Обзор американских кардиологических журналов за неделю (ссылки)

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Title: A Sensitive Cardiac Troponin T Assay in Stable Coronary Artery Disease
Topic: General Cardiology
Date Posted: 1/19/2010
Author(s): Omland T, de Lemos JA, Sabatine MS, et al., on behalf of the Prevention of Events With Angiotensin Converting Enzyme Inhibition (PEACE) Trial Investigators.
Citation: N Engl J Med 2009;361:2538-2547.
Clinical Trial: No
Study Question: What are the prognostic implications of elevated troponin T levels in stable coronary artery disease (CAD) patients?
Methods: A new highly sensitive troponin T assay was used in 3,679 patients with stable CAD and preserved left ventricular function. Patients were followed for an average of 5.2 years for cardiovascular (CV) events.
Results: Concentrations of cardiac troponin T were at or above detection limit (0.001 μg/L) in 97.7% of patients (n = 3,593) and at or above the 99th percentile for apparently healthy subjects (0.0133 μg/L) in 11.1% of patients (n = 407). After adjustment for other prognostic indicators, there was a strong and graded increase in the cumulative incidence of CV death (hazard ratio [HR] per unit increase in natural log of troponin T level, 2.09; 95% confidence interval [CI], 1.60-2.74; p < 0.001) and of heart failure (HR, 2.20; 95% CI, 1.66-2.90; p < 0.001). Increased risk with higher troponin T levels was evident well below the limit of detection of conventional cardiac troponin T assays and below the 99th percentile of values in a healthy population. There was no association between troponin T levels, as measured with this assay, and incidence of myocardial infarction (MI) (HR, 1.16; 95% CI, 0.97-1.40; p = 0.11).
Conclusions: The authors concluded that after adjustment for other prognostic indicators, cardiac troponin T levels, as measured with a highly sensitive assay, were significantly associated with incidence of CV death and congestive heart failure, but not with MI in patients with stable CAD.
Perspective: Troponins T and I have become the ‘gold standard’ for the diagnosis of myocardial necrosis. However, low level elevations of cardiac troponins have been shown to be elevated in a small percentage of stable patients without evidence of acute coronary syndromes. These minor elevations are associated with adverse cardiac outcomes indicating that circulating levels of these contractile proteins may provide useful information beyond that gleaned in the setting of acute MI. With development of a highly sensitive troponin T assay, the authors of the current study have demonstrated that low troponin T levels may be useful in predicting some adverse CV outcomes, independent of conventional risk factors. Several questions are raised including the cellular source and mechanism of low level troponin generation, which may provide guidance to the appropriate management of these patients. The clinical utility of this sensitive screening assay will require additional studies. Daniel T. Eitzman, M.D., F.A.C.C.

Title: Perioperative Practice: Time to Throttle Back
Topic: General Cardiology
Date Posted: 1/25/2010
Author(s): Chopra V, Flanders SA, Froehlich JB, Lau WC, Eagle KA.
Citation: Ann Intern Med 2010;152:47-51.
Clinical Trial: No
Perspective: This perspective discusses how the current practice of perioperative risk assessment often conflicts with trial-based evidence; and advocates that, by heeding existing evidence and by implementing the American College of Cardiology (ACC)/American Heart Association (AHA) guidelines, perioperaive costs can be reduced while outcomes are improved. The following are points to remember.

1. Screening stable patients for coronary artery disease (CAD) before noncardiac surgery does not improve perioperative outcomes.
Data suggesting benefit came from retrospective studies conducted almost exclusively in patients undergoing vascular surgery (and therefore predominantly at high risk).
In those retrospective trials, patients who underwent revascularization may have done so for indications other than upcoming surgery, again implying an independent assessment of high risk.

2. The preoperative identification of significant CAD does not necessarily lead to the identification of patients at increased perioperative cardiac risk.
Preoperative testing, whether noninvasive or invasive, screens for obstructive coronary lesions.
Data from autopsy studies reveal that fatal perioperative myocardial infarction frequently originated with a nonstenotic coronary lesion.
Increased perioperative risk often is associated with an angiographically low-grade lesion vulnerable to plaque rupture.

3. Preoperative coronary revascularization does not lower perioperative cardiac risk.
Among patients with stable CAD, coronary revascularization has no advantage over medical therapy in the prevention of myocardial infarction or death.
Among patients undergoing vascular surgery, randomized, prospective data demonstrate no advantage associated with revascularization compared to good medical therapy.
One relatively small study even demonstrated no clinical benefit associated with preoperative coronary revascularization among patients with high-risk coronary anatomy undergoing high-risk surgery.

4. Failure of a strategy to reduce risk using preoperative coronary revascularization might fail for several reasons.
The existing ‘gold standard’ for detecting CAD using coronary angiography is flawed.
Coronary artery biology appears to matter more than anatomy in defining risk.
Preoperative coronary revascularization is, as with any interventional procedure, associated with inherent risk.

5. The routine use in all patients of perioperative beta-adrenergic antagonists does not reduce perioperative adverse events.
Bradycardia and hypotension associated with indiscriminate beta-blocker use presumably add to adverse perioperative outcomes.
One large study found that perioperative beta-blocker therapy was beneficial only in patients at intermediate or higher risk.

6. Data support a strategy of beta-blocker therapy, titrated to hemodynamic variables, in high-risk patients with ischemic heart disease who are undergoing high-risk surgery.
These recommendations are reflected in the 2009 ACC/AHA Focused Update on Perioperative Beta-Blockers.

7. The implementation of an evidence-based doctrine of selective beta-blocker therapy among high-risk patients with ischemic heart disease undergoing high-risk surgery, selective preoperative functional testing only to identify those high-risk patients, and preoperative coronary revascularization only in very selected cases, is not necessarily the current standard of practice.
Factors affecting this might include legal concerns, pressure from surgeons, and provider bias caused by testing- and procedure-related income.

8. At the authors’ institution, two educational initiatives supporting the ACC/AHA perioperative guideline recommendations resulted in lower costs associated with preoperative risk assessment, but preserved or improved perioperative patient outcomes. David S. Bach, M.D., F.A.C.C.

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Title: Systematic Review: Prediction of Perioperative Cardiac Complications and Mortality by the Revised Cardiac Risk Index
Topic: General Cardiology
Date Posted: 1/25/2010
Author(s): Ford MK, Beattie WS, Wijeysundera DN.
Citation: Ann Intern Med 2010;152:26-35.
Clinical Trial: No
Study Question: What is the ability of the Revised Cardiac Risk Index (RCRI) to predict cardiac complications and death after noncardiac surgery?
Methods: MEDLINE, EMBASE, and ISI Web of Science (1966 to December 31, 2008) were searched for cohort studies that reported the association of the RCRI with major cardiac complications (cardiac death, myocardial infarction, and nonfatal cardiac arrest) or death (in-hospital or within 30 days of surgery). Two reviewers independently extracted study characteristics, documented outcome data, and evaluated study quality.
Results: Of 24 studies (including 792,740 patients), 18 studies reported cardiac complications; 6 of the 18 studies were prospective and had uniform outcome surveillance and blinded outcome adjudication. The RCRI discriminated moderately well between patients at low versus high risk for cardiac events after mixed noncardiac surgery (area under the receiver-operating characteristic curve [AUC] 0.75 [95% confidence interval [CI], 0.72-0.79]), sensitivity 0.65 [CI, 0.46-0.81], specificity 0.76 [CI 0.58-0.88], positive likelihood ratio 2.78 [CI, 1.74-4.45], negative likelihood ratio 0.45 [CI, 0.31-0.67]). Prediction of cardiac events after vascular noncardiac surgery was less accurate (AUC 0.64 [CI, 0.61-0.66], sensitivity 0.70 [CI, 0.53-0.82], specificity 0.55 [CI, 0.45-0.66], positive likelihood ratio 1.56 [CI, 1.42-1.73], negative likelihood ratio 0.55 [CI, 0.40-0.76]). Six studies reported death, with a median AUC of 0.62 (range, 0.54-0.78). A pooled AUC for predicting death could not be calculated because of very high heterogeneity.
Conclusions: The authors concluded that RCRI discriminated moderately well between patients at low versus high risk for cardiac events after mixed noncardiac surgery. However, it did not perform well at predicting cardiac events after vascular noncardiac surgery, or at predicting death.
Perspective: Perioperative adverse cardiac events complicating noncardiac surgery are responsible for significant morbidity and mortality. The RCRI is a multivariable index that uses readily available clinical information in an attempt to predict perioperative risk. (The model uses equally weighted components of coronary artery disease, heart failure, cerebrovascular disease, insulin-requiring diabetes mellitus, renal insufficiency [creatinine >2 mg/dl], and high-risk [suprainguinal vascular, intrathoracic, or intraperitoneal] surgery.) In its original, defining, single-institutional cohort of almost 3,000 patients over age 50 years who were undergoing major, elective noncardiac surgery; the model was shown to have good discriminatory power. However, the present study shows that the same index was more limited when tested in different patient populations in varying geographic locations. It is common that a study concludes that there is predictive power of a multivariate model because it correlates with the desired outcome in the population in which it was derived. Importantly, retrospective correlation, even among prospectively collected data, does not prove that a model will be predictive in other populations. The present study is an important reality check proving just that. David S. Bach, M.D., F.A.C.C.

