Interruprtions of Warfarin for procedures

Circulation: Cardiovascular Quality and Outcomes
2011;4(2):206-210

Guideline-Discordant Periprocedural Interruptions in Warfarin Therapy

Skolarus, Lesli E. MD, MS; Morgenstern, Lewis B. MD; Froehlich, James B. MD, MPH; Lisabeth, Lynda D. PhD; Brown, Devin L. MD, MS

Abstract

Background—: Periprocedural interruptions in warfarin therapy increase thromboembolic risks to patients and are not indicated for all procedures. We sought to determine the frequency and guideline concordance of periprocedural warfarin interruptions to inform a future educational intervention.

Methods and Results—: In October and November of 2009, an anonymous postal survey was sent to all patients followed for more than 1 year by the University of Michigan Anticoagulation service. Patients were asked how many times in the prior year they were requested to interrupt warfarin therapy for a medical or dental procedure or test and the specific indication for the requested interruption in warfarin therapy. A total of 1686 of 2133 (79%) subjects responded. The mean age of respondents was 69 years (SD=14 years). The majority were men (56%) and white (93%). Atrial fibrillation was the most common indication for warfarin therapy (n=966, 57%). At least 1 request to interrupt warfarin therapy in the prior year was given by 819 of 1648 (50%) respondents, including 481 of the 947 (51%) respondents taking warfarin for atrial fibrillation. Forty-eight percent of requests to interrupt warfarin among all respondents and 50% of requests to interrupt warfarin among those taking warfarin, specifically for atrial fibrillation, were for indications not supported by guideline statements.

Conclusions—: Periprocedural requests to interrupt warfarin therapy are common and are often discordant with current guidelines. Educational interventions may decrease risk of periprocedural thromboembolic complications.

Risk Categories in Cath Procedures

Circulation: Cardiovascular Interventions.
2011; 4: 188-194

Procedure-Type Risk Categories for Pediatric and Congenital Cardiac Catheterization

Lisa Bergersen, MD, MPH, Kimberlee Gauvreau, ScD, Audrey Marshall, MD, Jacqueline Kreutzer, MD, Robert Beekman, MD, Russel Hirsch, MD, Susan Foerster, MD, David Balzer, MD, Julie Vincent, MD, William Hellenbrand, MD, Ralf Holzer, MD, John Cheatham, MD, John Moore, MD, James Lock, MD and Kathy Jenkins, MD, MPH

Abstract

Background— The Congenital Cardiac Catheterization Project on Outcomes (C3PO) was established to develop outcome assessment methods for pediatric catheterization.

Methods and Results— Six sites have been recording demographic, procedural and immediate outcome data on all cases, using a web-based system since February 2007. A sample of data was independently audited for validity and data completeness. In 2006, participants categorized 84 procedure types into 6 categories by anticipated risk of an adverse event (AE). Consensus and empirical methods were used to determine final procedure risk categories, based on the outcomes: any AE (level 1 to 5); AE level 3, 4, or 5; and death or life-threatening event (level 4 or 5). The final models were then evaluated for validity in a prospectively collected data set between May 2008 and December 31, 2009. Between February 2007 and April 2008, 3756 cases were recorded, 558 (14.9%) with any AE; 226 (6.0%) level 3, 4, or 5; and 73 (1.9%) level 4 or 5. General estimating equations models using 6 consensus-based risk categories were moderately predictive of AE occurrence (c-statistics: 0.644, 0.664, and 0.707). The participant panel made adjustments based on the collected empirical data supported by clinical judgment. These decisions yielded 4 procedure risk categories; the final models had improved discrimination, with c-statistics of 0.699, 0.725, and 0.765. Similar discrimination was observed in the performance data set (n=7043), with c-statistics of 0.672, 0.708, and 0.721.

Conclusions— Procedure-type risk categories are associated with different complication rates in our data set and could be an important variable in risk adjustment models for pediatric catheterization.

Genetic diagnosis of Cardiomyopathies

Circulation: Cardiovascular Genetics.
2011; 4: 110-122

Targeted Next-Generation Sequencing for the Molecular Genetic Diagnostics of Cardiomyopathies

Benjamin Meder, MD*, Jan Haas, MS*, Andreas Keller, PhD, Christiane Heid, MS, Steffen Just, PhD, Anne Borries, MS, Valesca Boisguerin, PhD, Maren Scharfenberger-Schmeer, PhD, Peer Stähler;, Markus Beier, PhD, Dieter Weichenhan, PhD, Tim M. Strom, MD, Arne Pfeufer, MD, PhD, Bernhard Korn, PhD, Hugo A. Katus, MD and Wolfgang Rottbauer, MD
+ Author Affiliations

From the Department of Internal Medicine III (B.M., J.H., C.H., S.J., H.A.K., W.R.), University of Heidelberg; Biomarker Discovery Center (A.K.); febit biomed gmbh (A.B., V.B., P.S., M.B.); and German Cancer Research Center (DKFZ) (M.S.-S., D.W., B.K.), Heidelberg, Germany; Institute of Human Genetics (T.M.S.), Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Institute of Human Genetics (A.P.), Klinikum rechts der Isar, Technische Universität München, Munich, Germany; and Department of Internal Medicine II (W.R.), University of Ulm, Ulm, Germany.

