Circulation. 2008;117:453-455
doi: 10.1161/CIRCULATIONAHA.107.188518
doi: 10.1161/CIRCULATIONAHA.107.188518
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(Circulation. 2008;117:453-455.)
© 2008 American Heart Association, Inc.
Clinical Summaries
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Catheter Ablation for the Treatment of Electrical Storm in Patients With Implantable Cardioverter-Defibrillators: Short- and Long-Term Outcomes in a Prospective Single-Center Study |
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Catheter Ablation for the...
Pulmonary Vein Region Ablation...Multiple shocks resulting from repetitive episodes of ventricular tachycardia, known as electrical storm (ES), occur in 10% to 20% of patients with implantable cardioverter-defibrillators. This frightening clinical emergency also predicts an increased risk of subsequent cardiac death among survivors. This case series assesses the role of catheter ablation in controlling ES and the subsequent long-term incidence of recurrent ventricular tachycardia and cardiac mortality. Ninety-five patients with structural heart disease undergoing catheter ablation for drug-refractory ES were prospectively evaluated. Advanced strategies of mapping and ablation were used in most patients. After 1 to 3 procedures, ES was suppressed in all patients. Programmed electrical stimulation showed that all inducible clinical ventricular tachycardias were abolished in 89% of patients. At a median follow-up of 22 months, 92% of patients were free of ES; 8 patients had recurrent ES, 4 of whom died despite implantable cardioverter-defibrillator intervention. The total cardiac mortality rate was 12%, which compares favorably with the reported late mortality rates for patients who suffer ES. Acute results of catheter ablation predicted the absence of ES recurrence and correlated with reduced cardiac mortality. These observations support the early use of catheter ablation as adjunctive therapy for the treatment of ES. This experience lays the foundation for further studies to determine whether controlling ES with catheter ablation improves long-term survival. See p 462.
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Pulmonary Vein Region Ablation in Experimental Vagal Atrial Fibrillation: Role of Pulmonary Veins Versus Autonomic Ganglia |
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Ablation procedures directed at the pulmonary vein (PV) region have had a very important impact on the management of atrial fibrillation (AF). PV-directed procedures initially targeted highly localized arrhythmogenic PV foci but now focus on larger lesions that isolate the PVs by encompassing the PV ostia and are now effective in a broader range of patients. Vagal discharge is a strong AF promoter in humans and experimental models, and PV-directed procedures can be effective in AF cases with particular dependency on vagal tone (vagal AF). There is evidence from animal models of vagal AF that PVs may act as "drivers" that maintain AF. On the other hand, there also are autonomic ganglia near the PV ostia. Thus, there are 2 potential mechanisms for efficacy of PV-directed procedures in vagal AF: elimination of AF-maintaining PV drivers and damage to autonomic ganglia that act as essential vagal "relay stations." We assessed these mechanisms by targeted ablation in canine models of vagal AF. Eliminating potential PV drivers by isolating or removing the PVs did not prevent AF maintenance during vagal activation. On the other hand, ablation of the autonomic ganglia near the PV ostia suppressed vagal effects and made it impossible for AF to sustain itself in the presence of strong vagal nerve stimulation. Thus, it appears that the PVs are not essential for AF maintenance in the presence of strong vagal tone and that ablation of autonomic ganglia near PV ostia may be an important contributor to the efficacy of PV-directed ablation procedures in some types of AF. See p 470.
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Risk Associated With Preoperative Anemia in Cardiac Surgery: A Multicenter Cohort Study |
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In this multicenter cohort study of 3500 patients who underwent cardiac surgery with cardiopulmonary bypass, preoperative anemia (hemoglobin <12.5 g/dL) was found to be a strong, independent risk factor for adverse outcomes. After risk adjustment, anemic patients (n=774) had 2-fold (95% confidence interval, 1.4 to 2.8) greater odds for the composite adverse outcome of in-hospital death, stroke, or acute kidney injury than did nonanemic patients. If this is a causal relationship and preoperative anemia is not simply a marker for severity of illness, then diagnosing and correcting preoperative anemia may improve outcomes. Because available therapies (iron and erythropoietin) are not risk free and may necessitate delay of surgery, however, randomized controlled clinical trials are warranted to determine whether treating preoperative anemia improves outcomes in patients undergoing cardiac surgery. See p 478.
