- Determinants of Prolonged QT Interval and Their Contribution to Sudden Death Risk in Coronary Artery Disease: The Oregon Sudden Unexpected Death Study
- Fluid Retention Is Associated With Cardiovascular Mortality in Patients Undergoing Long-Term Hemodialysis
- Randomized Comparison of Everolimus-Eluting and Paclitaxel-Eluting Stents: Two-Year Clinical Follow-Up From the Clinical Evaluation of the Xience V Everolimus Eluting Coronary Stent System in the Treatment of Patients With De Novo Native Coronary Artery Lesions (SPIRIT) III Trial
- Early Stent Thrombosis in Patients With Acute Coronary Syndromes Treated With Drug-Eluting and Bare Metal Stents: The Acute Catheterization and Urgent Intervention Triage Strategy Trial
- Dual Angiogenic and Neurotrophic Effects of Bone Marrow–Derived Endothelial Progenitor Cells on Diabetic Neuropathy
- Preoperative Brain Injury in Transposition of the Great Arteries Is Associated With Oxygenation and Time to Surgery, Not Balloon Atrial Septostomy
- Waiting List Mortality Among Children Listed for Heart Transplantation in the United States
- Continuous Improvements in “Chain of Survival” Increased Survival After Out-of-Hospital Cardiac Arrests: A Large-Scale Population-Based Study
- Retrograde Type A Aortic Dissection After Endovascular Stent Graft Placement for Treatment of Type B Dissection
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Determinants of Prolonged QT Interval and Their Contribution to Sudden Death Risk in Coronary Artery Disease: The Oregon Sudden Unexpected Death Study
In this population-based study, determinants of QT interval prolongation were evaluated among patients with coronary disease. These patients were compared with cases of sudden cardiac death who also had coronary disease to identify risk predictors of sudden cardiac death. Gender, diabetes mellitus, and QT-prolonging drugs were determinants of QT prolongation in coronary artery disease. In addition, diabetes mellitus and QT-prolonging drugs were identified as significant predictors of sudden cardiac death risk. However, QT interval prolongation of unknown origin (in the absence of diabetes or QT-prolonging drugs) was an even stronger predictor of sudden death risk, resulting in a 5-fold increase in sudden death risk among patients with coronary disease. These findings have significant implications for improvement of sudden death risk stratification among patients with coronary artery disease. Risk stratification with the prolonged corrected QT interval may allow us to extend beyond the left ventricular ejection fraction, which we are learning is, at best, a modest predictor of risk of sudden death. Other recent research suggests that relatively common gene variations may contribute to the idiopathic QT prolongation observed among patients with coronary artery disease. Therefore, to optimize the effectiveness of the prolonged QT interval as a risk stratification tool, a continued search for novel determinants of QTc prolongation such as genomic factors is warranted. See p 663.
Fluid Retention Is Associated With Cardiovascular Mortality in Patients Undergoing Long-Term Hemodialysis
Management of fluid status is a significant clinical challenge in both individuals with heart failure and those with chronic kidney disease who undergo hemodialysis treatment. Volume overload may be associated with poor clinical outcomes, but it is not clear whether greater amounts of fluid retention are associated with increased mortality. In this 2-year cohort of 34 107 long-term hemodialysis patients across the United States, patients with an average weight gain of at least 0.5 kg between 2 consecutive (thrice-weekly) hemodialysis treatments were studied. We found that 86% of patients gained 1.5 kg or more between 2 hemodialysis sessions, probably due to fluid retention. After controlling for demographics and measures of nutritional status, higher weight gains were incrementally associated with higher all-cause and cardiovascular mortality. These associations remained consistent across different subgroups of hemodialysis patients. Although the mechanisms by which fluid retention influences cardiovascular survival in hemodialysis patients remain unknown, these associations may better justify ongoing efforts to restrict fluid retention in these patients. Given the striking similarities between hemodialysis and heart failure patients and the recently heightened enthusiasm about ultrafiltration treatment in heart failure patients, these findings may have clinical implications for current management of patients with edematous states. See p 671.
Randomized Comparison of Everolimus-Eluting and Paclitaxel-Eluting Stents: Two-Year Clinical Follow-Up From the Clinical Evaluation of the Xience V Everolimus Eluting Coronary Stent System in the Treatment of Patients With De Novo Native Coronary Artery Lesions (SPIRIT) III Trial
Because >1 million drug-eluting stents are implanted each year in patients with coronary artery disease, the safety and efficacy of these devices continue to be of paramount importance. The Clinical Evaluation of the Xience V Everolimus Eluting Coronary Stent System in the Treatment of Patients with de novo Native Coronary Artery Lesions (SPIRIT) III trial was a prospective, randomized trial that evaluated a second-generation everolimus-eluting stent (EES) compared with a widely used paclitaxel-eluting stent (PES) in 1002 patients at 75 US sites. At 2 years of follow-up, the EES compared with the PES resulted in a 32% reduction (10.7% versus 15.4%; P=0.04) in the composite safety and efficacy measure of target vessel failure (cardiac death, myocardial infarction, or recurrent ischemia necessitating target vessel revascularization with either repeat percutaneous coronary intervention or bypass graft surgery). Major adverse cardiac events (cardiac death, myocardial infarction, or ischemia-driven target lesion revascularization) also were reduced by 45% (7.3% versus 12.8%; P=0.004) with the EES compared with the PES. The 2-year rates of all-cause death or myocardial infarction tended to be reduced with EES compared with PES (4.8% versus 8.1%; P=0.055). This favorable balance of safety and efficacy with the EES was driven by fewer episodes of early and late myocardial infarctions and fewer target lesion revascularization procedures required between 6 and 12 months. Between 1 and 2 years, there tended to be fewer stent thrombosis events with the EES compared with the PES, especially in patients who had discontinued clopidogrel after 6 months, which in part contributed to the improved outcomes. Larger studies are underway to further evaluate the encouraging trends toward less composite death or myocardial infarction and late stent thrombosis seen with the EES in the present study. See p 680.
