Jennifer T. Thibodeau

Relationship of Right- to Left-Sided Ventricular Filling Pressures in Advanced Heart Failure Insights From the ESCAPE Trial

Background—Although right atrial pressure (RAP) and pulmonary capillary wedge pressure (PCWP) are correlated in heart failure, in a sizeable minority of patients, the RAP and PCWP are not tightly coupled. The basis of this variability in the RAP/PCWP ratio, and whether it conveys prognostic value, is not known. Methods and Results—We analyzed the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial database. Baseline characteristics, including echocardiographic assessment of right ventricular (RV) structure and function, and invasively measured hemodynamic parameters, were compared among tertiles of the RAP/PCWP ratio. Multivariable Cox proportional hazard models assessed the association of RAP/PCWP ratio with the primary ESCAPE outcome (6-month death or hospitalization [days]) adjusting for systolic blood pressure, blood urea nitrogen, 6-minute walk distance, and PCWP. The RAP/PCWP tertiles were 0.27 to 0.4 (tertile 1); 0.41 to 0.615 (tertile 2), and 0.62 to 1.21 (tertile 3). Increasing RAP/PCWP was associated with increasing median right atrial area (23, 26, 29 cm2, respectively; P<0.005), RV area in diastole (21, 27, 27 cm2, respectively; P<0.005), and pulmonary vascular resistance (2.4, 2.9, 3.6 woods units, respectively; P=0.003), and lower RV stroke work index (8.6, 8.4, 5.5 g·m/m2 per beat, respectively; P<0.001). RAP/PCWP ratio was associated with death or hospitalization within 6 months (hazard ratio, 1.16 [1, 1.4]; P<0.05). Conclusions—Increased RAP/PCWP ratio was associated with higher pulmonary vascular resistance, reduced RV function (manifest as a larger right atrium and ventricle and lower RV stroke work index), and an increased risk of adverse outcomes in patients with advanced heart failure.

Inaccuracy of Estimated Resting Oxygen Uptake in the Clinical Setting

Background— The Fick principle (cardiac output = oxygen uptake ( O2)/systemic arterio-venous oxygen difference) is used to determine cardiac output in numerous clinical situations. However, estimated rather than measured O2 is commonly used because of complexities of the measurement, though the accuracy of estimation remains uncertain in contemporary clinical practice. Methods and Results— From 1996 to 2005, resting O2 was measured via the Douglas bag technique in adult patients undergoing right heart catheterization. Resting O2 was estimated by each of 3 published formulae. Agreement between measured and estimated O2 was assessed overall, and across strata of body mass index, sex, and age. The study included 535 patients, with mean age 55 yrs, mean body mass index 28.4 kg/m2; 53% women; 64% non-white. Mean (±standard deviation) measured O2 was 241 ± 57 ml/min. Measured O2 differed significantly from values derived from all 3 formulae, with median (interquartile range) absolute differences of 28.4 (13.1, 50.2) ml/min, 37.7 (19.4, 63.3) ml/min, and 31.7 (14.4, 54.5) ml/min, for the formulae of Dehmer, LaFarge, and Bergstra, respectively (P<0.0001 for each). The measured and estimated values differed by >25% in 17% to 25% of patients depending on the formula used. Median absolute differences were greater in severely obese patients (body mass index > 40 kg/m2), but were not affected by sex or age. Conclusions— Estimates of resting O2 derived from conventional formulae are inaccurate, especially in severely obese individuals. When accurate hemodynamic assessment is important for clinical decision-making, O2 should be directly measured.

Utilization of Cardiac Computed Tomography Angiography for the Diagnosis of Left Ventricular Assist Device Thrombosis

The use of left ventricular assist devices (LVADs) in the management of advanced heart failure has grown substantially in recent years, with implantation of these devices increasing 10-fold since the approval of a continuous-flow device for destination therapy in January 2010. With the significant increase in use of this technology comes the potential for an increased incidence of complications associated with these devices. One such complication that can be fatal if not urgently recognized is device thrombosis, which has been reported to occur in approximately 1% of patients receiving the HeartMate II LVAD.1 Cardiologists, radiologists, and other health care professionals must become increasingly more adept …

High-Sensitivity Cardiac Troponin I Assay to Screen for Acute Rejection in Patients With Heart Transplant

