Обзор американских кардиологических журналов за неделю (ссылки)

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Extended-Release Niacin or Ezetimibe and Carotid Intima-Media Thickness
Taylor AJ, Villines TC, Stanek EJ, et al.
N Engl J Med 2009;Nov 15:[Epub ahead of print].
Study Question: What is the effect of niacin or ezetimibe on common carotid intima-media thickness (CIMT) when added to statin therapy?
[Ссылки доступны только зарегистрированным пользователям ]

Cardiovascular and Noncardiovascular Mortality Among Patients Starting Dialysis
de Jager DJ, Grootendorst DC, Jager KJ, et al.
JAMA 2009;302:1782-1789.
Study Question: Cardiovascular (CV) mortality is considered the main cause of death in patients receiving dialysis and is 10 to 20 times higher in such patients than in the general population. Is the high overall mortality in patients with end-stage renal disease (ESRD) starting dialysis a consequence of increased CV mortality risk only, or is non-CV mortality equally increased?
[Ссылки доступны только зарегистрированным пользователям ]

Ferric Carboxymaltose in Patients With Heart Failure and Iron Deficiency
Anker SD, Colet JC, Filippatos G, et al., on behalf of the FAIR-HF Trial Investigators.
N Engl J Med 2009;Nov 17:[Epub ahead of print].
Study Question: Does treatment with intravenous iron (ferric carboxymaltose) improve symptoms in systolic HF and iron deficiency, either with or without anemia?
[Ссылки доступны только зарегистрированным пользователям ]

Effects of High-Dose Versus Low-Dose Losartan on Clinical Outcomes in Patients With Heart Failure (HEAAL Study): A Randomized, Double-Blind Trial
Konstam MA, Neaton JD, Dickstein K, et al.
Lancet 2009;374:1840-8.
Study Question: How does high-dose losartan (an angiotensin-receptor blocker [ARB]) compare versus low-dose losartan on clinical outcomes in patients with heart failure (HF)?
[Ссылки доступны только зарегистрированным пользователям ]

Advanced Heart Failure Treated With Continuous-Flow Left Ventricular Assist Device
Slaughter MS, Rogers JG, Milano CA, et al., on behalf of the HeartMate II Investigators.
N Engl J Med 2009;Nov 17:[Epub ahead of print].
Study Question: How does the newer HeartMate II left ventricular assist device (LVAD; a continuous-flow device) compare with the older more durable HeartMate XVE (a pulsatile-flow device)?
[Ссылки доступны только зарегистрированным пользователям ]

Platelet Inhibition With Cangrelor in Patients Undergoing PCI
Harrington RA, Stone GW, McNulty S, et al., on behalf of CHAMPION PCI Investigators.
N Engl J Med 2009;Nov 15:[Epub ahead of print].
Study Question: What is the benefit of cangrelor, a reversible adenosine diphosphate (ADP) receptor antagonist, in patients undergoing percutaneous coronary intervention (PCI)?
[Ссылки доступны только зарегистрированным пользователям ]

Intravenous Platelet Blockade With Cangrelor During PCI
Bhatt DL, Lincoff AM, Gibson CM, et al., on behalf of the CHAMPION PLATFORM Investigators.
N Engl J Med 2009;Nov 15:[Epub ahead of print].
Study Question: What is the benefit of cangrelor, a reversible adenosine diphosphate (ADP) receptor antagonist, in patients undergoing percutaneous coronary intervention (PCI)?
[Ссылки доступны только зарегистрированным пользователям ]

Absolute Myocardial Blood Flow Determination Using Real-Time Myocardial Contrast Echocardiography During Adenosine Stress: Comparison With Single-Photon Emission Computed Tomography
Abdelmoneim SS, Dhoble A, Bernier M, et al.
Heart 2009;95:1662-1668.
Study Question: What is the feasibility and accuracy of real-time myocardial contrast echocardiography (MCE) to detect myocardial perfusion abnormalities using simultaneous technetium 99 m sestamibi single-photon emission computed tomography (SPECT) as a standard?
[Ссылки доступны только зарегистрированным пользователям ]

A Selective Endothelin-Receptor Antagonist to Reduce Blood Pressure in Patients With Treatment-Resistant Hypertension: A Randomised, Double-Blind, Placebo-Controlled Trial
Weber MA, Black H, Bakris G, et al.
Lancet 2009;374:1423-1431.
Study Question: What is the blood pressure-lowering effect of the new vasodilatory, selective endothelin type A antagonist, darusentan, in patients with treatment-resistant hypertension?
[Ссылки доступны только зарегистрированным пользователям ]

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Choosing Your Fish - Mercury and BP

EVAR vs. Surgery for AAA

The French TAVI Registry
[Ссылки доступны только зарегистрированным пользователям ]

National Efforts to Improve D2B Time (J Am Coll Cardiol).
[Ссылки доступны только зарегистрированным пользователям ]

Prognostic implications of elevated troponin T levels in Stable CAD (NEJM).
[Ссылки доступны только зарегистрированным пользователям ]

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Cardiovascular Diseases and Risk of Hip Fracture
Sennerby U, Melhus H, Gedeborg R, et al.
JAMA 2009;302:1666-1673.
Study Question: Is there an association between cardiovascular disease (CVD) and risk of hip fracture, and if so, is this association due to genetic or lifestyle factors?
[Ссылки доступны только зарегистрированным пользователям ]

A Sensitive Cardiac Troponin T Assay in Stable Coronary Artery Disease
Omland T, de Lemos JA, Sabatine MS, et al.
N Engl J Med 2009;Nov 25:[Epub ahead of print].
Study Question: What are the prognostic implications of elevated troponin T levels in stable coronary disease patients?
[Ссылки доступны только зарегистрированным пользователям ]

C-Reactive Protein and the Risk of Stent Thrombosis and Cardiovascular Events After Drug-Eluting Stent Implantation
Park DW, Yun SC, Lee JY, et al.
Circulation 2009;120:1987-1995.
Study Question: What is the predictive usefulness of C-reactive protein (CRP) among patients treated with drug-eluting stents (DES)?
[Ссылки доступны только зарегистрированным пользователям ]

Incidence and Predictors of Drug-Eluting Stent Fracture in Human Coronary Artery: A Pathologic Analysis
Nakazawa G, Finn AV, Vorpahl M, et al.
J Am Coll Cardiol 2009;54:1924-1931
Study Question: What is the incidence of, and what are the pathological correlates of coronary stent fracture at autopsy?
[Ссылки доступны только зарегистрированным пользователям ]

