Обзор американских кардиологических журналов за неделю (ссылки)

[Chevychelov]

Title: Circumferential Pulmonary Vein Isolation and Linear Left Atrial Ablation as a Single-Catheter Technique to Achieve Bidirectional Conduction Block: The Pace-and-Ablate Approach
Topic: Arrhythmias
Date Posted: 2/25/2010
Author(s): Eitel C, Hindricks G, Sommer P, et al.
Citation: Heart Rhythm 2010;7:157-164.
Clinical Trial: No
Study Question: Can conduction block in the atrium after radiofrequency catheter ablation (RFCA) be accurately assessed with a single catheter?
Methods: RFCA to achieve antral pulmonary vein isolation (PVI) in all patients and also block across posterior left atrial ablation lines in patients with persistent atrial fibrillation (AF) was performed in 147 patients (mean age 57 years) with AF. A single irrigated-tip ablation catheter was used for antral PVI and linear ablation. Global atrial capture during pacing at 10 volts from the ablation catheter along the ablation line was used to identify gaps where additional RFCA was necessary to attain complete exit block. PVI was then verified with a conventional ring catheter.
Results: Using the “pace-and-ablate” approach, complete PVI was achieved in 95% of patients and confirmed with a ring catheter in 94% of patients. Complete conduction block was achieved across 74% of the posterior left atrial ablation lines. There was freedom from AF in 84% of patients at 12 months.
Conclusions: Conduction block can be reliably achieved across circumferential and linear atrial ablation lines using a single ablation catheter that is used to confirm conduction block by the absence of atrial capture when pacing along the ablation line.
Perspective: Conventional PVI is performed using an ablation catheter and a ring catheter to monitor the pulmonary veins. The advantage of the 'pace-and-ablate' strategy used in this study is that only a single catheter is necessary in the left atrium. A disadvantage of this technique is that it does not identify the number or locations of the gaps in the ablation lines. Fred Morady, M.D., F.A.C.C.

Title: Diagnosis of Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia: Proposed Modification of the Task Force Criteria
Topic: Arrhythmias
Date Posted: 2/25/2010
Author(s): Marcus FI, McKenna WJ, Sherrill D, et al.
Citation: Circulation 2010;Feb 19:[Epub ahead of print].
Clinical Trial: No
Study Question: How can the sensitivity and specificity of the original Task Force criteria for the diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) be improved?
Methods: One hundred eight patients with genetically confirmed ARVC/D were compared to normal subjects. Multiple parameters were analyzed and diagnostic criteria were selected based on receiver operating characteristic curves that identified optimal sensitivity and specificity.
Results: A definite diagnosis of ARVC/D is warranted in the presence of two major criteria, one major plus two minor criteria, or four minor criteria. The major criteria identified in this study were: 1) right ventricular (RV) akinesia, dyskinesia, or aneurysm by magnetic resonance imaging (MRI), echocardiography, or angiography; 2) fibrous replacement (>50%) of RV myocardium on biopsy; 3) T-wave inversion in V1-V3; 4) epsilon wave in V1-V3; 5) ventricular tachycardia (VT) with a left bundle branch block morphology and superior axis; 6) ARVC/D in a first-degree relative based on Task Force criteria or pathologic confirmation; and 7) the presence of an ARVC/D-related mutation. The minor criteria included (but were not limited to) an abnormal signal-averaged electrocardiogram, VT with a left bundle branch block morphology and inferior axis, and confirmed ARVC/D in a second-degree relative.
Conclusions: The updated Task Force criteria are likely to improve the accuracy with which ARVC/D is diagnosed based on structural, histological, electrocardiographic, arrhythmic, and genetic criteria.
Perspective: ARVC/D is characterized by fibrofatty replacement of the RV myocardium. In the past, thinning of the RV wall and fatty infiltration identified by MRI were felt to be reliable diagnostic criteria. However, normal subjects now are recognized as sometimes having fatty replacement without any fibrous component, and this has impaired the specificity of MRI. Fred Morady, M.D., F.A.C.C.

[Chevychelov]

Title: Early and Late Outcome of Treated Patients Referred for Syncope to Emergency Department: the EGSYS 2 Follow-Up Study
Topic: Arrhythmias
Date Posted: 2/24/2010
Author(s): Andrea U, Attilio DR, Franco G, et al., on behalf of the Evaluation of Guidelines in Syncope Study 2 (EGSYS 2) Group.
Citation: Eur Heart J 2010;Feb 18:[Epub ahead of print].
Clinical Trial: yes
Study Question: What is the prognosis of patients with syncope?
Methods: This was a multicenter, prospective study of 380 patients (mean age 66 years) with syncope initially evaluated in an emergency department (ED). Therapy was at the discretion of the treating physician. The mean duration of follow-up was 20 months. The 1° endpoint was death from any cause or syncope recurrence.
Results: The most common causes of syncope were neurocardiogenic syncope in 64% of patients, orthostatic hypotension in 17%, cardiac syncope in 15%, and an arrhythmia in 11%. All-cause mortality was 9.2%. The strongest predictors of mortality were structural heart disease or an abnormal electrocardiogram (hazard ratio [HR], 5.6), hypertension (HR, 3.0), and trauma from syncope (HR, 2.24). Mortality in patients with cardiac syncope was significantly higher than in patients with other causes of syncope (37% vs. 7-11%). Syncope recurred in 16% of patients and the recurrence rate was unrelated to the etiology of syncope. The strongest predictors of recurrent syncope were palpitations before syncope (HR, 3.4), male gender (HR, 1.8), and absence of prodrome (HR, 0.4).
Conclusions: The risk of death during follow-up in patients with syncope is related to associated cardiac disease. Syncope recurrence is unrelated to the cause of syncope.
Perspective: A limitation of this study is that left ventricular ejection fraction was not included in the analysis and probably would have been a stronger predictor of mortality than simply the presence of structural heart disease. Fred Morady, M.D., F.A.C.C.

Title: Structural Abnormalities of the Pulmonary Trunk in Tetralogy of Fallot and Potential Clinical Implications: A Morphological Study
Topic: Congenital Heart Disease
Date Posted: 3/1/2010
Author(s): Bйdard E, McCarthy KP, Dimopoulos K, Giannakoulas G, Gatzoulis MA, Ho SY.
Citation: J Am Coll Cardiol 2009;54:1883-1890.
Clinical Trial: No
Study Question: Are intrinsic histological abnormalities present from birth in the pulmonary trunk of patients with tetralogy of Fallot (TOF)?
Methods: A review of 39 formalin-fixed necropsy heart specimens of patients with TOF was performed, and compared with 17 normal control specimens. Histological specimens were studied with light microscopy using standard stains, and findings were graded according to severity.
Results: Of the 39 patients in the TOF group, 11 had undergone palliative surgeries while 10 had undergone complete repair at a median age of 8 years (range 2.5-18 years). Histological changes of grade 2 were common, including medionecrosis in 59%, fibrosis in 36%, cyst-like formation in 56%, and abnormal elastic tissue configuration in 56%. Patients with TOF were found to have higher total histology grading scores (median 6, range 1-9) than controls (median 1, range 1-9). Histological abnormalities were noted in all TOF populations, including infants (median 3.5, range 1-9), patients post-palliative surgery (median score 5, range 2-9), and patients post-complete repair (median score 7.5, range 4-9).
Conclusions: Significant histological abnormalities of the pulmonary trunk in hearts with TOF are present from birth, and are seen in patients prior to and after palliative surgery or complete repair.
Perspective: Previous research has demonstrated histological abnormalities in the aortic root of patients with TOF. This study demonstrates similar abnormalities in the pulmonary tract, and shows them to be present even in fetal life. Although further study will be required to determine the clinical significance of these findings, it is possible that these histological abnormalities might predispose patients to pulmonary regurgitation and/or right ventricular dysfunction. Timothy B. Cotts, M.D., F.A.C.C.

[Chevychelov]

Title: Thiazolidinedione Drugs and Cardiovascular Risks: A Science Advisory From the American Heart Association and American College of Cardiology Foundation
Topic: General Cardiology
Date Posted: 2/23/2010
Author(s): Kaul S, Bolger AF, Herrington D, et al.
Citation: J Am Coll Cardiol2010;Feb 23:[Epub ahead of print].
Clinical Trial: No
Perspective: The following are 10 points to remember about this science advisory.

1. The thiazolidinedione class of drugs, ligands of the peroxisome-proliferator–activated receptor-γ, which is intricately involved in insulin signaling, were the first drugs developed that directly targeted insulin resistance.