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.

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Title: Dynamic Cardiovascular Risk Assessment in Elderly People: The Role of Repeated N-Terminal Pro–B-Type Natriuretic Peptide Testing
Topic: Heart Failure/Transplant
Date Posted: 1/25/2010 5:00:00 PM
Author(s): deFilippi CR, Christenson RH, Gottdiener JS, Kop WJ, Seliger SL.
Citation: J Am Coll Cardiol 2010;55:441-450.
Clinical Trial: No
Study Question: Does serial measurement of N-terminal pro–B-type natriuretic peptide (NT-proBNP) in community-dwelling elderly people provide additional prognostic information to that from traditional risk factors?
Methods: The study cohort was comprised of 2,975 community-dwelling older adults free of heart failure (HF) in the longitudinal Cardiovascular Health Study. NT-proBNP was measured at baseline and 2-3 years later in the cohort. The risk of new-onset HF and mortality from cardiovascular causes was associated with baseline NT-proBNP and changes in NT-proBNP levels, adjusting for potential confounders.
Results: The study investigators found that NT-proBNP levels in the highest quintile (>267.7 pg/ml) were independently associated with greater risks of HF (hazard ratio [HR], 3.05; 95% confidence interval [CI], 2.46-3.78) and cardiovascular mortality (HR, 3.02; 95% CI, 2.36-3.86) compared with the lowest quintile (<47.5 pg/ml). Another important finding was that the inflection point for elevated risk occurred at NT-proBNP 190 pg/ml. Among subjects with initially low NT-proBNP (<190 pg/ml), those who developed a >25% increase on follow-up to >190 pg/ml (21%) were at greater adjusted risk of HF (HR, 2.13; 95% CI, 1.68-2.71) and cardiovascular mortality (HR, 1.91; 95% CI, 1.43-2.53) compared with those with sustained low levels. Among participants with initially high NT-proBNP, those who developed a >25% increase (40%) were at higher risk of HF (HR, 2.06; 95% CI, 1.56-2.72) and cardiovascular mortality (HR, 1.88; 95% CI, 1.37-2.57), whereas those who developed a <25% decrease to ≤190 pg/ml (15%) were at lower risk of HF (HR, 0.58; 95% CI, 0.36-0.93) and cardiovascular mortality (HR, 0.57; 95% CI, 0.32-1.01) compared with those with unchanged high values.
Conclusions: The authors concluded that NT-proBNP levels independently predict HF and cardiovascular mortality in older adults. NT-proBNP levels frequently change over time, and these fluctuations reflect dynamic changes in cardiovascular risk.
Perspective: This is an important study because it suggests NT-proBNP is an important long-term predictor of HF in the elderly and possibly an indicator of ‘subclinical’ heart failure. Another important take-away is that a level of 190 pg/ml may possibly be a cut-off point in patients without a ‘dry’ BNP (i.e., BNP at euvolemia). Further studies are required to validate these results. From a mechanistic perspective, I would be interested to know whether NT-proBNP level fluctuations reflect changes in left ventricular function such as E/E’ on tissue Doppler and other indicators of left ventricular diastolic function. Also, more data are needed to determine whether a single marker or a panel of biomarkers is superior in accurately predicting cardiovascular risk (Braunwald E. Heart Fail Clin 2009;4:xiii-xiv). Ragavendra R. Baliga, M.B.B.S.

Title: Supported High-Risk Percutaneous Coronary Intervention With the Impella 2.5 Device: The Europella Registry
Topic: Interventional Cardiology
Date Posted: 1/22/2010
Author(s): Sjauw KD, Konorza T, Erbel R, et al.
Citation: J Am Coll Cardiol 2009;54:2430-2434.
Clinical Trial: No
Study Question: What is the safety and feasibility of left ventricular (LV) support with the Impella 2.5 device during high-risk percutaneous coronary intervention (PCI)?
Methods: The Europella registry was comprised of patients from 10 tertiary PCI centers across Europe. It was designed to evaluate the safety and feasibility of all patients undergoing elective high-risk PCI with prophylactic mechanical cardiac support with the Impella 2.5. The Impella 2.5 (Abiomed, Inc.) is a novel catheter-mounted (9-F) micro-axial rotary blood pump (12-F), designed for short-term circulatory support. The registry was supported by Abiomed Europe GmbH. Safety and feasibility endpoints included incidence of 30-day adverse events and successful device function.
Results: Patients were older (62% were >70 years of age), 54% had an LV ejection fraction ≤30%, and the prevalence of comorbid conditions was high. Mean European System for Cardiac Operative Risk Evaluation score was 8.2 (standard deviation 3.4), and 43% of the patients were refused for coronary artery bypass grafting. A PCI was considered high-risk due to left main disease, last remaining vessel disease, multivessel coronary artery disease, and low LV function in 53%, 17%, 81%, and 35% of the cases, respectively. Mortality at 30 days was 5.5%. Rates of myocardial infarction, stroke, bleeding requiring transfusion/surgery, and vascular complications at 30 days were 0%, 0.7%, 6.2%, and 4.0%, respectively.
Conclusions: The authors concluded that this registry supports the safety, feasibility, and potential usefulness of hemodynamic support with Impella 2.5 in high-risk PCI.
Perspective: The present study shows that periprocedural support with the Impella 2.5 for elective high-risk PCI is safe and feasible and extends prior observations from three smaller case series. It should be noted that all adverse events were based on clinical diagnoses assigned by the patient's physician. Overall, this multicenter registry supports the safety, feasibility, and potential usefulness of hemodynamic support with Impella 2.5 in high-risk PCI, but needs to be evaluated in prospective randomized clinical trials. Debabrata Mukherjee, M.D., F.A.C.C.

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Title: ST Elevation on the Exercise ECG in Patients Presenting With Chest Pain and No Prior History of Myocardial Infarction
Topic: Noninvasive Cardiology
Date Posted: 1/20/2010
Author(s): Murphy JC, Scott PJ, Shannon HJ, et al.
Citation: Heart 2009;95:1792-1797.
Clinical Trial: No
Study Question: What is the etiology of ST-segment elevation (STE) noted during exercise stress testing (EST) in patients with chest pain, but without a prior history of myocardial infarction (MI)?
Methods: Stress testing with ECG monitoring was undertaken in 19,189 patients over an 8-year period. EST was performed with a standard Bruce protocol, and beta-blockers were held prior to testing. There was evidence of prior MI in 4,248, leaving 14,941 EST for evaluation. Within this cohort, 116 (0.78%) patients had STE during or after exercise. STE was defined as ≥1 mm STE 0.08 second after the J-point, occurring in two or more contiguous leads.
Results: All patients were Caucasian with an average age of 57 ± 11.1 years, and 79.3% were male. Mean exercise duration was 6 minutes (1.3-15) and mean maximum predicted heart rate achieved was 86.7% (61-115%). EST was terminated for chest pain in 56 and STE in 39. STE first occurred in stage 1 in 30%, in stage 2 in 30%, and was noted only in recovery in 24.1% of patients. Coronary arteriography was performed in 108 of the 116 patients, and coronary stenosis >70% was noted in all. Single-vessel disease was noted in 60 patients, 14 of whom had occluded or subtotally occluded arteries. Anterior STE was seen in 41 subjects, 40 of whom had severe disease in the left anterior descending coronary artery, and inferior STE was noted in 66, 63 of whom had either right or circumflex coronary disease. Only one subject had lateral STE.
Conclusions: STE on exercise treadmill testing is a rare but highly specific finding for severe coronary artery disease, and the location of STE predicts the anatomical location of the disease.
Perspective: STE on exercise electrocardiography has been noted for decades. It has been associated with a significant underlying wall motion abnormality and prior MI, and in some patient populations, has been hypothesized to relate to exercise-induced or post-exercise coronary vasospasm as well. In this exclusively Caucasian population, the incidence of STE during or after exercise was low, but the finding was highly specific for severe fixed obstructive coronary disease, with many patients having totally or subtotally occluded coronary arteries. The location of STE was 95% predictive of the anatomical disease location. Other studies with demographically different patient populations have suggested that STE may be more predictive of coronary vasospasm. Although rarely noted, STE on stress testing should probably prompt further assessment with coronary arteriography. William F. Armstrong, M.D., F.A.C.C.

