Pacemaker therapy for early and late sinus node dysfunction in orthotopic heart transplant recipients: a single-center experience.

BACKGROUND: Sinus node dysfunction (SND) is a well-known early complication of orthotopic heart transplantation (OHT). Its incidence over the lifetime of transplant recipients is less well characterized. The goal of this study was to determine the incidence and timing of SND treated with a permanent pacemaker in a large cohort of OHT recipients. METHODS: The databases of the Yale University Heart Transplant and Electrophysiology Services were reviewed and cross referenced. Patients who received pacemakers for SND were identified for analysis. A total of 241 patients underwent OHT using biatrial anastamoses from 1984 to 2006. Two hundred sixteen patients, 149 men and 55 women, mean age 50.2 +/- 11.6 years, survived > 5 days post-OHT. These, minus 12 lost to follow-up, were included in the analysis. RESULTS: These 204 patients were followed in the Yale Heart Transplant Clinic and had yearly electrocardiograms and 24-hour ambulatory monitoring. Of these patients, 24 (four female, 20 male, mean age at transplant 49 +/- 12 years) were felt to have clinically significant SND and received a pacemaker. Fourteen patients received pacemakers within 30 days of OHT; 10 patients received pacemakers 45 to 4,329 days after OHT. CONCLUSIONS: Although frequently seen as an early complication of OHT, SND remains a risk throughout the lifetime of OHT recipients. Its mechanism is likely multifactorial, and whether this risk can be mitigated over the long term by newer techniques such as bicaval anastamoses remains to be established.

Effect of acetylcholinesterase inhibition with pyridostigmine on cardiac parasympathetic function in sedentary adults and trained athletes.

Heart rate variability and postexercise heart rate recovery are used to assess cardiac parasympathetic tone in human studies, but in some cases these indexes appear to yield discordant information. We utilized pyridostigmine, an acetylcholinesterase inhibitor that selectively augments the parasympathetic efferent signal, to further characterize parasympathetic regulation of rest and postexercise heart rate. We measured time- and frequency-domain indexes of resting heart rate variability and postexercise heart rate recovery in 10 sedentary adults and 10 aerobically trained athletes after a single oral dose of pyridostigmine (30 mg) and matching placebo in randomized, double-blind, crossover trial. In sedentary adults, pyridostigmine decreased resting heart rate [from 66.7 (SD 12.6) to 58.1 beats/min (SD 7.6), P = 0.005 vs. placebo] and increased postexercise heart rate recovery at 1 min [from 40.7 (SD 10.9) to 45.1 beats/min (SD 8.8), P = 0.02 vs. placebo]. In trained athletes, pyridostigmine did not change resting heart rate or postexercise heart rate recovery when compared with placebo. Time- and frequency-domain indexes of resting heart rate variability did not differ after pyridostigmine versus placebo in either cohort and were not significantly associated with postexercise heart rate recovery in either cohort. The divergent effects of pyridostigmine on resting and postexercise measures of cardiac parasympathetic function in sedentary subjects confirm that these measures characterize distinct aspects of cardiac parasympathetic regulation. The lesser effect of pyridostigmine on either measure of cardiac parasympathetic tone in the trained athletes indicates that the enhanced parasympathetic tone associated with exercise training is at least partially attributable to adaptations in the efferent parasympathetic pathway.

Long-term assessment of cardiac function after dose-dense and -intense sequential doxorubicin (A), paclitaxel (T), and cyclophosphamide (C) as adjuvant therapy for high risk breast cancer.

OBJECTIVES: This study evaluated the incidence of late cardiotoxicity after dose-dense and -intense adjuvant sequential doxorubicin (A), paclitaxel (T), and cyclophosphamide (C) for breast cancer (BC) with > or = 4 involved ipsilateral axillary lymph nodes. METHODS: Patients were enrolled from 1994 to 2001 after definitive BC surgery if > or =4 axillary nodes were involved. Planned treatment was A 90 mg/m(2) q 14 days x 3, T 250 mg/m(2) q 14 days x 3, C 3 g/m(2 )q 14 days x 3 with filgrastim (G) support. Left ventricular ejection fraction (LVEF) was monitored using equilibrium radionuclide angiography (ERNA) before the initiation of chemotherapy, and after three cycles of each chemotherapeutic agent. At a median follow-up of 7 years, we obtained ERNA scans on 32 patients to evaluate the long-term cardiotoxicity of this regimen. RESULTS: Eighty-five eligible patients enrolled on the treatment protocol. Clinical heart failure developed in one patient. Seven (8%) patients had LVEF < 50% at the end of therapy. No cardiac-related deaths occurred. Thirty-two (46%) of 69 surviving patients have consented to late cardiac imaging. At a median follow-up of 7 years, the median absolute change in LVEF from baseline was -5.5%; [range (-8%) to (+36%)], and from the end of chemotherapy was -2.0%; [range (-25%) to (+16%)]. Four patients (12%) had a LVEF < 50%; two of these four patients had an LVEF of < 50% at the end of chemotherapy. CONCLUSIONS: Late development of asymptomatic decline in cardiac function may occur after dose-dense and -intense adjuvant therapy, but is uncommon.