2. Two thiazolidinediones are currently available in the United States, rosiglitazone (Avandia) and pioglitazone (Actos).

3. To date, there has been only one randomized clinical trial prospectively designed to assess the effect of rosiglitazone on cardiovascular outcomes, the Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes (RECORD) trial.

4. The majority of evidence regarding the cardiovascular effects of rosiglitazone is derived from meta-analyses of randomized clinical trials that evaluated the effects of rosiglitazone on glycemic control.

5. An association between rosiglitazone and ischemic heart disease (IHD) outcomes has not yet been firmly established. Additional prospective clinical trials designed for the specific purpose of establishing the cardiovascular benefit or risk of rosiglitazone would be the best way to resolve the uncertainties regarding the safety of rosiglitazone.

6. However, sufficient evidence has emerged to raise concerns about a potential adverse effect of rosiglitazone. The Food and Drug Administration’s decision on November 14, 2007, to allow rosiglitazone to remain on the market with an additional boxed warning about the risk of IHD events further reflects these uncertainties.

7. The majority of published studies do not suggest an increased hazard for IHD events in pioglitazone-treated patients. Accordingly, there is no boxed warning on the risk of IHD for pioglitazone.

8. On the basis of all available evidence, thiazolidinediones should not be used with an expectation of benefit with respect to IHD events, and should be used with the understanding that they might increase the risk of heart failure.

9. More data are urgently needed to clarify the effects of all existing and future glucose-lowering agents, including thiazolidinediones, on IHD events.

10. The ongoing Thiazolidinedione Intervention With Vitamin D Evaluation (TIDE) study will test the cardiovascular effects of rosiglitazone or pioglitazone when used as part of standard of care compared to similar standard of care without rosiglitazone or pioglitazone in patients with type 2 diabetes who have a history of or are at risk for cardiovascular disease. Debabrata Mukherjee, M.D., F.A.C.C.

Title: Survival as a Function of HbA1c in People With Type 2 Diabetes: A Retrospective Cohort Study
Topic: General Cardiology
Date Posted: 2/25/2010
Author(s): Currie CJ, Peters JR, Tynan A, et al.
Citation: Lancet 2010;375:481-489.
Clinical Trial: No
Study Question: What are survival rates as a function of glycated hemoglobin (HbA1c) in people with type 2 diabetes?
Methods: Two cohorts of patients ages 50 years and older with type 2 diabetes were generated from the United Kingdom General Practice Research Database from November 1986 to November 2008. Investigators identified 27,965 patients whose treatment had been intensified from oral monotherapy to combination therapy with oral blood-glucose lowering agents, and 20,005 who had changed to regimens that included insulin. Those with diabetes secondary to other causes were excluded. All-cause mortality was the primary outcome. Age, sex, smoking status, cholesterol, cardiovascular risk, and general morbidity were identified as important confounding factors, and Cox survival models were adjusted for these factors accordingly.
Results: For combined cohorts, compared with the HbA1c decile with the lowest hazard (median HbA1c 7.5%, interquartile range [IQR], 7.5-7.6%), the adjusted hazard ratio (HR) of all-cause mortality in the lowest HbA1c decile (6.4%, 6.1-6.6) was 1.52 (95% confidence interval [CI], 1.32-1.76), and in the highest HbA1c decile (median 10.5%, IQR 10.1-11.2%) was 1.79 (95% CI, 1.56-2.06). Results showed a general U-shaped association, with the lowest HR at an HbA1c of about 7.5%. HR for all-cause mortality in people given insulin-based regimens (2,834 deaths) versus those given combination oral agents (2,035) was 1.49 (95% CI, 1.39-1.59).
Conclusions: The authors concluded that low and high mean HbA1c values were associated with increased all-cause mortality and cardiac events.
Perspective: The study suggests that an HbA1c of ~7.5% is associated with lowest all-cause mortality and lowest progression to large-vessel disease events in type 2 diabetes. An increase or decrease from this mean HbA1c value appears to be associated with heightened risk of adverse outcomes. The study data also suggests that oral combination therapy in a wide HbA1c range is safe with respect to all-cause mortality and large-vessel events, but for insulin-based therapy, a narrower range might be desirable. Whether intensification of glucose control with insulin therapy alone further heightens risk of death in patients with diabetes needs additional study. It should be noted that in the ADVANCE study, intensive glycemic control significantly reduced the primary endpoint, which was a combination of microvascular events and major adverse cardiovascular events. For now, the totality of evidence supports the 2010 American Diabetes Association recommendations for the HbA1c goal for adults in general to be <7%. Additional prospective studies are needed to refine optimal HbA1c levels in patients with diabetes. Debabrata Mukherjee, M.D., F.A.C.C

[Chevychelov]

Title: Natural History and Expansive Clinical Profile of Stress (Tako-Tsubo) Cardiomyopathy
Topic: General Cardiology
Date Posted: 3/1/2010
Author(s): Sharkey SW, Windenburg DC, Lesser JR, et al.
Citation: J Am Coll Cardiol 2010;55:333-341.
Clinical Trial: No
Related Resources
JACC Article: Natural History and Expansive Clinical Profile of Stress (Tako-Tsubo) Cardiomyopathy

Study Question: What is the clinical profile and natural history of stress cardiomyopathy?
Methods: The authors prospectively followed 136 consecutive patients who presented with stress-induced cardiomyopathy to their institution. This is a report of their clinical profile and outcome. The average follow-up was 2.3 years.
Results: Almost all the patients were women (n = 130; 96%), with an average age of 68 years (range 32-94 years). Most of the cases (121 patients, 89%) were precipitated by intensely stressful emotional (n = 64) or physical (n = 57) events, including 22 associated with sympathomimetic drugs or medical/surgical procedures. No precipitating stressor was identified in 15 (11%) patients. Stress cardiomyopathy developed on a background of beta-blocker in 25 (18%) patients. Twenty-five patients (18%) were taking beta-blockers at the time of stress cardiomyopathy events. Cardiovascular magnetic resonance (CMR) imaging identified three distinct patterns of involvement with mid left ventricular and apex involvement being most common, with the remainder of patients presenting with only apical, or only mid left ventricular involvement. Right ventricular involvement occurred in approximately 25% of patients. Rapid recovery to normal systolic function was common, although it was delayed >2 months in a small number of patients (5%). Right and/or left ventricular thrombi were identified in five patients (predominantly by CMR imaging), including two with embolic events. Three patients (2%) died in-hospital. Among those surviving to hospital discharge, 17 patients died, with most deaths within the first year and related to a noncardiac cause. Recurrent stress-induced cardiomyopathy developed in 5% of the survivors.
Conclusions: Stress-induced cardiomyopathy is a heterogeneous disorder with a generally good cardiac prognosis.
Perspective: This is an interesting paper that adds to the growing body of data on this increasingly recognized albeit rare disorder. The study corroborates earlier series suggesting generally good cardiac outcome in these patients. A small number of patients will develop recurrence of symptoms, and it is unclear how to identify these patients and if beta-blockers are truly protective. Multicentric registries are needed to better define the outcome and best treatment for these patients. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

Title: Carotid Artery Stenting Compared With Endarterectomy in Patients With Symptomatic Carotid Stenosis (International Carotid Stenting Study): An Interim Analysis of a Randomised Controlled Trial
Topic: Interventional Cardiology
Date Posted: 3/1/2010
Author(s): International Carotid Stenting Study Investigators.
Citation: Lancet 2010;Feb 26:[Epub ahead of print].
Clinical Trial: yes
Related Resources
Trial: International Carotid Stenting Study (ICSS)
Trial: Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST)

