Circulation: Clinical Summaries
Original Research Put Into Perspective for the Practicing Clinician
- Contemporary Trends of Hospitalization for Atrial Fibrillation in the United States, 2000 Through 2010: Implications for Healthcare Planning
- Heart Failure With Recovered Ejection Fraction: Clinical Description, Biomarkers, and Outcomes
- Five-Year Outcomes in Patients With Left Main Disease Treated With Either Percutaneous Coronary Intervention or Coronary Artery Bypass Grafting in the Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery Trial
- Percutaneous Closure of Postinfarction Ventricular Septal Defect: In-Hospital Outcomes and Long-Term Follow-Up of UK Experience
- Inhibition of Glycosphingolipid Synthesis Ameliorates Atherosclerosis and Arterial Stiffness in Apolipoprotein E−/− Mice and Rabbits Fed a High-Fat and -Cholesterol Diet
- Coinhibitory Suppression of T Cell Activation by CD40 Protects Against Obesity and Adipose Tissue Inflammation in Mice
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Contemporary Trends of Hospitalization for Atrial Fibrillation in the United States, 2000 Through 2010: Implications for Healthcare Planning
Atrial fibrillation (AF) is one of the most frequently encountered arrhythmias in the hospital. A multidisciplinary approach is required to recognize and treat AF appropriately; to limit the catastrophic consequences such as stroke, heart failure, and dementia; and to decrease the burden on the healthcare system. Hospitalization related to AF is the single largest contributor to overall cost of care in managing AF patients. In this study, we examined the trends of AF hospitalizations in the United States and assessed the effects of patient demographics and comorbid diagnoses on in-hospital mortality, length of stay, and total cost of care. Understanding these factors helps us understand the health economics of AF better. There has been a significant increase in AF hospitalizations over the last decade, with a large contribution from patients >65 years of age, especially among those >80 years of age. The overall length of hospital stay has remained unchanged; however, the cost of inpatient care has increased tremendously, from approximately $2.15 billion in 2001 to $3.46 billion in 2010. To the best of our knowledge, this is the first study to assess the trends of AF-related inpatient care at a national level from the actual hospital discharge database. Such data, although they have inherent limitations, tend to provide more accurate financial trajectory of the problem. See p 2371.
Heart Failure With Recovered Ejection Fraction: Clinical Description, Biomarkers, and Outcomes
Recovery of left ventricular function is a primary therapeutic goal in heart failure (HF) with reduced ejection fraction (HF-REF) and may be accomplished by revascularization, optimal pharmacological therapy, device therapy, or even ventricular assist device placement. Little is known, however, about the clinical characteristics and natural history of HF patients who recover their EF (HF-Recovered). As a result, the need to continue long-term therapies in this population is unclear. Some patients continue to be treated as having HF-REF; some discontinue or reduce therapy; others are misclassified as having HF with preserved ejection fraction (HF-PEF). By using data from the Penn Heart Failure Study, we were able to compare and contrast clinical characteristics, baseline biomarker profiles, and long-term outcomes among HF-Recovered, HF-PEF, and HF-REF. Our analysis showed that the HF-Recovered population has distinct demographics, comorbidities, and symptom severity compared with HF-REF and HF-PEF patients. By using both traditional and novel biomarkers, we found that a substantial number of HF-Recovered patients had evidence of persistent neurohormonal activation, cardiomyocyte injury, and oxidative stress, although less than in the HF-REF and HF-PEF populations. HF-Recovered patients had the best prognosis for death, transplantation, or ventricular assist device placement compared with the other groups, but it was not normal. HF-Recovered patients continued to experience HF with symptomatology and number of cardiac hospitalizations similar to those in HF-PEF patients. We believe that this finding provides a rationale for continuing medical/device therapy in the HF-Recovered population and highlights the need for further investigation of pathophysiological differences between the HF populations to better tailor therapy. See p 2380.
Five-Year Outcomes in Patients With Left Main Disease Treated With Either Percutaneous Coronary Intervention or Coronary Artery Bypass Grafting in the Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery Trial
Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) is a landmark trial with the goal of assessing the optimal revascularization strategy for patients with de novo 3-vessel or unprotected left main (LM) disease. We present here the 5-year results of the LM subgroup. In view of the 1-year outcome achieved in this subgroup, percutaneous coronary intervention (PCI) has been given, in the current guidelines, a Class IIa indication for unprotected LM disease in selected patients without additional multivessel disease. This analysis aims to add additional data to support these recommendations. The SYNTAX study is remarkable for a number of reasons including its all-comers design, limited exclusion criteria, use of a Heart Team and development of the SYNTAX score. There were 705 patients in the LM subgroup, making this the largest powered, randomized comparison of revascularization treatment for LM disease. After a 5-year follow-up in the LM cohort, no difference in overall major adverse cardiac and cerebrovascular events was found between treatment groups. Stroke was significantly increased in the coronary artery bypass graft surgery LM group and repeat revascularization was significantly increased in the PCI LM arm at 5 years. These results suggest that revascularization with PCI has comparable safety and efficacy outcomes to coronary artery bypass graft surgery for patients with LM disease. Major adverse cardiac and cerebrovascular events were similar, if not better for PCI, between PCI and coronary artery bypass graft surgery in patients with low or intermediate SYNTAX scores but significantly increased in PCI patients with high scores (≥33). This suggests that PCI can be a viable alternative to surgery in the treatment of patients with LM disease of mild or moderate extent and severity (higher tercile of the SYNTAX score). See p 2388.
