Обзор американских кардиологических журналов за неделю (ссылки)

[Chevychelov]

Ablation Beats Drug Rx in PAF
Varenicline for Smokers with CAD
Ablate VT Before ICD Implant
[Ссылки доступны только зарегистрированным пользователям ]

[Chevychelov]

Title: Endovascular Aortic Repair Versus Open Surgical Repair for Descending Thoracic Aortic Disease: A Systematic Review and Meta-Analysis of Comparative Studies
Topic: Cardiovascular Surgery
Date Posted: 2/3/2010 5:00:00 PM
Author(s): Cheng D, Martin J, Shennib H, et al.
Citation: J Am Coll Cardiol 2010;Feb 3:[Epub ahead of print].
Clinical Trial: No
Study Question: Does thoracic endovascular aortic repair (TEVAR) reduce death and morbidity compared with open surgical repair for descending thoracic aortic disease?
Methods: Data from 42 studies (four multicenter, 35 single center, and three registries) of TEVAR versus open repair of the descending aorta were examined by meta-analysis to determine mortality and morbidity rates for each approach. Meta-regression was performed to account for baseline risk factor imbalances, study design, and thoracic pathology. Registry data were analyzed separately from comparative studies, as these data were thought to be too heterogeneous.
Results: The 42 nonrandomized studies included 5,888 patients. Patient characteristics were balanced, except that patients undergoing TEVAR tended to be older (p < 0.001). In comparative studies, all-cause mortality at 30 days (odds ratio [OR], 0.44; 95% confidence interval [CI], 0.33-0.59) and paraplegia (OR, 0.42; 95% CI, 0.28-0.63) were reduced for TEVAR versus open surgery. In addition, cardiac complications, transfusions, reoperation for bleeding, renal dysfunction, pneumonia, and length of stay were reduced. There was no significant difference in stroke, myocardial infarction (MI), aortic reintervention, and mortality at 2-3 years. Meta-regression to adjust for age imbalance, study design, and pathology did not materially change the results. Registry data suggested that overall perioperative complications were reduced. However, registry data did not demonstrate alterations in 30-day, 1-year, and 2- to 3-year mortality, or any of the single complications (stroke, acute MI, renal failure, ischemia to the gut or limb) examined.
Conclusions: This meta-analysis suggests that TEVAR reduces early mortality, paraplegia, renal insufficiency, transfusions, reoperation for bleeding, cardiac complications, pneumonia, and length of stay compared with open surgery. Moderate-term follow-up (2-3 years) failed to show a sustained survival benefit.
Perspective: I suspect anyone who performs or performed open and TEVAR for thoracic aortic aneurysms (TAAs) recognizes that short-term mortality and morbidity is lower in patients undergoing TEVAR. Importantly, of all the devastating complications associated with TAA repair, paraplegia risk is reduced almost 58%. The fact that no sustained benefit is obtained is likely due to one of two reasons: 1) the small collection of studies with moderate-term follow-up were underpowered to show a difference, or 2) the patients die from nonthoracic aortic disease (i.e., MIs). Even more so than endovascular repair of abdominal aortic aneurysms, TEVAR will completely dominate the landscape of repair over the next decade. Gilbert Upchurch, Jr., M.D.

Title: Sibutramine Cardiovascular Morbidity/Mortality Outcomes in Overweight or Obese Subjects at Risk of a Cardiovascular Event (SCOUT)
Topic(s): General Cardiology, Prevention/Vascular
Summary Posted: 2/1/2010
Writer: Anthony A. Bavry, M.D., M.P.H., F.A.C.C.
Author Disclosure: This author has nothing to disclose.
Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C.
Author Disclosure: Research/Research Grants: Astra Zeneca; Consultant Fees/Honoraria: Duke Clinical Research Institute; Research/Research Grants: Heartscape; Research/Research Grants: PLx Pharma; Research/Research Grants: Cogentus; Research/Research Grants: Sanofi Aventis; Data Safety Monitoring Board (Gov’t/Nonprofit): Duke Clinical Research Institute; Research/Research Grants: Bristol Myers Squibb; Research/Research Grants: Eisai; Research/Research Grants: Takeda; Research/Research Grants: The Medicines Company; Research/Research Grants: Ethicon
Description
The goal of the trial was to evaluate treatment with the weight loss agent sibutramine (Meridia) compared with placebo among overweight or obese individuals.
Hypothesis
Sibutramine would reduce cardiovascular events.
Drugs/Procedures Used
Obese patients were randomized to sibutramine versus placebo.
Principal Findings
Approximately 10,000 patients were randomized. Interim analysis revealed that the primary outcome of death, myocardial infarction, stroke, or resuscitated cardiac arrest occurred in 11.4% of the sibutramine group versus 10% of the placebo group.

Adverse events appeared to disproportionately occur in diabetics with cardiovascular disease. The primary outcome occurred in 6.5% versus 6.5% (p = 0.95) among diabetics without evident cardiovascular disease, 10.1% versus 8.3% (p = 0.15) among individuals with history of cardiovascular disease, and 13.9% versus 11.9% (p = 0.023) among diabetics with cardiovascular disease, respectively, for sibutramine versus placebo.
Interpretation
Interim analysis revealed that sibutramine may be associated with increased adverse cardiovascular events. Accordingly, new product labeling has been expanding to state that sibutramine should be avoided in individuals with a history of coronary artery disease, congestive heart failure, arrhythmia, peripheral arterial disease, uncontrolled hypertension, or stroke. The FDA is conducting an expedited safety review to determine if additional regulatory actions are needed.
Conditions
• Prevention
• Coronary heart disease
Therapies
• Medical
Study Design
Placebo controlled. Randomized. Parallel.
Primary Endpoints
Composite of death, myocardial infarction, stroke, or resuscitated cardiac arrest
Patient Population
Obese patients at least 55 years of age with:
Body mass index ≥30 kg/m2, or
Body mass index ≥27 kg/m2 with an additional cardiovascular risk factor (diabetes, high cholesterol, or hypertension)
References: U.S. Food and Drug Administration. Postmarket Drug Safety Information for Patients and Providers.

FDA: sibutramine now contraindicated in people with cardiovascular disease. CardioBrief, January 21, 2010.

[Chevychelov]

Title: Association of a Functional Polymorphism in the Cholesteryl Ester Transfer Protein (CETP) Gene With Memory Decline and Incidence of Dementia
Topic: General Cardiology
Date Posted: 2/5/2010
Author(s): Sanders AE, Wang C, Katz M, et al.
Citation: JAMA 2010;303:150-158.
Clinical Trial: No
Study Question: A single-nucleotide polymorphism (SNP) at CETP codon 405 (isoleucine to valine) in the cholesteryl ester transfer protein (CETP) gene has been associated with exceptional longevity and lower cardiovascular risk. Is it associated with less memory decline and dementia risk?
Methods: This is a prospective cohort study comprising 608 community-dwelling adults without dementia, ages 70 years or older, from the Einstein Aging Study with CETP genotype available. Standardized neuropsychological and neurological measures were administered annually from 1994-2009. Linear mixed-effects models adjusted for sex, education, race, medical comorbidities, and apolipoprotein (APOE) ε4 examined associations of V405 genotype with longitudinal performance on cognitive tests of episodic memory, attention, and psychomotor speed (Digit Symbol Substitution). The V405 genotype was the main predictor of incident dementia or Alzheimer’s disease (AD) in similarly adjusted Cox proportional hazards models with age as the time scale. Primary outcome was memory decline and incident dementia.
Results: Fifteen participants with baseline dementia and 70 without follow-up were excluded, leaving 523 participants for the Cox analysis. Mean age was 78.2 (standard deviation [SD] 8.1) years, 61% were female, 69% white, 25.6% African-American, and 30% Ashkenazi Jewish. Valine allele frequency was 43.5% and did not differ by race. A total of 40 cases of incident dementia occurred during a mean follow-up of 4.3 [SD 3.1] years. Compared with isoleucine homozygotes, valine homozygotes had significantly slower memory decline (difference in linear age slope, 0.22; 95% confidence interval [CI], 0.02-0.41; p = 0.03) and no significant differences on psychomotor speed. Valine homozygotes also had a lower risk of dementia (hazard ratio, 0.28; 95% CI, 0.10-0.85; p = 0.02) and AD (hazard ratio, 0.31; 95% CI, 0.10-0.95; p = 0.04).
Conclusions: This preliminary report suggests that CETP V405 valine homozygosity is associated with slower memory decline and lower incident dementia and AD risk.
Perspective: CETP V405 valine homozygosity is associated with lower CETP protein serum concentration and activity and corresponding increases in high-density lipoprotein (HDL) cholesterol levels and an increase in lipoprotein (HDL and low-density lipoprotein) particle size, each of which is associated with a decrease in cardiovascular event rates. The genotype was characterized as the ‘longevity gene’ in a New York community of Ashkenazi Jews who had an uncommon number of centenarians. Now we have evidence that living longer with this gene is associated with less cognitive loss per year. While the African-American participants had a similar incidence of CETP V405, there was not a protective effect from cognitive decline. The mechanism of decreasing dementia could be related to the vascular protective effect—not a bad thing to inherit from mom and dad. Melvyn Rubenfire, M.D., F.A.C.C.

