Circulation: Clinical Summaries
Original Research Put Into Perspective for the Practicing Clinician
- In-Hospital Complications Associated With Catheter Ablation of Atrial Fibrillation in the United States Between 2000 and 2010: Analysis of 93 801 Procedures
- Effect of the Proprotein Convertase Subtilisin/Kexin 9 Monoclonal Antibody, AMG 145, in Homozygous Familial Hypercholesterolemia
- Diagnostic Accuracy of Placental Growth Factor in Women With Suspected Preeclampsia: A Prospective Multicenter Study
- Mechanistic Target of Rapamycin Complex 2 Protects the Heart From Ischemic Damage
- Interplay Between Mitral Regurgitation and Transcatheter Aortic Valve Replacement With the CoreValve Revalving System: A Multicenter Registry
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In-Hospital Complications Associated With Catheter Ablation of Atrial Fibrillation in the United States Between 2000 and 2010: Analysis of 93 801 Procedures
Atrial fibrillation ablation is becoming increasingly popular in many cardiac electrophysiological laboratories around the world. Therefore, preventing, recognizing, avoiding, or treating procedure-related complications is of utmost importance. As the procedure has moved from select centers and select hands to a more a mainstream procedure, the efficacy and safety of the procedure has had a paradigm shift. Currently, the complication rates reported are between 1% and 8%. We assessed the frequency and predictors of in-hospital complications in an everyday-clinical-practice population of patients undergoing atrial fibrillation ablation to determine in-hospital mortality associated with atrial fibrillation ablation and to assess the association between annual operator volume and hospital volume with adverse outcomes. The overall frequency of complications was 6.29% with combined cardiac complications (2.54%) being the most frequent. These complications were followed by vascular complications (1.53%), respiratory complications (1.3%), and neurological complications (1.02%). The in-hospital mortality was 0.46%. Annual operator (<25 procedures) and hospital volume (<50 procedures) were significantly associated with adverse outcomes. There was a small (nonsignificant) rise in overall complication rates. We also found that the majority of the procedures were performed by low-volume operators. We propose setting up a national registry to further assess the safety of the procedure, real-world patterns in complications, and evaluation of other unusual adverse events. Finally, a volume threshold considered optimum for the operators and hospital should be ascertained to enhance the safety of the procedure. This could be a stepping stone to establish atrial fibrillation centers of excellence. See p 2104.
Effect of the Proprotein Convertase Subtilisin/Kexin 9 Monoclonal Antibody, AMG 145, in Homozygous Familial Hypercholesterolemia
Homozygous familial hypercholesterolemia, a rare, serious clinical disorder caused by severe impairment in low-density lipoprotein (LDL) receptor function, results in very high LDL cholesterol and very early coronary artery disease. Current therapies fail to achieve optimal LDL cholesterol. Proprotein convertase subtilisin/kexin (PCSK9) monoclonal antibodies effectively reduce LDL cholesterol in heterozygous familial hypercholesterolemia. The effect in homozygous familial hypercholesterolemia is unknown and uncertain. We evaluated AMG 145, a fully human PCSK9 monoclonal antibody, in a pilot study in patients with homozygous familial hypercholesterolemia already on maximally tolerated lipid-lowering therapy. The open-label trial enrolled 8 patients with a mean baseline LDL cholesterol of 11.4 mmol/L (441 mg/dL) who received 420 mg AMG 145 every 4 weeks and then every 2 weeks. The mean LDL cholesterol reduction after 12 weeks was 17% and 14% with 4- and 2-week dosing, respectively. Two patients with negative LDL receptor activity had no reduction in LDL cholesterol. Significant (P=0.03) reductions occurred in the 6 receptor-defective patients; mean LDL cholesterol, averaged over the monthly visits during the 12-week treatment periods, decreased 19.3% and 26.3% with 4- and 2-week dosing, respectively. Although the percentage reductions were substantially lower than in prior patient populations in AMG 145 trials, the mean absolute LDL cholesterol reduction with 4-week dosing of 2.1 mmol/L (81.5 mg/dL) is similar to that seen in patients without familial hypercholesterolemia, and the reduction with 2-week dosing of 3 mmol/L (115 mg/dL) exceeds that in heterozygous familial hypercholesterolemia trials. No serious side effects were seen. This study demonstrates LDL cholesterol lowering with a PCSK9 monoclonal antibody in patients with homozygous familial hypercholesterolemia with defective LDL receptor activity. See p 2113.
