Обзор американских кардиологических журналов за неделю (ссылки)

[Chevychelov]

Title: Effect of Cyclosporine on Left Ventricular Remodeling After Reperfused Myocardial Infarction
Topic: Interventional Cardiology
Date Posted: 4/27/2010
Author(s): Mewton N, Croisille P, Gahide G, et al.
Citation: J Am Coll Cardiol 2010;55:1200-1205.
Clinical Trial: No
Related Resources
JACC Article: Effect of Cyclosporine on Left Ventricular Remodeling After Reperfused Myocardial Infarction

Study Question: What is the effect of a single dose of cyclosporine administered at the time of reperfusion on left ventricular (LV) remodeling and function 5 days and 6 months after myocardial infarction (MI)?
Methods: The authors randomly assigned 58 patients with acute ST-elevation MI to placebo versus 2.5 mg of cyclosporine immediately before undergoing percutaneous coronary intervention. This trial demonstrated a reduction in infarct size with cyclosporine. This paper reports the results of the magnetic resonance imaging (MRI) substudy.
Results: Twenty-eight patients underwent an MRI at 5 days and 6 months. The infarct size at 6 months was smaller in the cyclosporine group (29 ± 15 g vs. 38 ± 14 g, p = 0.04). There was a significant reduction of LV end-systolic volume (72 ± 20 ml vs. 91 ± 36 ml, p = 0.04 at 5 days and 67 ± 24 vs. 84 ± 29, p = 0.05 at 6 months) in the cyclosporine group. There was no significant difference between the two groups in global LV mass or regional wall thickness of the remote noninfarcted myocardium at 5 days or 6 months.
Conclusions: Cyclosporine used prior to reperfusion of acute MI persistently reduces infarct size and does not have a detrimental effect on LV remodeling.
Perspective: This interesting pilot study suggests that a single dose of cyclosporine may be particularly beneficial in reducing reperfusion injury and may prevent adverse remodeling in patients with ST-elevation MI. Larger studies are needed to confirm the findings of this study before this approach can be incorporated into clinical practice. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

Title: Coronary Artery Calcium Score and Risk Classification for Coronary Heart Disease Prediction
Topic: Prevention/Vascular
Date Posted: 4/27/2010 4:00:00 PM
Author(s): Polonsky TS, McClelland RL, Jorgensen NW, et al.
Citation: JAMA 2010;303:1610-1616.
Clinical Trial: No
Study Question: To what degree does adding the coronary artery calcium score (CACS) to traditional risk factors improve the prediction model for cardiovascular events?
Methods: CACS was measured by computed tomography in 6,814 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based cohort without known cardiovascular disease. Participants with diabetes were excluded from the primary analysis. Five-year risk estimates for incident coronary heart disease (CHD) were categorized as 0% to less than 3%, 3% to less than 10%, and 10% or more using Cox proportional hazards models. Model 1 used age, sex, tobacco use, systolic blood pressure, antihypertensive medication use, total and high-density lipoprotein cholesterol, and race/ethnicity. Model 2 used these risk factors plus CACS. The net reclassification was used to demonstrate the improvement for predicting CHD events using model 2 versus model 1.
Results: Mean age was 62 years and 46% were men. At baseline, about 5% (mean age 75 years) were in the high-risk group and >60% (mean age 58 years) were in the low-risk group. During a median of 5.8 years of follow-up among a final cohort of 5,878 patients, 209 CHD events occurred, of which 122 were myocardial infarction, death from CHD, or resuscitated cardiac arrest. Model 2 resulted in significant improvements in risk prediction compared with model 1 (net reclassification improvement = 0.25; 95% confidence interval, 0.16-0.34; p < 0.001). In model 1, 69% of the cohort was classified in the highest or lowest risk categories compared with 77% in model 2. An additional 23% of those who experienced events were reclassified as high risk, and an additional 13% without events were reclassified as low risk using model 2. The use of statins or presence of diabetes did not influence the results.
Conclusions: In this multi-ethnic cohort, addition of CACS to a prediction model based on traditional risk factors significantly improved the classification of risk and placed more individuals in the most extreme risk categories.
Perspective: The intermediate-risk group achieved a substantially higher net reclassification than the overall cohort and, therefore, appears to benefit the most from a CACS-adjusted strategy. The 6% incident CHD in the high-risk subjects with a zero CACS, supports a recommendation that high-risk persons do not benefit from CACS and rather should be treated based on standard guidelines. Melvyn Rubenfire, M.D., F.A.C.C.

[Chevychelov]

Title: The Impact of Transcatheter Atrial Septal Defect Closure in the Older Population: A Prospective Study
Topic: Congenital Heart Disease
Date Posted: 4/28/2010
Author(s): Khan AA, Tan JL, Li W, et al.
Citation: JACC Cardiovasc Interv 2010;3:276-281.
Clinical Trial: No
Related Resources
JACC Cardiovasc Interv Article: The Impact of Transcatheter Atrial Septal Defect Closure in the Older Population: A Prospective Study

Study Question: What is the safety and efficacy of transcatheter atrial septal defect (ASD) closure in an older population?
Methods: In this single-center, prospective clinical trial, consecutive patients ages >40 years with hemodynamically significant ASD (defined by right heart dilation and Qp:Qs ≥1.5 by echocardiogram) were enrolled. Study protocol included laboratory testing (atrial and brain natriuretic peptides), electrocardiogram, chest X-ray, transthoracic echocardiogram (ECHO), 6-minute walk test (6MWT), quality of life (QOL; assessed with short form 36, version 2), and assessment of New York Heart Association (NYHA) functional class, with all tests performed immediately prior to ASD closure and at 6 weeks and 1 year post-closure. Transcatheter ASD closure was performed with the Amplatzer septal occluder (AGA Medical) using balloon sizing or intraprocedural echocardiography.
Results: Twenty-three patients (57% female, mean 69 years) were enrolled and all underwent successful device implantation. Significant comorbidities included atrial fibrillation (21%), hypertension (30%), hypercholesterolemia (26%), ischemic heart disease (13%), and chronic renal failure (4%). At the time of device implantation, mean pulmonary artery (PA) pressure was 22 mm Hg, Qp:Qs was 2.2, and ASD size was 18 mm. Mean implanted device size was 24 mm (range 10-36 mm), with two patients requiring implantation of two devices for separate defects. New-onset atrial fibrillation in one patient was the only significant periprocedural complication reported. NYHA functional class improved in the majority of patients from predominately class II (70%) preclosure to predominately class I (78%) at 1-year follow-up (p < 0.0001). 6MWT distance improved from 400 m at baseline to 451 and 493 m at 6-week and 1-year follow-up, respectively (p = 0.001). QOL physical and mental health scores increased significantly at 1 year (p ≤ 0.007). One-year ECHO follow-up demonstrated significant reduction in right ventricular diastolic dimension and right atrial volume, and increase in left ventricular diastolic and systolic dimensions and ejection fraction (p ≤ 0.004).
Conclusions: Percutaneous ASD closure is feasible in an older population and results in functional and anatomic improvements at 1 year.
Perspective: This prospective study, although nonrandomized, demonstrates that transcatheter ASD device closure can be undertaken in an older population with minimal procedural adverse effects. Efficacy of ASD device closure (i.e., presence of residual atrial level shunt) is not reported. The study cohort is small (n = 23), generally healthy (only 13% had ischemic heart disease), and uncommonly encountered clinically (no subjects had significant pulmonary hypertension despite a mean ASD size of 18 mm, Qp:Qs of >2:1, and age of nearly 70 years), all factors that limit the generalizability of this study. Timothy B. Cotts, M.D., F.A.C.C., Bryan Goldstein, M.D.