Study Question: What is the relative safety and efficacy of carotid artery stenting (CAS) compared with carotid endarterectomy (CEA) in patients with symptomatic carotid artery stenosis?
Methods: The ICSS (International Carotid Stenting Study) investigators randomized 1,713 patients with a recently symptomatic carotid artery lesion to CEA (n = 858) or CAS (n = 855). The primary endpoint of the trial is 3-year rate of fatal or disabling stroke. This paper reported the results of the interim safety endpoint of stroke death or procedural myocardial infarction (MI) at 120 days.
Results: At 120 days after randomization, the rate of disabling stroke or death was similar between the two groups (4.0% with CAS vs. 3.2 % in the CEA arm, hazard ratio [HR], 1.28; confidence interval [CI], 0.77-2.11). The incidence of stroke, death, or procedural MI (8.5% vs. 5.2%, HR, 1.69; p = 0.006) was higher in patients randomized to CAS. Patients randomized to CAS had an exaggerated hazard of mortality (HR, 2.76; 1.16-6.56) or any stroke (HR, 1.92; 1.27-2.89). There were three fatal MIs in the CAS arm and four nonfatal MIs in the CEA arm. Two centers had unexpectedly high rates of major adverse events (five deaths or disabling strokes among 11 patients undergoing CAS and one fatal stroke among those undergoing CEA) and enrollment from those centers was stopped prematurely.
Conclusions: Compared with CEA, CAS is associated with a greater risk for procedural stroke in patients with symptomatic carotid stenosis.
Perspective: This study adds to the ongoing debate on the relative safety and efficacy of CAS and CEA. The totality of available evidence suggests similar long-term efficacy of CEA and CAS (Meier et al., BMJ 2010), whereas the risk of procedural non-disabling stroke appears to be higher with CAS. The outcome of this study is in contrast to that of the recently reported CREST trial, where there was no difference in the primary endpoint (death, stroke, and procedural MI), although the risk of non-disabling stroke was lower with CEA, whereas the risk of MI was lower with CAS. The results of these trials suggest that the optional revascularization strategy (CAS vs. CEA) should be based on the patient’s unique risk of procedural complications, operator experience, and patient and physician preference. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

[Chevychelov]

Title: Comparison of Platelet Function Tests in Predicting Clinical Outcome in Patients Undergoing Coronary Stent Implantation
Topic: Interventional Cardiology
Date Posted: 2/23/2010 4:00:00 PM
Author(s): Breet NJ, van Werkum JW, Bouman HJ, et al.
Citation: JAMA 2010;303:754-762.
Clinical Trial: No
Study Question: Can platelet function tests performed at time of percutaneous coronary intervention (PCI) predict clinical outcome?
Methods: The authors prospectively studied 1,069 consecutive patients that underwent elective stent-based PCI at their institution between December 2005 and December 2007. All patients were on clopidogrel, and on-treatment platelet reactivity was measured in all patients using light transmittance aggregometry, VerifyNow P2Y12 assay, Plateletworks assay, IMPACT-R, and the platelet function analysis system (PFA-100). Cut-off values for high on-treatment platelet reactivity were established by receiver operating characteristic curve analysis. The primary endpoint was a composite of all-cause death, nonfatal acute myocardial infarction, stent thrombosis, and ischemic stroke. The primary safety endpoint included TIMI major and minor bleeding.
Results: One-year follow-up was available for 99.8% of the patients. Adherence to clopidogrel was 95% after 6 months and 82% at 1 year. Over 1-year follow-up, there were 18 deaths (1.7%), 6.0% had nonfatal acute myocardial infarction, 1.2% presented with definite stent thrombosis, and 1.3% had a nonfatal ischemic stroke. There were three possible stent thromboses (0.3%), and bleeding events occurred in 5.1% of the patients (TIMI-major 3.1%, TIMI-minor bleeding 2.2%).The primary endpoint occurred more frequently in patients with high on-treatment platelet reactivity when assessed by light transmittance aggregometry (11.7% vs. 6.0%; p < 0 .001 area under the curve [AUC], 0.63), VerifyNow (13.3% vs. 5.7%, p < 0.001, AUC 0.62), and Plateletworks (12.6% vs. 6.1%, p = 0.005, AUC 0.61). The other assays were not able to discriminate between those with or without ischemic events. None of the tests identified patients at risk for bleeding.
Conclusions: Assessment of platelet function using light transmittance aggregometry, VerifyNow, and Plateletworks was significantly but modestly associated with ischemic events at 1 year.
Perspective: Multiple studies have established an association between a lesser degree of platelet inhibition and the occurrence of atherothrombotic events. The field has been clouded by the use of multiple platelet function assays with little inter-assay correlation. This study, with its large population and nearly 100% follow-up, provides much needed clarity to the field. Only three assays demonstrated a significant albeit moderate association between ischemic outcomes and degree of platelet inhibition. Given the moderate strength of the association, it would be premature to use platelet function testing to guide routine clinical practice at present. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

Title: Vascular Inflammation in Obesity and Sleep Apnea
Topic: Prevention/Vascular
Date Posted: 2/24/2010
Author(s): Jelic S, Lederer DJ, Adams T.
Citation: Circulation 2010;121:1014-1021.
Clinical Trial: No
Study Question: Both obesity and obstructive sleep apnea (OSA) are associated with vascular endothelial inflammation and increased risk for cardiovascular diseases. Are the endothelial alterations that are attributed commonly to obesity in fact related to OSA?
Methods: Seventy-one subjects with a body mass index ranging from normal to obese underwent attended polysomnography. To assess vascular inflammation and oxidative stress directly, the expression of nuclear factor-ĸB and nitrotyrosine were quantified by immunofluorescence in freshly harvested venous endothelial cells. Basal endothelial nitric oxide (NO) production and activity were quantified by the expression of endothelial NO synthase (eNOS) and phosphorylated eNOS. Vascular reactivity was measured by brachial artery flow-mediated dilation.
Results: Expression of eNOS and phosphorylated eNOS and flow-mediated dilation were significantly lower, whereas expression of nitrotyrosine was significantly greater in OSA patients (n = 38) than in OSA-free subjects (n = 33) regardless of central adiposity. Expression of nuclear factor-ĸB was greater in obese OSA patients than in obese OSA-free subjects (p = 0.004). Protein expression and flow-mediated dilation were not significantly affected by increasing body mass index or central obesity in OSA patients and in OSA-free subjects. After 4 weeks of continuous positive airway pressure therapy, flow-mediated dilation and expression of eNOS and phosphorylated eNOS significantly increased, whereas expression of nitrotyrosine and nuclear factor-ĸB significantly decreased in OSA patients who adhered to continuous positive airway pressure ≥4 hours daily.
Conclusions: Untreated OSA rather than obesity is a major determinant of vascular endothelial dysfunction, inflammation, and elevated oxidative stress in obese patients.
Perspective: This study adds to the body of evidence that OSA may contribute to coronary risk and cardiovascular events. A few of the cardiometabolic effects of OSA include hypertension, increase in high-sensitivity C-reactive protein, heightened sympathetic tone, reactive platelets, dysglycemia, insulin resistance, and increase in cortisol, leptin, and growth hormone. Melvyn Rubenfire, M.D., F.A.C.C.

[Chevychelov]

Title: Coronary Heart Disease in Postmenopausal Recipents of Estrogen Plus Progestin Therapy: Does the Increased Risk Ever Disappear? A Randomized Trial
Topic: Prevention/Vascular
Date Posted: 2/25/2010
Author(s): Toh S, Hernandez-Diaz S, Logan R, Rossouw JE, Hernan MA.
Citation: Ann Intern Med 2010;152:211-217.
Clinical Trial: No
Study Question: Does risk for coronary heart disease (CHD) associated with hormonal replacement decrease over time?
Methods: Data from the Women’s Health Initiative (WHI), a randomized double-blinded, placebo-controlled trial, were used for this analysis. A total of 16,608 postmenopausal women (from 40 clinical centers in the United States) were included. Baseline data were collected from 1993 to 1998. Women with an intact uterus were randomized to either conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) or placebo. The primary outcome of interest was CHD events including acute myocardial infarction, silent myocardial infarction identified through serial electrocardiograms, or death due to CHD.
Results: Women randomized to continuous hormonal replacement were at increased CHD risk compared to the placebo group for the initial 2 years (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.55-3.62) and for the first 8 years (HR, 1.69; 95% CI, 0.98-2.98). Among women within 10 years of menopause, the risk was also increased for those receiving continuous hormone therapy for the first 2 years (HR, 1.29; 95% CI, 0.52-3.18), with nonsignificant differences observed for the first 8 years (HR, 0.64; 95% CI, 0.21-1.99). The survival curves for continuous use and placebo crossed at about the 6-year time point (95% CI, 2-10 years).
Conclusions: The authors concluded that no suggestion of decreased risk for CHD was observed over the first 2 years of estrogen plus progesterone use, including among women who were less than 10 years postmenopausal.
Perspective: These data support recommendations that hormonal replacement therapy with conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) is not recommended for modification of CHD risk. In terms of CHD risk, other forms of hormonal replacement have not been studied; therefore, whether these data are generalizable to all forms of hormone therapy is not clear. Elizabeth A. Jackson, M.D., F.A.C.C.

