Circulation: Clinical Summaries
Original Research Put Into Perspective for the Practicing Clinician
- Implantable Cardioverter-Defibrillator Registry Risk Score Models for Acute Procedural Complications or Death After Implantable Cardioverter-Defibrillator Implantation
- Plasma B-Type Natriuretic Peptide Levels and Recurrent Arrhythmia After Successful Ablation of Lone Atrial Fibrillation
- Mechanical Coupling Between Myofibroblasts and Cardiomyocytes Slows Electric Conduction in Fibrotic Cell Monolayers
- Atrial Fibrillation and Death After Myocardial Infarction: A Community Study
- Growth-Differentiation Factor-15 Is a Robust, Independent Predictor of 11-Year Mortality Risk in Community-Dwelling Older Adults: The Rancho Bernardo Study
- Declining Stroke and Vascular Event Recurrence Rates in Secondary Prevention Trials Over the Past 50 Years and Consequences for Current Trial Design
- Antenatal Sildenafil Treatment Attenuates Pulmonary Hypertension in Experimental Congenital Diaphragmatic Hernia
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Implantable Cardioverter-Defibrillator Registry Risk Score Models for Acute Procedural Complications or Death After Implantable Cardioverter-Defibrillator Implantation
Implantable cardioverter-defibrillators represent a potentially lifesaving therapy for patients at high risk of sudden cardiac death. In general, the procedure is safe, but complications can and do occur, even among the most experienced implanters. The present study examined data from the National Cardiovascular Data Registry (NCDR) ICD Registry, which has prospectively gathered data on patients undergoing ICD implantation since 2006. The rates of in-hospital complication and mortality were studied in patients from 268 701 hospitalizations at 1300 hospitals. Clinical variables available to the clinician before the procedure were then used to derive a model identifying factors associated with adverse events. This information was used to create a simple risk score to identify patients at high and low risk of adverse events. Patients with low risk scores may not require the level of care usually provided to patients undergoing ICD implantation. Conversely, among patients with high risk scores, the timing of ICD implantation may warrant reevaluation. Practically, the model will be a valuable tool in prospectively assessing whether patients should be admitted to the hospital or remain as outpatients. See p 2069.
Plasma B-Type Natriuretic Peptide Levels and Recurrent Arrhythmia After Successful Ablation of Lone Atrial Fibrillation
The exact pathophysiology of atrial fibrillation (AF) is obscured by the effects of the arrhythmia itself because it leads to both mechanical and electric remodeling. This is particularly true for patients with lone AF, which is AF in the absence of heart disease or comorbidities predisposing to the arrhythmia. Plasma B-type natriuretic peptide is abnormally elevated in patients with lone AF, but the exact significance and prognostic implications of this elevation have yet to be determined. In the present study, we followed up 726 patients with lone AF undergoing first-time arrhythmia ablation over a median of 26 months after the ablation procedure. B-type natriuretic peptide levels were found to correlate with lone AF burden (chronicity, altered hemodynamics, and anatomic remodeling with left atrial dilation) and to be a stronger predictor of arrhythmia recurrence after AF ablation than previously described risk factors. This robust and graded association persisted in multivariable analyses. Elevated B-type natriuretic peptide levels may reflect increased cardiac chamber wall stress and/or intrinsic atrial disease in these patients, thus increasing the risk of arrhythmia recurrence. See p 2077.
Mechanical Coupling Between Myofibroblasts and Cardiomyocytes Slows Electric Conduction in Fibrotic Cell Monolayers
Myocardial infarction engages a fibrotic process in which myofibroblasts secrete extracellular matrix proteins to replace the injured tissue. The contractile properties of myofibroblasts help to ensure a smaller and stronger scar area and to preserve mechanical function. However, in the infarct border zone, arrhythmias are prone to initiate owing to slowed and heterogeneous conduction. Although fibrosis has classically been considered arrhythmogenic because of the creation of an inexcitable region, together with zigzag conduction in the border zone, we tested the hypothesis that myofibroblasts can actively influence electrophysiological function through mechanoelectric coupling to the cardiomyocytes. In this study, impaired electric conduction in cocultured monolayers of myofibroblasts and cardiomyocytes can be dramatically improved by applying an excitation-contraction inhibitor or mechanosensitive channel blockers. Our findings advocate a novel mechanism whereby cardiac myofibroblasts exert tension on the myocyte membrane, which leads to slowed and heterogeneous electric conduction through the action of mechanosensitive ion channels. Provided that these in vitro results are corroborated in the intact heart, inhibition of this form of mechanoelectric interaction in the heart may be a way to decrease susceptibility to arrhythmias. See p 2083.
