Обзор американских кардиологических журналов за неделю (ссылки)

[Chevychelov]

Title: Recommendations for Interpretation of 12-Lead Electrocardiogram in the Athlete
Topic: Arrhythmias
Date Posted: 1/8/2010
Author(s): Corrado D, Pelliccia A, Heidlbuchel H, et al.
Citation: Eur Heart J 2009;Dec 22:[Epub ahead of print].
Clinical Trial: No
Perspective: The following are 10 points to remember from this position paper formulated by the European Society of Cardiology:

1. Electrocardiographic findings that are common and training-related and that do not require additional evaluation are sinus bradycardia, 1° atrioventricular block (AVB), incomplete right bundle branch block (BBB), early repolarization, and isolated voltage criteria for left ventricular hypertrophy (LVH).

2. Uncommon and training unrelated electrocardiographic findings that mandate further evaluation include T-wave inversion, ST-segment depression, pathological Q waves, atrial enlargement, a hemiblock, right ventricular hypertrophy, a BBB, or a Brugada-pattern of ST-segment elevation.

3. Training-related electrocardiographic findings are more common in men than women, athletes of African descent, and high-endurance athletes such as cyclists.

4. Sinus rates <30 bpm and sinus pauses >2 seconds are common in highly trained athletes, particularly during sleep.

5. A normal chronotropic response to exertion and the absence of bradycardia-related symptoms distinguishes training-related sinus bradycardia from sinus node dysfunction.

6. 1° AVB and Mobitz I 2° AVB are common, but Mobitz II 2° AVB or 3° AVB should not be assumed to be training-related and require evaluation.

7. Early repolarization in Caucasian athletes most commonly consists of upwardly concave ST-segments and tall and peaked T waves; in black athletes, there often is convex ST-segment elevation and negative T waves, mimicking a Brugada pattern.

8. In the presence of voltage criteria for LVH, pathological hypertrophy should be suspected if there is left atrial enlargement, left-axis deviation, repolarization abnormalities, or pathological Q waves.

9. T-wave inversion ≥2 mm in ≥2 adjacent leads should prompt evaluation for structural heart disease.

10. Electrophysiological testing for risk stratification with possible catheter ablation is appropriate in athletes with ventricular pre-excitation. Fred Morady, M.D., F.A.C.C.

Title: Improved Survival Among Patients With Eisenmenger Syndrome Receiving Advanced Therapy for Pulmonary Arterial Hypertension
Topic: Arrhythmias
Date Posted: 1/11/2010
Author(s): Dimopoulos K, Inuzuka R, Goletto S, et al.
Citation: Circulation 2010;121:20-25.
Clinical Trial: No
Study Question: Advanced therapy (AT) for pulmonary arterial hypertension (PAH) in the context of congenital heart disease improves pulmonary hemodynamics, functional class, and the 6-minute walk test. Has there been an effect of AT on survival in the Eisenmenger syndrome?
Methods: Data on all Eisenmenger patients attending a single center over the past decade were collected. Survival rates were compared between patients on and off AT with the use of a modified version of the Cox model, which treats modern AT as a time-varying covariate. Baseline differences were adjusted for the use of propensity scores.
Results: A total of 229 patients (ages 34.5 ± 12.6 years; 35.4% male) were included. The majority had complex anatomy, and 53.7% were in New York Heart Association (NYHA) class ≥III at baseline. Mean resting oxygen saturation was 84.3%. Sixty-eight patients (29.7%) either were on AT or had AT initiated during follow-up. During a median follow-up of 4.0 years, 52 patients died, only 2 of them while on AT. Patients on AT were at a significantly lower risk of death, both unadjusted and after adjustment for baseline clinical differences by propensity score regression adjustment (C statistic = 0.80; hazard ratio, 0.16; 95% confidence interval, 0.04-0.71; p = 0.015) and propensity score matching (hazard ratio, 0.10; 95% confidence interval, 0.01-0.78; p = 0.028). Despite being older and sicker, only 2 of the 68 patients who received AT for a median period of 2.4 years died, compared with 50 deaths in those not receiving AT.
Conclusions: Advanced treatment for PAH in a contemporary cohort of adults with Eisenmenger syndrome was associated with a lower risk of death. Survival benefits should be considered together with improved hemodynamics and functional class when decisions are made about treatment in this population.
Perspective: The prostanoids, endothelin antagonists, and phosphodiesterase-5 inhibitors (advanced therapies) have each alone and in combination been effective at improving quality of life in PAH. A meta-analysis of randomized controlled trials of PH-specific therapies in various types of PAH recently showed a 43% reduction in overall mortality rate, but did not include the Eisenmenger syndrome. Placebo-controlled trials in congenital heart disease are limited, and placebo-controlled trials to assess the effects on mortality rate would be considered unethical. The survival advantage of those treated with advanced therapy in this single center as measured by the hazard ratio is over ninefold, despite the fact that patients receiving the novel drugs were more often NYHA class IV, older, and had more syncope. Melvyn Rubenfire, M.D., F.A.C.C.

[Chevychelov]

Title: Protective Effect of Periconceptional Folic Acid Supplements on the Risk of Congenital Heart Defects: A Registry-Based Case-Control Study in the Northern Netherlands
Topic: Congenital Heart Disease
Date Posted: 12/31/2009
Author(s): van Beynum IM, Kapusta L, Bakker MK, den Heijer M, Blom HJ, de Walle HE.
Citation: Eur Heart J 2009;Dec 1:[Epub ahead of print].
Clinical Trial: No
Study Question: Is there a protective effect of periconceptional folic acid use on the risk of congenital heart disease (CHD)?
Methods: A case control study was performed using the EUROCAT–Northern Netherlands registry. All infants registered with CHD from 1996-2005 were included. Patients with CHD were categorized as having either: 1) an isolated single heart defect, 2) multiple heart defects, 3) heart defects associated with other congenital anomalies, or 4) a genetic anomaly with associated cardiac defect, such as in trisomy 21. Parents of registered infants completed questionnaires with items related to demographics, medications, vitamin intake, smoking habits, and alcohol consumption. Mothers were defined as using periconceptional folic acid if they took folic acid supplementation through the entire advised period of 4 weeks prior to conception and 8 weeks post-conception, or if they took folic acid following conception, regularly through the advised period. Others were categorized as nonusers, except when the use of folic acid was unknown or when a folic acid antagonist use was reported, which resulted in exclusion from the analysis. Analysis for potential confounders, including association of folic acid use with maternal age, maternal body mass index (BMI), smoking, ethyl alcohol (ETOH) use, year of birth, and maternal education level, was performed. Relative risk for CHD was calculated with odds ratios from logistic regression models.
Results: Complete data were available from the registry on 3,836 mothers, with 3,012 remaining after exclusion for maternal diabetes, reported use of folic acid antagonists, or presence of defects, which can be reduced with the use of folic acid (neural tube defects, oral clefts, hypospadias, and limb reduction anomalies). There were 611 cases with CHD, and 2,401 controls. The controls included infants with chromosomal or genetic aberrations or other congenital anomalies. There were no differences between cases and controls in maternal age, BMI, educational level, smoking, ETOH use, or year of birth. Adequate use of periconceptional folic acid was found in 56% of cases, and 61% of controls. Mothers who had periconceptional folic acid use were 18% less likely to deliver an infant with any type of CHD, and 38% less likely to deliver an infant with a septal defect. Subgroup analysis did not demonstrate a lower risk with the use of folic acid for conotruncal defects, atrioventricular septal defects, right-sided obstruction, or left-sided obstruction lesions. With adjustment for previously described potential confounders (maternal age, BMI, smoking, ETOH, educational level, and year of birth), the odds ratio was 0.82 (95% confidence interval, 0.68-0.997).
Conclusions: The use of periconceptional folic acid was found to reduce the risk of CHD compared to other nonfolic acid–related malformations. The overall risk reduction from this case control study was 18%, with 38% reduction in risk for septal defects.
Perspective: Reduction of risk for CHD with the use of folic acid has been debated in the literature. The investigators have demonstrated in this well-described study the risk reduction for CHD that is accompanied by the use of folic acid in the periconceptional period. Although a randomized trial on folic acid intake would provide a more certain answer to this research question, because folic acid is recommended during the periconceptional period to reduce other birth defects including neural tube defects, such a trial would be unethical. Case control trials are limited by the ability to adjust for potential confounders. In this study, van Bynum and colleagues did adjust for major confounders including the use of folic acid antagonists. The control group was a group of patients with anomalies thought unrelated to folic acid use. This is not a perfect substitute for the general population, but likely provides a more conservative estimate of the effect of folic acid. In conclusion, these data are supportive of a role of folic acid during the periconceptional period to reduce the risk of CHD by nearly 20%, with a 38% reduction in the rate of septal defects. The optimal dose and method of intake of folic acid through supplemented food, multivitamins, or an isolated folic acid supplement remains unclear. Caren S. Goldberg, M.D., F.A.C.C.