Title: Statins, Fibrates, and Venous Thromboembolism: A Meta-Analysis
Topic: Prevention/Vascular
Date Posted: 1/20/2010
Author(s): Squizzato A, Galli M, Romualdi E, et al.
Citation: Eur Heart J 2009;Dec 22:[Epub ahead of print].
Clinical Trial: No
Study Question: Is there an effect of lipid-lowering drugs on venous thromboembolism (VTE) occurrence?
Methods: MEDLINE and EMBASE databases were searched to identify studies that evaluated the effect of lipid-lowering drugs, in particular statins and fibrates, on VTE risk until April 2009. A scoring system was used to divide studies into two quality categories. Odds ratios (ORs) and 95% confidence intervals (CIs) were then calculated and pooled using a fixed and a random-effects model. Statistical heterogeneity was evaluated through the use of I2 statistics.
Results: Three randomized controlled trials (RCTs), three cohorts, and eight case-control studies were included in a systematic review, for a total of 863,805 patients. Statin use significantly reduced VTE risk (OR, 0.81; 95% CI, 0.66-0.99, random-effect model). There was a very high heterogeneity among the studies (I2 > 80%). The use of fibrates was associated with a significant increase in the risk of VTE (OR, 1.58; 95% CI, 1.23-2.02), without heterogeneity (I2 = 0%).
Conclusions: This meta-analysis of available literature suggests that statins may lower the risk of VTE, whereas fibrates may increase the risk. Due to several methodological limitations, this conclusion should be considered with caution, and additional, specifically designed RCTs are warranted.
Perspective: Meta-analysis should be used primarily for hypothesis generating, but it is not likely that RCTs will be performed specifically to determine the impact of lipid therapies on incident VTE. I think the data are strong enough to use fibrates with care in persons with a history of VTE and who are at high risk, as well as to consider them a risk factor when assessing for clinical VTE. The antithrombotic effects of statins could be related to lipid effects on endothelial function, antiplatelet effects, and anti-inflammatory effects. The only posit for fibrates increasing VTE is an increase in homocysteine levels, a relatively weak explanation. Melvyn Rubenfire, M.D., F.A.C.C.

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Title: Prevalence of High Body Mass Index in US Children and Adolescents, 2007-2008
Topic: Prevention/Vascular
Date Posted: 1/22/2010
Author(s): Ogden CL, Carroll MD, Curtin MM, Flegal KM.
Citation: JAMA 2010;303:242-249.
Clinical Trial: No
Study Question: What is the prevalence of high body mass index (BMI) among children and adolescents in the United States?
Methods: Using data from the National Health and Nutrition Examination Survey, 2007-2008, BMI was estimated for 3,281 children (ages 2-19 years) and 719 infants and toddlers (ages birth to 2 years). Prevalence of high weight for recumbent length (≥95th percentile, based on Centers for Disease Control and Prevention growth charts) for infants and toddlers was calculated for five time periods from 1999 to 2008. Prevalence of high BMI was calculated for children (over the age of 2) and adolescents with high BMI defined as three groups: BMI ≥97th percentile, BMI ≥95th percentile, and BMI ≥85th percentile for age. Trends over time were examined by age, sex, and race/ethnicity.
Results: The prevalence of high BMI in 2007-2008 was 9.5% (95% confidence interval [CI], 7.3%-11.7%) for infants and toddlers. For children over the age of 2 and adolescents, the prevalence of those at or above the 97th percentile for BMI was 11.9% (95% CI, 9.8%-13.9%), 16.9% (95% CI, 14.1%-9.6%) for BMI ≥95th percentile, and 31.7% (95% CI, 29.2%-34.1%) for BMI ≥85th percentile. No significant trends over time were observed between 1999-2000 and 2007-2008, with the exception of boys, ages 6-19 years, with BMIs ≥97th percentile (odds ratio [OR], 1.52; 95% CI, 1.17-2.01) and for non-Hispanic white boys ages 6-19 years (OR, 1.87; 95% CI, 1.22-2.94).
Conclusions: The authors concluded that no significant linear trends were observed for high BMI over the past 11 years, with the exception of boys in the highest BMI category.
Perspective: These data suggest a leveling off of the prevalence of overweight and obese children in the United States. However, given the numbers of children with high BMI, aggressive prevention of obesity among US children is still warranted. Elizabeth A. Jackson, M.D., F.A.C.C.

Title: Two Self-Management Interventions to Improve Hypertension Control: A Randomized Trial
Topic: Prevention/Vascular
Date Posted: 1/22/2010
Author(s): Bosworth HB, Olsen MK, Grubber JM, et al.
Citation: Ann Intern Med 2009;151:687-695.
Clinical Trial: yes
Study Question: What is the effectiveness of blood pressure (BP) self-management, or a tailored, nurse-administered health behavior intervention, or both, in the improvement of BP?
Methods: The authors reported the results of a 2 x 2 randomized trial, stratified by enrollment site and patient health literacy status, to either usual care, versus home BP monitoring thrice weekly, versus a tailored behavioral telephone intervention, versus behavioral intervention plus BP monitoring. Primary outcome was BP control at 6-month intervals over 24 months.
Results: Of 636 hypertensive patients, 475 (75%) completed the 24-month follow-up. The proportion of patients with controlled BP beyond that seen with usual care was 4.3% (95% confidence interval [CI], -4.5% to 12.9%) in the behavioral intervention group, 7.6% (95% CI, -1.9% to 17.0%) in the home BP monitoring group, and 11.0% (95% CI, 1.9% to 19.8%) in the combined intervention group. Relative to the usual care group, the change in systolic BP was 0.6 mm Hg (95% CI, -2.2 to 3.4 mm Hg) for the behavioral group, -0.6 mm Hg (95% CI, -3.6 to 2.3 mm Hg) for the BP monitoring group, and -3.9 mm Hg (95% CI, -6.9 to -0.9 mm Hg) for the combined intervention group. Similar findings occurred for diastolic BP.
Conclusions: The authors concluded that combined home BP monitoring and tailored behavioral telephone intervention improved BP control, both systolic and diastolic BP at 24 months, compared with usual care.
Perspective: This important study examines the relative effectiveness of simple home BP monitoring, versus continual behavioral 'coaching' regarding exercise, diet, weight, and other healthy lifestyle interventions. This study showed a trend toward improvement in BP with each intervention, but suggests that the only significant improvement came with using both home BP monitoring and the behavioral intervention. We know that home BP measurement is essential to accurately measuring BP (avoiding the very prevalent problem of white coat hypertension), as well as monitoring response to therapy. This study suggests that there are added benefits to combining behavioral intervention with this. Programs based on this type of intervention could have great health and cost benefits, if we could design a health care system with the capacity to efficiently provide this type of support. James B. Froehlich, M.D., F.A.C.C.

