- Radiofrequency Ablation of Atrial Fibrillation: Is the Persistence of All Intraprocedural Targets Necessary for Long-Term Maintenance of Sinus Rhythm?
- Reversibility of PRKAG2 Glycogen-Storage Cardiomyopathy and Electrophysiological Manifestations
- Proarrhythmic Aspects of Atrial Fibrillation Surgery: Mechanisms of Postoperative Macroreentrant Tachycardias
- Relation Between Red Blood Cell Distribution Width and Cardiovascular Event Rate in People With Coronary Disease
- Adherence to the Mediterranean Diet Is Inversely Associated With Circulating Interleukin-6 Among Middle-Aged Men: A Twin Study
- Extreme Lipoprotein(a) Levels and Risk of Myocardial Infarction in the General Population: The Copenhagen City Heart Study
- Lack of Association Between the MEF2A Gene and Myocardial Infarction
- Initial Aspirin Dose and Outcome Among ST-Elevation Myocardial Infarction Patients Treated With Fibrinolytic Therapy
- Renal Vasodilatory Action of Dopamine in Patients With Heart Failure: Magnitude of Effect and Site of Action
- Platelet-Derived Stromal Cell–Derived Factor-1 Regulates Adhesion and Promotes Differentiation of Human CD34+ Cells to Endothelial Progenitor Cells
- Adiponectin Prevents Cerebral Ischemic Injury Through Endothelial Nitric Oxide Synthase–Dependent Mechanisms
- High Absolute Risks and Predictors of Venous and Arterial Thromboembolic Events in Patients With Nephrotic Syndrome: Results From a Large Retrospective Cohort Study
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Radiofrequency Ablation of Atrial Fibrillation: Is the Persistence of All Intraprocedural Targets Necessary for Long-Term Maintenance of Sinus Rhythm?
Radiofrequency catheter ablation has emerged as an important therapeutic option in patients with drug-resistant atrial fibrillation. Different approaches have been tested, but specific intraprocedural targets and end points remain controversial. Demonstration that a particular procedural end point, such as conduction block into a pulmonary vein (PV), is critical requires the demonstration of persistence of that end point during follow-up. Recovery of ablation lesions is well reported, so the demonstration of persistence and relation of this to prevention of atrial fibrillation requires repeat electrophysiological study in asymptomatic patients after an effective ablation procedure. The aim of the present study was to verify the long-term result of encircling PV ablation with the end point of atrial potential abatement plus PV disconnection confirmed with a multipolar catheter. Repeat electrophysiology study was performed 2.5 years after successful ablation in a series of patients in stable sinus rhythm after previously persistent atrial fibrillation. These data were compared with those obtained from redo ablation procedures because of atrial fibrillation recurrences. In patients in stable sinus rhythm after ablation, only 37.5% of the PVs remained disconnected, and 60% of the PVs had recovered electrogram voltage within the ablation region. No statistically significant differences were noted between patients with and without recurrences after the initial ablation procedure. This study suggests that common intraprocedural end points such as voltage abatement and PV disconnection persist only in a limited number of patients, even when the outcome is favorable during follow-up. Further studies will be required to confirm these data in larger populations and to determine their implications for ablation strategies. See p 136.
Reversibility of PRKAG2 Glycogen-Storage Cardiomyopathy and Electrophysiological Manifestations
Patients with glycogen-storage–associated cardiomyopathy due to PRKAG2 mutations generally have a poor prognosis because of severe cardiac dysfunction, ventricular preexcitation, and progressive conduction system disease. This study used a system that allows regulation of the timing of expression of the PRKAG2N488I mutation in mice during development. Altering the timing of glycogen depletion in the heart prevents or reverses cardiac hypertrophy, cardiac dysfunction, ventricular preexcitation, and conduction system disease in PRKAG2 glycogen-associated cardiomyopathy. In the era of such advanced therapeutic approaches as gene therapy and enzyme replacement, these data imply that myocardial dysfunction and conduction system disease in glycogen-storage cardiomyopathy could potentially be treated by modulation of glycogen content in the heart and that early initiation of treatment is critical to prevent the development of accessory pathways. Lowering cardiac glycogen content significantly ameliorates morbidity in PRKAG2 cardiomyopathy and could eventually be a viable alternative treatment option to device implantation and heart transplantation for patients who have PRKAG2 mutations with glycogen-storage cardiomyopathy and arrhythmias. See p 144.
