9

Deepak Voora, Geoffrey S. Ginsburg

Pharmacogenetics uses genetic variation to identify subgroups of patients that may respond differently to a certain medication. Three principle classes of pharmacogenetic markers have emerged: 1) pharmacokinetic; 2) pharmacodynamic; and 3) underlying disease mechanism. Voora and Ginsburg review the association data for the major pharmacogenetic variants associated with commonly used cardiovascular medications: antiplatelet agents, warfarin, statins, beta-blockers, diuretics, and antiarrhythmic drugs. While ongoing clinical trials will determine if routine use of pharmacogenetic testing may be beneficial, the data today support pharmacogenetic testing for certain variants on an individualized, case-by-case basis.

21

Florence Dumas, Lindsay White, Benjamin A. Stubbs, Alain Cariou, Thomas D. Rea

Patients with therapeutic hypothermia (TH) and/or, in particular, percutaneous coronary intervention (PCI) resuscitated after out-of-hospital cardiac arrest (OHCA) can improve survival to hospital discharge, but less is known about long-term prognosis. Dumas and colleagues performed a cohort investigation of nearly 6,000 persons who received emergency medical service-attempted resuscitation, 17% of whom were discharged alive from the hospital. Of those discharged alive, PCI was performed in 38% and TH in 26%. The 5-year survival was significantly higher in those treated with PCI (79% vs. 54%), and in those treated with TH (78% vs. 60%) in this nonrandomized cohort with similar results after multivariable adjustment. These findings suggest that both PCI and TH improve long-term survival after OHCA.

28

Saswata Deb, Eric A. Cohen, Steve K. Singh, Dai Une, Andreas Laupacis, Stephen E. Fremes, for the RAPS Investigators

Deb and colleagues present their findings of radial and saphenous vein graft occlusion rates >5 years after coronary artery bypass surgery (CABG). A total of 510 patients undergoing CABG, with 3-vessel disease were within-patient randomization; the radial artery was randomized to either the right or circumflex territory, and a saphenous vein graft (SVG) was used for the other territory. At a mean of 7.8 years after surgery, the frequency of functional graft occlusion was lower in radial arteries compared with SVGs (12% vs. 20%). Radial artery conduits are less likely than SVGs to be occluded more than 5 years after surgery.

36

Todd Dardas, Nahush A. Mokadam, Francis Pagani, Keith Aaronson, Wayne C. Levy

Patients with left ventricular assist devices (LVAD) are historically given 30 days of elective status 1A time. Dardas and colleagues analyzed the Scientific Registry of Transplant Recipients database to determine if this still makes sense given the improved outcomes with LVAD. Status 1A registrants supported with dual inotropes and right heart monitoring had a higher risk of adverse events when compared to those supported with implanted LVADs using elective 1A time. The odds of receiving a transplant were higher for those with implanted LVADs (odds ratio: 1.5) compared with dual-inotrope and intra-aortic balloon pump support. These results suggest that the historic allowance for 30 days of elective status 1A time after LVAD should be reconsidered given their comparably low risk of death or being delisted because they are too ill.

44

Jeffrey J. Teuteberg, Greg A. Ewald, Robert M. Adamson, Katherine Lietz, Leslie W. Miller, Antone J. Tatooles, Robert L. Kormos, Kartik S. Sundareswaran, David J. Farrar, Joseph G. Rogers

The Destination Therapy Risk Score (DTRS) was developed from retrospective data for the pulsatile-flow HeartMate XVE (Thoratec Corporation, Pleasanton, California) left ventricular assist device (LVAD) implanted as destination therapy (DT). Teuteberg and colleagues tested the utility of the DTRS for predicting 90-day in-hospital mortality, its original application, and long-term mortality in patients receiving newer generation continuous flow LVADs. The risk of 90-day mortality was more than 2-fold higher in subjects with a high DTRS (>16) compared with the low risk group. However, area under the receiver-operating characteristic curve analysis showed only modest discriminatory ability. The DTRS was predictive of 2-year survival in patients implanted for DT but not for bridge to transplantation. These data suggest the need for a more contemporary risk assessment score.

Editorial Comment: Sean P. Pinney, page52

54

Laurent Pison, Mark La Meir, Jurren van Opstal, Yuri Blaauw, Jos Maessen, Harry J. Crijns

The combination of a transvenous endocardial approach and a thoracoscopic epicardial approach in a single atrial fibrillation (AF) ablation procedure has the potential to result in better outcomes then either procedure alone. Pison and colleagues studied the feasibility, safety, and clinical outcomes up to 1 year for 26 patients undergoing a combined simultaneous thoracoscopic and transvenous AF ablation. There were no procedural complications. In 23% of the patients, the epicardial lesions were not transmural, and endocardial touch-up was necessary. A combined transvenous endocardial and thoracoscopic epicardial ablation procedure for AF, is a feasible and safe procedure with a single-procedure success rate of 83% at 1 year.

Editorial Comment: Hugh Calkins, page62

64

Thierry Bove, Stefaan Bouchez, Stefan De Hert, Patrick Wouters, Filip De Somer, Daniel Devos, Pamela Somers, Guido Van Nooten

Bove and colleagues developed an experimental model in growing pigs, to study the acute and chronic physiological effects of surgical right ventricular outflow tract (RVOT) reconstruction. In the pulmonary valve insufficiency (PI) group, an isolated pulmonary valve insufficiency was created by excision of 1 pulmonary vein leaflet through a transverse pulmonary arteriotomy. In the infundibular dysfunction (INF) group, INF was obtained by infundibulotomy and closure with a polytetrafluorethylene patch. The transannular patch (TAP) third group, had both interventions. In animals with PI, pulmonary regurgitant fraction progressed more in presence of concomitant INF with higher rates of decreased ejection fraction after 3 months. Systolic indices showed acute impairment of right ventricular contractility in all treatment groups, but more in animals with infundibular scarring (INF and TAP). These findings support the adoption of a RVOT-sparing strategy to treat tetralogy of Fallot.

72

Michael S. Lauer

While mistaking randomness for cohesive stories may seem innocent enough when talking about professional basketball, Tversky's analysis revealed a truth about human psychology that has far reaching implications. People are resistant to ascribe unexpected observations to random chance and much prefer to tell stories.