Jane Sparrow

Predictors of prognosis in severe chronic heart failure

A total of 127 patients with chronic heart failure referred to our exercise laboratory were studied retrospectively to identify parameters predictive of prognosis. Patients were followed for a mean of 14.6 months. The group as a whole had severe ventricular dysfunction with a median ejection fraction of 17% and a median peak rate of oxygen consumption of 13.7 ml/kg/min. During the follow-up period 23 patients (18%) died and 18 (14%) underwent cardiac transplantation. The effect of the following variables on outcome (death or transplantation) were examined: age, cause of heart failure, cardiothoracic ratio on chest radiography, left ventricular end-systolic dimension on echocardiography, left ventricular ejection fraction on radionuclide ventriculography, mean dose of diuretic, plasma sodium and urea concentrations, and peak oxygen consumption during exercise. Although all variables except cause of heart failure affected outcome on univariate analysis, multivariate analysis identified three variables that were statistically significant and independent predictors of outcome. In order of importance these were plasma sodium level, left ventricular ejection fraction and peak oxygen consumption. Even in this group of patients with severe heart failure, these variables were predictive of outcome.

Ischemia in the ambulatory setting—The total ischemic burden: Relation to exercise testing and investigative and therapeutic implications☆

To establish the relation between treadmill exercise testing and ambulatory St segment monitoring in the detection of ischemia in patients with coronary artery disease, and to assess whether standard medical therapy affects any such relation, 277 patients with stable angina and angiographically documented coronary artery disease were studied with treadmill exercise testing and 48 h ambulatory ST segment monitoring. One hundred forty-six patients (52%) were studied while receiving no routine antianginal therapy, and 131 (48%) while receiving standard medical therapy. In 187 patients (67%) the exercise test was positive for ischemia. During 11,964 h of ambulatory monitoring, 881 episodes of ischemia (645 [73%] silent) were recorded, of which 809 (92%) occurred in patients with a positive exercise test. The mean heart rate at the onset of ischemic episodes during ambulatory monitoring was significantly less than that at the onset of 1 mm ST segment depression during exercise testing (94.5 versus 105.9 beats/min, p less than 0.0001). However, the frequency of ambulatory ischemic episodes was strongly related to a positive exercise test (p less than 0.001), and this relation was similar for both silent and painful ischemia (p less than 0.0001 for both) and in patients who were and were not receiving therapy (p less than 0.0001 for both). The total duration of ischemia was similarly related to a positive exercise test (p less than 0.0001). Only one patient with a negative exercise test had frequent (greater than 5/day) episodes of ischemia on ambulatory monitoring and had documented coronary artery spasm. Thus, exercise testing identifies the majority of patients likely to have significant ischemia during their daily activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Heart rate and blood pressure consequences of an afternoon SIESTA (Snooze-Induced Excitation of Sympathetic Triggered Activity).

Abstract With the increased interest shown in the area of arcadian variations in physiologic parameters and cardiovascular disease processes in recent years, it has been demonstrated that there are distinct circadian rhythms in cardiovascular events, with a surge in ischemia,1 onset of acute myocardial infarction2 and sudden cardiac death3 in the morning waking hours, and a trough in such events at night. Such peaks in ischemia and onset of acute myocardial infarction are particularly related to actual time of waking and commencing activities. Because there are surges in heart rate (HR) and systolic blood pressure (BP) in the morning waking hours,4 and because β-adrenergic blocking agents blunt the morning peaks in HR,5 in addition to those of ischemia,5 onset of acute myocardial infarction2 and sudden cardiac death,6 it has been suggested that activation of the sympathetic adrenergic system may play an important role in the increased cardiovascular event rate in the period soon after waking and commencing activities. We have assessed HR and BP responses before, during and after an afternoon siesta in apparently normal subjects, and compared the changes with those recorded on waking and commencing activities in the morning to establish whether the morning waking hours are particularly associated with increases in the determinants of myocardial oxygen demand, or whether this response is reproducible after any period of “sleep”.

