Circulation: Clinical Summaries
Original Research Put Into Perspective for the Practicing Clinician
- Net Clinical Benefit of Warfarin in Patients With Atrial Fibrillation: A Report From the Swedish Atrial Fibrillation Cohort Study
- Risk of Arrhythmia and Sudden Death in Patients With Asymptomatic Preexcitation: A Meta-Analysis
- Association of Fetuin-A With Incident Diabetes Mellitus in Community-Living Older Adults: The Cardiovascular Health Study
- Chronic Inhibition of cGMP Phosphodiesterase 5A Improves Diabetic Cardiomyopathy: A Randomized, Controlled Clinical Trial Using Magnetic Resonance Imaging With Myocardial Tagging
- Magnetic Resonance Imaging With 3-Dimensional Analysis of Left Ventricular Remodeling in Isolated Mitral Regurgitation: Implications Beyond Dimensions
- Long-Term (>10 Years) Clinical Outcomes of First-in-Human Biodegradable Poly-l-Lactic Acid Coronary Stents: Igaki-Tamai Stents
- Effects of Phosphodiesterase Type 5 Inhibition on Systemic and Pulmonary Hemodynamics and Ventricular Function in Patients With Severe Symptomatic Aortic Stenosis
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Net Clinical Benefit of Warfarin in Patients With Atrial Fibrillation: A Report From the Swedish Atrial Fibrillation Cohort Study
Atrial fibrillation is a major cause of ischemic stroke. Oral anticoagulants give good protection against ischemic stroke but also increase the risk of bleeding. Intracranial hemorrhage is the most feared complication with high mortality and morbidity. We investigated how to maximize the net clinical benefit by balancing ischemic stroke against intracranial hemorrhage in 182 678 atrial fibrillation patients in the Swedish National Hospital Discharge Register. Patients were classified according to stroke risk (CHADS2 and CHA2DS2-VASc) and bleeding risk (HAS-BLED [hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly]). As the risk of ischemic stroke increased, the risk of intracranial hemorrhage and other bleeding also increased. Patients with high bleeding risk scores suffered more ischemic strokes than bleeding events, so the net clinical benefit favored anticoagulation for almost all patients except those patients with very low embolic risk; the CHA2DS2-VASc was able to identify those patients (3.9% of all patients) who had no net clinical benefit or even some disadvantage from anticoagulant treatment with warfarin. Thus, we conclude that in almost all patients with atrial fibrillation, the risk of ischemic stroke without anticoagulant treatment is far higher than the risk of intracranial hemorrhage with anticoagulant treatment and that most atrial fibrillation patients should be offered effective thromboprophylaxis with oral anticoagulation. See p 2298.
Risk of Arrhythmia and Sudden Death in Patients With Asymptomatic Preexcitation: A Meta-Analysis
The incidence of sudden cardiac death (SCD) and the management of this risk in patients with asymptomatic preexcitation remain controversial. We performed a meta-analysis of 20 studies reporting on asymptomatic patients (n=1869) with preexcitation who did not undergo ablation (11 722 person-years of follow-up). A total of 10 SCDs were reported with 9 SCDs from studies originating from Italy. The risk of SCD is estimated at 1.25 per 1000 person-years (95% confidence interval, 0.57–2.19). The risk of supraventricular tachycardia was 16 (95% confidence interval, 10–24) events per 1000 person-years of follow-up. The risk of SCD was statistically significantly lower in the non-Italian compared with the Italian studies (P=0.0044). Children had a numerically higher SCD event rate (P=0.07) and supraventricular tachycardia event rate (P=0.38) compared with adults. Therefore, a higher index of suspicion for arrhythmia is warranted, and careful follow-up with monitoring for arrhythmia in children seems prudent. When considering management options in patients with asymptomatic preexcitation, a carefully informed patient (or parent) needs to choose between the risk of SCD and the success and complication rates associated with electrophysiological study and ablation. The evolution of the clinical status from an asymptomatic state to symptoms likely portends a higher risk for SCD, and these patients should seek medical review. See p 2308.
Association of Fetuin-A With Incident Diabetes Mellitus in Community-Living Older Adults: The Cardiovascular Health Study
Unlike adipocytokines, fetuin-A is produced in the liver. It is secreted by hepatocytes into serum, and induces peripheral insulin resistance in vitro. We sought to evaluate the association of fetuin-A with incident diabetes mellitus in older persons, and to determine if associations differ by age, sex, and race, and among persons with CVD. Among 3,710 persons aged 65 years and with 10.6 years follow-up, we observed that higher serum fetuin-A concentrations were independently associated with incident diabetes mellitus. The association was similar by sex, race, and among those with or without CVD, but appeared weaker among those aged ≥75 years at baseline. Future mechanistic studies focused on the liver-secreted protein fetuin-A may provide new insights to mechanisms leading to diabetes in older adults. See p 2316.