Effects of psychologic stress on repolarization and relationship to autonomic and hemodynamic factors.

INTRODUCTION: Psychological stress can precipitate ventricular arrhythmias in patients with ICDs, as well as sudden death. However, the physiologic pathways remain unknown. We sought to determine whether psychological stress induced in the laboratory setting alters indices of repolarization associated with arrhythmogenesis. METHODS AND RESULTS: Patients with ICDs and a history of ventricular arrhythmia underwent ambulatory ECG monitoring during a laboratory mental stress protocol (anger recall and mental arithmetic). Continuous changes in repolarization indices which have correlated with temporal and spatial myocardial heterogeneity of repolarization, including T-wave alternans (TWA), T-wave amplitude (Tamp), and T-wave area (Tarea) were analyzed in the time domain. In the 33 patients (85% male, 88% with coronary artery disease, mean ejection fraction 30%), norepinephrine, epinephrine, BP, and HR increased during mental stress. TWA increased from 22 (interquartile range 16-27) at baseline to 29 (21-38) uV during mental stress (P < 0.001). Changes in TWA correlated with changes in HR, systolic BP, and catecholamines. Tamp and Tarea also increased with mental stress (P < 0.01) but did not correlate with changes in other variables. CONCLUSION: Psychological stress increased TWA, Tamp, and Tarea. Autonomically mediated repolarization changes may be a pathophysiologic link between emotion and arrhythmia in susceptible patients.

Comparative costs of home positive inotropic infusion versus in-hospital care in patients awaiting cardiac transplantation.

BACKGROUND: Outpatient positive inotropic support combined with implantation of an automatic implantable cardioverter defibrillator (AICD) may be used as a successful bridge to cardiac transplantation in patients with end-stage heart failure. A detailed comparative cost analysis of this outpatient strategy versus in-hospital care has not been previously reported. METHODS AND RESULTS: Twenty-one United Network for Organ Sharing 1B patients awaiting cardiac transplantation received continuous outpatient inotropic therapy for a total of 3070 patient-days. Daily costs for outpatient and in-hospital treatment were calculated. Nonparametric decision analysis was used to determine the strategy with greatest cost savings (immediate hospital discharge after AICD implantation versus in-hospital care). A threshold analysis was performed to test the robustness of the decision analysis model. The outpatient strategy realized an average savings of $71,300 to $120,500 per patient. Decision analysis showed that no fixed period of in-hospital monitoring was more cost-saving than immediate hospital discharge after AICD implantation. Threshold analysis revealed that AICD costs would need to exceed $82,000 (currently $62,000) or that the difference between the outpatient and the in-hospital costs would need to be < or = $475 per day for any other intermediate strategy to be considered cost-saving. CONCLUSION: Outpatient inotropic therapy combined with AICD implantation in selected patients awaiting cardiac transplantation is an effective cost-minimizing strategy.

Home continuous positive inotropic infusion as a bridge to cardiac transplantation in patients with end-stage heart failure.