Title: Use of Genetics in the Clinical Evaluation of Cardiomyopathy
Topic: Heart Failure/Transplant
Date Posted: 12/29/2009
Author(s): Judge DP.
Citation: JAMA 2009;302:2471-2476.
Clinical Trial: No
Perspective: The following are 10 points to remember about use of genetics in the clinical evaluation of cardiomyopathy:

1. Dilated cardiomyopathy (DCM) occurs in approximately 1 in 2,500 persons in the United States, and at least 20-35% of these patients have an affected family member. Every patient presenting with DCM should have a family history taken, including information about CM, sudden cardiac death, and syndromic features over at least three generations. DCM in a single additional family member establishes the diagnosis of familial DCM, in the absence of other factors associated with CM such as severe hypertension, severe coronary artery disease, and excessive chronic ethyl alcohol use.

2. Since early treatment with angiotensin-converting enzyme (ACE) inhibitors has been shown to be beneficial in patients with left ventricular (LV) dysfunction, recognition of patients predisposed to DCM is clinically important. For example, a small study showed that incident CM was reduced in patients with Duchenne muscular dystrophy if they were treated with an ACE inhibitor prior to the onset of LV dysfunction.

3. Marked genetic heterogeneity complicates genetic testing for CM. Mutations in more than 35 genes have been associated with DCM, and genetic testing is clinically available for about half of these.

4. Mutations in the lamin A/C gene are found in 5-20% of patients with DCM, and may result in a worse prognosis. Ten percent of DCM patients have a mutation in a sarcomere gene.

5. Hypertrophic CM (HCM) occurs in about 1 in 500 persons in the United States, and is the most common cause of sudden death in young athletes. Most mutations identified are found in sarcomere genes. Sarcomere mutations can thus cause either HCM or DCM.

6. Fabry disease is an X-linked lysosomal storage disease due to deficiency of α-galactosidase A that may lead to LV hypertrophy, which is difficult to distinguish from HCM due to other mutations. Other features associated with Fabry disease include skin angiokeratomas, corneal clouding, neuropathy, anhidrosis, and renal failure. The Food and Drug Administration has approved recombinant enzyme treatment for this disease.

7. Familial amyloidosis may present with similar features to other forms of HCM, but with echocardiograms showing LV hypertrophy and electrocardiograms showing low voltage. Monoclonal light chains should be measured in the serum and urine in these cases, and a cardiac biopsy can confirm the diagnosis with appropriate staining. Familial cardiac amyloid is often due to mutations in the transthyretin gene, and may be associated with neuropathy and chronic diarrhea.

8. The development of genomic DNA sequencing chips will reduce the cost and increase the feasibility of genetic testing to become more widely applied in clinical practice; however, translating the information into clinical practice will be a major hurdle.

9. Genetic testing may provide the diagnostic gold standard for screening of relatives, thus allowing for more vigilant follow-up of those with positive testing. However, decisions not to undergo screening are based on issues such as: a) concern about establishing a pre-existing condition, b) potential negative impact on future insurance premiums and employment (although subjects should be protected by the Genetic Information Nondiscrimination Act [GINA]), and c) uncertainty regarding mutation pathogenicity.

10. Genetic counseling should be provided prior to genetic testing. Daniel T. Eitzman, M.D., F.A.C.C.

[Chevychelov]

Title: Novel Approaches for Preventing or Limiting Events (Naples) II Trial: Impact of a Single High Loading Dose of Atorvastatin on Periprocedural Myocardial Infarction
Topic: Interventional Cardiology
Date Posted: 1/7/2010
Author(s): Briguori C, Visconti G, Focaccio A, et al.
Citation: J Am Coll Cardiol 2009;54:2157-2163.
Clinical Trial: yes
Study Question: What is the effect of a single, high (80 mg) loading dose of atorvastatin on the rate of periprocedural myocardial infarction (MI)?
Methods: The day before the elective percutaneous coronary intervention (PCI), 668 statin-naive patients were randomly assigned to atorvastatin 80 mg (atorvastatin group; n = 338) or no statin treatment (control group; n = 330). Creatine kinase-myocardial isoenzyme (CK-MB) (upper limit of normal [ULN] 3.5 ng/ml) and cardiac troponin I (ULN 0.10 ng/ml) were assessed before and 6 and 12 hours after the intervention. Periprocedural MI was defined as a CK-MB elevation >3Ч ULN alone or associated with chest pain or ST-segment or T-wave abnormalities. The primary endpoint of the study was the rate of periprocedural MI, defined as a CK-MB elevation >3Ч ULN alone or associated with chest pain or ST-segment or T-wave abnormalities (new definition of MI), in the two study groups.
Results: The incidence of a periprocedural MI was 9.5% in the atorvastatin group and 15.8% in the control group (odds ratio, 0.56; 95% confidence interval, 0.35-0.89; p = 0.014). Median CK-MB peak after PCI was 2.10 ng/ml (interquartile range 1.00-12.50 ng/ml) in the atorvastatin group and 3.20 ng/ml (interquartile range 1.37-16.07 ng/ml) in the control group (p = 0.014). The incidence of cardiac troponin I elevation >3Ч ULN was 26.6% in the atorvastatin group and 39.1% in the control group (odds ratio, 0.56; 95% confidence interval, 0.40-0.78; p < 0.001).
Conclusions: The authors concluded that a single, high (80 mg) loading (within 24 hours) dose of atorvastatin reduces the incidence of periprocedural MI in elective PCI.
Perspective: This randomized study demonstrated that a single high (80 mg) loading dose of atorvastatin administered within 24 hours before stenting is effective in reducing the rate of periprocedural MI. This result confirms previous observations demonstrating that statins prevent MI after coronary stent implantation. However, in prior studies such as ARMYDA, statin administration was started several days before the procedure. The effectiveness of a single, high loading dose of a statin administered within 24 hours before stenting extends our knowledge of the cardioprotective effect of statin, obviating the need to postpone PCI in all statin-naive patients undergoing elective coronary procedures. The findings of this study need to be validated in a larger blinded study, but it makes clinical sense to administer a high dose of a potent statin prior to performing PCI. Debabrata Mukherjee, M.D., F.A.C.C.

Title: A Randomized Comparison of Transradial Versus Transfemoral Approach for Coronary Angiography and Angioplasty
Topic: Interventional Cardiology
Date Posted: 1/4/2010
Author(s): Brueck M, Bandorski D, Kramer W, Wieczorek M, Hцltgen R, Tillmanns H.
Citation: JACC Cardiovasc Interv 2009;2:1047-1054.
Clinical Trial: No
Study Question: What is the relative safety and feasibility of the transradial versus transfemoral approach for coronary angiography and intervention?
Methods: The authors randomized a total of 1,024 patients undergoing coronary catheterization to the transradial or transfemoral approach. Patients with an abnormal Allen's test, history of coronary artery bypass surgery, simultaneous right heart catheterization, chronic renal insufficiency, or known difficulties with the radial or femoral access were excluded.
Results: Successful catheterization was more common in the femoral (99.8% vs. 96.5%) compared with the radial group. Procedure time (median procedural duration 37.0 minutes vs. 40.2 minutes, p = 0.046) and radiation exposure (median dose area product 38.2 Gycm2 vs. 41.9 Gycm2, p = 0.034) were significantly lower in the transfemoral group compared with the transradial access group. There was no difference in the amount of contrast media use between the two groups. Vascular access site complications were higher in the transfemoral group (3.71% vs. 0.58%, p = 0.0008).
Conclusions: The use of radial access is associated with an increased procedural duration and radiation exposure, and a marked reduction in vascular complications.
Perspective: The reduction in groin complications and bleeding with the use of a radial approach has been highlighted in multiple studies. However, the increased radiation exposure to the patient and the operator is increasingly being recognized, and may translate into an increased late risk of malignancies. Better shielding strategies are needed to reduce this exposure so that the benefits of the radial approach can be obtained at minimal hazard to the patients or the operators. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

[Chevychelov]

Title: Enoxaparin Versus Unfractionated Heparin in Elective Percutaneous Coronary Intervention: 1-Year Results From the STEEPLE (SafeTy and Efficacy of Enoxaparin in Percutaneous Coronary Intervention Patients, An InternationaL randomized Evaluation) Trial
Topic: Interventional Cardiology
Date Posted: 1/5/2010
Author(s): Montalescot G, Gallo R, White HD, et al., on behalf of the STEEPLE Investigators.
Citation: JACC Cardiovasc Interv 2009;2:1083-1091.
Clinical Trial: yes
Study Question: What are the comparative long-term outcomes of patients who receive enoxaparin versus intravenous unfractionated heparin (UFH) for elective percutaneous coronary intervention (PCI)?
Methods: The authors reported the 1-year results of the STEEPLE trial. This trial randomized 3,528 patients undergoing elective PCI to receive either intravenous 0.50 mg/kg or 0.75 mg/kg enoxaparin or intravenous UFH during elective PCI procedures. All-cause mortality at 1 year after index PCI was the main outcome measure for this analysis.
Results: One-year follow-up data were available for 2,636 patients. There was no difference in the risk of death from randomization to 1 year among patients treated with 0.50 mg/kg enoxaparin (2.3%), 0.75 mg/kg enoxaparin (2.2%), or UFH (1.9%). Independent predictors of 1-year mortality were nonfatal myocardial infarction and/or urgent target vessel revascularization up to 30 days after index PCI (hazard ratio, 3.5; 95% CI, 1.7-7.3; p < 0.001), and major bleeding within 48 hours (hazard ratio, 3.0; 95% CI, 1.1-8.5; p = 0.04).
Conclusions: There was no difference in the long-term outcome of patients undergoing elective PCI who were treated with enoxaparin or UFH.
Perspective: This study provides two important messages. First, there is no difference in the 1-year outcome of patients undergoing PCI who are treated with UFH or enoxaparin, and either drug can be used based on physician and patient preference and cost. Second, both bleeding and ischemic events are associated with an increased risk of long-term mortality, and further efforts to improve outcome need to focus on a balanced reduction in ischemic and bleeding complications. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

