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BACKGROUND: Short- and intermediate-term use of cardiac glycosides promotes inotropy and improves the ejection fraction in systolic heart failure. AIM: To determine whether chronic digitalization alters left ventricular function and performance. METHODS: Eighty patients with mild-to-moderate systolic heart failure (baseline ejection fraction < or =45%) participated from our institution in a multi-center, chronic, randomized, double-blind study of digitalis vs. placebo. Of the 40 survivors, 38 (20 allocated to the digitalis arm and 18 to the placebo arm) were evaluated at the end of follow-up (mean, 48.4 months). Left ventricular systolic function was assessed by both nuclear ventriculography and echocardiography. The ejection fraction was measured scintigraphically, while the ventricular volumes were computed echocardiographically. RESULTS: The groups did not differ, at baseline or end-of-study, with respect to the ejection fraction and the loading conditions (arterial pressure, ventricular volumes and heart rate) by either intention-to-treat or actual-treatment-received analysis. Over the course of the trial, the digitalis arm exhibited no significant increase in the use of diuretics (18%, P=0.33), in distinction from the placebo group (78%, P=0.004), and a longer stay on study drug among those patients who withdrew from double-blind treatment (28.6 vs. 11.4 months, P=0.01). CONCLUSION: Following chronic use of digitalis for mild-to-moderate heart failure, cross-sectional comparison with a control group from the same inception cohort showed no appreciable difference in systolic function or performance. Thus, the suggested clinical benefit cannot be explained by an inotropic effect.

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A recent study showed that, in a select patient population with no drug use and no cardiac or other illness, an increase in heart rate equal to or less than 18 beats per minute from baseline in the first 6 minutes of a tilt-table test at 60 degrees identifies patients who will not develop syncope during prolonged tilting, with specificity and positive predictive value nearing 100 percent. We retrospectively reviewed 110 consecutive tilt-table tests at an angle of 70 degrees or more, performed at our institutions between 1994 and 1999 in patients with and without cardiac disease or drug use. Excluded were 320 additional patients due to either incomplete heart rate documentation or development of syncope in the first ten minutes of tilting. The difference between maximal heart rate in the first ten minutes during tilting and the average of at least two baseline heart rate measurements was used to assess correlation with the non-occurrence of syncope during the same test. The tilt-table angle used varied from 70 degrees to 90 degrees (80 degrees in 89 percent of patients). There was a strongly significant (p < 0.0001) correlation between a sustained rise in heart rate equal to or less than 18 beats per minute in the first ten minutes of tilting and the non-occurrence of subsequent syncope during the test. The sensitivity, specificity, positive and negative predictive values were 75.7 percent, 65.0 percent, 79.1 percent and 60.47 percent, respectively. These data indicate that even in the routine setting, that is, a non-select population and at a higher tilt-table angle, an increase in heart rate equal to or less than 18 beats per minute in the first ten minutes of tilting constitutes a good predictor of a negative test. However, the specificity and positive predictive value of this criterion were not high enough to justify an early termination of the test.

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BACKGROUND: The efficacy of short-term digitalization on exercise tolerance may, in part, reflect enhanced diastolic performance. However, cardiac glycosides can impair ventricular relaxation from cytosolic Ca++ overload. To detect any time-dependent adverse effect, we assessed the diastolic function after long-term use of digitalis in patients with mild to moderate systolic left ventricular failure. METHODS AND RESULTS: From a cohort of 80 patients who received long-term, randomized, double-blind treatment with digitalis versus placebo at the WJB Dorn Veterans Affairs Medical Center, 38 survivors were evaluated at the end of follow-up (mean 48.4 months) with evaluators blinded to treatment used. Each survivor underwent equilibrium scintigraphic and echocardiographic assessment of diastolic function. Peak and mean filling rates normalized with filling volume (FV), diastolic phase durations normalized with duration of diastole, and filling fractions were measured from the time-activity curve. The isovolumic relaxation period and ventricular dimensions were computed echocardiographically. By actual-treatment-received analysis, treated versus untreated patients manifested a trend toward longer isovolumic relaxation (80.76 ms vs 61.54 ms, P = .06) but a markedly lower peak rapid filling rate (6.39 FV/sec vs 10.56 FV/sec, P = .02) despite comparable loading conditions. In addition, treated patients exhibited a lower mean rate of rapid filling (2.75 FV/sec vs 3.78 FV/sec, P = .05) in the absence of a longer rapid filling duration. However, the end-diastolic ventricular dimension did not differ between the 2 groups. Similar results were obtained by intention-to-treat analysis. Importantly, the mortality rate from worsening heart failure in the inception cohort was lower in the digitalis group versus the placebo group (P = .05) with no difference in total cardiac or all-cause mortality. CONCLUSIONS: After long-term digitalization for systolic left ventricular failure, cross-sectional comparison with a control group from the same inception cohort shows a decrease in the rate and degree of ventricular relaxation. This effect did not interfere with the overall ventricular filling or with a favorable impact on outcome from worsening heart failure.

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Although left ventricular (LV) aneurysm is associated with increased mortality, its independent prognostic significance is controversial. To determine the effect of LV aneurysm on risk, 121 patients with healed myocardial infarction (MI), 55 manifesting akinesia on ventriculography (MI group) and 66 with LV aneurysm characterized by diastolic deformity (eccentricity) and systolic dyskinesia (LV aneurysm group) were studied. At a mean follow-up of 5.7 years, there were 32 cardiac deaths (12 MI vs 20 LV aneurysm), including 9 sudden deaths (1 MI vs 8 LV aneurysm). Multivariate analysis revealed decreasing ejection fraction to be the best predictor of total cardiac death, and revascularization to be protective. Nonsudden cardiac death was predicted by ejection fraction, absence of revascularization and right coronary artery disease, whereas sudden cardiac death was predicted by LV aneurysm and the frequency of ventricular ectopic complexes on Holter monitoring. In the MI group, ejection fraction was the only significant predictor of total cardiac death and nonsudden cardiac death. In the LV aneurysm group, total cardiac death, as well as nonsudden cardiac death, were predicted by ejection fraction, ventricular tachycardia and right coronary artery disease, whereas ventricular tachycardia predicted sudden cardiac death. It is concluded that the risk profile for total cardiac death differs between LV aneurysm and MI patients, and that LV aneurysm constitutes an independent predictor of late sudden cardiac death after MI. Moreover, on a substrate of LV aneurysm, the risk factors for sudden cardiac death and nonsudden cardiac death differ, with ventricular tachycardia being the sole predictor of sudden cardiac death. Furthermore, Holter monitoring is valuable in identifying patients at persistent risk of sudden cardiac death.

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