Original Research Put Into Perspective for the Practicing Clinician
- Cryoablation Versus Radiofrequency Energy for the Ablation of Atrioventricular Nodal Reentrant Tachycardia (the CYRANO Study): Results From a Large Multicenter Prospective Randomized Trial
- Dabigatran and Warfarin in Vitamin K Antagonist–Naive and –Experienced Cohorts With Atrial Fibrillation
- Mortality Resulting From Congenital Heart Disease Among Children and Adults in the United States, 1999 to 2006
- Temporal Trends in Survival to Adulthood Among Patients Born With Congenital Heart Disease From 1970 to 1992 in Belgium
- Adverse Bioenergetic Consequences of Na+-Ca2+ Exchanger–Mediated Ca2+ Influx in Cardiac Myocytes
- Prevalence and Clinical Significance of Papillary Muscle Infarction Detected by Late Gadolinium-Enhanced Magnetic Resonance Imaging in Patients With ST-Segment Elevation Myocardial Infarction
- Intracoronary Optical Coherence Tomography and Histology at 1 Month and 2, 3, and 4 Years After Implantation of Everolimus-Eluting Bioresorbable Vascular Scaffolds in a Porcine Coronary Artery Model: An Attempt to Decipher the Human Optical Coherence Tomography Images in the ABSORB Trial
- Evaluation of the Second Generation of a Bioresorbable Everolimus Drug-Eluting Vascular Scaffold for Treatment of De Novo Coronary Artery Stenosis: Six-Month Clinical and Imaging Outcomes
- Inhibition of Hyaluronan Synthesis Accelerates Murine Atherosclerosis: Novel Insights Into the Role of Hyaluronan Synthesis
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Cryoablation Versus Radiofrequency Energy for the Ablation of Atrioventricular Nodal Reentrant Tachycardia (the CYRANO Study): Results From a Large Multicenter Prospective Randomized Trial
This large prospective randomized study including 509 patients compares the short- and long-term efficacy and complications of radiofrequency catheter ablation (RFCA) versus cryoablation of the slow atrioventricular (AV) pathway in AV nodal reentrant tachycardia (AVNRT). Significantly more patients in the cryoablation than in the RFCA group reached the combined primary end point of immediate ablation failure, permanent AV block, and AVNRT recurrence (12.6% versus 6.3%; P=0.018). The difference in primary end point was driven almost exclusively by the significantly higher rate of AVNRT recurrence after cryoablation (9.4% versus 4.4%; P=0.029), although short-term success was equally high in both groups (96.8% for cryoablation versus 98.4% for RFCA). Occurrence of permanent AV block (0% for cryoablation versus 0.4% for RFCA) was rare. Cryoablation procedures lasted significantly longer than RFCA, and significantly more device-related problems occurred with cryoablation than with RFCA. Pain perception was lower in the cryoablation group (P<0.001). In summary, cryoablation in patients with AVNRT is associated with a comparably high immediate success rate as RF. However, the significantly higher recurrence rate after cryoablation is probably the main limitation of using this energy form for AVNRT ablation, especially because the potential safety benefit of cryoenergy seems negligible. The advantage of less pain perception with cryoablation is counterbalanced by longer procedure times and frequent device functionality failure. See p 2239.
Dabigatran and Warfarin in Vitamin K Antagonist–Naive and –Experienced Cohorts With Atrial Fibrillation
This report compares the novel anticoagulant dabigatran with the current standard, warfarin, in vitamin K antagonist–naive and –experienced populations of patients with atrial fibrillation who are at risk of stroke. It was believed that patients who were vitamin K antagonist experienced were likely to do better than patients who are new to anticoagulation because they have demonstrated the ability to comply with an anticoagulation regimen, they have a personalized dose of warfarin that achieves a therapeutic international normalized ratio value, and they have passed the “vitamin K antagonist stress test,” thereby reducing the chance of uncovering major sources of bleeding. This report found that dabigatran, the novel direct thrombin inhibitor, was better than the comparator warfarin for both vitamin K antagonist–naive and –experienced patients and therefore could be used clinically in both cases. See p 2246.
Mortality Resulting From Congenital Heart Disease Among Children and Adults in the United States, 1999 to 2006
Among infants and young children, congenital heart disease (CHD) is responsible for the largest proportion, 30% to 50%, of mortality resulting from birth defects. Mortality caused by CHD during infancy and childhood is reportedly decreasing, and the prevalence of CHD among adults is increasing. Until recently, limited population-based data have been available on CHD mortality through adulthood. Using US multiple cause-of-death data from the National Center for Health Statistics from 1999 to 2006, the present study examined recent temporal trends in mortality resulting from CHD, explored differences in CHD mortality by race-ethnicity (non-Hispanic whites, non-Hispanic blacks or African Americans, Hispanics, and other non-Hispanic race-ethnicities), and determined whether CHD mortality has declined to the same extent among all race-ethnicities. Although CHD mortality continued to decline among both children and adults, differences between race-ethnicities persist. A large proportion of CHD-related mortality continued to occur during infancy, although significant CHD mortality occurred during adulthood. As CHD mortality continues to decline and people with CHD live longer, managing care into adulthood is increasingly important, particularly during the transition from pediatric to adult specialty care. See p 2254.
