Обзор американских кардиологических журналов за неделю (ссылки)

[Chevychelov]

Title: Frequency of Late Drug-Eluting Stent Thrombosis With Non-Cardiac Surgery
Topic: General Cardiology
Date Posted: 5/25/2010
Author(s): Chia KK, Park JJ, Postle J, Cottrill A, Ward MR.
Citation: Am J Cardiol 2010;May 17:[Epub ahead of print].
Clinical Trial: No
Study Question: What is the risk for late stent thrombosis (LAST) with cessation of antiplatelet therapy prior to noncardiac surgery?
Methods: Using billing data from two large health funds, members who had drug-eluting stent (DES) insertion (n = 9,321) with subsequent noncardiac surgery (n = 4,126) were mailed a questionnaire regarding their noncardiac procedures, antiplatelet use, and subsequent coronary events. All events were verified with the medical records.
Results: From 1,086 returned, 710 were suitable for inclusion, identifying 11 patients (1.5%) with perioperative myocardial infarctions confirmed by medical records. Angiography showed that only two had stent thromboses, whereas seven had a new culprit lesion (two patients did not undergo angiography). Before their noncoronary procedures, 66% were receiving dual antiplatelet therapy, and 30% were taking single agents. Surgery was performed on dual therapy in 18%, on single agents in 23%, and with no antiplatelet therapy in 59%. The mean time to surgery from stent implantation was 348 days, with 56% in <12 months.
Conclusions: The authors concluded that noncardiac surgery after DES implantation is frequent and appears to have low cardiac morbidity despite variable antiplatelet cessation.
Perspective: This study suggests that noncardiac surgery after DES implantation is performed frequently, that the acute coronary syndrome event rate is low, and that most events occur because of new culprit lesions. These data also suggest that concerns regarding the risks of LAST in this setting may have been overestimated. An important limitation of this study was the low response rate, with only a quarter or so of patients responding. For now, premature cessation of antiplatelet therapy should be considered as a strong predictor of stent thrombosis, and patients scheduled to undergo noncardiac surgery within a year should not undergo DES implantation. Debabrata Mukherjee, M.D., F.A.C.C.

Title: Racial and Ethnic Differences in the Treatment of Acute Myocardial Infarction. Findings From the Get With The Guidelines–Coronary Artery Disease Program
Topic: General Cardiology
Date Posted: 5/25/2010
Author(s): Cohen MG, Fonarow GC, Peterson ED, et al.
Citation: Circulation 2010;121:2294-2301.
Clinical Trial: No
Study Question: Are the well documented racial/ethnic differences in evidence-based acute myocardial infarction (AMI) care eliminated in hospitals participating in a national quality improvement program?
Methods: This study assessed care in 142,593 AMI patients (121,528 whites, 10,882 blacks, and 10,183 Hispanics) at 443 hospitals participating in the Get With the Guidelines–Coronary Artery Disease (GWTG-CAD) program between January 2002 and June 2007. Individual and overall composite rates of defect-free care, defined as the proportion of patients receiving all eligible performance measures, were examined, as well as temporal trends in use of performance measures according to race/ethnicity by calendar quarter.
Results: Overall, individual performance measure use was high, ranging from 78% for use of angiotensin-converting enzyme inhibitors to 96% for use of aspirin at discharge. Use of each of these improved significantly over the 5 years of study. Overall, defect-free care was 80.9% for whites, 79.5% for Hispanics (adjusted odds ratio vs. whites, 1.00; 95% confidence interval, 0.94-1.06; p = 0.94), and 77.7% for blacks (adjusted odds ratio vs. whites, 0.93; 95% confidence interval, 0.87-0.98; p = 0.01). A significant gap in defect-free care was observed for blacks mostly during the first half of the study, which was no longer present during the remainder of the study. Overall, progressive improvements in defect-free care were observed regardless of race/ethnic groups.
Conclusions: Among hospitals engaged in a national quality monitoring and improvement program, evidence-based care for AMI appeared to improve over time for patients irrespective of race/ethnicity, and differences in care by race/ethnicity care were reduced or eliminated.
Perspective: This very important study demonstrates how discharge protocols requiring opt out of care standards can improve quality and eliminate disparities by ethnicity, race, and socioeconomic variables. The next and major step is to assess the short- and long-term compliance with discharge recommendations and methods to improve outcome by enhancing compliance. This costly process should be helped by the promised national health care database. Melvyn Rubenfire, M.D., F.A.C.C.

[Chevychelov]

Title: Relationship of Functional Mitral Regurgitation to New-Onset Atrial Fibrillation in Acute Myocardial Infarction
Topic: Arrhythmias
Date Posted: 5/26/2010
Author(s): Bahouth F, Mutlak D, Furman M, et al.
Citation: Heart 2010;96:683-688.
Clinical Trial: No
Study Question: Does functional mitral regurgitation (FMR) occurring after acute myocardial infarction (AMI) promote atrial fibrillation (AF) by producing left atrial volume overload?
Methods: A total of 1,920 patients admitted with AMI were studied; patients with known AF were excluded. FMR using echocardiography was classified into three groups: none, mild FMR, and moderate or severe FMR. The relationship between FMR and AF occurring at any time during the hospital course was examined using multivariable logistic regression.
Results: Mild FMR was present in 744 patients (38.8%) and moderate or severe FMR was present in 150 patients (7.8%). AF developed in 51 (5.0%), 83 (11.2%), and 28 (18.7%) patients with no FMR, mild FMR, and moderate or severe FMR, respectively (p < 0.001). In multivariable logistic regression, both mild (odds ratio [OR], 1.6; 95% CI, 1.1-2.3; p = 0.02) and moderate or severe FMR (OR, 2.1; 95% CI, 1.2-3.6; p = 0.007) were independent predictors of AF. There was a significant interaction between the left ventricular ejection fraction and FMR (p = 0.003), such that mild FMR was predictive of AF only in patients with a reduced (<45%) ejection fraction. After discharge, new AF complicating AMI was strongly associated with subsequent readmission for heart failure (hazard ratio, 3.7). Although subsequent mortality also was higher among patients with new AF complicating AMI, independent predictors of mortality were renal insufficiency, Killip class, ejection fraction, and severity of FMR.
Conclusions: The authors concluded that there is a graded independent association between the severity of FMR and the new onset of AF in patients with AMI.
Perspective: It makes sense that increased left atrial volume and increased left atrial pressure associated with FMR (as well as impaired left ventricular systolic function) predispose to the development of AF among patients presenting with AMI. Although mortality after hospital discharge was significantly worse among patients with AF, AF was not an independent predictor of mortality in this study. It remains to be seen whether (and it seems unlikely that) restoration of sinus rhythm would improve prognosis. Rather, new AF during admission for AMI should be considered a marker for other conditions that define a poor prognosis. David S. Bach, M.D., F.A.C.C.

Title: Transapical Transcatheter Aortic Valve Implantation: Follow-up to 3 Years
Topic: Cardiovascular Surgery
Date Posted: 5/26/2010
Author(s): Ye J, Cheung A, Lichtenstein SV, et al.
Citation: J Thorac Cardiovasc Surg 2010;139:1107-1113.
Clinical Trial: No
Study Question: What are the clinical and echocardiographic outcomes of transapical aortic valve implantation?
Methods: Between October 2005 and February 2009, 71 patients (44 female) underwent transcatheter transapical aortic valve implantation with either 23- or 26-mm Edwards Lifesciences transcatheter bioprostheses. All patients with symptomatic aortic stenosis were declined for conventional aortic valve replacement owing to unacceptable operative risks and were not candidates for transfemoral aortic valve implantation because of poor arterial access. Clinical and echocardiographic follow-up was performed before discharge, at 1 and 6 months, and then yearly. Mean follow-up was 12.9 ± 11.5 months, with a total follow-up of 917.3 patient-months.
Results: Mean age was 80.0 ± 8.1 years; predicted operative mortality was 34.5% ± 20.4% by logistic EuroSCORE and 12.1% ± 7.7% by the Society of Thoracic Surgeons Risk Calculator. Valves were successfully implanted in all patients. Twelve patients died within 30 days (30-day mortality: 16.9% in all patients, 33% in the first 15 patients, and 12.5% in the remainder), and 10 patients died subsequently. Overall survival at 24 and 36 months was 66.3% ± 6.4% and 58.0% ± 9.5%, respectively. Among 59 patients who survived at least 30 days, 24- and 36-month survivals were 79.8% ± 6.4% and 69.8% ± 10.9%, respectively. Late valve-related complications were rare. New York Heart Association functional class improved significantly from preoperative 3.3 ± 0.8 to 1.8 ± 0.8 at 24 months. The aortic valve area and mean gradient remained stable at 24 months (1.6 ± 0.3 cm2 and 10.3 ± 5.9 mm Hg, respectively).
Conclusions: The results suggest that transapical transcatheter aortic valve implantation provides sustained clinical and hemodynamic benefits for up to 36 months in selected high-risk patients with symptomatic severe aortic stenosis.
Perspective: Physicians and patients in Europe and Canada have had access to, and have been using for several years, approved devices for transcatheter aortic valve replacement (TAVI). Reserved for patients with very high or prohibitive estimated operative risks, these devices offer a form of therapy for patients with a mortal disease and no other realistic option. Although transfemoral retrograde TAVI might be suitable for the majority of patients, vascular access limits this approach in some. A transapical approach serves as an alternative means for TAVI in such patients. As valves and their delivery systems evolve, with smaller and more flexible systems, vascular access for transfemoral retrograde TAVI might be expected to be less prohibitive. These data suggest that the transapical approach, in the right hands and after a significant initial learning curve, appears to be a viable option for what may be the highest risk patients––inoperable patients with vascular access inadequate for retrograde TAVI. David S. Bach, M.D., F.A.C.C.