Title: Primary Transcatheter Patent Foramen Ovale Closure Is Effective in Improving Migraine in Patients With High-Risk Anatomic and Functional Characteristics for Paradoxical Embolism
Topic: Congenital Heart Disease
Date Posted: 4/28/2010
Author(s): Rigatelli G, Dell’Avvocata F, Ronco F, et al.
Citation: JACC Cardiovasc Interv 2010;3:282-287.
Clinical Trial: yes
Related Resources
JACC Cardiovasc Interv Article: Primary Transcatheter Patent Foramen Ovale Closure Is Effective in Improving Migraine in Patients With High-Risk Anatomic and Functional Characteristics for Paradoxical Embolism

Study Question: What is the effectiveness of transcatheter patent foramen ovale (PFO) closure in improving migraine in a group of patients with high-risk anatomic and functional characteristics for paradoxical embolism?
Methods: In this single-center, nonrandomized, prospective trial, patients with medication-refractory migraine and PFO referred for consideration of transcatheter PFO closure were enrolled. The Migraine Disability Assessment Score (MIDAS) was administered to all patients for evaluation of migraine severity. Device closure of PFO was performed in patients meeting high-risk inclusion criteria, including: curtain shunt pattern of right-to-left (R-L) shunt on transcranial Doppler (TC-D) and transesophogeal echocardiography (TEE), refractory and disabling migraine (MIDAS class 3-4), PFO, R-L shunt during normal respiration, atrial septal aneurysm, coagulation abnormalities, and presence of eustachian valve. Transcatheter PFO closure was performed using devices from AGA Medical Corporation and St. Jude Medical Incorporated, based on specific intracardiac echocardiographic findings. Follow-up included TEE, TC-D, MIDAS, and clinical interviews.
Results: Eighty-six patients (79% female, mean 35 ± 6.7 years) were enrolled and 40 met criteria for transcatheter PFO closure. Patients ineligible for PFO closure received standard of care medical management. Transcatheter PFO closure was successful and performed without periprocedural complications in all 40 subjects. The Amplatzer PFO Occluder was used in eight patients, Amplatzer Cribriform Occluder in 14 patients, and Premere occlusion system in 18 patients. At a mean follow-up of 29.2 ± 14.8 months, mean MIDAS score had fallen from 35.8 ± 4.7 to 8.3 ± 7.8 (p < 0.03) in the PFO closure group, and from 22.6 ± 7.1 to 19.1 ± 8.2 (p = 0.06) in the medical management group. PFO closure without residual shunt was achieved in 95% of subjects. Of 32 subjects who reported migraine with aura at baseline, all subjects reported abolishment of aura at follow-up. New-onset atrial fibrillation developed in 5% of PFO closure patients during follow-up.
Conclusions: In a highly selected population of patients with medically-refractory migraines and PFO with certain proposed high-risk anatomic and functional features, transcatheter PFO closure resulted in a marked reduction in migraine severity and abolition of aura.
Perspective: The MIST (Migraine Intervention with Starflex Technology) study, a large, randomized, sham-controlled study, failed to demonstrate significant symptomatic improvement in patients with migraine undergoing PFO closure. The question remains as to whether a subset of selected patients with migraine might benefit from PFO closure. This nonrandomized, possibly nonconsecutive, series reported by Rigatelli et al. is unique in its selection of patients with high-risk characteristics (for R-L shunt and microembolism) for PFO closure. This kind of highly selected group (whether using the described characteristics or others) may represent a subset of migraineurs more likely to respond to transcatheter therapy. However, the absence of a sham-control group and randomization of consecutive subjects severely limit the generalization of these data. Timothy B. Cotts, M.D., F.A.C.C., Bryan Goldstein, M.D.

[Chevychelov]

Title: Gene-Expression Profiling for Rejection Surveillance After Cardiac Transplantation
Topic: Heart Failure/Transplant
Date Posted: 4/28/2010
Author(s): Pham MX, Teuteberg JJ, Kfoury AG, et al., on behalf of the IMAGE Study Group.
Citation: N Engl J Med 2010;Apr 22:[Epub ahead of print].
Clinical Trial: yes
Study Question: What is the utility of peripheral blood gene-expression profiling compared to endomyocardial biopsy for monitoring of rejection in patients following heart transplantation?
Methods: A total of 602 patients who had undergone cardiac transplantation 6 months to 5 years previously were randomly assigned to be monitored for rejection with the use of gene-expression profiling or with the use of routine endomyocardial biopsies, in addition to clinical and echocardiographic assessment of graft function. A noninferiority comparison of the two approaches was performed with respect to the composite primary outcome of rejection with hemodynamic compromise, graft dysfunction due to other causes, death, or retransplantation.
Results: During a median follow-up period of 19 months, patients who were monitored with gene-expression profiling and those who underwent routine biopsies had similar 2-year cumulative rates of the composite primary outcome (14.5% and 15.3%, respectively; hazard ratio with gene-expression profiling, 1.04%; 95% confidence interval, 0.67-1.68). The 2-year rates of death from any cause were also similar in the two groups (6.3% and 5.5%, respectively; p = 0.82). Patients who were monitored with the use of gene-expression profiling underwent fewer biopsies per person-year of follow-up than did patients who were monitored with the use of endomyocardial biopsies (0.5 vs. 3.0, p < 0.001).
Conclusions: The authors concluded that among selected patients who had received a cardiac transplant more than 6 months previously and who were at a low risk for rejection, a strategy of monitoring for rejection that involved gene-expression profiling, as compared with routine biopsies, was not associated with an increased risk of serious adverse outcomes and resulted in the performance of significantly fewer biopsies.
Perspective: Routine endomyocardial biopsy is the standard method of monitoring for rejection in recipients of a cardiac transplant; however, this is an invasive procedure associated with risks and patient discomfort. Previous studies have demonstrated that scores derived from analysis of the expression of 11 informative genes from peripheral blood mononuclear cells correlate well with histologic rejection, leading to a commercially available test (Allomap). This test may be useful in reducing the need for some endomyocardial biopsies, although the current study was not blinded and only 20% of eligible patients were enrolled due to patient or physician preferences. The applicability of this approach to the general transplant population will require further study with additional larger trials. Daniel T. Eitzman, M.D., F.A.C.C.

[Chevychelov]

Title: Carotid Intima-Media Thickness and Presence or Absence of Plaque Improves Prediction of Coronary Heart Disease: The ARIC (Atherosclerosis Risk In Communities) Study
Topic: Noninvasive Cardiology
Date Posted: 4/29/2010
Author(s): Nambi V, Chambless L, Folsom AR, et al.
Citation: J Am Coll Cardiol 2010;55:1600-1607.
Clinical Trial: No
Related Resources
JACC Article: Carotid Intima-Media Thickness and Presence or Absence of Plaque Improves Prediction of Coronary Heart Disease: The ARIC (Atherosclerosis Risk In Communities) Study
Trial: Atherosclerosis Risk in Communities (ARIC)

Study Question: Does carotid intima-media thickness (CIMT) and the presence of plaque improve coronary heart disease (CHD) risk prediction when used with traditional risk factors?
Methods: Data from the Atherosclerosis Risk in Communities (ARIC) study, of 15,792 subjects (between 45 and 64 years old) from four US communities were used for the present analysis. Risk factor prediction models were considered for the total cohort of men and women. Models included traditional risk factors only, or risk factors with CIMT. Additional models included traditional risk factors and the presence of carotid plaque, and the traditional risk factors with CIMT together with plaque. Models were compared using the receiver-operating characteristic curve (AUC). Cox proportional hazard models were used to estimate 10-year risk for CHD. Number of subjects reclassified was also determined for each of the models.
Results: Of the 13,145 subjects included (5,682 men and 7,463 women), there were 1,812 CHD events over a 15.1-year follow-up. Plaque was observed in 13.6% of those with a CIMT in the <25th percentile, in 26.6% of those with a CIMT in the 25th-75th percentile, and 65.3% of those with a CIMT in the >75th percentile. An estimated 23% of the subjects were reclassified when CIMT and plaque were added to the models. CIMT and plaque resulted in the greatest improvement in the AUC; increasing from 0.742 for traditional risk factors only to 0.755 when both CIMT and plaque were added to the model. These models (containing both CIMT and plaque) also had the best net reclassification index in the overall population. For women, adding plaque to the traditional risk factors model had a more pronounced effect on the AUC than did the addition of CIMT. In contrast, adding CIMT to the traditional risk factors model had a more pronounced effect on the AUC than did the addition of plaque for men.
Conclusions: The authors concluded that the addition of CIMT and plaque to traditional risk factors improved risk prediction for CHD events.
Perspective: Addition of characteristics to present risk prediction models is in part dependent on added accuracy in prediction. However, examining the cost-benefit is needed prior to wide-scale adoption of measures such as CIMT. Elizabeth A. Jackson, M.D., F.A.C.C.