Abstract

Background— Today, mutations in more than 30 different genes have been found to cause inherited cardiomyopathies, some associated with very poor prognosis. However, because of the genetic heterogeneity and limitations in throughput and scalability of current diagnostic tools up until now, it is hardly possible to genetically characterize patients with cardiomyopathy in a fast, comprehensive, and cost-efficient manner.

Methods and Results— We established an array-based subgenomic enrichment followed by next-generation sequencing to detect mutations in patients with hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). With this approach, we show that the genomic region of interest can be enriched by a mean factor of 2169 compared with the coverage of the whole genome, resulting in high sequence coverage of selected disease genes and allowing us to define the genetic pathogenesis of cardiomyopathies in a single sequencing run. In 6 patients, we detected disease-causing mutations, 2 microdeletions, and 4 point mutations. Furthermore, we identified several novel nonsynonymous variants, which are predicted to be harmful, and hence, might be potential disease mutations or modifiers for DCM or HCM.

Conclusions— The approach presented here allows for the first time a comprehensive genetic screening in patients with hereditary DCM or HCM in a fast and cost-efficient manner.

ACC 2011: On-X valve & INR

From Heartwire:

PROACT: Early results show high-risk patients do well with low warfarin and carbon valveApril 13, 2011 Reed Miller New Orleans - Preliminary results from the high-risk arm of PROACT presented at the American College of Cardiology (ACC) 2011 Scientific Sessions show the all-carbon On-X valve (On-X Life Technologies, Austin, TX) is safe with lower levels of anticoagulant therapy than normally prescribed to patients with mechanical aortic valves [1]. Primary investigator Dr John Puskas (Emory University, Atlanta, GA) presented early results from the high-risk aortic-valve-replacement arm of PROACT, the only arm of the trial that is fully enrolled. As hypothesized, patients with an On-X valve treated with lower-than-standard doses of aspirin and warfarin after three months on a standard regimen had the same composite rate of thromboembolism and hemorrhage as On-X patients who stayed on the standard regimen throughout the follow-up. On-X valve [Source: On-X Life Technologies] All 185 patients in the high-risk arm received an On-X valve as a replacement for a defective aortic valve and were considered to have a high potential for thrombotic or bleeding events. All patients were maintained with standard anticoagulation therapy for the first three months after surgery and then randomized into the low-anticoagulant group or the control group. The low-anticoagulant group was switched to a daily dose of either 81 or 325 mg of aspirin plus warfarin to achieve an INR target of 1.5 to 2.0. Patients randomized to the control group continued with standard anticoagulation therapy—aspirin and warfarin to achieve an INR of 2.0 to 3.5 throughout the trial, the target set in the ACC/AHA guidelines for treatment of patients with a replacement aortic valve. The average follow-up so far is about 16 months, with a total of 247 patient-years of data collected. Eventually, the investigators expect to collect 6000 patient-years of data. During the study period, five low-anticoagulant and four control patients died. The low-anticoagulant group had 2.5 bleeding events per patient-year, vs 4.4 per patient year in the control group, but the stroke rate was 1.3% per patient-year in the low-anticoagulant group vs 0.4% per patient-year in the control group. For the combined end point of stroke and thrombotic and bleeding events, the rates were 3.8% per patient-year in the low-anticoagulant group and 4.9% per patient-year in the control group. Puskas said that the goal of the study is to convince the FDA to let On-X label the valve as safe with lower doses of anticoagulation, thereby providing the durability of a mechanical valve with doses of anticoagulant drugs closer to those given tissue-valve recipients. And "one day we may be able to offer a durable mechanical heart valve with no blood thinner in selected patients," he said. The PROACT study, launched in 2006 at 40 centers, is also enrolling a lower-risk arm and a mitral-valve arm. The aortic-valve arm is comparing standard anticoagulant therapy with clopidogrel therapy in patients with the On-X aortic valve considered at relatively low risk for thrombotic or bleeding events. The mitral-valve arm is comparing anticoagulant therapy targeted to INRs of 2.0 to 2.5 vs standard anticoagulant therapy in patients with an On-X mitral valve. The company expects to complete the trial by 2014.Valve material reduces clot risk Puskas explained that patients with an On-X valve, which has been on the US market for about 10 years, may be able to get by with lower doses of anticoagulant because of the unique all-carbon material and design of the device. The On-X carbon material is a pure form of isotropic pyrolytic carbon created with a patented process that, unlike other carbon materials used for heart valves, does not require silicon alloying to ensure wear resistance. Earlier carbon valves were made out of carbon with about 8% silicon, because the technology did not exist to mill pure carbon thin enough to make a valve leaflet, Puskas explained. "When you polish pure carbon you can get an exceedingly smooth surface, to which platelets and blood don't really stick very much, but if you polish a silicon-carbon composite, the silicon over time tends to pit and leave very tiny irregularities in the surface." The valve's "trumpet-mouth end" guides blood through with a laminar—instead of turbulent—flow at a lower pressure gradient than most mechanical valves, preventing damage to the blood. The laminar flow also allows the leaflets inside the cylinder to close more quickly and to open more completely than leaflets in most valve designs, Puskas said. Because the leaflets close faster, they regurgitate less blood back through the valve, and "as a result of that lesser leak, the designers of the valve are able to be luxurious about intentionally allowing some leakage around the hinge points of the leaflets, and it's those hinge points where clotting can occur and the valve can stick," Puskas said. "So by designing leaflets that intentionally leak a little bit around the hinges, but close so quickly that the overall leakage is much less than in the predecessor valves, you can have your cake and eat it too. You have a valve that leaks very little, but leaks where you want it to leak; it washes the hinges to prevent clots from forming there." INR monitoring at home Puskas told heartwire that he expects one of the "important contributions of PROACT will be to show the superiority of home INR monitoring" vs periodic monitoring at the physician's office. On-X has provided all of the patients in the study with home INR monitoring so that they can keep continuous track of their blood's ability to clot and adjust the anticoagulant therapy accordingly. The Home INR Study (THINRS) found that weekly self-testing of INR levels did not significantly delay the time to a first stroke, major bleed, or death in patients on warfarin compared with monthly in-office testing with a higher-than-average level of clinical care, but home INR testing did help patients keep their INR within therapeutic range and improved patients' satisfaction with their anticoagulation therapy and quality of life. Puskas said that there is already evidence that patients whose INR varies widely are more prone to complications than patients who can keep their INR more stable, and he expects that the trial will be able to show that patients are better able to maintain a level INR if they can monitor it on their own without visiting their doctor. He said the trial will collect over 100 000 data points on home INR testing.