Proarrhythmic Aspects of Atrial Fibrillation Surgery: Mechanisms of Postoperative Macroreentrant Tachycardias
Surgical procedures to prevent atrial fibrillation are being performed much more commonly with advances in surgical technologies for lesion creation. As a result, more patients are likely to experience proarrhythmic effects of these operations. Late macroreentrant atrial tachycardias may occur in either atria and may be the result of incomplete surgical lines (such as within the cavotricuspid isthmus or adjacent to the mitral valve annulus). Macroreentry also may occur at the site where surgical boundaries have not been extended through all conducting atrial myocardium (such as at the superior vena caval–right atrial junction). Additional mechanisms may involve the creation of slowly conducting zones of atrium based on the anisotropic conduction properties of structures such as the crista terminalis or Bachmann’s bundle. Although the precise mechanism of these functional central obstacles has not been completely defined, such structures appear to be the site of successful ablation for some arrhythmias in the right atrial free wall and in the roof of the left atrium. A critical aspect of any successful surgical program is close collaboration between the cardiovascular surgeon who is performing these operations and an experienced cardiac electrophysiologist capable of mapping and ablating these arrhythmias. Patients undergoing surgical ablation of atrial fibrillation require close follow-up postoperatively. See p 155.
Relation Between Red Blood Cell Distribution Width and Cardiovascular Event Rate in People With Coronary Disease
Red blood cell distribution width (RDW) is a numerical measure of the variability in size of circulating erythrocytes and is routinely reported as part of the complete blood count as an aid in the differential diagnosis of anemia. A strong independent association between RDW and the risk of adverse outcomes was recently reported in patients with heart failure. However, whether RDW is associated with adverse outcomes in other populations is unknown. In this study, we found a graded, independent association between baseline RDW level and the risk of all-cause death, the development of new heart failure, and coronary events in this population of individuals with previous myocardial infarction who were free of clinically evident heart failure at baseline, most of whom had RDW levels within the normal range. Adjustment for multiple potential confounders attenuated but did not eliminate the association between higher RDW levels and the adverse clinical outcomes. In addition to reaching statistical significance, the magnitude of the increased risk associated with higher levels of RDW was clinically relevant. For example, the risk of all-cause death in participants with RDW in the highest quartile was nearly 80% higher than those in the lowest quartile, similar to the adjusted risk of a recurrent cardiovascular event among Cholesterol and Recurrent Events study participants with C-reactive protein in the highest quintile compared with the lowest. These findings are notable given that RDW is widely available to clinicians as part of the complete blood count and therefore incurs no additional costs, in contrast to other novel markers of cardiovascular risk. See p 163.
Adherence to the Mediterranean Diet Is Inversely Associated With Circulating Interleukin-6 Among Middle-Aged Men: A Twin Study
The Mediterranean diet is protective against cardiovascular disease; a proposed mechanism is through reducing systemic inflammation. Dietary habits are acquired while growing up and may be confounded by other behavioral, environmental, or genetic factors shared by family members. It is unknown to what extent the association between the Mediterranean diet and inflammation is due to other familial factors. We used data on identical and fraternal twins raised together to answer this question because twins are naturally matched for measured and unmeasured common environmental factors while growing up. Monozygotic twin pairs are also 100% matched for genetic factors, whereas fraternal pairs share on average 50% of their genes. We constructed a 10-unit diet score to measure adherence to the Mediterranean diet; a higher score indicates greater adherence to the Mediterranean diet. We found that a 1-unit increase in the Mediterranean diet score was associated with a 5% decrease in systemic inflammation measured by means of plasma interleukin-6 concentration. After further controlling for shared familial and genetic factors by examining differences between twins in a pair, we found that a twin with a 1-unit-higher Mediterranean diet score than his twin brother had a 9% lower interleukin-6 concentration. In contrast, shared familial and genetic factors did not significantly contribute to the association between MDS and inflammation. Our findings substantiate the protective role of the Mediterranean diet on cardiovascular risk and support the importance of consuming a healthier diet to prevent cardiovascular disease. See p 169.