Title: Lipoprotein-Associated Phospholipase A2 and Risk of Coronary Disease, Stroke, and Mortality: Collaborative Analysis of 32 Prospective Studies
Topic: Prevention/Vascular
Date Posted: 4/29/2010 8:00:00 PM
Author(s): The Lp-PLA2 Studies Collaboration.
Citation: Lancet 2010;375:1536-1544.
Clinical Trial: No
Study Question: What is the association between circulating lipoprotein-associated phospholipase A2 (Lp-PLA2) mass and activity with risk of coronary heart disease (CHD), stroke, and mortality under different circumstances?
Methods: A meta-analysis was performed using individual records from 79,036 participants in 32 prospective studies (yielding 17,722 incident fatal or nonfatal outcomes during 475,000 person-years at risk). Within study regressions were used to calculate risk ratios (RRs) per 1 standard deviation (SD) higher value of Lp-PLA2 or other risk factor. The primary outcome was CHD.
Results: Mean age at entry of the 79,036 participants was 64 years (SD 10). Lp-PLA2 activity and mass were associated with each other (r = 0.51; 95% confidence interval, 0.47-0.56) and pro-atherogenic lipids. There were rough log-linear associations of Lp-PLA2 activity and mass with risk of CHD and vascular death. RRs, adjusted for conventional risk factors, were 1.10 with Lp-PLA2 activity and 1.11 with Lp-PLA2 mass for CHD; 1.08 and 1.14 for ischemic stroke; 1.16 and 1.13 for vascular mortality; and 1.10 and 1.0 for nonvascular mortality, respectively. RRs with Lp-PLA2 were similar in people with and without initial stable vascular disease, apart from vascular death with Lp-PLA2 mass. Adjusted RRs for CHD were 1.10 with non–high-density lipoprotein (HDL) cholesterol and 1.10 (1.00-1.21) with systolic blood pressure.
Conclusions: Lp-PLA2 activity and mass each show continuous associations with risk of CHD, similar in magnitude to that with non-HDL cholesterol or systolic blood pressure in this population. Associations of Lp-PLA2 mass and activity are not exclusive to vascular outcomes, and the vascular associations depend at least partly on lipids.
Perspective: The additive relative risk of cardiovascular events associated with Lp-PLA2, an inflammatory enzyme expressed in atherosclerotic plaques, is modest. It is presently being evaluated as a therapeutic target for vascular disease prevention. Melvyn Rubenfire, M.D., F.A.C.C.

[Chevychelov]

Title: Digital Assessment of Endothelial Function and Ischemic Heart Disease in Women
Topic: Prevention/Vascular
Date Posted: 4/30/2010
Author(s): Matsuzawa Y, Sugiyama S, Sugamura K, et al.
Citation: J Am Coll Cardiol 2010;55:1688-1696.
Clinical Trial: No
Related Resources
JACC Article: Digital Assessment of Endothelial Function and Ischemic Heart Disease in Women

Study Question: Does reactive hyperemia peripheral arterial tonometry predict ischemic heart disease in women?
Methods: The study population was comprised of postmenopausal women scheduled for cardiac catheterization as an evaluation of chest pain. Digital reactive hyperemia peripheral arterial tonometry was measured prior to catheterization. Nonobstructive coronary artery disease (CAD) was diagnosed by angiography, including measurement of coronary blood flow and cardiac lactate production during intracoronary acetylcholine provocation testing and cardiac scintigraphy with stress test.
Results: Of the 140 women in whom digital reactive hyperemia peripheral arterial tonometry was measured, 68 (49%) had obstructive CAD and 42 (30%) had nonobstructive CAD. Reactive hyperemia peripheral arterial tonometry indexes were attenuated in both women with obstructive and nonobstructive CAD. In multivariate models, only the digital reactive hyperemia peripheral arterial tonometry index was significantly associated with ischemic heart disease, including obstructive CAD and nonobstructive CAD (odds ratio, 0.51; 95% confidence interval, 0.38-0.68). Reactive hyperemia peripheral arterial tonometry was a significant predictor of ischemic heart disease when added to risk models (area under the curve 0.85).
Conclusions: The investigators concluded that digital reactive hyperemia peripheral arterial tonometry is attenuated in women with ischemic heart disease, including women with nonobstructive CAD. Reactive hyperemia peripheral arterial tonometry may be a useful tool for identification of high-risk women.
Perspective: Further research is warranted to determine if reactive hyperemia peripheral arterial tonometry may assist in the identification of women at greatest risk for CHD events and to understand management of patients with nonobstructive CAD, which can assist in both symptom improvement and reduction in risk of events. Elizabeth A. Jackson, M.D., F.A.C.C.

Title: Long-Term Clinical Consequences of Intense, Uninterrupted Endurance Training in Olympic Athletes
Topic: General Cardiology
Date Posted: 4/30/2010
Author(s): Pelliccia A, Kinoshita N, Pisicchio C, et al.
Citation: J Am Coll Cardiol 2010;55:1619-1625.
Clinical Trial: No
Related Resources
JACC Article: Long-Term Clinical Consequences of Intense, Uninterrupted Endurance Training in Olympic Athletes

Study Question: What is the incidence of cardiac events and/or left ventricular (LV) dysfunction in athletes exposed to strenuous and uninterrupted training for extended periods of time?
Methods: Clinical profile and cardiac dimensions and function were assessed in 114 Olympic athletes (78% male, mean age 22 ± 4 years) free of cardiovascular disease and participating in endurance disciplines, and who experienced particularly intensive and uninterrupted training for 2-5 consecutive Olympic games (total 344 Olympic events), over a 4- to 17-year period (mean 8.6 ± 3 years).
Results: Over the extended period of training and competition, no cardiac events or new diagnoses of cardiomyopathies occurred in the 114 Olympic athletes. Global LV systolic function was unchanged (ejection fraction 62 ± 5% to 63 ± 5%, p = NS), and wall motion abnormalities were absent. In addition, LV diastolic volumes (142 ± 26 ml to 144 ± 25 ml, p = 0.52) and LV mass index (109 ± 21 g/m2 to 110 ± 22 g/m2, p = 0.74) were unchanged, and LV filling patterns remained within normal limits; left atrial dimension showed a mild increase (37.8 ± 3.7 mm to 38.9 ± 3.2 mm, p < 0.001).
Conclusions: In young Olympic athletes, extreme and uninterrupted endurance training over long periods of time (up to 17 years) was not associated with deterioration in LV function, significant changes in LV morphology, or occurrence of cardiovascular symptoms or clinical events.
Perspective: Despite general recommendations for regular physical activity, the world of medicine has a somewhat schizophrenic relationship with athletics. Even though regular physical exercise is associated with a lower incidence of mortal and morbid cardiac events, there remains some trepidation about the safety of more intense athletic competition. These data confirm that athletes who maintain very intense training over an extended period do not suffer cardiac consequences as a result of their athletic conditioning. It seems reasonable to encourage physical activity in practice as well as in principle, now armed with additional data showing that even intense physical conditioning does not represent a cardiac risk. David S. Bach, M.D., F.A.C.C.