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INSTEAD – Type B Dissection
Omega-3 Fatty Acid Levels
The Future of Cardiology is in Atlanta
[Ссылки доступны только зарегистрированным пользователям ]

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Title: The Response of the QT Interval to the Brief Tachycardia Provoked by Standing: A Bedside Test for Diagnosing Long QT Syndrome
Topic: Arrhythmias
Date Posted: 1/27/2010 5:00:00 PM
Author(s): Viskin S, Postema PG, Bhuiyan ZA, et al.
Citation: J Am Coll Cardiol 2010;Jan 27:[Epub ahead of print].
Clinical Trial: No
Study Question: Is the response of the QT interval during an orthostatic increase in sinus rate useful for the diagnosis of long QT syndrome (LQTS)?
Methods: The QT interval was measured while supine and after standing in 68 patients with LQTS (mean age 32 years) and in 82 control subjects (mean age 35 years).
Results: The mean baseline corrected QT (QTc) was significantly longer in the LQTS group (465 ms) than in the control group (405 ms). After standing, the heart rate increased by a mean of 28 bpm in the control group and 26 bpm in the LQTS group. The mean QT interval during the maximum increase in sinus rate decreased by a mean of 21 ms in the control group and increased by a mean of 4 ms in the LQTS group. The mean QTc after standing increased to a significantly greater degree in the LQTS group (89 ms) than in the control group (50 ms).
Conclusions: An exaggerated increase in QTc during transient orthostatic acceleration of the sinus rate is helpful for identifying patients with LQTS.
Perspective: Prior studies have demonstrated impaired adaptation of the QTc to a gradual increase in sinus rate, such as during exercise. This study demonstrates that there also is impaired adaptation of the QTc to a brief and transient orthostatic increase in heart rate. The simple bedside maneuver of recording an electrocardiogram when an individual suddenly changes from the supine to upright position is most likely to be useful in patients suspected of having QTc who have only borderline prolongation of the baseline QTc. Fred Morady, M.D., F.A.C.C.

Title: ThermoCool AF (ThermoCool AF)
Trial Sponsor: Biosense Webster (makers of the NaviStar ThermoCool Irrigated Tip Catheter)
Year Published 2010
Topic(s): Arrhythmias
Summary Posted: 1/27/2010 4:00:00 PM
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

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Продолжение ThermoCool AF (ThermoCool AF)
Description
Numerous small studies have demonstrated the utility of catheter ablation with pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF), as compared with antiarrhythmic drug therapy (ADT). ThermoCool AF is the largest trial to study this question in patients with symptomatic paroxysmal AF, who had not improved with at least one drug.
Hypothesis
Catheter ablation would be superior to ADT in patients with symptomatic AF.
Drugs/Procedures Used
Patients were randomized in a 2:1 fashion to either catheter ablation, or a previously unused antiarrhythmic drug (AAD) (Vaughn class I or III). In the catheter ablation group, PVI was performed using the NaviStar ThermoCool Irrigated Tip Catheter, and the Carto Navigation system. Additional ablation was left to the discretion of the investigator. In the ADT arm, a previously unused Food and Drug Administration approved medication for treating AF (dofetilide, flecainide, propafenone, sotalol, quinidine) at dosages recommended by the American College of Cardiology/American Heart Association/European Society of Cardiology was used. The choice of the drug was at the discretion of the investigator.
Concomitant Medications
Warfarin for 3 months
Principal Findings
A total of 167 patients were randomized, 106 to catheter ablation, and 61 to ADT. The trial was stopped after the first 150 patients were randomized, when interim analysis suggested a strong benefit with catheter ablation. Baseline characteristics were fairly similar between the two groups. The median duration of AF was about 5.7 years. Structural heart disease was present in about 11%, hypertension was present in about 49%, and cerebrovascular accident/transient ischemic attack was noted in 3% of the patients. The mean atrial diameter was about 4.2 cm. The majority of prior AAD failures were due to propafenone (50.3%). Others included sotalol (35.2%), flecainide (27.9%), amiodarone (7.9%), and dofetilide (2.4%). The mean number of class I/III drugs at baseline was 1.3. Most patients in the ADT arm received either flecainide (36%) or propafenone (41%).

Protocol-defined treatment failure was significantly lower in the catheter ablation arm compared with the ADT arm (66% vs. 16%, hazard ratio 0.30, 95% confidence interval 0.19-0.47, p < 0.001). Freedom from symptomatic (70% vs. 19%, p < 0.001) and any (63% vs. 17%, p < 0.001) recurrent atrial arrhythmia was also improved with catheter ablation. There was a high rate of cross-over from the ADT to catheter ablation arm (77%), at a mean of 3.9 months after the onset of the effectiveness evaluation period. Quality of life and symptom severity scores were significantly better in the catheter ablation arm, as compared with the ADT arm at 3 months.

The rate of major treatment-related adverse events at 30 days was similar between the catheter ablation and ADT arms (4.9% vs. 8.8, p = NS), including one pericardial effusion in the catheter ablation arm, and two life-threatening arrhythmias in the ADT arm.
Interpretation
The results of this multicenter trial indicate that catheter ablation with PVI is associated with significantly less treatment failure at 9 months, as compared with ADT, in patients with symptomatic AF, who have failed at least one AAD. There is also a significant reduction in recurrent atrial arrhythmias, a significant improvement in quality of life, without a significant difference in major treatment-related adverse events at 30 days. One limitation of this trial is that even though more than 5,000 patients were screened, only 167 were enrolled. This raises issues with generalizability of these findings. Additionally, all investigators in this trial had extensive experience with catheter ablation, which is a technically challenging procedure. Moreover, ablation practices are not standardized, and a variety of additional ablations besides PVI were frequently employed even in this trial. Hence, outcomes at less experienced centers are likely to be less impressive. Details of rate control between the two groups are also unavailable. Long-term outcomes and cost-effectiveness analyses are also necessary. However, this trial provides supportive evidence regarding the use of catheter ablation for symptomatic AF in patients who have failed at least one AAD.
Conditions
• Arrhythmias / Atrial fibrillation
Therapies
• Electrophysiologic study
Study Design
Randomized. Parallel.
Patients Screened: 5,545
Patients Enrolled: 167
NYHA Class (% I, II, II, IV): I (87%), II (13%)
Mean Follow-Up: 9 months (with a 3-month blanking period)
Mean Patient Age: 55.7 years
% Female: 34

Mean Ejection Fraction: 62.5%
Primary Endpoints
Freedom from protocol-defined treatment failure, which included documented symptomatic paroxysmal AF during the effectiveness evaluation period
Secondary Endpoints
Major treatment-related adverse events at 30 days
Patient Population
At least three symptomatic AF episodes within 6 months prior to randomization (≥1 episode verified by electrocardiography)
Lack of response to at least one AAD (class I, class III, or atrioventricular nodal blocker)
Exclusions:
AF >30 days in duration
Age <18 years
Ejection fraction <40%
Previous catheter ablation for AF
Documented left atrial thrombus
Amiodarone therapy in the preceding 6 months
New York Heart Association class III or IV symptoms
Myocardial infarction within past 2 months, or coronary artery bypass grafting within past 6 months
Thromboembolic event within the past 12 months
Severe pulmonary disease
Prior valvular cardiac surgical procedure
Presence of implantable cardioverter defibrillator
Contraindication to ADT or anticoagulation
Life expectancy <12 months
Left atrial size >5 cm in parasternal view
References: Wilber DJ, Pappone C, Neuzil P, et al. Comparison of antiarrhythmic drug therapy and radiofrequency catheter ablation in patients with paroxysmal atrial fibrillation: a randomized controlled trial. JAMA 2010;303:333-40.

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Title: Best Bypass Surgery trial (BBS)
Trial Sponsor:
Danish Heart Foundation
Danish Medical Research Council
Copenhagen Hospital Corporations Medical Research Council
Rigshospitalet Research Council
Aase and Ejnar Danielsens Foundation
Gangsted Foundation
Danish Agency for Science, Technology, and Innovation

Year Published 2010
Topic(s): Cardiovascular Surgery, General Cardiology, Prevention/Vascular
Summary Posted: 1/27/2010
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 coronary artery bypass graft surgery (CABG) performed off-pump versus on-pump in patients with coronary artery disease.
Hypothesis
Off-pump CABG would be associated with improved adverse outcomes in high-risk patients.
Drugs/Procedures Used
High-risk patients (EuroSCORE ≥5) with three-vessel coronary disease were randomized to off-pump CABG (n = 177) versus on-pump CABG (n = 164).
Concomitant Medications
Patients in the off-pump group were given 100 U/kg of unfractionated heparin to achieve an activated clotting time >200 seconds. Patients in the on-pump group were given 300 U/kg to achieve an activated clotting time >480 seconds, which was reversed with protamine sulfate at the end of the procedure.
Principal Findings
Overall, 341 patients were randomized. There was no difference in baseline characteristics between the groups. In the off-pump arm, the mean age was 76 years, 35% were women, body mass index was 26.3 kg/m2, 18% had diabetes, 11% had chronic obstructive pulmonary disease, 21% were current smokers, 51% had an ejection fraction >50%, and the mean EuroSCORE was 6.9. The predicted 30-day mortality was approximately 3%.

