Circulation: Clinical Summaries
Original Research Put Into Perspective for the Practicing Clinician
- Five-Year Survival in Patients With ST-Segment–Elevation Myocardial Infarction According to Modalities of Reperfusion Therapy: The French Registry on Acute ST-Elevation and Non–ST-Elevation Myocardial Infarction (FAST-MI) 2005 Cohort
- Comparison of Electrocardiographic Criteria for the Detection of Cardiac Abnormalities in Elite Black and White Athletes
- Hypoxic Response Contributes to Altered Gene Expression and Precapillary Pulmonary Hypertension in Patients With Sickle Cell Disease
- Systolic and Diastolic Mechanics in Stress Cardiomyopathy
- Predictors of Long-Term Recurrent Vascular Events After Ischemic Stroke at Young Age: The Italian Project on Stroke in Young Adults
- Innate Response Activator B Cells Aggravate Atherosclerosis by Stimulating T Helper-1 Adaptive Immunity
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Five-Year Survival in Patients With ST-Segment–Elevation Myocardial Infarction According to Modalities of Reperfusion Therapy: The French Registry on Acute ST-Elevation and Non–ST-Elevation Myocardial Infarction (FAST-MI) 2005 Cohort
Although primary percutaneous coronary intervention (PCI) is the reference reperfusion modality in patients with ST-segment–elevation myocardial infarction, it remains difficult to implement in due time. Since the early trials comparing primary PCI and intravenous fibrinolysis, this latter method of reperfusion has evolved toward an integrated pharmaco-invasive approach, with intravenous fibrinolysis followed by delayed coronary angiography and PCI within 24 hours of lytic administration. Recently, the Strategic Reperfusion Early after Myocardial Infarction (STREAM) trial has compared such a pharmaco-invasive approach with primary PCI in patients seen early after the onset of chest pain, when PCI could not be performed within 60 minutes of first medical contact. Thirty-day outcomes were not statistically different. How a pharmaco-invasive strategy compares with primary PCI in the long term is not known. We assessed 5-year survival in patients with ST-segment–elevation myocardial infarction included in the French Registry on Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction (FAST-MI) 2005 registry according to the initial choice of reperfusion strategy. Survival at 5 years was higher with the pharmaco-invasive strategy, with a difference reaching statistical significance in multivariate analyses. In the replication of the STREAM population, pharmaco-invasive strategy was associated with marginally higher survival compared with delayed primary PCI. In a real-world setting, on a nationwide scale, a pharmaco-invasive strategy constitutes a valid alternative to primary PCI, with 5-year survival at least equivalent to that of the reference reperfusion method. See p 1629.
Comparison of Electrocardiographic Criteria for the Detection of Cardiac Abnormalities in Elite Black and White Athletes
Despite efforts to improve the specificity of ECG screening criteria in athletes, the issue of high false-positive rates is concerning. Athletes of African/Afro-Caribbean origin (black athletes; BAs) exhibit more profound electric changes compared with white athletes (WAs) and may be more susceptible to false-positive results and erroneous disqualification. The established 2010 European Society of Cardiology recommendations for ECG interpretation in athletes are derived exclusively from WAs and have not been tested in BAs. This study reports the performance of current ECG interpretation criteria in elite BAs and WAs compared with proposed “refined criteria,” which incorporate new research findings on benign ECG patterns in athletes and the effect of black ethnicity. The European Society of Cardiology recommendations, the more recent Seattle criteria, and the refined criteria were tested in 1208 BAs and 4297 WAs. All 3 criteria were applied to 103 young, asymptomatic athletes with hypertrophic cardiomyopathy. The European Society of Cardiology recommendations resulted in 40.4% BAs and 16.2% WAs exhibiting a positive ECG that would require investigation. The Seattle criteria reduced the number of positive ECGs to 18.4% in BAs and 7.1% in WAs. The refined criteria produced the greatest reduction, to 11.5% in BAs and 5.3% in WAs. All 3 criteria maintained 98% sensitivity to detect hypertrophic cardiomyopathy. Incorporation of the refined criteria into future ECG interpretation guidelines in athletes will reduce the burden of false-positive results in both WAs and BAs. The 71% reduction in positive ECGs in BAs compared with European Society of Cardiology recommendations has huge implications in countries accommodating a large population of BAs. See p 1637.