Temporal Trends in Survival to Adulthood Among Patients Born With Congenital Heart Disease From 1970 to 1992 in Belgium
This study investigated the actual prospects to survive into adulthood, explored temporal trends in survival over the past decades, and evaluated survival according to the type of heart defect. The information provided is important for clinicians to gain insight into the survival rates of different groups of patients with congenital heart disease. Furthermore, this article shows that survival is determined by decade of birth, disease complexity, type of heart defect, and pulmonary hypertension. This finding can assist clinicians in estimating the risk of mortality in their patients. In addition, this study can be used for future workforce planning. Based on the prevalence of heart defects and survival curves presented in this study, the need for outpatient facilities and required manpower can be estimated at the program, hospital, or country level. See p 2264.
Adverse Bioenergetic Consequences of Na+-Ca2+ Exchanger–Mediated Ca2+ Influx in Cardiac Myocytes
Defects in excitation-contraction coupling and energy starvation are central mechanisms that cause systolic and diastolic dysfunction of the failing heart. Here, by using a patch-clamp–based approach in cardiac myocytes, we reveal a mechanism by which these 2 defects are causally linked. Mitochondria are the primary source for cellular ATP, which is replenished by oxidative phosphorylation. To match ATP supply and demand, Ca2+ stimulates rate-controlling dehydrogenases of the Krebs cycle, which provides NADH for the respiratory chain. Mitochondria take up Ca2+ via a uniporter (MCU) with a rather low affinity for Ca2+. Our results indicate that the efficiency of mitochondrial Ca2+ uptake critically depends on the source and kinetics of cytosolic Ca2+ transients, with optimal efficiency after rapid Ca2+ release from the sarcoplasmic reticulum. This supports the concept of a “mitochondrial Ca2+ microdomain,” in which the close association of mitochondria to the sarcoplasmic reticulum is required to produce high local Ca2+ concentrations sufficient to overcome the low Ca2+ affinity of the MCU. In the failing heart, sarcoplasmic reticulum Ca2+ load is depleted, whereas more Ca2+ enters the cell via the sarcolemmal Na+-Ca2+ exchanger, which in normal hearts only extrudes Ca2+. Because Na+-Ca2+ exchanger–mediated Ca2+ influx is much slower and presumably more remote than sarcoplasmic reticulum Ca2+ release, mitochondrial Ca2+ uptake and stimulation of NADH production were impaired. Such energetic mismatch may explain why treating heart failure with drugs that increase Na+-Ca2+ exchanger–mediated Ca2+ influx (eg, cardiac glycosides) is less efficient than treatment with drugs that restore defective excitation-contraction coupling (eg, β-blockers and angiotensin type 1 blockers). See p 2273.
Prevalence and Clinical Significance of Papillary Muscle Infarction Detected by Late Gadolinium-Enhanced Magnetic Resonance Imaging in Patients With ST-Segment Elevation Myocardial Infarction
Although late gadolinium-enhanced magnetic resonance imaging provides superb imaging of the heart with high tissue contrast and spatial resolution, little attention has been given to the detection of papillary muscle infarction (PapMI). In addition, the relationship between papillary muscle dysfunction and mitral regurgitation has been controversial in patients with ST-segment elevation myocardial infarction. In the present study, we assessed the incidence of PapMI without rupture and its effects on left ventricular morphology and mitral regurgitation using cardiac magnetic resonance imaging in 118 patients with ST-segment elevation myocardial infarction. PapMI was identified in up to 40% of patients, mainly in nonanterior myocardial infarction. The posterior papillary muscle was involved more frequently than the anterior papillary muscle (77% versus 26%; P<0.001). At the acute phase, mitral regurgitation was observed in 34 patients (28.8%). Coaptation height was the independent predictor of the presence of mitral regurgitation by multiple logistic regression analysis. At the 8-month follow-up, infarct size showed a positive correlation with left ventricular end-diastolic volume (r=0.41, P<0.001), and the presence of PapMI was not associated with left ventricular remodeling. Deterioration of mitral regurgitation did not occur in patients with PapMI. Larger-scale and longer-term follow-up studies are required to confirm the impact of PapMI on left ventricular remodeling, mitral regurgitation, and prognosis in patients with ST-segment elevation myocardial infarction. See p 2281.
