[进展翻译]Circulation2007年5月29日

Arrhythmia/Electrophysiology

1、Major Hemorrhage and Tolerability of Warfarin in the First Year of Therapy Among Elderly Patients With Atrial Fibrillation
Elaine M. Hylek, MD, MPH; Carmella Evans-Molina, MD; Carol Shea, RN; Lori E. Henault, MPH; Susan Regan, PhD

Background— Warfarin is effective in the prevention of stroke in atrial fibrillation but is under used in clinical care. Concerns exist that published rates of hemorrhage may not reflect real-world practice. Few patients 80 years of age were enrolled in trials, and studies of prevalent use largely reflect a warfarin-tolerant subset. We sought to define the tolerability of warfarin among an elderly inception cohort with atrial fibrillation.

Methods and Results— Consecutive patients who started warfarin were identified from January 2001 to June 2003 and followed for 1 year. Patients had to be 65 years of age, have established care at the study institution, and have their warfarin managed on-site. Outcomes included major hemorrhage, time to termination of warfarin, and reason for discontinuation. Of 472 patients, 32% were 80 years of age, and 91% had 1 stroke risk factor. The cumulative incidence of major hemorrhage for patients 80 years of age was 13.1 per 100 person-years and 4.7 for those <80 years of age (P=0.009). The first 90 days of warfarin, age 80 years, and international normalized ratio (INR) 4.0 were associated with increased risk despite trial-level anticoagulation control. Within the first year, 26% of patients 80 years of age stopped taking warfarin. Perceived safety issues accounted for 81% of them. Rates of major hemorrhage and warfarin termination were highest among patients with CHADS2 scores (an acronym for congestive heart failure, hypertension, age 75, diabetes mellitus, and prior stroke or transient ischemic attack) of 3.

Conclusions— Rates of hemorrhage derived from younger noninception cohorts underestimate the bleeding that occurs in practice. This finding coupled with the short-term tolerability of warfarin likely contributes to its underutilization. Stroke prevention among elderly patients with atrial fibrillation remains a challenging and pressing health concern.

Arrhythmia/Electrophysiology

2、Catheter Ablation of Multiple Ventricular Tachycardias After Myocardial Infarction Guided by Combined Contact and Noncontact Mapping
Hanno U. Klemm, MD, MSc*; Rodolfo Ventura, MD*; Daniel Steven, MD; Christin Johnsen, MD; Thomas Rostock, MD; Boris Lutomsky, MD; Tim Risius, MD; Thomas Meinertz, MD; Stephan Willems, MD

Background— Insights gained from noncontact mapping of ventricular tachycardia (VT) have not been systematically applied to contact maps. This study sought to unify both techniques for an individualized approach to the patient with multiple ischemic VTs irrespective of cycle length.

Methods and Results— For 12 consecutive patients with chronic myocardial infarction and recurrent VT, bipolar contact maps were acquired during sinus or paced rhythm. Additional noncontact maps were obtained during 48 induced VTs (cycle length 192 to 579 ms). Endocardial exit sites were superimposed on contact maps and verified by pace-mapping. Radiofrequency lesions were extended for critical borders defined by multiple neighboring exits and followed the isovoltage contour line of contact maps. Nine critical borders were identified in 8 patients and constituted the substrate for 31 VTs. The voltage at exit sites was 0.8 mV (range 0.1 to 2.3). Noncontact maps revealed 23±18% of isthmus conduction. Thirty-seven (77%) of all and 83% of clinically documented VTs were rendered noninducible irrespective of cycle length by application of 27 radiofrequency lesions (range 18 to 56). Spontaneous transitions between distinct VTs along critical borders were demonstrated in 4 patients. Pace-mapping reproduced the QRS morphology of 81% of VTs and was associated with successful ablation (P<0.01). Noninducibility of any sustained VT was reached for 8 (67%) patients. During 15 months (range 5 to 28) of follow-up, 8 patients remained without recurrence, and VT episodes were reduced in the other 4 patients (P<0.01). VT cycle length was not predictive for acute or long-term success.

Conclusion— The combined approach of contact and noncontact mapping effectively defines critical borders as the substrate of multiple VTs without limitation for unstable VTs.

Arrhythmia/Electrophysiology

3、View-Synchronized Robotic Image-Guided Therapy for Atrial Fibrillation Ablation
Experimental Validation and Clinical Feasibility
Vivek Y. Reddy, MD; Petr Neuzil, MD; Zachary J. Malchano, BS; Ragu Vijaykumar, BS; Ricardo Cury, MD; Suhny Abbara, MD; Jiri Weichet, MD; Christina D. McPherson, BS; Jeremy N. Ruskin, MD

Background— A robotic catheter navigation system has been developed that provides a significant degree of freedom of catheter movement. This study examines the feasibility of synchronizing this robotic navigation system with electroanatomic mapping and 3-dimensional computed tomography imaging to perform view-synchronized left atrial (LA) ablation.