Title: Systematic Review of Guidelines on Cardiovascular Risk Assessment: Which Recommendations Should Clinicians Follow for a Cardiovascular Health Check?
Topic: General Cardiology
Date Posted: 2/3/2010
Author(s): Ferket BS, Colkesen EB, Visser JJ, et al.
Citation: Arch Intern Med 2010;170:27-40.
Clinical Trial: No
Study Question: Is there a reasonable correlation between the various guidelines on cardiovascular risk assessment to guide selection of screening interventions for a health check?
Methods: Guidelines in the English language published between January 1, 2003, and May 2, 2009, were retrieved using MEDLINE and CINAHL. This was supplemented by searching the National Guideline Clearinghouse, National Library for Health, Canadian Medical Association Infobase, and G-I-N International Guideline Library. The authors selected guidelines developed on behalf of professional organizations from Western countries, containing recommendations on cardiovascular risk assessment for the apparently healthy population. Twenty-seven guidelines met their criteria. One reviewer extracted information on conflicts of interest and recommendations.
Results: Sixteen of 27 guidelines reported conflicts of interest and 17 showed considerable rigor. These included recommendations on assessment of total cardiovascular risk (7 guidelines), dyslipidemia (2), hypertension (2), and dysglycemia (7). Recommendations on total cardiovascular risk and dyslipidemia included prediction models integrating multiple risk factors, whereas remaining recommendations were focused on single risk factors. No consensus was found on recommended target populations, treatment thresholds, and screening tests.
Conclusions: Differences among the guidelines imply important variation in allocation of preventive interventions. To make informed decisions, physicians should use only the recommendations from rigorously developed guidelines.
Perspective: The authors state: ‘Complete and unbiased information on benefits and harms is thus desirable. Transparency about how judgments have been made within guidelines allows physicians to make informed decisions on adopting recommendations.’ While a noble effort, the reality is that national guidelines are rarely followed, but are invaluable for providing health care systems, payers, and individual physicians with information from which to make an informed decision on standards for their patient cohorts and individual patients. That the guidelines differ significantly despite that each was developed by experts in their field and sponsored by national organizations or governments is not surprising. The reasons for the differences are not subtle. Some focus on societal costs, some include only evidenced-based data, some combine evidence and ‘expert opinion,’ and some focus on optimizing risk assessment and treatment for the individual rather than a population. Melvyn Rubenfire, M.D., F.A.C.C.

[Chevychelov]

The Response of the QT Interval to the Brief Tachycardia Provoked by Standing: A Bedside Test for Diagnosing Long QT Syndrome
Viskin S, Postema PG, Bhuiyan ZA, et al.
J Am Coll Cardiol 2010;Jan 27:[Epub ahead of print].
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)?

Title: Relation Between Kidney Function, Proteinuria, and Adverse Outcomes
Topic: General Cardiology
Date Posted: 2/4/2010
Author(s): Hemmelgarn BR, Manns BJ, Lloyd A, et al., on behalf of the Alberta Kidney Disease Network.
Citation: JAMA 2010;303:423-429.
Clinical Trial: No
Study Question: What is the association between reduced glomerular filtration rate (GFR), proteinuria, and adverse clinical outcome?
Methods: The participants were from a community-based cohort study comprised of 920,985 adults who had at least one outpatient serum creatinine measurement and who did not require renal replacement treatment at baseline. Proteinuria was assessed by urine dipstick or albumin-creatinine ratio (ACR). All-cause mortality, myocardial infarction, and progression to kidney failure were the main outcome measures. The median follow-up period was 35 months (range 0-59 months).
Results: The investigators found that a majority of individuals (89.1%) had an estimated GFR (eGFR) of ≥60 ml/min/1.73 m2. Over a median follow-up of 35 months, 3% of the participants (n = 27,959) died. The fully adjusted rate of all-cause mortality was higher in study participants with lower eGFRs or heavier proteinuria. Adjusted mortality rates were more than twofold higher among individuals with heavy proteinuria measured by urine dipstick and eGFR of ≥60 ml/min/1.73 m2, as compared with those with eGFR of 45-59.9 ml/min/1.73 m2 and normal protein excretion (rate, 7.2 [95% CI, 6.6-7.8] vs. 2.9 [95% CI, 2.7-3.0] per 1,000 person-years, respectively; rate ratio, 2.5 [95% CI, 2.3-2.7]). Similar results were observed when proteinuria was measured by ACR (15.9 [95% CI, 14.0-18.1] and 7.0 [95% CI, 6.4-7.6] per 1,000 person-years for heavy and absent proteinuria, respectively; rate ratio, 2.3 [95% CI, 2.0-2.6]) and for the outcomes of hospitalization with acute myocardial infarction, end-stage renal disease, and doubling of serum creatinine level.
Conclusions: The authors concluded that risks of mortality, myocardial infarction, and progression to kidney failure associated with a given level of eGFR are independently increased in patients with higher levels of proteinuria.
Perspective: Proteinuria and eGFR are two ‘independent’ (i.e., they do not go hand in hand) indicators of renal disease, and this study suggests that when both are abnormal, poorer outcomes, including all-cause mortality, progression to kidney failure, and acute myocardial infarction, are more likely to occur. The CHARM study suggested that proteinuria (spot urinary albumin-to-creatinine ratio) is an important prognostic predictor in patients with heart failure (Lancet 2009;374:543-550). Clearly the next step is to prevent target-organ damage, particularly prevention and control of diabetes and hypertension. The MICRO-HOPE (Lancet 2000;355:253-259) study suggested that angiotensin-converting enzyme inhibitor therapy with ramipril in diabetics is associated with a lower incidence of nephropathy. Ragavendra R. Baliga, M.B.B.S.

Title: N-Terminal Pro–B-Type Natriuretic Peptide-Guided Treatment for Chronic Heart Failure: Results From the BATTLESCARRED (NT-proBNP–Assisted Treatment To Lessen Serial Cardiac Readmissions and Death) Trial
Topic: Heart Failure/Transplant
Date Posted: 2/2/2010
Author(s): Lainchbury JG, Troughton RW, Strangman KM, et al.
Citation: J Am Coll Cardiol 2010;55:53-60.
Clinical Trial: yes
Study Question: What are the effects of N-terminal pro–B-type natriuretic peptide (NT-proBNP)-guided therapy on clinical outcomes in heart failure (HF)?
Methods: The study cohort included 364 HF patients admitted to a single hospital for HF. The investigators randomly allocated 1:1:1 (stratified by age) to therapy guided by NT-proBNP levels or by intensive clinical management, or according to usual care (UC). The therapeutic strategies were applied for 2 years, with a follow-up period of 3 years.
Results: The investigators found that 1-year mortality was less in both the NT-proBNP- (9.1%) and clinically-guided (9.1%) groups compared with UC (18.9%; p = 0.03). Three-year mortality was selectively reduced in patients ≤75 years of age receiving NT-proBNP–guided therapy (15.5%) compared with their peers receiving either clinically managed treatment (30.9%; p = 0.048) or UC (31.3%; p = 0.021).
Conclusions: The authors concluded that intensive management of HF improves 1-year mortality compared with UC. Compared with clinically guided treatment and UC, NT-proBNP–guided treatment selectively improves longer-term mortality in patients ≤75 years of age.
Perspective: This is an important study because it supports the findings from the STARS-BNP study, which showed that titrating BNP therapy to <100 pg/ml reduced the composite endpoint of mortality and hospitalization due to HF compared with guideline-directed therapy. Ragavendra R. Baliga, M.B.B.S.

[Chevychelov]

Title: A Double-Blind, Randomized Study on Prevention and Existence of a Rebound Phenomenon of Platelets After Cessation of Clopidogrel Treatment
Topic: Interventional Cardiology
Date Posted: 2/1/2010 5:00:00 PM
Author(s): Sibbing D, Stegherr J, Braun S, et al.
Citation: J Am Coll Cardiol 2010;55:558-565.
Clinical Trial: No
Study Question: What is the evidence that a platelet rebound exists, and can it be attenuated by clopidogrel tapering?
Methods: Patients (n = 69) receiving clopidogrel treatment due to prior drug-eluting stent placement and planning to stop clopidogrel were recruited in a double-blind, randomized trial. Patients were randomized to either receive a prespecified tapering regimen (tapering group; n = 35) for 4 weeks with complete discontinuation of clopidogrel thereafter or continue a daily clopidogrel intake for 4 more weeks with abrupt discontinuation afterwards (off group; n = 34). Platelet aggregation (PA) was assessed with light transmission aggregometry (LTA) and multiple electrode aggregometry (MEA) simultaneously at study inclusion and at weeks 2 to 8 after randomization. The primary endpoint was the highest value of adenosine diphosphate–induced PA measured with LTA in the weeks after complete cessation of clopidogrel in both groups.
Results: The highest values of adenosine diphosphate–induced PA after complete cessation of clopidogrel were similar between both groups (p = 0.21 with LTA, and p = 0.55 with MEA).
Conclusions: The authors concluded that tapering of clopidogrel does not result in lower platelet aggregation values after clopidogrel withdrawal.
Perspective: The primary finding of the study is that a tapering of clopidogrel treatment, as compared with abrupt cessation of the drug, does not result in significantly lower platelet aggregation values in the time period after complete cessation of clopidogrel treatment. Overall, the course of platelet aggregation values after clopidogrel cessation does not support the existence of a rebound phenomenon of platelets after discontinuation of clopidogrel. The clinical safety and efficacy of abrupt versus tapered interruption of chronic clopidogrel therapy after DES implantation is being addressed in the ISAR-CAUTION trial, and will provide additional clinical insight on the optimal method to discontinue clopidogrel therapy. Debabrata Mukherjee, M.D., F.A.C.C.