[Chevychelov]

Title: Is Early Antithrombotic Therapy Necessary in Patients With Bioprosthetic Aortic Valves in Normal Sinus Rhythm?
Topic: Cardiovascular Surgery
Date Posted: 5/26/2010
Author(s): ElBardissi AW, DiBardino DJ, Chen FY, Yamashita MH, Cohn LH.
Citation: J Thorac Cardiovasc Surg 2010;139:1137-1145.
Clinical Trial: No
Study Question: Is early antithrombotic therapy necessary in patients undergoing isolated bioprosthetic aortic valve replacement (AVR), who are discharged in normal sinus rhythm?
Methods: From December 2001 to October 2008, 1,131 patients underwent isolated bioprosthetic AVR at one academic center. After exclusion of patients who underwent concomitant operations (n = 138, 12%), patients who were anticoagulated preoperatively (n = 4, 0.4%), and patients who experienced postoperative refractory atrial fibrillation requiring anticoagulation at discharge (n = 128, 11%), the study cohort comprised 861 patients. Patients were followed for 90 days postoperatively for the occurrence of thromboembolism, including stroke, transient ischemic attack, peripheral thromboembolic events, and bleeding complications.
Results: Of 861 patients included in this study, 133 (15%) were anticoagulated with warfarin postoperatively (AC+) and 728 (85%) were not (AC–). Patients who received postoperative anticoagulation were older; had a higher incidence of hypertension, cerebrovascular accident, and pulmonary vascular disease; and were more symptomatic at presentation. The 90-day risk of thromboembolism (cerebrovascular accident, transient ischemic attack, or peripheral thromboembolism) after surgery was 5% (n = 6) in those who were anticoagulated and 5% (n = 39) in those who were not (p = 0.67). Independent predictors of thromboembolism were increasing age (odds ratio [OR], 1.03; p = 0.03), female gender (OR, 2.23; p = 0.005), short stature (OR, 0.97; p = 0.002), smoking status (p = 0.05), New York Heart Association class III/IV (OR, 1.77; p = 0.04), and a 19-mm bioprosthetic aortic valve prosthesis (OR, 2.22; p = 0.03). Evaluation of each predictor with postoperative acetylsalicylic acid use (ASA+) and AC+ interaction terms revealed that female patients (OR, 0.75; p = 0.03 AC+; OR, 0.66; p = 0.02 ASA+) and patients with a 19-mm bioprosthetic aortic valve (OR, 0.65; p = 0.02 AC+; OR, 0.36; p = 0.01 ASA+) had a reduction in the incidence of thromboembolism when administered ASA or warfarin. Patients who were in New York Heart Association class III/IV also had a reduction of thromboembolism when treated with warfarin (OR, 0.73; p = 0.04); a similar trend was observed in patients treated with ASA (odds ratio, 0.34; p = 0.06).
Conclusions: Early anticoagulation after isolated bioprosthetic AVR in patients in normal sinus rhythm does not seem to reduce the risk of thromboembolism, except in high-risk groups. In this study, the only patients who may benefit from anticoagulation are those who are female, those who are highly symptomatic, and those with a small aortic prosthesis.
Perspective: Current American Heart Association/American College of Cardiology guidelines recommend anticoagulation and antiplatelet therapy during the first 90 postoperative days after bioprosthetic AVR; however, there is wide variability in practice. This retrospective, observational, single-center study suggests that a practice of using warfarin after bioprosthetic AVR might be reasonably reserved for patients at increased risk of thromboembolism, including women, patients with more advanced preoperative symptoms, and patients who underwent AVR with a small bioprosthesis. David S. Bach, M.D., F.A.C.C.

Title: Processes of Care Associated With Acute Stroke Outcomes
Topic: Prevention/Vascular
Date Posted: 5/26/2010
Author(s): Bravata DM, Well CK, Lo AC, et al.
Citation: Arch Intern Med 2010;170:804-810.
Clinical Trial: No
Study Question: What factors related to the management of stroke are associated with outcomes such as mortality?
Methods: This was a retrospective cohort study of patients admitted to the hospital for ischemic stroke or transient ischemic attack (TIA) onset within 2 days of admission, and a neurologic deficit on admission. Patients were excluded if they resided in a skilled nursing facility, were transferred from another hospital, or were already admitted to the hospital. Seven processes of care were evaluated: fever management, hypoxia management, blood pressure management, neurological evaluation, swallowing evaluation, deep vein thrombosis (DVT) prophylaxis, and early mobilization. Processes of care were determined through review of recommendations of the National Expert Stroke Panel and a national organization interested in stroke care, prior evidence of improved mortality or reduced institutionalization, and inclusion in management of acute stroke care. The primary outcome of interest was a combined outcome, which included in-hospital mortality, discharge to hospice, or discharge to a skilled nursing facility. Models were adjusted for age, comorbidities, concomitant medical illness present at admission, preadmission symptom course, prestrike functional status, modified APACHE (Acute Physiology and Chronic Health Evaluation) III score, and admission brain imaging findings.
Results: A total of 1,487 patients, ages 18 or older (mean age 74 years), were included in the study. A total of 1,363 patients experienced definite stroke, 34 had definite TIA, 28 had stroke versus TIA, and 62 had a probably stroke or TIA. The primary outcome was observed in 239 (16%) patients. In-hospital death was experienced by 91 patients. Neurologic worsening or death was experienced by 208 patients. After adjustment for age, comorbidities, and stroke severity, the process of care associated with improved outcomes included swallowing evaluation (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.43-0.94), DVT prophylaxis (OR, 0.60; 95% CI, 0.37-0.96), and treatment of all hypoxic episodes with supplemental oxygen (OR, 0.26; 95% CI, 0.09-0.73).
Conclusions: The authors concluded that improvement in outcomes among stroke patients can be observed with attention to specific processes of care including swallowing evaluation, DVT prophylaxis, and treatment of hypoxia.
Perspective: This study suggests simple, cost-effective management, which can improve outcomes among patients with ischemic stroke. Quality improvement initiatives should consider inclusion of these processes of care for patients with ischemic stroke. Elizabeth A. Jackson, M.D., F.A.C.C.

[Chevychelov]

Title: Advances in Antiplatelet Treatment for Acute Coronary Syndromes
Topic: General Cardiology
Date Posted: 5/28/2010
Author(s): Eshaghian S, Shah PK, Kaul S.
Citation: Heart 2010;96:656-661.
Clinical Trial: No
Perspective: The following are 10 points to remember about antiplatelet treatment for acute coronary syndromes (ACS).

1. Dual antiplatelet inhibition with aspirin and clopidogrel has been shown to result in a reduction in cardiovascular events in a variety of settings.

2. Attempts to improve outcomes further have led to the development of more potent antiplatelet agents, but at a cost of increased bleeding complications.

3. The search for an antiplatelet agent with optimal ischemic protection and an acceptable bleeding risk remains the ‘holy grail’ of antiplatelet drug development.