In the off-pump group, 4.5% of patients crossed over to on-pump CABG (mainly due to hemodynamic instability). In the on-pump group, 3.7% of patients crossed over to off-pump CABG (mainly due to severe aortic calcification). The mean number of grafts per patient was 3.22 in the off-pump group versus 3.34 in the on-pump group (p = 0.11), whereas the mean number of grafts to the lateral wall of the heart was 0.97 versus 1.14 (p = 0.01), respectively.

The 30-day composite primary outcome occurred in 15% of the off-pump group versus 18% of the on-pump group (p = 0.47). Death was 3.4% versus 6.7%, myocardial infarction was 5.1% versus 9.2%, stroke was 4.0% versus 3.7%, coronary re-intervention was 0.6% versus 1.8%, new-onset atrial fibrillation was 43% versus 44%, re-operation for bleeding was 5.1% versus 2.4%, and hemodialysis was 4.0% versus 4.9%, respectively for off-pump versus on-pump (p = NS, for all comparisons).
Interpretation
Among patients with three-vessel coronary artery disease and elevated clinical risk, the use of off-pump CABG is feasible. This method of revascularization is associated with similar short-term adverse events compared with on-pump CABG. While the mean number of grafts was similar between the groups, fewer grafts were placed to the lateral wall of the heart with off-pump CABG. This might affect long-term outcomes, which were shown to be worse with off-pump CABG in the larger ROOBY trial. The current trial was conducted at a single center and only reported outcomes to 30 days.
Conditions
• Coronary heart disease
• Coronary heart disease / Angina pectoris / Stable
Therapies
• CABG
Study Design
Randomized. Blinded. Parallel. Stratified.
Patients Screened: 2,578
Patients Enrolled: 341
NYHA Class (% I, II, II, IV): NYHA class III or IV: 29%
Mean Follow-Up: 30 days
Mean Patient Age: 76 years
% Female: 35

Mean Ejection Fraction: 51% with ejection fraction >50%
Primary Endpoints
Composite of all-cause mortality, acute myocardial infarction, resuscitated cardiac arrest, low cardiac output/cardiogenic shock, stroke, or coronary re-intervention at 30 days
Secondary Endpoints
Hyperdynamic shock
New-onset atrial fibrillation
Need for pacing more than 24 hours
Renal failure
Re-operation
Respiratory failure requiring re-intubation
Pneumonia
Length of stay in the intensive care unit and the hospital
Patient Population
Patients at least 54 years of age with EuroSCORE ≥5 and three-vessel coronary disease involving a marginal artery
Elective or subacute indication for surgery
Exclusions:
Previous heart surgery
Left ventricular ejection fraction <30%
Inability to provide informed consent
Unstable preoperative condition
References: Moller CH, Perko MJ, Lund JT, et al. No major differences in 30-day outcomes in high-risk patients randomized to off-pump versus on-pump coronary bypass surgery. The Best Bypass Surgery Trial. Circulation 2010;121:498-504.

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Title: Optimizing Hemodynamics in Heart Failure Patients by Systematic Screening of Left Ventricular Pacing Sites: The Lateral Left Ventricular Wall and the Coronary Sinus Are Rarely the Best Sites
Topic: Arrhythmias
Date Posted: 2/1/2010 5:00:00 PM
Author(s): Derval N, Steendijk P, Gula LJ, et al.
Citation: J Am Coll Cardiol 2010;55:566-575.
Clinical Trial: No
Study Question: What is the optimal left ventricular (LV) pacing site for cardiac resynchronization therapy (CRT)?
Methods: Thirty-five patients (mean age 63 years) with a nonischemic cardiomyopathy (mean ejection fraction 28%) and left bundle branch block underwent hemodynamic measurements during dual-chamber (DDD) pacing from a lateral branch of the coronary sinus (CS) and at 10 prespecified endocardial LV sites. Hemodynamic results at pacing sites were expressed as a percentage variation from the hemodynamics during atrial pacing.
Results: There was a large range in the hemodynamic response to pacing at different sites within individual patients (+19% to +93%), and between different patients (-31% to +93%). None of the 11 pacing sites was consistently associated with the best hemodynamic response to pacing. DDD pacing at the best LV site yielded a better hemodynamic response (+31%) compared to CS pacing (+15%). The CS was the pacing site that yielded the best hemodynamic response in only 9% of patients.
Conclusions: The optimal LV site for CRT is unpredictable, must be identified on an individualized basis by testing, rarely is in the CS, and often is endocardial.
Perspective: The response rate to conventional CRT, with the LV lead in a branch of the CS, has been 60-80%. The results of this study suggest that the response rate to CRT can be improved by identifying the optimal pacing site on an individualized basis. Widespread adaptation of this approach into clinical practice may be hampered by the rigorous and lengthy testing protocol and by the potential problems associated with long-term endocardial LV pacing. Fred Morady, M.D., F.A.C.C.

Title: Comparison of Antiarrhythmic Drug Therapy and Radiofrequency Catheter Ablation in Patients With Paroxysmal Atrial Fibrillation: A Randomized Controlled Trial
Topic: Arrhythmias
Date Posted: 1/28/2010
Author(s): Wilber DJ, Pappone C, Neuzil P, et al., on behalf of the ThermoCool AF Trial Investigators.
Citation: JAMA 2010;303:333-340.
Clinical Trial: yes
Study Question: Is radiofrequency catheter ablation (RFCA) more effective than antiarrhythmic drug therapy (ADT) in patients with paroxysmal atrial fibrillation (PAF)?
Methods: The subjects of this study were 159 patients (mean age 56 years) with symptomatic PAF who had failed to respond to treatment with ≥1 rhythm- or rate-control agent. The patients were randomized to RFCA (n = 103) with an irrigated-tip ablation catheter or ADT (n = 56) with flecainide, propafenone, dofetilide, sotalol, or quinidine. The ablation strategy was a minimum of wide-area pulmonary vein isolation, with additional ablation at the operator’s discretion. Redo RFCA was allowed during a 3-month blanking phase. Efficacy was assessed at clinic visits and with serial transtelephonic monitoring. The 1° endpoint was freedom from symptomatic AF during the 9 months after the blanking period.
Results: A redo ablation procedure was performed in 12.6% of patients in the RFCA group. The 1° endpoint was achieved significantly more often in the RFCA group (66%) than in the ADT group (16%). The rate of major adverse events was higher in the ADT group (8.8%) than in the RFCA group (4.9%).
Conclusions: RFCA is more effective than ADT for preventing PAF in patients who already have not responded to one antiarrhythmic drug.
Perspective: The results confirm that patients with AF who do not respond to one trial of ADT are unlikely to respond to subsequent ADTs, and support the current practice guidelines that consider catheter ablation of AF to be appropriate second-line therapy after failure of initial ADT. The modest efficacy of RFCA (66%) most likely reflects the difficulty in achieving permanent isolation of the pulmonary veins. Fred Morady, M.D., F.A.C.C.

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Title: Risk for Incident Atrial Fibrillation in Patients Who Receive Antihypertensive Drugs: A Nested Case-Control Study
Topic: Arrhythmias
Date Posted: 1/26/2010
Author(s): Schaer BA, Schneider C, Jick SS, Conen D, Osswald S, Meier CR.
Citation: Ann Intern Med 2010;152:78-84.
Clinical Trial: No
Study Question: Is the risk of developing atrial fibrillation (AF) affected by the type of medication used to treat hypertension?
Methods: The subjects of this retrospective study were selected from a primary-care database in the United Kingdom and all received monotherapy for hypertension. There were 4,661 patients who developed AF during follow-up and 18,642 matched control subjects who did not. Approximately 70% of patients in both groups were at least 70 years old. The class of drug used to treat the hypertension was analyzed in both groups.
Results: Compared to patients whose hypertension was treated with a calcium-channel blocker (CCB), recipients of an angiotension-converting enzyme inhibitor (ACEI) had a 25% lower risk of developing AF, recipients of an angiotension II-receptor blocker (ARB) had a 29% lower risk, and recipients of a beta-blocker had a 22% lower risk.
Conclusions: Treatment of hypertension with an ACEI, ARB, or beta-blocker reduces the risk of new-onset AF compared to CCBs.
Perspective: Several prior studies have demonstrated that ACEIs and ARBs reduce the risk of AF. Possible mechanisms include lowering of blood pressure, prevention or treatment of heart failure, and prevention of atrial fibrosis. CCBs lower the blood pressure, but do not prevent heart failure or atrial fibrosis. Therefore, the results of this study suggest that prevention of heart failure and/or atrial fibrosis explain the lower risk of AF when hypertension is treated with an ACEI, ARB, or beta-blockers. However, it should be noted that the study does not rule out the possibility of a proarrhythmic effect of CCBs compared to a neutral effect of ACEIs, ARBs, and beta-blockers on the risk of AF. Fred Morady, M.D., F.A.C.C.