Title: Endothelial Function, Carotid-Femoral Stiffness, and Plasma Matrix Metalloproteinase-2 in Men With Bicuspid Aortic Valve and Dilated Aorta
Topic: Noninvasive Cardiology
Date Posted: 2/8/2010 5:00:00 PM
Author(s): Tzemos N, Lyseggen E, Silversides C, et al.
Citation: J Am Coll Cardiol 2010;55:660-668.
Clinical Trial: No
Study Question: What is the relationship between proximal aortic dilation and systemic vascular function in men with bicuspid aortic valve (BAV)?
Methods: Thirty-two men (median age 31 years [range 28-32 years]) with nonstenotic BAV were categorized into two subgroups according to proximal ascending aorta dimensions (nondilated ≤35 mm and dilated ≥40 mm, respectively). Sixteen healthy men were studied as control subjects. Flow-mediated dilation in response to hyperemia, and carotid–femoral pulse wave velocity were assessed, and peripheral blood was sampled for matrix metalloproteinases (MMP-2 and -9) and their tissue inhibitors (TIMP-1 and -2), respectively. Cardiac chamber and aortic dimensions were assessed by echocardiography and cardiac magnetic resonance imaging, respectively.
Results: Despite similar severity of aortic stenosis, and left ventricular mass and function, men with dilated aortas had blunted brachial flow-mediated vasodilation to hyperemia (5% [interquartile range (IQR) 4-6%] vs. 8% [IQR 7-9%] change, p = 0.001), higher carotid–femoral pulse wave velocity (9.3 cm/s [IQR 9-10 cm/s] vs. 7 cm/s [IQR 6.9-7.4 cm/s], p = 0.001), and significantly higher plasma levels of MMP-2 (1,523 [IQR 1,460-1,674] vs. 1,036 [IQR 962-1,167], p = 0.001) compared to men with BAV and nondilated aorta.
Conclusions: The authors concluded that young men with BAV and dilated proximal aortas manifest systemic endothelial dysfunction, increased carotid–femoral pulse wave velocity, and higher plasma levels of MMP-2. These observations could introduce new targets for screening and perhaps for therapeutic intervention.
Perspective: BAV is the most common congenital heart malformation, occurring in 1-2% of the population. In addition to valvular dysfunction, BAV is associated with dilatation of the aortic root, which can lead to aortic dissection and rupture. The reason for this association is not clear and does not appear to be related to the degree of valvular dysfunction. The current study demonstrates that systemic changes in vascular function and stiffness, along with evidence of increased metalloprotease activity, are present in subjects with BAV and root dilatation. Additional confirmatory studies in a broader population (including women and patients with more stenotic BAV), along with genome-wide analyses, may lead to identification of novel biomarkers and treatment strategies for patients with BAV. Daniel T. Eitzman, M.D., F.A.C.C.

[Chevychelov]

Title: Cardiovascular Magnetic Resonance in Patients With Myocardial Infarction: Current and Emerging Applications
Topic: Noninvasive Cardiology
Date Posted: 2/2/2010
Author(s): Kim HW, Farzaneh-Far A, Kim RJ.
Citation: J Am Coll Cardiol 2009;55:1-16.
Clinical Trial: No
Perspective: This is a state-of-the-art review of the role of cardiac magnetic resonance imaging (CMR) in patients with acute and chronic myocardial infarction (MI). Ten points to remember include:

1. MI is a leading cause of morbidity and mortality for which a broad range of ever-changing therapeutic and diagnostic options are available. Outcomes are directly related to MI size. Similarly, diagnostic tests for detection of MI are also dependent on a critical mass of involved myocardium for detection. Current recommendations suggest a combination of electrocardiographic, enzymatic, and imaging techniques including CMR, echocardiography, and radionuclide imaging to establish the diagnosis.

2. CMR is a multi-technique imaging modality dependent on both hardware and software for acquisition. Acquisition software can be modified with different pulse sequences to obtain different unique and nonoverlapping data. A comprehensive CMR exam will include multiple pulse sequences designed to define cardiac anatomy and blood flow and to detect thrombus, infarction, perfusion, etc. Many CMR artifacts are specific to the pulse sequence utilized and, as such, will not be present on all images.

3. Commonly used CMR techniques include cine imaging for cardiac function, determination of ventricular volumes, and left ventricular mass as well as valvular morphology. CMR determined chamber size and mass are highly accurate and reproducible.

4. Other CMR techniques include specific imaging for acute myocardial injury as well as perfusion imaging at stress and with rest.

5. Use of gadolinium contrast for delayed imaging is a highly specific marker of MI. Gadolinium is excluded from normal, active myocytes and is sequestered in the interstitium. As such, when detected late after injection, it is a marker of nonviable areas of myocardium, but is not necessarily specific for ischemic heart disease.

6. The specific pattern of late gadolinium enhancement may allow a more specific diagnosis. The effects of coronary occlusion, typically spread in a wavefront from the endocardium to the epicardium and a matching pattern of gadolinium hyperenhancement, may be specific for the effects of coronary occlusion. Other diseases, such as acute myocarditis, present with patchy or mid-myocardial enhancement.

7. The spatial resolution of delayed enhancement (DE)-CMR is exceptionally high and in the clinical setting allows detection of MI involving as little as 1 g of myocardium. In comparison, wall motion abnormalities detected with echocardiography or other techniques will be dependent on a threshold of subendocardial involvement, and SPECT imaging may require >10 g of myocardial involvement before an abnormality is reliably detected.

8. In addition to detecting both acute and chronic MI, CMR may be useful for detecting complications such as aneurysm formulation, right ventricular involvement, pericarditis, and left ventricular thrombus.

9. Using DE-CMR as a marker for MI, a substantial number of clinically and electrocardiographically silent MIs are detected. DE-CMR detects 2-3 times more clinically occult MIs than does an electrocardiogram.

10. Because of the high spatial resolution and reproducibility of CMR for detecting and quantifying MI, it may serve as an accurate endpoint for clinical trials in which reduction in myocardial size rather than mortality is a surrogate endpoint. It has implications for allowing reduced sample size to be used in clinical trials. William F. Armstrong, M.D., F.A.C.C.

Title: Ginkgo Biloba for Preventing Cognitive Decline in Older Adults: A Randomized Trial
Topic: Prevention/Vascular
Date Posted: 2/5/2010
Author(s): Snitz BE, O’Meara ES, Carlson MC, et al., on behalf of the Ginkgo Evaluation of Memory (GEM) Study Investigators.
Citation: JAMA 2009;302:2663-2670.
Clinical Trial: yes
Study Question: Does the herbal product Ginkgo biloba have an effect on long-term cognitive functioning in older adults?
Methods: The Ginkgo Evaluation of Memory (GEM) study is a randomized, double-blind, placebo-controlled clinical trial of 3,069 community-dwelling participants ages 72-96 years, which was conducted in six academic medical centers in the United States between 2000 and 2008. Median follow-up was 6.1 years. Participants received either twice-daily dose of 120 mg extract of G. biloba (n = 1,545) or identical appearing placebo (n = 1,524). Primary outcome was the rates of change over time in the Modified Mini-Mental State Examination (3MSE), in the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-Cog), and in neuropsychological domains of memory, attention, visual-spatial construction, language, and executive functions, based on sums of z scores of individual tests.
Results: Annual rates of decline in z scores did not differ between G. biloba and placebo groups in any domains, including memory, attention, visuospatial abilities, language, and executive functions. For the 3MSE and ADAS-Cog, rates of change varied by baseline cognitive status (mild cognitive impairment), but there were no differences in rates of change between treatment groups. There was no significant effect modification of treatment on rate of decline by age, sex, race, education, APOE*E4 allele, or baseline mild cognitive impairment.
Conclusions: Compared with placebo, the use of G. biloba, 120 mg twice daily, did not result in less cognitive decline in older adults with normal cognition or with mild cognitive impairment.
Perspective: Like the great majority of studies funded by the National Institutes of Health designed to test the value of vitamin and herbal supplements, this excellent study shows no value for ginkgo, which has been taken by at least one third of my older patients over the past 15 years. The cost of the studies has been substantial and seems to have done little to reduce the excessive use and marketing of supplements. Melvyn Rubenfire, M.D., F.A.C.C.

[Chevychelov]

Title: Optimizing Statin Treatment for Primary Prevention of Coronary Artery Disease
Topic: Prevention/Vascular
Date Posted: 2/4/2010
Author(s): Hayward RA, Krumholz HM, Zulman DM, Timble JW, Vijan S.
Citation: Ann Intern Med 2010;152:69-77.
Clinical Trial: No
Study Question: Would a tailored treatment approach compare favorably to a treat-to-target approach for primary prevention of coronary artery disease (CAD)?
Methods: A simulated model of population-level effects was used to compare treat-to-target and tailored treatment approaches to statin therapy. Data sources included statin trials from 1994 to 2009 and nationally representative CAD risk factor data. The target population was U.S. persons ages 30-75 years with no history of myocardial infarction. Tailored treatment was based on a person’s 5-year CAD risk (simvastatin, 40 mg, for 5-15% CAD risk; and atorvastatin, 40 mg, for CAD risk >15%) versus treat-to-target approaches that escalate statin dose per National Cholesterol Education Program (NCEP) III guidelines (including an intensive approach that advances treatment whenever intensification is optional by NCEP III criteria). Outcomes included lifetime effects of 5 years of treatment, as measured by quality-adjusted life-years (QALYs) from a societal and patient perspective.
Results: The standard NCEP III treat-to-target approach would recommend that 37.9 million U.S. persons should receive statins, of which 7.9 million should receive high dose–potency therapy. Compared with no treatment, the standard NCEP III approach was estimated to save 48 QALYs per 1,000 persons treated for 5 years, resulting in about 1.83 million total QALYs saved in the United States. Compared with the standard NCEP III approach, the intensive NCEP III approach treated 15 million more persons and saved 570,000 more QALYs over 5 years. The tailored strategy treated a similar number of persons, as did the intensive NCEP III approach, but saved 500,000 more QALYs and treated fewer persons with high-dose statins. No circumstances were found in which a treat-to-target approach was preferable to tailored treatment.
Conclusions: A tailored treatment strategy prevents more CAD events while treating fewer persons with high-dose statins than low-density lipoprotein cholesterol–based target approaches. Results were robust, even with assumptions favoring a treat-to-target approach.
Perspective: I suspect there are two patterns of statin use in the United States. One group of physicians and their patients underuse and underdose, and the other is aggressive, sometimes overtreating, but usually appropriate dosing in patients at high risk. Very few actually use the guidelines. The approach suggested by Rod Hayward may underestimate the value of a tailored but simple treatment strategy, which might be benefited by further risk stratification with a coronary calcium score in middle-aged and older men and women. Melvyn Rubenfire, M.D., F.A.C.C.