4. Prasugrel is a new and more potent thienopyridine. Similar to clopidogrel, it irreversibly binds and blocks the ADP P2Y12 receptor. It has a more rapid onset of action and a stronger inhibitory effect than clopidogrel.

5. Ticagrelor is an orally active drug that binds the P2Y12 receptor. Unlike clopidogrel and prasugrel, it is not a thienopyridine; rather, it is a new class of antiplatelet agent termed ‘cyclopentyl-triazolo-pyrimidine.’ More importantly, its binding to the P2Y12 receptor is reversible. Distinct from previous agents, it does not require metabolic conversion or hepatic activation to an active form.

6. Clopidogrel is the only P2Y12 antagonist that has been approved for the medical management of patients with non-ST-elevation ACS. It also appears to have the best safety profile among the P2Y12 antagonists. Therefore, clopidogrel should be considered the treatment of choice in patients at high risk of bleeding (elderly, low body weight, history of transient ischemic attack or strokes) undergoing medical or invasive therapy.

7. Prasugrel, because of its faster onset of action, should be the preferred agent in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention because of short time window to preload clopidogrel in these patients, or in patients who continue to have recurrent ischemic events, particularly stent thrombosis, despite treatment with clopidogrel (so-called ‘clopidogrel-resistant’ patients).

8. Another group of patients in whom prasugrel might provide superior efficacy are patients with diabetes who are at high risk of thrombotic events (although the evidence base is not robust, as it is derived from a post-hoc analysis).

9. As a result of its reversible nature of platelet inhibition, ticagrelor should be the preferred agent in patients in whom coronary anatomy is unknown and/or urgent coronary artery bypass grafting cannot be deferred. Ticagrelor should be discouraged or used cautiously in patients who develop acute severe dyspnea on treatment or those with a history of severe dyspnea/chronic obstructive pulmonary disease, hyperuricaemia, moderate to severe renal insufficiency, and bradyarrhythmias unprotected by a pacemaker.

10. Prasugrel and ticagrelor are potent agents with improved ischemic benefits in comparison with clopidogrel. The improved benefit comes with the price of increased bleeding. As such, careful patient selection and balancing of benefit–risk is warranted to optimize their use in clinical practice. Debabrata Mukherjee, M.D., F.A.C.C.

Title: The Effects of Growth Hormone on Body Composition and Physical Performance in Recreational Athletes: A Randomized Trial
Topic: General Cardiology
Date Posted: 5/27/2010
Author(s): Meinhardt U, Nelson AE, Hansen JL, et al.
Citation: Ann Intern Med 2010;152:568-577.
Clinical Trial: yes
Study Question: What are the effects of growth hormone alone, or in combination with testosterone, on body composition and measures of athletic performance?
Methods: In a randomized, placebo-controlled, blinded study sponsored by the World Anti-Doping Agency, 96 recreationally trained athletes (63 men and 33 women, mean age 27.9 ± 5.7 years) underwent treatment for 8 weeks followed by a 6-week washout period. Men were randomly assigned to receive placebo, growth hormone (2 mg/d subcutaneously), testosterone (250 mg/wk intramuscularly), or combined growth hormone and testosterone. Women were randomly assigned to receive either placebo or growth hormone (2 mg/d). Body composition (fat mass, lean body mass, extracellular water mass, and body cell mass) and physical performance variables (endurance [maximum oxygen consumption], strength [dead lift], power [jump height], and sprint capacity [Wingate value]) were assessed.
Results: Body cell mass was correlated with all measures of performance at baseline. In men, growth hormone co-administered with testosterone significantly reduced fat mass, increased lean body mass through an increase in extracellular water, and increased body cell mass. Growth hormone significantly increased sprint capacity by 0.71 kJ (95% confidence interval [CI], 0.1-1.3 kJ, relative increase 3.9% [CI, 0.0%-7.7%]) in men and women combined, and by 1.7 kJ (CI, 0.5-3.0 kJ, relative increase 8.3% [CI, 3.0%-13.6%]) when co-administered with testosterone in men; other performance measures did not significantly change. The increase in sprint capacity was not maintained 6 weeks after discontinuation of the drug. The authors note that growth hormone dosage may have been lower than that used covertly by competitive athletes; the athletic significance of the observed improvements in sprint capacity is unclear; and the study was too small to draw conclusions about safety.
Conclusions: Growth hormone supplementation influenced body composition and increased sprint capacity when administered alone and in combination with testosterone.
Perspective: Growth hormone is widely abused by athletes, frequently in combination with androgenic steroids. Although I suppose there could be surprises in the world, this study serves to confirm that people do things for a reason. Growth hormone makes you faster. David S. Bach, M.D., F.A.C.C.

[Chevychelov]

Title: Comparison of Shunt Types in the Norwood Procedure for Single-Ventricle Lesions
Topic: Congenital Heart Disease
Date Posted: 5/27/2010
Author(s): Ohye RG, Sleeper LA, Mahoney L, et al., on behalf of the Pediatric Heart Network Investigators.
Citation: N Engl J Med 2010;362:1980-1992.
Clinical Trial: No
Study Question: In patients undergoing single-ventricle palliations, are outcomes better with a modified Blalock-Taussig (MBT) shunt or a right ventricle-to-pulmonary artery (RVPA) shunt?
Methods: A prospective, multicenter, randomized, controlled trial was performed. A total of 549 patients were randomized, with 275 patients receiving an MBT shunt and 274 patients receiving an RVPA shunt. The primary endpoint was death or cardiac transplantation 12 months after randomization. Multiple secondary endpoints were studied, including the need for nonplanned cardiac interventions, RV size and function at 14 months, and transplant-free survival for all enrolled patients until the final enrolled patient reached 14 months of age.
Results: Patients undergoing RVPA shunt at the time of the Norwood procedure had greater transplant-free survival 12 months after randomization (74% as compared with 64% in the MBT shunt group, p = 0.01). Patients undergoing the RVPA shunt had a higher rate of unintended interventions, often attributable to stenting or ballooning of the shunt or branch pulmonary arteries after discharge from the Norwood procedure (p = 0.003). There was no difference in RV size and function between groups at 14 months of age. At longer-term follow-up (mean 32 ± 11 months), the transplant-free survival benefit for the RVPA shunt was no longer significant (p = 0.06).
Conclusions: Transplant-free survival at 12 months is higher with infants undergoing MBT shunt as compared with RVPA shunt at the time of the Norwood procedure, although this difference is no longer significant beyond 12 months of age.
Perspective: This paper reports the results of the first randomized, controlled, multicenter trial comparing two surgical techniques in congenital heart surgery. The benefit of the RVPA shunt over the MBT shunt has been postulated to be improved hemodynamic stability in the early postoperative period because of lack of diastolic runoff and the potential for 'coronary steal.' The concerns for the RVPA shunt have been long-term effects on RV function and PA growth. The MBT shunt was superior for the primary endpoint of death/transplant-free survival at 12 months of age. This effect was no longer significant after extension of follow-up. An extension of the original study is in progress to further understand the intermediate- and long-term differences in outcomes between the two shunt types. This study is extremely important in proving the feasibility of a large-scale, multicenter trial comparing surgical approaches in congenital heart disease, where most studies are limited by sample size and retrospective study design. The study also shows room for further investigation of the multiple practice pattern variations that occur between centers as well as individual surgeons. Such variations may have as much an impact on survival as the type of shunt chosen at the initial surgery. Timothy B. Cotts, M.D., F.A.C.C.

Title: Red and Processed Meat Consumption and Risk of Incident Coronary Heart Disease, Stroke, and Diabetes Mellitus: A Systematic Review and Meta-Analysis
Topic: Prevention/Vascular
Date Posted: 5/27/2010
Author(s): Micha R, Wallace SK, Mozaffarian D.
Citation: Circulation 2010;121:2271-2283.
Clinical Trial: No
Study Question: Is red or processed meat consumption associated with risk for cardiovascular disease and diabetes?
Methods: A systematic review and meta-analysis was performed, which included 1,598 abstracts, of which 20 studies were included (17 prospective cohorts, and 3 case-control studies). Random-effects generalized least squares models of trend estimation were used to derive pooled dose-response estimates.
Results: Of the 20 studies selected, 1,218,380 subjects were included. Cardiovascular events included 23,889 coronary heart disease (CHD) cases, 2,280 strokes, and 10,797 cases of diabetes. Red meat was not associated with heart disease (relative risk [RR] per 100 gram serving per day, 1.00; 95% confidence interval [CI], 0.81-1.23) or diabetes mellitus (RR, 1.16; 95% CI, 0.92-1.46). In contrast, processed meat intake was associated with a significantly increased risk of CHD (RR per 50 gram serving per day, 1.42; 95% CI, 1.07-1.89) and diabetes (RR, 1.19; 95% CI, 1.11-1.27). Associations were intermediate for total meat intake. Only three studies evaluated incidence of stroke and meat consumption. Intake of red meat was not associated with stroke (RR, 1.17; 95% CI, 0.40-3.43); neither were processed meats (RR, 1.14; 95% CI, 0.94-1.39).
Conclusions: The authors concluded that consumption of processed meats, rather than red meats, was associated with increased incidence of heart disease and diabetes.
Perspective: These findings support the importance of a diet low in processed foods. A cardiac healthy diet does not necessarily mean a vegetarian one; however, moderation in consumption of foods such as meat and reductions in processed foods are likely to translate into improved wellness. Elizabeth A. Jackson, M.D., F.A.C.C.