Methods and Results— This study consisted of a porcine experimental validation phase (9 animals) and a clinical feasibility phase (9 atrial fibrillation patients). Preprocedural computed tomography images were reconstructed to provide 3-dimensional surface models of the LA pulmonary veins and aorta. Aortic electroanatomic mapping was performed manually, followed by registration with the corresponding computed tomography aorta image using custom software. The mapping catheter was remotely manipulated with the robotic navigation system within the registered computed tomography image of the LA pulmonary veins. The point-to-surface error between the LA electroanatomic mapping data and the computed tomography image was 2.1±0.7 and 1.6±0.1 mm in the preclinical and clinical studies, respectively. The catheter was remotely navigated into all pulmonary veins, the LA appendage, and circumferentially along the mitral valve annulus. In 7 of 9 animals, circumferential radiofrequency ablation lesions were applied periostially to ablate 11 pulmonary veins. In patients, all of the pulmonary veins were remotely electrically isolated in an extraostial fashion. Adjunctive ablation included superior vena cava isolation in 6 patients, cavotricuspid isthmus ablation in 5 patients, and ablation of sites of complex fractionated activity and atypical LA flutters in 3 patients.

Conclusions— This study demonstrates the safety and feasibility of an emerging paradigm for atrial fibrillation ablation involving the confluence of 3 technologies: 3-dimensional imaging, electroanatomic mapping, and remote robotic navigation.

Coronary Heart Disease

4、Local Production of Lipoprotein-Associated Phospholipase A2 and Lysophosphatidylcholine in the Coronary Circulation
Association With Early Coronary Atherosclerosis and Endothelial Dysfunction in Humans
Shahar Lavi, MD; Joseph P. McConnell, PhD; Charanjit S. Rihal, MD; Abhiram Prasad, MD; Verghese Mathew, MD; Lilach O. Lerman, MD, PhD; Amir Lerman, MD
From the Division of Cardiovascular Diseases (S.L., C.S.R., A.P., V.M., L.O.L., A.L.), Department of Laboratory Medicine and Pathology (J.P.M.), and Division of Nephrology and Hypertension (L.O.L.), Mayo Clinic, Rochester, Minn.

Background— Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a novel marker and participant in vascular inflammation. Inflammation also is associated with coronary atherosclerosis. We tested the hypothesis that local coronary production of Lp-PLA2 is enhanced in patients with early coronary atherosclerosis and associated with local endothelial function.

Methods and Results— Coronary angiography, blood flow, flow reserve, endothelial function assessment, and intravascular ultrasound with volumetric analysis were performed in 15 patients with mild coronary atherosclerosis and in 15 control subjects. Plasma samples were collected simultaneously from the left main coronary artery and coronary sinus for measurement of Lp-PLA2, lysophosphatidylcholine (a product of Lp-PLA2), and C-reactive protein. Hemodynamic parameters and cholesterol were similar in both groups. Arterial Lp-PLA2 levels were similar in patients and control subjects: 225 ng/mL (interquartile range [IQR], 196 to 273 ng/mL) versus 221 ng/mL (IQR, 177 to 294 ng/mL). Lp-PLA2 net production in the coronary circulation was higher in patients compared with control subjects: 519 ng/min (IQR, 198 to 1276 ng/min) versus –529 ng/min (IQR, –872 to –79 ng/min; P=0.001) and correlated with percent atheroma volume (rs=0.37, P=0.04). Net production of lysophosphatidylcholine was higher in patients compared with control subjects: 199 ng/min (IQR, –592 to 470 ng/min) versus –505 ng/min (IQR, –1119 to 0 ng/min; P=0.03) and correlated with coronary endothelial dysfunction (rs=0.5, P=0.005). C-reactive protein was not significantly different between the groups.

Conclusions— Early coronary atherosclerosis in humans is characterized by local production of Lp-PLA2. Local coronary production of lysophosphatidylcholine, the active product of Lp-PLA2, is associated with endothelial dysfunction. These results support the role for Lp-PLA2 in the mechanism of regional vascular inflammation and atherosclerosis in humans.

