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ACC 2013: Highlights of Interest to ISHLT Members


Eugene DePasquale
Clinical Instructor
Ahmanson-UCLA Cardiomyopathy Center
Mechanical Circulatory Support and Heart Transplantation Program
edepasquale@mednet.ucla.edu

Richard Cheng
Fellow in Advanced Heart Failure and Transplant Cardiology
Ahmanson-UCLA Cardiomyopathy Center
Mechanical Circulatory Support and Heart Transplantation Program
rcheng@mednet.ucla.edu

Leigh Reardon
Clinical Instructor
Pediatric Cardiology
Ahmanson-UCLA Adult Congenital Heart Disease Center
lreardon@mednet.ucla.edu



The 2013 Scientific Sessions of the American College of Cardiology were held in San Francisco, CA from March 9-12, 2013. The sheer size of the meeting made it challenging even for ISHLT members to attend all sessions relevant to Advanced Heart Failure and Transplantation. To assist in summarizing important studies presented at this year's meeting, I have asked other ISHLT members to help assemble a list of presentations of significant interest to ISHLT members. My thanks to Richard Cheng and Leigh Reardon for helping to compile this list of highlights.

Three late breaking clinical trial presentations have the potential to significantly impact the care of patients with advanced heart disease including:

  1. RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction): This randomized trial, conducted at 26 centers in the United States and Canada, compared the effect of phosphodiesterase-5 inhibitor sildenafil to placebo on exercise capacity and clinical status in heart failure with preserved ejection fraction in 216 stable outpatients with heart failure. Sildenafil was administered orally at 20 mg three times daily for 12 weeks followed by 60 mg three times daily for 12 weeks. At 24 weeks, there was no benefit in regards to peak oxygen consumption and 6-minute walk distance. The RELAX study, therefore does not support the use of sildenafil in heart failure with preserved ejection fraction patients. This study has been subsequently published in the Journal of the American Medical Association (JAMA 2013; 309(12):1268-1277).
  2. RED-HF (Reduction of Events by Darbepoetin Alfa in Heart Failure): The RED-HF study compared the use of darbepoetin alfa and placebo in 2278 patients with systolic heart failure and mild-to-moderate anemia (hemoglobin level, 9.0 to 12.0 g per deciliter). The primary outcome, a composite of death from any cause or hospitalization from worsening heart failure, was met in 50.7% of the darbopoetin alfa group compared to 49.5% of the placebo group (hazard ratio in the darbopoetin alfa group 1.01; 95% confidence interval, 0.90 to 1.13; P=0.87). Thromboembolic events were significantly higher in the treatment group (13.5% vs 10.0%, P=0.01). The RED-HF study does not support the use of darbopoetin alfa in patients with systolic heart failure and mild-to-moderate anemia. This study has been subsequently published in the New England Journal of Medicine (NEJM 2013; 368:1210-1219).
  3. ASTRONAUT (Aliskiren Trial on Acute Heart Failure Outcomes): This study sought to assess whether aliskiren, a direct renin inhibitor, would reduce the rate of cardiovascular death or heart failure rehospitalizations compared to placebo in heart failure with reduced ejection fraction when added to standard therapy in 1639 patients. There was no difference in heart failure rehospitalizations at 6 or 12 months. In addition, the rates of hyperkalemia, hypotension and renal impairment/failure were higher in the aliskiren group compared with placebo. The ASTRONAUT study does not support the addition of aliskiren to standard therapy, failing to reduce cardiovascular death or heart failure rehospitalization at 6 or 12 months after discharge.