Extreme Lipoprotein(a) Levels and Risk of Myocardial Infarction in the General Population: The Copenhagen City Heart Study
In this study of the adult Danish general population, the Copenhagen City Heart Study, which included 9330 men and women followed-up for 10 years, we observed a stepwise increase in risk of myocardial infarction with increasing levels of lipoprotein(a) in both genders, with no evidence of a threshold effect. We found that extreme lipoprotein(a) levels >95th percentile predict a 3- to 4-fold increase in risk of myocardial infarction and absolute 10-year risks of 20% and 35% in high-risk women and men. At present, no acceptable means of lowering lipoprotein(a) levels exist. However, lipoprotein(a) measurements among medium-risk individuals will help to identify as yet unidentified high-risk individuals who could benefit from other aggressive, prophylactic measures, including statins directed at elevated cholesterol levels. Indeed, the influence of lipoprotein(a) in causing myocardial infarction and ischemic heart disease is muted with substantial cholesterol reductions in hypercholesterolemic patients. In particular, individuals with a strong family history of ischemic heart disease would be candidates for lipoprotein(a) measurements because lipoprotein(a) levels are predominantly genetically determined and lipoprotein(a) is considered a quantitative genetic trait. See p 176.
Lack of Association Between the MEF2A Gene and Myocardial Infarction
After the initial report of a 21-bp deletion in the MEF2A gene as the disease-causing genetic variant in a large family with autosomal-dominant inheritance of coronary artery disease, case-control studies on single genetic variants within the MEF2A gene revealed controversial results. In the present, and thus far the largest, analysis, no evidence was found for a significant association of the MEF2A gene with myocardial infarction. We studied defined genetic variants in 2 large study populations of patients with familial and sporadic myocardial infarction and 2 control populations and also analyzed single-nucleotide polymorphisms from a genome-wide association study comprehensively covering the MEF2A gene. Thus, MEF2A is added to a growing list of candidate genes for complex diseases in which no consistent association with a defined phenotype across various populations could be observed. Therefore, results from molecular genetic association studies have to be interpreted with caution and should not yet be transferred or should be transferred in only a very limited fashion to clinical practice (eg, estimating the individual genetic risk for a complex disease). However, genome-wide association studies analyzing hundreds of thousands of single-nucleotide polymorphisms might offer new opportunities in this regard. Recently, 4 genome-wide association studies for myocardial infarction and coronary artery disease revealed very promising results in that chromosomal regions could be identified that displayed robust association with myocardial infarction and coronary artery disease in various independent populations. See p 185.
Initial Aspirin Dose and Outcome Among ST-Elevation Myocardial Infarction Patients Treated With Fibrinolytic Therapy
The International Study of Infarct Survival (ISIS-2) trial demonstrated that treatment with 162.5 mg aspirin reduces morbidity and mortality in ST-elevation myocardial infarction (STEMI). On the basis of these data, the American College of Cardiology, American Heart Association, and European Society of Cardiology gave a class I level of evidence A to immediate use of 162 mg of aspirin. Nevertheless, the most common initial dose of aspirin in the immediate setting of STEMI is 325 mg (class I level of evidence C). Given the uncertainty of immediate aspirin dose, we performed a retrospective analysis of 2 large STEMI fibrinolytic trials (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries [GUSTO I] and Global Use of Strategies to Open Occluded Coronary Arteries [GUSTO III]) to assess the relationship between aspirin dose (162 versus 325 mg) and short-term outcomes after STEMI. We demonstrated no significant association between initial aspirin dose (162 versus 325 mg) and risk of death, myocardial infarction, or stroke. However, the initial dose of 325 mg was associated with a significant increase in the risk of moderate or severe bleeding compared with 162 mg. Although these data are nonrandomized, they suggest that for the first dose of aspirin, 162 mg may be as effective as and safer than 325 mg for the acute treatment of STEMI. Until future randomized data are provided to support the use of 325 mg in the setting of STEMI, it may be worthwhile to use 162 mg, a dose previously established to lessen cardiovascular morbidity and mortality in this setting. See p 192.
Renal Vasodilatory Action of Dopamine in Patients With Heart Failure: Magnitude of Effect and Site of Action
Decreased renal function is common in hospitalized patients with heart failure, and attempts to improve it with a number of vasoactive medications have not resulted in a consistent favorable effect. A “renal dose” of dopamine has been used by clinicians for many years to enhance renal function in critically ill patients. The renal circulatory effect of dopamine, however, has not been well studied in patients with heart failure. The results of the present study demonstrated a significant vasodilatory effect of dopamine in doses between 2 and 10 μg · kg−1 · min−1 on both resistance and conductance renal arteries. This effect resulted in a significant reduction in renal vascular resistance and a rise in renal blood flow. In addition, intravenous dopamine resulted in a marked effect on cardiac output. These beneficial effects of intravenous dopamine both on the systemic and renal circulation are encouraging and suggest that further research on the effect of dopamine on renal function and outcome in hospitalized patients with heart failure is warranted. See p 200.