Early Stent Thrombosis in Patients With Acute Coronary Syndromes Treated With Drug-Eluting and Bare Metal Stents: The Acute Catheterization and Urgent Intervention Triage Strategy Trial
In the multicenter, prospective, randomized Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial, coronary stents were implanted in 7162 patients with moderate- and high-risk acute coronary syndromes, and angiographic core laboratory analysis was performed in 3405 patients as part of a formal substudy, representing the largest angiographic stent database to date. ACUITY thus provided a unique opportunity to investigate the prognostic utility of clinical and angiographic findings in patients with acute coronary syndromes. Stent thrombosis (ST) within 30 days occurred in ≈1 in 70 patients with acute coronary syndromes who received either drug-eluting or bare metal stents, a rate higher than previously described in patients with more stable ischemic heart disease. The risk of ST was independent of treatment with heparin plus a glycoprotein IIb/IIIa inhibitor or bivalirudin with or without a IIb/IIIa inhibitor and of the timing of glycoprotein IIb/IIIa inhibitor use. Several risk factors for ST were identified in the present report that may be under the control of the patient or the physician. Maximizing the stent luminal dimensions by using high-pressure or appropriately sized balloons for postdilatation, administering a thienopyridine before the procedure, and emphasizing the importance of antiplatelet agent compliance after stenting may lessen the frequency of ST in patients with acute coronary syndromes, thereby improving event-free survival in these high-risk patients. See p 687.
Dual Angiogenic and Neurotrophic Effects of Bone Marrow–Derived Endothelial Progenitor Cells on Diabetic Neuropathy
In the United States alone, >18 million people suffer from diabetes mellitus. Peripheral neuropathy is the most common complication of diabetes mellitus, affecting up to 60% of long-standing diabetic patients. Diabetic neuropathy (DN) commonly manifests with loss of sensation in the feet, frequently leading to foot problems such as ulcers. Despite a continuous increase in the incidence of diabetes and DN, current treatments have yet to effectively treat DN. Recent evidence suggests that DN is causally related to impaired angiogenesis and deficient neurotrophic factors. Endothelial progenitor cells exist in peripheral blood and bone marrow. Therapeutically, preclinical and clinical pilot studies have demonstrated that endothelial progenitor cells are effective in repairing various cardiovascular diseases via differentiation into new vessels and production of angiogenic and neurotrophic factors. In this study, we demonstrate that local injection of endothelial progenitor cells reversed functional impairments of DN in experimental DN by augmenting neovascularization and providing angiogenic and neurotrophic factors in diabetic nerves. Our study suggests a novel therapeutic strategy, the application of stem/progenitor cell therapy, for DN and provides new insight into the pathophysiological features of DN. Considering that DN is frequently combined with diabetic foot ulcers, limb ischemia, or both, an approach that uses endothelial progenitor cells could have additional clinical benefits for treating complicated DN. See p 699.
Preoperative Brain Injury in Transposition of the Great Arteries Is Associated With Oxygenation and Time to Surgery, Not Balloon Atrial Septostomy
As survival after surgery for congenital heart disease has improved, attention has appropriately shifted to the cognitive and developmental outcomes of these children. Increased recognition of neurological injury in neonates before cardiac surgery has prompted efforts to discern the cause of such injury to ensure that optimal neuroprotective strategies are practiced. Reports have been published that link postoperative hypoxemia in neonates with congenital heart disease with periventricular leukomalacia, a form of hypoxic white matter injury. Recently, concern has been raised that balloon atrial septostomy, a procedure that improves oxygenation in cyanotic neonates with transposition of the great arteries, is associated with preoperative stroke. We report our experience with neonates with transposition of the great arteries. Among 26 neonates who underwent screening preoperative brain MRI scans, no preoperative stroke was found. Periventricular leukomalacia was seen, however, in 10 patients (38%). Periventricular leukomalacia was associated with lower preoperative oxygenation, as reflected on routine arterial blood gases, and with longer time to surgery. Brain injury was not associated with performance of balloon atrial septostomy. Of the 14 patients who underwent balloon atrial septostomy, those with a greater improvement in Po2 had a lower rate of periventricular leukomalacia. These findings demonstrate that exposure to hypoxemia places these neonates at risk of brain injury. Balloon atrial septostomy should continue to be considered in the hypoxic preoperative neonate with transposition of the great arteries as a procedure that improves oxygenation and diminishes this exposure. Further prospective studies are needed to determine the outcomes of neonates found to have periventricular leukomalacia and to determine the neuroprotection afforded by performance of balloon atrial septostomy. See p 709.