Additional presentations of interest to ISHLT members included the following:

  1. Lactate dehydrogenase is Superior to Serum-Free Hemoglobin as a Marker of Pump Thrombosis in Left Ventricular Assist Devices (P Shah, V Mehta, JA Cowger et al, Abstract 915-6): Shah and colleagues from the University of Michigan sought to establish a threshold value for lactate dehydrogenase (LDH) to identify clinically significant hemolysis in patients with LVADs (axial and centrifugal). Mean LDH was higher in axial LVADs than centrifugal devices. LDH was demonstrated to be a better marker of device thrombosis than serum-free haptoglobin (AUC=0.94 ± 0.01). In axial devices, a threshold of 573 resulted in 85% sensitivity and 95% specificity for pump thrombosis. This study demonstrates the clinical significance of LDH as a marker of clinically significant hemolysis.
  2. Survival of Heart Transplant Recipients Bridged with LVAD Support by Gender (E DePasquale, RK Cheng, et al, Abstract 915-3): DePasquale and colleagues from the University of California, Los Angeles examined gender differences of heart transplant recipients in those bridged with LVAD support. 3020 were identified from the UNOS registry and were demonstrated to have similar 1-, 3- and 5-year survival. There was a non-statistically significant trend towards increased LVAD utilization in women highlighting continued disparities in LVAD use in this population.
  3. Adult and Pediatric Congenital Heart Disease Hospitalizations in the United States (O'Leary, de Ferranti, Siddiqi et al, Abstract 1290-120): This observational study demonstrated that the annual adult congenital heart disease hospitalizations increased from 72,656 ± 5,258 in 2005 to 117,483 ± 8994 in 2009, representing 42.2% of congenital heart disease admissions in 2009. This has increased from 25.4% in 1998. The continued growth in adult congenital heart disease hospitalizations in the United States highlights the growing needs of this population. Increasingly, this challenging patient population will have increasing needs for advanced heart failure treatment, mechanical support and heart transplant.

Three studies at ACC assessed the use of off-pump as compared to on-pump coronary artery bypass graft (CABG) surgery. The two larger studies, German Off-Pump CABG in Elderly Trial (GOB-CABE), containing 2539 patients, and the 12-month follow-up to the Coronary Artery Bypass Grafting Surgery Off or On Pump Revascularization Study (CORONARY), containing 4752 patients, demonstrated no clear benefit to off-pump surgery. A smaller study, PRAGUE-6 appeared to show some benefit to off-pump surgery, but it contained only 206 patients.

  1. GOB-CABE: This study randomized 2539 patients aged 75 years or older undergoing elective first-time CABG to either off-pump or on-pump CABG. Mean age was 78.5 years. The primary composite endpoint was death, stroke, myocardial infarction (MI), repeat revascularization, or need for renal-replacement therapy. They demonstrated no significant difference in the primary endpoint for off-pump as compared to on-pump CABG at 30 days [OR 0.95, 95% CI 0.71-1.28, p = 0.74] or at 1 year [OR 0.93, 95% CI 0.76-1.16, p = 0.48]. Per protocol analysis excluding cross over patients also found no significant difference between the two arms. This study has been subsequently published in the New England Journal of Medicine (N Engl J Med 2013;368:1189-98).
  2. The CORONARY trial investigators provided 1 year follow up to their initial study (N Engl J Med 2013;368:1179-88) in which 4752 patients with coronary artery disease who were scheduled to undergo CABG were randomized to either off-pump or on-pump surgery at 79 centers in 19 countries. The primary endpoint was a composite of death, stroke, MI, and renal failure. One year follow up continued to demonstrate that there was no significant difference between the surgical approaches (HR 0.91, 95% CI 0.77-1.07, p = 0.24). Further, there was no difference in measures of quality of life or neurocognitive function at 1 year - however, there was significant loss of follow-up for the neurocognitive testing and as such this should be interpreted with caution (Lamy, Devereaux, Pogue, et al, Abstract 303-13).
  3. 3. The PRAGUE-6 study was a smaller study randomizing 206 high-risk patients with stable coronary artery disease, unstable angina, or acute myocardial infarction with EuroScore ≥ 6 to off-pump versus on-pump surgery. Mean age was 74 years, 62% of patients had recent myocardial infarction, and 11% of patients had LVEF < 30%. At 30 days, there was a significant reduction in the combined primary endpoint of death, MI, stroke, or new renal failure for off-pump compared to on-pump surgery [HR 0.41, 95% CI 0.19-0.91, p = 0.028]. These findings were mostly driven by a reduction in acute MI, without any significant difference in the individual endpoints of death, stroke, or renal failure.


Disclosure Statement: The authors have no conflicts of interest to disclose.