Title: Fulminant Myocarditis Associated With Pandemic H1N1 Influenza A Virus in Children
Topic: Heart Failure/Transplant
Date Posted: 2/10/2010 5:00:00 PM
Author(s): Bratincsak A, El-Said HG, Bradley JS, Shayan K, Grossfeld PD, Cannavino CR.
Citation: J Am Coll Cardiol 2010;Feb 10:[Epub ahead of print].
Clinical Trial: No
Study Question: Is fulminant myocarditis associated with pandemic H1N1 influenza A virus in children?
Perspective: Acute myocarditis is a well-described manifestation of numerous viral infections, and may present with a broad spectrum of symptoms and clinical features. Fulminant myocarditis is thought to be rarely associated with influenza A and may present with fatal arrhythmias, high grade atrioventricular block, and even cardiogenic shock. The true prevalence of influenza-associated fulminant myocarditis is not known because of the lack of comprehensive screening, with only a few cases reported in the literature. The four documented cases of myocarditis in the current study, and other prior reports, raise the concern that the novel H1N1 influenza A virus may be more commonly associated with a severe form of myocarditis than previously seen influenza strains. These observations warrant a high index of clinical suspicion for myocarditis in children with H1N1 influenza A infection. Early diagnosis and rapid intervention with circulatory support may decrease morbidity and mortality, with the potential for saving myocardium and lives. Debabrata Mukherjee, M.D., F.A.C.C.

[Chevychelov]

Title: Altitude and the Heart: Is Going High Safe for Your Cardiac Patient?
Topic: General Cardiology
Date Posted: 2/8/2010
Author(s): Higgins JP, Tuttle T, Higgins JA.
Citation: Am Heart J 2010;159:25-32.
Clinical Trial: No
Perspective: Ease of travel and an interest in high altitude recreation exposes patients to the acute physiologic effects of high altitude and lower oxygen availability. Acute exposure to high altitude is associated with significant alterations to the cardiovascular system, with acute hypoxia, increased myocardial work, increased epinephrine release, and increased pulmonary artery pressures. This review summarized the physiology and clinical evidence regarding acute altitude exposure on the cardiopulmonary system, and made practical recommendations for patients with cardiovascular disease. Points to remember are:

1. Environmental changes when moving from sea level to high altitude include reductions in atmospheric pressure, oxygen pressure, humidity, and temperature. Significant changes typically begin at about 2500 m (8200 ft). The effect on patients depends on the degree of hypoxia, change in elevation, rate of ascent, level of acclimatization, exercise intensity at altitude, age, and genetics.

2. Moderate altitude is defined as 1500-2500 m (4950-8250 ft). High altitude is defined as >2500 m (8250 ft).

3. The acute cardiopulmonary effects of altitude include:
Tissue hypoxia, as a result of the significant decrease in oxygen availability in inspired air. Pulmonary vascular resistance increases 50-300%.
Initial hyperventilation leads to respiratory alkalosis that transiently shifts leftward the oxygen-hemoglobin dissociation curve. (After a few hours, increased red cell production of 2,3-diphosphoglycerate shifts the curve back to the right.)
Heart rate increased at rest. There is only a minimal reduction in resting stroke volume, but a decrease in maximal heart rate response lowers peak cardiac output.
A reduction in plasma volume caused by increased respiratory, urinary, and cutaneous losses. The resulting increased hematocrit is responsible for higher oxygen-carrying capacity per unit blood volume, helping maintain resting stroke volume.
Parasympathetic nervous system deactivation, with predomination of sympathetic nervous responses.
Glycogenolysis stimulated by the increase in epinephrine, causing increased use of glucose at rest and with exercise, and increased blood lactate levels.

4. Coronary artery disease. The acute physiological changes associated with high altitude result in earlier onset of ischemia and symptomatic angina in patients with coronary artery disease, and at a lower pressure-rate product.

5. Heart failure. Increased sympathetic activity results in vasoconstriction and tachycardia, as well as release of inflammatory mediators. Increased sympathetic activity results in increased heart rate and systemic vascular resistance. Pulmonary vasoconstriction leads to pulmonary hypertension (exacerbated with exercise), probably the most significant factor in reducing cardiopulmonary performance at altitude in patients with heart failure.

6. High altitude pulmonary edema. High-altitude (noncardiogenic) pulmonary edema affects unacclimatized people with a genetic predisposition, typically within 4 days of arriving at altitude. Causes are probably multifactorial, including pulmonary vascoconstriction leading to increased intravascular pressure.
Slow ascent serves as a preventative measure. (For ascent >3050 m [10,000 ft], ascent should be ≤305 m [1000 ft] daily with a rest every 1000 m [3300 ft].)
If suspected, immediate descent and administration of supplemental oxygen is the treatment of choice.
Nifedipine (sustained release 20-30 mg orally q 6 to 12 h) can both prevent and treat high-altitude pulmonary edema.
Tadalafil 10 mg bid or sildenafil 50 mg q 8h can be used to prevent high-altitude pulmonary edema, but treatment doses have not been established.

7. Arrhythmia. Increased sympathetic activity associated with high altitude can increase the frequency and duration of supraventricular and ventricular arrhythmias with or without underlying heart disease.

8. Congenital heart disease. In simple uncomplicated congenital heart disease (including atrial septal defect, restrictive ventricular septal defects, and patent ductus arteriosus), arterial oxygen desaturation can occur at high altitude when the usual left-to-right shunting of blood reverses, owing to increased right-sided pressures.

9. Recommendations for all people. The following recommendations apply to all individuals who plan to ascend to high altitude and/or exercise at elevation:
Limit activity to a lower maximal level than at sea level.
Raise sleeping altitude gradually.
At least moderate physical conditioning at sea level is encouraged before exercise at altitude.
Alcohol consumption should be minimized, and hydration should be maintained.
If cardiac status is unknown, exercise testing can be considered prior to travel.

10. Recommendations for patients with cardiovascular disease. The following recommendations apply to individuals with known cardiovascular disease who plan to ascend to high altitude and/or exercise at elevation:
Patients with unstable cardiac disease (unstable angina, uncontrolled ventricular arrhythmias, decompensated heart failure) should not exercise at high altitude.
Patients with severe cardiac diseases (including severe angina, heart failure, or valve disease) should not ascend to high altitude. Patients should avoid traveling to high altitude for 14 days after an acute coronary event. Patients with stable heart disease should limit physical activity for the first few days after ascent. Patients should be advised that they could become symptomatic at lower workloads when at altitude. Patients with prior high-altitude pulmonary edema and known intracardiac shunt should be advised to avoid travel to high altitude. Patients with pacemakers can safely travel to high altitude with no impact on ventricular stimulation thresholds.
David S. Bach, M.D., F.A.C.C.

Importance of MOC
Prevention of Torsades de Pointes in Hospital Settings
[Ссылки доступны только зарегистрированным пользователям ]

[Chevychelov]

Title: Endovascular Aortic Repair Versus Open Surgical Repair for Descending Thoracic Aortic Disease: A Systematic Review and Meta-Analysis of Comparative Studies
Topic: Cardiovascular Surgery
Date Posted: 2/3/2010 5:00:00 PM
Author(s): Cheng D, Martin J, Shennib H, et al.
Citation: J Am Coll Cardiol 2010;Feb 3:[Epub ahead of print].
Clinical Trial: No
Study Question: Does thoracic endovascular aortic repair (TEVAR) reduce death and morbidity compared with open surgical repair for descending thoracic aortic disease?
Methods: Data from 42 studies (four multicenter, 35 single center, and three registries) of TEVAR versus open repair of the descending aorta were examined by meta-analysis to determine mortality and morbidity rates for each approach. Meta-regression was performed to account for baseline risk factor imbalances, study design, and thoracic pathology. Registry data were analyzed separately from comparative studies, as these data were thought to be too heterogeneous.
Results: The 42 nonrandomized studies included 5,888 patients. Patient characteristics were balanced, except that patients undergoing TEVAR tended to be older (p < 0.001). In comparative studies, all-cause mortality at 30 days (odds ratio [OR], 0.44; 95% confidence interval [CI], 0.33-0.59) and paraplegia (OR, 0.42; 95% CI, 0.28-0.63) were reduced for TEVAR versus open surgery. In addition, cardiac complications, transfusions, reoperation for bleeding, renal dysfunction, pneumonia, and length of stay were reduced. There was no significant difference in stroke, myocardial infarction (MI), aortic reintervention, and mortality at 2-3 years. Meta-regression to adjust for age imbalance, study design, and pathology did not materially change the results. Registry data suggested that overall perioperative complications were reduced. However, registry data did not demonstrate alterations in 30-day, 1-year, and 2- to 3-year mortality, or any of the single complications (stroke, acute MI, renal failure, ischemia to the gut or limb) examined.
Conclusions: This meta-analysis suggests that TEVAR reduces early mortality, paraplegia, renal insufficiency, transfusions, reoperation for bleeding, cardiac complications, pneumonia, and length of stay compared with open surgery. Moderate-term follow-up (2-3 years) failed to show a sustained survival benefit.
Perspective: I suspect anyone who performs or performed open and TEVAR for thoracic aortic aneurysms (TAAs) recognizes that short-term mortality and morbidity is lower in patients undergoing TEVAR. Importantly, of all the devastating complications associated with TAA repair, paraplegia risk is reduced almost 58%. The fact that no sustained benefit is obtained is likely due to one of two reasons: 1) the small collection of studies with moderate-term follow-up were underpowered to show a difference, or 2) the patients die from nonthoracic aortic disease (i.e., MIs). Even more so than endovascular repair of abdominal aortic aneurysms, TEVAR will completely dominate the landscape of repair over the next decade. Gilbert Upchurch, Jr., M.D.