Waiting List Mortality Among Children Listed for Heart Transplantation in the United States
Despite improvements in pediatric heart allocation over the past decade, children listed for heart transplantation face the highest waiting list mortality in solid-organ transplant medicine. Data on waiting list outcomes since the pediatric heart-allocation system was revised in 1999 are limited. This study examines waiting list outcomes from all 3098 children <18 years of age listed in the United States for primary heart transplant during the period from 1999 to 2006. Overall, 533 children (17%) died, whereas 63% received transplants and 8% recovered. Although status 1A patients were at higher risk of waiting list mortality than status 1B or status 2 patients, waiting list mortality varied by a greater degree within status 1A and was best predicted by the level of invasive hemodynamic support (defined as extracorporeal membrane oxygenation versus ventilator versus neither). The study thus demonstrates that the current pediatric heart-allocation system captures medical urgency among those waiting for a heart poorly. Because patients on a higher level of invasive support at listing may also be at higher risk of posttransplantation death, further research is needed to determine what changes in the current pediatric allocation system will reduce overall (pretransplantation and posttransplantation) mortality in children listed for a heart transplant. Lastly, the study demonstrates that the vast majority of children who die on the waiting list weigh <10 to 15 kg, which underscores the need to develop and refine new technologies to support the smallest children with advanced heart failure and to expand opportunities for infant organ donation. See p 717.
Continuous Improvements in “Chain of Survival” Increased Survival After Out-of-Hospital Cardiac Arrests: A Large-Scale Population-Based Study
This large, population-based study covering 8.8 million residents and ranging from 1998 to 2006 demonstrates a continuous increase in out-of-hospital cardiac arrest survival with improvements in the “chain of survival.” Among 42 873 resuscitation-attempted adult out-of-hospital cardiac arrests, 8782 bystander-witnessed arrests of presumed cardiac origin were analyzed. During the study period, the proportion of those who received bystander-initiated cardiopulmonary resuscitation increased from 19% to 36%, and the median time interval from collapse to initiation of cardiopulmonary resuscitation decreased from 9 to 7 minutes. The median interval from collapse to first shock decreased from 19 to 9 minutes because of improvements in the emergency medical service response. Neurologically intact 1-month survival after all rhythms and after ventricular fibrillation of witnessed cardiac arrests increased from 2% to 6% and from 6% to 17%, respectively. The concept that survival improves as response times decrease and bystander efforts increase is widely accepted, but few reports have shown the potential impact of ongoing efforts to improve the chain of survival. In multivariable analyses, earlier cardiopulmonary resuscitation (odds ratio per minute 0.89) and earlier intubation (odds ratio per minute 0.96) were associated with better neurological outcome. For ventricular fibrillation, only earlier shock was associated with better outcome (odds ratio 0.84). The incremental benefit of early advanced care on out-of-hospital cardiac arrest survival is also suggested. Emphasis should be placed on increasing bystander-initiated cardiopulmonary resuscitation and integrating such changes with improvements in advanced life support to save more lives. See p 728.
Retrograde Type A Aortic Dissection After Endovascular Stent Graft Placement for Treatment of Type B Dissection
Retrograde type A dissection after stent grafting for type B dissection is a life-threatening complication. However, it remains underrecognized, and the scattered reports have been based on isolated cases. Thus, we were prompted to initiate a systematic investigation into its cause and prevention through a retrospective analysis of 11 retrograde type A aortic dissections of 443 patients undergoing endografting for type B dissection in our center from August 2000 to June 2007. The outcomes revealed that its occurrence and mortality rates reached 2.5% and 27.3%, respectively, and that 2 main aspects collectively contributed to its development: fragility of the aortic wall and disease progression as the pathological background, particularly in patients with Marfan syndrome, and stent grafting–related injury provoked by the proximal bare spring of the endoprosthesis, stress generated by the endograft placed at the aortic arch and passively curved, or endovascular manipulation. Correspondingly, the following strategies could be conducive to lessening the occurrence of retrograde type A aortic dissection. First is careful patient and device selection. Stent grafting at the aortic arch should be avoided in Marfan patients unless the candidate has had a previous graft replacement of the ascending aorta, arch, or both; the device without the proximal bare spring is recommended when endografting is to be applied in patients with a kinked aortic arch or with Marfan syndrome (without previous graft replacement). The second strategy involves improving the stent graft design to develop the device specific for dissection, ideally with given biomechanical properties to minimize the stress yielded by the passively curved stent graft. The final strategy is standardized and careful endovascular manipulation. See p 735.
- Waiting List Mortality Among Children Listed for Heart Transplantation in the United States
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