[Chevychelov]

Title: Diagnostic Accuracy and Clinical Utility of Noninvasive Testing for Coronary Artery Disease
Topic: Noninvasive Cardiology
Date Posted: 5/28/2010
Author(s): Weustink AC, Mollet NR, Neefjes LA, et al.
Citation: Ann Intern Med 2010;152:630-639.
Clinical Trial: No
Study Question: What is the relative accuracy and clinical utility of stress testing and computed tomographic coronary arteriography (CTCA) for identifying patients who require invasive coronary angiography (ICA)?
Methods: This observational study was conducted in patients referred for chest pain in a single academic center. In 2004 to 2006, 297 patients underwent stress testing with electrocardiogram (ECG) and nuclear imaging (exercise or pharmacologic), CTCA, and ICA. In 2006 to 2008, all 220 patients who met eligibility criteria underwent stress testing and CTCA. The 141 patients with a normal stress ECG and imaging and normal CTCA were considered to have no coronary disease. Diagnostic accuracy of stress testing and CTCA was compared with ICA; pretest probabilities of disease by Duke clinical score; and clinical utility of noninvasive testing, defined as a pretest or post-test probability that suggests how to proceed with testing (no further testing if ≤5%, proceed with ICA if between 5% and 90%, and refer directly for ICA if ≥90%). For both CTCA and ICA, significant coronary stenosis was defined as >50% luminal narrowing in all coronary segments.
Results: Mean age was 58.9 years, and 61% were men; chest pain was typical angina in 43.1%, atypical angina in 21.5%, and nonangina in 35%. Significant obstructive CAD on ICA was present in 53%, nonsignificant in 11%, and no CAD in 35%. Stress testing was not as accurate as CTCA; CTCA sensitivity approached 100%. In patients with a low (≤20%) pretest probability of disease, negative stress test, or CTCA results suggested no need for ICA. In patients with an intermediate (20-80%) pretest probability, a positive CTCA result suggested need to proceed with ICA (post-test probability, 93%), and a negative result suggested no need for further testing (post-test probability, 1%). Physicians could proceed directly with ICA in patients with a high (≥80%) pretest probability (91%).
Conclusions: The authors concluded that CTCA seems most valuable in patients with intermediate pretest probability of disease, because the test can distinguish which of these patients need ICA. These findings need to be confirmed before CTCA can be routinely recommended for these patients.
Perspective: The authors correctly commented that referral and verification bias might have influenced findings; and stress testing provides functional information that may add value to that from anatomical (CTCA or ICA) imaging. The study does little to add to the decision process for invasive coronary arteriography, particularly in the post-COURAGE trial era, but does add to the body of literature that CTCA can be very useful in the evaluation of chest pain. If it were not for relatively high radiation exposure (8-13 mSv), it would be the diagnostic tool of choice both for accuracy and ability to identify plaque burden that is not hemodynamically significant. Melvyn Rubenfire, M.D., F.A.C.C.

[Chevychelov]

Title: Prospective Associations Between Early Childhood Television Exposure and Academic, Psychosocial, and Physical Well-Being by Middle Childhood
Topic: Prevention/Vascular
Date Posted: 5/28/2010
Author(s): Pagani LS, Fitzpatrick C, Barnett TA, Dubow E.
Citation: Arch Pediatr Adolesc Med 2010;164:425-431.
Clinical Trial: No
Study Question: Is watching television during early childhood associated with health behaviors several years later?
Methods: This was a longitudinal study of child development, which included infants born between 1997 and 1998 in Quebec, Canada. Parents were asked to report on weekly hours of television exposure at 29 and 53 months of age. Outcomes of interest included parental and teacher reports of the children’s academic, psychosocial, health behaviors, and body mass index (BMI) at 10 years of age.
Results: A total of 1,314 children were included in this analysis. Television exposure at 29 months was a mean of 8.82 hours per week; however, 11% of the cohort viewed 2 or more hours of television daily. After adjustment for pre-existing individual and family factors, each additional hour of television exposure correlated with a 7% unit decrease in classroom engagement (p ≤ 0.05) and a 6% decrease in math achievement (p ≤ 0.05). Increases in victimization by classmates (p < 0.001), and decreases in time spent doing weekend physical activity (-13% units, 95% confidence interval, 0.81-2.25) were also noted. Higher consumption for soft drinks and snacks also correlated with exposure to television at a young age.
Conclusions: The authors concluded that long-term risks associated with higher levels of exposure to television may include increased BMI and unhealthy behaviors in adolescence.
Perspective: These findings are concerning regarding the long-term implications of television. This study, together with prior studies which have found associations between television watching and increased weight and poor diet, suggest that clinicians should counsel families to limit television exposure. Elizabeth A. Jackson, M.D., F.A.C.C.

Title: Right Ventricular Failure in Patients With the HeartMate II Continuous-Flow Left Ventricular Assist Device: Incidence, Risk Factors, and Effects on Outcomes
Topic: Heart Failure/Transplant
Date Posted: 5/28/2010
Author(s): Kormos RL, Teuteberg JJ, Pagani FD, et al., on behalf of the HeartMate II Clinical Investigators.
Citation: J Thorac Cardiovasc Surg 2010;139;1316-1324.
Clinical Trial: No
Study Question: What is the cumulative incidence of postoperative right ventricular failure (RVF) development following HeartMate II left ventricular assist device (LVAD) placement, and what are preoperative risks for RVF?
Methods: A retrospective analysis of clinical, laboratory, and cardiopulmonary hemodynamic data from 484 patients enrolled into the HeartMate II bridge-to-transplant trial was conducted. RVF had three definitions: RVAD requirement, need for intravenous inotropes >14 days after LVAD placement (combined with former group into an “early RVF group”), or inotrope requirement beginning >14 days after LVAD. Preoperative variables in those with and without postoperative RVF were compared to identify correlates of early RVF development.
Results: Ninety-eight (20%) subjects developed postoperative RVF: 30 (6%) required an RVAD, 35 (7%) required inotrope support for >14 days immediately after implant, and 33 (7%) required initiation of delayed inotrope support. The 180-day survival for those with and without early RVF was 66 ± 0.06% and 85 ± 0.02%, respectively, and individuals with RVF had longer bypass times, more perioperative bleeding, and longer hospital stays. Several preoperative univariable correlates (central venous pressure [CVP], CVP/pulmonary capillary wedge pressure [WP] ratio, RVSWi, ventilator support, blood urea nitrogen [BUN], AST, Right Ventricular Failure Risk Score) of “early RVF” development were identified, but only an elevated preoperative AST was associated with late RVF onset. Multivariable correlates of “early RVF” included a preoperative CVP/WP ratio >0.63 (odds ratio [OR], 2.3 [1.2-4.3]), preoperative ventilator support (OR, 5.5 [2.3-13.2]), and BUN >39 mg/dl (OR, 2.1 [1.1-4.1]).
Conclusions: The authors concluded that RVF continues to be a problem following continuous-flow LVAD support. Preoperative optimization of RV function or planned biventricular support may be beneficial.
Perspective: While the morbidity and mortality associated with post-LVAD RVF is well known, this is the first study examining RVF in a large cohort of individuals undergoing implant of a commonly employed, contemporary, continuous-flow device. Preoperative univariable predictors may have been correlated, variable dichotomization was potentially biased, and power was limited to perform detailed multivariable analyses required to identify truly independent RVF risk predictors. Regardless, this study again highlights the importance of closely examining preoperative laboratory and cardiopulmonary hemodynamics in order to gauge RVF risk. It also identifies a weakness in predicting delayed RVF in LVAD patients. As we design future trials and registries of LVAD support, a consensus definition of RVF will be critical to allow comparison of results across studies. Likewise, longer-term follow-up of RV function in patients on prolonged LVAD support (especially those on destination therapy) is warranted. Jennifer Cowger, M.D.