Title: Role of the CHADS2 Score in the Evaluation of Thromboembolic Risk in Patients With Atrial Fibrillation Undergoing Transesophageal Echocardiography Before Pulmonary Vein Isolation
Topic: Noninvasive Cardiology
Date Posted: 1/5/2010
Author(s): Puwanant S, Varr BC, Shrestha K, et al.
Citation: J Am Coll Cardiol 2009;54:2032-2039.
Clinical Trial: No
Study Question: What is the role of the CHADS2 score in predicting left atrial (LA)/left atrial appendage (LAA) clot in patients scheduled for pulmonary vein isolation (PVI) for atrial fibrillation (AF)?
Methods: Transesophageal echocardiograms (TEEs) were performed prior to PVI in 1,058 AF patients and reviewed for presence of spontaneous echo contrast (SEC), sludge, or thrombus. A CHADS2 score was calculated for all patients who were subsequently followed for thromboembolic events after PVI.
Results: Patient age was 57 ± 11 years and 80% were male. CHADS2 scores of 0, 1, 2, 3, and ≥4 were present in 47%, 33%, 14%, 5%, and 1.3%. Paroxysmal AF was present in 81% and persistent or permanent AF in 9%. On TEE, SEC was noted in 374 (35%), sludge in 1.5%, and thrombus in 0.6%, with the remainder having no evidence of SEC, sludge, or thrombus. In the 498 patients with a CHADS2 score of 0, SEC was noted in 121 (24%) and sludge and thrombus was noted in none. For CHADS2 scores of 0, 1, 2, 3, and ≥4, SEC was noted in 24%, 33%, 59%, 74%, and 83%; sludge was noted in 0%, 2%, 4%, 9%, and 6%; thrombus in 0%, 1%, 2%, 0%, and 6% and a combination of sludge and thrombus in 0%, 2%, 5%, 9%, and 11%. LA emptying velocities (cm/s) for CHADS2 of 0 was 49 ± 20 and was 22 ± 15 in patients with CHADS2 score of 4-6. LAA sludge or thrombus was noted in eight patients with a CHADS2 score of 1, four of whom had left ventricular ejection fraction ≤35% and seven were in AF at the time of TEE. Sludge or thrombus was noted in 1% of patients with paroxysmal AF who were in normal sinus rhythm at the time of TEE compared to 2% and 5% for paroxysmal AF at the time of TEE or persistent AF. In the 3 months following PVI, 21 patients (1.8%) had an embolic event, only one of whom had LA/LAA thrombus/sludge at the time of TEE.
Conclusions: The prevalence of LA/LAA sludge and thrombus in patients undergoing AF ablation is low on screening TEE, but increases with increasingly higher CHADS2 score. The likelihood of thrombus/sludge in patients with CHADS2 score of 0 in sinus rhythm at the time of TEE who are adequately anticoagulated is negligible. TEE prior to PVI may be reserved for patients with CHADS2 score ≥1 or with persistent AF who are not adequately anticoagulated at the time of procedure.
Perspective: Over the past decade, LA ablative procedures for AF have dramatically increased in number. In many institutions, they consume substantial imaging resources, including a perceived need for routine preprocedure TEE to ensure absence of LA thrombus, which would be considered a contraindication to proceeding with the procedure. Most high-volume laboratories have anecdotally noted a remarkably low prevalence of thrombus in patients at clinically low risk of thrombus formation who are in sinus rhythm and adequately anticoagulated. This large study, from a highly experienced group, very nicely confirms that suspicion and hopefully may allow a more rational decision-making process with respect to preprocedure TEE. It should be emphasized that the patients reported here predominantly had paroxysmal AF and there are few enough patients with persistent AF that perhaps more caution would be advised in that setting. This study certainly suggests that patients with paroxysmal AF, in sinus rhythm at the time of evaluation, who have had adequate preprocedure anticoagulation have a negligible likelihood of pre-existing LA/LAA thrombus and that screening TEE is probably not needed. Screening should be reserved, even despite the overall low prevalence of LA thrombus, for those with a CHADS2 score ≥1 or persistent AF and/or inadequate preprocedure anticoagulation. Another critical finding was that the majority of post-procedural embolic events occurred in patients without pre-existing LA/LAA thrombus and are presumed to arise from thrombus developing either as a complication of the procedure or spontaneously in the LA/LAA as a result of less than ideal anticoagulation. An additional message of this study is obviously the need for scrupulous attention to adequate anticoagulation both pre- and post-procedure in these patients. William F. Armstrong, M.D., F.A.C.C.

Title: Physical Exercise Prevents Cellular Senescence in Circulating Leukocytes and in the Vessel Wall
Topic: Prevention/Vascular
Date Posted: 12/29/2009
Author(s): Werner C, Fьrster T, Widmann T, et al.
Citation: Circulation 2009;120:2438-2447.
Clinical Trial: No
Study Question: Telomere erosion is a central component of aging, and telomere-associated proteins regulate cellular senescence and survival. What are the effects of exercising on vascular telomere biology and endothelial apoptosis in mice, and what are the effects of long-term endurance training on telomere biology in humans?
Methods: C57/Bl6 mice were randomized to voluntary running or no running wheel conditions for 3 weeks. Exercise telomerase activity was evaluated in the thoracic aorta and in circulating mononuclear cells and compared with sedentary controls. Telomere biology in circulating leukocytes of young and middle-aged track and field athletes was analyzed and compared to untrained individuals.
Results: Exercise upregulated telomerase activity in the thoracic aorta and in circulating mononuclear cells compared with sedentary controls including increased vascular expression of telomere repeat-binding factor, and reduced expression of vascular apoptosis regulators. Mice preconditioned by running exhibited a marked reduction in lipopolysaccharide-induced aortic endothelial apoptosis. Transgenic mouse studies showed endothelial stress resistance after physical activity. Peripheral blood leukocytes isolated from endurance athletes showed increased telomerase activity, expression of telomere-stabilizing proteins, and downregulation of cell-cycle inhibitors compared with untrained individuals. Long-term endurance training was associated with reduced leukocyte telomere erosion compared with untrained controls.
Conclusions: Physical activity regulates telomere-stabilizing proteins in mice and in humans and thereby protects from stress-induced vascular apoptosis.
Perspective: Regular exercise training and better fitness are associated with many positive effects including blood pressure control, insulin sensitivity, less abdominal fat, better lipid profile, reduction in systemic inflammatory markers, and improved stress response and reduction in depression and anxiety. This study provides evidence for one of many potential molecular explanations for decreasing cardiovascular and overall mortality in fit men and women. Melvyn Rubenfire, M.D., F.A.C.C.

[Chevychelov]

Title: Cholesterol-Lowering Interventions and Stroke: Insights From a Meta-Analysis of Randomized Controlled Trials
Topic: Prevention/Vascular
Date Posted: 1/11/2010 5:00:00 PM
Author(s): De Caterina R, Scarano M, Marfisi RM, et al.
Citation: J Am Coll Cardiol 2010;55:198-211.
Clinical Trial: No
Study Question: Statins reduce the incidence of stroke. Is it related to cholesterol lowering or explained by alternative mechanisms?
Methods: A meta-analysis was performed of randomized trials of cholesterol-lowering treatments in cardiovascular disease reporting on stroke, involving 266,973 patients investigated and a cumulative 946,582 person-years of exposure. A meta-regression analysis was conducted regarding the extent of stroke reduction as a function of changes in total cholesterol.
Results: The odds ratio (OR) for the incidence of stroke in actively treated groups versus controls was 0.88 (95% confidence interval [CI], 0.83-0.94; p < 0.001). No treatment affected fatal strokes. Whereas statins decreased the risk of total stroke significantly (OR, 0.85; 95% CI, 0.78-0.92; p < 0.001), the benefit of nonstatin interventions was smaller and not statistically significant (diet OR, 0.92; fibrates OR, 0.98; other treatments OR, 0.81). They found a significant relationship between percent reduction of total (and low-density lipoprotein) cholesterol and percent reduction of total strokes (p = 0.0017), with each 1% reduction of total cholesterol predicting a 0.8% relative risk reduction of stroke. There was no significant association between stroke reduction and changes of high-density lipoprotein cholesterol levels, and inconsistent associations with reduction of triglycerides.
Conclusions: Among cholesterol-lowering treatments, statins are the most effective at decreasing the risk of total stroke, but their benefit is proportional to the percent reduction of total cholesterol and low-density lipoprotein cholesterol. No lipid-lowering intervention was associated with a reduction of fatal stroke.
Perspective: Observational studies have suggested that the relationship between strokes and lipids and lipoproteins in patients with strokes varies from coronary heart disease. This meta-analysis reports that the relationship between cholesterol and stroke reduction with statins is linear (1% reduction in total cholesterol predicts a 0.8% relative risk reduction of a stroke), with no evidence for pleiotropic effects. This is supported in a low-risk population without high-risk lipids. In the JUPITER trial, in which patients had a median total cholesterol of 186 mg/dl and a C-reactive protein >2 mg/dl, rosuvastatin 20 mg was associated with a 48% relative risk reduction for strokes. Melvyn Rubenfire, M.D., F.A.C.C.