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Utility of Cardiac Monitoring in Fetuses at Risk for Congenital Heart Block: The PR Interval and Dexamethasone Evaluation (PRIDE) Prospective Study |
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Anti–SSA/Ro-SSB/La antibody–associated congenital heart block is identified most often between 18 and 24 weeks of gestation, and to date, third-degree congenital heart block is irreversible. Intrauterine therapy should be possible, prompting a search for early markers and effective therapy. Fetal echocardiograms were performed serially in 98 pregnancies in antibody-positive women. Fetal Doppler mechanical PR intervals >150 ms were considered prolonged. Three fetuses had third-degree block before 24 weeks, none with preceding abnormal PR intervals, although 1 had preceding tricuspid regurgitation and another had unexplained atrial echodensities. Thus, advanced block and cardiomyopathy can occur within 1 week of a normal echocardiogram without initial first-degree block. Three fetuses had prolonged PR intervals, 2 of which reversed with dexamethasone. Congenital heart block occurred in 19% of pregnancies in mothers of previous congenital heart block children and in 4% of pregnancies in women without a previously affected child. Prolongation of the fetal Doppler mechanical PR interval may be a useful, albeit not a definitive, tool to detect early signs of anti-SSA/Ro–associated cardiac disease. However, spontaneous reversal of a prolonged PR interval is as yet unaddressed. The goal of this monitoring would be to identify a biomarker of reversible injury such as a PR interval prolongation >150 ms, moderate/severe tricuspid regurgitation, and/or an atrial echodensity, each of which might prompt repeat evaluation within 48 hours and/or consideration of a short course of dexamethasone. The morbidity and mortality of third-degree block suggest the need for a prophylactic therapy early in pregnancy before disease onset, targeted at pregnancies in women with prior affected offspring. See p 485.
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Usefulness of Pravastatin in Primary Prevention of Cardiovascular Events in Women: Analysis of the Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA Study) |
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The beneficial effect of statin treatment in reducing the risk of cardiovascular disease is well known from the findings of many large-scale randomized clinical trials. However, there has been some debate about the use of statins in women because of their lower cardiovascular risk compared with men. Notably, a similar reduction in cardiovascular end points was demonstrated with statin use in women and men in the present analysis of the Management of Elevated Cholesterol in the Primary Prevention Groups of Adult Japanese (MEGA) study. Specifically, pravastatin reduced coronary heart disease by 25% and 35%, coronary heart disease and cerebral infarction by 26% and 41%, stroke by 37% and 34%, and total mortality by 41% and 19% in women and men, respectively. Moreover, the beneficial primary prevention effect was more marked in older women. Thus, these findings indicate that it is appropriate and beneficial to consider statin treatment in women with elevated lipids but without a history of cardiovascular disease to reduce their future risk, especially in older women. Long-term use of statin therapy was shown to be safe in the MEGA study, without any increase in serious adverse problems, including female specific cancer. See p 494.