Background—A noninvasive biomarker that could accurately diagnose acute rejection (AR) in heart transplant recipients could obviate the need for surveillance endomyocardial biopsies. We assessed the performance metrics of a novel high-sensitivity cardiac troponin I (cTnI) assay for this purpose. Methods and Results—Stored serum samples were retrospectively matched to endomyocardial biopsies in 98 cardiac transplant recipients, who survived ≥3 months after transplant. AR was defined as International Society for Heart and Lung Transplantation grade 2R or higher cellular rejection, acellular rejection, or allograft dysfunction of uncertain pathogenesis, leading to treatment for presumed rejection. cTnI was measured with a high-sensitivity assay (Abbott Diagnostics, Abbott Park, IL). Cross-sectional analyses determined the association of cTnI concentrations with rejection and International Society for Heart and Lung Transplantation grade and the performance metrics of cTnI for the detection of AR. Among 98 subjects, 37% had ≥1 rejection episode. cTnI was measured in 418 serum samples, including 35 paired to a rejection episode. cTnI concentrations were significantly higher in rejection versus nonrejection samples (median, 57.1 versus 10.2 ng/L; P<0.0001) and increased in a graded manner with higher biopsy scores (Ptrend<0.0001). The c-statistic to discriminate AR was 0.82 (95% confidence interval, 0.76–0.88). Using a cut point of 15 ng/L, sensitivity was 94%, specificity 60%, positive predictive value 18%, and negative predictive value 99%. Conclusions—A high-sensitivity cTnI assay seems useful to rule out AR in cardiac transplant recipients. If validated in prospective studies, a strategy of serial monitoring with a high-sensitivity cTnI assay may offer a low-cost noninvasive strategy for rejection surveillance.

Relationship of Right- to Left-Sided Ventricular Filling Pressures in Advanced Heart FailureClinical Perspective

Background—Although right atrial pressure (RAP) and pulmonary capillary wedge pressure (PCWP) are correlated in heart failure, in a sizeable minority of patients, the RAP and PCWP are not tightly coupled. The basis of this variability in the RAP/PCWP ratio, and whether it conveys prognostic value, is not known. Methods and Results—We analyzed the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial database. Baseline characteristics, including echocardiographic assessment of right ventricular (RV) structure and function, and invasively measured hemodynamic parameters, were compared among tertiles of the RAP/PCWP ratio. Multivariable Cox proportional hazard models assessed the association of RAP/PCWP ratio with the primary ESCAPE outcome (6-month death or hospitalization [days]) adjusting for systolic blood pressure, blood urea nitrogen, 6-minute walk distance, and PCWP. The RAP/PCWP tertiles were 0.27 to 0.4 (tertile 1); 0.41 to 0.615 (tertile 2), and 0.62 to 1.21 (tertile 3). Increasing RAP/PCWP was associated with increasing median right atrial area (23, 26, 29 cm2, respectively; P<0.005), RV area in diastole (21, 27, 27 cm2, respectively; P<0.005), and pulmonary vascular resistance (2.4, 2.9, 3.6 woods units, respectively; P=0.003), and lower RV stroke work index (8.6, 8.4, 5.5 g·m/m2 per beat, respectively; P<0.001). RAP/PCWP ratio was associated with death or hospitalization within 6 months (hazard ratio, 1.16 [1, 1.4]; P<0.05). Conclusions—Increased RAP/PCWP ratio was associated with higher pulmonary vascular resistance, reduced RV function (manifest as a larger right atrium and ventricle and lower RV stroke work index), and an increased risk of adverse outcomes in patients with advanced heart failure.

A Sensitive Cardiac Troponin I Assay to Screen for Acute Rejection in Heart Transplant Patients

Background—A noninvasive biomarker that could accurately diagnose acute rejection (AR) in heart transplant recipients could obviate the need for surveillance endomyocardial biopsies. We assessed the performance metrics of a novel high-sensitivity cardiac troponin I (cTnI) assay for this purpose. Methods and Results—Stored serum samples were retrospectively matched to endomyocardial biopsies in 98 cardiac transplant recipients, who survived ≥3 months after transplant. AR was defined as International Society for Heart and Lung Transplantation grade 2R or higher cellular rejection, acellular rejection, or allograft dysfunction of uncertain pathogenesis, leading to treatment for presumed rejection. cTnI was measured with a high-sensitivity assay (Abbott Diagnostics, Abbott Park, IL). Cross-sectional analyses determined the association of cTnI concentrations with rejection and International Society for Heart and Lung Transplantation grade and the performance metrics of cTnI for the detection of AR. Among 98 subjects, 37% had ≥1 rejection episode. cTnI was measured in 418 serum samples, including 35 paired to a rejection episode. cTnI concentrations were significantly higher in rejection versus nonrejection samples (median, 57.1 versus 10.2 ng/L; P<0.0001) and increased in a graded manner with higher biopsy scores (Ptrend<0.0001). The c-statistic to discriminate AR was 0.82 (95% confidence interval, 0.76–0.88). Using a cut point of 15 ng/L, sensitivity was 94%, specificity 60%, positive predictive value 18%, and negative predictive value 99%. Conclusions—A high-sensitivity cTnI assay seems useful to rule out AR in cardiac transplant recipients. If validated in prospective studies, a strategy of serial monitoring with a high-sensitivity cTnI assay may offer a low-cost noninvasive strategy for rejection surveillance.