Percutaneous Closure of Postinfarction Ventricular Septal Defect: In-Hospital Outcomes and Long-Term Follow-Up of UK Experience
Postinfarction ventricular septal defect (PIVSD) is a catastrophic complication of myocardial infarction that is associated with poor outcomes, especially if treated conservatively. The current American College of Cardiology Foundation/American Heart Association and European Society of Cardiology guidelines both recommend early surgery. However, surgery is often withheld or delayed, and outcomes after surgery remain poor, with repeat intervention often required for dehiscence. This study assesses the long-term mortality of those patients with PIVSD who underwent attempted percutaneous closure in the United Kingdom between 1997 and 2012. In those with technically successful device closure of the PIVSD (89%), there was an immediate reduction in shunt in 96%. Major immediate complications included procedural death (3.8%) and emergency cardiac surgery (7.5%). Survival to discharge occurred in 58%, with only an additional 4 patients (7.5%) dying thereafter. Factors associated with long-term death included age, female sex, raised serum creatinine, defect size, New York Heart Association class IV dyspnea, cardiogenic shock, and use of inotropes. Prior surgical closure, revascularization therapy, and immediate shunt reduction were all associated with long-term survival. Percutaneous PIVSD closure is a technically challenging procedure. Our experience suggests that arteriovenous loops are invaluable, as are braided guiding catheters to prevent kinking. The defects are often complex, serpiginous, multiple, and difficult to size. Three-dimensional transesophageal echocardiography is useful in understanding the anatomy. The rims are usually friable, and significant oversizing of the device is recommended. Percutaneous device closure of PIVSD is a challenging but viable option for these critically unwell patients. See p 2395.
Inhibition of Glycosphingolipid Synthesis Ameliorates Atherosclerosis and Arterial Stiffness in Apolipoprotein E−/− Mice and Rabbits Fed a High-Fat and -Cholesterol Diet
Current strategies for the treatment and prevention of atherosclerosis and related conditions are targeted mainly at lowering blood levels of low-density lipoprotein cholesterol by the use of statins, a family of compounds that inhibit cholesterol biosynthesis. Zetia (ezetimibe) is also prescribed to block intestinal uptake of dietary cholesterol. However, for the treatment of residual risk for atherosclerosis, much effort has been exerted with minimal gain. Glycosphingolipids are associated with lipoproteins with blood levels tied to cholesterol. We report here that blocking the biosynthesis of glycosphingolipids in a transgenic mouse model (apolipoprotein E–deficient) fed a Western diet (high cholesterol and high fat) can prevent atherosclerosis and vastly improve arterial elasticity. In particular, treatment with D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol increased the expression of protein ABCG5/8 responsible for pumping cholesterol from liver and intestine into the blood circulation for removal. Increased levels of high-density lipoprotein cholesterol, apolipoprotein A1 gene, and scavenger receptor-1 expression responsible for reverse transport of cholesterol from macrophage/peripheral tissue to the liver occurred in treated mice. Here too treatment improved the expression of the Cyp7A gene responsible for the conversion of cholesterol to bile acid and its subsequent excretion. Treatment also improved the expression of the lipoprotein lipase gene, which binds to very-low-density lipoprotein (triglyceride-rich lipoproteins) and to very-low-density lipoprotein receptors facilitating triglyceride metabolism. Thus, treatment with a glycosphingolipid glycosyltransferase inhibitor provides a novel strategy to prevent atherosclerosis by upregulating/downregulating multiple genes in cholesterol and fat metabolism. This compound could be useful in patients who do not respond favorably to statin treatment. See p 2403.
Coinhibitory Suppression of T Cell Activation by CD40 Protects Against Obesity and Adipose Tissue Inflammation in Mice
Cardiovascular mortality caused by atherosclerosis, myocardial infarction, and stroke accounts for the majority of deaths worldwide. The metabolic syndrome, a cluster of cardiovascular risk factors including obesity, insulin resistance, hepatic steatosis, and dyslipidemia, is associated with chronic, low-grade inflammation in visceral adipose tissue. Notably, targeting adipose tissue inflammation can improve cardiovascular risk and outcome. However, the exact signaling pathways linking adipose tissue inflammation and cardiovascular disease, as ultimately required for establishing novel therapeutic strategies against cardiometabolic disease, remain poorly understood. Considerable evidence implicates the recruitment and activation of lymphocytes such as T cells in the regulation of adipose tissue inflammation. Modulation of anticipated proinflammatory pathways such as the CD40L/CD40 costimulatory dyad holds great promise in inflammation, but this concept has received scant attention in adipose tissue inflammation. In this study, we observed that mice deficient for CD40 exhibited dysmetabolism and increased adipose tissue inflammation. Conversely, activation of CD40 signaling by a stimulating antibody improved adipose tissue inflammation and dysmetabolism. Moreover, we found that elevated plasma levels of CD40 are associated with clinical obesity in humans. These findings support the functional involvement of CD40 in obesity. Targeting CD40 has the potential of modulating various human diseases, and stimulating anti-CD40 antibodies are currently under investigation in cancer, in the prevention of transplant rejection, and in autoimmune disease. Activation of the CD40 pathway with drugs already in clinical trials therefore might provide a novel, rapidly available therapeutic concept to combat cardiometabolic disease. See p 2414.
- © 2014 American Heart Association, Inc.
- Heart Failure With Recovered Ejection Fraction: Clinical Description, Biomarkers, and Outcomes
- Info & Metrics