[Chevychelov]

Gene Expression Profiles Rejection in Transplants
Three Studies Look at CV
Risk Markers
[Ссылки доступны только зарегистрированным пользователям ]

[Chevychelov]

Title: Effects of Polyunsaturated Omega-3 Fatty Acids on Responsiveness to Dual Antiplatelet Therapy in Patients Undergoing Percutaneous Coronary Intervention The OMEGA-PCI (OMEGA-3 Fatty Acids After PCI to Modify Responsiveness to Dual Antiplatelet Therapy) Study
Topic: Interventional Cardiology
Date Posted: 4/30/2010
Author(s): Gajos G, Rostoff P, Undas A, Piwowarska W.
Citation: J Am Coll Cardiol 2010;55:1671-1678.
Clinical Trial: yes
Related Resources
JACC Article: Effects of Polyunsaturated Omega-3 Fatty Acids on Responsiveness to Dual Antiplatelet Therapy in Patients Undergoing Percutaneous Coronary Intervention The OMEGA-PCI Study

Study Question: What is the effect of omega-3 polyunsaturated fatty acids (PUFAs) on platelet response to dual antiplatelet therapy in patients undergoing percutaneous coronary intervention (PCI)?
Methods: This was an investigator-initiated, prospective, single-center, double-blind, placebo-controlled, randomized study. Patients receiving standard dual antiplatelet therapy (aspirin 75 mg/day and clopidogrel 600 mg loading dose followed by 75 mg/day) were randomly assigned to receive the addition of 1 g of omega-3 ethyl esters (n = 33) or placebo (n = 30) for 1 month. Platelet function was measured serially by light transmission aggregometry (adenosine diphosphate and arachidonic acid [AA] were used as agonists) and assessment of the phosphorylation status of the vasodilator-stimulated phosphoprotein at baseline, 12 hours, 3-5 days, and 30 days after randomization.
Results: The P2Y12 reactivity index was significantly lower, by 22.2%, after 1 month of treatment with omega-3 PUFAs compared with placebo when used in addition to dual antiplatelet therapy (p = 0.020). Maximal platelet aggregation induced by 5 and 20 µmol/L adenosine diphosphate was lower by 13.3% (p = 0.026) and 9.8% (p = 0.029), respectively, after 1 month of treatment with omega-3 PUFAs compared with placebo. Platelet aggregation after AA stimulation was low and did not change significantly throughout the study.
Conclusions: The addition of omega-3 ethyl esters to the combination of aspirin and clopidogrel significantly potentiates platelet response to clopidogrel after PCI.
Perspective: The effectiveness of dual antiplatelet therapy with aspirin and clopidogrel towards reducing stent thrombosis and other ischemic events in patients at high vascular risk has stimulated further interest in refining this therapeutic strategy. Several factors have been shown to contribute to variation in platelet response to clopidogrel, including CYP polymorphisms and interactions with other drugs. Omega-3 PUFAs, at higher doses than the current study, have been previously shown to exert antiplatelet and antithrombotic effects. The current study demonstrates that omega-3 PUFAs are also effective in potentiating the antiplatelet effects of clopidogrel. It will be especially interesting to determine whether omega-3 PUFAs will be effective in reducing stent thrombosis when added to aspirin and clopidogrel, although this will require a much larger study. Daniel T. Eitzman, M.D., F.A.C.C.

Title: Efficacy and Safety of Mipomersen, an Antisense Inhibitor of Apolipoprotein B, in Hypercholesterolemic Subjects Receiving Stable Statin Therapy
Topic: Prevention/Vascular
Date Posted: 4/30/2010
Author(s): Akdim F, Stroes ES, Sijbrands EJ, et al.
Citation: J Am Coll Cardiol 2010;55:1611-1618.
Clinical Trial: No
Related Resources
JACC Article: Efficacy and Safety of Mipomersen, an Antisense Inhibitor of Apolipoprotein B, in Hypercholesterolemic Subjects Receiving Stable Statin Therapy

Study Question: How effective is antisense inhibition of apolipoprotein (apo) B in reducing low-density lipoprotein (LDL) cholesterol when patients are already on statin therapy?
Methods: This was a randomized, placebo-controlled, dose-escalation Phase 2 study designed to evaluate the effects of mipomersen in hypercholesterolemic subjects taking stable statin therapy. Seventy-four subjects were enrolled sequentially into one of six dose cohorts at a 4:1 (active/placebo) ratio. Subjects received seven doses of 300-400 mg over 5 weeks in the first five cohorts and 15 doses of 200 mg over 13 weeks in the sixth cohort. Prespecified endpoints included percentage change from baseline in apo B and LDL cholesterol. Safety was assessed with laboratory test results and by the incidence and severity of adverse events.
Results: The apo B and LDL cholesterol were reduced by 19% to 54% and 21% to 52%, respectively, at doses of 100 mg/wk mipomersen and higher in the 5-week treatment cohorts. Efficacy seemed to increase upon treatment for 13 weeks at a dose of 200 mg/wk. Injection site reactions (mild to moderate erythema [90%]) and hepatic transaminase increases (17%) were the most common adverse events, leading to discontinuation in two subjects and one subject, respectively. In the 13-week treatment cohort, 5 of 10 subjects (50%) had elevations ≥3x the upper limit of normal, four of which persisted on two consecutive occasions.
Conclusions: The authors concluded that mipomersen might hold promise for treatment of patients not reaching target LDL cholesterol levels on stable statin therapy.
Perspective: Reduction of LDL with statin therapy has proven to be effective in reducing cardiovascular events. However, not all patients reach target LDL levels with statins, and additional LDL-lowering therapies may be beneficial for these patients. The current study demonstrates that targeting apo B with antisense therapy may be beneficial in further lowering LDL. Several issues need to be addressed in additional trials including: the effect of mipomersen on LDL in patients treated with higher-dose statins, the implications of transaminase elevations, and whether beneficial effects on atherosclerosis will be achieved with mipomersen. Daniel T. Eitzman, M.D., F.A.C.C.

[Chevychelov]

Title: Finding the Right Job in Clinical Practice or Academia: Advice for Young Clinicians and Investigators
Topic: General Cardiology
Date Posted: 5/3/2010
Author(s): Alpert JS.
Citation: Circulation 2010;121:1862-1865.
Clinical Trial: No
Perspective: The following are 10 points to remember about finding the right job in clinical practice or academia.

1. Before one starts a job search, it is essential to make the very personal decision concerning what type of job one is seeking (i.e., clinical investigation, basic science investigation, clinical practice, clinical practice combined with teaching, industry-related positions, hospital-based employment, and health care administration).

2. To base a career decision on geographic considerations may seem frivolous in this day and age of enhanced communications and travel, but that is to deny the primordial influence that climate, locale, customs, and mores have on our evolving maturation.

3. The kind of job setting that one seeks will determine to a large degree the environment in which you will work. For example, for those who would like to work as a clinician/investigator, it is more than likely that they will find a job in a university hospital or a large private referral hospital linked to a medical school.

4. The curriculum vitae (CV) should be carefully prepared and read by a knowledgeable writer.

5. There are many ways to find job openings (journals, training sites, faculty mentors, etc.). There are many physician placement services that find doctors for a variety of practices. The placement service charges the practice for this service; the trainee does not have to pay anything initially, but the practice may attempt to recoup its investment by placing the cost of the placement service in the newly hired physician’s overhead budget.

6. Once the applicant has been invited to come for an interview with a prospective practice, it is important to gain as much knowledge as possible about the practice, the partners, the environment, the hospitals used by the practice, the status of the financial health of the practice, and the level of happiness of the physicians and staff who work in this setting.

7. Applicants should be friendly, positive, honest, and engaging during the interview and try to give the impression that they would be an asset to the practice or institution that is interviewing them.

8. One should not typically accept the first offer made because it makes the other party to the negotiations feel either that they offered too much at the start or that you are easily convinced to accept anything they propose. It is usually a good idea to have an attorney review the contract and discuss its terms and conditions with you before signing it.

9. Candidates who are international medical graduates must pay attention to the visa requirements for the United States. The prospective employer should be willing to offer them an H-1B visa, and some underserved positions will enable them to get an H-1B visa more easily than others.

10. There is an organization that specializes in helping physicians with opportunities for those who want to devote part of their workday to family concerns such as child rearing ([Ссылки доступны только зарегистрированным пользователям ]). Debabrata Mukherjee, M.D., F.A.C.C.