CLINICAL PERSPECTIVE
Epidemiology

5、Risk Factors for the Progression of Coronary Artery Calcification in Asymptomatic Subjects
Results From the Multi-Ethnic Study of Atherosclerosis (MESA)
Richard A. Kronmal, PhD; Robyn L. McClelland, PhD; Robert Detrano, MD; Steven Shea, MD, MS; João A. Lima, MD; Mary Cushman, MD, MS; Diane E. Bild, MD, MPH; Gregory L. Burke, MD

Background— The Multi-Ethnic Study of Atherosclerosis (MESA) provides an opportunity to study the association of traditional cardiovascular risk factors with the incidence and progression of coronary artery calcium (CAC) in a large community-based cohort with no evidence of clinical cardiovascular disease.

Methods and Results— Follow-up CAC measurements were available for 5756 participants with an average of 2.4 years between scans. The incidence of newly detectable CAC averaged 6.6% per year. Incidence increased steadily across age, ranging from <5% annually in those <50 years of age to >12% in those >80 years of age. Median annual change in CAC for those with existing calcification at baseline was 14 Agatston units for women and 21 Agatston units for men. Most traditional cardiovascular risk factors were associated with both the risk of developing new incident coronary calcium and increases in existing calcification. These included age, male gender, white race/ethnicity, hypertension, body mass index, diabetes mellitus, glucose, and family history of heart attack. Factors also existed that were related only to incident CAC risk, such as low- and high-density lipoprotein cholesterol and creatinine. Diabetes mellitus had the strongest association with CAC progression for blacks and the weakest for Hispanics, with intermediate associations for whites and Chinese.

Conclusions— This is the first large multiethnic study reporting on the incidence and progression of CAC. Standard coronary risk factors were generally related to both CAC incidence and progression. Whites had more incident CAC and CAC progression than the other 3 racial/ethnic groups. Except for diabetes mellitus, risk factor relationships were similar across racial/ethnic groups.

CLINICAL PERSPECTIVE

Molecular Cardiology

6、Biglycan Deficiency Causes Spontaneous Aortic Dissection and Rupture in Mice
Anne-Marie Heegaard, MD, PhD*; Alessandro Corsi, MD, PhD*; Carl Christian Danielsen, MD; Karina L. Nielsen, PhD; Henrik L. Jorgensen, MD, PhD; Mara Riminucci, MD, PhD; Marian F. Young, PhD; Paolo Bianco, MD
From the Department of Pharmacology and Pharmacotherapy (A.H.), Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark; Nordic Bioscience A/S (A.H., K.L.N.), Herlev, Denmark; Department of Experimental Medicine and Pathology (A.C., P.B.), Università La Sapienza, Rome, Italy; Department of Connective Tissue Biology (C.C.D.), Institute of Anatomy, University of Aarhus, Aarhus, Denmark; Department of Clinical Biochemistry (H.L.J.), Bispebjerg University Hospital, Copenhagen, Denmark; Department of Experimental Medicine (M.R.), Università dell’Aquila, L’Aquila, Italy; Parco Scientifico Biomedico San Raffaele (M.R., P.B.), Rome, Italy; Craniofacial and Skeletal Diseases Branch (M.F.Y.), National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland.

Background— For the majority of cases, the cause of spontaneous aortic dissection and rupture is unknown. An inherited risk is associated with Marfan syndrome, Ehlers-Danlos syndrome type IV, and loci mapped to diverse autosomal chromosomes. Analysis of pedigrees however has indicated that it may be also inherited as an X-linked trait. The biglycan gene, found on chromosome X in humans and mice, encodes a small leucine-rich proteoglycan involved in the integrity of the extracellular matrix. A vascular phenotype has never been described in mice deficient in the gene for small leucine-rich proteoglycans. In the breeding of BALB/cA mice homozygous for a null mutation of the biglycan gene, we observed that 50% of biglycan-deficient male mice died suddenly within the first 3 months of life.

Methods and Results— Necropsies revealed a major hemorrhage in the thoracic or abdominal cavity, and histology showed aortic rupture that involved an intimal and medial tear as well as dissection between the media and adventitia. By transmission electron microscopy and biomechanical testing, the aortas of biglycan-deficient mice showed structural abnormalities of collagen fibrils and reduced tensile strength. Similar collagen fibril changes were observed in male as well as in female biglycan-deficient mice, which implies a role of additional determinants such as gender-related response to stress in the development of this vascular catastrophe only in male mice.

Conclusions— The spontaneous death of biglycan-deficient male mice from aortic rupture implicates biglycan as essential for the structural and functional integrity of the aortic wall and suggests a potential role of biglycan gene defects in the pathogenesis of aortic dissection and rupture in humans.