Title: Laparoscopic Adjustable Gastric Banding in Severely Obese Adolescents: A Randomized Trial
Topic: Congenital Heart Disease
Date Posted: 2/11/2010
Author(s): O’Brien PE, Sawyer SM, Laurie C, et al.
Citation: JAMA 2010;303:519-526.
Clinical Trial: yes
Study Question: Is gastric banding comparable to optimal lifestyle intervention for weight loss among severely obese adolescents?
Methods: This was a prospective randomized controlled trial of adolescents (ages 14-18 years) comparing supervised lifestyle intervention or gastric banding. All subjects were severely obese, with a body mass index (BMI) greater than 35 kg/m2. Follow-up continued for 2 years, with a main outcome of weight loss. Secondary outcomes included changes in metabolic syndrome, insulin resistance, quality of life, and adverse outcomes.
Results: A total of 24 of the 25 subjects who received gastric banding and 18 of the 25 subjects who received supervised lifestyle modification completed the study. More gastric banding patients lost >50% of excess weight (corrected for age), as compared to the lifestyle intervention patients (84% vs. 12%). Mean weight change in the gastric banding group was 34.6 kg of weight loss (95% confidence interval [CI], 30.2-39.0%), representing an excess weight loss of 78.8% (95% CI, 66.6-91.0%) or 12.7 BMI units (95% CI, 11.3-14.2). The mean weight loss in the lifestyle intervention group was 3.0 kg (95% CI, 2.1-8.1), representing an excess weight loss of 13.2% (95% CI, 2.6%-21.0%) or 1.3 BMI units (95% CI, 0.4-2.9). At the end of the 2-year follow-up, no subjects in the gastric banding group had the metabolic syndrome, compared to 4 of the 18 completers in the lifestyle group. Improved quality of life was also observed among subjects who underwent gastric banding; however, seven patients required revisional procedures during the follow-up period.
Conclusions: The investigators concluded that among severely obese adolescents, gastric banding was associated with significant long-term weight loss and improvement in metabolic syndrome criteria.
Perspective: This study suggests that gastric banding is a potential therapy for adolescents who require significant weight loss. Larger-scale studies are warranted, which includes data on adverse effects after such procedures. Elizabeth A. Jackson, M.D., F.A.C.C.

[Chevychelov]

Title: Standards of Medical Care in Diabetes—2010
Topic: General Cardiology
Date Posted: 2/12/2010
Author(s): American Diabetes Association.
Citation: Diabetes Care 2010;33:S11-S61.
Clinical Trial: No
Perspective: The following are 10 points to remember about standards of medical care in diabetes:

1. Criteria for the diagnosis of diabetes now include glycated hemoglobin (HbA1C) ≥6.5%. The testing should be performed in a National Glycohemoglobin Standardization Program–certified lab. Other criteria include fasting plasma glucose (FPG) ≥126 mg/dl (7.0 mmol/L), 2-hour plasma glucose ≥200 mg/dl (11.1 mmol/L) during an oral glucose tolerance testing (OGTT) (protocol defined by World Health Organization), or if a patient has symptoms of hyperglycemia and a random plasma glucose of ≥200 mg/dl. (Note that conditions of abnormal red cell turnover reduce accuracy of HbA1C; then glucose criteria should be used.)

2. Categories of increased risk for development of diabetes include impaired FPG (100-125 mg/dl [5.6-6.9 mmol/L]) or impaired OGTT (140-199 mg/dl [7.8-11.0 mmol/L]). Such patients should have structured lifestyle interventions to improve diet and physical activity and promote weight loss if warranted.

3. Criteria for testing for diabetes in asymptomatic adults include body mass index (BMI) ≥25 kg/m2 and additional risk factors such as physical inactivity, first-degree relative with diabetes, member of a high-risk ethnic group (African-American, Latino, Native American, Asian American, Pacific Islander), women diagnosed with gestational diabetes or who delivered babies >9 lbs., medical history of hypertension or blood pressure ≥140/90 mm Hg, high-density lipoprotein cholesterol <35 mg/dl and/or triglycerides >250 mg/dl, women with polycystic ovarian syndrome, HbA1C ≥5.7 or impaired fasting glucose on prior testing, conditions associated with diabetes (severe obesity, acanthosis nigrans), or history of CVD. If no risk factors, then testing is recommended after the age of 45 years. If testing is normal, repeat testing at 3-year intervals is recommended, with more frequent testing for those at increased risk or with borderline prior test results.

4. Women with gestational diabetes mellitus should be screened for diabetes at 6-12 weeks postpartum. Women at risk for gestational diabetes include those with severe obesity, prior history of gestational diabetes, polycystic ovarian syndrome, or a strong family history of diabetes. Women with those risk factors should be screened for gestational diabetes at the first prenatal visit.

5. Prevention and delay of type 2 diabetes include weight loss with recommended moderate physical activity of 150 minutes/week or greater (50-70% of maximum heart rate). Lifestyle counseling should also include nutritional advice, follow-up counseling to support these behavioral changes, and yearly monitoring for development of diabetes.

6. Recommendations for glycemic control in nonpregnant adults with diabetes include an HbA1C <7.0%, preprandial plasma glucose between 70 and 130 mg/dl (3.9-7.2 mmol/L), and peak postprandial plasma glucose 180 mg/dl (<10.0 mmol/L). HbA1C is the primary target for glycemic control and should be tested at least two times per year or at least quarterly in patients who are not at goal or whose therapy has changed.

7. Dietary recommendations for adults with diabetes include saturated fat intake <7% of total calories, minimal intake of trans fats, monitoring intake of carbohydrates, and digestible carbohydrates of 130 g/day. Meal planning can assist patients with adhering to these recommendations. Routine supplementation with antioxidants such as vitamin E, vitamin C, or carotene is not recommended.

8. Bariatric surgery should be considered for adults with a BMI >35 kg/m2 and type 2 diabetes, especially if comorbidities exist, which limit lifestyle modifications and/or pharmacologic therapy. Long-term benefits and cost-effectiveness including risks of bariatric surgery should be studied further in large populations of diabetics.

9. Psychosocial assessment should be included in ongoing management of diabetes. Screening for depression or other psychological problems including eating disorders or cognitive impairment is recommended when self-management is poor.

10. Other processes of care include an annual influenza vaccination and pneumococcal vaccination, blood pressure control goal of <130/80 mm Hg, and statin therapy (regardless of lipid levels) for diabetes with CVD, or without CVD over the age of 40 and with one or more risk factors. Goal LDL is <100 mg/dl (<2.6 mmol/l; <70 mg/dl if history of CVD is an option). Elizabeth A. Jackson, M.D., F.A.C.C.

Title: Jet Lag
Topic: General Cardiology
Date Posted: 2/12/2010
Author(s): Sack RL.
Citation: N Engl J Med 2010;362:440-447.
Clinical Trial: No
Perspective: The following are 10 points to remember about jet lag:

1. Jet lag is a sleep disorder that results from crossing time zones too rapidly for the circadian clock to keep pace. The latter is normally synchronized to the solar light-dark cycle and promotes alertness during the day and sleep at night. Jet lag is compounded by travel fatigue, dehydration, and prolonged immobility.

2. Symptoms of jet lag include insomnia and daytime sleepiness, as well as dysfunction of mood, and physical and cognitive performance.

3. Melatonin is a hormone secreted for about 10-12 hours at night and is synchronized to the light-dark cycle by the circadian clock.

4. For short trips, jet lag can be minimized by maintaining the home sleep-wake schedule if it is possible, or alternatively for 2 days prior to the flight, shift the sleep schedule by 1-2 hours toward the destination time zone.

5. Treatment for jet lag includes use of appropriate exposure to light, melatonin, or both; supplement as needed with medication to counteract insomnia or daytime sleepiness.

6. In a comparison with melatonin, zolpidem 10 mg was more effective at reducing symptoms of jet lag, but it is not ideal because of duration of action. Upon landing in the new time zone, melatonin 0.5-3 mg may be helpful to promote sleep when traveling west to east.

7. Hypnosedatives need to be used with caution, as they may be expected to further increase the elevated risk for deep vein thrombosis.

8. A short-acting sleeping pill during the flight is preferred, such as zaleplon 5-10 mg. Sedatives should not be combined with alcohol.