Title: Glycated Hemoglobin, Diabetes, and Cardiovascular Risk in Nondiabetic Adults
Topic: Prevention/Vascular
Date Posted: 3/3/2010 5:00:00 PM
Author(s): Selvin E, Steffes MW, Zhu H, et al.
Citation: N Engl J Med 2010;362:800-811.
Clinical Trial: No
Study Question: Is the glycated hemoglobin in persons without diabetes predictive of cardiovascular outcomes?
Methods: The prognostic value of glycated hemoglobin and fasting glucose were assessed for their ability to identify adults at risk for diabetes or cardiovascular disease. Glycated hemoglobin (glycohemoglobin or HgA1c) was measured in whole-blood samples from 11,092 black or white adults who did not have a history of diabetes or cardiovascular disease and who attended the second visit (occurring in the 1990–1992 period) of the Atherosclerosis Risk in Communities (ARIC) study.
Results: Fifty-eight percent were women, 77% were white, 32% had hypertension, and 22.7% had a family history of diabetes. Mean values for risk factors were as follows: age 57 years, fasting blood sugar (FBS) 105 mg/dl, glycated hemoglobin 5.5%, low-density lipoprotein cholesterol 133 mg/dl, high-density lipoprotein cholesterol 51 mg/dl, and body mass index 27.7 kg/m2. The glycated hemoglobin value at baseline was associated with newly diagnosed diabetes and cardiovascular outcomes. For glycated hemoglobin values of less than 5.0%, 5.0 to less than 5.5%, 5.5 to less than 6.0%, 6.0 to less than 6.5%, and 6.5% or greater, the multivariable-adjusted hazard ratios for diagnosed diabetes were 0.52, 1.00 (reference), 1.86, 4.48, and 16.47, respectively. For coronary heart disease, the hazard ratios were 0.96, 1.00 (reference), 1.23, 1.78, and 1.95, respectively. The hazard ratios for stroke were similar. In contrast, glycated hemoglobin and death from any cause were found to have a J-shaped association curve. All these associations remained significant after adjustment for the baseline fasting glucose level. The association between the fasting glucose levels and the risk of cardiovascular disease or death from any cause was not significant in models with adjustment for all covariates as well as glycated hemoglobin. For coronary heart disease, measures of risk discrimination showed significant improvement when glycated hemoglobin was added to models including fasting glucose.
Conclusions: In this community-based population of nondiabetic adults, glycated hemoglobin was similarly associated with a risk of diabetes and more strongly associated with risks of cardiovascular disease and death from any cause, as compared with fasting glucose. These data add to the evidence supporting the use of glycated hemoglobin as a diagnostic test for diabetes.
Perspective: Persons with a glycated hemoglobin ≥6.5% or FBS >126 mg/dl are characterized as diabetics. The former represent the average blood sugar over 2 to 3 months. A level greater than 5.5% is associated with an increase in risk for diabetes and coronary disease independent of other variables, and the relative risk for 0.5% increments is considerable. The authors concluded that a glycated hemoglobin exceeding 6% may be a useful marker to identify persons at risk for development of diabetes, and cardiovascular disease and death. Consideration should be given to replacing the FBS with glycated hemoglobin for risk stratification of adults with and without vascular disease. Melvyn Rubenfire, M.D., F.A.C.C.

[Chevychelov]

Members Encouraged to Take RUC Surveys
ACC.10 Hybrid Suite - New Learning Destination
Perc. Ao Valve Results from Canada
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[Chevychelov]

Title: Characteristics, Performance Measures, and In-Hospital Outcomes of the First One Million Stroke and Transient Ischemic Attack Admissions in Get With The Guidelines-Stroke
Topic: Prevention/Vascular
Date Posted: 2/26/2010
Author(s): Fonarow GC, Reeves MJ, Smith EE, et al.
Citation: Circ Cardiovasc Qual Outcomes 2010;Feb 22:[Epub ahead of print].
Clinical Trial: No
Study Question: What are the demographics, treatments received, quality of care, and early clinical outcomes of the first million patients entered into the Get With The Guidelines (GWTG-Stroke) program?
Methods: The authors reported their analysis of data from an ongoing voluntary, continuous registry and performance improvement initiative that collects patient-level data on subjects with transient ischemic attack (TIA), stroke, subarachnoid hemorrhage, ischemic stroke, and intracerebral hemorrhage. Collected data included patient characteristics, performance measures, and in-hospital outcomes. Seven performance measures based on the American Heart Association/American Stroke Association and Joint Commissions Primary Stroke Centers Certification criteria for quality of care for stroke patients were observed. The authors defined all-or-none as a measure of the proportion of patients who received all of the performance measure interventions for which they were eligible.
Results: The authors reported data on the first million eligible patients at 1,392 participating hospitals between 2003 and 2009. There were 601,599 (60.2%) ischemic strokes, 108,671 (10.9%) intracerebral hemorrhages, 34,945 (3.5%) subarachnoid hemorrhages, 26,977 (2.7%) strokes otherwise not classified, and 227,788 (22.8%) TIAs. In-hospital mortality was significantly higher for both subarachnoid and intracerebral hemorrhage (20.4% and 25.0%, respectively), than for patients suffering ischemic stroke (5.5%) or TIA (0.3%). From 2003 to 2009 there were significant improvements, almost doubling the percentage of patients who received all of the indicated interventions (44.0-84.3%; + 40.3%, p < 0.0001). The authors also reported temporal improvements in the length of stay and risk-adjusted in-hospital mortality rate.
Conclusions: The authors concluded that the GWTG-Stroke program represents an integrated stroke and TIA registry that supports national surveillance, innovative research, and sustained quality improvement efforts facilitating evidence-based stroke/TIA care.
Perspective: This report represents a milestone in observational registries for stroke care in the United States. It is gratifying to note that adherence to agreed-upon quality of care interventions have improved significantly over the decade. It is particularly interesting and also gratifying to note that the use of thrombolytic therapy within 2 hours of presentation increased from <30% in 2003 to >70% of eligible patients in 2009 (p < 0.0001). Although the authors observed a significant improvement in quality of care as well as outcomes, the observational nature of these data makes it impossible to infer a causal relationship. Other temporal trends and changes in care may have contributed to the improvement in outcomes. This study does, however, demonstrate the feasibility of prospectively collected data on a national scale, providing nationally representative information and benchmarks for both care and outcomes of patients with all types of stroke. The GWTG-Stroke program will provide an excellent opportunity to study changes in stroke care nationally going forward. James B. Froehlich, M.D., F.A.C.C.

[Chevychelov]

Title: Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST)
Trial Sponsor: National Institute of Neurological Diseases and Stroke
Year Presented: 2010
Topic(s): General Cardiology, Interventional Cardiology, Prevention/Vascular
Summary Posted: 2/27/2010
Writer: Dharam J. Kumbhani, M.D., S.M.
Author Disclosure: This author has nothing to disclose.
Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C.
Author Disclosure: Research/Research Grants: Astra Zeneca; Consultant Fees/Honoraria: Duke Clinical Research Institute; Research/Research Grants: Heartscape; Research/Research Grants: PLx Pharma; Research/Research Grants: Cogentus; Research/Research Grants: Sanofi Aventis; Data Safety Monitoring Board (Gov’t/Nonprofit): Duke Clinical Research Institute; Research/Research Grants: Bristol Myers Squibb; Research/Research Grants: Eisai; Research/Research Grants: Takeda; Research/Research Grants: The Medicines Company; Research/Research Grants: Ethicon
Related Resources
Related Trial: Endarterectomy Versus Angioplasty in Patients With Symptomatic Severe Carotid Stenosis (EVA-3S: 30-Day and 4-Year Results)
Related Trial: Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE)
Related Trial: Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS)
Related Trial: Stent-Protected Angioplasty Versus Carotid Endarterectomy (SPACE: 30-Day and 2-Year Results)
Related Trial: International Carotid Stenting Study (ICSS)
Journal Scan: Carotid Artery Stenting Compared With Endarterectomy in Patients With Symptomatic Carotid Stenosis (International Carotid Stenting Study): An Interim Analysis of a Randomised Controlled Trial

Description
Current literature indicates that carotid artery stenting (CAS) is not superior to carotid endarterectomy (CEA), with a potentially higher risk of complications. Accordingly, CAS is currently reserved for high-risk patients, who are not good candidates for surgery. However, there has been a significant improvement in CAS and CEA techniques over the past few years. Therefore, the CREST study sought to compare outcomes between CAS and CEA in a contemporary population.
Hypothesis
Carotid stenting would be as safe and effective as carotid surgery in patients at risk for stroke.
Drugs/Procedures Used
In patients undergoing CAS, stenting was undertaken using the Rx Acculink stent. Embolic protection was achieved using the Rx Accunet system. CEA was performed using standard techniques.
Concomitant Medications
All patients were optimally treated with aspirin, antihypertensives, and other medications for stroke.
Principal Findings
A total of 2,502 patients were randomized, of which 1,262 were randomized to CAS and 1,240 to CEA. Of the total, 1,326 were symptomatic, and the rest were asymptomatic. The majority of patients had risk factors for cardiovascular disease, including diabetes (30%), hypertension (85%), dyslipidemia (83%), current smokers (25%), and prior coronary artery bypass grafting (21%).