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Vitamin D Deficiency and Risk of Cardiovascular Disease |
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Vitamin D deficiency is highly prevalent in the United States and worldwide. Low levels of 25-hydroxyvitamin D (25-OH D), the principal circulating storage form of vitamin D, are present in as many as one third to one half of otherwise healthy middle-aged to elderly adults. Although the best-characterized sequelae of vitamin D deficiency involve the musculoskeletal system, a growing body of experimental evidence suggests that low levels of vitamin D may adversely affect the cardiovascular system. We studied 1739 Framingham Offspring Study participants without prior cardiovascular disease; 28% had 25-OH D levels <15 ng/mL, and 9% had levels <10 ng/mL. During a mean follow-up of 5.4 years, 120 individuals developed a first cardiovascular event. Individuals with 25-OH D <15 ng/mL had a multivariable-adjusted hazard ratio of 1.62 (95% confidence interval 1.11 to 2.36; P=0.01) for incident cardiovascular events compared with those with 25-OH D
15 ng/mL. This effect was evident in participants with hypertension (hazard ratio 2.13, 95% confidence interval 1.30 to 3.48) but not in those without hypertension (hazard ratio 1.04, 95% confidence interval 0.55 to 1.96). There was a graded increase in cardiovascular risk across categories of 25-OH D, with multivariable-adjusted hazard ratios of 1.53 (95% confidence interval 1.00 to 2.36) for levels 10 to <15 ng/mL and 1.80 (95% confidence interval 1.05 to 3.08) for levels <10 ng/mL (P for linear trend=0.01). In summary, moderate to severe vitamin D deficiency is associated with increased risk for developing cardiovascular disease. Further prospective studies may be warranted to determine whether correction of vitamin D deficiency could contribute to the prevention of cardiovascular disease. See p 503. |
Egg Consumption and Risk of Heart Failure in the Physicians’ Health Study |
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Heart failure (HF) is a major cause of hospitalization and emergency department visits among older adults. Although previous studies have examined the influence of lifestyle and dietary factors on the risk of HF, it is not known whether egg consumption is associated with an increased risk of HF. An egg can contain as much as 200 mg of dietary cholesterol. In the present study, we followed 21 276 participants from the Physicians’ Health Study I for an average of
20 years to examine the association between egg consumption and the risk of HF. Egg consumption was assessed with the use of a simple abbreviated food questionnaire. During the follow-up, a total of 1001 new HF cases occurred in this cohort. Although egg consumption up to 6 times per week was not associated with incident HF, consumption of 1 egg per day was associated with a 30% increased risk of HF, whereas consumption of 2 eggs per day was associated with a 59% increased risk of HF after accounting for confounding factors. Similar results were obtained for HF without antecedent myocardial infarction. Overall, our data suggest that although infrequent egg consumption has no influence on the risk of HF, frequent consumption may increase the risk of HF among US male physicians. See p 512. |
Genetic Variation Within Adrenergic Pathways Determines In Vivo Effects of Presynaptic Stimulation in Humans |
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Hypertension is a major risk factor for cardiovascular disease, renal disease, and stroke. Although the complex phenotype of human hypertension is in part genetically determined (estimated
30%), how individual genes ultimately contribute to the disease is not well understood. Blood pressure is regulated closely by the sympathetic nervous system, which is activated during periods of stress. The sympathetic nervous system has been implicated in the pathogenesis of hypertension, with most research focusing on the postsynaptic aspect of the neuroeffector junction with evaluation of genetic variation of adrenergic receptors. Presynaptically, catecholamines, the sympathetic neurotransmitters, are synthesized by a cascade of steps for synthesis, storage, transport, and metabolism. The present study focused on common genetic variation in the presynaptic catecholaminergic pathway as a cause of interindividual variation in local vascular reactivity. We used the dorsal hand vein, which avoids systemic baroreceptor responses and the hydrostatic pressures in the arterial tree, to measure vascular changes that resulted from a probe of endogenous catecholamine release using the indirect sympathomimetic agent tyramine. Family history of hypertension and female sex predicted blunted vascular responses. Genetic variation at loci for chromogranin B, which aids in formation of the catecholamine storage vesicle, and cytochrome B-561, a storage vesicle membrane electron shuttle for catecholamine synthesis, also predicted vascular response. These polymorphisms illustrate a heritable contribution to adrenergic responses and, when altered, may ultimately contribute to risk for hypertension. Determination of genetic contributors to adrenergic response and hypertension may enable clinicians to identify patients at risk sooner and implement genotype-directed therapy. See p 517. |
Randomized Double-Blind Trial of Darbepoetin Alfa in Patients With Symptomatic Heart Failure and Anemia |
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Anemia is common in heart failure (HF) patients and is associated with worse symptoms and outcomes. Several early studies suggested that anemic HF patients may benefit from therapy with erythropoiesis-stimulating agents. In this 1-year, prospective, randomized, double-blind, placebo-controlled trial in patients with symptomatic HF and anemia, treatment with the erythropoiesis-stimulating agent darbepoetin alfa effectively raised hemoglobin concentration compared with placebo. There were no clinically or statistically significant differences between treatment groups in exercise time, New York Heart Association class, quality of life, or adverse event profile. A prespecified analysis showed a nonsignificant trend toward lower risk of all-cause mortality or first HF hospitalization. The contrast between results of earlier studies, which demonstrated improvements in exercise capacity, New York Heart Association class, and quality of life, and our study highlights the equipoise that clinicians face regarding the management of anemia in HF and the importance of conducting rigorous, well-powered trials. These observations regarding long-term outcomes require further investigation in an adequately powered outcomes trial that will provide the direction that the medical community needs and deserves for the appropriate treatment of anemia in HF. See p 526.
