg/kg, p = 0.016). No significant differences were noted between the 2 groups with respect to various side effects. These data demonstrate that a high-dose, single-stage dobutamine echocardiographic stress protocol is a feasible, well-tolerated alternative to standard dobutamine stress echocardiography, and results in a substantial reduction in test time while maintaining a low complication rate.     

Peripheral sympathetic control during dobutamine infusion: effects of aging and heart failure

OBJECTIVES: We assessed the effects of beta-adrenergic agonism on muscle sympathetic nerve activity (MSNA) in patients with congestive heart failure (CHF) and young and matched controls. BACKGROUND: Myocardial response to beta-adrenergic stimulation decreases with aging and with CHF. METHODS: In CHF patients, we measured cardiac hemodynamics and MSNA (microneurography) before, with short-term (n = 5), and after 48-h (n = 9) of dobutamine infusion (10 microg/kg/min). In eight young controls and nine controls matched to the CHF patients, we measured cardiac hemodynamics and MSNA during randomized short-term dobutamine (10 microg/kg/min) and placebo infusions. RESULTS: In CHF patients, short-term dobutamine infusion did not modify mean blood pressure (MBP), MSNA, or heart rate (HR). Moreover, 48-h dobutamine infusion increased cardiac index (3.1 +/- 0.2 vs. 2.2 +/- 0.2 l/min/m(2), p = 0.006), decreased mean pulmonary pressure (28 +/- 7 vs. 38 +/- 7 mm Hg, p = 0.0001) and peripheral resistance (1,099 +/- 112 vs. 1,759 +/- 263, p = 0.03), but did not change MBP, HR, or MSNA in the patients. In matched controls, dobutamine increased HR (87 +/- 5 vs. 65 +/- 2 beats/min, p = 0.0009) but did not change MBP or MSNA. In young controls, dobutamine increased MBP (102 +/- 2 vs. 90 +/- 2 mm Hg, p = 0.0003) and decreased MSNA (28 +/- 5 vs. 35 +/- 3 bursts/min, p = 0.03) but did not change HR (p = 0.054). In the controls, the largest increases in MBP with dobutamine were associated with the most marked reductions in MSNA (r = -0.49, p = 0.04) and the smallest increases in HR (r = -0.70, p = 0.001). CONCLUSIONS: Arterial baroreceptor activation during increases in MBP inhibits MSNA and limits the HR response to dobutamine in controls. This mechanism, together with peripheral vasodilation, probably contributes to the absence of peripheral sympathetic withdrawal despite substantial hemodynamic improvements in CHF patients.     

Left ventricular dynamics and plasma catecholamines during isometric exercise in patients following cardiac transplantation

Haemodynamics and plasma catecholamine responses to isometric exercise were evaluated invasively in 11 orthotopic heart transplant recipients and seven control subjects. Differences in haemodynamic responses between the two groups were already apparent after one min of handgrip at 30% of maximal voluntary contraction, and very pronounced at the end of the fourth minute. At this point transplanted patients showed smaller increments in heart rate (4.8 +/- 3.2 vs 20.4 +/- 14.1 beats.min-1, P less than 0.001), mean arterial pressure (13.7 +/- 7.2 vs 31.5 +/- 12.2 mmHg, P less than 0.001) and cardiac index (0.51 +/- 0.22 vs 1.02 +/- 0.53 L.min-1.m-2, P less than 0.01), whereas left ventricular end-diastolic pressure increased to a greater extent (8.8 +/- 4.9 vs 2.2 +/- 1.8 mmHg, P less than 0.01). Stroke volume index increased similarly (3.8 +/- 1.8 vs 2.0 +/- 3.5 ml beat-1.m-2, NS) and systemic vascular resistance remained unchanged in both groups. The slopes of the left ventricular function curves (ratio of change in left ventricular work to change in left ventricular end-diastolic pressure) indicated depressed left ventricular function in the transplanted patients. The two groups showed similar increments in mixed venous plasma norepinephrine and epinephrine indicating normal sympathoadrenal activation in the transplanted patients. In conclusion, transplanted hearts respond to handgrip with attenuated increases in heart rate, cardiac output and arterial pressure and by increasing left ventricular filling pressure, suggesting a poor contractile reserve probably due to denervation. Circulating catecholamines, especially epinephrine, probably contribute to the cardiac responses to isometric exercise.     