Preliminary findings indicate that the primary endpoint of death, myocardial infarction (MI), or stroke at 30 days plus ipsilateral stroke thereafter was similar between the two arms (7.2% vs. 6.8%, hazard ratio 1.11, 95% confidence interval 0.81-1.51, p = 0.51). The incidence of death, MI, or stroke at 30 days was similar between the two arms (5.2% vs. 4.5%, p = 0.38). Periprocedural strokes were higher in the CAS arm (4.1% vs. 2.3%, p = 0.01). However, the incidence of debilitating and major strokes was similar between the two arms (0.9% vs. 0.7%, p = 0.52). Minor strokes were more frequent in the CAS group (2.7% vs. 1.5%, p < 0.05). The incidence of MI was significantly lower in the CAS arm, as compared with the CEA arm (1.1% vs. 2.3%, p = 0.03). Cranial nerve palsies were also more common in the CEA arm (0.3% vs. 4.8%, p < 0.0001). Long-term follow-up suggested that the incidence of ipsilateral stroke after the periprocedural period (approximately 4 years of follow-up) was similar between the two arms (2.0% vs. 2.4%, p = 0.85).

Subgroup analyses suggested that there was no difference based on gender or prior stroke/transient ischemic attack (TIA) status. However, there seemed to be evidence of effect modification by age, such that patients ≤69 years did better with CAS, whereras those ≥70 years did better with CEA. Moreover, the younger the patient, the greater the benefit with CAS, and conversely, the older the patient, the greater the benefit with CEA.
Interpretation
The results of the CREST trial indicate that CAS is associated with similar 30-day outcomes, as compared with CEA in a contemporary population. The risk of minor strokes is higher with CAS, whereas the risk of MI is higher with CEA. Older patients derive more benefit from CEA, whereas younger patients derive more benefit from CAS.

These findings are very interesting. Final full publication of these results is eagerly awaited. Perhaps based on this study, the Centers for Medicare and Medicaid (CMS) will reconsider its current coverage decision regarding CAS.
Conditions
• Carotid stenosis
Therapies
• Stent
Study Design
Randomized. Parallel.
Patients Enrolled: 2,502
Mean Follow-Up: 4 years
Mean Patient Age: 69.1 years
% Female: 37

Primary Endpoints
Occurrence of any stroke, MI, or death during a 30-day periprocedural period
Ipsilateral stroke during follow-up of up to 4 years
Secondary Endpoints
Restenosis
Health-related quality of life
Patient Population
Age >18 years
Symptomatic patients with recent neurological events (TIA or non-disabling stroke) with an associated carotid stenosis ≥50% by angiography, ≥70% by ultrasound, or ≥70% by computed tomography angiography (CTA) or magnetic resonance angiography (MRA)
Asymptomatic patients with no recent (in the last 6 months) neurological events referable to the study with artery and carotid stenosis (patients with symptoms beyond 180 days are considered asymptomatic) ≥60% by angiography or ≥70% by ultrasound or ≥80% by CTA or MRA
Exclusions:
Conditions that: 1) interfere with the evaluation of endpoints, 2) are known to interfere with the completion of CEA or CAS, or 3) affect the likelihood of survival for the study period (4 years)
Chronic atrial fibrillation and/or anticoagulation or episodic atrial fibrillation within the last 6 months
References: Presented by Dr. Wayne M. Clark at the International Stroke Conference, San Antonio, TX, February 26, 2010.

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Title: International Carotid Stenting Study (ICSS)
Trial Sponsor: Medical Research Council, the Stroke Association, Sanofi-Synthйlabo, European Union
Year Presented: 2009
Year Published 2010
Topic(s): General Cardiology, Interventional Cardiology, Prevention/Vascular
Summary Posted: 2/28/2010
Writer: Anthony A. Bavry, M.D., M.P.H., F.A.C.C.
Author Disclosure: This author has nothing to disclose.
Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C.
Author Disclosure: Research/Research Grants: Astra Zeneca; Consultant Fees/Honoraria: Duke Clinical Research Institute; Research/Research Grants: Heartscape; Research/Research Grants: PLx Pharma; Research/Research Grants: Cogentus; Research/Research Grants: Sanofi Aventis; Data Safety Monitoring Board (Gov’t/Nonprofit): Duke Clinical Research Institute; Research/Research Grants: Bristol Myers Squibb; Research/Research Grants: Eisai; Research/Research Grants: Takeda; Research/Research Grants: The Medicines Company; Research/Research Grants: Ethicon
Related Resources
Related Trial: Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST)
Related Trial: Endarterectomy Versus Angioplasty in Patients With Symptomatic Severe Carotid Stenosis (EVA-3S: 30-Day and 4-Year Results)
Related Trial: Stent-Protected Angioplasty Versus Carotid Endarterectomy (SPACE: 30-Day and 2-Year Results)
Journal Scan: Carotid Artery Stenting Compared With Endarterectomy in Patients With Symptomatic Carotid Stenosis (International Carotid Stenting Study): An Interim Analysis of a Randomised Controlled Trial

Description
The goal of the trial was to evaluate treatment with carotid artery stenting compared with carotid endarterectomy among patients with recently symptomatic carotid artery stenosis.
Hypothesis
Carotid artery stenting would be more effective at preventing major cerebrovascular accidents.
Drugs/Procedures Used
Patients with recently symptomatic carotid artery stenosis were randomized to carotid artery stenting (n = 855) versus carotid endarterectomy (n = 858). The use of an embolic protection device was encouraged, but not mandatory during stenting.
Concomitant Medications
Patients who received a carotid stent were pretreated with aspirin and clopidogrel, and for 30 days after the procedure.
Principal Findings
Overall, 1,713 patients were randomized. In the stent group, the mean age was 70 years, 30% were women, the degree of carotid stenosis was 70-99% in 89% of patients, 32% had a recent transient ischemic attack, and 46% had a recent ischemic hemispheric stroke. Carotid stenting was performed at experienced centers in 88% and carotid endarterectomy was performed at experienced centers in 89%.

At 4 months, the composite outcome of death, stroke, or procedural myocardial infarction occurred in 8.5% of the stent group versus 5.2% of the endarterectomy group (p = 0.006). Similarly, any stroke occurred in 7.7% versus 4.1% (p = 0.002), any stroke or death 8.5% versus 4.7% (p = 0.001), any stroke or procedural death 8.0% versus 4.2% (p = 0.001), disabling stroke or death 4.0% versus 3.2% (p = 0.34), and all-cause death 2.3% versus 0.8% (p = 0.017), respectively for stent versus endarterectomy.

In the stent group, most of the strokes within 4 months were ipsilateral and ischemic in etiology (non-disabling and lasting more than 7 days). Cranial nerve palsy occurred in 1 versus 34 (p < 0.0001), and severe hematoma occurred in 9 versus 28 (p = 0.0007), respectively.
Interpretation
Among patients with a recent transient ischemic attack or stroke attributable to significant carotid artery stenosis, the use of carotid stenting was not superior to endarterectomy. Carotid artery stenting was associated with an increased hazard of death, stroke, or myocardial infarction within 4 months. There was also an excess of: 1) any stroke, 2) any stroke or death, 3) any stroke or procedural death, and 4) all-cause death among patients who received a carotid stent. There were fewer cranial nerve palsies and hematomas in the stent group. In the stent group, most strokes were ipsilateral, ischemic in etiology, and non-disabling, although lasting for >7 days.

The investigators performed a meta-analysis on three trials that enrolled symptomatic patients with carotid stenosis (EVA-3S, SPACE, and ICSS) and documented increased hazard of death, stroke, or myocardial infarction at 30 days with carotid stenting (p = 0.0002).