[Chevychelov]

Title: Multimarker Prediction of Coronary Heart Disease Risk: The Women’s Health Initiative
Topic: Prevention/Vascular
Date Posted: 5/3/2010 5:00:00 PM
Author(s): Kim HC, Greenland P, Rossouw JE, et al.
Citation: J Am Coll Cardiol 2010;55:2080-2091.
Clinical Trial: No
Related Resources
JACC Article: Multimarker Prediction of Coronary Heart Disease Risk: The Women’s Health Initiative

Study Question: To what degree do biomarkers contribute to improved coronary heart disease (CHD) risk prediction in postmenopausal women compared with assessment using traditional risk factors (TRFs) only?
Methods: The Women’s Health Initiative Hormone Trials enrolled 27,347 postmenopausal women ages 50-79 years. Associations of TRFs and 18 biomarkers were assessed in a nested case-control study including 321 patients with CHD and 743 controls. Four prediction equations for 5-year CHD risk were compared: two Framingham risk score covariate models; a TRF model including statin treatment, hormone treatment, and cardiovascular disease history as well as the Framingham risk score covariates; and an additional biomarker model that also included the five significantly associated markers of the 18 tested (interleukin-6, D-dimer, coagulation factor VIII, von Willebrand factor, and homocysteine).
Results: The TRF model showed an improved C-statistic (0.729 vs. 0.699, p = 0.001) and net reclassification improvement (6.42%) compared with the Framingham risk score model. The additional biomarker model showed additional improvement in the C-statistic (0.751 vs. 0.729, p = 0.001) and net reclassification improvement (6.45%) compared with the TRF model. Predicted CHD risks on a continuous scale showed high agreement between the TRF and additional biomarker models (Spearman’s coefficient = 0.918). Among the 18 biomarkers measured, C-reactive protein (CRP) level did not significantly improve CHD prediction either alone or in combination with other biomarkers.
Conclusions: Moderate improvement in CHD risk prediction was found when an 18-biomarker panel was added to predictive models using TRFs in postmenopausal women.
Perspective: While very interesting, this case-control study of the value of biomarkers in predicting CHD events in women adds little for the clinician who would like to know whether the high-sensitivity CRP (hs-CRP) is useful for assessing CHD event risk. The TRF model, which found no value to hs-CRP, included use of statins, hormone treatment, and a history of cardiovascular disease (not defined in the manuscript but prevalence of 14% in the control and 27% in the cases) at baseline. Each was independently associated with increased risk for CHD, but is expected to reduce the incremental value of hs-CRP. Ridker and colleagues demonstrated that the hs-CRP can be used to help decide the value of statin therapy in relatively low-risk men and women (JUPITER study), and that it adds considerably to risk prediction in intermediate- and high-risk women (JAMA 2007;297:611-9). Using the Woman’s Health Study of 24,558 healthy US women followed for cardiovascular events for a median of 10.2 years, adding hs-CRP to TRFs, resulted in reclassification of 40-50% of intermediate-risk into higher- or lower-risk categories with improved accuracy compared to other models. The model that has received the most attention is the Reynold’s Risk Score, which is a simplified model limited to age, systolic blood pressure, glycated hemoglobin if diabetic, current smoking, total and high-density lipoprotein cholesterol, hs-CRP, and parental history of myocardial infarction before age 60 years. Melvyn Rubenfire, M.D., F.A.C.C.

Title: The Prognostic Value of N-Terminal Pro–B-Type Natriuretic Peptide for Death and Cardiovascular Events in Healthy Normal and Stage A/B Heart Failure Subjects
Topic: Heart Failure/Transplant
Date Posted: 5/3/2010 5:00:00 PM
Author(s): McKie PM, Cataliotti A, Lahr BD, et al.
Citation: J Am Coll Cardiol 2010;55:2140-2147.
Clinical Trial: No
Related Resources
JACC Article: The Prognostic Value of N-Terminal Pro–B-Type Natriuretic Peptide for Death and Cardiovascular Events in Healthy Normal and Stage A/B Heart Failure Subjects

Study Question: What is the prognostic value of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) for death and cardiovascular events among subjects without risk factors for heart failure (HF), which we term healthy normal?
Methods: The investigators included a community-based cohort of 2,042 subjects in Olmsted County, Minnesota. Subjects with symptomatic (stage C/D) HF were excluded. The remaining 1,991 subjects underwent an echocardiogram and NT-proBNP measurement. They further defined healthy normal (n = 703) and stage A/B HF (n = 1,288) subgroups. They defined healthy normal as the absence of traditional clinical cardiovascular risk factors and echocardiographic structural cardiac abnormalities. They followed the study participants for mortality, HF, cerebrovascular accident, and myocardial infarction with median follow-up of 9.1, 8.7, 8.8, and 8.9 years, respectively.
Results: The investigators found that NT-proBNP was not predictive of death or cardiovascular events in the healthy normal subgroup. Similar to previous reports, in stage A/B HF, plasma NT-proBNP values greater than age-/sex-specific 80th percentiles were associated with increased risk of mortality, HF, cerebrovascular accident, and myocardial infarction (p < 0.001 for all) even after adjustment for clinical risk factors and structural cardiac abnormalities.
Conclusions: The investigators concluded that these findings do not support the use of NT-proBNP as a cardiovascular biomarker in healthy normal subjects, and have important implications for NT-proBNP–based strategies for early detection and primary prevention of cardiovascular disease.
Perspective: The ability of any diagnostic test, including biomarkers, to enhance the quality and efficacy of clinical care depends on several factors, including pretest probability, sensitivity and specificity, cost, benefits, risks, patient preference, and alternatives (such as continued observation, or proceeding to another test or empirical treatment). An important assumption in the Bayesian model is that a test adds new additional information above and beyond what is already known (Heart Fail Clin 2009;5:463-70). The findings of these investigators suggest that NT-proBNP does not add further value in risk stratification of healthy normal subjects. Other studies have suggested that biomarkers are indeed useful in screening for preclinical disease (N Engl J Med 2004;350:655-63). Larger studies are required to determine the precise utility of biomarkers in healthy subjects. Ragavendra R. Baliga, M.B.B.S.

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Title: Heart Failure With Preserved Ejection Fraction in Outpatients With Unexplained Dyspnea: A Pressure-Volume Loop Analysis
Topic: Heart Failure/Transplant
Date Posted: 5/4/2010
Author(s): Penicka M, Bartunek J, Trakalova H, et al.
Citation: J Am Coll Cardiol 2010;55:1701-1710.
Clinical Trial: No
Related Resources
JACC Article: Heart Failure With Preserved Ejection Fraction in Outpatients With Unexplained Dyspnea: A Pressure-Volume Loop Analysis

Study Question: Is heart failure with preserved ejection fraction (HFPEF) present in outpatients with unexplained chronic dyspnea, and does it elucidate its underlying mechanisms in this population, using invasive pressure-volume loop analysis?
Methods: The study cohort, comprised of 30 patients (ages 67 ± 8.6 years, 27% males) with preserved left ventricular (LV) EF (≥50%) and unexplained chronic New York Heart Association functional class II-III dyspnea, underwent heart catheterization. Patients with significant coronary artery stenosis (≥50%) were excluded. Pressure-volume loops were assessed using a conductance catheter at rest, hand-grip exercise, leg lifting, and nitroprusside and dobutamine infusion.
Results: Sixty-six percent (n = 20) of patients showed LV end-diastolic pressure >16 mm Hg (normal LV systolic function), whereas the remaining 10 patients served as controls. Patients with HFPEF had significantly higher end-diastolic stiffness (0.205 ± 0.074 vs. 0.102 ± 0.017, p < 0.001) at rest, and their end-diastolic pressure-volume relationship showed a consistent upward and leftward shift during all hemodynamic interventions compared with controls. Regarding the underlying mechanism of HFPEF, 70% (n = 14) of patients had markedly increased end-diastolic stiffness, which was considered a sufficient single pathology to induce increased LV end-diastolic pressure. Twenty percent (n = 4) of patients showed a concomitant presence of moderately increased stiffness and severe LV dyssynchrony, and the remaining 10% (n = 2) of patients, with normal stiffness, showed significant exercise-induced mitral regurgitation at hand-grip exercise. According to the study investigators, if the invasive pressure measurements were absent, only 25% (n = 5) of the outpatients with HFPEF fulfilled the European Society of Cardiology definition of HFPEF.
Conclusions: The authors concluded that a significant proportion of stable outpatients with unexplained chronic dyspnea may have HFPEF. In this cohort, increased LV stiffness, dyssynchrony, and dynamic mitral regurgitation were the major mechanisms underlying development of HFPEF.
Perspective: This is an important study because it suggests that patients with unexplained dyspnea may benefit from a right heart catheterization to determine the pulmonary capillary wedge pressure (as a surrogate for LV end-diastolic pressure) to make a diagnosis of HF. It has always been argued that HF is a ‘clinical’ diagnosis, but as technology evolves, we may continue to detect new HF patients that were hitherto undetected. Ragavendra R. Baliga, M.B.B.S.