Benefit of Facilitated Percutaneous Coronary Intervention in High-Risk ST-Segment Elevation Myocardial Infarction Patients Presenting to Nonpercutaneous Coronary Intervention Hospitals
Herrmann HC, Lu J, Brodie BR, et al., on behalf of the FINESSE Investigators.
JACC Cardiovasc Interv 2009;2:917-924.
Study Question: What is the benefit of facilitated percutaneous coronary intervention (PCI) in high-risk ST-segment elevation myocardial infarction (STEMI) patients presenting to non-PCI hospitals?
[Ссылки доступны только зарегистрированным пользователям ]

Systematic Review: Sodium Bicarbonate Treatment Regimens for the Prevention of Contrast-Induced Nephropathy
Zoungas S, Ninomiya T, Huxley R, et al.
Ann Intern Med 2009;151:631-638.
Study Question: What is the benefit of using sodium bicarbonate-based hydration for prevention of contrast-induced nephropathy (CIN)?
[Ссылки доступны только зарегистрированным пользователям ]

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Non Fasting Lipid Assessment is OK
Patch Plus Lozenge Best for Smoking Cessation
Plaque and Acute Coronary Thrombosis
[Ссылки доступны только зарегистрированным пользователям ]

PROVE IT-TIMI 22: Reduction in recurrent CV events with intensive vs. moderate lipid-lowering statin therapy after ACS (J Am Coll Cardiol).
[Ссылки доступны только зарегистрированным пользователям ]

IDEAL: Total CV disease burden: intensive vs. moderate statin therapy (J Am Coll Cardiol).
[Ссылки доступны только зарегистрированным пользователям ]

CABG vs. PCI in diabetic patients (CARDia)
[Ссылки доступны только зарегистрированным пользователям ]

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A Randomized Trial
Olasveengen TM, Sunde K, Brunborg C, Thowsen J, Steen PA, Wik L.
JAMA 2009;302:2222-2229.
Study Question: Does elimination of intravenous (IV) access and drug administration from advanced cardiac life support (ACLS) affect the outcome of cardiopulmonary resuscitation (CPR) in patients with out-of-hospital cardiac arrest (OHCA)?
[Ссылки доступны только зарегистрированным пользователям ]

Triggering of Nocturnal Arrhythmias by Sleep-Disordered Breathing Events
Monahan K, Storfer-Isser A, Mehra R, et al.
J Am Coll Cardiol 2009;54:1797-1804.
Study Question: Does hypopnea or apnea during sleep trigger atrial fibrillation (AF) or nonsustained ventricular tachycardia (NSVT)?
[Ссылки доступны только зарегистрированным пользователям ]

Survival Implication of Left Ventricular End-Systolic Diameter in Mitral Regurgitation due to Flail Leaflets: A Long-Term Follow-Up Multicenter Study
Tribouilloy C, Grigioni F, Avierinos JF, et al.
J Am Coll Cardiol 2009;54:1961-1968.
Study Question: Is there an association between left ventricular end-systolic diameter (LVESD) with survival after diagnosis in organic mitral regurgitation (MR) due to flail leaflet?
[Ссылки доступны только зарегистрированным пользователям ]

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Pooled Analysis of Rofecoxib Placebo-Controlled Clinical Trial Data: Lessons for Postmarket Pharmaceutical Safety Surveillance
Ross JS, Madigan D, Hill KP, Egilman DS, Wang Y, Krumholz HM.
Arch Intern Med 2009;169:1976-1985.
Study Question: When could the analysis of published and unpublished placebo-controlled trials have revealed cardiovascular risk associated with rofecoxib before its withdrawal?
[Ссылки доступны только зарегистрированным пользователям ]

Intracoronary Optical Coherence Tomography: A Comprehensive Review: Clinical and Research Applications
Bezerra HG, Costa MA, Guagliumi G, Rollins AM, Simon DI.
JACC Cardiovasc Interv 2009;2:1035-1046.
Perspective: The following are 10 points to remember about intracoronary optical coherence tomography (OCT)
[Ссылки доступны только зарегистрированным пользователям ]

Association of Hospital Primary Angioplasty Volume in ST-Segment Elevation Myocardial Infarction With Quality and Outcomes
Kumbhani DJ, Cannon CP, Fonarow GC, et al., on behalf of the Get With the Guidelines Steering Committee and Investigators.
JAMA 2009;302:2207-2213.
Study Question: What is the impact of hospital primary percutaneous coronary intervention (PCI) volume on outcomes and quality of care measures in patients presenting with ST-segment elevation myocardial infarction (STEMI)?
[Ссылки доступны только зарегистрированным пользователям ]

National Efforts to Improve Door-to-Balloon Time: Results From the Door-to-Balloon Alliance
Bradley EH, Nallamothu BK, Herrin J, et al.
J Am Coll Cardiol 2009;54:2423-2429.
Study Question: What was the impact of the door-to-balloon (D2B) alliance on the time to reperfusion among patients undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI)?
[Ссылки доступны только зарегистрированным пользователям ]

Outcomes With Drug-Eluting Versus Bare-Metal Stents in Saphenous Vein Graft Intervention: Results From the STENT (Strategic Transcatheter Evaluation of New Therapies) Group
Brodie BR, Wilson H, Stuckey T, et al., on behalf of the STENT Group.
JACC Cardiovasc Interv 2009;2:1105-1112.
Study Question: What are the outcomes of drug-eluting stents (DES) versus bare-metal stents (BMS) in patients undergoing saphenous vein graft (SVG) intervention?
[Ссылки доступны только зарегистрированным пользователям ]

Safety of Contrast Agent Use During Stress Echocardiography: A 4-Year Experience From a Single-Center Cohort Study of 26,774 Patients
Abdelmoneim SS, Bernier M, Scott CG, et al.
JACC Cardiovasc Imaging 2009;2:1048-1056.
Study Question: What is the short- and long-term safety of ultrasound contrast agents used during stress echocardiography (SE)?
[Ссылки доступны только зарегистрированным пользователям ]

Effects of Liraglutide in the Treatment of Obesity: A Randomised, Double-Blind, Placebo-Controlled Study
Astrup A, Rössner S, Van Gaal L, et al., on behalf of the NN8022-1807 Study Group.
Lancet 2009;374:1606-1616.
Study Question: What is the effect of liraglutide, a glucagon-like peptide-1, on bodyweight and tolerability in obese individuals without type 2 diabetes?
[Ссылки доступны только зарегистрированным пользователям ]

10-Year Follow-up of Diabetes Incidence and Weight Loss in the Diabetes Prevention Program Outcomes Study
Diabetes Prevention Program Research Group.
Lancet 2009;374:1677-1686.
Study Question: What is the persistence of the benefit seen from metformin and intensive lifestyle intervention in preventing diabetes in high-risk patients enrolled in the Diabetes Prevention Program (DPP) randomized clinical trial?
[Ссылки доступны только зарегистрированным пользователям ]