Randomized double-blind placebo-controlled comparison of nicardipine and nifedipine in patients with chronic stable angina pectoris

Forty-one patients were studied in a randomized double-blind placebo-controlled crossover trial to compare the antianginal actions of nicardipine 30 mg thrice daily and nifedipine 10 mg thrice daily. Efficacy was assessed using objective criteria from computer-assisted multistage graded exercise testing, performed after a two-week placebo run-in period and at the end of each four-week active treatment period. Thirty-seven patients completed both legs of the crossover trial. The mean (+/- standard error of the mean) baseline exercise time to development of angina was 6.7 +/- 0.4 min and this increased to 9.5 +/- 0.6 min on nicardipine (p less than 0.001) and 9.5 +/- 0.5 min on nifedipine (p less than 0.001 vs baseline; NS vs nicardipine). Both drugs significantly prolonged the time to the development of 1mm ST segment depression. The baseline resting heart rate of 83 +/- 2 beats/min increased to 87 +/- 3 beats/min during nicardipine (p less than 0.05) and remained unaltered at 83 +/- 2 beats/min during nifedipine therapy (p = NS vs baseline and p less than 0.02 vs nicardipine). Similarly, both drugs increased significantly the maximal heart rate at peak exercise. One patient was lost to follow-up during the placebo run-in period and four patients (two each on nicardipine and nifedipine) were withdrawn due to adverse effects. Our results indicate that nicardipine is comparable in efficacy to nifedipine and has a similar adverse effect profile and can also be considered a useful therapeutic agent for the treatment of chronic stable angina pectoris.     

Changes in sinus function at rest and during physical exertion after permanent atrial electrostimulation in patients with sick sinus syndrome

We studied the unnatural history of sinus node function in severe sick sinus syndrome treated with AAI or DDD pacemakers. In 19 patients (10 m; 9 f; mean age +/- 1 SD 69 +/- 7 years) we executed serial bicycle exercise tests and electrophysiological studies before, 7 days and 3 months after pacemaker implant. Sinus heart rate at maximum effort was: 118 +/- 23 beats/min and 117 +/- 23 beats/min (two different evaluations) before pacemaker implant, 125 +/- 21 beats/min after 7 days (p less than 0.05) and 133 +/- 20 beats/min after 3 months (p less than 0.001) with an average increment of 12.7%. A positive correlation (y = 50.4 + 0.7 X beats/min; p less than 0.001) between the first basal test and the third month one was found. In analogy exercise test lasted 8.7 +/- 3, 8.6 +/- 2.8, 9.5 +/- 2.5, 9.7 +/- 2.5 minutes respectively, with an average increment of 11.5% between the first basal test and the third month one. Sinus heart rate at maximum effort in 14 age matched normal subjects was 138 +/- 15 beats/min. The difference with sick sinus syndrome patients was statistical (p less than 0.05) when compared with the basal test but not with 3rd month test. Parameters determined during electrophysiological studies were: spontaneous heart rate, corrected sinus node recovery time, sino-atrial conduction time evaluated before and after autonomic blockade (propranolol 0.2 mg/kg i.v. plus atropine 0.04 mg/kg i.v.). All these parameters, excepting basal corrected sinus node recovery time, improved significantly after pacemaker implant.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of partial neuromuscular blockade on sympathetic nerve responses to static exercise in humans