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Title: Evidence That D-Dimer Levels Predict Subsequent Thromboembolic and Cardiovascular Events in Patients With Atrial Fibrillation During Oral Anticoagulant Therapy
Topic: Arrhythmias
Date Posted: 5/31/2010
Author(s): Sadanaga T, Sadanaga M, Ogawa S.
Citation: J Am Coll Cardiol 2010;55:2225-2231.
Clinical Trial: No
Related Resources
JACC Article: Evidence That D-Dimer Levels Predict Subsequent Thromboembolic and Cardiovascular Events in Patients With Atrial Fibrillation During Oral Anticoagulant Therapy

Study Question: Is an elevated D-dimer level associated with adverse outcomes in patients with atrial fibrillation (AF)?
Methods: The subjects of this prospective study were 269 patients (mean age 74 years) with AF who were anticoagulated with warfarin. The D-dimer level was measured upon entry into the study. The endpoints were thromboembolic events and combined cardiovascular events (thromboembolic events, cerebral hemorrhage, myocardial infarction, and cardiovascular deaths). The mean duration of follow-up was 25 months.
Results: The mean international normalized ratio (INR) at entry was 1.93 and there was no relationship between INR and D-dimer level. The incidence of thromboembolic events was 1.8%/year and the incidence of cardiovascular events was 4.8%/year. D-dimer levels were categorized as high (≥0.5 µg/ml) in 63/269 patients. The independent predictors of a high D-dimer level were heart failure, age ≥75 years, and history of stroke. The strongest predictor of thromboembolic events was a high D-dimer level (hazard ratio [HR], 15.7). The strongest predictor of cardiovascular events was heart failure (HR, 19.2) followed by a high D-dimer level (HR, 7.6).
Conclusions: A D-dimer level ≥0.5 µg/ml is predictive of thromboembolic and cardiovascular events in patients with AF.
Perspective: A modest elevation in D-dimer level reflects mild increases in coagulation, thrombin formation, and fibrin turnover. Along with stasis in the left atrial appendage, an increase in coagulation factors has been implicated in the pathophysiology of thromboembolic events during AF, explaining the elevated D-dimer levels. The clinically-relevant and unanswered question is whether the heightened risk of thromboembolic events in patients with a high D-dimer level can be attenuated by more intense anticoagulation with warfarin. Fred Morady, M.D., F.A.C.C.

Title: Altered Na+ Currents in Atrial Fibrillation: Effects of Ranolazine on Arrhythmias and Contractility in Human Atrial Myocardium
Topic: Arrhythmias
Date Posted: 5/31/2010
Author(s): Sossalla S, Kallmeyer B, Wagner S, et al.
Citation: J Am Coll Cardiol 2010;55:2330-2342.
Clinical Trial: No
Related Resources
JACC Article: Altered Na+ Currents in Atrial Fibrillation: Effects of Ranolazine on Arrhythmias and Contractility in Human Atrial Myocardium

Study Question: Is atrial fibrillation (AF) associated with altered peak or late Na+ current (INa) or altered Na+ channel expression, and what are the effects of ranolazine on INa in atrial myocardium?
Methods: The right atrial appendage was excised during open heart surgery in 23 patients with persistent AF and 79 patients in sinus rhythm (SR). INa, protein expression, and the effects of ranolazine were studied in vitro.
Results: Peak INa was significantly reduced by 16% in patients with AF compared to SR, but late INa was significantly greater by 26% in the AF patients. Ranolazine reduced both peak and late INa in patients with SR. In AF patients, ranolazine preferentially reduced late INa over peak INa. Exposure of isolated atrial trabeculae to calcium induced atrial ectopy significantly less frequently in preparations that were pre-treated with ranolazine (9% vs. 32%).
Conclusions: Persistent AF is associated with alterations in the function of sodium channels, with an increase in late INa that is preferentially blocked by ranolazine.
Perspective: Ranolazine is an antianginal agent, and was found to reduce the incidence of AF in a large clinical trial in patients with acute coronary syndromes. This sodium channel blocker has generated interest as a possible antiarrhythmic drug because it selectively blocks the late component of INa. This may reduce the risk of ventricular proarrhythmia that is associated with other sodium channel blockers such as quinidine. Fred Morady, M.D., F.A.C.C.

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Title: Radiation Safety Among Cardiology Fellows
Topic: Interventional Cardiology
Date Posted: 6/1/2010
Author(s): Kim C, Vasaiwala S, Haque F, Pratap K, Vidovich MI.
Citation: Am J Cardiol 2010;May 17:[Epub ahead of print].
Clinical Trial: No
Study Question: What is the current level of fellow training with respect to radiation exposure minimization and management?
Methods: The authors invited 2,545 general and subspecialty cardiology fellows to participate in a survey on knowledge and practice of radiation safety.
Results: The survey was returned by 10.5% of the cohort. Of the 267 respondents, 82% had undergone formal radiation safety training. Approximately 60% of the fellows were aware of their hospital’s pregnancy radiation policy and knew how to contact the hospital’s radiation safety officer. Over half (52%) of the fellows always wore a dosimeter, yet most (81%) did not know their level of radiation exposure in the previous year. Formal training was associated with a greater awareness of institutional radiation pregnancy policy, knowledge of the contact information of the radiation safety officer, awareness of safe levels of radiation exposure, and consistent use of dosimeters and RadPads.
Conclusions: There are significant lacunae in the education of cardiology fellows with respect to radiation safety.
Perspective: This survey, despite its small sample, raises real concerns. Lack of fellow education likely results in increased radiation exposure, not only to the fellows, but also to patients and to others involved in the procedure. Hopefully this paper will lead to fellowship programs across the country examining their radiation safety education and rectifying the shortcomings that may exist therein. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

Title: Excimer Laser to Open Refractory Subclavian Occlusion in 12 Consecutive Patients
Topic: Cardiovascular Surgery
Date Posted: 6/2/2010
Author(s): Worley SJ, Gohn DC, Pulliam RW.
Citation: Heart Rhythm 2010;7:634-638.
Clinical Trial: No
Study Question: What is the safety and efficacy of using laser to treat chronic occlusion of the subclavian vein?
Methods: The authors describe their experience in treating 12 subclavian vein occlusions in patients requiring device upgrades.
Results: The authors successfully used laser to cross wire refractory subclavian vein occlusions in 11 of 12 cases. There were no major complications. The laser was required for an average of 19.9 mm of occlusion. Contrast stains were seen in eight patients and were mild in three (<1 cm), and moderate in another three (1-2 cm).
Conclusions: Chronic subclavian occlusions can be safely and successfully treated with excimer laser.
Perspective: Venous stenosis is an uncommon problem, and perhaps because of that, there are limited devices available to treat these patients. The authors have pioneered the use of laser to treat subclavian occlusions successfully and without any major complications. Further studies are needed to evaluate the safety of the procedure, as it is used in centers with less experienced operators. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