BACKGROUND: The clinical use of positive inotropic therapy at home in patients awaiting cardiac transplantation has not been reported since United Network for Organ Sharing (UNOS) regulations were changed to allow home infusions in Status 1B patients. METHODS: We observed 21 consecutive patients with UNOS 1B status during positive inotropic therapy at home. We used hemodynamic monitoring at the initiation of therapy to optimize dosing. We selected for home therapy patients with stable clinical status and improved functional capacity during inotropic treatment. Implantable cardioverter defibrillators were placed in all but 1 patient before discharge. RESULTS: Initial positive inotropic therapy included dobutamine in 12 patients (mean dose, 4.5 mcg/kg/min; range, 2.5-7.5 mcg/kg/min), milrinone in 8 patients (mean dose, 0.44 mcg/kg/min; range, 0.375-0.55 mcg/kg/min), and dopamine at a dose of 3 mcg/kg/min in 1 patient. Patients had improved functional capacity (New York Heart Association Class 3.7 +/- 0.1 to 2.4 +/- 0.2, p < 0.01), improved renal function (serum creatinine, 1.5 +/- 0.1 to 1.3 +/- 0.1, p < 0.01), improved resting hemodynamics, and decreased number of hospitalizations during positive inotropic infusion therapy when compared with pre-treatment baseline. Implantable cardioverter defibrillator discharges were infrequent (0.19 per 100 patient days of follow-up). Actuarial survival to transplantation at 6 and 12 months was 84%. CONCLUSIONS: Continuous positive inotropic therapy at home was safe and was associated with decreased health care costs in selected patients awaiting cardiac transplantation.

Effects of propranolol on recovery of heart rate variability following acute myocardial infarction and relation to outcome in the Beta-Blocker Heart Attack Trial.

This study evaluated the effects of propranolol on recovery of heart rate variability (HRV) after acute myocardial infarction and its relation to outcome in the Beta-blocker Heart Attack Trial (BHAT). Beta blockers improve mortality after acute myocardial infarction, but through an unknown mechanism. Depressed HRV, a measure of autonomic tone, predicts mortality after acute myocardial infarction. Whether beta blockers influence recovery of HRV after acute myocardial infarction, and thereby improve outcome, is unknown. We compared 24-hour HRV parameters at 1 week after acute myocardial infarction and after 6 weeks of treatment with propanolol (n = 88) or placebo (n = 96). The relation between 25-month outcome (death/acute myocardial infarction/congestive heart failure), propranolol treatment, and HRV was further analyzed. After 6 weeks, high-frequency (HF) power (log-normalized), an index of vagal tone, increased more in propranolol-treated patients (4.28 +/- 0.1 to 5.17 +/- 0.09 ms(2)) than in placebo-treated patients (4.26 +/- 0.09 to 4.77 +/- 0.1 ms(2), p <0.05). Sympathovagal balance measured by the low-frequency (LF) to HF ratio increased in placebo-treated patients (3.55 +/- 0.24 to 3.86 +/- 0.24) but decreased in those treated with propranolol (3.76 +/- 0.29 to 3.17 +/- 0.23, p <0.01). Other frequency-domain parameters increased over time but were not affected by propranolol. Propranolol blunted the morning increase in the LF/HF ratio. Recovery of HF, the strongest HRV predictor of outcome, and propranolol therapy independently predicted outcome. In summary, after acute myocardial infarction, propranolol therapy improves recovery of parasympathetic tone, which correlates with improved outcome, and decreases morning sympathetic predominance. These findings may elucidate the mechanisms by which beta blockers decrease mortality and reduce the early morning risk of sudden death after acute myocardial infarction.

Racial differences in the use of cardiac procedures in patients with acute myocardial infarction.

BACKGROUND: Although numerous studies have shown that Black patients are less likely than White patients to undergo cardiac procedures, most of these studies did not consider clinical and demographic factors that could account for observed racial differences. OBJECTIVE: To determine if there are racial differences in the use of coronary angiography and revascularization procedures in patients with acute myocardial infarction, while controlling for multiple potentially important demographic and clinical variables. METHODS: In this retrospective cohort study, data were obtained from medical records of 642 consecutive Black and White patients with acute myocardial infarction at a regional cardiac referral center in southern New England. RESULTS: Blacks were significantly less likely than Whites to undergo angiography (p =.004; adjusted odds ratio =.36; 95% confidence interval =.18 -.72) and revascularization procedures (p =.006; adjusted odds ratio =.21; 95% confidence interval =.07 -.64). In the subgroup admitted directly to the hospital (n = 465), rather than transferred in from outlying hospitals, there were no racial differences in the use of angiography, but Blacks were significantly less likely to undergo revascularization procedures (p =.004; adjusted odds ratio =.18; 95% confidence interval =.06 -.58). CONCLUSIONS: In patients hospitalized with acute myocardial infarction, there are substantial racial differences in the use of angiography and revascularization procedures that cannot be explained by clinical or demographic factors.