Cardiac lymphatics

Cardiac lymphatics in pigs (Deutsche Landrasse pigs):

Image from Vazques-Jimenez, JF. et al. Cannulation of the cardiac lymphatic system in swine. Eur J Cardiothorac Surg 2000;18:228-32. Reprint provided by Dr. M. Thapar. Read also the letters to the editor on this article.

Adult CHD: Transition from Adolescent to Adult care (AHA Scientific Statement)

Circulation 2011;123:1454-1485

Best Practices in Managing Transition to Adulthood for Adolescents With Congenital Heart Disease: The Transition Process and Medical and Psychosocial Issues

A Scientific Statement From the American Heart Association

Craig Sable, MD, FAHA, et al. on behalf of the American Heart Association Congenital Heart Defects Committee of the Council on Cardiovascular Disease in the Young, Council on Cardiovascular Nursing, Council on Clinical Cardiology, and Council on Peripheral Vascular Disease

	Introduction

Many children born with complex childhood illnesses that historically caused early death are now surviving into adulthood with the expectation of leading meaningful and productive lives. They will ultimately need to transition their care from pediatric to adult-centered care. Unfortunately, in the absence of structured programs to guide this transition, there is often delayed or inappropriate care, improper timing of the transfer of care, and undue emotional and financial stress on the patients, their families, and the healthcare system. At its worst, and as frequently happens now, patients are lost to appropriate follow-up. In fact, the number of adults with congenital heart disease (CHD) in the United States is rising exponentially and now exceeds 1 000 000.^1–7 At least half of these patients may have complex CHD. Fewer than 30% of adults with CHD are seen by appropriatespecialized providers. Fewer than 15% of these patients, who are seen in specialty adult CHD (ACHD) clinics, have CHD that is classified as severe.⁸ Thus, adolescents with CHD constitute a growing population of individuals for whom a well-planned and well-executed "transition process" is essential.

The goals of a formal transition program are to prepare young adults for transfer of care. It should provide uninterrupted health care that is patient centered, age and developmentally appropriate, flexible, and comprehensive. It should include age-appropriate education about medical conditions and promote skills in communication, decision making, self-care, and self-advocacy.^9–13 It should foster greater personal and medical independence and a greater sense of control over health, healthcare . . . [Full Text of this Article]

MRI: Embolism During MRI

Circulation 2011;123 e388-e389

Thombus in LV noted at 16 minutes of scan

Thrombus not seen at 18 minutes of scan

~ 3 hrs later, Renal embolism noted.