Effects of High-Dose Modified-Release Nicotinic Acid on Atherosclerosis and Vascular Function: A Randomized, Placebo-Controlled, Magnetic Resonance Imaging Study
Lee JM, Robson MD, Yu LM, et al.
J Am Coll Cardiol 2009;54:1787-1794.
Study Question: What are the effects of high-dose (2 g) nicotinic acid (NA) on progression of atherosclerosis and measures of vascular function?
[Ссылки доступны только зарегистрированным пользователям ]

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Atorvastatin Reduces MI in PCI
Sibutramine & CV Risk
New-Onset HF Predicted by Gated SPECT
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Projected cancer risks from CT scans (Archives).
Study Question: What is the future cancer risk from current computed tomographic (CT) scan use in the United States?
[Ссылки доступны только зарегистрированным пользователям ]

Relationship between coffee consumption and risk of type 2 diabetes (Archives).
Study Question: What is the relationship between coffee consumption and risk of type 2 diabetes mellitus?
[Ссылки доступны только зарегистрированным пользователям ]

Mutations in Alpha-Actinin-2 Cause Hypertrophic Cardiomyopathy (J Am Coll Cardiol).
Study Question: What gene mutation is associated with hypertrophic cardiomyopathy (HCM) in a large family with a heterogenous HCM phenotype?
[Ссылки доступны только зарегистрированным пользователям ]

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Американская Ассоциация Сердца выпустила список 10 основных достижений в исследованиях заболеваний сердца и инсульта за 2009 год. Отмечено, что достижения расположены в нем по названию соответствующей публикации, но тем не менее 2 первых места занимают имеющие большое общественное значение работы по профилактике
[Ссылки доступны только зарегистрированным пользователям ]

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Women Have a Lower Prevalence of Structural Heart Disease as a Precursor to Sudden Cardiac Arrest: The Ore-SUDS (Oregon Sudden Unexpected Death Study)
Chugh SS, Uy-Evanado A, Teodorescu C, et al.
J Am Coll Cardiol 2009;54:2006-2011.
Study Question: Are there gender-based differences in the clinical predictors of sudden cardiac arrest (SCA)?
Title: Women Have a Lower Prevalence of Structural Heart Disease as a Precursor to Sudden Cardiac Arrest: The Ore-SUDS (Oregon Sudden Unexpected Death Study)
Topic: Arrhythmias
Date Posted: 12/8/2009
Author(s): Chugh SS, Uy-Evanado A, Teodorescu C, et al.
Citation: J Am Coll Cardiol 2009;54:2006-2011.
Clinical Trial: No
Study Question: Are there gender-based differences in the clinical predictors of sudden cardiac arrest (SCA)?
Methods: The medical records of 1,568 adults with SCA were reviewed. Clinical predictors of SCA were compared between men (n = 1,012) and women (n = 556).
Results: The women (mean age 71 years) were significantly older than the men (mean age 65 years). In a multivariate analysis of multiple clinical variables, the predictors of SCA that were significantly less prevalent in women than men were prior documentation of coronary artery disease (odds ratio 0.34) and a left ventricular ejection fraction ≤35%.
Conclusions: Recognized structural heart disease prior to SCA is less prevalent in women than men.
Perspective: Prior studies have demonstrated that the implantation rate of implantable cardioverter-defibrillators (ICDs) is lower in women than men. The results of this study provide a possible explanation for the gender discrepancy in the ICD implantation rate. Because women are less likely to have recognized coronary artery disease or severe left ventricular dysfunction before SCA, they are less likely to meet the conventional criteria for ICD implantation. This emphasizes the need for identification of more accurate clinical predictors of SCA than simply prior myocardial infarction or a low ejection fraction. Fred Morady, M.D., F.A.C.C.
Source
Content provided by the American College of Cardiology Foundation

The RYR2-Encoded Ryanodine Receptor/Calcium Release Channel in Patients Diagnosed Previously With Either Catecholaminergic Polymorphic Ventricular Tachycardia or Genotype Negative, Exercise-Induced Long QT Syndrome: A Comprehensive Open Reading Frame Mutational Analysis
Medeiros-Domingo A, Bhuiyan ZA, Tester DJ, et al.
J Am Coll Cardiol 2009;54:2065-2074.
Study Question: What is the prevalence of RYR2 mutations in subjects with exertional syncope and normal QT interval (previously classified as probable catecholaminergic polymorphic ventricular tachycardia [CPVT], possible CPVT, or atypical long QT syndrome)?
Title: The RYR2-Encoded Ryanodine Receptor/Calcium Release Channel in Patients Diagnosed Previously With Either Catecholaminergic Polymorphic Ventricular Tachycardia or Genotype Negative, Exercise-Induced Long QT Syndrome: A Comprehensive Open Reading Frame Mutational Analysis
Topic: Arrhythmias
Date Posted: 12/18/2009
Author(s): Medeiros-Domingo A, Bhuiyan ZA, Tester DJ, et al.
Citation: J Am Coll Cardiol 2009;54:2065-2074.
Clinical Trial: No
Study Question: What is the prevalence of RYR2 mutations in subjects with exertional syncope and normal QT interval (previously classified as probable catecholaminergic polymorphic ventricular tachycardia [CPVT], possible CPVT, or atypical long QT syndrome)?
Methods: Mutational analysis of all RYR2 exons was performed using DNA sequencing on 155 unrelated patients (49% females, 96% Caucasian, age at diagnosis 20 ± 15 years, mean QTc 428 ± 29 ms), with either clinical diagnosis of CPVT (n = 110) or an initial diagnosis of exercise-induced long QT syndrome, but with QTc <480 ms and a subsequent negative long QT syndrome genetic test (n = 45).
Results: A total of 63 (34 novel) possible CPVT1-associated mutations, absent in 400 reference alleles, were detected in 73 unrelated patients (47%). Thirteen new mutation-containing exons were identified. Two-thirds of the CPVT1-positive patients had mutations that localized to 1 of 16 exons.
Conclusions: Possible CPVT1 mutations in RYR2 were identified in nearly one-half of this cohort; 45 of the 105 translated exons are now known to host possible mutations. Considering that approximately 65% of CPVT1-positive cases would be discovered by selective analysis of 16 exons, a tiered targeting strategy for CPVT genetic testing should be considered.
Perspective: CPVT is a malignant cardiac channelopathy that leads to mortality rates approaching 50% by age 35. CPVT is associated with gain of function mutations in RYR2, a large gene that codes for a protein involved in sarcoplasmic reticulum calcium release. However, mutation analysis of RYR2 in patients with CPVT has previously been limited without complete exon sequencing. The current study expanded this analysis to all exons in a cohort of unrelated subjects and control alleles, and found additional disease-associated mutations in 13 exons not typically sequenced. Validation of these findings (case-control) and proof of pathogenicity of these novel mutations will require additional study. Daniel T. Eitzman, M.D., F.A.C.C.
Source
Content provided by the American College of Cardiology Foundation