Title: Treatment of Aspirin-Resistant Patients With Omega-3 Fatty Acids Versus Aspirin Dose Escalation
Topic: Prevention/Vascular
Date Posted: 1/4/2010 5:00:00 PM
Author(s): Lev EI, Solodky A, Harelet N, et al.
Citation: J Am Coll Cardiol 2010;55:114-121.
Clinical Trial: No
Study Question: What is the effect of addition of omega-3 fatty acids or increase in aspirin dose on response to low-dose aspirin among patients who are aspirin-resistant?
Methods: Patients (n = 485) with stable coronary artery disease (CAD), taking low-dose aspirin (75-162 mg) for at least 1 week were screened for aspirin response with the VerifyNow Aspirin assay (Accumetrics, San Diego, CA). Further testing was performed by platelet aggregation. Aspirin resistance was defined by ≥2 of 3 criteria: VerifyNow score ≥550, 0.5 mg/ml arachidonic acid (AA)-induced aggregation ≥20%, and 10-µmol/L adenosine diphosphate (ADP)-induced aggregation ≥70%. Thirty patients (6.2%) were found to be aspirin resistant and randomized to receive either low-dose aspirin + omega-3 fatty acids (4 capsules daily) or aspirin 325 mg daily. After 30 days of treatment, patients were re-tested.
Results: Both groups (n = 15 each) had similar clinical characteristics. After treatment, significant reductions in AA- and ADP-induced aggregation and the VerifyNow score were observed in both groups. Plasma levels of thromboxane B2 were also reduced in both groups (56.8% reduction in the omega-3 fatty acids group, and 39.6% decrease in the aspirin group). Twelve patients (80%) who received omega-3 fatty acids and 11 (73%) who received aspirin 325 mg were no longer aspirin resistant after treatment.
Conclusions: The authors concluded that treatment of aspirin-resistant patients by adding omega-3 fatty acids or increasing the aspirin dose seems to improve response to aspirin and effectively reduces platelet reactivity.
Perspective: This study suggests that either adding omega-3 fatty acids or increasing the aspirin dose can improve response to aspirin and reduce residual platelet reactivity in stable patients with CAD. Treatment with both regimens was associated with a reduction in aspirin-resistance rates. Furthermore, omega-3 fatty acid supplementation might have independent favorable effects in the secondary prevention of CAD and its complications. The investigators did not examine the clinical impact of their therapeutic interventions or whether routine monitoring of aspirin response has any impact on clinical outcomes. Further larger studies are required to assess hard clinical endpoints and evaluate whether the strategy tested in this pilot study has any clinical benefit in patients with cardiovascular disease found to be resistant to aspirin. Debabrata Mukherjee, M.D., F.A.C.C.

Title: Community-Based Interventions to Promote Blood Pressure Control in a Developing Country: A Cluster Randomized Trial
Topic: Prevention/Vascular
Date Posted: 12/31/2009
Author(s): Jafar TH, Hatcher J, Poulter N, et al., on behalf of the Hypertension Research Group.
Citation: Ann Intern Med 2009;151:593-601.
Clinical Trial: yes
Study Question: How effective are community-based interventions to control blood pressure in a developing country?
Methods: The authors reported the results of the Control Of Blood Pressure And Risk Attenuation-1 (COBRA-1) trial, a cluster randomized, 2 x 2 factorial, controlled trial of family-based home health education (HHE) using lay health workers and hypertension management training for general practitioners (GPs), conducted in Karachi, Pakistan. Subjects were over age 40 with known hypertension living in 12 randomly selected communities, with three clusters randomly assigned to each of the following groups: HHE alone, GP alone, HHE and GP combined, or no intervention. Outcome was reduction in systolic blood pressure from baseline to 2-year follow-up.
Results: Among 1,341 subjects, systolic blood pressure decrease was significantly greater in the HHE plus GP group (10.8 mm Hg; 95% confidence interval [CI], 8.9-12.8 mm Hg) compared with GP alone, HHE alone, or no intervention groups (5.8 mm Hg; 95% CI 3.9-7.7 mm Hg in each; p < 0.001), after adjusting for age, sex, and baseline blood pressure. The interaction between the main effect of GP training and HHE on the primary outcome was significant (p = 0.004 by intention-to-treat analysis; p = 0.0445 per protocol analysis).
Conclusions: The authors concluded that family-based HHE delivered by trained lay health workers, coupled with educating GPs about hypertension, can lead to significant blood pressure reductions among patients with hypertension in Pakistan. The authors opined that both strategies in combination may be feasible for upscaling within the existing health systems of Indo-Asian countries.
Perspective: The authors demonstrated the efficacy of combining MD training with lay health education in improving blood pressure in a developing country. In some situations, it may be that overcoming barriers or lack of information is as important as selecting the best pharmaceutical agent. In addition to blood pressure lowering, the authors demonstrated that improvements in smoking, physical activity, and medication adherence were also associated with the combined use of HHE and GP training. It is interesting to note that the use of only HHE or GP training alone offered no benefit over no intervention. This suggests that, without the reinforcement of home intervention, improved training of GPs offers little improvement in blood pressure control. Although this study was done in a developing country where the challenges are different, this finding may have important lessons for improving health care in developed countries. James B. Froehlich, M.D., F.A.C.C.

[Chevychelov]

Anthracycline-Induced Cardiomyopathy
Mortality Same for Low vs High Volume PCI
Mummies Have Atherosclerosis
[Ссылки доступны только зарегистрированным пользователям ]

[Chevychelov]

Title: Prevalence and Trends in Obesity Among US Adults, 1999-2008
Topic: Prevention/Vascular
Date Posted: 1/13/2010 11:00:00 AM
Author(s): Flegal KM, Carroll MD, Ogden CL, Curtin LR.
Citation: JAMA 2010;Jan 13:[Epub ahead of print].
Clinical Trial: No
Study Question: Has there been a change in the trend for increasing prevalence of obesity and overweight from 1999 through 2008?
Methods: The results are based on the analysis of height and weight measurements from 5,555 adult men and women ages 20 years or older obtained in 2007-2008 as part of the National Health and Nutrition Examination Survey (NHANES). Data from NHANES obtained in 2007-2008 were compared with results obtained from 1999 through 2006. Overweight was defined as a body mass index (BMI) of 25.0-29.9 kg/m2 and obesity was defined as a BMI of 30.0 kg/m2 or higher.
Results: In 2007-2008, the age-adjusted prevalence of obesity was 33.8% (95% confidence interval [CI], 31.6-36.0%) overall, 32.2% among men, and 35.5% among women. The corresponding prevalence estimates for overweight and obesity combined were 68.0%, 72.3%, and 64.1%. Obesity prevalence varied by age group and by racial and ethnic group for both men and women. Over the 10-year period, obesity showed no significant trend among women (adjusted odds ratio [AOR] for 2007-2008 vs. 1999-2000, 1.12 [95% CI, 0.89-1.32]). For men, there was a significant linear trend (AOR for 2007-2008 vs. 1999-2000, 1.32 [95% CI, 1.12-1.58]); however, the three most recent data points did not differ significantly from each other.
Conclusions: The increase in the prevalence of obesity previously observed does not appear to be continuing at the same rate over the past 10 years, particularly for women and possibly for men.
Perspective: That the trend for increasing obesity appears to have stopped is not much of an accomplishment. Very few adults in the United States are unaware of the increased risk for cardiovascular disease, diabetes, and other disorders associated with obesity. The US population-based efforts to impact the prevalence of obesity from 1999-2008 by education have been impressive, but the results are disappointing. In 2007-2008, nearly 20% of men and women had a BMI >35 kg/m kg/m2, which underscores the need for novel and safe drugs for targeting weight loss. Melvyn Rubenfire, M.D., F.A.C.C.