Chronic Inhibition of cGMP Phosphodiesterase 5A Improves Diabetic Cardiomyopathy: A Randomized, Controlled Clinical Trial Using Magnetic Resonance Imaging With Myocardial Tagging
Type 2 diabetes mellitus is associated with cardiac remodeling that may occur independently of ischemic heart disease, hypertension, or macrovascular complications. Cardiac magnetic resonance can be used to measure diabetic cardiomyopathy, for which there is currently no specific treatment. In vitro studies have shown that phosphodiesterase 5 overexpression reduces cGMP levels and exacerbates remodeling. Inhibiting cGMP hydrolysis in stimulated cardiomyocytes can prevent hypertrophy. We studied the effects of 3-month daily sildenafil treatment (a phosphodiesterase 5A inhibitor) on cardiac remodeling in a cohort of asymptomatic, middle-aged men with type 2 diabetes mellitus. Cardiac magnetic resonance imaging revealed that diabetic cardiomyopathy in these patients produced an uncoupling in left ventricular contraction between longitudinal strain, which is reduced, and cardiac axial rotation, which is increased. We found that long-term sildenafil treatment restored coupling by reducing torsion and improving strain. It also reduced the ratio of left ventricular mass to end-diastolic volume that is increased in the presence of concentric hypertrophy. These data suggest that phosphodiesterase 5 inhibition could work as an antiremodeling drug by acting directly on cardiac tissue, independently of other secondary vascular, endothelial, or metabolic effects. Our findings also have an impact on the clinical monitoring of patients with type 2 diabetes mellitus. We showed that (1) asymptomatic diabetic men may already be undergoing cardiac remodeling; (2) monocyte chemotactic protein-1 [MCP1] could be included as a new potential marker related to diabetic cardiomyopathy evolution; and (3) sildenafil can partially reverse these changes. Large-scale studies are needed to test whether phosphodiesterase 5A inhibition could become a new target for antiremodeling drugs and to discover the molecular pathways affected by this class of drugs. See p 2323.
Magnetic Resonance Imaging With 3-Dimensional Analysis of Left Ventricular Remodeling in Isolated Mitral Regurgitation: Implications Beyond Dimensions
Although surgery is indicated in patients with mitral regurgitation when left ventricular (LV) end-systolic dimension is >40 mm, LV ejection fraction may decrease after mitral valve surgery. A major finding of the present investigation is that LV end-systolic dimension does not accurately reflect the extent of LV remodeling, largely because of spherical LV remodeling from the mid to apical LV by magnetic resonance imaging with 3-dimensional analysis. This study demonstrates that even when LV end-systolic dimension remains below the accepted target of 40 mm for surgical intervention of isolated mitral regurgitation, its associated LV end-systolic volume can range as high as twice that of normal control subjects. Magnetic resonance imaging with 3-dimensional analysis– or 3-dimensional echocardiography–derived LV volumes may be preferred to evaluate disease progression in isolated mitral regurgitation. See p 2334.
Long-Term (>10 Years) Clinical Outcomes of First-in-Human Biodegradable Poly-l-Lactic Acid Coronary Stents: Igaki-Tamai Stents
The Igaki-Tamai stent is the first-in-man fully biodegradable coronary stent made of poly-l-lactic acid (PLLA). In the present study, there was a high survival rate free of cardiac death (98% at 10 years) demonstrating the long-term safety of this stent. In the intravascular ultrasound echogenicity analysis, the Igaki-Tamai stent required 3 years to disappear from human coronary arteries. During the process of biodegradation (1–3 years), target lesion revascularization and target vessel revascularization reached a near plateau, suggesting that the process of PLLA biodegradation does not correlate with increased risk of clinical events. Although the mechanism of vessel healing in a chronic phase may not be the same between Igaki-Tamai stents and bioabsorbable drug-eluting PLLA stents, our study is essential in paving the way for a bioabsorbable drug-eluting PLLA stent, especially from the standpoint of long-term safety. See p 2343.
Effects of Phosphodiesterase Type 5 Inhibition on Systemic and Pulmonary Hemodynamics and Ventricular Function in Patients With Severe Symptomatic Aortic Stenosis
Pressure overload resulting from aortic stenosis causes maladaptive ventricular and vascular remodeling that has deleterious consequences. Patients often present when compensatory mechanisms have been exhausted with advanced heart failure and abnormal hemodynamics characterized by pulmonary venous congestion, pulmonary hypertension, and afterload mismatch. These patients are either inoperable or at increased risk for surgery. Other patients have valve replacement before this clinical decompensation, but their outcomes are worse if there is associated hypertrophic ventricular remodeling and diastolic dysfunction. Existing experimental and clinical studies raise the interesting possibility that phosphodiesterase type 5 inhibition may both favorably alter abnormal hemodynamics and retard or reverse maladaptive remodeling in patients with aortic stenosis. Here, we show that a single dose of a phosphodiesterase type 5 inhibitor is safe in patients with severe symptomatic aortic stenosis and is associated with acute improvements in pulmonary and systemic hemodynamics, resulting in biventricular unloading. Importantly, these data suggest that afterload is not necessarily fixed in patients with aortic stenosis and that reducing vascular afterload may improve hemodynamics in these patients. If it is demonstrated that these hemodynamic benefits can be sustained, perhaps adjunctive medical therapy with phosphodiesterase type 5 inhibition in symptomatic patients with advanced heart failure could serve as a stabilizing bridge to definitive therapy with valve replacement with less risk than a balloon valvuloplasty. Our findings support the need for longer-term studies to evaluate the role of phosphodiesterase type 5 inhibition as adjunctive medical therapy in patients with aortic stenosis to address these clinical needs. See p 2353.
- © 2012 American Heart Association, Inc.
- Risk of Arrhythmia and Sudden Death in Patients With Asymptomatic Preexcitation: A Meta-Analysis
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