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Title: US Trends in Prevalence, Awareness, Treatment, and Control of Hypertension, 1988-2008
Topic: Prevention/Vascular
Date Posted: 6/2/2010
Author(s): Egan BM, Zhao Y, Axon RN.
Citation: JAMA 2010;303:2043-2050.
Clinical Trial: No
Study Question: Has the prevalence, awareness, and treatment of hypertension (HTN) changed over the past 20 years?
Methods: Data from the National Health and Nutrition Examination Survey (NHANES) 1988-1994 and 1999-2008 were used for the present analysis. A total of 42,856 adults ages 18 years or older were included in a probability sample, which is representative of the general US population. Hypertension was defined as either systolic blood pressure (SBP) of 140 mm Hg or greater, diastolic blood pressure (DBP) of 90 mm Hg or greater, or self-reported use of antihypertensive medications. Controlled HTN was defined as SBP <140 mm Hg and DBP <90 mm Hg. All results were age-adjusted for the year 2000 US population.
Results: HTN has increased over time from 23.9% (95% confidence interval [CI], 22.7%-25.2%) in 1988-1994 to 28.5% (95% CI, 25.9%-31.3%) in 1999-2000 (p < 0.0001). From 1999-2000 to 2007-2008, no change in the rate of HTN was observed. HTN control increased from 27.3% (95% CI, 25.6%-29.1%) in 1988-1994 to 50.1% (95% CI, 46.8%-53.5%) in 2007-2008 (p = 0.006). Blood pressure among adults with HTN decreased from 143.0/80.4 mm Hg to 135.2/74.2 mm Hg (p = 0.02 for SBP and p < 0.001 for DBP). Blood pressure control improved significantly more in absolute percentages between 1999-2000 and 2007-2008 versus 1988-1994 and 1999-2000. Better control reflected improvements in awareness, treatment, and proportion of patients who were treated and had controlled HTN. HTN control improved significantly across age, race, and sex groups, but was lower among individuals ages 18-39 years (vs. 40-59 years, p < 0.001) and 60 years or greater (p < 0.001), and in Hispanic versus white individuals (p = 0.004).
Conclusions: The authors concluded that blood pressure control in patients with HTN has improved with most of the improvement observed after 1999-2000. HTN is lower among young adults as compared to middle-aged and older adults, and in Hispanics as compared to whites.
Perspective: These findings suggest improved awareness and control of HTN in the United States. Understanding what factors explain the reduction in uncontrolled HTN will allow for further gains in the management of HTN to be made. It is likely that increased prevalence of quality assessment has assisted in general improvements. Elizabeth A. Jackson, M.D., F.A.C.C.

Title: Reducing Consumption of Sugar-Sweetened Beverages Is Associated With Reduced Blood Pressure: A Prospective Study Among United States Adults
Topic: Prevention/Vascular
Date Posted: 6/2/2010
Author(s): Chen L, Caballero B, Mitchell DC, et al.
Citation: Circulation 2010;121:2398-2406.
Clinical Trial: No
Related Resources
Trial: PREMIER

Study Question: Is consumption of sweetened beverages associated with increases in blood pressure?
Methods: Data from the PREMIER study were used for this analysis. The PREMIER study was an 18-month randomized controlled trial of two behavioral interventions to reduce blood pressure. Adults with systolic blood pressures (SBP) between 120 and 159 mm Hg and diastolic blood pressures (DBP) 80 to 95 mm Hg were included from four study centers in the United States. Subjects were randomized into three groups: advice only; lifestyle modification which focused on weight loss, increased physical activity, and reducing sodium intake; and the DASH dietary pattern with lifestyle modification. Diet was assessed through two 24-hour recall measures at baseline, 6 months, and 18 months, for a total of six dietary recalls. Blood pressure was measured at baseline, 3, 6, 12, and 18 months.
Results: A total of 810 subjects, ages 25-79, participated. Mean sugar-sweetened beverage consumption was 0.9 ± 1.0 servings per day, and mean SBP was 134.0 ± 9.6 mm Hg, and mean DBP was 84.8 ± 4.1 mm Hg. Sugar-sweetened beverage consumption was associated with younger age, being less fit, lower household income, and less consumption of alcohol. Men had higher intake of sugar-sweetened beverages compared to women, and blacks had higher intake compared to whites. A reduction in sugar-sweetened beverages of one serving per day was associated with a 1.8 mm Hg reduction in SBP (95% confidence interval [CI], 1.2-2.4), and a 1.1 mm Hg reduction in DBP (95% CI, 0.7-1.4) over the 18 months of the study, after adjustment for multiple confounders. After additional adjustment for weight change over the 18 months, reducing sugar-sweetened beverages remained significantly associated with reductions in both SBP and DBP (p < 0.05). Reduction in the intake of sugar in general was associated with an improvement in blood pressure. No association was observed for diet beverages or caffeine intake and blood pressure.
Conclusions: The authors concluded the sugar-sweetened beverages were associated with reductions in blood pressure, suggesting that this may be an important dietary strategy in lowering blood pressure.
Perspective: These findings support the recommendation to avoid sweetened drinks as one component of reducing risk of cardiovascular risk factors such as blood pressure. Elizabeth A. Jackson, M.D., F.A.C.C.

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Title: Are Atrial Fibrillation Patients Receiving Warfarin in Accordance With Stroke Risk?
Topic: Arrhythmias
Date Posted: 6/2/2010
Author(s): Zimetbaum PJ, Thosani A, Yu HT, et al.
Citation: Am J Med 2010;123:446-453.
Clinical Trial: No
Study Question: To what extent are guidelines for anticoagulation of patients with atrial fibrillation (AF) adhered to in clinical practice?
Methods: This was a retrospective analysis of 171,393 patients with AF entered into a MarketScan claims and encounters database in 2003-2007. The CHADS2 score (1 point each for congestive heart failure, hypertension, age >75 years, and diabetes, and 2 points for prior stroke or thromboembolism) was calculated for each patient. Anticoagulation with warfarin was noted.
Results: Overall, warfarin was prescribed for 42.6% of the study population. There were no significant differences in warfarin utilization between the individual CHADS2 score categories. In high-risk patients with a CHADS2 score of 3-6, 42.1% received a prescription for warfarin.
Conclusions: Warfarin is underutilized in high-risk AF patients in clinical practice in the United States.
Perspective: The 2006 American College of Cardiology/American Heart Association/European Society of Cardiology guidelines for AF management recommend anticoagulation with warfarin for patients with a CHADS2 score >2. The results of this study suggest that this recommendation often is not incorporated into clinical practice. However, the CHADS2 scoring system was not widely recognized until the AF guidelines were published in 2006. Although adherence to guidelines has hopefully improved in the past 4 years, it is likely that there still is underutilization of warfarin. To what extent this underutilization is due to the reluctance of physicians to expose patients to the perceived risk of bleeding complications and/or to the reluctance of patients to take a ‘rat poison’ is unclear. It seems likely that both physician and patient compliance will improve once a direct thrombin inhibitor becomes available in clinical practice. Fred Morady, M.D., F.A.C.C.

Title: A Risk Score to Predict Bleeding in Patients With Acute Coronary Syndromes
Topic: General Cardiology
Date Posted: 5/31/2010 5:00:00 PM
Author(s): Mehran R, Pocock SJ, Nikolsky E, et al.
Citation: J Am Coll Cardiol 2010;55:2556-2566.
Clinical Trial: No
Study Question: What are the risk factors that predict the risk and implications of major bleeding in acute coronary syndromes (ACS)?
Methods: A total of 17,421 patients with ACS (including non–ST-segment elevation myocardial infarction [STEMI], STEMI, and biomarker-negative ACS) were studied in the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) and the HORIZONS-AMI (Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial Infarction) trials. An integer risk score for major bleeding within 30 days was developed from a multivariable logistic regression model.
Results: Non-coronary artery bypass graft surgery (CABG)-related major bleeding within 30 days occurred in 744 patients (7.3%) and had six independent baseline predictors (female sex, advanced age, elevated serum creatinine and white blood cell count, anemia, non–STEMI, or STEMI) and one treatment-related variable (use of heparin + a glycoprotein IIb/IIIa inhibitor rather than bivalirudin alone) (model c-statistic = 0.74). The integer risk score differentiated patients with a 30-day rate of non–CABG-related major bleeding ranging from 1% to over 40%. In a time-updated covariate-adjusted Cox proportional hazards regression model, major bleeding was an independent predictor of a 3.2-fold increase in mortality. The link to mortality risk was strongest for non–CABG-related Thrombolysis In Myocardial Infarction (TIMI)-defined major bleeding followed by non-TIMI major bleeding with or without blood transfusions, whereas isolated large hematomas and CABG-related bleeding were not significantly associated with subsequent mortality.
Conclusions: The authors concluded that a simple risk score based on seven variables identifies patients at increased risk for non–CABG-related bleeding and subsequent 1-year mortality.
Perspective: The present analysis suggests that the risk of experiencing a non–CABG-related major bleed within 30 days of presentation varies greatly, depending to a large extent on baseline clinical characteristics, laboratory results, and choice of anticoagulation regimen. A simple integer-based scoring system incorporating six readily available baseline clinical and laboratory variables plus the antithrombotic regimen demonstrated good performance in identifying patients with different risks for major bleeding. Although the risk score needs to be externally validated in another large data set, this knowledge will aid in the accurate risk stratification of patients with ACS, facilitating individualized and optimal decision-making for the patient at high risk of bleeding and mortality. Debabrata Mukherjee, M.D., F.A.C.C.