The recently presented CREST trial, which enrolled asymptomatic and symptomatic patients with carotid artery stenosis, found a similar incidence of death, stroke, or myocardial infarction within 30 days; however, minor strokes were increased with stenting, and myocardial infarctions were increased with carotid endarterectomy.
Conditions
• Carotid stenosis
• Cerebrovascular disease
• Prevention
Therapies
• Stent
• Carotid endarterectomy
Study Design
Randomized. Blinded. Parallel. Stratified.
Patients Enrolled: 1,713
Mean Follow-Up: 3 years
Mean Patient Age: 70 years
% Female: 30%

Primary Endpoints
3-year composite of fatal or disabling stroke in any territory
Secondary Endpoints
4-month composite of death, stroke, or procedural myocardial infarction
Any stroke
Any stroke or death
Any stroke or procedural death
Disabling stroke or death
All-cause death
Patient Population
Patients at least 40 years of age
Carotid artery stenosis >50%
Symptoms attributable to the carotid artery stenosis within the preceding 12 months
Exclusions:
Major stroke without recovery of function
Previous carotid artery stenting or endarterectomy or any contraindication for either procedure
Planned coronary artery bypass grafting or other major surgery
References: International Carotid Stenting Study Investigators. Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial. Lancet 2010;Feb 26:[Epub ahead of print].

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Title: Aspirin for Asymptomatic Atherosclerosis (AAA)
Trial Sponsor: British Heart Foundation, Chief Scientist Office of the Scottish Executive, and Bayer Healthcare
Year Presented: 2009
Year Published 2010
Topic(s): General Cardiology, Prevention/Vascular
Summary Posted: 3/2/2010 4:00:00 PM
Writer: Ms. Sabina A. Murphy
Author Disclosure: Consulting Fees: Eli Lilly
Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C.
Author Disclosure: Research/Research Grants: Astra Zeneca; Consultant Fees/Honoraria: Duke Clinical Research Institute; Research/Research Grants: Heartscape; Research/Research Grants: PLx Pharma; Research/Research Grants: Cogentus; Research/Research Grants: Sanofi Aventis; Data Safety Monitoring Board (Gov’t/Nonprofit): Duke Clinical Research Institute; Research/Research Grants: Bristol Myers Squibb; Research/Research Grants: Eisai; Research/Research Grants: Takeda; Research/Research Grants: The Medicines Company; Research/Research Grants: Ethicon
Supplemental Reviewer: Anthony A. Bavry, M.D., M.P.H., F.A.C.C.
Author Disclosure: This author has nothing to disclose.

Related Resources
Summary Slide: AAA Trial
Related Trial: Physicians' Health Study (Aspirin component) (Physicians' Health (Aspirin))
Related Trial: Women's Health Study: Low-Dose Aspirin in Primary Prevention

Description
The goal of the trial was to evaluate treatment with aspirin compared with placebo for primary prevention among patients with a low ankle brachial index (ABI).
Hypothesis
Use of low-dose aspirin would be associated with a reduction in the composite outcome of a fatal or nonfatal coronary event, stroke, or revascularization for primary prevention in patients with a low ABI.
Drugs/Procedures Used
Subjects (n = 28,980) free of cardiovascular disease underwent ABI screening (ratio of systolic pressure in the ankle to that in the arm). Patients with low ABI (≤0.95) were randomized in a double-blind manner to 100 mg enteric coated aspirin (n = 1,675) versus matching placebo (n = 1,675). The trial was powered to detect a 25% reduction in events with aspirin versus placebo.
Concomitant Medications
At baseline, in the aspirin group, diuretics were used in 15.5%, beta-blockers in 10.0%, nitrates/calcium channel blockers in 6.6%, angiotensin-converting inhibitors/angiotensin-receptor blockers in 6.3%, and lipid-lowering agents in 4.1%.
Principal Findings
The mean ABI at study entry was 0.86. Mean age was 62 years, and 72% were women.

There was no difference in the primary endpoint of fatal or nonfatal coronary event, stroke, or revascularization between the aspirin and placebo groups (10.8% vs. 10.5%, respectively, hazard ratio [HR] 1.03, 95% confidence interval [CI] 0.84-1.27, p = NS). Likewise, there was no difference between the aspirin and placebo groups in the secondary composite endpoint, which included the primary endpoint plus angina, intermittent claudication, and transient ischemic attack (HR 1.00, 95% CI 0.85-1.17, p = NS) or in the secondary endpoint of all-cause mortality (HR 0.95, 95% CI 0.77-1.16, p = NS). There was also no difference in nonfatal stroke (2.2% vs. 2.3%, p = NS) or nonfatal myocardial infarction (MI) (3.7% vs. 4.1%, p = NS). Major bleeding requiring hospital admission occurred in 2.0% of the aspirin group and 1.2% of the placebo group (HR 1.71, 95% CI 0.99-2.97).
Interpretation
Among patients with a low ABI but no known cardiovascular disease, treatment with enteric coated aspirin was not associated with a difference in the composite endpoint of a fatal or nonfatal coronary event, stroke, or revascularization at a mean follow-up of 8.2 years compared with placebo. Aspirin therapy was associated with an increase in major bleeding.

The efficacy of aspirin for secondary prevention following a cardiovascular event has been well established in several large-scale trials, as well as in a patient-level meta-analysis by the Antithrombotic Trialists' Collaboration. However, the effect of aspirin for primary prevention has not been studied as extensively and has shown mixed results in the trials that are available. Low-dose aspirin decreased the risk of first MI by 44% compared with placebo in the Physician's Health Study. In the Women’s Health Study, there was no significant difference in major cardiovascular events, but stroke was lower in women randomized to aspirin compared with placebo.

Healthy subjects with a low ABI have previously been shown to be at high risk for future vascular events independent of other clinical cardiovascular risk factors. Despite the higher risk for vascular events, aspirin had no impact on vascular events in the present study, but did increase major bleeding. The compliance was relatively low in the study (60%), which could have contributed to the null findings. In addition, a relatively large treatment effect (25% RRR) was needed to detect a difference and it is possible that the study was underpowered to detect a smaller difference.
Conditions
• Prevention/Primary
Therapies
• Antiplatelet agent / Aspirin
Study Design
Placebo controlled. Randomized. Blinded.
Patients Screened: 28,980
Patients Enrolled: 3,350
Mean Follow-Up: 8.2 years
Mean Patient Age: 62 years
% Female: 72

Primary Endpoints
Composite of initial fatal or nonfatal coronary event or stroke or revascularization
Secondary Endpoints
All initial vascular events defined as a composite of a primary endpoint event or angina, intermittent claudication, or transient ischemic attack
All-cause mortality
Patient Population
Men and women ages 50-80 years and free of cardiovascular disease were recruited from general practice registers in Lanarkshire, Glasgow, and Edinburgh in Scotland and had an ABI screening test.
Those with a low ABI (≤0.95) who were not already taking routine aspirin or warfarin and volunteered were included.
Exclusions:
Severe indigestion
History of MI, stroke, angina, or peripheral arterial disease
Chronic liver or kidney disease
Chemotherapy
Contraindications to treatment with aspirin
An abnormally high or low packed cell volume
References: Fowkes FG, Price JF, Stewart MC, et al. Aspirin for prevention of cardiovascular events in a general population screened for a low ankle brachial index: a randomized controlled trial. JAMA 2010;303:841-8.

Presented by Dr. Gary Fowkes at the European Society of Cardiology Congress, Barcelona, Spain, August 2009.

[Chevychelov]

Title: Warfarin and Aspirin Use in Atrial Fibrillation Among Practicing Cardiologists (From the AFFECTS Registry)
Topic: Arrhythmias
Date Posted: 3/4/2010
Author(s): Kowey PR, Reiffel JA, Myerburg R, et al.
Citation: Am J Cardiol 2010;Feb 22:[Epub ahead of print].
Clinical Trial: No
Related Resources
Journal Scan: Practice Patterns Among United States Cardiologists for Managing Adults With Atrial Fibrillation (From the AFFECTS Registry)

Study Question: What is the pattern of anticoagulation use in patients with atrial fibrillation (AF) in contemporary practice?
Methods: This was an analysis of 1,461 patients (mean age 66 years) who had AF (paroxysmal in 80%) without structural heart disease and who were enrolled in a multicenter registry. Participating cardiologists were trained in the practice guidelines of the American College of Cardiology/American Heart Association/European Society of Cardiology. Follow-up data were gathered for 1 year after enrollment. The choice of therapy was at the treating physician’s discretion. The Congestive heart failure, Hypertension, Age, Diabetes, Stroke (CHADS2) score was determined by post-hoc record review. A CHADS2 score ≥2 was considered indicative of a high risk of stroke.
Results: A rhythm-control strategy was used in 64% of patients and a rate-control strategy in 36%. Overall, 83% of patients received either warfarin (64%) or aspirin (32%), with no significant difference between the rhythm-control and rate-control groups. Among the high-risk patients, warfarin was used in 66% of rhythm-control patients and 73% of rate-control patients. Among the low-risk patients (CHADS2 <2), warfarin was used in 49% of rhythm-control patients and 60% of rate-control patients. The combined rate of embolism and cerebral nervous system bleeding was 0.9%.
Conclusions: Anticoagulation use in patients with AF often is inconsistent with practice guidelines.
Perspective: Several studies have indicated that warfarin is underused in patients with AF. The registry data in this study demonstrate that this continues to be the case, with approximately 25-35% of high-risk patients not receiving warfarin despite the guidelines training provided to the treating physicians. The results emphasize the need for more effective dissemination and implementation of practice guidelines. Fred Morady, M.D., F.A.C.C.