CLINICAL PERSPECTIVE

Pericardial Disease

7、Indicators of Poor Prognosis of Acute Pericarditis
Massimo Imazio, MD; Enrico Cecchi, MD; Brunella Demichelis, MD; Salvatore Ierna, MD; Daniela Demarie, MD; Aldo Ghisio, MD; Franco Pomari, MD; Luisella Coda, MD; Riccardo Belli, MD; Rita Trinchero, MD

Background— The clinical search for indicators of poor prognosis of acute pericarditis may be useful for clinical triage of patients at high risk of specific causal conditions or complications. The aim of the present article is to assess the relationship between clinical features at presentation and specific causes or complications.

Methods and Results— A total of 453 patients aged 17 to 90 years (mean age 52±18 years, 245 men) with acute pericarditis (post–myocardial infarction pericarditis was excluded) were prospectively evaluated from January 1996 to August 2004. A specific cause was found in 76 of 453 patients (16.8%): autoimmune in 33 patients (7.3%), neoplastic in 23 patients (5.1%), tuberculous in 17 patients (3.8%), and purulent in 3 patients (0.7%). In multivariable analysis, women (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.03 to 2.70; P=0.036) and patients with fever >38°C (HR 3.56, 95% CI 1.82 to 6.95; P<0.001), subacute course (HR 3.97, 95% CI 1.66 to 9.50; P=0.002), large effusion or tamponade (HR 2.15, 95% CI 1.09 to 4.23; P=0.026), and failure of aspirin or of nonsteroidal anti-inflammatory drugs (HR 2.50, 95% CI 1.28 to 4.91; P=0.008) were at increased risk of specific causal conditions. After a mean follow-up of 31 months, complications were detected in 95 patients (21.0%): recurrences in 83 patients (18.3%), tamponade in 14 patients (3.1%), and constriction in 7 patients (1.5%). In multivariable analysis, women (HR 1.65, 95% CI 1.08 to 2.52; P=0.020) and patients with large effusion or tamponade (HR 2.51, 95% CI 1.37 to 4.61; P=0.003) and failure of aspirin or of nonsteroidal anti-inflammatory drugs (HR 5.50, 95% CI 3.56 to 8.51; P<0.001) were at increased risk of complications.

Conclusions— Specific clinical features (fever >38°C, subacute course, large effusion or tamponade, and aspirin or NSAID failure) may be useful to identify higher risk of specific causal conditions and complications.

CLINICAL PERSPECTIVE

Vascular Medicine

8、Sustained Benefit at 2 Years of Primary Femoropopliteal Stenting Compared With Balloon Angioplasty With Optional Stenting
Martin Schillinger, MD; Schila Sabeti, MD; Petra Dick, MD; Jasmin Amighi, MD; Wolfgang Mlekusch, MD; Oliver Schlager, MD; Christian Loewe, MD; Manfred Cejna, MD; Johannes Lammer, MD; Erich Minar, MD
From the Departments of Angiology (M.S., S.S., P.D., J.A., W.M., O.S., E.M.) and Cardiovascular and Interventional Radiology (C.L., M.C., J.L.), Medical University, Vienna, Austria.

Background— Primary stenting with self-expanding nitinol stents of the superficial femoral artery yielded improved morphological and clinical results compared with balloon angioplasty with optional stenting until 12 months in a randomized controlled trial. We now report 2-year data on restenosis and clinical outcomes of these patients.

Methods and Results— Of 104 patients with chronic limb ischemia and superficial femoral artery obstructions, 98 (94%) could be followed up until 2 years after intervention for occurrence of restenosis (>50%) by duplex ultrasound and for clinical and hemodynamic outcome by treadmill walking distance and ankle brachial index. Restenosis rates at 2 years were 45.7% (21 of 46) versus 69.2% (36 of 52) in favor of primary stenting compared with balloon angioplasty with optional secondary stenting by an intention-to-treat analysis (P=0.031). Consistently, stenting (whether primary or secondary; n=63) was superior to plain balloon angioplasty (n=35) with respect to the occurrence of restenosis (49.2% versus 74.3%; P=0.028) by a treatment-received analysis. Clinically, patients in the primary stent group showed a trend toward better treadmill walking capacity (average, 302 versus 196 m; P=0.12) and better ankle brachial index values (average, 0.88 versus 0.78; P=0.09) at 2 years, respectively. Reintervention rates tended to be lower after primary stenting (17 of 46 [37.0%] versus 28 of 52 [53.8%]; P=0.14).

Conclusions— At 2 years, primary stenting with self-expanding nitinol stents for the treatment of superficial femoral artery obstructions yields a sustained morphological benefit and a trend toward clinical benefit compared with balloon angioplasty with optional stenting.