Genotype-Phenotype Aspects of Type 2 Long QT Syndrome
Shimizu W, Moss AJ, Wilde AA, et al.
J Am Coll Cardiol 2009;54:2052-2062.
Study Question: Does the type of KCNH2 mutation affect the clinical course of patients with type 2 long QT syndrome (LQTS)?
Title: Genotype-Phenotype Aspects of Type 2 Long QT Syndrome
Topic: Arrhythmias
Date Posted: 12/17/2009
Author(s): Shimizu W, Moss AJ, Wilde AA, et al.
Citation: J Am Coll Cardiol 2009;54:2052-2062.
Clinical Trial: No
Study Question: Does the type of KCNH2 mutation affect the clinical course of patients with type 2 long QT syndrome (LQTS)?
Methods: The subjects of this study were 858 patients with type 2 LQTS. The KCNH2 mutations were characterized and correlated with the time to first cardiac event (syncope, cardiac arrest, or sudden cardiac death).
Results: A total of 162 mutations of KCNH2 were identified in the 858 patients. A missense mutation, with a single amino acid substitution, had a prevalence of 62% and was the most common type of mutation. The mutation that was associated with the highest risk of a first cardiac event (hazard ratio 2.87) was a missense mutation in the transmembrane pore (S5-loop-S6). Therapy with a beta-blocker was associated with a 63% reduction in the risk of a first cardiac event, but only a 29% reduction in the risk of a lethal cardiac event.
Conclusions: In patients with type 2 LQTS, the highest risk of syncope, cardiac arrest, or sudden cardiac death is associated with a missense mutation in the transmembrane pore.
Perspective: The results suggest that genetic analysis may be useful in guiding the prophylactic therapy of asymptomatic patients with type 2 LQTS. An implantable cardioverter-defibrillator might be appropriate for patients with a high-risk mutation, whereas a beta-blocker could be used in patients with the low-risk mutations. Fred Morady, M.D., F.A.C.C.

[Chevychelov]

Title: Endovascular Stent-Grafts for the Treatment of Abdominal Aortic Aneurysms: NICE Technology Appraisal Guidance
Topic: Cardiovascular Surgery
Date Posted: 12/9/2009
Author(s): Hay N, McCracken F, Richardson J, George E, Barnett D.
Citation: Heart 2009;95:1798-800.
Clinical Trial: No
Perspective: The top 10 points to remember about the NICE guidance on the use of stent-grafts to treat abdominal aortic aneurysms (AAAs) are:

1. Endovascular aneurysm repair (EVAR) is recommended as a treatment option in patients with infrarenal AAAs for whom repair is considered appropriate.

2. Decisions as to whether to pursue EVAR or open AAA repair should be made jointly by the patient and his/her clinician.

3. Aneurysm size and morphology, patient age, life expectancy and fitness, and long- and short-term benefits and risks of the procedures should figure into the decision about which route of AAA repair is appropriate.

4. EVAR should only be performed in centers of excellence by clinical teams experienced in the management of patients with AAAs.

5. EVAR was not recommended for ruptured AAAs, except in the context of research.

6. EVAR has lower medium-term reduced rates of operative and aneurysm mortality.

7. EVAR, however, is not associated with a reduction in all-cause mortality long-term. In addition, EVAR is associated with increased rates of complications and reinterventions compared with open repair.

8. As most reports comparing open repair and EVAR use older devices, the appraisal committee suggested that the benefits of EVAR were likely greater than that seen in randomized control trials.

9. Assuming an endograft cost of 5000 pounds, the committee concluded that there was little or no difference in the initial procedure costs between EVAR and open repair.

10. In determining the fitness for surgery, which impacts cost-effectiveness, the group agreed that decisions over recommending EVAR versus open repair should be made on an individual basis, jointly between the patient and his/her clinician. Gilbert Upchurch, Jr., M.D.

Title: Mitral-Valve Repair for Mitral-Valve Prolapse
Topic: Cardiovascular Surgery
Date Posted: 12/9/2009
Author(s): Verma S, Mesana TG.
Citation: N Engl J Med 2009;361:2261-2269.
Clinical Trial: No
Perspective: This summary describes a case of a patient presenting with myxomatous degeneration of the mitral valve and severe mitral regurgitation (MR), and then discusses the clinical problem and the benefits and risks of mitral valve repair. Ten points to remember are:

1. ‘Mitral valve prolapse’ (myxomatous degeneration of the mitral valve) is the most common cause of MR in developed countries, with a prevalence of ~2.5%. There is a heterogeneous natural history of disease. In some patients, MR does not progress to severe, and life expectancy is normal; whereas in other patients (estimated at 5-10%), MR progresses to severe, with associated adverse outcomes.

2. The mitral valve apparatus is comprised of mitral leaflets, annulus, chordae tendinae, papillary muscles, and the associated left ventricular (LV) myocardium. The posterior mitral valve has three scallops. One terminology refers to the posterior scallops as P1, P2, and P3 (from anterolateral to posteromedial). MR can be caused by malcoaptation of myxomatous, prolapsing leaflets, potentially exacerbated by mitral annular dilation. (Although not discussed, MR also can be caused by partial flail of a leaflet, typically associated with rupture of one or more chordae.)

3. When present, chronic severe MR leads to volume overload of the LV, with LV dilation, hypertrophy, neurohumeral activation, and heart failure. Elevation of left atrial pressure leads to left atrial enlargement, atrial fibrillation, pulmonary venous congestion, and pulmonary hypertension.

4. There are no randomized trials comparing medical therapy with surgery for MR caused by mitral valve prolapse. However, some (but not all) observational studies suggest that survival is superior with early surgical intervention.

5. Mitral valve surgery can take the form of mitral valve replacement (with a mechanical or a tissue prosthesis) or mitral valve repair. There are no randomized trials comparing mitral valve repair and mitral valve replacement for MR caused by mitral valve prolapse. However, most (but not all) observational studies suggest that outcomes (including survival) are superior with mitral valve repair.