High early event rates in patients with questionable eligibility for advanced heart failure therapies: Results from the Medical Arm of Mechanically Assisted Circulatory Support (Medamacs) Registry

BACKGROUND The prognosis of ambulatory patients with advanced heart failure (HF) who are not yet inotrope dependent and implications for evaluation and timing for transplant or destination therapy with a left ventricular assist device (DT-LVAD) are unknown. We hypothesized that the characteristics defining eligibility for advanced HF therapies would be a primary determinant of outcomes in these patients. METHODS Ambulatory patients with advanced HF (New York Heart Association class III-IV, Interagency Registry for Mechanically Assisted Circulatory Support profiles 4-7) were enrolled across 11 centers from May 2013 to February 2015. Patients were stratified into 3 groups: likely transplant eligible, DT-LVAD eligible, and ineligible for both transplant and DT-LVAD. Clinical characteristics were collected, and patients were prospectively followed for death, transplant, and left ventricular assist device implantation. RESULTS The study enrolled 144 patients with a mean follow-up of 10 ± 6 months. Patients in the ineligible cohort (n = 43) had worse congestion, renal function, and anemia compared with transplant (n = 51) and DT-LVAD (n = 50) eligible patients. Ineligible patients had higher mortality (23.3% vs 8.0% in DT-LVAD group and 5.9% in transplant group, p = 0.02). The differences in mortality were related to lower rates of transplantation (11.8% in transplant group vs 2.0% in DT-LVAD group and 0% in ineligible group, p = 0.02) and left ventricular assist device implantation (15.7% in transplant group vs 2.0% in DT-LVAD group and 0% in ineligible group, p < 0.01). CONCLUSIONS Ambulatory patients with advanced HF who were deemed ineligible for transplant and DT-LVAD had markers of greater HF severity and a higher rate of mortality compared with patients eligible for transplant or DT-LVAD. The high early event rate in this group emphasizes the need for timely evaluation and decision making regarding lifesaving therapies.

Sirolimus use and incidence of venous thromboembolism in cardiac transplant recipients

Sirolimus is an immunosuppressive agent increasingly used in cardiac transplant recipients in the setting of allograft vasculopathy or worsening renal function. Recently, sirolimus has been associated with increased risk of venous thromboembolism (VTE) in lung transplant recipients. To investigate whether this association is also present in cardiac transplant recipients, we retrospectively reviewed the charts of 67 cardiac transplant recipients whose immunosuppressive regimen included sirolimus and 134 matched cardiac transplant recipients whose regimen did not include sirolimus. Rates of VTE were compared. Multivariable Cox proportional hazards models tested the association of sirolimus use with VTE. A higher incidence of VTE was seen in patients treated with vs. without sirolimus (8/67 [12%] vs. 9/134 [7%], log‐rank statistic: 4.66, p = 0.03). Lower body mass index (BMI) and total cholesterol levels were also associated with VTE (p < 0.05). The association of sirolimus with VTE persisted when adjusting for BMI (hazard ratio [95% confidence interval]: 2.96 [1.13, 7.75], p = 0.03) but not when adjusting for total cholesterol (p = 0.08). These data suggest that sirolimus is associated with an increased risk of VTE in cardiac transplant recipients, a risk possibly mediated through comorbid conditions. Larger, more conclusive studies are needed. Until such studies are completed, a heightened level of awareness for VTE in cardiac transplant recipients treated with sirolimus appears warranted.

Health insurance as a requirement to undergo cardiac transplantation: A national survey of transplant program practices

BACKGROUND Recent limitations in Medicaid coverage of transplantation in Arizona jeopardized transplantation of potential recipients in that state and called attention to financial barriers inherent in the present organ allocation system. Policies of cardiac transplant centers regarding insurance requirements for transplantation have not been previously assessed. We sought to determine the policies of adult cardiac transplant programs nationwide regarding insurance requirements for evaluation and listing for cardiac transplantation. METHODS From December 15, 2008 to November 16, 2010, all active adult cardiac transplant programs in the United States were surveyed regarding insurance requirements for evaluation and listing for cardiac transplantation. RESULTS Surveys were completed by 62 of 101 programs, accounting for 71% of adult cardiac transplants in 2007. Only 2% of recipients were uninsured. Insurance was required by 48% of programs to evaluate and 84% to list for transplantation. For uninsured patients, 81% of programs required a large amount of money upfront (median,

Bendopnea and risk of adverse clinical outcomes in ambulatory patients with systolic heart failure.

200,000; interquartile range,