Title: Aortic Elasticity and Size Are Associated With Aortic Regurgitation and Left Ventricular Dysfunction in Tetralogy of Fallot After Pulmonary Valve Replacement
Topic: Congenital Heart Disease
Date Posted: 1/26/2010
Author(s): Grotenhuis HB, Ottenkamp J, de Bruijn L, et al.
Citation: Heart 2009;95:1931-1936.
Clinical Trial: No
Study Question: What are the relationships between aortic elasticity, aortic valve competence, and biventricular function in patients with repaired tetralogy of Fallot (TOF) who have undergone pulmonary valve replacement?
Methods: A prospective case-controlled study was performed. Sixteen patients with TOF and 16 age- and gender-matched controls underwent cardiac magnetic resonance imaging for evaluation of aortic root dimensions, biventricular function, aortic elasticity, and quantification of aortic regurgitation.
Results: Aortic root dimensions at the sinuses of ******** were larger in the TOF patients (39.3 ± 5.4) compared with the controls (30.4 ± 3.1). Reduced aortic elasticity was also seen in the TOF group (pulse wave velocity in the aortic arch of 5.5 ± 1.2 m/s compared with 4.6 ± 0.9 m/s). TOF patients were also found to have increased aortic regurgitation (regurgitant fraction of 6% vs. 1%, p < 0.01) and decreased left ventricular ejection fraction (LVEF) (51% vs. 58%, p = 0.01), whereas right ventricular ejection fraction (RVEF) was preserved in both groups. The degree of aortic regurgitation fraction was associated with dilatation of the aortic root (r = 0.39-0.49, p < 0.05) and reduced aortic root distensibility (r = 0.44, p = 0.02). Reduced LVEF correlated with degree of aortic regurgitation and RVEF (r = 0.41, p = 0.02 and r = 0.49, p < 0.01, respectively).
Conclusions: Aortic root dilatation and reduced aortic elasticity are frequently seen in patients following repair of TOF and pulmonary valve replacement. Aortic wall pathology may contribute to LV dysfunction in this patient population.
Perspective: This paper studies the relationship between aortic root pathology and LV function in patients following TOF repair and subsequent pulmonary valve replacement. LV dysfunction has been well-documented in patients after TOF repair, and has often been attributed to intraventricular dependence, as well as perioperative insults with early bypass techniques. This study shows a relationship between relatively mild degrees of aortic insufficiency and root dilatation with LV dysfunction. Although the correlation coefficients are relatively weak, it appears that this was a consistent finding in a relatively small patient population. This study emphasizes the complexity of etiologies contributing to LV dysfunction in patients following repair of TOF. Timothy B. Cotts, M.D., F.A.C.C.

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Title: Use of Herbal Products and Potential Interactions in Patients With Cardiovascular Disease
Topic: General Cardiology
Date Posted: 2/1/2010 5:00:00 PM
Author(s): Tachjian A, Maria V, Jahangir A, et al.
Citation: J Am Coll Cardiol 2010;55:515-525.
Clinical Trial: No
Study Question: How does the use of herbal supplements affect patients with cardiovascular disease?
Methods: This review was based on a search of PubMed and MEDLINE databases, for literature on herbal supplements published between 1966 and 2008. Search terms included cardiovascular agents, complementary therapies, herb–drug interactions, and cardiovascular disease interactions.
Results: Over 15 million children and adults in the United States consume herbal remedies or high-dose vitamins. Herbal remedies include plants or plant products. They compose a large majority of complementary alternative medicine therapies used with an estimated 30,000 dietary supplements sold in the United States. Herbs are considered food products and are not regulated as drugs. Lack of quality control has resulted in significant variation in herb supplements and inconsistent labeling of products. In one study, more than 40% of herbal products examined had incorrect labeling for amounts of ingredients listed. In addition, contamination of the supplement with heavy metals has been reported and pharmaceuticals have been found in herbal supplements. Since controlled trials are not available for most herbal remedies, an understanding of the efficacy of many of these therapies is not available. Reporting of adverse events related to herbal remedies is not mandatory; therefore, information on potential adverse effects is not well understood either.

Commonly used herbal supplements include St. John’s wort, motherwort, ginseng, ginkgo, grapefruit juice, saw palmetto, danshen, tetrandine and yohimbine, and licorice. St. John’s wort increases the hepatic cytochrome P450 system and thus can reduce levels of medications including cyclosporine. St. John’s wort may also reduce prothrombin time in patients talking warfarin. Motherwort can reduce platelet aggregation and increase risk of bleeding. Ginseng can affect blood pressure, causing both hypertension and hypotension. Ginkgo, when used in combination with antiplatelet agents, can increase bleeding time. Grapefruit juice can inhibit CYP3A4 enzyme and thus increase levels of calcium channel blockers, cyclosporine, and statins. Saw palmetto can increase bleeding risk among patients taking warfarin. Danshen reduces elimination of warfarin and may interfere with digoxin assays. Tetrandine is a vasoactive alkaloid, which can cause hepatotoxicity and renal toxicity. Yohimbine can increase blood pressure. Licorice is often used as an expectorant and can cause pseudoaldosteronism and hypokalemia.
Conclusions: The authors encourage physicians to ask patients about concomitant use of herbal therapies, in particular among patients who are taking cardiovascular medications with narrow therapeutic windows such as digoxin and warfarin. Increases in research, which provides controlled clinical evaluations of herbal therapies and improvements in regulation and oversight of such therapies, are warranted.
Perspective: This review outlines a number of concerns regarding the use of herbal therapies among patients taking cardiovascular medications. Improved education for both health care providers and patients, along with systematic evaluation of these therapies, will allow for safe and effective use of such therapies among patients with heart disease. Elizabeth A. Jackson, M.D., F.A.C.C.

Title: Relationship of Thrombus Healing to Underlying Plaque Morphology in Sudden Death
Topic: General Cardiology
Date Posted: 1/29/2010
Author(s): Kramer MCA, Rittersma SZ, deWinter RJ, et al.
Citation: J Am Coll Cardiol 2010;55:122-132.
Clinical Trial: No
Study Question: What is the relationship of thrombus healing to underlying plaque morphology in sudden death?
Methods: All sudden death cases referred to the Examiner’s Office between 2005 and 2006 were reviewed. Of the 345 deaths reviewed, 181 died from coronary thrombi (129 ruptures and 52 erosions). A total of 111 cases with available demographic and pathologic data were included in this analysis. Sudden death was defined as natural deaths without extracardiac causes occurring within 6 hours after onset of anginal symptoms or last seen alive within 24 hours in a normal healthy state. Plaque ruptures (n = 65) were compared to plaque erosions (n = 50). Thrombus healing was classified as early (<1 day) or late stage. Late stage was further classified into lytic (1-3 days), infiltrating (4-7 days), or healing (>7 days). Morphology was examined including vessel dimensions, necrotic core size, and macrophage density.
Results: A total of 74 deaths were witnessed, of which 51 had typical cardiac symptoms, 8 had atypical symptoms, and 15 were asymptomatic. Sudden death victims with ruptures were older then those with erosions. Early thrombi were observed more often with plaque rupture. Late-stage thrombi comprised 69% of lesions (70/115). Women were more likely to have erosions than ruptures (26% vs. 11%, p = 0.06). Women were observed to have erosions with a greater prevalence of late-stage thrombi (44/50 or 88%), as compared to ruptures (35/65 or 54%). The internal elastic lamina area and percent stenosis were significantly smaller in erosions compared with ruptures, whereas plaque burden was higher. Less macrophage infiltration was observed in erosions compared to ruptures; however, no relationship was noted with thrombus organization. No association between healing and thrombus length or other parameters was observed.
Conclusions: The investigators concluded that many thrombi are late stage, organizing thrombi. Furthermore erosions, more often observed in younger age victims and women, were associated with late-stage thrombi.
Perspective: This study suggests the need to further characterize thrombi and examine outcomes such as sudden death in younger patients and women. Potentially, plaque erosions may warrant different management than plaque rupture; however, further study is needed to make such a determination. Elizabeth A. Jackson, M.D., F.A.C.C.

