Berlin Heart

• Circulation 2013;127:1702-11
• Pediatric Cardiology

Berlin Heart EXCOR Pediatric Ventricular Assist Device for Bridge to Heart Transplantation in US Children

1. Christopher S. Almond, MD, MPH*; et al.

1. From Boston Children’s Hospital, Boston, MA (C.S.A.); Cincinnati Children’s Hospital, Cincinnati, OH (D.L.M.); Heart and Vascular Institute and Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH (E.H.B., L.T.); Riley Hospital for Children, Indianapolis, IN (M.W.T.); Arkansas Children’s Hospital, Little Rock (M.I.); Stollery Children’s Hospital, Edmonton, AB, Canada (M.P.M., H.B.); Vanderbilt University Medical Center, Nashville, TN (L.C.J.); C.S. Mott Children’s Hospital, Ann Arbor, MI (E.J.D.); Children’s Hospital of Philadelphia, Philadelphia, PA (C.R.); Children’s Healthcare of Atlanta, Atlanta, GA (K.R.K.); University of Alabama at Birmingham, Birmingham (W.H.); Berlin Heart, Inc, The Woodlands, TX (R.K., C.T.); Children’s Hospital and Regional Medical Center Seattle, Seattle, WA (G.A.C.); University of Minnesota, Minneapolis (J.D.S.L.); Mount Sinai, New York, NY (K.N.); Medical College of Wisconsin, Milwaukee (R.A.N.); Children’s Hospital of Michigan, Detroit (H.L.W.); Mattel Children’s Hospital UCLA, Los Angeles, CA (B.R.); Children’s Hospital of Pittsburgh, Pittsburgh, PA (P.D.W.); Stanford University, Palo Alto, CA (O.R.); Children’s Medical Center Dallas, Dallas, TX (K.J.G.); Children’s Hospital Colorado, Aurora (M.B.M.); University of Florida, Gainesville (M.S.B.); St. Louis Children’s Hospital, St. Louis, MO (C.E.C.); and The Hospital for Sick Children, Toronto, ON, Canada (T.H.). Dr Morales was formerly at the Texas Children’s Hospital, Houston.

1. Correspondence to Christopher S. Almond, MD, MPH, The Heart Center, Boston Children’s Hospital, Department of Pediatrics, Harvard Medical School, 300 Longwood Ave, Boston, MA 02115. E-mailchristopher.almond@childrens.harvard.edu

1. Abstract

Background—Recent data suggest that the Berlin Heart EXCOR Pediatric ventricular assist device is superior to extracorporeal membrane oxygenation for bridge to heart transplantation. Published data are limited to 1 in 4 children who received the device as part of the US clinical trial. We analyzed outcomes for all US children who received the EXCOR to characterize device outcomes in an unselected cohort and to identify risk factors for mortality to facilitate patient selection.

Methods and Results—This multicenter, prospective cohort study involved all children implanted with the Berlin Heart EXCOR Pediatric ventricular assist device (47 centers; May 2007 to Dec 2010). n = 204 children. Median duration of support was 40 days (range, 1–435 days). Survival at 12 months was 75%, including 64% who reached transplantation, 6% who recovered, and 5% who were alive on the device. Multivariable analysis identified lower weight, biventricular assist device support, and elevated bilirubin as risk factors for early mortality and bilirubin extremes and renal dysfunction as risk factors for late mortality. Neurological dysfunction occurred in 29% and was the leading cause of death.

Conclusions—Use of the Berlin Heart EXCOR has risen dramatically over the past decade. The EXCOR has emerged as a new treatment standard in the United States for pediatric bridge to transplantation. Three-quarters of children survived to transplantation or recovery; an important fraction experienced neurological dysfunction. Smaller patient size, renal dysfunction, hepatic dysfunction, and biventricular assist device use were associated with mortality, whereas extracorporeal membrane oxygenation before implantation and congenital heart disease were not.

PFO closure - North American Trial. No significant benefit. But...

