The role of repeating optimization of atrioventricular interval during interim and long-term follow-up after cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) is an effective therapy for heart failure patients with electromechanical delay. Optimization of atrioventricular interval (AVI) is a cardinal component for the benefits. However, it is unknown if the AVI needs to be re-optimized during long-term follow-up. METHODS: Thirty-one patients (66+/-11 years, 20 males) with sinus rhythm who received CRT underwent serial optimization of AVI at day 1, 3-month and during long-term follow-up by pulse Doppler echocardiography (PDE). At long-term follow-up, the optimal AVI and cardiac output (CO) estimated by non-invasive impedance cardiography (ICG) were compared with those by PDE. RESULTS: The follow-up was 16+/-11 months. There was no significant difference in the mean optimal AVI when compared between any 2 time points among day 1 (99+/-30 ms), 3-month (97+/-28 ms) and long-term follow-up (94+/-28 ms). However, in individual patient, the optimal AVI remained unchanged only in 14 patients (44%), and was shortened in 12 (38%) and lengthened in 6 patients (18%). During long-term follow-up, although the mean optimal AVIs obtained by PDE or ICG (94+/-28 vs. 92+/-29 ms) were not different, a discrepancy was found in 14 patients (45%). For the same AVI, the CO measured by ICG was systematically higher than that by PDE (3.5+/-0.8 Vs. 2.7+/-0.6 L/min, p<0.001). CONCLUSION: Optimization of AVI after CRT appears necessary during follow-up as it was readjusted in 55% of patients. Although AVI optimization by ICG was feasible, further studies are needed to confirm its role in optimizing AVI after CRT.

Are left ventricular diastolic function and diastolic asynchrony important determinants of response to cardiac resynchronization therapy?

Cardiac resynchronization therapy (CRT) has been shown to reduce symptoms and reverse left ventricular (LV) remodeling. It is not known, however, whether diastolic function will improve after CRT and diastolic asynchrony will predict LV reverse remodeling. Seventy-six patients (mean age 65 +/- 12 years, 74% men) who received CRT were studied at baseline and after 3 months. Diastolic function was assessed by transmitral Doppler and tissue Doppler imaging. LV systolic and diastolic asynchrony were assessed by the time to peak myocardial contraction (Ts) and early diastolic relaxation (Te) using the 6 basal, 6 mid-segmental model. There were 42 responders (55%) with LV reverse remodeling (defined as a reduction of LV end-systolic volume >or=15%). Parameters of systolic function were significantly improved only in the responders. For diastolic function, there were reductions of transmitral E velocity in the 2 groups, without any change in atrial velocity or the E/A ratio. Tissue Doppler imaging revealed that myocardial early diastolic velocity was unchanged in responders but was significantly worsened in nonresponders. The systolic asynchrony index (the SD of Ts of 12 LV segments) correlated significantly with LV reverse remodeling (r = -0.64, p <0.001) but not the diastolic asynchrony index (the SD of Te of 12 LV segments) (r = -0.10, p = NS). The systolic asynchrony index was the only independent predictor of reverse remodeling (beta = -0.99, 95% confidence interval -1.41 to -0.58, p <0.001). In conclusion, CRT improves systolic function and systolic asynchrony but has a neutral effect on diastolic function and diastolic asynchrony. LV reverse remodeling response is determined by the severity of prepacing systolic asynchrony but not diastolic asynchrony or the diastolic filling pattern.

Do metoprolol and carvedilol have equivalent effects on diurnal heart rate in patients with chronic heart failure?