6. Surgical intervention generally is recommended for chronic severe MR and the presence of any symptoms, LV systolic dysfunction (in this review defined as an ejection fraction <60%, but based on American College of Cardiology [ACC]/American Heart Association [AHA] guidelines the threshold is ≤60%), significant LV enlargement (in this review defined as a systolic diameter >40 mm, but based on ACC/AHA guidelines the threshold is ≥40 mm), pulmonary arterial hypertension, or new atrial fibrillation. When surgery is indicated, current ACC/AHA and European Society of Cardiology (ESC) guidelines recommend preferential use of repair over replacement. If valve replacement is performed, subvalvular chordal attachments should be preserved.

7. There is debate regarding the use of ‘prophylactic’ mitral valve repair, used to treat chronic severe MR in an asymptomatic patient with none of the usual indications for surgery (see #6, above). ACC/AHA guidelines recommend prophylactic mitral valve repair if the likelihood of successful repair is >90%; the ESC guidelines recommend a more conservative approach.

8. Mitral valve repair is a specialized technique that should be carried out by an experienced repair surgeon. Individual and institutional experience is crucial; and high volumes are associated with both greater likelihood of valve repair rather than replacement, and lower procedural mortality.

9. Surgical valve repair can include resection of redundant or flail posterior segment(s); ‘sliding plasty’ to decrease posterior leaflet height; and chordal transposition, the use of artificial chordae, and edge-to-edge repair for anterior leaflet pathology.

10. Adverse outcomes associated with surgery include death, requirement for prolonged ventilatory support, renal insufficiency, stroke, thromboembolism, and late recurrence of MR sometimes requiring reoperation. David S. Bach, M.D., F.A.C.C.

Title: The Yield of Risk Stratification for Sudden Cardiac Death in Hypertrophic Cardiomyopathy Myosin-Binding Protein C Gene Mutation Carriers: Focus on Predictive Screening
Topic: Heart Failure/Transplant
Date Posted: 12/21/2009
Author(s): Christiaans I, Birnie E, van Langen IM, et al.
Citation: Eur Heart J 2009;Dec. 16:[Epub ahead of print].
Clinical Trial: No
Study Question: What is the value of risk stratification with genetic screening and clinical evaluations in patients with MYBPC3 gene mutations?
Methods: Two hundred and thirty-five mutation carriers were evaluated for the presence of hypertrophic cardiomyopathy (HCM) and risk factors. A clinical diagnosis of HCM was made in 53 carriers (22.6%).
Results: Disease penetrance was variable for all types of MYBPC3 gene mutations, and women were affected less often than men (15% and 32%, respectively; p = 0.003). One risk factor was present in 87 carriers and 9 had two or more risk factors. Twenty-five carriers (11%) with one or more risk factors and manifest HCM could be at risk for sudden cardiac death (SCD).
Conclusions: At first evaluation, one-quarter of asymptomatic carriers were diagnosed with HCM. Risk factors for SCD were frequently present, and 11% of carriers could be at risk for SCD. The authors concluded that predictive genetic testing in HCM families and frequent cardiac evaluation for the presence of HCM and risk factors for SCD are justified until advanced age.
Perspective: Close clinical follow-up is indicated in relatives of patients with HCM. Knowledge of the mutation status may aid in follow-up if a likely causative mutation is identified. Most mutation carriers in the current study had the same Dutch founder mutation. However, because of the uncertainty of mutation causality in a diverse population and incomplete penetrance of mutation carriers, the added value of genetic testing remains unclear. Clinical outcomes data in HCM families managed with and without genetic screening would be necessary to address this question. Daniel T. Eitzman, M.D., F.A.C.C.

[Chevychelov]

Title: Mutations in Alpha-Actinin-2 Cause Hypertrophic Cardiomyopathy: A Genome-Wide Analysis
Topic: Heart Failure/Transplant
Date Posted: 12/16/2009
Author(s): Chiu C, Bagnall RD, Ingles J, et al.
Citation: J Am Coll Cardiol 2009;Dec 16:[Epub ahead of print].
Clinical Trial: No
Study Question: What gene mutation is associated with hypertrophic cardiomyopathy (HCM) in a large family with a heterogenous HCM phenotype?
Methods: History, physical examination, electrocardiography, and two-dimensional echocardiography were performed, and blood was collected from family members (n = 23) for DNA analysis. The family was genotyped with markers from the 10-cM AB PRISM Human Linkage mapping set (Applied Biosystems, Foster City, CA), and 2-point linkage analysis was performed.
Results: Affected family members showed marked clinical diversity, ranging from asymptomatic individuals to those with syncope, heart failure, and premature sudden death. The disease locus for this family was mapped to chromosome 1q42.2-q43, near the marker D1S2850 (logarithm of odds ratio = 2.82, Ө = 0). A missense mutation, Ala119Thr, in the alpha-actinin-2 (ACTN2) gene was identified that segregated with disease in the family. An additional 297 HCM probands were screened for mutations in the ACTN2 gene using high-resolution melt analysis. Three causative ACTN2 mutations, Thr495Met, Glu583Ala, and Glu628Gly, were identified in an additional four families (total 1.7%) with HCM.
Conclusions: The authors concluded that this is the first genome-wide linkage analysis, which shows that mutations in ACTN2 cause HCM.
Perspective: ACTN2 is a multifunctional actin binding protein found in skeletal and cardiac muscle, where it is a major component of the Z-disc. A previous study using a candidate gene approach in a large HCM cohort identified ACTN2 mutations in 1.3% of the patients. By using a genome-wide approach, the current study confirms these previous findings, and provides stronger support for a causal relationship between ACTN2 mutations and HCM phenotypes. Additional confirmatory clinical studies as well as basic functional studies of these mutations to determine how they predispose to HCM will add important insight into the pathophysiology of this disease process. Daniel T. Eitzman, M.D., F.A.C.C.