Objective assessment of the response to treatment of severe heart failure using a 9-minute walk test on a patient-powered treadmill*

BACKGROUND No previous studies have demonstrated the changes in exercise capacity that occur during treatment of decompensated severe heart failure. The authors assessed the efficacy and safety of using a patient-powered treadmill to objectively measure exercise capacity and its relationships, if any, to symptom scores and body weight. METHODS AND RESULTS Changes in time-limited exercise capacity on a patient-powered treadmill were assessed during inpatient treatment of 12 patients with decompensated chronic heart failure (New York Heart Association classes III and IV). Patients performed a 9-minute walk test daily for 7 days and again at the 6-week follow-up examination. They also completed a 24-item symptom score questionnaire. After treatment, there was a rapid, significant increase in total distance walked, with the increase beginning as early as the second day after admission (mean distance walked +/- SEM, 54 +/- 27 m and 174 +/- 54 m on admission and on day 2, respectively, P < .05). Improvement was maintained throughout the period in the hospital and at 6 weeks (P < .001). Patients reported symptomatic improvement, but this did not reach significance until 4 days after admission (P < .05). Weight loss was not significant. Improved exercise capacity correlated with reduced symptoms and weight loss, but preceded these by several days. CONCLUSIONS In patients with decompensated chronic heart failure, this exercise test provides a safe, practical, inexpensive, and objective assessment of functional capacity, providing certain advantages over other indices of response to therapy, such as symptom scores and weight loss. Improvement of exercise capacity does not occur concurrently with relief of symptoms and weight loss.

Atenolol or nicardipine alone is as efficacious in stable angina as their combination: a double blind randomised trial

BACKGROUND Beta blockers and calcium antagonists are widely used in the management of angina pectoris in the belief that the combination is more efficacious than either drug alone. METHODS This double blind randomised crossover placebo controlled study compares the effects of nicardipine, atenolol and their combination in 30 patients with chronic stable angina. Each treatment period lasted 6 weeks with dose titration after 3 weeks. Symptom limited treadmill exercise testing and radionuclide ventriculography at rest was carried out at the end of each treatment period. RESULTS Total exercise duration and time to 1-mm ST-segment depression was significantly prolonged by nicardipine and atenolol when compared to placebo, the combination offered no additional benefit. Time to onset of angina was significantly prolonged by nicardipine and the combination but not by atenolol. Indices of left ventricular function were not significantly affected by any treatment other than an increase in left ventricular end diastolic volume on atenolol and the combination. CONCLUSIONS Nicardipine and atenolol are equally effective in prolonging exercise duration and time to onset of ischemia in patients with chronic stable angina while the combination appeared to offer no additional benefit. Nicardipine prolonged the time to onset of angina significantly; again there was no further improvement with the combination. Neither drug appears to have an important effect on the parameters of diastolic function studied in patients with chronic stable angina.

Effects of coronary artery bypass surgery and angioplasty on the total ischemic burden: A study of exercise testing and ambulatory ST segment monitoring