Hypoxic Response Contributes to Altered Gene Expression and Precapillary Pulmonary Hypertension in Patients With Sickle Cell Disease
Pulmonary hypertension is a complication of sickle cell disease (SCD) that is associated with high mortality. Chronic hypoxia may lead to the development of hypertension, and increased hypoxia-inducible factor-1, the master regulator of the hypoxic response, is implicated in forms of pulmonary hypertension not associated with hypoxia. As the hypoxic response is chronically elevated in SCD because of chronic anemia, we investigated the hypoxic transcriptional response in peripheral blood mononuclear cells. MAPK8, encoding mitogen-activated protein kinase 8, a key regulator of apoptosis, proliferation, differentiation, and transcription, was identified as a hypoxia downregulated gene. A single nucleotide polymorphism (SNP) that further downregulates MAPK8 expression, rs10857560, was associated with right heart catheterization-documented precapillary pulmonary hypertension in 2 large SCD cohorts composed of 764 subjects; all 14 of the identified patients with precapillary pulmonary hypertension were homozygotes (P=6×10–6). A possible mechanism for the risk for pulmonary hypertension associated with decreased MAPK8 expression in SCD is decreased apoptosis in pulmonary vascular cells permitting excessive proliferation. Future studies should examine the molecular role of MAPK8 in protection from precapillary pulmonary hypertension in SCD and whether interventions targeting this pathway can be developed for prevention or treatment. Genotyping for rs10857560 might also be a useful screening test for precapillary pulmonary hypertension in SCD. See p 1650.
Systolic and Diastolic Mechanics in Stress Cardiomyopathy
Stress cardiomyopathy (SCM) is an increasingly recognized syndrome seen predominantly in women and occurs in response to emotional or physical stress. SCM is thought to be related to acute catecholamine myocardial injury and is reversible, whereas the ischemic injury underlying acute myocardial infarction (MI) is not. We hypothesized that these fundamental mechanistic differences between SCM and acute MI would be associated with different profiles of systolic and diastolic function. We therefore examined 3 groups, all women: an SCM group (n=24; mean age, 63±12 years), a left anterior (LAD) ST-segment–elevation MI group (n=36; mean age, 63±10 years), and a referent control group (n=30; mean age, 62±8 years). All underwent angiography, ventriculography, and pressure measurements within 48 hours of presentation. Echocardiography documented return to normal systolic function in all SCM patients, per inclusion criteria. Our principal findings were the following: Left ventricular diastolic pressures and diastolic stiffness were similarly elevated in the SCM and LAD MI groups compared with the control group; left ventricular end-systolic and end-diastolic volumes in the 2 disorders were correspondingly higher than in control subjects but no different from each other; and (3) indexes of contractility and ventricular-arterial coupling were similarly abnormal in SCM and LAD MI. Functionally, in the initial hours to days after presentation, SCM is indistinguishable from acute LAD-territory MI. This is surprising in view of the completely different pathophysiology and prospects for reversibility. The similarity of these phenotypes suggests to us the controversial hypothesis that some of the left ventricular dysfunction in patients with acute ischemic injury (LAD MI) may be due to catecholamine injury. See p 1659.
Predictors of Long-Term Recurrent Vascular Events After Ischemic Stroke at Young Age: The Italian Project on Stroke in Young Adults
Data on long-term risk of recurrent thrombotic events in young adults with first-ever ischemic stroke are limited, and scarce information is available on what factors may predict such a risk. In the present investigation, we evaluated the impact of age-specific risk factors on thrombotic recurrence in a cohort of 1867 patients with ischemic stroke aged 18 to 45 years, in the setting of the multicentric Italian Project on Stroke at Young Age (IPSYS). The average rate of recurrence was 2.26 per 100 person-years at risk. The 14.7% cumulative risk of recurrence we observed 10 years after the index event suggests that young adults are at substantial risk of further thrombotic episodes over a long-term follow-up. Our findings also indicate that a familial history of stroke, circulating antiphospholipid antibodies, discontinuation of antiplatelet and antihypertensive medications for secondary prevention, and a personal history of migraine with aura, as well, and, to a lesser extent, of traditional vascular risk factors (arterial hypertension, diabetes mellitus, smoking, hypercholesterolemia) are independent predictors of this risk. This emphasizes the need for appropriate prevention therapies and the importance of specific lifestyle treatment strategies in this age category. Additionally, we generated and internally validated a risk prediction algorithm (the IPSYS score, whose values range between 0 and 4 depending on the combination of these predictors) which might serve as a tool in the clinical and public health setting for estimating the individual propensity to long-term thrombotic recurrence of young ischemic stroke patients. See p 1668.
Innate Response Activator B Cells Aggravate Atherosclerosis by Stimulating T Helper-1 Adaptive Immunity
Atherosclerosis is a lipid-driven inflammatory disease, yet treatment regimens currently lack genuinely anti-inflammatory approaches. The growth of human and mouse atherosclerotic lesions is characterized by the influx of functionally diverse leukocytes to the vessel wall. Because leukocytosis is a risk factor for complications of atherosclerosis in humans, understanding how leukocytes affect the course of disease is important and may lead to new strategies that either augment or attenuate particular leukocyte function. This study shows that a previously unknown leukocyte population plays an important role in atherosclerosis. Innate response activator B cells develop in lymphoid organs in humans with atherosclerosis at high numbers and in the 2 major mouse models. Functionally, innate response activator B cells aggravate atherosclerosis by shaping Th1-type adaptive immunity. The study identifies an upstream node of leukocyte communication and suggests that targeting innate response activator B cell function might be a strategy for the treatment of cardiovascular disease. See p 1677.
- © 2014 American Heart Association, Inc.
- Systolic and Diastolic Mechanics in Stress Cardiomyopathy
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