Title: Relationship Between Early Physician Follow-up and 30-Day Readmission Among Medicare Beneficiaries Hospitalized for Heart Failure
Topic: Heart Failure/Transplant
Date Posted: 5/4/2010 4:00:00 PM
Author(s): Hernandez AF, Greinger MA, Fonarow GC, et al.
Citation: JAMA 2010;303:1716-1722.
Clinical Trial: No
Study Question: What is the association between outpatient follow-up within 7 days after discharge from a heart failure (HF) hospitalization and readmission within 30 days?
Methods: The study cohort consisted of 30,136 patients from 225 hospitals. The study was an observational analysis of patients ages ≥65 years with HF and discharged to home from hospitals participating in the HF quality improvement program from January 1, 2003, through December 31, 2006. The main outcome measure was all-cause readmission within 30 days after discharge.
Results: Median length of stay was 4 days (interquartile range, 2-6) and 21.3% of patients were readmitted within 30 days. At the hospital level, the median percentage of patients who had early follow-up after discharge from the index hospitalization was 38.3% (interquartile range, 32.4-44.5%). Compared with patients whose index admission was in a hospital in the lowest quartile of early follow-up (30-day readmission rate, 23.3%), the rates of 30-day readmission were 20.5% among patients in the second quartile (risk adjusted hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.78-0.93), 20.5% among patients in the third quartile (risk-adjusted HR, 0.87; 95% CI, 0.78-0.96), and 20.9% among patients in the fourth quartile (risk-adjusted HR, 0.91; 95% CI, 0.83-1.00).
Conclusions: The authors concluded that patients who are discharged from hospitals that have higher early follow-up rates have a lower risk of 30-day readmission.
Perspective: From Ragavendra R. Baliga, M.B.B.S.: This is an important study because it confirms what HF physicians have always known about the importance of timely follow-up of patients after discharge from an index HF hospitalization. The data from this study are particularly helpful to hospitals trying to put together a strategy to reduce re-admission rates for hospitalizations. It has been argued that all HF patients who are admitted to a hospital be managed by a Heart Failure Response Team whose responsibilities include ensuring that patients are scheduled for early follow-up (Heart Fail Clin 2009;5:xi-xiv). It would be interesting to know whether early and regular follow-up of HF patients eventually also results not only in reduced hospitalizations, but also in improved long-term survival.

Expert Commentary From Alfred A. Bove, M.D.: Until now, early follow-up for HF patients after discharge had face validity only. This study confirms the importance of establishing coordinated systems of care in which patients are evaluated early after discharge.

The American College of Cardiology's national quality improvement initiative, Hospital to Home (H2H), identifies early follow-up as one of three core concepts for reducing hospital readmissions. Discharged patients should have a follow-up visit scheduled within 1 week of discharge, as well as the means of getting to that appointment.

Providing support during the transition from inpatient to outpatient status is essential. Hospitals participating in the H2H initiative have increased scheduled appointments by having office practices block appointment slots for discharged patients and by having prepurchased time available.

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Title: Pneumococcal Vaccination and Risk of Acute Myocardial Infarction and Stroke in Men
Topic: Prevention/Vascular
Date Posted: 5/4/2010 4:00:00 PM
Author(s): Tseng HF Slezak JM, Quinn VP, et al.
Citation: JAMA 2010;303:1699-1706.
Clinical Trial: No
Study Question: Multiple studies have shown that preventing influenza by vaccination reduces the risk of vascular events. What is the association between pneumococcal vaccination and risk of acute myocardial infarction (MI) and stroke among men?
Methods: A prospective cohort study was conducted in participants in the California Men’s Health Study (ages 45-69 years) recruited between January 2002 and December 2003, and followed up until December 31, 2007. Demographic and detailed lifestyle characteristics were collected from surveys. Vaccination records were obtained from the Kaiser Immunization Tracking System. Primary outcome was the incidence of acute MI and stroke during the follow-up period in men who had no previous events.
Results: Of the nearly 400,000 men, 63% were white, 14% Hispanic, 7% black, and 8.2% Asian. Hypertension, diabetes, heart failure, and peripheral vascular disease were lower in those unvaccinated. During follow-up, there were 1,211 first MIs in vaccinated person-years (10.73 per 1,000 person-years) compared with 1,494 first MI events in unvaccinated person-years (6.07 per 1,000 person-years). For stroke, there were 651 events in vaccinated person-years (5.30 per 1,000 person-years) compared with 483 events in unvaccinated person-years (1.90 per 1,000 person-years). With propensity score adjustment, there was no evidence for an association between pneumococcal vaccination and reduced risk of acute MI (adjusted hazard ratio [HR], 1.09; 95% confidence interval [CI], 0.98-1.21) or stroke (adjusted HR, 1.14; 95% CI, 1.00-1.31). An inverse association was also not found in men of different age and risk groups.
Conclusions: Among a cohort of men ages 45 years or older, receipt of pneumococcal vaccine was not associated with subsequent reduced risk of acute MI and stroke.
Perspective: The relationship between inflammatory markers and acute and chronic inflammation and infections and development of acute coronary syndromes is well established. Guidelines recommend pneumococcal vaccine for men and women with cardiovascular disease, diabetics, and all persons over 65 years old. About one-third of participants in this cohort study were given vaccines. From available data, those who received the vaccine were higher risk, yet accrued no benefit. Should this study be used to change the present guidelines? Certainly not for patients with established coronary disease and strokes who were excluded from this study. As with so many other preventive measures, the results of this study should be considered hypothesis generating for a controlled trial, perhaps in middle-aged and elderly men who are at intermediate risk for coronary events and strokes. The impact of other preventive treatments such as aspirin and statins on the relative value of pneumococcal vaccine cannot be assessed with this study. Melvyn Rubenfire, M.D., F.A.C.C.

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Title: Blood-Pressure Reduction With LCZ696, A Novel Dual-Acting Inhibitor of the Angiotensin II Receptor and Neprilysin: A Randomized, Double-Blind, Placebo-Controlled, Active Comparator Study
Topic: Prevention/Vascular
Date Posted: 5/5/2010
Author(s): Ruilope LM, Dukat A, Bohm M, Lacourciere Y, Gong J, Lefkowitz MP.
Citation: Lancet 2010;375:1255-1266.
Clinical Trial: yes
Study Question: Does the added effect of neprilysin inhibition to angiotensin II blockade improve blood pressure control?
Methods: A total of 1,328 patients ages 18-75 years with mild-to-moderate hypertension were randomly assigned (double-blind) to 8 weeks’ treatment in one of eight groups: 100 mg (n = 156 patients), 200 mg (n = 169), or 400 mg (n = 172) LCZ696; 80 mg (n = 163), 160 mg (n = 166), or 320 mg (n = 164) valsartan; 200 mg AHU377 (n = 165); or placebo (n = 173). The primary endpoint was the mean difference across the three single-dose pair-wise comparisons of LCZ696 versus valsartan (100 mg vs. 80 mg, 200 mg vs. 160 mg, and 400 mg vs. 320 mg) in mean sitting diastolic blood pressure during the 8-week treatment period. Analysis was by intention to treat.
Results: The reduction in diastolic blood pressure across the doses of LCZ696 versus the appropriate comparator dose of valsartan showed significantly greater reductions with LCZ696 (mean reduction, –2.17 mm Hg; 95% confidence interval [CI], –3.28 to –1.06; p < 0.0001). The reduction in diastolic blood pressure was significantly different for 200 mg LCZ696 versus 160 mg valsartan (–2.97 mm Hg; 95% CI, –4.88 to –1.07; p = 0.0023) and for 400 mg LCZ696 versus 320 mg valsartan (–2.70 mm Hg; –4.61 to –0.80; p = 0.0055). LCZ696 was well tolerated and no cases of angioedema were reported.
Conclusions: The authors concluded that compared with valsartan, dual-acting LCZ696 provides complementary and fully additive reduction of blood pressure.
Perspective: Neprilysin is an endopeptidase that may play a role in a variety of disease processes, including hypertension. A previous clinical study using an inhibitor of neprilysin alone did not demonstrate meaningful reductions in blood pressure, which may have been due to reduced neprilysin-dependent breakdown of angiotensin II. The current study thus demonstrates that in the setting of angiotensin II inhibition, additional reduction of blood pressure occurs with inhibition of neprilysin (although in this trial, monotherapy with a neprilysin inhibitor also reduced blood pressure slightly). In contrast to previous trials with the vasopeptidase inhibitor, omapatrilat, angioedema did not occur. Additional trials in a more diverse population are necessary to determine safety and also assess which patients are likely to benefit from this type of treatment. Daniel T. Eitzman, M.D., F.A.C.C.