[Chevychelov]

Title: Catheter Ablation of Stable Ventricular Tachycardia Before Defibrillator Implantation in Patients With Coronary Heart Disease (VTACH): A Multicentre Randomised Controlled Trial
Topic: Arrhythmias
Date Posted: 1/14/2010
Author(s): Kuck KH, Schaumann A, Eckardt L, et al., on behalf of the VTACH Study Group.
Citation: Lancet 2010;375:31-40.
Clinical Trial: yes
Study Question: What is the clinical value of prophylactic radiofrequency catheter ablation (RFCA) of ventricular tachycardia (VT) before implantation of an implantable cardioverter/defibrillator (ICD)?
Methods: One hundred seven patients (mean age 66 years) with stable VT, prior myocardial infarction (MI), and an ejection fraction ≤50% (mean 34%) were randomly assigned to undergo RFCA plus ICD implantation (n = 52) or only ICD implantation (n = 55). Stored electrograms were analyzed to identify VT events during follow-up. Quality of life was measured at each clinic visit. The 1° endpoint was time to first episode of VT/ventricular fibrillation.
Results: Approximately 30% of patients in both groups received amiodarone during follow-up, and the mean follow-up duration was 22 months. The first episode of VT occurred at a median follow-up of 18.6 months in the ablation group, compared to only 5.9 months in the control group. Cardiac hospitalizations were significantly reduced in the ablation group compared to the control group (67% vs. 45%, respectively, at 24 months), but there were no significant differences in mortality or quality of life. The mean number of appropriate ICD shocks per patient per year was 0.6 in the ablation group and a significantly higher 3.4 in the control group.
Conclusions: RFCA of VT significantly reduces the incidence of VT during follow-up in post-MI patients treated with an ICD.
Perspective: In the OPTIC trial, amiodarone reduced ICD shocks by 73%. Instead of prophylactic RFCA of VT in all patients at the time of ICD implantation, one could make the case for treatment with amiodarone, with RFCA being reserved for patients who do not tolerate or who fail therapy with amiodarone. Fred Morady, M.D., F.A.C.C.

Title: Diabetic and Nondiabetic Patients With Left Main and/or 3-Vessel Coronary Artery Disease: Comparison of Outcomes With Cardiac Surgery and Paclitaxel-Eluting Stents
Topic: Cardiovascular Surgery
Date Posted: 1/15/2010
Author(s): Banning AP, Westaby S, Morice MC, et al.
Citation: J Am Coll Cardiol 2010;Jan 13:[Epub ahead of print].
Clinical Trial: No
Study Question: What is the impact of diabetes on outcome of patients with complex three-vessel or left main coronary artery disease who are treated with coronary artery bypass grafting (CABG) or paclitaxel-eluting stents (PES)?
Methods: The authors reported the outcome of diabetic patients enrolled in the Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) study. This study randomized 1,800 patients (452 with diabetes) to receive PES or CABG.
Results: Major adverse cardiac and cerebrovascular event rate at 1 year was higher among diabetic patients treated with PES compared with CABG (15.1 % vs. 11.8% ). There was no difference in the death/stroke/myocardial infarction rate with either revascularization strategy for nondiabetic patients (6.8% CABG vs. 6.8% PES, p = 0.97) or for diabetic patients (10.3% CABG vs. 10.1% PES, p = 0.96). Diabetic patients were at an increased risk of death after both CABG and PES. Mortality was higher after PES use (4.1% vs. 13.5%, p = 0.04) for diabetic patients with highly complex lesions (defined as a SYNTAX score ≥33). Compared with CABG, treatment with PES resulted in higher repeat revascularization for both nondiabetic patients (5.7% vs. 11.1%, p < 0.001) and diabetic patients (6.4% vs. 20.3%, p < 0.001).
Conclusions: Diabetes is associated with worse outcome among patients undergoing PES-based revascularization for complex coronary artery disease.
Perspective: Diabetes is associated with a greater prevalence of coronary artery disease and diabetic patients have a worse outcome after coronary revascularization compared with nondiabetics. The pre-eminence of CABG over PCI for revascularization of diabetics in the angioplasty and bare-metal stent era was based on higher rates of target vessel revascularization with PCI. The results of this and other studies (i.e., CARDia) suggest that drug-eluting stents have not been able to completely bridge this gap, and CABG remains the revascularization strategy for diabetic patients with multivessel coronary artery disease. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

[Chevychelov]

Title: Strength of Study Evidence Examined by the FDA in Premarket Approval of Cardiovascular Devices
Topic: General Cardiology
Date Posted: 1/15/2010
Author(s): Dhruva SS, Bero LA, Redberg RF.
Citation: JAMA 2009;302:2679-2685.
Clinical Trial: No
Study Question: What is the type and strength of evidence on which premarket approval (PMA)—the most stringent Food and Drug Administration (FDA) review process is based?
Methods: This was a systematic review of 123 summaries of safety and effectiveness data for 78 PMAs for high-risk cardiovascular devices that received PMA between January 2000 and December 2007. Examination of the methodological characteristics considered essential to minimize confounding and bias, as well as the primary endpoints of the 123 studies supporting the PMAs, was performed.
Results: Thirty-three of 123 studies (27%) used to support recent FDA approval of cardiovascular devices were randomized and 17 of 123 (14%) were blinded. Fifty-one of 78 PMAs (65%) were based on a single study. One hundred eleven of 213 primary endpoints (52%) were compared with controls and 34 of 111 controls (31%) were retrospective. One hundred eighty-seven of 213 primary endpoints (88%) were surrogate measures and 122 of 157 (78%) had a discrepancy between the number of patients enrolled in the study and the number analyzed.
Conclusions: The authors concluded that PMA of cardiovascular devices by the FDA is often based on studies that lack adequate strength and may be prone to bias.
Perspective: This analysis suggests that the evidence presented for FDA-approved cardiovascular device PMAs came mostly from studies that were not blinded or randomized. The FDA approval process is an important determinant of health care spending, and spending on new devices increases when the FDA approves devices more quickly. Cost containment would likely occur if rigorous clinical effectiveness reviews were used for new drugs and technologies, and spending concentrated on devices shown to benefit patients definitively. This study further suggests that the FDA device approval process would benefit from rigorous research, using meaningful clinical outcomes and valid, active (not historical) controls in randomized, blinded studies (when possible) conducted in populations that reflect the US population. The emphasis of FDA in the future should be research that meets rigorous scientific standards for evidence of benefit and lack of harm to patients. Debabrata Mukherjee, M.D., F.A.C.C.

Title: Familial Dilated Cardiomyopathy Caused by an Alpha-Tropomyosin Mutation: The Distinctive Natural History of Sarcomeric Dilated Cardiomyopathy
Topic: Heart Failure/Transplant
Date Posted: 1/18/2010 5:00:00 PM
Author(s): Lakdawala NK, Dellefave L, Redwood CS, et al.
Citation: J Am Coll Cardiol 2009;55:320-329.
Clinical Trial: No
Study Question: Are there sarcomere gene mutations responsible for dilated cardiomyopathy (DCM)?
Methods: Direct sequencing of six sarcomere genes was performed on 334 probands with DCM. A novel D230N missense mutation in the gene encoding alpha-tropomyosin (TPM1) was identified. Functional assessment was performed by the use of an in vitro reconstituted sarcomere complex to evaluate ATPase regulation and Ca2+ affinity as correlates of contractility.
Results: TPM1 D230N segregated with DCM in two large unrelated families. This mutation altered a conserved residue and was absent in >1,000 control chromosomes. In vitro studies demonstrated major inhibitory effects on sarcomere function with reduced Ca2+ sensitivity, maximum activation, and Ca2+ affinity compared with wild-type TPM1. Clinical manifestations ranged from decompensated heart failure or sudden death in those presenting early in life to asymptomatic left ventricular dysfunction in those diagnosed during adulthood.
Conclusions: Genetic segregation in two unrelated families and functional analyses demonstrate a pathogenic role for TPM1 mutations in DCM. In vitro results demonstrate contrasting effects of DCM and HCM mutations inTPM1, suggesting that specific functional consequences shape cardiac remodeling. Along with previous reports, data support a distinctive, age-dependent phenotype with sarcomere-associated DCM where presentation early in life is associated with severe, sometimes lethal disease.
Perspective: About one third of subjects with DCM have evidence of familial inheritance, most of whom show autosomal dominant transmission. Mutations in many genes have been linked to DCM, many of which are thought to affect myocyte force generation or energy production. While mutations in alpha-tropomysin are known to cause HCM, their role in DCM has been less conclusive. By showing segregation of TPM1 in two unrelated families, along with an in vitro phenotype, the current study provides very strong evidence for a causal role of TPM function in DCM. Interestingly, three of five infants with TPM1 showed marked recovery of left ventricular function. Additional studies aimed at determining mechanisms responsible for phenotypic heterogeneity and recovery potential of mutation carriers may lead to novel DCM screening and treatment strategies. Daniel T. Eitzman, M.D., F.A.C.C.

[Chevychelov]

Title: Cardio-Renal Syndromes: Report From the Consensus Conference of the Acute Dialysis Quality Initiative
Topic: Heart Failure/Transplant
Date Posted: 1/18/2010
Author(s): Ronco C, McCullough P, Anker SD, et al.
Citation: Eur Heart J 2009;Dec 25:[Epub ahead of print].
Clinical Trial: No
Perspective: The following are 10 points to remember about cardio-renal syndromes.

1. The Consensus Conference on Cardio-Renal Syndromes identified five subtypes that have different pathophysiology (refer to Figures 1-5 in J Am Coll Cardiol 2008;52:1527-39), prevention, and management strategies (refer to Table 1 in this article).