Title: Practice Patterns Among United States Cardiologists for Managing Adults With Atrial Fibrillation (From the AFFECTS Registry)
Topic: Arrhythmias
Date Posted: 3/4/2010
Author(s): Reiffel JA, Kowey PR, Myerburg R, et al.
Citation: Am J Cardiol 2010;Feb 22:[Epub ahead of print].
Clinical Trial: No
Related Resources
Journal Scan: Warfarin and Aspirin Use in Atrial Fibrillation Among Practicing Cardiologists (From the AFFECTS Registry)

Study Question: How do community-based cardiologists treat atrial fibrillation (AF)?
Methods: This was an analysis of 1,461 patients (mean age 66 years) who had AF (paroxysmal in 80%, symptomatic in 77%) without structural heart disease and who were enrolled in a multicenter, prospective registry. Participating cardiologists were trained in the practice guidelines of the American College of Cardiology/American Heart Association/European Society of Cardiology (ACC/AHA/ESC). Follow-up data were gathered for 1 year after enrollment. The choice of therapy was at the treating physician’s discretion.
Results: At baseline, a rhythm-control strategy was chosen for 64% of patients and a rate-control strategy for 36%. Rhythm control was attempted significantly more often for paroxysmal AF (67%) than for persistent AF (55%). A rhythm-control strategy also was selected more often for symptomatic than asymptomatic persistent AF (60% vs. 40%, respectively), but in a similar proportion of patients with symptomatic and asymptomatic paroxysmal AF (68% and 63%, respectively). The most common first-line rhythm-control drugs were sustained-release propafenone (43%) and sotalol (17%), and the most common second-line drugs were sustained-release propafenone (36%) and amiodarone (22%).
Conclusions: Community-based treatment of AF in patients without structural heart disease is fairly compliant with ACC/AHA/ESC practice guidelines.
Perspective: The ACC/AHA/ESC guidelines recommend that a rate-control strategy be used for patients with minimally symptomatic or asymptomatic AF. It is noteworthy that a large proportion of patients with asymptomatic AF nevertheless are treated with rhythm-control drugs in community practice. It appears that, despite current guidelines, many cardiologists have not abandoned the deep-rooted (and logical) belief that sinus rhythm is better than AF for many patients. Fred Morady, M.D., F.A.C.C.

[Chevychelov]

Title: Inadvertent Electrical Isolation of the Left Atrial Appendage During Catheter Ablation of Persistent Atrial Fibrillation
Topic: Arrhythmias
Date Posted: 3/2/2010
Author(s): Chan CP, Wong WS, Pumprueg S, et al.
Citation: Heart Rhythm 2010;7:173-180.
Clinical Trial: No
Study Question: What are the mechanisms of inadvertent isolation of the left atrial appendage (LAA) during atrial fibrillation (AF) ablation?
Methods: This study consisted of 11 patients (ejection fraction 0.43 ± 0.18, left atrial diameter 51 ± 8 mm) with persistent AF who had LAA conduction block during a procedure for AF (n = 8) or atrial tachycardia (AT) (n = 3). LAA isolation was defined as the complete elimination or dissociation of LAA potentials.
Results: LAA conduction block occurred during ablation at the Bachmann bundle region in six patients, mitral isthmus in three, LAA base in two, and coronary sinus in one. The mean distance from the ablation site to the LAA base was 5.0 ± 1.9 cm. LAA isolation was transient in all six patients in whom LAA conduction was monitored and was permanent in the four patients in whom conduction was not monitored during energy delivery. The remaining patient was noted to have LAA isolation during a redo procedure before any ablation. Nine of (82%) the 11 patients have remained arrhythmia-free without antiarrhythmic drugs at mean follow-up of 6 ± 7 months, and all have continued taking warfarin.
Conclusions: The authors concluded that electrical isolation of the LAA may occur during ablation of persistent AF and AT, and is due to disruption of the Bachmann bundle and its leftward extension.
Perspective: The primary finding of this study is that inadvertent LAA isolation may occur in patients undergoing a catheter ablation procedure for persistent AF or postablation AT, even if the ablation site is far removed from the appendage. The mechanism most likely is due to injury to the leftward extension of the Bachmann bundle and its branches that surround the base of the LAA. Although LAA conduction slowing was observed within seconds of initiation of RF current, the results of this study should not necessarily imply that the appendage may be isolated with a single lesion. It is more likely that LAA conduction was severely impaired either by prior ablation or as a result of a myopathic process in those patients, such that further injury (related to ablation) to the existing intra-atrial routes readily resulted in LAA isolation. Overall, the study suggests that monitoring LAA conduction during the procedure would be important in preventing LAA isolation. Debabrata Mukherjee, M.D., F.A.C.C.

Title: Analysis of the Impact of Early Surgery on In-Hospital Mortality of Native Valve Endocarditis: Use of Propensity Score and Instrumental Variable Methods to Adjust for Treatment-Selection Bias
Topic: Cardiovascular Surgery
Date Posted: 3/3/2010
Author(s): Lalani T, Cabell CH, Benjamin DK, et al.
Citation: Circulation 2010;121:1005-1013.
Clinical Trial: No
Study Question: Is there a beneficial role for early surgical intervention in patients with native valve infective endocarditis (IE)?
Methods: Using a prospective, multinational cohort of patients with definite native valve IE, the effect of early surgery on in-hospital mortality was assessed by propensity-based matching adjustment for survivor bias and by instrumental variable analysis. Patients were stratified by propensity quintile, paravalvular complications, valve perforation, systemic embolization, stroke, Staphylococcus aureus infection, and congestive heart failure.
Results: Of the 1,552 patients with native valve IE, 720 (46%) underwent early surgery and 832 (54%) were treated with medical therapy. Compared with medical therapy, early surgery was associated with a significant reduction in mortality in the overall cohort (12.1% [87/720] vs. 20.7% [172/832]) and after propensity-based matching and adjustment for survivor bias (absolute risk reduction [ARR] –5.9%, p < 0.001). With a combined instrument, the instrumental-variable adjusted ARR in mortality associated with early surgery was –11.2% (p < 0.001). In subgroup analysis, surgery was found to confer a survival benefit compared with medical therapy among patients with a higher propensity for surgery (ARR –10.9% for quintiles 4 and 5, p = 0.002) and those with paravalvular complications (ARR –17.3%, p < 0.001), systemic embolization (ARR –12.9%, p = 0.002), S. aureus native valve IE (ARR –20.1%, p < 0.001), and stroke (ARR –13%, p = 0.02), but not those with valve perforation or congestive heart failure.
Conclusions: This retrospective propensity-matched study suggests that early surgery for native valve IE is associated with an in-hospital mortality benefit compared with medical therapy alone.
Perspective: Traditional treatment of IE is extended antimicrobial therapy; surgical intervention is reserved for either specific early indications (persistent fevers or bacteremia despite appropriate antibiotic therapy, recurrent embolic events despite appropriate antibiotic therapy, or hemodynamic compromise as a result of valve destruction), or for later sequelae of valve destruction. This study, and some similar studies presented at recent meetings, suggests a possible shift in thinking, with a stated conclusion that earlier surgery is better. However, caveats abound. First, early surgery in this study was defined only as surgery during the initial hospitalization––not as surgery as soon as endocarditis is diagnosed. Second, as always (and unlike prospective, randomized trials), propensity score matching controls only for identified variables. At my institution, and I suspect at most others, there still needs to be a reason to operate ‘early.’ This means that, despite propensity score matching, patients operated early probably were different from those who were operated late (but in ways that were not identified). After the dust has settled, a fair conclusion might turn out to be that surgery to repair the damage done from IE might best be done after initial treatment of infection, but before months have passed. In the meantime, a bit of caveat emptor seems in order: Out of concern for early re-infection, it is doubtful that elective surgery for native valve IE should be done before a healthy amount of antimicrobial therapy has been administered. David S. Bach, M.D., F.A.C.C.