Atrial Fibrillation and Death After Myocardial Infarction: A Community Study
Atrial fibrillation (AF) often coexists with myocardial infarction (MI), yet its prognostic influence is in dispute. Prior reports studied the role of AF during the early hospitalization for acute MI on the risk of death and could not address the timing of AF in relation to the MI. Furthermore, the applicability of existing data to the community was uncertain. We assessed the occurrence of AF among MI patients, determined whether it has changed over time, and quantified its impact on mortality after MI. Among 3220 patients hospitalized with incident (first-ever) MI from 1983 to 2007 in the community, AF preceding MI was identified in 304 patients, and 729 developed AF after MI. The cumulative incidence of AF after MI at 5 years was 19%, and did not change over the calendar year of MI (the incidence of AF was the same regardless of when the MI occurred). During follow-up, 1638 deaths occurred, and AF was associated with a large increase in risk of death, independently of clinical characteristics at the time of MI and heart failure. This risk was the greatest for AF occurring later after the MI. Thus, in the community, AF is frequent in the setting of MI and carries an excess risk of death. See p 2094.
Growth-Differentiation Factor-15 Is a Robust, Independent Predictor of 11-Year Mortality Risk in Community-Dwelling Older Adults: The Rancho Bernardo Study
The goal of risk stratification for primary prevention of cardiovascular disease is to identify individuals who may be candidates for interventions that could improve outcomes. Current risk stratification tools remain imperfect, and biomarkers that reflect novel pathophysiological pathways could improve risk assessment as well as provide insight into potential therapeutic targets. Growth differentiation factor-15 (GDF-15) is a divergent member of the transforming growth factor-β cytokine superfamily that is upregulated in the myocardium after ischemic injury. Previous community-based studies have shown that higher levels of GDF-15 are associated with prevalent cardiovascular disease. The present study of older community-dwelling adults free of known cardiovascular disease from the Rancho Bernardo Study evaluated the association of GDF-15 levels with cardiovascular outcomes and mortality and found that GDF-15 was a robust predictor of all-cause, cardiovascular, and noncardiovascular mortality even after adjustment for traditional cardiovascular disease risk factors, renal function, and body size. In models containing all 3 markers, both GDF-15 and N-terminal pro-B-type natriuretic peptide, but not C-reactive protein, added incremental value for prediction of cardiovascular and all-cause mortality. When associations are confirmed in other cohorts and when further studies clarify the mechanism of action, GDF-15 may ultimately be a worthy target for therapeutic interventions to prevent cardiovascular and all-cause death. See p 2101.
Declining Stroke and Vascular Event Recurrence Rates in Secondary Prevention Trials Over the Past 50 Years and Consequences for Current Trial Design
Formal analysis of secondary stroke prevention trials over the last 5 decades confirms that vascular event rates in control arms have declined substantially. Annual recurrent stroke rates in control arms fell from 8.71% in trials launched in the 1960s to 6.10% in the 1970s, 5.41% in the 1980s, 4.04% in the 1990s, and 4.98% in the 2000s. Annual event rates for fatal stroke decreased from 2.87±1.04% in the 1960s to 0.36±0.14% in the 2000s, and those for major vascular events declined from 10.91±1.29% in the 1960s to 6.29±0.68% in the 2000s. Multivariate analysis suggests that increasing antithrombotic use and lower blood pressures were the most important drivers of vascular event rate reduction. The sample size required for adequately powered trials more than doubled during the study period. If a continued linear decline is assumed, the annual recurrent stroke rate in trial control arms in the coming decade is projected to be 2.25%, and control group sample size requirements would increase to 15 983 patients for a trial designed to detect a 20% relative risk reduction in the frequency of recurrent stroke, with 2 years of follow-up, 80% power, and 5% α error. The introduction into clinical practice of successive waves of therapies with proven efficacy in stroke prevention has been notably successful, resulting in a substantial decline in the rate of recurrent vascular events in the control arms of secondary stroke prevention trials. Consequently, trials of new therapies are more arduous, requiring ever larger sample sizes to confirm treatment efficacy, and clinical investigators must cope with the paradox of progress. See p 2111.
Antenatal Sildenafil Treatment Attenuates Pulmonary Hypertension in Experimental Congenital Diaphragmatic Hernia
Congenital Diaphragmatic Hernia (CDH) remains the most life-threatening cause of respiratory failure in newborns. Lung hypoplasia and pulmonary hypertension refractory to inhaled nitric oxide are the main factors limiting survival. Currently, there is no specific treatment for CDH. Here, we show in a herbicide-induced CDH rat model that maternal treatment with sildenafil, a strategy reminiscent of antenatal steroid treatment given to women in preterm labor to mature the fetal lung, effectively crosses the placenta, increases fetal lung cyclic GMP, promotes lung growth, attenuates features of pulmonary hypertension and increases pulmonary artery relaxation in response to a nitric oxide donor in vitro. Our findings open new therapeutic avenues for pharmacological antenatal strategies to improve the outcome of infants with CDH. Given the high mortality/morbidity of CDH, the relative pulmonary vascular specificity of sildenafil, its low cost, and its postmarketing safety record make it an attractive therapeutic option that warrants further studies in infants with CDH. See p 2120.
- © 2011 American Heart Association, Inc.
- Atrial Fibrillation and Death After Myocardial Infarction: A Community Study
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