Diagnostic Accuracy of Placental Growth Factor in Women With Suspected Preeclampsia: A Prospective Multicenter Study
Current management of women who present with hypertension in pregnancy or other features of suspected preeclampsia is hampered by the use of signs (high blood pressure) or tests (proteinuria, abnormal platelets, uric acid, alanine transaminase) that reflect end-organ disease and are poorly predictive of subsequent adverse outcomes. In our study, we report the first prospective multicenter study of a biomarker in which we evaluated the diagnostic accuracy of placental growth factor (PlGF) in women presenting with suspected preeclampsia between 20 and 41 weeks' gestation. In women presenting before 35 weeks, low PlGF (<5th centile) had high sensitivity (0.96; 95% confidence interval, 0.89-0.99) and negative predictive value (0.98; 0.93-0.995) in determining delivery for confirmed preeclampsia within 14 days. The area under the receiver operating characteristics curve for low PlGF (0.87, standard error 0.03) was greater than all other commonly used tests, singly or in combination (range, 0.58-0.76). Suspected preeclampsia is the most frequent clinical presentation to obstetric assessment units, and those with early-onset disease are at greatest risk. We hypothesize that adding the PlGF measurement to the current clinical assessment of women with suspected preeclampsia before 37 (and particularly before 35) weeks' gestation could improve risk stratification, achieve an earlier diagnosis based on underlying pathophysiology, enable individualized management of women with the disease, with the potential to reduce associated maternal morbidity and unnecessary health service usage. There may be double benefit: targeting of resources to those at highest risk, while minimizing excessive assessment and intervention in women at lower risk. See p 2121.
Mechanistic Target of Rapamycin Complex 2 Protects the Heart From Ischemic Damage
The mechanistic target of rapamycin (mTOR), an atypical Ser/Thr protein kinase and central regulator of cell function, is deregulated after myocardial infarction. mTOR comprises 2 structurally distinct multiprotein complexes, mTOR complexes 1 and 2 (mTORC1 and mTORC2). mTORC1 controls cell growth; mTORC2 controls cellular survival. Inhibiting mTORC1 with rapamycin is already an established clinical application to prevent restenosis after percutaneous coronary stent implantation, and rapamycin is an inherent component of pharmacological cancer therapeutic regimens. Although oral administration of rapamycin to inhibit mTORC1 has been successfully used in rodent models of heart failure, clinical administration raises concerns about potential side effects of systemic mTOR inhibition in other organs with concomitant risk of immunosuppression. This study shows that inhibition of mTORC1 specifically in cardiomyocytes with PRAS40, an endogenous mTORC1 inhibitor, enhances cardioprotection after myocardial infarction. A unique molecular feature of PRAS40 is the inhibition of mTORC1 while simultaneously increasing mTORC2 activation, which increases cellular survival. The findings presented in this study demonstrate that a clinically relevant adeno-associated virus serotype 9 gene therapy with PRAS40 is protective in response to infarction injury and reduced mortality after infarction. Most existing therapies target outside-in signaling in cardiac cells but are limited in effectiveness in preventing cardiac remodeling. Targeting intracellular mTORC1 signaling in cardiomyocytes with PRAS40 using the recent advancements in the development of adeno-associated virus serotype 9 vectors might have better therapeutic potential than existing therapies to blunt remodeling and to potentiate cell survival and is unlike rapamycin without systemic side effects. See p 2132.
Interplay Between Mitral Regurgitation and Transcatheter Aortic Valve Replacement With the CoreValve Revalving System: A Multicenter Registry
Patients with severe aortic stenosis and concomitant moderate or severe mitral regurgitation (MR) deemed at high or prohibitive risk for surgery have an overtly poor prognosis when treated medically. The coexistence of moderate or severe MR in patients undergoing transcatheter aortic valve replacement implies a higher risk of overall and cardiac mortality at 1 month and 1 year after transcatheter aortic valve replacement. There is a stepwise increase in the risk of mortality in patients with no/mild, moderate, or severe MR; on the other hand, after transcatheter aortic valve replacement, we observed an improvement in MR severity in a significant proportion of patients. Our data, from a large multicenter registry, ruled out the hypothesis that the nitinol frame of the CoreValve might interfere with the anterior leaflet of the mitral valve. A functional type of MR and the absence of severe pulmonary hypertension and atrial fibrillation were independent predictors of improvement in MR severity. Severe pulmonary hypertension, atrial fibrillation, and MR more than mild, but not an improvement of >1 grade in MR severity, were independent predictors of mortality at 1 year. Moderate or severe MR is not a contraindication for transcatheter aortic valve replacement; however, the expected benefit is smaller with respect to patients with no/mild MR. See p 2145.
- © 2013 American Heart Association, Inc.
- Mechanistic Target of Rapamycin Complex 2 Protects the Heart From Ischemic Damage
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