BACKGROUND: Carvedilol exerted a greater reduction in mortality than metoprolol tartrate in the Carvedilol or Metoprolol European Trial (COMET). However, it is unclear if the degree and time course of beta1-blockade during a 24-h period was similar with each agent at the doses used. Therefore we analyzed 24-h ECG Holter recordings from a study which compared the long-term clinical efficacy of metoprolol tartrate to carvedilol in chronic heart failure patients using the same dosing regimen as in COMET. METHODS AND RESULTS: Fifty-one patients with chronic heart failure with a mean LVEF 26+/-1.8% were randomized in a double-blind fashion to receive metoprolol tartrate 50 mg bid or carvedilol 25 mg bid. 24-h ECG monitoring (Holter) was performed at baseline, 12 weeks and 1 year. Adequate quality recordings for analysis were obtained from 43 subjects at baseline, 42 at 12 weeks and 29 subjects at 1 year. Both drugs produced a fall in average 24-h heart rate from baseline at 12 weeks and at 1 year: metoprolol 88+/-3 to 71+/-2 and 69+/-3 bpm; carvedilol 83+/-3 to 70+/-2 and 70+/-3 bpm respectively (all p<0.001). The pattern of suppression of heart rate during the 24-h period was similar for both drugs. CONCLUSION: Metoprolol tartrate 50 mg bid and carvedilol 25 mg bid had similar effects on 24-h heart rate. This result suggests that the degree of beta1-blockade produced by these two drugs in these doses is comparable and the superior survival effect of carvedilol compared to metoprolol seen in COMET is likely to be due to actions of carvedilol other than beta1-blockade.

Effect of beta blockade (carvedilol or metoprolol) on activation of the renin-angiotensin-aldosterone system and natriuretic peptides in chronic heart failure.

Beta blockers are known to suppress renin release in hypertension and in patients taking angiotensin-converting enzyme (ACE) inhibitors. This study sought to explore the effect of additional beta blockade on neurohumoral modulation in patients with severe heart failure (HF) who received ACE inhibitors. Forty-nine patients with chronic HF who received ACE inhibitors were given metoprolol 50 mg or carvedilol 25 mg twice daily after a 4-week dose titration period in addition to standard therapy in a prospective trial. Samples of plasma renin activity (PRA), aldosterone, aminoterminal B-type natriuretic peptide (N-BNP), and atrial natriuretic peptide (ANP) were taken at baseline and at 4, 12, and 52 weeks after starting therapy. Treatment with either beta blocker significantly lowered PRA at 4 weeks compared with baseline (-2.0 +/- 0.6 nmol/L/hour, p = 0.006), but at 12 weeks, PRA had reduced to -1.1 +/- 0.6 nmol/L/hour (p = 0.08), but at 52 weeks, it was not significantly different from baseline (+1.05 +/- 0.6 nmol/L/hour, p = 0.13). Aldosterone levels did not change significantly from baseline at 4 or 12 weeks, although there was a nonsignificant trend for lower levels at 52 weeks (baseline 232 +/- 154 pmol/L, 52 weeks 192 +/- 100 pmol/L, p = 0.09). There was significant reduction in N-BNP and ANP together with an improvement in symptom and left ventricular systolic function at 1-year follow-up. These results indicate that the suppressive effect of beta blockers on PRA in patients with HF taking ACE inhibitors is temporary, and that there is no significant effect on serum aldosterone levels.

Is beta-blockade useful in heart failure patients with atrial fibrillation? An analysis of data from two previously completed prospective trials.

BACKGROUND: Beta-adrenergic blockade is of proven value in chronic heart failure. It is uncertain, however, if beta-blockade provides a similar degree of clinical benefit for heart failure patients with atrial fibrillation (AF) as those in sinus rhythm (SR). AIMS: To compare the effectiveness of beta blockade in patients with heart failure and AF. METHODS: Patients with chronic heart failure were randomized to treatment (double blind) with metoprolol 50 mg twice daily or carvedilol 25 mg twice daily in addition to standard therapy. Response was assessed after 12 weeks by a quality of life questionnaire, New York Heart Association class, exercise capacity (6-min walk test), radionucleotide ventriculography for LVEF, 2-D echocardiography measurement of left ventricular (LV) dimensions and diastolic filling and 24-h electrocardiograph monitoring to assess heart rate changes. RESULTS: Both beta-blockers produced significant improvements in LVEF in both the SR group: (+6+/-10% at 12-week, P<0.001) and the AF group: (+11+/-9% at 12-week, P<0.05). However, significant improvement in symptoms (P<0.001) and exercise capacity (P<0.001) were observed only in the SR group but not in the AF group despite a significant improvement in LVEF. CONCLUSION: Beta-blockers were effective in improving LV ejection fraction in chronic heart failure patients in either SR or AF but had less effect on symptoms and exercise capacity in those with AF.