Title: Prevention of Disease Progression by Cardiac Resynchronization Therapy in Patients With Asymptomatic or Mildly Symptomatic Left Ventricular Dysfunction: Insights From the European Cohort of the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) Trial
Topic: Heart Failure/Transplant
Date Posted: 12/10/2009
Author(s): Daubert C, Gold MR, Abraham WT, et al., on behalf of the REVERSE Study Group.
Citation: J Am Coll Cardiol 2009;54:1837-1846.
Clinical Trial: No
Study Question: Is cardiac resynchronization therapy (CRT) of value in patients with asymptomatic or mildly symptomatic left ventricular dysfunction?
Methods: A CRT device was implanted in 262 patients (mean age 61 years) with an ejection fraction (EF) ≤40% (mean EF 28%), QRS ≥120 ms, and a New York Heart Association (NYHA) functional class of I-II. The patients were randomly assigned to CRT on (n = 180) or CRT off (n = 82), and followed for 24 months. The 1° endpoint was the heart failure (HF) clinical composite response. The criteria for a worsened HF composite response were death, hospitalization or crossover to alternate therapy because of worsened HF, or an increase in NYHA functional class.
Results: At 24 months of follow-up, a worsened HF composite response was significantly less prevalent in the CRT-on group (19%) than in the CRT-off group (34%). The left ventricular end-systolic volume index decreased to a significantly greater extent in the CRT-on group (27.5 ml/m2) than in the CRT-off group (2.7 ml/m2). A significantly smaller proportion of patients required hospitalization for HF in the CRT-on group (7.2%) than in the CRT-off group (17.1%).
Conclusions: CRT improves clinical outcomes and reverses remodeling in patients with asymptomatic or mildly symptomatic left ventricular function.
Perspective: The MADIT-CRT study recently demonstrated that CRT reduces the risk of HF events and reverses remodeling in patients with asymptomatic or mildly symptomatic left ventricular dysfunction. The present study provides further support for broadening the indications for CRT to include patients with a functional class of I-II. Fred Morady, M.D., F.A.C.C.

Title: Risk of Bleeding in Patients With Acute Myocardial Infarction Treated With Different Combinations of Aspirin, Clopidogrel, and Vitamin K Antagonists in Denmark: A Retrospective Analysis of Nationwide Registry Data
Topic: General Cardiology
Date Posted: 12/14/2009
Author(s): Sшrensen R, Hansen ML, Abildstrom SZ, et al.
Citation: Lancet 2009; 374:1967-1974.
Clinical Trial: No
Study Question: What is the long-term risk of bleeding among patients with myocardial infarction (MI) who are treated with aspirin, clopidogrel, or Coumadin or any combination of these agents?
Methods: The authors used nationwide registries from Denmark to identify patients ages 30 years or older who had been admitted to the hospital with first-time MI between 2000 and 2005. Prescription claims starting at hospital discharge were used to determine the regimen prescribed according to the following groups: monotherapy with aspirin, clopidogrel, or vitamin K antagonist; dual therapy with aspirin plus clopidogrel, aspirin plus vitamin K antagonist, or clopidogrel plus vitamin K antagonist; or triple therapy including all three drugs. Patients could be in only one group at a time, although they could change groups as medications were started or stopped. Risk of hospital admission for bleeding, recurrent MI, and death were assessed by Cox proportional hazards models with the drug exposure groups as time-varying covariates. Use of this model implies that patients were only deemed at risk for each exposure group while taking the corresponding antithrombotic drug(s).
Results: The total cohort was comprised of 40,812 patients. During a mean follow-up of 476 days, 1,852 (4.5%) patients required hospitalization for a nonfatal bleeding event. The annual incidence of bleeding was 2.6% for the aspirin group, 4.6% for clopidogrel, 4.3% for vitamin K antagonist, 3.7% for aspirin plus clopidogrel, 5.1% for aspirin plus vitamin K antagonist, 12.3% for clopidogrel plus vitamin K antagonist, and 12.0% for triple therapy. After adjusting for baseline differences, and using the aspirin group as a reference, adjusted hazard ratios for bleeding were 1.33 (95% confidence interval [CI], 1.11-1.59) for clopidogrel, 1.23 (95% CI, 0.94-1.61) for vitamin K antagonist, 1.47 (95% CI, 1.28-1.69) for aspirin plus clopidogrel, 1.84 (95% CI, 1.51-2.23) for aspirin plus vitamin K antagonist, 3.52 (95% CI, 2.42-5.11) for clopidogrel plus vitamin K antagonist, and 4.05 (95% CI, 3.08-5.33) for triple therapy. Patients with nonfatal bleeding were at a higher risk of recurrent MI or death (37.9% vs. 18.4%; HR, 3.00; 95% CI, 2.75-3.27; p < 0.001) compared with patients without any bleeding events. Mean time from claiming a prescription of an antithrombotic treatment to occurrence of a bleeding event varied from 169 days for clopidogrel monotherapy to 275 days for monotherapy with a vitamin K antagonist. Most nonfatal bleeding events were gastrointestinal.
Conclusions: Risk of hospital admission for bleeding increased with the number of antithrombotic drugs used in patients with MI.
Perspective: This study adds to the evidence base guiding physicians contemplating use of Coumadin in patients with a recent MI. Both triple therapy and dual therapy with a vitamin K antagonist and clopidogrel was associated with extremely high risk of bleeding. Triple therapy or combination of Coumadin and clopidogrel should only be used after careful assessment of the risk–benefit ratio of the individual patient. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

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Title: C-Reactive Protein Concentration and Risk of Coronary Heart Disease, Stroke, and Mortality: An Individual Participant Meta-Analysis
Topic: Prevention/Vascular
Date Posted: 12/21/2009 8:00:00 PM
Author(s): The Emerging Risk Factors Collaboration.
Citation: Lancet 2009;Dec 22:[Epub ahead of print].
Clinical Trial: No
Study Question: What is the association of C-reactive protein (CRP) concentration and risk of vascular and nonvascular outcomes, and is the relationship causal?
Methods: A collaborative study using meta-analysis was conducted between investigators of 54 prospective studies of cardiovascular risk factors who provided individual subject data regarding CRP and outcomes. The cohort included 160,309 people without a history of vascular disease (i.e., 1.31 million person-years at risk, 27,769 fatal or nonfatal disease outcomes). Within-study regression analyses were adjusted for within-person variation in risk factor levels. The primary outcome was coronary heart disease (CHD) (i.e. first-ever myocardial infarction or fatal CHD), with subsidiary analyses of stroke by subtype, death from vascular disease, and aggregate of nonvascular death.
Results: Loge CRP concentration was linearly associated with several conventional risk factors and inflammatory markers, and nearly log-linearly with the risk of ischemic vascular disease and nonvascular mortality. Significant increases in risk ratios (RRs) were found for CHD per 1-standard deviation higher loge CRP concentration (threefold higher) RR 1.63 when initially adjusted for age and sex only, and RR 1.37 when adjusted further for conventional risk factors; 1.44 and 1.27 for ischemic stroke; 1.71 and 1.55 for vascular mortality; and 1.55 and 1.54 for nonvascular mortality. RRs were largely unchanged after exclusion of smokers or initial follow-up. After further adjustment for fibrinogen, the corresponding RRs were 1.23 for CHD; 1.32 for ischemic stroke; 1.34 for vascular mortality; and 1.34 for nonvascular mortality.
Conclusions: CRP concentration has continuous associations with the risk of CHD, ischemic stroke, vascular mortality, and death from several cancers and lung disease that are each of broadly similar size. Associations with ischemic vascular disease depend considerably on conventional risk factors and other markers of inflammation.
Perspective: There is debate about the clinical utility of CRP for risk assessment in cardiovascular disease as well as whether it is a causal relationship or simply a biomarker of risk. This study adds to the abundant literature supporting CRP as a risk marker for cardiovascular events and mortality. And the JUPITER trial provided clinical evidence that it may be useful to risk stratify persons with relatively normal lipid profiles for deciding statin therapy. CRP binds to low-density lipoprotein, and is found in atherosclerotic plaque, suggesting causality. However, this study showing attenuation of attributable risk when corrected for fibrinogen, and recent studies showing no relationship between genetic polymorphisms associated with a higher level of CRP and cardiovascular disease imply that CRP is a risk marker, but not a risk factor for cardiovascular events. And the important saga continues. Melvyn Rubenfire, M.D., F.A.C.C.