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Title: Medical Clinics Versus Usual Care for Patients With Both Diabetes and Hypertension: A Randomized Trial
Topic: General Cardiology
Date Posted: 6/3/2010
Author(s): Edelman D, Fredrickson SK, Melnyk SD, et al.
Citation: Ann Intern Med 2010;152:689-696.
Clinical Trial: No
Study Question: Are group medical clinics (GMCs) effective in the management of comorbid diabetes and hypertension?
Methods: A randomized controlled trial was conducted in two Veterans Affairs Medical Centers. A total of 239 patients with poorly controlled diabetes (glycated hemoglobin [HbA1c] level ≥7.5%) and hypertension (systolic blood pressure [SBP] >140 mm Hg or diastolic blood pressure >90 mm Hg) were randomly assigned within each center to either attend a GMC or receive usual care. Clinics comprised 7-8 patients and a care team that consisted of a primary care general internist, a pharmacist, and a nurse or other certified diabetes educator. Each session included structured group interactions moderated by the educator. The pharmacist and physician adjusted medication to manage each patient’s HbA1c level and blood pressure. Measurements were obtained at baseline, study midpoint (median, 6.8 months), and study completion (median follow-up, 12.8 months). Linear mixed models, adjusted for clustering within GMCs, were used to compare HbA1c levels and SBP between the intervention and control groups.
Results: Mean baseline SBP and HbA1c level were 152.9 mm Hg (standard deviation [SD], 14.2) and 9.2% (SD, 1.4), respectively. At the end of the study, mean SBP improved by 13.7 mm Hg in the GMC group and 6.4 mm Hg in the usual care group (p = 0.011 by linear mixed model), whereas mean HbA1c level improved by 0.8% in the GMC group and 0.5% in the usual care group (p = 0.159). Measurements of effectiveness may have been limited by concomitant improvements in the usual care group that were due to co-intervention.
Conclusions: Group medical clinics are a potent strategy for improving blood pressure, but not HbA1c level in diabetic patients.
Perspective: Nurse and pharmacist facilitated care is effective in both inpatient and outpatient settings, and when combined with physician care/supervision, is often superior to standard practice. Among the many reasons are the time spent by the nonphysician and the use of evidence-based algorithms. The study was not powered adequately to draw negative conclusions regarding the use of GMC in poorly controlled diabetes. Other areas where the GMC has been shown to be helpful include inpatient diabetic and antibiotic management, wound care, and outpatient lipid management. Melvyn Rubenfire, M.D., F.A.C.C.

Title: Familial Transposition of the Great Arteries Caused by Multiple Mutations in Laterality Genes
Topic: Congenital Heart Disease
Date Posted: 6/3/2010
Author(s): De Luca A, Sarkozy A, Consoli F, et al.
Citation: Heart 2010;96:673-677.
Clinical Trial: No
Study Question: How common is sequence variation in candidate laterality genes in transposition of the great arteries (TGA) probands from families with a history of congenital heart disease?
Methods: Probands of seven families with isolated TGA and a family history of concordant or discordant congenital heart disease were screened for mutations in the ZIC3, ACVR2B, LEFTYA, CFC1, NODAL, FOXH1, GDF1, CRELD1, GATA4 and NKX2.5 genes by sequence analysis of exons and portions of flanking introns.
Results: Three sequence variations were identified in two out of seven TGA probands. A FOXH1 (Pro21Ser) missense variant was found in a proband who was also heterozogous for an amino acid substitution (Gly17Cys) in the ZIC3 gene. This ZIC3 variant was also found in another family member with a second sequence variation (Val150Ile) in the NKX2.5 gene homeodomain who was affected by multiple ventricular septal defects. A second proband was found to harbour a splice site variant (IVS2-1G/C) in the NODAL gene.
Conclusions: The authors concluded that this study provides evidence that some cases of familial TGA are caused by mutations in laterality genes and, therefore, are part of the same disease spectrum of heterotaxy syndrome, and argues for an oligogenic or complex mode of inheritance in these pedigrees.
Perspective: TGA is the most common cyanotic congenital heart lesion diagnosed in neonates. The etiology is thought to be multifactorial with genetic and environmental contributions. The current study supports the possibility that the mode of inheritance of TGA is complex and related to heterotaxy syndromes. The effects of these mutations on protein function are unclear; however, in-silico predictions were made. Additional study with more extensive genome sequencing and pedigree analysis may identify other genetic variants and provide greater support for establishing causal relationships between the sequence variants and phenotypes. Daniel T. Eitzman, M.D., F.A.C.C.

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Title: The Associations of Fibroblast Growth Factor 23 and Uncarboxylated Matrix Gla Protein With Mortality in Coronary Artery Disease: The Heart and Soul Study
Topic: General Cardiology
Date Posted: 6/3/2010
Author(s): Parker BD, Schurgers LJ, Brandenburg VM, et al.
Citation: Ann Intern Med 2010;152:640-648.
Clinical Trial: No
Study Question: Is there an association between circulating levels of fibroblast growth factor 23 (FGF23), uncarboxylated matrix Gla protein (ucMGP), and fetuin-A with mortality and cardiovascular disease (CVD) events?
Methods: Blood levels of FGF23, ucMGP, and fetuin-A were measured in 833 outpatients with stable coronary artery disease (CAD). Participants were followed for a median of 6 years for mortality and CVD events.
Results: A total of 220 participants died and 182 had CVD events during the study period. Compared with participants with FGF23 levels in the lowest tertile, those in the highest tertile had twofold greater risk for mortality (hazard ratio [HR], 2.15; 95% confidence interval [CI], 1.43-3.24) and CVD events (HR, 1.83; CI, 1.15-2.91) after adjustment for traditional CVD risk factors, C-reactive protein levels, and kidney function. The highest ucMGP tertile was associated with lower mortality risk (HR, 0.48; CI, 0.31-0.75) and showed a nonsignificant trend toward lower CVD event risk by tertile analysis (HR, 0.65; CI, 0.40-1.05)—an association that was significant when modeled continuously (p = 0.029). No significant association of fetuin-A with mortality (HR, 0.84; CI, 0.55-1.27) or CVD events (HR, 0.99; CI, 0.64-1.55) was observed.
Conclusions: In outpatients with stable CAD, higher FGF23 and lower ucMGP levels are independently associated with mortality and CVD events.
Perspective: Preclinical and clinical studies have suggested that factors involved in regulating calcium metabolism may affect arterial calcification and progression of vascular disease. This study strongly supports these previous observations with regard to FGF23 and ucMGP, and suggests that processes involved in tissue mineral deposition may serve as therapeutic targets for prevention of CVD. Additional mechanistic and clinical studies are necessary to confirm these intriguing findings. Daniel T. Eitzman, M.D., F.A.C.C.

Title: Association Between Use of Bleeding Avoidance Strategies and Risk of Periprocedural Bleeding Among Patients Undergoing Percutaneous Coronary Intervention
Topic: Interventional Cardiology
Date Posted: 6/1/2010 4:00:00 PM
Author(s): Marso SP, Amin AP, House JA, et al.
Citation: JAMA 2010;303:2156-2164.
Clinical Trial: No
Study Question: What is the association between the use of two bleeding avoidance strategies, vascular closure devices and bivalirudin, and post–percutaneous coronary intervention (PCI) bleeding rates in a nationally representative PCI population?
Methods: This was an analysis of data from 1,522,935 patients undergoing PCI procedures performed at 955 US hospitals participating in the National Cardiovascular Data Registry (NCDR) CathPCI Registry from January 1, 2004, through September 30, 2008. This registry is jointly sponsored by the American College of Cardiology (ACC) and the Society for Cardiovascular Angiography and Interventions. The primary outcome was periprocedural bleeding.
Results: Bleeding occurred in 30,654 patients (2%). Manual compression, vascular closure devices, bivalirudin, or vascular closure devices plus bivalirudin were used in 35%, 24%, 23%, and 18% of patients, respectively. Bleeding events were reported in 2.8% of patients who received manual compression, compared with 2.1%, 1.6%, and 0.9% of patients receiving vascular closure devices, bivalirudin, and both strategies, respectively (p < 0.001). Bleeding rates differed by preprocedural risk assessed with the NCDR bleeding risk model (low risk, 0.72%; intermediate risk, 1.73%; high risk, 4.69%). In high-risk patients, use of both strategies was associated with lower bleeding rates (manual compression, 6.1%; vascular closure devices, 4.6%; bivalirudin, 3.8%; vascular closure devices plus bivalirudin, 2.3%; p < 0.001). This association persisted following adjustment using a propensity-matched and site-controlled model. Use of both strategies was used least often in high-risk patients (14.4% vs. 21.0% in low-risk patients, p < 0.001).
Conclusions: The authors concluded that vascular closure devices and bivalirudin were associated with significantly lower bleeding rates, particularly among patients at greatest risk for bleeding.
Perspective: In this large, national PCI registry, the use of vascular closure devices and bivalirudin was associated with significantly lower rates of periprocedural bleeding. However, there was an apparent risk-treatment paradox, whereby patients at greatest risk of bleeding were least likely to receive a bleeding avoidance strategy. These findings emphasize the need for additional research to better understand why higher-risk patients are least likely to receive bleeding avoidance strategies but also suggest the need to test interventions to overcome the risk-treatment paradox, such as directing bleeding avoidance strategies to high-risk patients by providing preprocedural estimates of post-PCI bleeding. Quality improvement tools developed by the ACC NCDR are already helping with rapid adoption of bleeding avoidance and other quality initiative strategies by the cardiovascular community. Debabrata Mukherjee, M.D., F.A.C.C.