We used intraneural recordings of sympathetic nerve activity in conscious humans to determine if central command increases sympathetic discharge to resting skeletal muscle during static exercise. In nine healthy subjects, we measured arterial pressure, heart rate, and muscle sympathetic nerve activity with microelectrodes in the peroneal nerve of the resting leg during 1) static handgrip at 15% and 30% maximal voluntary contraction and 2) attempted handgrip during partial neuromuscular blockade produced by systemic administration of tubocurarine chloride (0.075 mg/kg i.v.). During curare, subjects reported that they used near-maximal motor effort to attempt a sustained handgrip contraction, but they generated almost no force. Without sustained contraction, the intent to exercise alone, that is, central command, caused statistically significant (p less than 0.05) increases in muscle sympathetic nerve activity as well as in arterial pressure and heart rate. However, the increases in muscle sympathetic nerve activity (+ 56 +/- 16% over control) and in mean arterial pressure (+ 12 +/- 2 mm Hg) during attempted handgrip were much smaller (p less than 0.05) than the sympathetic nerve response (+ 217 +/- 37% over control) and pressor response (+ 25 +/- 3 mm Hg) during an actual static handgrip at 30% maximal voluntary contraction. In contrast, heart rate increased as much during the attempted contraction (+ 18 +/- 2 beats/min) as during the actual contraction at 30% maximal voluntary contraction (+ 16 +/- 4 beats/min). In 11 additional subjects, the heart rate responses during curare were greatly attenuated (p less than 0.05) by atropine but were not significantly affected by propranolol.(ABSTRACT TRUNCATED AT 250 WORDS)     

Demonstration of training effect during chronic beta-adrenergic blockade in patients with coronary artery disease

Attenuation of exercise-induced increases in heart rate and cardiac output by chronic beta-adrenergic blockade has been thought to compromise benefit of exercise training in patients with coronary artery disease (CAD). To assess this important issue, 35 CAD patients were evaluated by a 3-month walk-jog-cycle training program: 14 patients received no beta blocker (group 1), 14 received propranolol, 30-80 mg/day (group 2), and seven patients received propranolol, 120-240 mg/day (group 3). The extent of CAD, resting heart rate before training blood pressure and VO2 max were similar (p = NS) in each group. The maximal exercise heart rate (mean +/- SD, 147 +/- 21 beats/min in group 1 vs 120 +/- 10 beats/min in group 2 and 115 +/- 12 beats/min in group 3 (both p less than 0.05 vs group 1). The VO2 max before training was 25 +/- 5.0 ml/kg/min in group 1 vs 23 +/- 3.2 ml/kg/min in group 2 and 26 +/- 2.8 ml/Kg/min in group 3 (all p = NS). Training consisted of three 1-hour periods per week at a heart rate of 70-85% of the maximal pretraining heart rate. In each group, VO2 increased (p less than 0.05) after training: group 1, 27%; group 2, 30%; group 3, 46%. The double product was unchanged after training (p = NS) in each group. These data indicate that substantial training effects may be achieved in CAD patients despite therapeutic doses of beta blockers and a reduced training HR. Thus, there appears to be no indication to reduce beta blockers in CAD patients engaged in cardiac rehabilitation.     

Failure of plasma norepinephrine to consistently reflect sympathetic activity in humans