Title: Minimally Invasive Versus Conventional Mitral Valve Surgery: A Propensity-Matched Comparison
Topic: Cardiovascular Surgery
Date Posted: 5/5/2010
Author(s): Svensson LG, Atik FA, Cosgrove DM, et al.
Citation: J Thorac Cardiovasc Surg 2010;139:926-932.
Clinical Trial: No
Study Question: How do outcomes compare after minimally invasive mitral valve surgery versus conventional surgery with medial sternotomy?
Methods: From January 1995 to January 2004 at a single, very large institution, 2,124 patients underwent isolated mitral valve surgery through a minimally invasive approach, and 1,047 underwent isolated mitral valve surgery through a conventional sternotomy. A propensity score based on 42 factors was used to obtain 590 well-matched patient pairs (56% of cases).
Results: In-hospital mortality was similar for propensity-matched patients: 0.17% (1 of 590) for those undergoing minimally invasive surgery and 0.85% (5 of 590) for those undergoing conventional surgery (p = 0.2). Occurrences of stroke (p = 0.8), renal failure (p > 0.9), myocardial infarction (p = 0.7), and infection (p = 0.8) also were similar. However, 24-hour mediastinal drainage was less after minimally invasive surgery (median 250 vs. 350 ml, p < 0.0001), and fewer patients received transfusions (30% vs. 37%, p = 0.01). More patients undergoing minimally invasive surgery were extubated in the operating room (18% vs. 5.7%, p < 0.0001), and postoperative forced expiratory volume in 1 second was higher. Early after operation, pain scores were lower (p < 0.0001) after minimally invasive surgery.
Conclusions: Within that portion of the spectrum of mitral valve surgery in which propensity matching was possible, minimally invasive mitral valve surgery had cosmetic, blood product use, respiratory, and pain advantages over conventional surgery, and no measured detriments. Mortality and morbidity for robotic and percutaneous procedures should be compared with these minimally invasive outcomes.
Perspective: This study from The Cleveland Clinic used propensity matching to attempt to compensate for differences between patients operated on using conventional sternotomy versus various less invasive approaches. (Minimally invasive operations involved an 8-10 cm [3-4 inch] skin incision, variably right paramedian including division of the third and fourth costal cartilages, a ‘J’ incision from the sternal notch to the fourth intercostal space, or partial right lower sternotomy; but not right minithoracotomy or robotic procedures.) The findings, and the thoughtful inclusion of study limitations in the manuscript, speak for themselves. There should be little debate that the same operation performed using a small incision would be better than that using a large incision. The debate is whether the operation is the same, and how universally applicable are the operative results. Ultimately, the ability to perform mitral valve repair rather than replacement, and the adequacy of the repair, should be more important issues than the size of the scar or even measures of postoperative mediastinal drainage and forced expiratory volume. At this high-volume center, surgeons were able to perform similar (and good) operations using a smaller incision compared to conventional sternotomy. But patients, providers, and insurers should remember and embrace that it is the quality of the surgery, not the size of the scar, that should be of paramount importance. David S. Bach, M.D., F.A.C.C.

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Title: Everolimus-Eluting Versus Paclitaxel-Eluting Stents in Coronary Artery Disease
Topic: Interventional Cardiology
Date Posted: 5/5/2010 4:00:00 PM
Author(s): Stone GW, Rizvi A, Newman W, et al.
Citation: N Engl J Med 2010;362:1663-1674.
Clinical Trial: yes
Study Question: What is the comparative efficacy of everolimus-eluting versus paclitaxel-eluting stents?
Methods: The investigators randomly assigned 3,687 patients at 66 US sites to receive everolimus-eluting or paclitaxel-eluting stents without routine follow-up angiography. The primary endpoint was a 1-year composter rate of target lesion failure (defined as cardiac death, target vessel myocardial infarction, or ischemia-driven target lesion revascularization).
Results: Everolimus-eluting stents were superior to paclitaxel-eluting stents with respect to the primary endpoint of target lesion failure (4.2% vs. 6.8%; relative risk, 0.62; 95% confidence interval, 0.46-0.82; p = 0.001). Everolimus-eluting stents were also superior with respect to the major secondary endpoint of the 1-year rate of ischemia-driven target lesion revascularization (p = 0.001) and were noninferior with respect to the major secondary endpoint of the 1-year composite rate of cardiac death target lesion myocardial infarction (p < 0.001 for noninferiority, p = 0.09 for superiority). The 1-year rates of myocardial infarction and stent thrombosis were also lower with everolimus-eluting stents than with paclitaxel-eluting stents (1.9% vs. 3.1%; p = 0.02 for myocardial infarction; 0.17% vs. 0.85%; p = 0.004 for stent thrombosis). Target lesion failure was consistently reduced with everolimus-eluting stents as compared with paclitaxel-eluting stents in 12 prespecified subgroups, except in the subgroup of patients with diabetes (6.4% vs. 6.9%, p = 0.80).
Conclusions: The authors concluded that everolimus-eluting as compared with paclitaxel-eluting stents, resulted in reduced rates of target vessel failure at 1 year.
Perspective: In this prospective, randomized trial, everolimus-eluting stents as compared with paclitaxel-eluting stents resulted in reduced 1-year rate of target lesion failure and ischemia-driven target lesion revascularization. The rates of myocardial infarction and stent thrombosis were also lower with everolimus-eluting stents. The study suggests that with drug-eluting stents, it is possible to achieve minimal late loss with improved clinical efficacy, but without sacrificing safety or any increase in stent thrombosis. The lack of superiority of everolimus-eluting stents among diabetics calls for additional research on newer drugs in this high-risk cohort. Additional studies comparing everolimus-eluting stents with sirolimus- and zotarolimus-eluting stents are also indicated to gauge comparative efficacy with other drug-eluting stents. Debabrata Mukherjee, M.D., F.A.C.C