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Title: Evaluating the Performance of the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines (CRUSADE) Bleeding Score in a Contemporary Spanish Cohort of Patients With Non-ST-Segment Elevation Acute Myocardial Infarction
Topic: General Cardiology
Date Posted: 6/1/2010
Author(s): Abu-Assi E, Gracнa-Acuсa JM, Ferreira-Gonzбlez I, Peсa-Gil C, Gayoso-Diz P, Gonzбlez-Juanatey JR.
Citation: Circulation 2010;May 24:[Epub ahead of print].
Clinical Trial: No
Related Resources
Guideline: Unstable Angina/Non-ST-Segment Elevation Myocardial Infarction: Guidelines for the Management of Patients With

Study Question: How well does the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines (CRUSADE) model perform in predicting bleeding in a cohort of Spanish patients hospitalized with non–ST-elevation myocardial infarction (NSTEMI)?
Methods: The study population was comprised of 782 consecutive patients admitted to one Spanish center between February 2004 and June 2009 with NSTEMI. For each patient, the CRUSADE risk score was calculated. The performance of the CRUSADE risk score was evaluated for the entire population and in subgroups of patients who were treated with or without two or more antithrombotic medications and those who underwent cardiac catheterization.
Results: The majority (84%) of patients were treated with two or more antithrombotic agents and 93% underwent cardiac catheterization. The overall incidence of major bleeding was 9.5%. This incidence increased with the risk category: very low (1.5%); low (4.3%), moderate (7.8%), high (11.8%), and very high (28.9%) (p < 0.001). The model demonstrated excellent discrimination and calibration for the entire patient population (c statistic 0.82), those treated with two or more antithrombotics (c statistic 0.80), those who underwent angiography (c statistic 0.70), and those who did not undergo angiography (0.80). In patients who were treated with two or more antithrombotics and did not undergo angiography, the model had poor discrimination (c statistic 0.56).
Conclusions: The CRUSADE bleeding model performed well in an external cohort in identifying patients at increased risk of bleeding.
Perspective: This study is one of the first to provide external validation of the CRUSADE risk model. It is somewhat surprising that the model discrimination in this cohort was even better than that seen in the derivation cohort. Further studies are needed to evaluate the clinical utility of incorporating this score into clinical practice. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

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Title: Differential Effects of Progenitor Cell Populations on Left Ventricular Remodeling and Myocardial Neovascularization After Myocardial Infarction
Topic: General Cardiology
Date Posted: 6/4/2010
Author(s): Dubois C, Liu X, Claus P, et al.
Citation: J Am Coll Cardiol 2010;55:2232-2243.
Clinical Trial: No
Study Question: What is the effect of late-outgrowth endothelial progenitor cells (EPCs) versus mesenchymal stem cells (MSCs) on left ventricular (LV) recovery following myocardial infarction (MI) in pigs?
Methods: In a blinded, randomized study, autologous late-outgrowth EPCs (n = 10, 34 ± 22 x 106 CD29-31-positive, capable of tube formation), allogeneic green fluorescent peptide-labeled MSCs (n = 11, 10 ± 2 x 106 CD29-44-90-positive, capable of adipogenic and osteogenic differentiation), or vehicle (CON) (n = 12) were infused in the circumflex artery 1 week after acute MI. Systolic function (ejection fraction), LV end-diastolic and end-systolic volumes, and infarct size were assessed with magnetic resonance imaging at 1 week and 7 weeks. Cell engraftment and vascular density were evaluated on postmortem sections.
Results: Recovery of LV ejection fraction from 1 to 7 weeks was similar between groups, but LV remodeling markedly differed with a greater increase of LV end-systolic volume in MSC and CON (+11 ± ml/m2 and +7 ± 8 ml/m2 vs. -3 ± 11 ml/m2 in EPC, respectively, p = 0.04), and a similar trend was noted for LV end-diastolic volume (p = 0.09). After EPC, infarct size decreased more in segments with >50% infarct transmurality (p = 0.02 vs. MSC and CON) and was associated with a greater vascular density (p = 0.01). Late outgrowth EPCs secrete higher levels of the pro-angiogenic placental growth factor (733 [277-1,214] pg/106 vs. 59 [34-88] pg/106 cells in MSC, p = 0.03) and incorporate in neovessels in vivo.
Conclusions: Infusion of late-outgrowth EPCs after acute MI improves MI remodeling via enhanced neovascularization, but does not mediate cardiomyogenesis.
Perspective: Most preclinical and clinical studies using cell-based therapies for MI have failed to show meaningful improvement in LV function. Replacement of infarcted myocardium with functional cardiomyocytes does not appear to occur with the cell-based strategies used to date. However, minor effects on LV remodeling may occur, especially in the setting of large MIs, due to ill-defined paracrine effects. Similarly, the current study shows only minor effects on LV remodeling with EPCs, but does show that late outgrowth EPCs can incorporate into neovessels and promote their growth. These pro-angiogenic effects may be potentially useful in the chronic setting in patients with refractory ischemic vascular disease. Daniel T. Eitzman, M.D., F.A.C.C.

Title: Characterization of the Arrhythmogenic Substrate in Ischemic and Nonischemic Cardiomyopathy: Implications for Catheter Ablation of Hemodynamically Unstable Ventricular Tachycardia
Topic: Arrhythmias
Date Posted: 6/4/2010
Author(s): Nakahara S, Tung R, Ramirez RJ, et al.
Citation: J Am Coll Cardiol 2010;55:2355-2365.
Clinical Trial: No
Study Question: How useful are late potentials (LPs) for guiding radiofrequency catheter ablation (RFCA) of ventricular tachycardia (VT) in patients with nonischemic cardiomyopathy (NICM) versus ischemic cardiomyopathy (ICM)?
Methods: Thirty-three patients (mean age 64 years, mean ejection fraction 24%) underwent detailed electroanatomical mapping and catheter ablation of VT. Sixteen patients had NICM and 17 patients had ICM. Endocardial mapping was performed in all patients and epicardial mapping was performed in 58%. Very late potentials (vLPs) were defined as LPs occurring >100 ms after the end of the QRS. Catheter ablation was guided by pace mapping and LPs within and around dense scars.
Results: There were fewer endocardial LPs in patients with NICM (median 9.5/patient) than in patients with ICM (median 32/patient). Epicardial LPs were equally prevalent in NICM and ICM, but epicardial vLPs were less prevalent in NICM (median 4.5/patient vs. 29/patient). The acute success rate of RFCA was 44% in patients with NICM compared to 82% in patients with ICM, and efficacy at a mean of 15 months of follow-up was 50% compared to 82% in the two groups, respectively.
Conclusions: LPs are not as useful for identifying VT ablation sites in NICM as in ICM.
Perspective: LPs are generated by slow or delayed conduction in surviving myocardial fibers surrounded by fibrosis. These myocardial fibers often are the substrate for scar-related VT. Compared to ICM, scars in NICM are less confluent and less often endocardial. The findings of this study demonstrate that a VT mapping strategy guided by identification of LPs is much less likely to be feasible in NICM than in ICM. Fred Morady, M.D., F.A.C.C.