To determine whether venous plasma norepinephrine concentrations consistently reflect changes in sympathetic nervous activity, the influence of mental arithmetic, static handgrip, and submaximal bicycle exercise on intra-arterial blood pressure, heart rate, and plasma norepinephrine was studied in 51 subjects with untreated essential hypertension (mean age, 46 years; range, 16-69 years). At rest, plasma norepinephrine was unrelated to age or blood pressure. Mental arithmetic increased mean arterial pressure from 108 +/- 18 to 127 +/- 18 mm Hg (mean +/- S.D.; p less than 0.001) and heart rate from 69 +/- 7 to 93 +/- 13 beats/min (p less than 0.001) but not plasma norepinephrine (547 +/- 297 to 518 +/- 250 pg/ml). Isometric exercise raised mean arterial pressure from 115 +/- 18 to 148 +/- 21 mm Hg (p less than 0.001) and heart rate from 76 +/- 9 to 95 +/- 13 beats/min (p less than 0.001) but not plasma norepinephrine (683 +/- 253 to 741 +/- 253 pg/ml). Bicycle exercise increased mean arterial pressure from 114 +/- 20 to 146 +/- 26 mm Hg (p less than 0.001), heart rate from 77 +/- 9 to 128 +/- 19 beats/min (p less than 0.001), and plasma norepinephrine from 645 +/- 228 to 1151 +/- 462 pg/ml (p less than 0.001). Both the maximum mean arterial pressure and the peak heart rate attained during bicycle exercise were related to the exercise plasma norepinephrine level (r = 0.33, p less than 0.02 and r = 0.28, p less than 0.03, respectively). Increases in plasma norepinephrine with exercise were not greater in older or more hypertensive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

A rapid stress-testing protocol for the detection of coronary artery disease: comparison of two-stage transesophageal atrial pacing stress echocardiography with dobutamine stress echocardiography

OBJECTIVES: We compared a new two-stage transesophageal atrial pacing stress echocardiography (TAPSE) protocol with a standard dobutamine stress echocardiography (DSE) protocol. BACKGROUND: Transesophageal atrial pacing stress echocardiography has been proposed as an efficient alternative to DSE. METHODS: Two-stage TAPSE (85% and 100% of age-predicted maximum heart rate) and DSE (5 to 40 microg/kg/min at 3-min stages with or without atropine) were both performed, in random sequence, in each patient of a study group of 36 patients. Regional wall-motion analysis, patient acceptance (1 = low, 5 = high), hemodynamics and duration for performing and interpreting tests were compared. RESULTS: Transesophageal atrial pacing stress echocardiography was successful in 35 of the 36 patients (feasibility 97%). More TAPSE than DSE studies were called "ischemic" (37% vs. 14%; p = 0.005). Peak heart rate was higher with TAPSE (144 +/- 18 vs. 129 +/- 15 beats/min, p = 0.0001). Peak cardiac index (4.6 +/- 2.1 vs. 5.1 +/- 1.9 liters/min/m2, p = 0.14), patient acceptance score (4.2 +/- 0.7 vs. 3.8 +/- 1.3, p = 0.17) and study duration (14.2 +/- 9.3 vs. 13.3 +/- 3.3 min, p = 0.59) were similar. Recovery time (7.1 +/- 7.6 vs. 16.2 +/- 15.9 min, p = 0.0003) and interpretation time (9.1 +/- 2.8 vs. 13.5 +/- 4.4 min, p = 0.0001) were shorter for TAPSE than for DSE. CONCLUSIONS: Two-stage TAPSE permits rapid evaluation of cardiac patients. Peak cardiac index and patient acceptance scores were similar for TAPSE and DSE. Ischemia was detected more often with TAPSE; this result was attributed to the higher peak heart rate obtained with this protocol.     

Heart rate response during exercise testing and ambulatory ECG monitoring in patients with syndrome X.

The response of the heart rate during exercise testing and 24-hour ambulatory electrocardiographic (ECG) monitoring performed with patients not receiving antianginal treatment was assessed in 26 patients (9 men and 17 women; mean age 51 +/- 8 years) with syndrome X (angina pectoris with normal coronary arteries), in 27 patients with coronary artery disease (10 men and 17 women; mean age 55 +/- 9 years), and in 21 healthy subjects (8 men and 13 women; mean age 47 +/- 11 years). In patients with syndrome X the slope of the regression line of heart rate versus time (heart rate/time slope) during exercise testing was similar to that of patients with coronary artery disease (3.3 +/- 0.8 versus 3.1 +/- 1.2 beats/min), but significantly lower than that in healthy subjects (4.2 +/- 1.1 beats/min; p less than 0.003). In patients with syndrome X the intercept of the heart rate/time slope was significantly higher than that in coronary artery disease patients and healthy subjects (102 +/- 15, 86 +/- 18, and 90 +/- 16 beats/min, respectively; p less than 0.015). Resting preexercise heart rate was also significantly higher in syndrome X, compared with coronary artery disease patients and healthy subjects (91 +/- 16, 79 +/- 16, and 80 +/- 14 beats/min, respectively). During ambulatory ECG monitoring, mean diurnal heart rate (from 6 AM to 6 PM) was higher in patients with syndrome X (83 +/- 8 beats/min) than in patients with coronary artery disease (75 +/- 8 beats/min) and healthy subjects (74 +/- 11 beats/min) (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)     