2. Type 1 or acute cardio-renal syndrome: acute worsening of heart function leading to kidney injury and/or dysfunction. About 27-40% of the patients with acute decompensated heart failure appear to develop acute kidney injury.

3 Type 2 or chronic cardio-renal syndrome: chronic abnormalities in heart function leading to kidney injury or dysfunction. This has been reported in 63% of patients hospitalized with congestive heart failure.

4. Type 3 or acute reno-cardiac syndrome: acute worsening of kidney function leading to heart injury and/or dysfunction. The effects on heart function are due to factors in addition to volume overload.

5. Type 4 or chronic reno-cardiac syndrome: chronic kidney disease leading to heart injury, disease, and/or dysfunction.

6. Type 5 or secondary cardio-renal syndrome: systemic conditions leading to injury and/or dysfunction of both heart and kidney (e.g., diabetes mellitus, sepsis, systemic lupus erythematosus, amyloidosis).

7. B-type natriuretic peptide (BNP) and NT-BNP may be elevated in cardio-renal syndrome types 1, 2, and 4.

8. Neutrophil gelatinase-associated lipocalin (NGAL) of urine and plasma and cystatin C are two biomarkers of renal injury that are most likely to be integrated in clinical practice and help with management of cardio-renal syndrome.

9. Bioimpedance vector analysis may contribute to better definition of the patient’s hydration status.

10. The presence of coronary artery disease should be excluded by stress echo or stress myocardial perfusion in types III, IV, and V and in types I and II cardio-renal syndrome when the primary disease is valvular, congenital, or myopathic to avoid contrast-induced renal damage. Ragavendra R. Baliga, M.B.B.S.

Title: Culprit Vessel Percutaneous Coronary Intervention Versus Multivessel and Staged Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction Patients With Multivessel Disease
Topic: Interventional Cardiology
Date Posted: 1/18/2010 5:00:00 PM
Author(s): Hannan EL, Samadashvili Z, Walford G, et al.
Citation: JACC Cardiovasc Interv 2010;3:22-31.
Clinical Trial: No
Study Question: What is the best time to intervene on nonculprit vessels in patients with ST-elevation myocardial infarction (STEMI) who have multivessel disease and undergo primary percutaneous coronary intervention (PCI)?
Methods: The authors assessed the outcome of STEMI patients with multivessel disease who underwent primary PCIs in New York between January 1, 2003, and June 30, 2006. Patients were categorized into those who underwent culprit vessel PCI only, those who underwent multivessel PCI during the index procedure, those undergoing nonculprit vessel PCI during the index admission, or those undergoing staged PCI to the nonculprit vessel within 60 days of the index admission. Propensity-matching was used to compare outcome within these subcategories.
Results: The study cohort was comprised of 4,024 patients of whom 3,521 patients (87.5%) underwent culprit vessel PCI only during the index procedure. Staged PCI during the index admission was performed in 259 patients, and 538 patients underwent staged PCI within 60 days of the index procedure. Among patients without hemodynamic compromise, those undergoing culprit vessel PCI during the index procedure had a lower in-hospital mortality than those undergoing multivessel PCI during the index procedure (0.9% vs. 2.4%, p = 0.04). There was no difference in long-term survival. There was no difference in outcome of those patients who underwent culprit vessel PCI only and those who underwent PCI to nonculprit vessel during the same hospitalization. Patients undergoing staged multivessel PCI within 60 days after the index procedure had a lower 12-month mortality rate than patients undergoing culprit vessel PCI only (1.3% vs. 3.3%, p = 0.04).
Conclusions: A strategy of culprit vessel PCI only at the time of STEMI is associated with the best outcome in patients with multivessel disease.
Perspective: Current American College of Cardiology/American Heart Association guidelines recommend culprit vessel PCI only in patients undergoing primary PCI (unless there is hemodynamic compromise). This study corroborates these findings, although the observational nature of the study and the fact that an overwhelming majority of patients were treated with culprit vessel PCI only, makes firm conclusions difficult. Since there are no data to the contrary, culprit vessel PCI only should remain the preferred revascularization strategy, and if there is an indication for PCI of a nonculprit vessel, such a procedure should be performed in a staged fashion. The optimal timing of such a staged procedure, however, remains unclear. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

[Chevychelov]

Title: Diagnostic Accuracy of 320-Row Multidetector Computed Tomography Coronary Angiography in the Non-invasive Evaluation of Significant Coronary Artery Disease
Topic: Noninvasive Cardiology
Date Posted: 1/14/2010
Author(s): de Graaf FR, Schuijf JD, van Velzen J, et al.
Citation: Eur Heart J 2010;Jan 4:[Epub ahead of print].
Clinical Trial: No
Study Question: What is the accuracy and feasibility of detecting obstructive coronary artery disease (CAD) with 320-row computed tomographic coronary angiography (CTA)?
Methods: CTA, using a new 320-row multidetector system and standard coronary arteriography, was performed in 64 patients with known or suspected CAD. CTA was analyzed on a per-segment, per-vessel, and per-patient basis. Usual selection criteria for CTA, including avoidance of atrial fibrillation, renal failure, and more, were employed. Beta-blockers were used when necessary to maintain heart rate <65 bpm. The 320-row CTA encompasses a 16 cm field of view, allowing imaging of the entire cardiac anatomy within a single heart beat.
Results: On a per-segment basis, 12 of 839 segments were deemed nondiagnostic. By standard coronary arteriography, 71 lesions ≥50% diameter stenosis were noted, 62 of which were detected with CTA. On a per-segment basis, the sensitivity, specificity, and positive and negative predictive values for detecting ≥50% coronary stenosis were 87%, 97%, 75%, and 99%. Data were nondiagnostic in 2 of 177 vessels containing 48 stenoses. Sensitivity, specificity, and positive and negative predictive values were 94%, 92%, 83%, and 97%. Data were analyzable in 60 of 64 patients resulting in sensitivity, specificity, and positive and negative predictive values of 100%, 88%, 92%, and 100%, respectively on a per-patient basis. On a per-segment basis, sensitivity, specificity, and positive and negative predictive values for detecting stenoses ≥70% were 96%, 99%, 74%, and 99.9%.
Conclusions: The study shows that 320-row CTA allows an accurate identification of obstructive CAD when compared to standard coronary arteriography.
Perspective: The 320-row multidetector scanner described here represents the latest generation of multidetector CTA. Multiple studies using the currently and commonly utilized 64-slice scanners have demonstrated excellent accuracy for detecting and excluding obstructive CAD in proximal coronary arteries, and CTA has been proposed as both a screening and prognostic tool in patients with known or suspected coronary disease. The potential advantages of a 320-row scanner are that it is capable of encompassing the entire length of the left ventricle in one heartbeat, thus reducing the likelihood of motion artifact. It also results in a reduced radiation and contrast dosage and less of a need for prolonged breath-holding. It is still dependent on a relative bradycardia, and an unstable rhythm such as atrial fibrillation or frequent premature ventricular contractions may interfere with gating. This relatively small study suggests that its overall accuracy with respect to sensitivity, specificity, and positive and negative predictive values are equivalent to that seen with the more well-established 64-slice scanner. When combined with what may be a more rapid throughput with less radiation and the ability to scan the entire heart in a single heartbeat, it may provide significant clinical and practical advantages in the future. William F. Armstrong, M.D., F.A.C.C.

Title: The Association Between Plaque Characterization by CT Angiography and Post-Procedural Myocardial Infarction in Patients With Elective Stent Implantation
Topic: Noninvasive Cardiology
Date Posted: 1/12/2010
Author(s): Uetani T, Amano T, Kunimura A, et al.
Citation: JACC Cardiovasc Imaging 2009;3:19-28.
Clinical Trial: No
Study Question: What is the association between volumetric characterization of target lesions by multidetector computed tomography (MDCT) angiography and the risk of postprocedural myocardial injury after elective stent implantation?
Methods: A total of 189 consecutive patients were enrolled; they underwent elective stent implantation after volumetric plaque analysis with 64-slice MDCT. Each plaque component and lumen (filled with dye) was defined as follows: 1) low-attenuation plaque (LAP) (<50 HU); 2) moderate-attenuation plaque (MAP) (50-150 HU); 3) lumen (151-500 HU); and 4) high-attenuation plaque (HAP) (>500 HU). The volume of each plaque component in the target lesion was calculated using Color Code Plaque. Post-procedural creatine kinase-MB isoform and troponin-T (TnT) at 18 hours after percutaneous coronary intervention were also evaluated.
Results: The volumes of LAP (87.9 ± 94.8 mm3 vs. 47.4 ± 43.7 mm3, p < 0.01) and MAP (111.6 ± 77.5 mm3 vs. 89.8 ± 67.1 mm3, p < 0.05) were larger in patients with post-procedural myocardial injury (defined as positive TnT) than in those with negative TnT. The volumes of LAP and MAP and fraction of LAP in total plaque (LAP volume/total plaque volume) correlated with biomarkers; the MAP fraction was inversely correlated with biomarkers. The volume of LAP was an independent predictor of positive TnT after adjusting for patient background, conventional intravascular ultrasound parameters, and procedural factors.
Conclusions: The authors concluded that post-procedural myocardial injury was associated with the volume and fraction of LAP, as detected by MDCT.
Perspective: This pilot study suggests a significant correlation between LAP volume within target lesions, as measured by MDCT, and post-procedural elevation of cardiac biomarker levels. The LAP volume was found to be an independent predictor of myocardial injury after elective stenting. Plaque evaluation by MDCT may, therefore, provide useful information to identify high-risk patients who are expected to have a better outcome with aggressive medical treatment or bypass surgery. However, evaluation of coronary plaque by MDCT involves significant exposure to radiation as well as use of iodinated contrast medium. Further evaluations with larger multicenter studies are indicated to validate the findings of this study and assess potential clinical utility/benefits. Debabrata Mukherjee, M.D., F.A.C.C.