To assess the effects of standard therapeutic interventions on the total ischemic burden, 86 patients with stable angina underwent 48 hours of ambulatory ST segment monitoring and treadmill exercise testing before and at a mean of 10 weeks after coronary artery bypass surgery (CABG) (group 1, N = 46) or percutaneous transluminal coronary angioplasty (PTCA) (group 2, N = 40). There were 72 male and 14 female patients with a mean age of 56.4 years. All patients had documented coronary artery disease (24, single-vessel; 28, two-vessel; 34, three-vessel disease). Both groups were characteristically similar apart from more severe coronary artery disease (p less than 0.001) and more previous myocardial infarctions (p less than 0.05) in group 1. Groups with CABG and PTCA had significant prolongation of exercise time after intervention (group 1: 7.6 to 9.8 minutes, p less than 0.0001; group 2: 8.1 to 10.0 minutes, p less than 0.001), and both interventions led to a significant reduction in ischemic responses (group 1: 33 to 4, p less than 0.001; group 2: 20 to 13, p less than 0.05) to exercise. During a total of 7643 hours of ST segment monitoring, 253 episodes of ischemia were recorded in 3768 hours before and 44 ischemic episodes in 3875 hours after intervention (group 1, 113 episodes in 24 patients and 21 episodes in 10 patients; group 2, 140 episodes in 13 patients and 23 episodes in six patients). Both interventions reduced the mean frequency of ischemia per 24 hours (group 1: 1.24 to 0.22 episodes per 24 hours; p less than 0.01; group 2: 1.9 to 0.3 episodes per 24 hours; p less than 0.05). Almost 28% (N = 24) of resting electrocardiographic findings were altered as a result of intervention.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of amlodipine versus diltiazem on morning peak in myocardial ischemic activity in angina pectoris

Abstract Many studies have confirmed a peak in the onset of acute myocardial infarction, sudden cardiac death and ischemic activity in the morning waking hours in patients with coronary artery disease. Factors potentially relevant to this observed surge in activity include marked increases in heart rate, blood pressure, catecholamine release, coronary artery tone and platelet aggregability, and a trough in the fibrinolytic state at this time. 1 Various studies have shown that β-adrenergic blockade is effective in blunting particularly the morning surge in ischemic activity, 2,3 onset of acute myocardial infarction, 4 and sudden cardiac death 5 ; however, despite the powerful coronary vasodilating and afterload-reducing properties of calcium antagonists, they have not been shown to alter the morning surge in ischemia 2,6 (except in high doses 7 ), or the morning peak in onset of myocardial infarction. 4 Although the recently published nifedipine Gastrointestinal Therapeutic System (GITS) study showed an overall modification of the circadian pattern of ischemia with nifedipine GITS as monotherapy, there appeared to be no difference in circadian patterns during such active therapy and subsequent placebo withdrawal. 8 It is possible that previous studies of calcium antagonists without either a 24-hour profile or chronotropic control have resulted in (1) the morning waking period being “unprotected” regarding efficacious plasma levels of drug on waking, and/or (2) an absence of modification of the heart rate response to increasing and commencing activity, a mechanism by which β blockers may, at least partially, exert their effects.

Effect of acadesine, a new metabolic agent, on exercise-induced myocardial ischemia in chronic stable angina.

SummaryAcadesine, the first of a class of adenosine-regulating agents, has been shown to possess antiischemic properties in animal models. The aim of the study was to assess the effect of acadesine on exercise-induced myocardial ischemia in patients with chronic stable angina pectoris. Twelve patients with stable angina entered a five-way, randomized double-blind study comparing the effects of four doses of acadesine with placebo on time to 1 mm ST-segment depression and other parameters of exercise tolerance. At each study period patients underwent baseline exercise testing, followed by drug or placebo infusion after a 60 minute rest period. The exercise test was repeated after 30 minutes infusion, which continued throughout recovery. Time to angina, time to 1 mm ST depression, and total exercise time during the placebo infusion were 301.1±45.3, 314.8±50.9, and 399.4±47.6 seconds. The placebo-adjusted percentage change in time to 1-mm ST segment with acadesine 6, 12, 24, and 48 mg/kg was −0.1±6.2%, 11.1±13.8%, 12.9±8.6%, and −3.2±6.8%, respectively (p=NS vs. baseline). Time to angina, total exercise time, and recovery time of the ST segment were not consistently altered by acadesine. The lack of effect across all acadesine doses is consistent with animal data from ischemia-reperfusion injury studies, where a clear dose dependency was present with a loss of effect at higher doses. Alternatively, the extent of ischemia induced by treadmill exercise may have been insufficient for the antiischemic activity of acadesine to be evident.