Impact of beta-blocker treatment on the prognostic value of currently used risk predictors in congestive heart failure

OBJECTIVES: This prospective study tested the impact of beta-blocker treatment on currently used risk predictors in congestive heart failure (CHF). BACKGROUND: Given the survival benefit obtained by beta-blockade, risk stratification by factors established in the "pre-beta-blocker era" may be questioned. METHODS: The study included 408 patients who had CHF with left ventricular ejection fraction (LVEF) <45%, all treated with an angiotensin-converting enzyme inhibitor or angiotensin type 1 receptor antagonist, who were classified into those receiving a beta-blocker (n = 165) and those who were not (n = 243). In all patients, LVEF, peak oxygen consumption (peakVO(2)), plasma norepinephrine (NE) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were determined. RESULTS: Although the New York Heart Association functional class (2.2 +/- 0.7 vs. 2.3 +/- 0.7), peakVO(2) (14.4 +/- 5.2 ml/min per kg vs. 14.4 +/- 5.5 ml/min per kg) and NT-proBNP (337 +/- 360 pmol/l vs. 434 +/- 538 pmol/l) were similar in the groups with and without beta-blocker treatment, the group with beta-blocker treatment had a lower heart rate (68 +/- 30 beats/min vs. 76 +/- 30 beats/min), lower NE (1.7 +/- 1.2 nmol/l vs. 2.5 +/- 2.2 nmol/l) and higher LVEF (24 +/- 10% vs. 21 +/- 9%; all p < 0.05). Within one year, 34% of patients without beta-blocker treatment, but only 16% of those with beta-blocker treatment (p < 0.001), reached the combined end point, defined as hospital admission due to worsening CHF and/or cardiac death. A beneficial effect of beta-blocker treatment was most obvious in the advanced stages of CHF, because the end-point rates were markedly lower (all p < 0.05) in the group with beta-blocker treatment versus the group without it, as characterized by peakVO(2) <10 ml/min per kg (26% vs. 64%), LVEF < or = 20% (25% vs. 45%), NE >2.24 nmol/l (18% vs. 40%) and NT-proBNP >364 pmol/l (27% vs. 45%), although patients with beta-blocker treatment received only 37 +/- 21% of the maximal recommended beta-blocker dosages. CONCLUSIONS: The prognostic value of variables used for risk stratification of patients with CHF is markedly influenced by beta-blocker treatment. Therefore, in the beta-blocker era, a re-evaluation of the selection criteria for heart transplantation is warranted.     

Efficacy and safety of medium- and high-dose diltiazem alone and in combination with digoxin for control of heart rate at rest and during exercise in patients with chronic atrial fibrillation