ORIGINAL ARTICLE

NEJM - online first

Closure of Patent Foramen Ovale versus Medical Therapy after Cryptogenic Stroke

John D. Carroll, M.D., Jeffrey L. Saver, M.D., David E. Thaler, M.D., Ph.D., Richard W. Smalling, M.D., Ph.D., Scott Berry, Ph.D., Lee A. MacDonald, M.D., David S. Marks, M.D., and David L. Tirschwell, M.D. for the RESPECT Investigators

N Engl J Med 2013; 368:1092-1100March 21, 2013DOI: 10.1056/NEJMoa1301440

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BACKGROUND

Whether closure of a patent foramen ovale is effective in the prevention of recurrent ischemic stroke in patients who have had a cryptogenic stroke is unknown. We conducted a trial to evaluate whether closure is superior to medical therapy alone in preventing recurrent ischemic stroke or early death in patients 18 to 60 years of age.

METHODS

In this prospective, multicenter, randomized, event-driven trial, we randomly assigned patients, in a 1:1 ratio, to medical therapy alone or closure of the patent foramen ovale. The primary results of the trial were analyzed when the target of 25 primary end-point events had been observed and adjudicated.

RESULTS

We enrolled 980 patients (mean age, 45.9 years) at 69 sites. The medical-therapy group received one or more antiplatelet medications (74.8%) or warfarin (25.2%). Treatment exposure between the two groups was unequal (1375 patient-years in the closure group vs. 1184 patient-years in the medical-therapy group, P=0.009) owing to a higher dropout rate in the medical-therapy group. In the intention-to-treat cohort, 9 patients in the closure group and 16 in the medical-therapy group had a recurrence of stroke (hazard ratio with closure, 0.49; 95% confidence interval [CI], 0.22 to 1.11; P=0.08). The between-group difference in the rate of recurrent stroke was significant in the prespecified per-protocol cohort (6 events in the closure group vs. 14 events in the medical-therapy group; hazard ratio, 0.37; 95% CI, 0.14 to 0.96; P=0.03) and in the as-treated cohort (5 events vs. 16 events; hazard ratio, 0.27; 95% CI, 0.10 to 0.75; P=0.007). Serious adverse events occurred in 23.0% of the patients in the closure group and in 21.6% in the medical-therapy group (P=0.65). Procedure-related or device-related serious adverse events occurred in 21 of 499 patients in the closure group (4.2%), but the rate of atrial fibrillation or device thrombus was not increased.

CONCLUSIONS

In the primary intention-to-treat analysis, there was no significant benefit associated with closure of a patent foramen ovale in adults who had had a cryptogenic ischemic stroke. However, closure was superior to medical therapy alone in the prespecified per-protocol and as-treated analyses, with a low rate of associated risks. (Funded by St. Jude Medical; RESPECT ClinicalTrials.gov number,NCT00465270.)

PFO closure did not result in reduction in recurrent embolic events - Europe, Canada, Brazil & Australia

ORIGINAL ARTICLE

NEJM - online first

Percutaneous Closure of Patent Foramen Ovale in Cryptogenic Embolism

Bernhard Meier, M.D., Bindu Kalesan, Ph.D., Heinrich P. Mattle, M.D., Ahmed A. Khattab, M.D., David Hildick-Smith, M.D., Dariusz Dudek, M.D., Grethe Andersen, M.D., Reda Ibrahim, M.D., Gerhard Schuler, M.D., Antony S. Walton, M.D., Andreas Wahl, M.D., Stephan Windecker, M.D., and Peter Jüni, M.D. for the PC Trial Investigators

N Engl J Med 2013; 368:1083-1091March 21, 2013DOI: 10.1056/NEJMoa1211716

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BACKGROUND

The options for secondary prevention of cryptogenic embolism in patients with patent foramen ovale are administration of antithrombotic medications or percutaneous closure of the patent foramen ovale. We investigated whether closure is superior to medical therapy.