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Title: Physical Activity Reduces Systemic Blood Pressure and Improves Early Markers of Atherosclerosis in Pre-Pubertal Obese Children
Topic: Noninvasive Cardiology
Date Posted: 1/26/2010
Author(s): Farpour-Lambert NJ, Aggoun Y, Marchand LM, Martin XE, Herrmann FR, Beghetti M.
Citation: J Am Coll Cardiol 2009;54:2396-2406.
Clinical Trial: yes
Study Question: Does physical activity improve systolic blood pressure and markers of atherosclerosis in pre-pubertal obese children?
Methods: This was a randomized controlled trial, which used an exercise intervention to improve cardiovascular markers in pre-pubertal obese children. Children were assigned to exercise or control groups, with 22 in each group. An additional 22 lean children were recruited as a comparison group. The exercise group performed 60 minutes of exercise three times per week during the 3-month intervention. After the initial 3 months, both the intervention and control groups performed exercise twice per week for a 2-month period. Clinical assessments were preformed at 3 and 6 months. Outcomes included change in office and 24-hour blood pressure, arterial intima-media thickness (IMT) and arterial stiffness, endothelial function (flow-mediated dilation), body mass index (BMI), body fat, cardiorespiratory fitness (maximal oxygen consumption [VO2max]), physical activity, and biological markers.
Results: At baseline, obese children had higher levels of blood pressure, arterial stiffness, body weight, BMI, abdominal fat, insulin resistance indexes, and C-reactive protein, and lower flow-mediated dilation, VO2max, physical activity, and high-density lipoprotein cholesterol compared to lean children. At 3 months, obese children in the exercise group had significant improvements in 24-hour systolic blood pressure, diastolic blood pressure, hypertension rate, office blood pressure, BMI z-scores, abdominal fat, and VO2max. At 6 months, changes in arterial stiffness and IMT were significant.
Conclusions: The authors concluded that regular exercise can reduce blood pressure, arterial stiffness, and abdominal fat, and can improve cardiorespiratory fitness and delay arterial wall remodeling among obese pre-pubertal children.
Perspective: This study demonstrates the importance of regular physical activity for the prevention of cardiovascular disease, starting at an early age. Clinicians should encourage families to incorporate regular physical activity for all members of a family, including young children. Elizabeth A. Jackson, M.D., F.A.C.C.

Title: The Coronary Artery Calcium Score and Stress Myocardial Perfusion Imaging Provide Independent and Complementary Prediction of Cardiac Risk
Topic: Noninvasive Cardiology
Date Posted: 1/28/2010
Author(s): Chang SM, Nabi F, Xu J, et al.
Citation: J Am Coll Cardiol 2009;54:1872-1882.
Clinical Trial: No
Study Question: What are the relative prognostic implications and relationships between coronary artery calcium score (CACS) and single-photon emission computed tomography (SPECT) results?
Methods: CACS and stress SPECT were performed in 1,128 patients without known coronary disease who were subsequently followed for nonfatal myocardial infarction, cardiac death, revascularization, and all-cause mortality.
Results: Average patient age was 58.4 ± 9.8 years and 73% were male. Median follow-up was 6.9 years. Diabetes was present in 10% and hypertension in 52%. CACS was 0-10 in 24%, 11-100 in 21%, 101-400 in 28%, and >400 in 27% (four strata). SPECT was abnormal in 149 (13%), and 43 (4%) had a perfusion defect size (PDS) ≥15% and 34 (3%) had ischemic PDS ≥10%. Across the four strata of CAC scores, there was a statistically significant increase in age and male gender as well as number of cardiovascular risk factors. Similarly, patients with a normal versus abnormal SPECT tended to be younger and have a lower prevalence of risk factors. For the four strata of CACS, the frequency of abnormal SPECT was 1%, 2.3%, 9.8%, and 31%. Across the four strata of CACS, total cardiac events occurred in 0.7%, 0.97%, 1.3%, and 2.97% of subjects with a normal SPECT. Annualized cardiac event rates were 9.6% in patients with ≥15% stress PDS. Survival curves suggested separation of survival between patients with minimal and severe CACS 3 years after normal SPECT. Global chi-square analysis suggested an incremental value of CACS when added to SPECT and clinical results for predicting total cardiac events and all-cause mortality/nonfatal myocardial infarction.
Conclusions: CACS and SPECT are independent, complementary predictors of cardiac events. Patients with a normal SPECT but markedly abnormal CACS have a worse long-term outcome with respect to cardiovascular events.
Perspective: Both CACS and SPECT have been associated with an adverse prognosis. There has been substantial controversy with respect to the relative role of these two studies for screening and prognostic purposes. This study nicely demonstrates a complementary and additive role of calcium scoring in patients with a broad range of SPECT abnormalities. The major message of this study is that, even in the presence of a normal SPECT thallium, prognosis may be worse with markedly abnormal CACS. Importantly, for patients with abnormal CACS and normal thallium, the prognosis over the ensuing first 3 years was benign and only after 3 years did survival curves diverge, suggesting a warranty period of 3 years in patients with a normal SPECT thallium and a markedly abnormal CACS. This ‘warranty period’ is similar to that suggested previously even without the addition of CACS. This observation may not apply to high-risk patients, including diabetics. Based on this study, as well as the bulk of previously published data, incorporating CACS into clinical decision making appears to be a reasonable strategy and may allow identification of relatively higher-risk patients with initially normal perfusion studies who may warrant closer follow-up. William F. Armstrong, M.D., F.A.C.C.

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Title: Delayed Hyper-Enhancement Magnetic Resonance Imaging Provides Incremental Diagnostic and Prognostic Utility in Suspected Cardiac Amyloidosis
Topic: Noninvasive Cardiology
Date Posted: 1/28/2010
Author(s): Austin BA, Wilson Tang WH, Rodriguez ER, et al.
Citation: JACC Cardiovasc Imaging 2009;2:1369-1377.
Clinical Trial: No
Study Question: What is the diagnostic accuracy and prognostic value of delayed hyper-enhancement on cardiac magnetic resonance imaging (DHE-CMR) compared to standard electrocardiographic (ECG) and echocardiographic parameters in patients with suspected cardiac amyloid?
Methods: Routine ECG, echocardiography for Doppler diastolic parameters, and DHE-CMR were available in 47 patients with suspected cardiac amyloid, all of whom underwent either endomyocardial (n = 38) or extracardiac biopsy. Diastolic parameters included deceleration time, E/E' ratio, and diastolic grade. Cardiac amyloid was considered present if CMR revealed diffuse DHE of the subendocardium. The endpoint of all-cause mortality was tabulated.
Results: Average patient age was 62 years and 70% were male. Biopsy was positive for amyloid in 25 and negative in 22 patients. New York Heart Association class >II was present in 55% of biopsy-negative and 56% of biopsy-positive patients. Low voltage on the ECG (Carroll criteria) was noted in 55% of biopsy-negative and 60% of biopsy-positive patients. A speckled appearance on echocardiography was noted in no biopsy-negative patients and in four (16%) biopsy-positive patients. Ventricular septal thickness averaged 1.3 cm (1.1-1.6) in biopsy-negative and 1.7 cm (1.4-2) in biopsy-positive patients. A deceleration time ≤150 ms was noted in six biopsy-negative patients (27%) and eight (32%) biopsy-positive patients. Grade II or worse diastolic dysfunction was noted in nine biopsy-negative patients (41%) and 13 (50%) biopsy-positive patients. DHE-CMR was characteristic of cardiac amyloid in three biopsy-negative patients (14%) versus 19 (76%) biopsy-positive patients (p < 0.0001). Sensitivity, specificity, positive, and negative predictive values for low-voltage ECG were 76%, 48%, 54%, and 71%, and 35%, 62%, 43%, and 54% for deceleration time ≤150 ms. DHE-CMR had corresponding values of 88%, 90%, 88%, and 90%. Of the preceding parameters (plus others), only DHE-CMR was predictive of cardiac amyloid on multivariable analysis. At 1 year following biopsy, there were nine (19%) deaths in biopsy-positive patients, including seven who were DHE-CMR positive. On multivariable analysis, only DHE-CMR was predictive of mortality.
Conclusions: DHE-CMR is more accurate than echocardiographic or ECG parameters for diagnosing cardiac amyloid, and a positive DHE-CMR confers a worse 1-year prognosis than does advanced diastolic dysfunction on Doppler.
Perspective: Several previous studies have suggested a characteristic pattern on gadolinium-enhanced CMR to be diagnostic of cardiac amyloid. This study compares this finding to traditional ECG and echocardiographic parameters of abnormal diastolic function, and suggests that the accuracy of CMR exceeds these more traditional and widespread techniques. Previous studies have suggested that advanced diastolic dysfunction confers an adverse prognosis in patients with documented cardiac amyloid. It should be noted that virtually all studies evaluating echocardiographic and other parameters in cardiac amyloid are relatively limited in scope. This study suggests that a typical pattern of diffuse hyper-enhancement on CMR is not only more accurate for the diagnosis of cardiac amyloid, but has independent adverse prognostic implications. William F. Armstrong, M.D., F.A.C.C.