Platelet-Derived Stromal Cell–Derived Factor-1 Regulates Adhesion and Promotes Differentiation of Human CD34+ Cells to Endothelial Progenitor Cells
The tissue-healing process in patients who have had a myocardial infarction or any ischemic disease is based on recruitment and subsequent differentiation of a small number of circulating stem cells. Understanding the mechanisms that are responsible for the local recruitment and differentiation of stem cells may enable us to better understand the pathophysiology of tissue remodeling and regeneration. This study investigated the role of platelet-derived stromal cell–derived factor-1 (SDF-1) in adhesion and subsequent differentiation of human CD34+ cells into endothelial progenitor cells. Adherent platelets express substantial amounts of SDF-1 and recruit CD34+ cells under high arterial shear in vitro and after carotid ligation in mice in vivo. Platelets that adhere to human arterial endothelial cells enhance the adhesion of CD34+ cells on endothelium under flow conditions, a process that is inhibited by anti-SDF-1. During intestinal ischemia/reperfusion in mice, anti-SDF-1 and anti-CXCR4, but not isotype control antibodies, abolish the recruitment of CD34+ cells in microcirculation. Moreover, platelet-derived SDF-1 binding to CXCR4 receptor promotes platelet-induced differentiation of CD34+ cells into endothelial progenitor cells, as verified by colony-forming assays in vitro. These findings imply that platelet-derived SDF-1 regulates adhesion of stem cells in vitro and in vivo and promotes differentiation of CD34+ cells to endothelial progenitor cells. Because tissue regeneration depends on recruitment of progenitor cells to peripheral vasculature and their subsequent differentiation, platelet-derived SDF-1 may contribute to vascular and myocardial regeneration. See p 206.
Adiponectin Prevents Cerebral Ischemic Injury Through Endothelial Nitric Oxide Synthase–Dependent Mechanisms
Obesity-linked diseases are linked to an increased risk for ischemic stroke. Adiponectin is a fat-derived hormone that is downregulated in obese subjects. In the present study, we examined the causal role of adiponectin in ischemic stroke. Adiponectin deficiency contributed to increased cerebral injury after ischemia-reperfusion. Conversely, adiponectin supplementation reduced cerebral ischemia-reperfusion injury. Adiponectin deficiency resulted in decreased cerebral blood flow and reduced endothelial nitric oxide synthase signaling during ischemia. The beneficial action of adiponectin was abolished in endothelial nitric oxide synthase–deficient mice. Thus, adiponectin protects the brain from acute ischemic injury through an endothelial nitric oxide synthase–dependent mechanism. Our data suggest that adiponectin represents a therapeutic target molecule for the prevention of ischemic stroke. See p 216.
High Absolute Risks and Predictors of Venous and Arterial Thromboembolic Events in Patients With Nephrotic Syndrome: Results From a Large Retrospective Cohort Study
The association between the nephrotic syndrome and thromboembolic events has been known for decades; however, no data are available on the absolute risk of either venous (VTE) or arterial thromboembolism (ATE). The reported risks of thromboembolism in patients with nephrotic syndrome are based on case reports and small studies, most with limited follow-up. Previous assessments of VTE risk have been based largely on asymptomatic cases of renal vein thrombosis, the clinical relevance of which is not clear. Moreover, predictive factors of both VTE and ATE in these patients have yet to be determined. In this study, the absolute risks of symptomatic VTE and ATE were assessed. Thromboembolism was many times higher than the estimated age- and sex-weighted absolute risks in the general population. The risk of thromboembolism was excessively high in the first 6 moths of observation. Whereas the risk of VTE was related to the severity of nephrotic syndrome, the risk of ATE was related to estimated glomerular filtration rate and classic risk factors for atherosclerosis. These findings highlight the need for prospective randomized trials to evaluate the effect of current antiproteinuric treatment on the risk of thromboembolism and the benefits of primary thromboprophylaxis. These findings also suggest that primary thromboprophylaxis could be beneficial, particularly during the first 6 months, for patients at highest risk, and further studies are needed to demonstrate clinical utility in this setting. See p 224.
- Reversibility of PRKAG2 Glycogen-Storage Cardiomyopathy and Electrophysiological Manifestations
- Lack of Association Between the MEF2A Gene and Myocardial Infarction
- Info & Metrics