Title: Association of Circulating Cholesteryl Ester Transfer Protein Activity With Incidence of Cardiovascular Disease in the Community
Topic: Prevention/Vascular
Date Posted: 12/16/2009
Author(s): Vasan RS, Pencina MJ, Robins SJ, et al.
Citation: Circulation 2009;120:2414-2420.
Clinical Trial: No
Study Question: What is the relationship between plasma cholesteryl ester transfer protein (CETP) activity and the incidence of cardiovascular disease (CVD)?
Methods: Plasma CETP activity was measured in 1978 Framingham Heart Study participants (mean age, 51 years; 54% women) who attended a routine examination from 1987 to 1990 and were free of CVD. On follow-up (mean, 15.1 years), 320 participants experienced a first CVD event (fatal or nonfatal coronary heart disease, cerebrovascular disease, peripheral vascular disease, or heart failure).
Results: In multivariable analyses adjusted for standard risk factors including high-density lipoprotein (HDL) cholesterol, plasma CETP activity was related inversely to the incidence of CVD events (hazard ratio [HR] for activity, at or above the median of 0.72; 95% confidence interval, 0.57-0.90; p = 0.004 [compared with below median]; HR per standard deviation increment, 0.86; 95% confidence interval, 0.76-0.97; p = 0.01). The inverse association of CETP activity with CVD incidence remained robust in time-dependent models updating standard risk factors every 4 years, and was maintained in analyses of incident “hard” CVD events (myocardial infarction, stroke, or heart failure).
Conclusions: In this prospective investigation of a community-based sample, lower plasma CETP activity was associated with greater CVD risk. These observations, if confirmed, challenge the concept that CETP inhibition may lower CVD risk.
Perspective: Although HDL levels are inversely related to the risk of CVD, pharmacologic strategies designed to raise HDL based on CETP inhibition have not produced beneficial vascular effects, and may even be harmful. Whether these adverse effects are due to off-target drug effects or to the mechanism of raising HDL is unclear and will be addressed in future clinical trials with other CETP inhibitors. Studies addressing relationships between genetic CETP abnormalities and circulating CETP concentrations with CVD have been controversial. The current study adds important prospective data to this controversial area and suggests CETP inhibitors will not have beneficial effects on CVD events, and may lead to harm. Daniel T. Eitzman, M.D., F.A.C.C.

Title: Total Cardiovascular Disease Burden: Comparing Intensive With Moderate Statin Therapy: Insights From the IDEAL (Incremental Decrease in End Points Through Aggressive Lipid Lowering) Trial
Topic: Prevention/Vascular
Date Posted: 12/11/2009 9:00:00 AM
Author(s): Tikkanen MJ, Szarek M, Fayyad R, et al., on behalf of the IDEAL Investigators.
Citation: J Am Coll Cardiol 2009;54:2353-2357.
Clinical Trial: No
Study Question: What is the comparative treatment efficacy of high-dose atorvastatin and usual-dose simvastatin for the prevention of events subsequent to the first event?
Methods: This was a post-hoc analysis of the Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL) trial, aimed to assess the comparative treatment efficacy of two statin regimens for the events beyond the first, using the broadest secondary endpoint (any cardiovascular disease [CVD]), consisting of the primary endpoint (coronary heart disease death, nonfatal myocardial infarction, and resuscitated cardiac arrest) plus the following: stroke, revascularization, hospitalization for unstable angina pectoris, hospitalization for congestive heart failure, and peripheral artery disease. The Wei, Lin, and Weissfeld method allows the analysis of repeated occurrence of events of the same type or of entirely different natures; it regards the recurrence times as multivariate event (failure) times, and models the marginal (individual) distribution for each event with the Cox proportional hazards model.
Results: In the IDEAL trial, compared with patients taking simvastatin 20-40 mg daily, patients receiving atorvastatin 80 mg daily had their relative risk of a first cardiovascular event reduced by 17% (p < 0.0001), of a second by 24% (p < 0.0001), of a third by 19% (p = 0.035), of a fourth by 24% (p = 0.058), and of a fifth by 28% (p = 0.117).
Conclusions: The authors concluded that intensive statin therapy continues to be more effective than standard statin therapy, even beyond the first event.
Perspective: This study explored the possibility that new information concerning treatment efficacy of intensive statin therapy compared with standard statin therapy could be gained by analysis of repeated occurrences (after the first event) of different types of CV events. The method allowed analysis of not only time to first CV event, but also time to second, third, fourth, and fifth events. The study results indicate that intensive statin therapy continued to be more effective than standard statin therapy even beyond the first event. This analysis provides new insights into the treatment of patients experiencing repeated occurrences of CVD and suggests that especially for such patients, intensive statin therapy is preferable to standard therapy. Debabrata Mukherjee, M.D., F.A.C.C.