Intracoronary Optical Coherence Tomography and Histology at 1 Month and 2, 3, and 4 Years After Implantation of Everolimus-Eluting Bioresorbable Vascular Scaffolds in a Porcine Coronary Artery Model: An Attempt to Decipher the Human Optical Coherence Tomography Images in the ABSORB Trial
Alterations of the reflectance characteristics of the everolimus-eluting bioresorbable vascular scaffold struts have been reported in humans. However, in the absence of histology, the interpretation of the appearances of the struts by optical coherence tomography (OCT) remains speculative. In the present animal study, the bioresorbable vascular scaffold (3.0×12.0 mm) was implanted in the coronary arteries of pigs that underwent OCT and then were examined by histology immediately or at 28 days or 2, 3, or 4 years after implantation. To assess the biodegradation, gel permeation chromatography was performed. At 2 years, OCT showed that 80.4% of the strut sites had a box-shaped appearance. On histology, these structures were composed of proteoglycan. By gel permeation chromatography, the polymeric material of bioresorbable vascular scaffold was no longer quantifiable, suggesting complete bioresorption. At 3 years, by OCT, most struts showed dissolved appearances (dissolved black, 43.7%; dissolved bright, 34.8%). Histology showed connective tissue cells within a proteoglycan-rich matrix, signifying the beginning of the integration process. At 4 years, only a few struts were recognizable by OCT, and on histology, struts indiscernible by OCT are also minimally detectable, which suggests complete integration. In summary, despite their defined appearance by OCT, struts at 2 years were largely bioresorbed, and at 4 years, struts indiscernible by OCT corresponded well to the completely integrated struts. OCT might be more sensitive to assess the integration process rather than the polymer alteration. This animal study will potentially serve as a guide for interpretation of OCT after bioresorbable vascular scaffold implantation in the clinical setting. See p 2288.
Evaluation of the Second Generation of a Bioresorbable Everolimus Drug-Eluting Vascular Scaffold for Treatment of De Novo Coronary Artery Stenosis: Six-Month Clinical and Imaging Outcomes
The first generation of the bioresorbable everolimus drug-eluting vascular scaffold showed signs of shrinkage at 6 months, which largely contributed to late luminal loss. To maintain the mechanical integrity of the device up to 6 months, the scaffold design and manufacturing process of its polymer were modified. Forty-five patients successfully received a second-generation bioresorbable everolimus drug-eluting vascular scaffold. One patient had postprocedural release of myocardial enzyme without Q-wave occurrence; 1 patient was treated 1 month later with a metallic drug-eluting stent. At the 6-month follow-up, quantitative coronary angiography disclosed 1 edge restenosis (in-segment binary restenosis, 2.4%). The backscattering of the polymeric struts did not decrease over time; the scaffold area was reduced by only 2.0% with intravascular ultrasound, and no change was noted with optical coherence tomography. The late lumen loss amounted to 0.19±0.18 mm with a limited relative decrease in minimal luminal area of 5.4% on intravascular ultrasound. Optical coherence tomography showed at follow-up that 96.8% of the struts were covered and that malapposition was detected at follow-up in only 3 scaffolds. Mean neointimal growth measured by optical coherence tomography between and on top of the polymeric struts equaled 1.25 mm2, or 16.6% of the scaffold area. A modified manufacturing process of the polymer and geometric changes in the polymeric platform have substantially improved the medium-term performance of the new generation of drug-eluting scaffold, making it comparable to that of current drug-eluting stents. The results constitute proof of concept that this device can adequately revascularize coronary vessels and prevent restenosis. See p 2301.
Inhibition of Hyaluronan Synthesis Accelerates Murine Atherosclerosis: Novel Insights Into the Role of Hyaluronan Synthesis
Hyaluronan is an integral extracellular matrix component that plays crucial roles in, for example, development and homeostasis of cartilage and skin. However, increased hyaluronan production is associated with tumor progression and vascular disease. Hyaluronan accumulates during neointimal thickening in atherosclerotic plaques and restenotic lesions. In the neointima, it contributes to volume expansion and supports the proliferative and secretory phenotype of vascular smooth muscle cells. Therefore, inhibition of hyaluronan synthesis has been considered as a strategy to limit neointimal thickening and atheroprogression. On the other hand, recent research has established hyaluronan on the luminal surface of vascular endothelial cells to be a critical constituent of the endothelial glycocalyx, which has strong vasoprotective functions. In the present study, it is shown in a murine model of atherosclerosis that inhibition of hyaluronan synthesis by an oral hyaluronan synthesis inhibitor surprisingly enhances inflammatory and thrombotic responses and in the long term increases atherosclerosis. This adverse effect was attributed to a partial loss of the endothelial glycocalyx. Of note, hyaluronan synthesis inhibitors are effective in inhibiting tumor progression in mouse models and may be tested clinically to enhance the response to antitumor strategies. In light of the present results, it may be crucial to avoid adverse effects on the endothelial glycocalyx because damage of the glycocalyx may lead to increased atherothrombotic risk and enhance inflammatory cell recruitment. See p 2313.
- © 2010 American Heart Association, Inc.
- Adverse Bioenergetic Consequences of Na+-Ca2+ Exchanger–Mediated Ca2+ Influx in Cardiac Myocytes
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