Title: Effects of the DASH Diet Alone and in Combination With Exercise and Weight Loss on Blood Pressure and Cardiovascular Biomarkers in Men and Women With High Blood Pressure: The ENCORE Study
Topic: Prevention/Vascular
Date Posted: 1/28/2010
Author(s): Blumenthal JA, Babyak MA, Hinderliter A, et al.
Citation: Arch Intern Med 2010;170:126-135.
Clinical Trial: No
Study Question: Does the DASH diet lower blood pressure and alter cardiovascular risk biomarkers among free-living adults?
Methods: This was a randomized controlled trial, which compared the DASH diet alone or in combination with a weight management program to usual diet controls. Participants were overweight or obese (body mass index 25-40 kg/m2) with prehypertension or stage one hypertension (130-149 mm Hg systolic blood pressure and/or 85-99 mm Hg diastolic blood pressure). Participants in the DASH diet alone or the usual diet groups consumed isocaloric meals with the goal of maintenance of their baseline weight. Those in the DASH plus weight management group consumed meals at a 500-caloric deficit. Exercise for this group consisted of three classes per week. The primary outcome of interest was clinic blood pressure and ambulatory blood pressure. Secondary outcomes included pulse wave velocity, flow-mediated dilation, baroreflex sensitivity, and left ventricular mass.
Results: Among the 144 participants, those randomized to the DASH diet plus weight management had the greatest reduction in clinic blood pressure (16.1/9.9 mm Hg), followed by the DASH diet alone (11.2/7.5 mm Hg), with the usual diet controls having the least change in blood pressure (3.4/3.8 mm Hg). Ambulatory blood pressure measures were similar. Greater improvements in pulse wave velocity, baroreflex sensitivity, and left ventricular mass were observed in participants randomized to the DASH diet and weight management, as compared to those randomized to the DASH diet alone.
Conclusions: The investigators concluded that for overweight or obese patients with prehypertension or stage one hypertension, the DASH diet with weight management resulted in significant reductions in blood pressure and improved vascular and autonomic tone.
Perspective: This study demonstrates the significance of combining dietary changes with increased physical activity. Incorporation of exercise to the DASH diet resulted in significant blood pressure reduction and improved vascular function. Elizabeth A. Jackson, M.D., F.A.C.C.

[Chevychelov]

Title: Association of Marine Omega-3 Fatty Acid Levels With Telomeric Aging in Patients With Coronary Heart Disease
Topic: Prevention/Vascular
Date Posted: 1/29/2010
Author(s): Farzaneh-Far R, Lin J, Epel ES, Harris WS, Blackburn EH, Whooley MA.
Citation: JAMA 2010;303:250-257.
Clinical Trial: No
Study Question: Is there a correlation between blood levels of omega-3 fatty acids and telomere length, a potential marker of biological age?
Methods: This was a prospective cohort study of 608 ambulatory outpatients with stable coronary artery disease recruited from the Heart and Soul Study between September 2000 and December 2002 and followed up to January 2009 (median, 6.0 years; range, 5.0-8.1 years). Leukocyte telomere length was measured at baseline and again after 5 years of follow-up. Multivariable linear and logistic regression models were used to investigate the association of baseline levels of omega-3 fatty acids (docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA]) with subsequent change in telomere length.
Results: Individuals in the lowest quartile of DHA+EPA experienced the fastest rate of telomere shortening (0.13 telomere-to-single-copy gene ratio [T/S] units over 5 years; 95% confidence interval [CI], 0.09-0.17), whereas those in the highest quartile experienced the slowest rate of telomere shortening (0.05 T/S units over 5 years; 95% CI, 0.02-0.08; p < 0.001 for linear trend across quartiles). Levels of DHA+EPA were associated with less telomere shortening before (unadjusted β coefficient x 10−3 = 0.06; 95% CI, 0.02-0.10) and after (adjusted β coefficient x 10−3 = 0.05; 95% CI, 0.01-0.08) sequential adjustment for established risk factors and potential confounders. Each 1-standard deviation increase in DHA+EPA levels was associated with a 32% reduction in the odds of telomere shortening (adjusted odds ratio, 0.68; 95% CI, 0.47-0.98).
Conclusions: Among a cohort of patients with coronary artery disease, there was an inverse relationship between baseline blood levels of marine omega-3 fatty acids and the rate of telomere shortening over 5 years.
Perspective: High dietary intake of marine omega-3 fatty acids has previously been associated with reduced risk of death and cardiovascular disease. Many mechanisms for these beneficial effects have been proposed including antiplatelet, anti-arrhythmic, anti-inflammatory, and triglyceride-lowering effects. The current study raises a new potential mechanism of benefit from omega-3 fatty acids, reduced telomere shortening. During cell division, there is progressive loss of tandem repeat DNA sequences (telomeres) that form protective caps at the end of chromosomes. Eventually, this process leads to cell death. Genetic and environmental factors may influence telomere shortening, and short telomeres have been associated with cardiovascular disease and death. Factors that prevent telomere loss could lead to reduced disease burden and increased longevity. Additional studies are necessary to establish a causal relationship between omega-3 fatty acids and prevention of telomere shortening, as well as to uncover mechanisms by which this may occur. Daniel T. Eitzman, M.D., F.A.C.C.

Title: Smoking Status and Long-Term Survival After First Acute Myocardial Infarction: A Population-Based Cohort Study
Topic: Prevention/Vascular
Date Posted: 1/29/2010
Author(s): Gerber Y, Rosen LJ, Goldbourt U, Benyamini Y, Drory Y, on behalf of the Israel Study Group on First Acute Myocardial Infarction.
Citation: J Am Coll Cardiol 2009;54:2382-2387.
Clinical Trial: No
Study Question: Is cigarette smoking reduction among persistent smokers associated with lower mortality?
Methods: Consecutive patients ≤65 years of age, discharged from eight hospitals in central Israel after first acute myocardial infarction (AMI) in 1992 to 1993, were followed through 2005. Extensive data, including self-reported smoking habits, were obtained at baseline and four times during follow-up. Cox proportional hazards regressions were used to assess the hazard ratios (HRs) for death associated with smoking categories modeled as time-dependent variables.
Results: At baseline, smokers were younger, more likely to be male, and had a lower prevalence of hypertension and diabetes than nonsmokers. Over a median follow-up of 13.2 years, 427 deaths occurred in 1,521 patients. The multivariable-adjusted hazard ratios for mortality were 0.57 (95% confidence interval [CI], 0.43-0.76) for never-smokers, 0.50 (95% CI, 0.36-0.68) for pre-AMI quitters, and 0.63 (95% CI, 0.48-0.82) for post-AMI quitters, compared with persistent smokers. Among persistent smokers, upon multivariable adjustment including pre-AMI intensity, each reduction of five cigarettes smoked daily after AMI was associated with an 18% decline in mortality risk (p < 0.001).
Conclusions: Smoking cessation either before or after AMI is associated with improved survival. Among persistent smokers, reducing intensity after AMI appears to be beneficial.
Perspective: The mechanisms leading to an increase in coronary events in smokers include that it promotes lipid oxidation, low high-density lipoprotein cholesterol, inflammation, thrombosis, oxidative stress, endothelial dysfunction, and coronary vasospasm. The type of coronary plaque and plaque rupture differ between smokers and nonsmokers. Despite the well known association of cigarette smoking and coronary events, the degree to which smoking cessation reduces very long-term mortality and the contribution of the degree of continuing abstinence or reduction over 10 years had not been studied. Further, the relationship between the value of total cessation and decreasing consumption was not known. The results provide very good evidence to enhance patient education in both primary and secondary prevention. Melvyn Rubenfire, M.D., F.A.C.C.