[Chevychelov]

Title: Efficacy and Safety of Rosuvastatin Therapy for Children With Familial Hypercholesterolemia
Topic: Congenital Heart Disease
Date Posted: 3/8/2010 5:00:00 PM
Author(s): Avis HJ, Hutten BA, Gagne C, et al.
Citation: J Am Coll Cardiol 2010;55:1121-1126.
Clinical Trial: yes
Related Resources
JACC Article: Efficacy and Safety of Rosuvastatin Therapy for Children With Familial Hypercholesterolemia

Study Question: What is the safety and efficacy of rosuvastatin therapy for children with familial hypercholesterolemia?
Methods: A 12-week, double-blind, randomized, placebo-controlled trial was performed, followed by a 40-week open-label extension phase. A total of 177 children (mean age 14.5 years) were enrolled, and were randomized either to placebo or rosuvastatin 5, 10, or 20 mg daily.
Results: Low-density lipoprotein cholesterol (LDL-C) reduction with 5, 10, and 20 mg of rosuvastatin was 38%, 45%, and 50%, respectively, as compared with placebo. During the open-label phase, maximum dosing of 20 mg daily resulted in 40% of patients achieving the treatment goal LDL-C of <110 mg/dl. No impact on growth or development was seen.
Conclusions: In children with familial hypercholesterolemia, rosuvastatin 20 mg resulted in LDL-C reductions of 50%. A minority of patients achieved the LDL-C target of 110 mg/dl, consistent with the high baseline LDL-C in this patient population.
Perspective: Familial hypercholesterolemia is associated with early atherosclerosis and cardiovascular events. This study demonstrates efficacy of the high potency HMG-CoA reductase inhibitor rosuvastatin in reducing LDL-C levels in adolescents. Despite a 50% reduction in LDL-C, a minority of patients reached the goal LDL-C, in large part due to the high baseline LDL-C level of 228-239 mg/dl. Compliance was an issue in the open-label extension of this study, with 60% of patients maintaining ≥80% compliance with the study drug. This is reflective of the challenge of compliance with drug therapy in adolescents. The long-term safety of these agents in adolescents has not yet been reported. Timothy B. Cotts, M.D., F.A.C.C.

Title: Cardiovascular Manifestations of Fabry Disease: Relationships Between Left Ventricular Hypertrophy, Disease Severity, and α-galactosidase A Activity
Topic: Congenital Heart Disease
Date Posted: 3/2/2010
Author(s): Wu JC, Ho CY, Skali H, et al.
Citation: Eur Heart J 2010;Jan 7:[Epub ahead of print].
Clinical Trial: No
Study Question: In patients with Fabry disease, what are the relationships between disease severity, α-galactosidase A (α-gal) activity, and cardiac abnormalities?
Methods: A prospective analysis of patients undergoing screening for clinical trials of enzyme replacement therapy was performed. Baseline echocardiograms, electrocardiograms, exams, basic laboratory studies, and α-gal activity were analyzed.
Results: A total of 139 patients (92 males and 47 females) were studied. Cardiovascular symptoms were reported in 60.4% of patients, while 84.8% of patients showed concentric left ventricular hypertrophy (LVH). In females, log-corrected α-gal activity was inversely associated with LV mass index (r = -0.45, p < 0.040). The most LVH and cardiac symptoms were seen in males with low α-gal activity, although LVH was present in females less than 20 years old.
Conclusions: Concentric LVH was the prominent cardiac pathology in patients with Fabry disease, occurring even in young females.
Perspective: Fabry disease is a rare X-linked recessive lysosomal storage disorder associated with infiltrative and occlusive disease of the heart, kidney, and in the brain. This study documents cardiac involvement in patients under consideration for enrollment in enzyme replacement therapy studies. As one of the studies required moderate renal dysfunction for participation, this analysis may have selected patients with more advanced disease. As even relatively young patients were seen to have cardiac involvement, there may be a role for early enzyme replacement therapy to positively impact the natural history of cardiac involvement. Timothy B. Cotts, M.D., F.A.C.C.

[Chevychelov]

Title: Anthracycline-Induced Cardiomyopathy: Clinical Relevance and Response to Pharmacologic Therapy
Topic: Heart Failure/Transplant
Date Posted: 3/2/2010
Author(s): Cardinale D, Colombo A, Lamantia G, et al.
Citation: J Am Coll Cardiol 2010;55:213-220.
Clinical Trial: No
Related Resources
JACC Article: Anthracycline-Induced Cardiomyopathy: Clinical Relevance and Response to Pharmacologic Therapy

Study Question: What is the clinical relevance of anthracycline-induced cardiomyopathy (AC-CMP) and its response to heart failure (HF) therapy?
Methods: The study cohort was comprised of 201 consecutive patients with a left ventricular ejection fraction (LVEF) <45% due to AC-CMP. Enalapril and, when possible, carvedilol were promptly initiated after detection of LV systolic dysfunction. LVEF was measured at enrollment, every month for the first 3 months, every 3 months during the first 2 following years, and every 6 months afterward (mean follow-up 36 ± 27 months). Patients were considered responders, partial responders, or nonresponders according to complete, partial, or no recovery in LVEF, respectively. They also evaluated major adverse cardiac events during follow-up.
Results: Forty-two percent of the patients (n = 85) were responders, 13% (n = 26) were partial responders, and 45% (n = 90) were nonresponders. The percentage of responders progressively decreased as the time from the end of chemotherapy to the start of HF treatment increased; no complete recovery of LVEF was observed after 6 months. Responders showed a lower rate of cumulative cardiac events than partial and nonresponders (5%, 31%, and 29%, respectively; p < 0.001).
Conclusions: The study investigators concluded that in cancer patients developing AC-CMP, LVEF recovery and cardiac event reduction may be achieved when cardiac dysfunction is detected early and a modern HF treatment is promptly initiated.
Perspective: This is an important study, which confirms that early initiation of therapy with angiotensin-converting enzyme inhibitors (Circulation 2006;114:2474-81) and beta-blockers (J Am Coll Cardiol 2006;48:2258-62) in AC-CMP is beneficial. Ragavendra R. Baliga, M.B.B.S.

Title: Triage After Hospitalization With Advanced Heart Failure: The ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) Risk Model and Discharge Score
Topic: Heart Failure/Transplant
Date Posted: 3/5/2010
Author(s): O’Connor CM, Hasselblad V, Mehta RH, et al.
Citation: J Am Coll Cardiol 2010;55:872-878.
Clinical Trial: No
Related Resources
JACC Article: Triage After Hospitalization With Advanced Heart Failure: The ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) Risk Model and Discharge Score

Study Question: What are the predictors of morbidity and mortality at hospital discharge?
Methods: The investigators used data from the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) trial to develop a predictive model, and internally validated their approach by the bootstrapping method. They used model coefficients to generate an additive risk score. They also used data from FIRST (Flolan International Randomized Survival Trial) to externally validate this model.
Results: This study found that among patients discharged with complete data (n = 423), the 6-month mortality and death and rehospitalization rates were 18.7% and 64%, respectively. Risk factors for mortality at discharge included B-type natriuretic peptide, per doubling (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.15-1.75), cardiopulmonary resuscitation or mechanical ventilation during hospitalization (HR, 2.54; 95% CI, 1.12-5.78), blood urea nitrogen, per 20-U increase (HR, 1.22; 95% CI, 0.96-1.55), serum sodium, per unit increase (HR, 0.93; 95% CI, 0.87-0.99), age >70 years (HR, 1.05; 95% CI, 0.51-2.17), daily loop diuretic, furosemide equivalents >240 mg (HR, 1.49; 95% CI, 0.68-3.26), lack of beta-blocker (HR, 1.28; 95% CI, 0.68-2.41), and 6-minute walk, per 100-foot increase (HR, 0.955; 95% CI, 0.99-1.00; c-index 0.76). A simplified discharge score discriminated mortality risk from 5% (score = 0) to 94% (score = 8). Bootstrap validation demonstrated good internal validation of the model (c-index, 0.78; 95% CI, 0.68-0.83).
Conclusions: The authors concluded that the ESCAPE study discharge risk model and score refine risk assessment after in-hospital therapy for advanced decompensated systolic heart failure, allowing clinicians to focus surveillance and triage for early life-saving interventions in this high-risk population.
Perspective: This is an important study because it identifies patients with risk ‘at the time of discharge.’ Further studies are needed to determine whether this score adds incremental value to currently used yardsticks such as the Heart Failure Survival Score developed by Aaronson et al., the MUSIC risk score (see Journal Scan), or the Seattle Heart Failure Model (Circulation 2006;113:1424-33). Overall, it is becoming increasingly clear that clinicians would be expected to calculate mortality risk for all heart failure patients at the time of hospital discharge to better manage their patients. Ragavendra R. Baliga, M.B.B.S.