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Acute Administration of Fish Oil Inhibits Triggered Activity in Isolated Myocytes From Rabbits and Patients With Heart Failure |
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Fish oil supplementation reduces sudden death in patients with recent myocardial infarction. Arrhythmias in these patients often are due to triggered arrhythmias that arise from early and/or delayed afterdepolarizations resulting from spontaneous intracellular calcium releases. The mechanism by which fish oil reduces sudden death in patients with a preexisting cardiac condition is unknown. In the present study, we tested whether fish oil fatty acids reduce arrhythmias that are evoked by tachycardia and administration of noradrenalin in heart failure. Our study shows that physiological plasma concentrations of fish oil fatty acids inhibit the formation of triggered arrhythmias in isolated myocytes of rabbits and in patients with heart failure. The mechanism underlying the antiarrhythmic action of fish oil fatty acids is a decrease in intracellular calcium and a reduced response to noradrenalin. Therefore, fish oil fatty acids prevent spontaneous intracellular calcium releases and depolarizations. These findings suggest that the mechanism by which circulating fish oil fatty acids prevent sudden death in patients with heart failure is, at least in part, due to inhibition of triggered arrhythmias. Whether fish oil supplements can be safely administered in heart failure to prevent arrhythmias warrants more extensive testing in clinical trials. See p 536.
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Apoptosis Signal-Regulating Kinase 1/p38 Signaling Pathway Negatively Regulates Physiological Hypertrophy |
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Exercise induces the physiological form of cardiac hypertrophy, which is a favorable adaptive response of the heart to increases in bodily demand. On the other hand, pathological hypertrophy is a maladaptive response to pathological stimuli such as pressure or volume overload and often progresses to heart failure. We have previously reported that the apoptosis signal-regulating kinase 1 (ASK1) is involved in the development of pathological cardiac remodeling. In this study, mice lacking ASK1 or its downstream mitogen-activated protein kinase, p38, showed exaggerated growth of the heart accompanied with increased Akt activity in response to swimming exercise. These results suggest that agents that inhibit ASK1 activation by pathological stimuli antagonize pathological cardiac remodeling while promoting physiological growth of the heart. Such agents could convert a maladaptive pathological type of hypertrophy to an adaptive physiological type and improve the function of diseased heart. It thus may be of benefit to selectively target ASK1 as a potential strategy for the treatment of patients with heart failure. See p 545.
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Dosing of Clopidogrel for Platelet Inhibition in Infants and Young Children: Primary Results of the Platelet Inhibition in Children On cLOpidogrel (PICOLO) Trial |
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Infants and young children with certain types of heart disease (including those with single ventricle after palliation with a systemic-to–pulmonary artery shunt, Kawasaki disease, and intracardiac stents or devices) are at risk for thrombotic events. Antiplatelet therapy with aspirin alone may not be sufficient to prevent thrombosis. The present study was a multicenter, randomized, double-blind, placebo-controlled, dose-ranging study performed to determine the dose of clopidogrel in infants and young children to achieve a mean 30% to 50% inhibition of 5-µmol/L ADP–induced platelet aggregation (ie, inhibition similar to that observed with 75 mg in adults) and to assess the safety and tolerability of clopidogrel in infants and young children. Compared with placebo, clopidogrel 0.20 mg · kg–1 · d–1 resulted in a mean 49.3% (95% confidence interval 25.7% to 72.8%) inhibition of the maximum extent of platelet aggregation and a mean 43.9% (95% confidence interval 18.6% to 69.2%) inhibition of the rate of platelet aggregation. No serious bleeding events occurred. These results show that clopidogrel 0.20 mg · kg–1 · d–1 in children aged 0 to 24 months achieves a platelet inhibition level similar to that in adults taking 75 mg/d. Thus, infants and young children require a considerably lower clopidogrel dose per kilogram than adults. Clopidogrel is well tolerated in infants and young children at this dose. See p 553.
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