9. Prior to and during the trip, hydration will help as well as avoiding caffeine for several hours prior to sleep time. When traveling east to west, seek bright sunlight in the evening; for west to east, seek bright sun in the morning.

10. Increased consumption of caffeinated beverages may counteract daytime sleepiness. An alternative to increase alertness and reduce other symptoms of jet lag my be slow-release caffeine (300 mg). This strategy needs to be weighed against possible increase in insomnia. Melvyn Rubenfire, M.D., F.A.C.C.

[Chevychelov]

Title: Altitude and the Heart: Is Going High Safe for Your Cardiac Patient?
Topic: General Cardiology
Date Posted: 2/8/2010
Author(s): Higgins JP, Tuttle T, Higgins JA.
Citation: Am Heart J 2010;159:25-32.
Clinical Trial: No
Perspective: Ease of travel and an interest in high altitude recreation exposes patients to the acute physiologic effects of high altitude and lower oxygen availability. Acute exposure to high altitude is associated with significant alterations to the cardiovascular system, with acute hypoxia, increased myocardial work, increased epinephrine release, and increased pulmonary artery pressures. This review summarized the physiology and clinical evidence regarding acute altitude exposure on the cardiopulmonary system, and made practical recommendations for patients with cardiovascular disease. Points to remember are:

1. Environmental changes when moving from sea level to high altitude include reductions in atmospheric pressure, oxygen pressure, humidity, and temperature. Significant changes typically begin at about 2500 m (8200 ft). The effect on patients depends on the degree of hypoxia, change in elevation, rate of ascent, level of acclimatization, exercise intensity at altitude, age, and genetics.

2. Moderate altitude is defined as 1500-2500 m (4950-8250 ft). High altitude is defined as >2500 m (8250 ft).

3. The acute cardiopulmonary effects of altitude include:
Tissue hypoxia, as a result of the significant decrease in oxygen availability in inspired air. Pulmonary vascular resistance increases 50-300%.
Initial hyperventilation leads to respiratory alkalosis that transiently shifts leftward the oxygen-hemoglobin dissociation curve. (After a few hours, increased red cell production of 2,3-diphosphoglycerate shifts the curve back to the right.)
Heart rate increased at rest. There is only a minimal reduction in resting stroke volume, but a decrease in maximal heart rate response lowers peak cardiac output.
A reduction in plasma volume caused by increased respiratory, urinary, and cutaneous losses. The resulting increased hematocrit is responsible for higher oxygen-carrying capacity per unit blood volume, helping maintain resting stroke volume.
Parasympathetic nervous system deactivation, with predomination of sympathetic nervous responses.
Glycogenolysis stimulated by the increase in epinephrine, causing increased use of glucose at rest and with exercise, and increased blood lactate levels.

4. Coronary artery disease. The acute physiological changes associated with high altitude result in earlier onset of ischemia and symptomatic angina in patients with coronary artery disease, and at a lower pressure-rate product.

5. Heart failure. Increased sympathetic activity results in vasoconstriction and tachycardia, as well as release of inflammatory mediators. Increased sympathetic activity results in increased heart rate and systemic vascular resistance. Pulmonary vasoconstriction leads to pulmonary hypertension (exacerbated with exercise), probably the most significant factor in reducing cardiopulmonary performance at altitude in patients with heart failure.

6. High altitude pulmonary edema. High-altitude (noncardiogenic) pulmonary edema affects unacclimatized people with a genetic predisposition, typically within 4 days of arriving at altitude. Causes are probably multifactorial, including pulmonary vascoconstriction leading to increased intravascular pressure.
Slow ascent serves as a preventative measure. (For ascent >3050 m [10,000 ft], ascent should be ≤305 m [1000 ft] daily with a rest every 1000 m [3300 ft].)
If suspected, immediate descent and administration of supplemental oxygen is the treatment of choice.
Nifedipine (sustained release 20-30 mg orally q 6 to 12 h) can both prevent and treat high-altitude pulmonary edema.
Tadalafil 10 mg bid or sildenafil 50 mg q 8h can be used to prevent high-altitude pulmonary edema, but treatment doses have not been established.

7. Arrhythmia. Increased sympathetic activity associated with high altitude can increase the frequency and duration of supraventricular and ventricular arrhythmias with or without underlying heart disease.

8. Congenital heart disease. In simple uncomplicated congenital heart disease (including atrial septal defect, restrictive ventricular septal defects, and patent ductus arteriosus), arterial oxygen desaturation can occur at high altitude when the usual left-to-right shunting of blood reverses, owing to increased right-sided pressures.

9. Recommendations for all people. The following recommendations apply to all individuals who plan to ascend to high altitude and/or exercise at elevation:
Limit activity to a lower maximal level than at sea level.
Raise sleeping altitude gradually.
At least moderate physical conditioning at sea level is encouraged before exercise at altitude.
Alcohol consumption should be minimized, and hydration should be maintained.
If cardiac status is unknown, exercise testing can be considered prior to travel.

10. Recommendations for patients with cardiovascular disease. The following recommendations apply to individuals with known cardiovascular disease who plan to ascend to high altitude and/or exercise at elevation:
Patients with unstable cardiac disease (unstable angina, uncontrolled ventricular arrhythmias, decompensated heart failure) should not exercise at high altitude.
Patients with severe cardiac diseases (including severe angina, heart failure, or valve disease) should not ascend to high altitude. Patients should avoid traveling to high altitude for 14 days after an acute coronary event. Patients with stable heart disease should limit physical activity for the first few days after ascent. Patients should be advised that they could become symptomatic at lower workloads when at altitude. Patients with prior high-altitude pulmonary edema and known intracardiac shunt should be advised to avoid travel to high altitude. Patients with pacemakers can safely travel to high altitude with no impact on ventricular stimulation thresholds.
David S. Bach, M.D., F.A.C.C.

Title: N-Terminal Pro–B-Type Natriuretic Peptide–Guided, Intensive Patient Management in Addition to Multidisciplinary Care in Chronic Heart Failure: A 3-Arm, Prospective, Randomized Pilot Study
Topic: Heart Failure/Transplant
Date Posted: 2/12/2010
Author(s): Berger R, Moertl D, Peter S, et al.
Citation: J Am Coll Cardiol 2010;55:645-653.
Clinical Trial: No
Study Question: Does the addition of N-terminal pro–B-type natriuretic peptide (BNP)–guided, intensive patient management (BM) to multidisciplinary care (MC) improve outcome in patients following hospitalization due to heart failure (HF)?
Methods: Hospitalized HF patients were randomized to BM, MC, or usual care (UC). MC included at least two consultations from an HF specialist who provided therapeutic recommendations and home care by a specialized HF nurse. In addition, BM included intensified up-titration of medication by HF specialists in high-risk patients. The investigators utilized NT-proBNP to define the level of risk and to monitor wall stress. This monitoring also allowed for anticipation of cardiac decompensation and adjustment of medication in advance.
Results: The study cohort was comprised of 278 patients. After 12 months, the BM group had the highest proportion of anti-neurohormonal triple-therapy (difference between all groups). Accordingly, BM reduced days of HF hospitalization (488 days) compared with the hospitalization for the MC (1,254 days) and UC (1,588 days) groups (p < 0.0001; significant differences among all groups). Using Kaplan-Meier analysis, the first HF rehospitalization (28%) was lower in the BM versus MC groups (40%; p = 0.06) and the MC versus UC groups (61%; p < 0.01). Moreover, the combined endpoint of mortality or HF rehospitalization was lower in the BM (37%) than in the MC group (50%; p < 0.05) and in the MC than in the UC group (65%; p = 0.04). Mortality rate was similar between the BM (22%) and MC groups (22%), but was lower compared with the UC group (39%; vs. BM: p < 0.02; vs. MC: p < 0.02).
Conclusions: The study authors concluded that when compared with MC alone, additional BM improves clinical outcome in patients after HF hospitalization.
Perspective: The main advantages of evaluating BNP in HF are for risk stratification, predicting mortality, confirming the diagnosis, and monitoring therapy. The findings of this study support the results of the BATTLESCARRED trial (J Am Coll Cardiol 2010;55:53-60), STARS-BNP trial (J Am Coll Cardiol 2007;49:1733-9), and the STARBRITE study (Am Heart J 2005;150:893-8), that BNP-guided therapy is beneficial, unlike the TIME-CHF study (JAMA 2009;301:383-92). Larger multicenter trials are needed to resolve these disparate results. Ragavendra R. Baliga, M.B.B.S.

[Chevychelov]

Title: Fulminant Myocarditis Associated With Pandemic H1N1 Influenza A Virus in Children
Topic: Heart Failure/Transplant
Date Posted: 2/10/2010 5:00:00 PM
Author(s): Bratincsak A, El-Said HG, Bradley JS, Shayan K, Grossfeld PD, Cannavino CR.
Citation: J Am Coll Cardiol 2010;Feb 10:[Epub ahead of print].
Clinical Trial: No
Study Question: Is fulminant myocarditis associated with pandemic H1N1 influenza A virus in children?
Perspective: Acute myocarditis is a well-described manifestation of numerous viral infections, and may present with a broad spectrum of symptoms and clinical features. Fulminant myocarditis is thought to be rarely associated with influenza A and may present with fatal arrhythmias, high grade atrioventricular block, and even cardiogenic shock. The true prevalence of influenza-associated fulminant myocarditis is not known because of the lack of comprehensive screening, with only a few cases reported in the literature. The four documented cases of myocarditis in the current study, and other prior reports, raise the concern that the novel H1N1 influenza A virus may be more commonly associated with a severe form of myocarditis than previously seen influenza strains. These observations warrant a high index of clinical suspicion for myocarditis in children with H1N1 influenza A infection. Early diagnosis and rapid intervention with circulatory support may decrease morbidity and mortality, with the potential for saving myocardium and lives. Debabrata Mukherjee, M.D., F.A.C.C.