We evaluated the efficacy and the safety of medium-(240 mn/day) and high-dose (360 mg/day) diltiazem alone and in combination with digoxin when used for control of heart rate in 12 patients with chronic atrial fibrillation. Medium-dose diltiazem was comparable to therapeutic dose of digoxin at rest (88 +/- 19 vs 86 +/- 12 beats/min) but superior during peak exercise (154 +/- 23 vs 170 +/- 20 beats/min; p less than .05). High-dose diltiazem resulted in better control of heart rate than digoxin both at rest (79 +/- 17 beats/min; p less than .05) and exercise (136 +/- 25 beats/min; p less than .05) but was associated with side effects in 75% of the patients. Combined therapy of digoxin and diltiazem enhanced the effect of digoxin alone and resulted in significantly better control of heart rate at rest (67 +/- beats/min with medium-dose and 65 +/- beats/min with high-dose diltiazem) and during peak exercise (132 +/- 32 and 121 +/- 24 beats/min, respectively). However, the difference in heart rate between these two doses was not significant. Reduction of heart rate combined with concomitant effect on blood pressure resulted in a significant fall in pressure-rate product at rest from 10,077 +/- 1708 mm Hg/min on digoxin alone to 7877 +/- 1818 mm Hg/min after the addition of medium-dose diltiazem (p less than .05) and during exercise form 25,670 +/- 3606 to 18,439 +/- 4115 mm Hg/min (p less than .05). Continued therapy with digoxin combined with diltiazem 240 mg/day for 21 +/- 8 days in nine patients showed persistent effect on heart rate and blood pressure without any toxic manifestations or change in serum digoxin (1.5 +/- 0.4 vs 1.3 +/- 0.4 ng/ml) or plasma diltiazem concentrations (204 +/- 72 vs 232 +/- 129 ng/ml). In conclusion, medium-dose diltiazem when combined with digoxin is an effective and safe regimen for the treatment of patients with chronic atrial fibrillation and enhances digoxin-mediated control of heart rate both at rest and during exercise.     

Response of upper limb blood flow to handgrip exercise after Blalock-Taussig operation (for tetralogy of Fallot) or subclavian flap operation (for aortic isthmic coarctation)

To evaluate the effects of long-term reductions in perfusion pressure on blood flow responses to increased functional demand, 5 patients (aged 12 to 26 years) without normal aortic to subclavian artery blood flow to 1 arm as a result of surgery to treat congenital heart disease were studied. Five age- and sex-matched healthy (control) subjects were also studied. In the patients, forearm blood flow was not different in the surgical and normal arms at rest (3.6 +/- 0.6 vs 4.0 +/- 0.7 ml/min/100 ml, respectively, mean +/- standard error, difference not significant) despite lower systolic blood pressure in the surgical arm (87 +/- 2 vs 115 +/- 2 mm Hg, p less than 0.05). The increases in heart rate, systolic blood pressure, forearm electromyographic activity (index of muscle fatigue) and postexercise forearm blood flow (index of muscle oxygen deficit) were not different in response to 2.5 minutes of submaximal rhythmic handgrip exercise (50% of maximal force) performed with the surgical versus the normal arms. Peak forearm blood flow elicited by combined ischemia and maximal isometric handgrip exercise was not significantly different in surgical and normal arms in the group as a whole (39 +/- 4 vs 43 +/- 3 ml/min/100 ml, difference not significant), although some bilateral deficit (20 to 38%) was observed in 2 patients. No bilateral differences were observed in the control subjects under any condition. The finding of normal physiologic adjustments to submaximal rhythmic handgrip exercise with the surgical arm suggests that oxygen delivery during exercise was adequate.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of early dobutamine stress echocardiography and exercise electrocardiographic testing for management of patients presenting to the emergency department with chest pain

This study compared the cost-effectiveness of dobutamine-atropine stress echocardiography (DASE) and electrocardiographic exercise testing (EET) implemented in emergency department accelerated diagnostic protocols for the early stratification of low-risk patients presenting with acute chest pain (ACP). One hundred ninety-nine patients with ACP, nondiagnostic electrocardiographic results, and negative biomarker results were randomized to DASE (n = 110) or EET (n = 89) <6 hours after emergency department presentation. Patients with negative risk assessment results were immediately discharged and followed for 2 months. Ninety patients (82%) in the DASE arm and 78 (88%) in the EET arm were discharged after the diagnosis of nonischemic ACP. The mean lengths of stay in the hospital were 23 +/- 12 and 31 +/- 23 hours in the DASE and EET arms, respectively (p = 0.01). No 2-month follow-up events occurred in DASE patients, and the event rate was significantly higher in EET patients (0% vs 11%, p = 0.004). The DASE strategy showed lower costs compared with the EET strategy at 1-month ($1,026 +/- $250 vs $1,329 +/- $1,288, p = 0.03) and 2-month ($1,029 +/- 253 vs $1,684 +/- $2,149, p = 0.005) follow-up. In conclusion, early DASE in emergency department triage of low-risk patients with ACP is safe and reduces costs of care compared to EET.     

