Serial Assessment of Coronary Flow Reserve by Rubidium-82 Positron Emission Tomography Predicts Mortality in Heart Transplant Recipients.

OBJECTIVES: This study aimed to evaluate the long-term prognostic value of serial assessment of coronary flow reserve (CFR) by rubidium Rb 82 (82Rb) positron emission tomography (PET) in heart transplantation (HT) patients. BACKGROUND: Cardiac allograft vasculopathy is a major determinant of late mortality in HT recipients. The long-term prognostic value of serial CFR quantification by PET imaging in HT patients is unknown. METHODS: A total of 89 patients with history of HT (71% men, 7.0 ± 5.7 years post-HT, age 57 ± 11 years) scheduled for dynamic rest and stress (dipyridamole) 82Rb PET between March 1, 2008 and July 31, 2009 (PET-1) were prospectively enrolled in a single-center study. PET myocardial perfusion studies were reprocessed using U.S. Food and Drug Administration-approved software (Corridor 4DM, version 2017) for calculation of CFR. Follow-up PET (PET-2) imaging was performed in 69 patients at 1.9 ± 0.3 years following PET-1. Patients were categorized based on CFR values considering CFR ≤1.5 as low and CFR >1.5 as high CFR. RESULTS: Forty deaths occurred during the median follow-up time of 8.6 years. Low CFR at PET-1 was associated with a 2.77-fold increase in all-cause mortality (95% confidence interval [CI]: 1.34 to 5.74; p = 0.004). CFR decreased over time in patients with follow-up imaging (PET-1: 2.11 ± 0.74 vs. PET-2: 1.81 ± 0.61; p = 0.003). Twenty-five patients were reclassified based on PET-1 and PET-2 (high to low CFR: n = 18, low to high CFR: n = 7). Overall survival was similar in patients reclassified from high to low as patients with low to low CFR, whereas patients reclassified from low to high had similar survival as patients with high to high CFR. In multivariate Cox regression of patients with PET-2, higher baseline CFR (hazard ratio [HR] for a 0.73 unit (one SD) increase: 0.36, 95% CI: 0.16 to 0.82) and reduction in CFR from PET-1 to PET-2 (HR for a 0.79 unit (one SD) decrease: 1.50 to 7.84) were independent predictors of all-cause mortality. CONCLUSIONS: Serial assessment of CFR by 82Rb PET independently predicts long-term mortality in HT patients.

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.

Depressed autonomic nervous system function in African Americans and individuals of lower social class: a potential mechanism of race- and class-related disparities in health outcomes.

BACKGROUND: Both race and social class influence cardiovascular outcomes, through mechanisms not yet fully understood. Minority race and lower social class are sources of chronic stress, which can alter autonomic nervous system function. Heart rate variability (HRV), a measure of autonomic function, is also an important predictor of cardiovascular outcomes. METHODS: To determine whether minority race/ethnicity and lower social class are associated with depressed HRV, we prospectively collected data on sociodemographic, clinical, psychological, and behavioral factors by survey in 360 outpatients undergoing ambulatory electrocardiographic monitoring. Heart rate variability (24-hour) was measured by frequency domain analysis. RESULTS: In unadjusted analysis, African Americans had lower HRV than whites, and individuals of lower social class as measured by education, occupation, and income had lower HRV than those of higher class. In multivariable analysis, both race and social class were independent predictors of ultralow frequency power after controlling for clinical and psychological factors. African Americans were 3.45 (95% CI 1.74-6.98, P = .0004) times as likely as whites to have depressed HRV (ultralow frequency power, lowest tertile), and non-college graduates 2.94 (95% CI, 1.71-5.14, P = .0001) times as likely as college graduates to have depressed HRV. CONCLUSIONS: Heart rate variability is lower in African Americans and individuals of lower social class, independent of the effects of measured clinical, psychological, or behavioral factors. This suggests that the adverse effects of minority race and lower social class on cardiovascular outcomes may be mediated by dysregulation of autonomic function.

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.