Daniel J. O'Rourke

Effect of Preoperative Pulmonary Hypertension on Outcomes in Patients With Severe Aortic Stenosis Following Surgical Aortic Valve Replacement

Pulmonary hypertension (PH) is prevalent in patients with aortic stenosis (AS); however, previous studies have demonstrated inconsistent results regarding the association of PH with adverse outcomes after aortic valve replacement (AVR). The goal of this study was to evaluate the effects of preoperative PH on outcomes after AVR. We performed a regional prospective cohort study using the Northern New England Cardiovascular Disease Study Group database to identify 1,116 consecutive patients from 2005 to 2010 who underwent AVR ± coronary artery bypass grafting for severe AS with a preoperative assessment of pulmonary pressures by right-sided cardiac catheterization. PH was defined as a mean pulmonary artery pressure of ≥25 mm Hg, with severity based on the pulmonary artery systolic pressure-mild, 35 to 44 mm Hg; moderate, 45 to 59 mm Hg; and severe, ≥60 mm Hg. We found that PH was present in 536 patients (48%). Postoperative acute kidney injury, low-output heart failure, and in-hospital mortality increased with worsening severity of PH. In multivariate logistic regression, severe PH was independently associated with postoperative acute kidney injury (adjusted odds ratio 4.1, 95% confidence interval [CI] 1.7 to 10, p = 0.002) and in-hospital mortality (adjusted odds ratio 6.9, 95% CI 2.5 to 19.1, p <0.001). There was a significant association between PH and decreased 5-year survival (adjusted log-rank p value = 0.006), with severe PH being associated with the poorest survival (adjusted hazard ratio 2.4, 95% CI 1.3 to 4.2, p = 0.003). In conclusion, severe PH in patients with severe AS is associated with increased rates of in-hospital adverse events and decreased 5-year survival after AVR.

Effect of Genetic Variants, Especially CYP2C9 and VKORC1, on the Pharmacology of Warfarin

The genes encoding the cytochrome P450 2C9 enzyme (CYP2C9) and vitamin K-epoxide reductase complex unit 1 (VKORC1) are major determinants of anticoagulant response to warfarin. Together with patient demographics and clinical information, they account for approximately one-half of the warfarin dose variance in individuals of European descent. Recent prospective and randomized controlled trial data support pharmacogenetic guidance with their use in warfarin dose initiation and titration. Benefits from pharmacogenetics-guided warfarin dosing have been reported to extend beyond the period of initial dosing, with supportive data indicating benefits to at least 3 months. The genetic effects of VKORC1 and CYP2C9 in African and Asian populations are concordant with those in individuals of European ancestry; however, frequency distribution of allelic variants can vary considerably between major populations. Future randomized controlled trials in multiethnic settings using population-specific dosing algorithms will allow us to further ascertain the generalizability and cost-effectiveness of pharmacogenetics-guided warfarin therapy. Additional genome-wide association studies may help us to improve and refine dosing algorithms and potentially identify novel biological pathways.

Results of Directional Coronary Atherectomy in Northern New England

The role of directional coronary atherectomy (DCA) in interventional cardiology remains uncertain. We report the Northern New England regional experience with DCA from 1991 to 1994. Data were collected on 11,178 patients having had an intervention on a single lesion in a single vessel (798 DCAs; 10,380 percutaneous transluminal angioplasties [PTCA]). The use of DCA increased from 1.8% of interventions in 1991 to 10% in 1994. Compared with PTCA, DCA patients were younger, more often men, had more 1-vessel disease and more coronary artery bypass surgery (CABG). DCA was more often used in the left anterior descending artery, in vein grafts, for restenoses, for subtotal occlusions, and with type A lesions. Angiographic success (96.7%) and clinical success (93%) were good. Adverse events were rare: mortality 0.9%, emergent CABG 2.2%, nonfatal myocardial infarction 2.8%. After adjusting for case-mix, there was no difference between DCA and PTCA for in-hospital mortality (odds ratio [OR] = 1.03, 95% confidence interval [CI] 0.44 to 2.43, p = 0.95) or need for emergent CABG (OR = 1.27, 95% CI 0.77 to 2.10, p = 0.34). Atherectomy patients were more likely to have a nonfatal myocardial infarction (OR = 2.0, 95% CI 1.26 to 3.20, p <0.01), to sustain an injury to the femoral or brachial artery (OR = 2.89, 95% CI 1.52 to 5.51, p <0.01), and to have a clinically successful procedure (OR = 1.37, 95% CI 1.01 to 1.88, p = 0.05). Our results support the relative safety and effectiveness of DCA as its use disseminated into the region.

SEVERE PULMONARY HYPERTENSION IS AN INDEPENDENT PREDICTOR OF IN-HOSPITAL MORTALITY AND ACUTE KIDNEY INJURY AFTER AORTIC VALVE REPLACEMENT FOR SEVERE AORTIC STENOSIS

Authors: David Zlotnick, Michelle L. Ouellette, Joseph DeSimone, Joseph D. Schmoker, Bruce Leavitt, David Malenka, Yvon Baribeau, Robert Helm, Anthony DiScipio, Gerald L. Sardella, Louis Russo, John D. Klemperer, Reed D. Quinn, Donato Sisto, Donald Likosky, Elaine M. Olmstead, Daniel O’Rourke, The Northern New England Cardiovascular Disease StudyGroup, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA, Northern New England Cardiovascular Disease Study Group, Lebanon, NH, USA