Title: Perioperative Management of Patients With Drug-Eluting Stents
Topic: Interventional Cardiology
Date Posted: 2/15/2010 5:00:00 PM
Author(s): Abualsaud AO, Eisenberg MJ.
Citation: JACC Cardiovasc Interv 2009;2:131-142.
Clinical Trial: No
Study Question: What is the best strategy for perioperative use of antiplatelet agents in patients with drug-eluting stents (DES) who need to undergo noncardiac surgery to avoid stent thrombosis?
Perspective: The following are 10 points to remember from this state-of-the-art paper about perioperative management of patients with DES:

1. DES are associated with a small, but significant increased risk of late and very late stent thrombosis compared with bare-metal stents.

2. Stent thrombosis is a platelet-mediated phenomenon that usually manifests as sudden death ST-segment elevation myocardial infarction, or malignant arrhythmias. It appears to be associated with a mortality ranging from 9-45%.

3. Premature cessation of dual antiplatelet therapy is the most important predictor of stent thrombosis. Current guidelines support continuation of dual antiplatelet therapy for 12 months after DES implantation.

4. The risk of perioperative stent thrombosis is increased in patients undergoing noncardiac surgery within 6 weeks of stent-based percutaneous coronary intervention (PCI).

5. In patients undergoing noncardiac surgery, continuation of aspirin is associated with a 1.5-fold increase in risk of bleeding while withdrawal of aspirin leads to an increase in cardiac, cerebral, and peripheral vascular events. Dual antiplatelet therapy is associated with an increased risk of bleeding complications.

6. All elective surgical procedures should be delayed by at least 6 months and ideally 12 months after DES placement.

7. Patients undergoing surgical procedures 12 months after PCI are at a lower risk of perioperative stent thrombosis compared with earlier surgery. However, if possible, dual antiplatelet therapy should be continued if bleeding risk is low. If the risk of perioperative bleeding is significantly high, then clopidogrel should be discontinued 5 days before surgery, and aspirin should be maintained. Clopidogrel should be restarted as soon as realistically feasible.

8. In patients with DES, when surgery cannot be delayed beyond a year after PCI and thienopyridine or dual antiplatelet therapy must be discontinued, intravenous small molecule glycoprotein IIb/IIIa inhibitors have been used as bridging therapy preoperatively, followed by early (usually immediately postop) resumption of dual antiplatelet therapy. The efficacy of this strategy has not been definitively proven. Use of heparin, low molecular weight heparin, Coumadin, or fondaparinux as bridge therapy for patients after discontinuing dual antiplatelet therapy is not advisable.

9. Primary PCI is the reperfusion therapy of choice in patients who develop perioperative myocardial infarction due to stent thrombosis.

10. The challenges associated with thienopyridine use could be overcome once ticagrelor is approved for clinical use. Its short half-life and its rapid onset of action would allow patients to discontinue ticagrelor only 1 day before surgery and resume it immediately after surgery, thereby potentially diminishing both the risk of perioperative bleeding and stent thrombosis. This hypothesis is also unproven at this point. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

[Chevychelov]

Title: Impact of Femoral Vascular Closure Devices and Antithrombotic Therapy on Access Site Bleeding in Acute Coronary Syndromes: The Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) Trial
Topic: Interventional Cardiology
Date Posted: 2/9/2010
Author(s): Sanborn TA, Ebrahimi R, Manoukian SV, et al.
Citation: Circ Cardiovasc Interv 2010;3:57-62.
Clinical Trial: No
Study Question: What is the impact of vascular closure devices (VCDs) on access site bleeding in patients undergoing an early invasive approach for acute coronary syndromes (ACS) and coronary angiography using femoral arterial access?
Methods: The authors assessed the impact of VCD use on access site bleeding (ASB) among 11,621 patients undergoing femoral angiography in the ACUITY trial. The ACUITY trial randomized patients with ACS to receive heparin (unfractionated or enoxaparin) plus glycoprotein IIb/IIIa inhibitor (GPI), bivalirudin plus GPI, or bivalirudin monotherapy in an open-label fashion. Major ASB was defined as ASB requiring interventional or surgical correction, hematoma ≥5 cm at the access site, retroperitoneal bleeding, or hemoglobin drop ≥3 g/dl with ecchymosis or hematoma <5 cm, oozing blood, or prolonged bleeding (>30 minutes) at the access site.
Results: A VCD was used in 4,307 (37.1%) patients, and 7,314 (62.9%) had manual compression. The rate of ASB was lower in patients treated with VCD (2.5% vs. 3.3%, relative risk, 0.76; 95% confidence interval [CI], 0.61-0.94; p = 0.01). Rates of bleeding were lowest in patients treated with bivalirudin monotherapy and a VCD (0.7%). After adjusting for differences in baseline variables, both VCD use (odds ratio, 0.78; 95% CI, 0.61-0.99; p = 0.04) and bivalirudin monotherapy (odds ratio, 0.35; 95% CI, 0.25-0.49; p < 0.0001) were both independently associated with freedom from ASB.
Conclusions: Use of VCD was associated with a reduced rate of ASB in patients with ACS undergoing an early invasive approach.
Perspective: There are no large well-designed randomized trials supporting a reduction in bleeding events with VCDs. Prior meta-analyses suggest worse outcome with VCDs, whereas observational studies suggest better outcomes in patients treated with VCDs. It is not clear whether the findings of the current study reflect inability to adjust for confounding or are truly reflective of better outcomes with VCDs. The most effective strategy for reducing access site bleeding complications is radial access, and this strategy should be considered in all patients at risk for ASB. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

Title: Comparison of Ticagrelor With Clopidogrel in Patients With a Planned Invasive Strategy for Acute Coronary Syndromes (PLATO): A Randomised Double-Blind Study
Topic: Interventional Cardiology
Date Posted: 2/10/2010
Author(s): Cannon CP, Harrington RA, James S, et al., on behalf of the PLATelet inhibition and patient Outcomes (PLATO) Investigators.
Citation: Lancet 2010;375:283-293.
Clinical Trial: yes
Study Question: What is the relative efficacy and safety of ticagrelor compared with clopidogrel in patients undergoing an early invasive approach for acute coronary syndromes (ACS)?
Methods: The authors reported the outcome of 13,408 patients who were treated with a planned invasive strategy for an ACS and were enrolled in the PLATO trial. In this trial, patients were randomly assigned in a double dummy fashion to ticagrelor and placebo (180 mg loading dose followed by 90 mg twice a day), or to clopidogrel and placebo (300-600 mg loading dose or continuation with maintenance dose followed by 75 mg per day) for 6-12 months. All patients were also treated with aspirin. The primary composite endpoint was cardiovascular death, myocardial infarction (MI), or stroke.
Results: PCI was performed in 76.8% of the cohort and coronary artery bypass grafting in 5.8%. The primary composite endpoint at 1 year was less frequent in the ticagrelor group compared with the clopidogrel group (9.0% vs. 10.7%; hazard ratio, 0.84; 95% confidence interval, 0.75-0.94; p = 0.0025). There was no difference between clopidogrel and ticagrelor groups in the rates of total major bleeding (11.6% vs. 11.5%, p = 0.8803) or GUSTO severe bleeding (3.2% vs. 2.9%, p = 0.3785). All-cause mortality was lower with ticagrelor (3.9% vs. 5.0%, p = 0.0103).
Conclusions: Ticagrelor seems to be preferable to clopidogrel for patients with ACS, for whom an early invasive strategy is planned.
Perspective: Ticagrelor is a reversible and direct-acting oral P2Y12- receptor antagonist with rapid onset and offset of action. It is a more potent platelet inhibitor compared with clopidogrel, and has demonstrated a reduction in ischemic events with no increase in bleeding over contemporary therapy. While the reduction in mortality may be a chance finding (there was no adjustment for multiple testing), the trends in both MI and death favor ticagrelor. This drug may displace the use of thienopyridines in patients with ACS. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

[Chevychelov]

Title: Stent Graft Versus Balloon Angioplasty for Failing Dialysis-Access Grafts
Topic: Interventional Cardiology
Date Posted: 2/10/2010 5:00:00 PM
Author(s): Haskal ZV, Trerotola S, Dolmatch B, et al.
Citation: N Engl J Med 2010;362:494-503.
Clinical Trial: yes
Study Question: What is the benefit of using polytetrafluoroethylene (PTFE) stent graft compared with balloon angioplasty only for treating patients with venous anastomosis stenosis associated with hemodialysis grafts?
Methods: The authors randomized 190 patients who had venous anastomosis stenosis to undergo angioplasty only versus treatment with a PTFE stent graft. Primary endpoint was patency of the access site at 6 months.
Results: Randomization to stent graft was associated with better patency of the treatment site (51% vs. 23%, p < 0.001) and patency of the access circuit (38% vs. 20%, p = 0.008). Binary restenosis was much greater with angioplasty (78% vs. 28%, p < 0.001). The stent graft arm was more likely to be free of need for subsequent intervention at 6 months.
Conclusions: Stent grafting is superior to balloon angioplasty only for the treatment of venous anastomosis stenosis associated with hemodialysis grafts.
Perspective: Dialysis access using prosthetic grafts is inferior to autogenous arterio-venous fistulas due to the high incidence of graft failure. Venous anastomosis stenosis is a recalcitrant problem and is responsible for a large proportion of graft failures. Balloon angioplasty has been traditionally used for these lesions, although it has been plagued with a high restenosis rate. This trial has established stent grafts as the current standard of care for these lesions even though the recurrence rate with stent grafts still remains unacceptably high. Further research is needed to identify effective therapeutic strategies that can be used to further reduce restenosis in these lesions. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