[Chevychelov]

Title: Prevalence and Trends in Obesity Among US Adults, 1999-2008
Topic: Prevention/Vascular
Date Posted: 1/13/2010 11:00:00 AM
Author(s): Flegal KM, Carroll MD, Ogden CL, Curtin LR.
Citation: JAMA 2010;Jan 13:[Epub ahead of print].
Clinical Trial: No
Study Question: Has there been a change in the trend for increasing prevalence of obesity and overweight from 1999 through 2008?
Methods: The results are based on the analysis of height and weight measurements from 5,555 adult men and women ages 20 years or older obtained in 2007-2008 as part of the National Health and Nutrition Examination Survey (NHANES). Data from NHANES obtained in 2007-2008 were compared with results obtained from 1999 through 2006. Overweight was defined as a body mass index (BMI) of 25.0-29.9 kg/m2 and obesity was defined as a BMI of 30.0 kg/m2 or higher.
Results: In 2007-2008, the age-adjusted prevalence of obesity was 33.8% (95% confidence interval [CI], 31.6-36.0%) overall, 32.2% among men, and 35.5% among women. The corresponding prevalence estimates for overweight and obesity combined were 68.0%, 72.3%, and 64.1%. Obesity prevalence varied by age group and by racial and ethnic group for both men and women. Over the 10-year period, obesity showed no significant trend among women (adjusted odds ratio [AOR] for 2007-2008 vs. 1999-2000, 1.12 [95% CI, 0.89-1.32]). For men, there was a significant linear trend (AOR for 2007-2008 vs. 1999-2000, 1.32 [95% CI, 1.12-1.58]); however, the three most recent data points did not differ significantly from each other.
Conclusions: The increase in the prevalence of obesity previously observed does not appear to be continuing at the same rate over the past 10 years, particularly for women and possibly for men.
Perspective: That the trend for increasing obesity appears to have stopped is not much of an accomplishment. Very few adults in the United States are unaware of the increased risk for cardiovascular disease, diabetes, and other disorders associated with obesity. The US population-based efforts to impact the prevalence of obesity from 1999-2008 by education have been impressive, but the results are disappointing. In 2007-2008, nearly 20% of men and women had a BMI >35 kg/m kg/m2, which underscores the need for novel and safe drugs for targeting weight loss. Melvyn Rubenfire, M.D., F.A.C.C.

Title: Does Erectile Dysfunction Contribute to Cardiovascular Disease Risk Prediction Beyond the Framingham Risk Score?
Topic: Prevention/Vascular
Date Posted: 1/18/2010 5:00:00 PM
Author(s): Araujo AB, Hall SA, Ganz P, et al.
Citation: J Am Coll Cardiol 2009;55:350-356.
Clinical Trial: No
Study Question: Is erectile dysfunction (ED) predictive of cardiovascular disease (CVD) beyond traditional risk factors?
Methods: The Massachusetts Male Aging Study (MMAS) trial is a prospective, observational cohort study of aging, health, and endocrine and sexual function in a population-based random sample of men between ages 40 and 70 years. This study was conducted in 1,709 men (of 3,258 eligible men). The ED data were measured by self-report. Data on CVD were obtained from self-reports, the National Death Index, and medical records. CVD endpoints included myocardial infarction, atherosclerosis, stroke, coronary artery bypass graft surgery, and congestive heart failure. Subjects were followed for CVD for an average follow-up of 11.7 years. The association between ED and CVD was examined using the Cox proportional hazards regression model. The discriminatory capability of ED was examined using C statistics. The reclassification of CVD risk associated with ED was assessed using a method that quantifies net reclassification improvement.
Results: Of the prospective population, 1,057 men with complete risk factor data who were free of CVD and diabetes at baseline were included. Men with ED were older (mean 59 years vs. 54 years), had a higher prevalence of hypertension and smoking, slightly higher body mass index, lower total and high-density lipoprotein cholesterol, and higher Framingham risk score. Overall, 37% of men with ED were in the highest risk category for Framingham risk score, compared with 17% of men without ED. During follow-up, 261 (25%) new cases of CVD occurred, of which 61 were obtained by self-report only. Of the CVD events, 71 (27.2%) were fatal. Men without ED at baseline (n = 879) were followed for an average of 12.0 years and men with ED (n = 178) for 10.3 years. ED was associated with CVD incidence controlling for age (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.05-1.90), age and traditional CVD risk factors (HR, 1.41; 95% CI, 1.05-1.90), as well as age and Framingham risk score (HR, 1.40; 95% CI, 1.04-1.88). Despite these significant findings, ED did not significantly improve the prediction of CVD incidence beyond traditional risk factors. The data did not differ assuming none of those without verifiable CVD had an event.
Conclusions: Independent of established CVD risk factors, ED is significantly associated with increased CVD incidence. Nonetheless, ED does not improve the prediction of who will and will not develop CVD beyond that offered by traditional risk factors.
Perspective: The results are in conflict with most other observational studies. Considering the high socioeconomic status of a significant percent of participants, and the long-term follow-up, I suspect treatment of risk factors with statins and other drugs may have influenced the outcome. For clinical purposes, despite this report, I would still consider ED a marker of CV risk in low-risk middle-aged and older men. Melvyn Rubenfire, M.D., F.A.C.C.

[Chevychelov]

Cancer Risks From CT Scans
Dabigatran not Inferior to Warfarin
Cholesterol-Lowering Interventions and Stroke
[Ссылки доступны только зарегистрированным пользователям ]

[Chevychelov]

Title: Use of Evidence-Based Therapies in Short-Term Outcomes of ST-Segment Elevation Myocardial Infarction and Non–ST-Segment Elevation Myocardial Infarction in Patients With Chronic Kidney Disease. A Report From the National Cardiovascular Data Acute Coronary Treatment and Intervention Outcomes Network Registry
Topic: General Cardiology
Date Posted: 1/19/2010
Author(s): Fox CS, Muntner P, Chen AY, et al.
Citation: Circulation 2010;121:357-365.
Clinical Trial: No
Study Question: What is the association between chronic kidney disease (CKD) severity and short-term outcomes and the use of in-hospital evidence-based therapies among patients with ST-segment elevation myocardial infarction (STEMI) and non–STEMI (NSTEMI)?
Methods: The study sample was drawn from the Acute Coronary Treatment and Intervention Outcomes Network registry, a nationwide sample of STEMI (n = 19,029) and NSTEMI (n = 30,462) patients. Estimated glomerular filtration rate was calculated with the Modification of Diet in Renal Disease equation in relation to use of immediate (first 24 hours) therapies and early (first 48 hours) cardiac catheterization as well as in-hospital major bleeding events and death.
Results: Overall, 30.5% and 42.9% of patients with STEMI and NSTEMI, respectively, had CKD. Regardless of MI type, patients with progressively more severe CKD had higher rates of death. For STEMI, the odds ratio for stage 3a, 3b, 4, and 5 CKD compared with patients with no CKD was 2.49, 3.72, 4.82, and 7.97, respectively (Ptrend < 0.0001). For NSTEMI, the analogous odds ratios were 1.81, 2.41, 3.50, and 4.09 (P for trend < 0.0001). In addition, patients with progressively more severe CKD were less likely to receive immediate evidence-based therapies including aspirin, beta-blockers, or clopidogrel, were less likely to undergo any reperfusion (STEMI) or revascularization (NSTEMI), and had higher rates of bleeding.
Conclusions: The authors concluded that patients with CKD still receive fewer evidence-based therapies and have substantially higher mortality rates.
Perspective: Several studies over the past decade have highlighted the importance and undertreatment of CKD among patients with MI. Data from this contemporary cohort suggest that patients with CKD still receive fewer evidence-based therapies and have substantially higher mortality rates. Clinicians should be aware of the high likelihood of concomitant CKD and cardiovascular disease in patients presenting with MI to allow for appropriate treatment decisions and to adjust medication dosing. The underutilization of evidence-based therapies and procedures in the CKD population is an important health care quality issue and an opportunity to develop appropriate quality improvement initiatives to optimize care in these high-risk patients. Debabrata Mukherjee, M.D., F.A.C.C.