Dynamic mitral regurgitation. An important determinant of the hemodynamic response to load alterations and inotropic therapy in severe heart failure

Cardiac performance and mitral regurgitation were measured by Doppler echocardiography and right heart catheterization in 12 patients with severe congestive heart failure who performed isometric exercise during control and intravenous administration of dobutamine and nitroglycerin. During control isometric exercise, mitral regurgitant volume increased from 18 +/- 13 to 31 +/- 17 ml (p less than 0.01), while forward stroke volume, by both thermodilution and Doppler echocardiography, substantially decreased. At rest, dobutamine decreased mitral regurgitant volume from 18 +/- 13 to 11 +/- 10 ml (p less than 0.05), while forward stroke volume increased from 46 +/- 13 to 55 +/- 15 ml (p less than 0.05). During isometric exercise, dobutamine tended to decrease mitral regurgitant volume (24 +/- 12 vs. 31 +/- 17 ml; NS) when compared with control exercise. At rest, nitroglycerin decreased mitral regurgitant volume from 18 +/- 13 to 11 +/- 11 ml (p less than 0.05), while forward stroke volume, by both thermodilution and Doppler echocardiography, substantially increased. Similarly, during isometric exercise, nitroglycerin decreased mitral regurgitant volume from 31 +/- 17 to 20 +/- 14 ml (p less than 0.05), while significantly increasing forward stroke volume. At control rest, the median mitral regurgitant fraction was 24% for the 12 patients. Neither dobutamine nor nitroglycerin changed significantly forward stroke and mitral regurgitant volumes at rest and during isometric exercise in the six patients with resting mitral regurgitant fraction below the median. In contrast, dobutamine and nitroglycerin significantly decreased mitral regurgitant volume and increased forward stroke volume both at rest and during isometric exercise in the six patients with mitral regurgitant fraction greater than the median.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of maintenance of cardiac output during DDD and VVI pacing by exercise Doppler echocardiography]

To evaluate the efficacy of DDD pacing for cardiac reserve, we assessed increases in the stroke volume and cardiac output during randomized treadmill exercise in 16 patients by DDD and fixed-rate ventricular (VVI) pacing. The stroke volume index and cardiac index were determined using suprasternal Doppler measurements. Ten patients who showed sinus rhythm during exercise were excluded from this study. Compared with the findings during VVI pacing, those during DDD pacing showed: 1) a greater exercise-induced positive chronotropic response (mean maximum heart rate 122 +/- 22 beats/min vs 70 beats/min, p < 0.01), 2) a lesser increase in the stroke volume index (34 +/- 7 to 39 +/- 9 ml/m2 vs 31 +/- 7 to 49 +/- 11 ml/m2, p < 0.05), 3) a greater increase in the cardiac index (2.43 +/- 0.45 to 4.48 +/- 1.36 L/min/m2 vs 2.22 +/- 0.47 to 3.43 +/- 0.45 L/min/m2, p < 0.05), and 4) prolongation of exercise duration (6.35 +/- 2.00 min vs 5.97 +/- 1.81 min, NS). These findings indicated that VVI pacing promoted a greater stroke volume than DDD pacing, which provides a compensatory increase in contractility and the preload in cases without an increase in heart rate during exercise, however, the increase in cardiac output was insufficient due to the absence of a chronotropic response. In conclusion, a DDD pacemaker could effectively increase heart rate, causing a significant increase in cardiac output and extending exercise duration.