Title: Physical Activity and Physiological Cardiac Remodelling in a Community Setting: The Multi-Ethnic Study of Atherosclerosis (MESA)
Topic: Noninvasive Cardiology
Date Posted: 2/9/2010
Author(s): Turkbey EB, Jorgensen NW, Johnson WC, et al.
Citation: Heart 2010;96:42-48.
Clinical Trial: No
Study Question: Is there an association between physical activity and left ventricular (LV) structure and function in the general population in a community setting?
Methods: Subjects included 4,992 multiethnic participants (age 45-84 years; 52% women) free of clinically apparent cardiovascular disease enrolled in a cross-sectional population-based study of subclinical atherosclerosis (The Multi-Ethnic Study of Atherosclerosis [MESA]). LV mass, volumes, and function were assessed by cardiac magnetic resonance imaging. Physical activity, defined as intentional exercise and total moderate and vigorous physical activity, was assessed by a standard semi-quantitative questionnaire.
Results: LV mass and end-diastolic volume were positively associated with physical activity (1.4 g/m2 [women] and 3.1 g/m2 [men] greater LV mass in the highest category of intentional exercise compared with individuals reporting no intentional exercise; p = 0.05 and p < 0.001, respectively). Relationships were nonlinear, with stronger positive associations at lower levels of physical activity (test for nonlinearity; p = 0.02 and p = 0.03, respectively). Cardiac output and ejection fraction were unchanged with increased physical activity levels. Resting heart rate was lower in women and men with higher physical activity levels (22.6 bpm lower resting heart rate in the highest category of intentional exercise compared with individuals reporting no intentional exercise; p < 0.001).
Conclusions: In a community-based population free of clinically apparent cardiovascular disease, higher physical activity levels were associated with proportionally greater LV mass and end-diastolic volume and lower resting heart rate.
Perspective: Predominantly studied in high-performance athletes, the ‘athlete’s heart’ has adapted to intense physical training with increased LV end-diastolic diameter, increased myocardial mass, and decreased resting heart rate. This study reveals that, among active individuals not trained as elite athletes, higher levels of physical activity are associated with cardiac changes similar to those seen with more intense training. It is important to note that increased LV mass, associated with increased cardiovascular risk among patients with hypertension, appears benign (or even beneficial) when it is acquired with physical activity. The known inverse relationship between moderate to vigorous physical activity and risk for premature death and other cardiovascular diseases occurs despite what is shown in this study. An increased LV mass, in other scenarios, would raise concern. David S. Bach, M.D., F.A.C.C.

[Chevychelov]

Title: Usefulness of Echocardiographic Dyssynchrony in Patients With Borderline QRS Duration to Assist With Selection for Cardiac Resynchronization Therapy
Topic: Noninvasive Cardiology
Date Posted: 2/15/2010
Author(s): Oyenuga O, Hara H, Tanaka H, et al.
Citation: JACC Cardiovasc Imaging 2009;2:1190-8.
Clinical Trial: No
Related Resources
JACC Cardiovasc Imaging Article: Usefulness of Echocardiographic Dyssynchrony in Patients With Borderline QRS Duration to Assist With Selection for Cardiac Resynchronization Therapy

Study Question: Does echocardiographic dyssynchrony assist in the selection of patients with borderline QRS duration for cardiac resynchronization therapy (CRT)?
Methods: Of 221 consecutive heart failure patients with a left ventricular ejection fraction (LVEF) ≤35% referred for CRT, 135 patients had increased QRS duration (>130 ms; 168 ± 26 ms) and 86 had a borderline increase in QRS duration (100-130 ms; 115 ± 8 ms). Dyssynchrony was assessed using interventricular mechanical delay, tissue Doppler imaging longitudinal velocity opposing wall delay, and speckle tracking radial strain for septal to posterior wall delay. Response to CRT was defined as ≥15% increase in EF, and reverse remodeling as ≥10% decrease in end-systolic volume.
Results: There were 201 patients with baseline quantitative echocardiographic data available, and 187 with follow-up data available 8 ± 5 months after CRT. A smaller proportion of borderline QRS duration patients (53%) were EF responders compared with 75% with widened QRS (p < 0.05). Interventricular mechanical delay ≥40 ms and opposing wall delay ≥65 ms were predictive of EF response in the wide QRS interval group, but not the borderline QRS duration group. However, speckle tracking radial dyssynchrony ≥130 ms was predictive of EF response in both wide QRS patients (88% sensitivity, 74% specificity) and borderline QRS patients (79% sensitivity, 82% specificity), and was associated with reverse remodeling with reduction in LV end-systolic volume (p < 0.0005).
Conclusions: Radial dyssynchrony by speckle tracking strain was associated with both EF and reverse remodeling responses to CRT in patients with borderline QRS duration, and has the potential to assist with patient selection.
Perspective: Among symptomatic patients with LV systolic dysfunction, CRT is associated with benefit in both symptoms and survival. However, as many as 30% of patients treated are ‘nonresponders,’ showing no demonstrable improvement after CRT. Current selection criteria for CRT include the presence of symptomatic heart failure, LV systolic dysfunction, and QRS prolongation. Although echocardiography has clear utility in the evaluation of LV mechanical dyssynchrony, it is not currently recommended for purposes of patient selection for CRT. Further, although a variety of measures of dyssynchrony can be examined on echocardiography, there is no consensus as to whether any one method has greater utility in predicting response to CRT. In this study, fewer patients with borderline QRS were responders than were patients with more prolonged QRS duration; however, echocardiographic assessment of radial dyssynchrony by speckle tracking had predictive power in determining response to CRT among patients with borderline QRS prolongation. Although echocardiography may not be needed for patient selection among those with QRS duration >130 ms, these data suggest that it could play a useful role among patients with heart failure, LVEF ≤35%, and borderline QRS prolongation. David S. Bach, M.D., F.A.C.C.

Title: Usefulness of Echocardiographic Dyssynchrony in Patients With Borderline QRS Duration to Assist With Selection for Cardiac Resynchronization Therapy
Topic: Noninvasive Cardiology
Date Posted: 2/15/2010
Author(s): Oyenuga O, Hara H, Tanaka H, et al.
Citation: JACC Cardiovasc Imaging 2009;2:1190-8.
Clinical Trial: No
Related Resources
JACC Cardiovasc Imaging Article: Usefulness of Echocardiographic Dyssynchrony in Patients With Borderline QRS Duration to Assist With Selection for Cardiac Resynchronization Therapy

Study Question: Does echocardiographic dyssynchrony assist in the selection of patients with borderline QRS duration for cardiac resynchronization therapy (CRT)?
Methods: Of 221 consecutive heart failure patients with a left ventricular ejection fraction (LVEF) ≤35% referred for CRT, 135 patients had increased QRS duration (>130 ms; 168 ± 26 ms) and 86 had a borderline increase in QRS duration (100-130 ms; 115 ± 8 ms). Dyssynchrony was assessed using interventricular mechanical delay, tissue Doppler imaging longitudinal velocity opposing wall delay, and speckle tracking radial strain for septal to posterior wall delay. Response to CRT was defined as ≥15% increase in EF, and reverse remodeling as ≥10% decrease in end-systolic volume.
Results: There were 201 patients with baseline quantitative echocardiographic data available, and 187 with follow-up data available 8 ± 5 months after CRT. A smaller proportion of borderline QRS duration patients (53%) were EF responders compared with 75% with widened QRS (p < 0.05). Interventricular mechanical delay ≥40 ms and opposing wall delay ≥65 ms were predictive of EF response in the wide QRS interval group, but not the borderline QRS duration group. However, speckle tracking radial dyssynchrony ≥130 ms was predictive of EF response in both wide QRS patients (88% sensitivity, 74% specificity) and borderline QRS patients (79% sensitivity, 82% specificity), and was associated with reverse remodeling with reduction in LV end-systolic volume (p < 0.0005).
Conclusions: Radial dyssynchrony by speckle tracking strain was associated with both EF and reverse remodeling responses to CRT in patients with borderline QRS duration, and has the potential to assist with patient selection.
Perspective: Among symptomatic patients with LV systolic dysfunction, CRT is associated with benefit in both symptoms and survival. However, as many as 30% of patients treated are ‘nonresponders,’ showing no demonstrable improvement after CRT. Current selection criteria for CRT include the presence of symptomatic heart failure, LV systolic dysfunction, and QRS prolongation. Although echocardiography has clear utility in the evaluation of LV mechanical dyssynchrony, it is not currently recommended for purposes of patient selection for CRT. Further, although a variety of measures of dyssynchrony can be examined on echocardiography, there is no consensus as to whether any one method has greater utility in predicting response to CRT. In this study, fewer patients with borderline QRS were responders than were patients with more prolonged QRS duration; however, echocardiographic assessment of radial dyssynchrony by speckle tracking had predictive power in determining response to CRT among patients with borderline QRS prolongation. Although echocardiography may not be needed for patient selection among those with QRS duration >130 ms, these data suggest that it could play a useful role among patients with heart failure, LVEF ≤35%, and borderline QRS prolongation. David S. Bach, M.D., F.A.C.C.