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Time to Reperfusion and Myocardial Damage
ACC Takes Legal Action
CardioSmart Atlanta Healthfair at ACC.10
[Ссылки доступны только зарегистрированным пользователям ]

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

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Title: NORwegian study on DIstrict treatment of ST-Elevation Myocardial Infarction (NORDISTEMI)
Trial Sponsor: Norwegian Health Authorities and AH Waage Foundation
Year Presented: 2009
Year Published 2009
Topic(s): General Cardiology, Interventional Cardiology
Summary Posted: 1/4/2010 5:00:00 PM
Writer: Ms. Sabina A. Murphy
Author Disclosure: Consulting Fees: Eli Lilly
Reviewer: Deepak L. Bhatt, M.D., F.A.C.C.
Author Disclosure: Research/Research Grants: Astra Zeneca; Research/Research Grants: Eisai; Research/Research Grants: Ethicon; Consultant Fees/Honoraria: Duke Clinical Research Institute; Research/Research Grants: Heartscape; Research/Research Grants: The Medicines Company; Research/Research Grants: Bristol Myers Squibb; Data Safety Monitoring Board (Gov’t/Nonprofit): Duke Clinical Research Institute; Research/Research Grants: Sanofi Aventis
Supplemental Reviewer: Anthony A. Bavry, M.D., M.P.H., F.A.C.C.
Author Disclosure: This author has nothing to disclose.
Description
The goal of the trial was to evaluate immediate transfer for percutaneous coronary intervention (PCI) compared with conservative, ischemia-guided treatment among patients with ST-elevation myocardial infarction (STEMI) treated with thrombolysis with very long transfer times to PCI hospitals.
Hypothesis
Patients treated with thrombolytic therapy for STEMI with a very long transfer time to a PCI hospital would have a reduction in major adverse cardiac events (MACE) with immediate transfer for angiography and PCI, as compared to ischemia-guided treatment in local hospitals with transfer for rescue PCI, if needed.
Drugs/Procedures Used
Patients were treated with optimal medical therapy (tenecteplase [TNK], aspirin, enoxaparin, and clopidogrel) and were then randomized to immediate transfer for angiography/PCI (n = 134) or ischemia-guided treatment in local hospitals with transfer for rescue PCI if needed (n = 132). SPECT was performed at 3 months of follow-up.
Concomitant Medications
Aspirin (300 mg), TNK, enoxaparin (30 mg IV 1 mg/kg subcutaneously), clopidogrel (300 mg)
Principal Findings
Median time from symptom onset to TNK administration was 117 minutes in the invasive group and 126 minutes in the conservative group (p = 0.72). There was a slight excess of patients with treated hypertension in the conservative group (38% vs. 25%, p = 0.03), but other baseline characteristics were well balanced between treatment groups. Infarct location was anterior in 41% of patients.

Angiography was performed in 99% of the invasive group and 95% of the conservative group, with median time from TNK administration to arrival in the catheterization laboratory of 130 minutes and 5.5 days, respectively. PCI was performed in 89% of the invasive group and 71% of the conservative group, with a median time from TNK to PCI of 163 minutes and 3.0 days, respectively. The median transfer distance to the PCI center was 158 km among invasive patients. There were few complications associated with the transport: one death in the invasive group, ventricular fibrillation in 3% of the invasive group, and ventricular tachycardia in 1.5% of the conservative group. Stents were used in a higher proportion of the invasive group (86% vs. 68%). Radial access was used in 86% and glycoprotein IIb/IIIa inhibitors in 9%.

The primary endpoint of death, reinfarction, stroke, or new ischemia at 1 year did not differ between treatment groups (20.9% for invasive vs. 27.3% for conservative, p = 0.18). However, there was a significant reduction in the secondary endpoint of death, MI, or stroke at 12 months with the invasive strategy (6.0% vs. 15.9%, p = 0.01). Death was 2.2% versus 3.0%, reinfarction was 3.0% versus 9.1%, stroke was 2.2% versus 5.3%, and recurrent ischemia was 15.0% versus 15.2%, respectively for invasive versus conservative therapy.

At 30 days, the composite of death, reinfarction, stroke, or new ischemia was lower in the invasive group (10% vs. 21%, p = 0.03), but there was no difference in death, reinfarction, or stroke (4.5% vs. 9.8%, p = 0.14). Total bleeding events at 30 days were similar in both groups (13% for invasive group vs. 14% for conservative group, p = 0.68), as was GUSTO severe bleeding (1.5% vs. 2.3%), moderate bleeding (0% vs. 2.3%), and minor bleeding (10% vs. 9.8%).
Interpretation
Among TNK-treated patients with STEMI with very long transfer times to PCI hospitals, immediate transfer for PCI did not lead to a significant reduction in the primary composite endpoint of death, reinfarction, stroke, or new ischemia at 1 year compared with conservative, ischemia-guided treatment; however, a significant benefit was seen with the secondary endpoint of death, reinfarction, or stroke.

Previous studies such as DANAMI-2 have demonstrated that transfer of patients for primary PCI reduces the risk of death, reinfarction, or stroke compared with thrombolytic therapy. However, limited data are available for the comparison of immediate transfer for PCI compared with conservative ischemia-guided therapy in STEMI patients with very long transfer times who were previously treated with thrombolytic therapy. In the CARESS-in-AMI trial of STEMI patients treated with thrombolytic therapy, transfer for immediate PCI was associated with a reduction in the primary endpoint of death, reinfarction, or refractory ischemia at 30 days compared with conservative strategy, but transfer times (and presumably distances) were shorter than in NORDISTEMI, particularly in the conservative group.

There was a reduction in the secondary endpoint of death, reinfarction, stroke, or new ischemia at 30 days with immediate transfer in the present study, as well as a reduction in death, MI, or stroke at 12 months. Despite randomization to the conservative group, a large percentage of patients underwent PCI (71%), albeit in a delayed manner (median 3.0 days). The safety profile of the two strategies appeared similar, with no difference in bleeding by a variety of definitions. The low bleeding rates were probably attributable to the high use of radial access and low use of glycoprotein IIb/IIIa inhibitors.
Conditions
• Coronary heart disease
• Coronary heart disease / Acute MI
Therapies
• Early invasive and conservative strategies
Study Design
Randomized.
Patients Screened: 526
Patients Enrolled: 266
Mean Follow-Up: 12 months
Mean Patient Age: 60 years
% Female: 24

Primary Endpoints
Composite of death, reinfarction, stroke, or new ischemia by 12 months
Secondary Endpoints
Composite of death, reinfarction, or stroke by 12 months; bleeding complications within 30 days; transport complications; infarct size at 3 months (SPECT); quality of life at 12 months; total costs over 12 months
Patient Population
Age 18-75 years, symptoms of MI for <6 hours, ST-segment elevation ≥1 mm in two contiguous extremity leads or ≥2 mm in two contiguous precordial leads or new LBBB, expected time delay from first medical contact to PCI >90 minutes, receiving thrombolytic treatment with tenecteplase
Exclusions:
Standard contraindication for thrombolytic treatment, known serious renal failure (creatinine >250 mmol/L), cardiogenic shock, diseases with life expectancy <12 months
References: Bшhmer E, Hoffmann P, Abdelnoor M, Arnesen H, Halvorsen S. Efficacy and safety of immediate angioplasty versus ischemia-guided management after thrombolysis in acute myocardial infarction in areas with very long transfer distances: results of the NORDISTEMI (NORwegian study on DIstrict treatment of ST-Elevation Myocardial Infarction). J Am Coll Cardiol 2010;55:102-10.

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