[进展翻译]Circulation 6月5日版

Cardiovascular Surgery

1、Meta-Analysis Comparing the Effectiveness and Adverse Outcomes of Antifibrinolytic Agents in Cardiac Surgery
Jeremiah R. Brown, PhD; Nancy J.O. Birkmeyer, PhD; Gerald T. O’Connor, PhD, ScD

Background— Since the 1980s, antifibrinolytic therapies have assisted surgical teams in reducing the amount of blood loss. To date, however, serious questions remain regarding the safety and effectiveness of these agents.

Methods and Results— We conducted a meta-analysis to compare aprotinin, -aminocaproic acid, and tranexamic acid with placebo and head to head on 8 clinical outcomes from 138 trials. Published randomized controlled trial data were collected from OVID/PubMed. Outcomes included total blood loss, transfusion of packed red blood cells, reexploration, mortality, stroke, myocardial infarction, dialysis-dependent renal failure, and renal dysfunction (0.5-mg/dL increase in creatinine from baseline). All agents were effective in significantly reducing blood loss by 226 to 348 mL and the proportion of patients transfused with packed red blood cells over placebo. Only high-dose aprotinin reduced the rate of reexploration (relative risk, 0.49; 95% CI, 0.33 to 0.73). There were no significant risks or benefits for any agent for mortality, stroke, myocardial infarction, or renal failure. However, high-dose aprotinin significantly increased the risk of renal dysfunction (relative risk, 1.47; 95% CI, 1.12 to 1.94), 12.9% versus 8.4%. Compared head to head, high-dose aprotinin demonstrated significant reduction in total blood loss over -aminocaproic acid (–184 mL; 95% CI, –256 to –112) and tranexamic acid (–195 mL; 95% CI, –286 to –105). There were no significant differences among any agent when compared head to head on other outcomes.

Conclusions— All antifibrinolytic agents were effective in reducing blood loss and transfusion. There were no significant risks or benefits for mortality, stroke, myocardial infarction, or renal failure. However, high-dose aprotinin was associated with a statistically significant increased risk of renal dysfunction.

Congenital Heart Disease

2、Congenital Heart Disease and Other Heterotaxic Defects in a Large Cohort of Patients With Primary Ciliary Dyskinesia
Marcus P. Kennedy, MD; Heymut Omran, MD; Margaret W. Leigh, MD; Sharon Dell, MD; Lucy Morgan, MD; Paul L. Molina, MD; Blair V. Robinson, MD; Susan L. Minnix, RN; Heike Olbrich, PhD; Thomas Severin, MD; Peter Ahrens, MD; Lars Lange, MD; Hilda N. Morillas, MD; Peadar G. Noone, MD; Maimoona A. Zariwala, PhD; Michael R. Knowles, MD

Background— Primary ciliary dyskinesia (PCD) is a recessive genetic disorder that is characterized by sinopulmonary disease and reflects abnormal ciliary structure and function. Situs inversus totalis occurs in 50% of PCD patients (Kartagener’s syndrome in PCD), and there are a few reports of PCD with heterotaxy (situs ambiguus), such as cardiovascular anomalies. Advances in diagnosis of PCD, such as genetic testing, allow the systematic investigation of this association.

Methods and Results— The prevalence of heterotaxic defects was determined in 337 PCD patients by retrospective review of radiographic and ultrasound data. Situs solitus (normal situs) and situs inversus totalis were identified in 46.0% and 47.7% of patients, respectively, and 6.3% (21 patients) had heterotaxy. As compared with patients with situs solitus, those with situs abnormalities had more ciliary outer dynein arm defects, fewer inner dynein arm and central apparatus defects (P<0.001), and more mutations in ciliary outer dynein arm genes (DNAI1 and DNAH5; P=0.022). Seven of 12 patients with heterotaxy who were genotyped had mutations in DNAI1 or DNAH5. Twelve patients with heterotaxy had cardiac and/or vascular abnormalities, and most (8 of 12 patients) had complex congenital heart disease.

Conclusions— At least 6.3% of patients with PCD have heterotaxy, and most of those have cardiovascular abnormalities. The prevalence of congenital heart disease with heterotaxy is 200-fold higher in PCD than in the general population (1:50 versus 1:10 000); thus, patients with PCD should have cardiac evaluation. Conversely, mutations in genes that adversely affect both respiratory and embryological nodal cilia are a significant cause of heterotaxy and congenital heart disease, and screening for PCD is indicated in those patients.

Coronary Heart Disease

3、Outcomes and Optimal Antithrombotic Therapy in Women Undergoing Fibrinolysis for ST-Elevation Myocardial Infarction
Jessica L. Mega, MD; David A. Morrow, MD, MPH; Erika Östör, MD; Maria Dorobantu, MD, PhD; Jie Qin, MS; Elliott M. Antman, MD; Eugene Braunwald, MD

Background— The manifestations, complications, and outcomes of cardiovascular disease differ between women and men. The safety and efficacy of pharmacological reperfusion therapy in women with ST-elevation myocardial infarction are of particular interest.