Title: The Effect of Optimal Medical Therapy on 1-Year Mortality After Acute Myocardial Infarction
Topic: General Cardiology
Date Posted: 5/6/2010
Author(s): Bramlage P, Messer C, Bitterlich N, et al.
Citation: Heart 2010;96:604-609.
Clinical Trial: No
Study Question: Five drug classes have been shown to improve the prognosis of acute myocardial infarction (AMI) in clinical trials: aspirin, beta-blockers, statins, renin angiotensin system (RAS) blockers, and thienopyridines. Does combining these drugs (termed optimal medical therapy [OMT]) result in a reduction in mortality in the clinical practice setting?
Methods: The SAMI (Secondary prevention after Acute Myocardial Infarction) registry was conducted in 2003-2004 in 5,353 patients with an AMI in 79 hospitals in Germany with a cardiology unit or internal medicine department. The primary outcome was the odds ratio (OR) and 95% confidence interval (CI) for mortality from MI in relationship to OMT adjusted for patient risk at baseline.
Results: Mean age was 66.3 years in the OMT group and 70.5 years in the suboptimal group; the type of AMI was ST-elevation MI (STEMI) in 54% in each group; and significantly more in the OMT group were taking one or more of the five drugs on admission. About 63% of each group had a percutaneous transluminal coronary angioplasty and 5% a coronary artery bypass graft (CABG), and >60% were given thrombolytics within 1 hour. At hospital discharge, 89% received aspirin, 90% beta-blockers, 84% statins, 81% RAS blockers, 70% a thienopyridine, and 46.2% OMT. Patients receiving OMT were younger, more frequently male, had more risk factors including nicotine use, hypertension, dyslipidemia, and more often had a history of a CABG. Total mortality was reduced by 74% in patients receiving OMT (adjusted OR, 0.26; 95% CI, 0.18-0.38) versus patients receiving one or no drug. This was consistent in subgroups defined by STEMI/NSTEMI, diabetes, and gender. Mortality was also reduced in patients receiving 2-4 drugs (adjusted OR, 0.49; 95% CI, 0.35-0.68), diabetic patients being the only subgroup with no significant effect. Analyses on the relative importance of either component revealed that withdrawal of beta-blockers (adjusted OR, 0.63; 95% CI, 0.34-1.16) and/or a combination of aspirin/clopidogrel (adjusted OR, 0.59; 95% CI, 0.20-1.17) abolished the risk reduction conferred by OMT.
Conclusions: OMT over 1 year was associated with a significantly lower mortality of patients with AMI in clinical practice. However, OMT is provided to less than half of eligible patients, leaving room for substantial improvement.
Perspective: The percentage of patients discharged on one or more of the five classes of drugs shown to have benefit in patients with an AMI in this study is impressive, but less than 50% received OMT. Increased mortality when withdrawing aspirin/clopidogrel from OMT is not surprising. I am particularly impressed with the impact of withdrawing beta-blockers from OMT on 1-year mortality, considering the mean left ventricular ejection fraction of 56% and the frequency of coronary revascularization. Melvyn Rubenfire, M.D., F.A.C.C.

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Title: The Temporal Variability of Dominant Frequency and Complex Fractionated Atrial Electrograms Constrains the Validity of Sequential Mapping in Human Atrial Fibrillation
Topic: Arrhythmias
Date Posted: 5/6/2010
Author(s): Habel N, Znojkiewicz P, Thompson N, et al.
Citation: Heart Rhythm 2010;7:586-593.
Clinical Trial: No
Study Question: Are dominant frequency (DF) and complex fractionated atrial electrograms (CFAEs) temporally stable during atrial fibrillation (AF)?
Methods: A 64-electrode basket catheter was used to simultaneously record multiple left atrial electrograms for 5 minutes during AF in 18 patients (mean age 60 years) prior to catheter ablation. DF was determined by fast Fourier transformation for each 5-second interval in the 5-minute recordings. CFAEs were identified using commercially available software.
Results: The mean temporal coefficient of variability for DF was 22.7%. CFAEs also were temporally unstable, having a mean duration of 8.8 seconds at individual sites. Sequential DF maps identified only 7% of DF sites, and sequential CFAE maps identified 64% of CFAE sites.
Conclusions: DF and CFAE maps created by sequential point-by-point acquisition of electrograms are of limited value because of temporal instability in DF and CFAEs.
Perspective: Ideally, DF and CFAE maps would be generated by simultaneous multisite recordings, but this is not clinically practical. However, the clinical impact of temporal instability in DF is unclear, particularly since it is not even clear that DF mapping is useful for identifying target sites for catheter ablation of AF. CFAEs commonly are used in clinical practice to select ablation sites, and this study shows that short sampling times may fail to identify CFAEs that are intermittent. However, intermittent CFAEs may not be as specific for appropriate target sites as are persistent CFAEs, so the clinical impact of temporal instability of CFAEs also is unclear. Fred Morady, M.D., F.A.C.C.

Title: Verapamil Eliminates the Hierarchical Nature of Activation Frequencies From the Pulmonary Veins to the Atria During Paroxysmal Atrial Fibrillation
Topic: Arrhythmias
Date Posted: 5/6/2010
Author(s): Kushiyama Y, Osaka T, Yokoyama E, et al.
Citation: Heart Rhythm 2010;7:577-583.
Clinical Trial: No
Study Question: How does verapamil affect dominant frequency (DF) in the pulmonary veins (PVs) and atria during atrial fibrillation (AF)?
Methods: Fast Fourier transform analysis to identify the DF was performed on electrograms recorded at the right atrial free wall (RAFW), coronary sinus (CS), left atrial appendage (LAA), and PVs during AF in 43 patients (mean age 57 years) with paroxysmal AF. Electrograms were recorded before and after infusion of 0.1 mg/kg of verapamil.
Results: At baseline, the maximum DF in the PVs (6.9 Hz) was significantly higher than the DF at the RAFW (6.2 Hz), CS (5.7 Hz), and LAA (5.9 Hz). Verapamil significantly increased DF at the RAFW, CS, and LAA to 6.9, 6.6, and 7.2 Hz, respectively. The maximum DF in the PVs increased to 7.1 Hz. After verapamil infusion, there was no significant difference in DF between the atria and PVs.
Conclusions: The frequency gradient between the PVs and atria during an episode of paroxysmal AF is abolished by verapamil.
Perspective: A higher DF in the PVs than in the atria is consistent with the observation that the PV muscle sleeves often provide the drivers that maintain an episode of paroxysmal AF. Verapamil increases DF in the atria by shortening action potential duration. Elimination of the DF gradient by verapamil suggests that the drug could be proarrhythmic by creating new high-frequency sources of AF in the atria during paroxysmal AF. Nevertheless, no studies have demonstrated clinically significant proarrhythmia from the use of calcium channel blockers in patients with AF. Fred Morady, M.D., F.A.C.C.

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Multi-marker Prediction of CHD Risk
Biomarkers, DES, and Vaccines
[Ссылки доступны только зарегистрированным пользователям ]


Title: Relationships Between Emerging Measures of Heart Failure Processes of Care and Clinical Outcomes
Topic: Heart Failure/Transplant
Date Posted: 5/7/2010
Author(s): Hernandez AF, Hammill BG, Peterson ED, et al.
Citation: Am Heart J 2010;159:406-413.
Clinical Trial: No
Study Question: What is the relationship between emerging measures of heart failure processes of care and clinical outcomes?
Methods: The investigators used data for 20,441 Medicare beneficiaries in the OPTIMIZE-HF trial from March 2003 through December 2004, which they linked to Medicare claims data. They examined associations between hospital-level processes of care and patient outcomes. Performance measures included any beta-blocker for patients with left ventricular systolic dysfunction (LVSD); evidence-based beta-blocker for patients with LVSD; warfarin for patients with atrial fibrillation; aldosterone antagonist for patients with LVSD; implantable cardioverter defibrillator for patients with ejection fraction ≤35%; and referral to disease management. Outcome measures were unadjusted and adjusted associations of each process measure with 60-day and 1-year mortality and cardiovascular readmission at the hospital level.
Results: The investigators found that adjusted hazard ratios for 1-year mortality with a 10% increase in hospital-level adherence were 0.94 for any beta-blocker (95% confidence interval [CI], 0.90-0.98; p = 0.004), 0.95 for evidence-based beta-blocker (95% CI, 0.92-0.98; p = 0.004), 0.97 for warfarin (95% CI, 0.92-1.03; p = 0.33), 0.94 for aldosterone antagonists (95% CI, 0.91-0.98; p = 0.006), 0.92 for implantable cardioverter defibrillator (95% CI, 0.87-0.98; p = 0.007), and 1.01 for referral to disease management (95% CI, 0.99-1.03; p = 0.21).
Conclusions: The authors concluded that several evidence-based processes of care are associated with improved outcomes, can discriminate hospital-level quality of care, and could be considered as clinical performance measures.
Perspective: This study suggests that including all the key indicators of quality makes a substantial impact on medication compliance and consequently morbidity and mortality. Currently, ‘core-measures’ include only ACE inhibitor usage in heart failure, but this study suggests that including all the other therapies including beta-blocker and aldosterone antagonist utilization in the ‘core-measures’ should considerably improve the quality of care. Ragavendra R. Baliga, M.B.B.S.