Title: Second-Generation Everolimus-Eluting and Paclitaxel-Eluting Stents in Real-Life Practice (COMPARE)
Trial Sponsor: Abbott Vascular and Boston Scientific
Year Presented: 2009
Year Published 2010
Topic(s): Interventional Cardiology
Summary Posted: 1/18/2010
Writer: Dharam J. Kumbhani, M.D., S.M.
Author Disclosure: This author has nothing to disclose.
Reviewer: Deepak L. Bhatt, M.D., F.A.C.C.
Author Disclosure: Research/Research Grants: Astra Zeneca; Research/Research Grants: Eisai; Research/Research Grants: Ethicon; Consultant Fees/Honoraria: Duke Clinical Research Institute; Research/Research Grants: Heartscape; Research/Research Grants: The Medicines Company; Research/Research Grants: Bristol Myers Squibb; Data Safety Monitoring Board (Gov’t/Nonprofit): Duke Clinical Research Institute; Research/Research Grants: Sanofi Aventis
Description
The current trial sought to compare outcomes between the everolimus-eluting stent (EES) (Xience V) and paclitaxel-eluting stent (PES) (Taxus Liberte) in a real-world situation.
Hypothesis
EES would be superior to PES in the treatment of coronary artery disease in unselected patients.
Drugs/Procedures Used
Patients meeting enrollment criteria were randomized to receive either EES or PES in a 1:1 fashion.
Concomitant Medications
Glycoprotein IIb/IIIa inhibitors (32%); aspirin 300 mg once, then 100 mg daily for life; clopidogrel 300 or 600 mg once, then 75 mg daily for 12 months.
Principal Findings
A total of 1,800 patients were randomized, 903 to PES and 897 to EES. Baseline characteristics were fairly similar between the two arms. About 25% of patients presented with acute myocardial infarction (MI), and 23% with non-ST-elevation MI. Multivessel disease was noted in 27% of the patients, and 18% were diabetic. Left main stenting was conducted in 2% of the patients. The mean stent length per lesion was 28 mm, and the mean number of lesions was 1.65 per patient.

The primary endpoint of major adverse cardiac events (MACE) at 1 year (all-cause mortality, nonfatal MI, and target vessel revascularization [TVR]) was significantly lower in the EES arm compared with PES (6.2% vs. 9.1%, hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.50-0.95, p = 0.023). Similarly, the incidence of death, MI, and target lesion revascularization (TLR) at 1 year was significantly lower in the EES arm compared with PES (4.9% vs. 8.2%, HR 0.60, 95% CI 0.42-0.86, p = 0.005).

In addition, the incidence of nonfatal MI (2.8% vs. 5.4%, p = 0.007) and TVR (2.4% vs. 6.0%, p = 0.0001) was significantly lower in the EES arm. The incidence of stent thrombosis at 1 year was also significantly lower in the EES arm (0.7% vs. 2.6%, HR 0.26, 95% CI 0.11-0.64, p = 0.002). This was mainly due to a reduction in early stent thrombosis (p = 0.002), rather than late stent thrombosis (p = 0.25).
Interpretation
The results of this trial indicate that EES is superior to PES (Taxus Liberte) in the reduction in clinical endpoints including MACE, nonfatal MI, and stent thrombosis at 1 year, when utilized in a real-world situation. These results are similar to those of the recently presented SPIRIT IV trial. Earlier studies had demonstrated a greater reduction in late lumen loss with EES. The current trial demonstrates that low late lumen loss can be achieved with EES without a concomitant increase in stent thrombosis, as compared with PES.
Conditions
• Coronary heart disease
Therapies
• Stent/drug-eluting
Study Design
Randomized. Blinded. Parallel.
Patients Enrolled: 1,800
Mean Follow-Up: 1 year
% Female: 30

Primary Endpoints
All-cause mortality, nonfatal MI, and TVR at 1 year
Secondary Endpoints
Cardiac death, nonfatal MI, and ischemia-driven TLR at 1 year
All-cause mortality, nonfatal MI, and TVR at 3 and 5 years
Incidence of stent thrombosis at 1, 3, and 5 years
Patient Population
Patient is suitable candidate for PCI
Life expectancy >5 years
Exclusions:
No dual antiplatelet therapy for 1 year
Cardiogenic shock at presentation
Planned major surgery within 1 month
Participation in another trial
References: Kedhi E, Joesoef KS, McFadden E, et al. Second-generation everolimus-eluting and paclitaxel-eluting stents in real-life practice (COMPARE): a randomised trial. Lancet 2010;375:201-9.

Presented by Dr. Pieter Smits at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2009), San Francisco, CA, September 23, 2009.

[Chevychelov]

Title: Efficacy and Safety of Varenicline for Smoking Cessation in Patients With Cardiovascular Disease (Efficacy and Safety of Varenicline)
Trial Sponsor: Pfizer
Year Published 2010
Topic(s): General Cardiology, Prevention/Vascular
Summary Posted: 1/14/2010
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., F.A.C.C.
Author Disclosure: Research/Research Grants: Astra Zeneca; Research/Research Grants: Eisai; Research/Research Grants: Ethicon; Consultant Fees/Honoraria: Duke Clinical Research Institute; Research/Research Grants: Heartscape; Research/Research Grants: The Medicines Company; Research/Research Grants: Bristol Myers Squibb; Data Safety Monitoring Board (Gov’t/Nonprofit): Duke Clinical Research Institute; Research/Research Grants: Sanofi Aventis
Description
The goal of the trial was to evaluate smoking cessation treatment with varenicline (Chantix), a partial α4β2 nicotinic acetylcholine receptor agonist, compared with placebo among patients with stable coronary disease.
Hypothesis
Varenicline would be more effective in smoking cessation.
Drugs/Procedures Used
In addition to smoking-cessation counseling, patients with stable coronary disease were randomized to varenicline 1 mg twice daily (n = 355) versus placebo (n = 359) for 12 weeks.
Principal Findings
Overall, 714 patients were randomized. There was no difference in baseline characteristics between the groups. In the varenicline group, the mean age was 57 years, 25% were women, body mass index was 27.5 kg/m2, mean duration of smoking was 40 years, mean number of cigarettes per day was 22.1, and the proportion of patients with previous serious attempts to quit smoking was 85.6%. Prior myocardial infarction was present in 45.9%, prior coronary revascularization in 46.2%, prior stroke in 4.5%, and peripheral arterial disease in 23.1%.

The continuous abstinence rate at 9-12 weeks was 47.0% for varenicline versus 13.9% for placebo (p < 0.0001). Abstinence diminished over time, although it was still better with varenicline. At 9-24 weeks, abstinence was 28.2% versus 9.5% (p < 0.001) and at 9-52 weeks, abstinence was 19.2% versus 7.2% (p < 0.001), respectively, for varenicline versus placebo.

All-cause mortality was 0.6% versus 1.4%, cardiovascular mortality was 0.3% versus 0.6%, and any cardiovascular event was 7.1% versus 5.7% (p = NS for all comparisons), respectively, for varenicline versus placebo. Study medication was stopped for an adverse event in 9.6% of the varenicline group versus 4.3% of the placebo group (p < 0.05). The most frequently reported adverse events were nausea (29.5% vs. 8.6%), vomiting (8.2% vs. 1.1%), insomnia (11.9% vs. 6.6%), abnormal dreams (7.9% vs. 1.7%), and constipation (6.5% vs. 2.0%), respectively, for varenicline versus placebo.
Interpretation
Among patients with stable coronary artery disease, the use of varenicline was effective at improving rates of smoking cessation compared with placebo. This was most evident from 9-12 weeks; however, it was also seen at 24-52 weeks. Cardiovascular outcomes were similar between the groups, although varenicline was associated with more gastrointestinal and sleep disturbances.

Varenicline has predominately been studied in otherwise healthy participants; therefore, the safety profile of this agent in individuals with documented coronary artery disease was unknown. Although not definitive, this trial documents that varenicline may be safe for use among individuals with stable coronary artery disease.
Conditions
• Coronary heart disease
• Prevention
Therapies
• Behavior Modification
Study Design
Randomized. Blinded. Parallel.
Patients Screened: 858
Patients Enrolled: 714
Mean Follow-Up: 52 weeks
Mean Patient Age: 57 years
% Female: 25

Primary Endpoints
Continuous abstinence rate for weeks 9-12
Patient Population
Patients 35-75 years of age who had smoked at least 10 cigarettes daily for the last year
Stable coronary artery disease diagnosed at least 2 months ago
Exclusions:
Cardiovascular procedure in the last 2 months
Any sign of cardiovascular instability
Uncontrolled hypertension
Significant cerebrovascular disease
Prior amputation from peripheral arterial disease
Severe congestive heart failure
Severe chronic obstructive pulmonary disease
Severe renal, hepatic, endocrine, or gastrointestinal disease
Cancer
Depression or treatment with antidepressants in the last month
Psychosis, panic, or bipolar disorder
Drug or alcohol dependence
Concurrent smoking cessation medication use including nicotine replacement therapy, bupropion, clonidine, or nortriptyline
References: Rigotti NA, Pipe AL, Benowitz NL, Arteaga C, Garza D, Tonstad S. Efficacy and safety of varenicline for smoking cessation in patients with cardiovascular disease: a randomized trial. Circulation 2010;121:221-9.