METHODS

We performed a multicenter, superiority trial in 29 centers in Europe, Canada, Brazil, and Australia in which the assessors of end points were unaware of the study-group assignments. Patients with a patent foramen ovale and ischemic stroke, transient ischemic attack (TIA), or a peripheral thromboembolic event were randomly assigned to undergo closure of the patent foramen ovale with the Amplatzer PFO Occluder or to receive medical therapy. The primary end point was a composite of death, nonfatal stroke, TIA, or peripheral embolism. Analysis was performed on data for the intention-to-treat population.

RESULTS

The mean duration of follow-up was 4.1 years in the closure group and 4.0 years in the medical-therapy group. The primary end point occurred in 7 of the 204 patients (3.4%) in the closure group and in 11 of the 210 patients (5.2%) in the medical-therapy group (hazard ratio for closure vs. medical therapy, 0.63; 95% confidence interval [CI], 0.24 to 1.62; P=0.34). Nonfatal stroke occurred in 1 patient (0.5%) in the closure group and 5 patients (2.4%) in the medical-therapy group (hazard ratio, 0.20; 95% CI, 0.02 to 1.72; P=0.14), and TIA occurred in 5 patients (2.5%) and 7 patients (3.3%), respectively (hazard ratio, 0.71; 95% CI, 0.23 to 2.24; P=0.56).

CONCLUSIONS

Closure of a patent foramen ovale for secondary prevention of cryptogenic embolism did not result in a significant reduction in the risk of recurrent embolic events or death as compared with medical therapy. (Funded by St. Jude Medical; ClinicalTrials.gov number,NCT00166257.)

Mediterranean Diet Decreases CV events.

ORIGINAL ARTICLE
NEJM 2013 online first

Primary Prevention of Cardiovascular Disease with a Mediterranean Diet

Ramón Estruch, M.D., Ph.D., Emilio Ros, M.D., Ph.D., Jordi Salas-Salvadó, M.D., Ph.D., Maria-Isabel Covas, D.Pharm., Ph.D., Dolores Corella, D.Pharm., Ph.D., Fernando Arós, M.D., Ph.D., Enrique Gómez-Gracia, M.D., Ph.D., Valentina Ruiz-Gutiérrez, Ph.D., Miquel Fiol, M.D., Ph.D., José Lapetra, M.D., Ph.D., Rosa Maria Lamuela-Raventos, D.Pharm., Ph.D., Lluís Serra-Majem, M.D., Ph.D., Xavier Pintó, M.D., Ph.D., Josep Basora, M.D., Ph.D., Miguel Angel Muñoz, M.D., Ph.D., José V. Sorlí, M.D., Ph.D., José Alfredo Martínez, D.Pharm, M.D., Ph.D., and Miguel Angel Martínez-González, M.D., Ph.D. for the PREDIMED Study Investigators

February 25, 2013DOI: 10.1056/NEJMoa1200303

BACKGROUND

Observational cohort studies and a secondary prevention trial have shown an inverse association between adherence to the Mediterranean diet and cardiovascular risk. We conducted a randomized trial of this diet pattern for the primary prevention of cardiovascular events.

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METHODS

In a multicenter trial in Spain, we randomly assigned participants who were at high cardiovascular risk, but with no cardiovascular disease at enrollment, to one of three diets: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat). Participants received quarterly individual and group educational sessions and, depending on group assignment, free provision of extra-virgin olive oil, mixed nuts, or small nonfood gifts. The primary end point was the rate of major cardiovascular events (myocardial infarction, stroke, or death from cardiovascular causes). On the basis of the results of an interim analysis, the trial was stopped after a median follow-up of 4.8 years.

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RESULTS

A total of 7447 persons were enrolled (age range, 55 to 80 years); 57% were women. The two Mediterranean-diet groups had good adherence to the intervention, according to self-reported intake and biomarker analyses. A primary end-point event occurred in 288 participants. The multivariable-adjusted hazard ratios were 0.70 (95% confidence interval [CI], 0.54 to 0.92) and 0.72 (95% CI, 0.54 to 0.96) for the group assigned to a Mediterranean diet with extra-virgin olive oil (96 events) and the group assigned to a Mediterranean diet with nuts (83 events), respectively, versus the control group (109 events). No diet-related adverse effects were reported.