Methods and Results— We investigated outcomes in the Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment–Thrombolysis in Myocardial Infarction (ExTRACT-TIMI) 25 study, which randomized ST-elevation myocardial infarction patients with planned fibrinolysis to enoxaparin or unfractionated heparin. Compared with men (n=15 696), women (n=4783) were older and more likely to have hypertension and diabetes (P<0.001). The unadjusted 30-day mortality rate for women was >2-fold higher than for men (13.2% versus 5.4%; odds ratio, 2.66; 95% CI, 2.40 to 2.96). After adjustment for age, fibrinolytic therapy, revascularization, region, and elements of the TIMI Risk Score, women had a 1.25-fold-higher 30-day risk of death (95% CI, 1.08 to 1.46) but similar risk of intracerebral hemorrhage (adjusted odds ratio, 0.81; 95% CI, 0.52 to 1.26). The 30-day rate of death or nonfatal MI in women was reduced by enoxaparin compared with unfractionated heparin in women (15.4% versus 18.3%; P=0.007). Major bleeding was more frequent in women receiving enoxaparin compared with those receiving unfractionated heparin (2.3% versus 1.4%; P=0.022) but similar among women and men receiving enoxaparin (2.3% versus 2.0%; P=0.39). The rates of death, nonfatal myocardial infarction, or nonfatal major bleeding (net clinical benefit) were lower with enoxaparin (absolute risk reduction, 2.6% in women [P=0.02] and 1.6% in men [P=0.001]).

Conclusions— In ExTRACT-TIMI 25, women presented with a profile of higher baseline risk and increased short-term mortality. In this large, contemporary clinical trial, women had similar relative and greater absolute risk reductions than men when treated with enoxaparin compared with unfractionated heparin as adjunctive therapy with fibrinolysis.

Health Services and Outcomes Research

4、Clinical Reminders Attached to Echocardiography Reports of Patients With Reduced Left Ventricular Ejection Fraction Increase Use of ß-Blockers
A Randomized Trial
Paul A. Heidenreich, MD, MS; Parisa Gholami, MPH; Anju Sahay, PhD; Barry Massie, MD; Mary K. Goldstein, MD, MS

Background— Although ß-blockers are known to prolong survival for patients with reduced left ventricular ejection fraction, they are often underused. We hypothesized that a reminder attached to the echocardiography report would increase the use of ß-blockers for patients with reduced left ventricular ejection fraction.

Methods and Results— We randomized 1546 consecutive patients with a left ventricular ejection fraction <45% found on echocardiography at 1 of 3 laboratories to a reminder for use of ß-blockers or no reminder. Patients were excluded from analysis if they died within 30 days of randomization (n=89), did not receive medications through the Veterans Affairs system after 30 days (n=180), or underwent echocardiography at >1 laboratory (n=6). The primary outcome was a prescription for an oral ß-blocker between 1 and 9 months after randomization. The mean age of the 1271 included patients was 69 years; 60% had a history of heart failure, and 51% were receiving treatment with ß-blockers at the time of echocardiography. More patients randomized to the reminder had a subsequent ß-blocker prescription (74%, 458 of 621) compared with those randomized to no reminder (66%, 428 of 650; P=0.002). The effect of the reminder was not significantly different for subgroups based on patient location (inpatient versus outpatient) or prior use of ß-blockers.

Conclusions— A reminder attached to the echocardiography report increased the use of ß-blockers in patients with depressed left ventricular systolic function.

Key Words: adrenergic beta-antagonists • echocardiography • health services research • heart failure • reminder systems

Interventional Cardiology

5、Twenty-Five–Year Trends in In-Hospital and Long-Term Outcome After Percutaneous Coronary Intervention
A Single-Institution Experience
Mandeep Singh, MD; Charanjit S. Rihal, MD; Bernard J. Gersh, MB, ChB, DPhil; Ryan J. Lennon, MS; Abhiram Prasad, MD; Paul Sorajja, MD; Rachel E. Gullerud, BS; David R. Holmes, Jr, MD

Background— Little is known about the impact of technological and pharmacological advances on long-term outcome after percutaneous coronary intervention in general clinical practice.

Methods and Results— We analyzed in-hospital and long-term outcome of 24 410 percutaneous coronary interventions among 18 575 unique patients who underwent percutaneous coronary intervention at Mayo Clinic over 25 years. The study population was divided into group 1 (n=3708), coronary interventions from 1979 to 1989; group 2 (n=7020), interventions from 1990 to 1996; group 3 (n=10 952), interventions from 1996 to 2003; and group 4 (n=2730), interventions from 2003 to 2004. Despite the fact that patients in groups 3 and 4 were significantly older, sicker, and had greater prevalence of comorbid conditions, heart failure, and previous revascularization than those in groups 1 and 2, procedural success in groups 3 and 4 improved significantly (94%) versus groups 2 (89%) and 1 (78%) (P<0.001). Significant reduction in in-hospital mortality (groups 4 to 1: 1.8%, 1.7%, 2.6%, 3.0%; P<0.001) and need for emergency bypass surgery (groups 4 to 1: 0.4%, 0.5%, 1.6%, 5%; P<0.001) was noted in groups 3 and 4 compared with groups 1 and 2. Better adherence to currently recommended evidence-based medications for secondary prevention was seen in the recent time periods. After adjustment, significant reduction in follow-up mortality (hazard ratio, 0.81 and 0.74 for groups 3 and 4, respectively); death or myocardial infarction (hazard ratio, 0.80 and 0.75 for groups 3 and 4, respectively); death, myocardial infarction, or revascularization (hazard ratio, 0.76 and 0.58 for groups 3 and 4, respectively) was noted in recent time periods.

Conclusions— Despite higher-risk profiles of patients who underwent percutaneous coronary intervention in recent time periods, procedural success as well as in-hospital and long-term outcomes improved significantly over the last 25 years.

Interventional Cardiology

6、Offsetting Impact of Thrombosis and Restenosis on the Occurrence of Death and Myocardial Infarction After Paclitaxel-Eluting and Bare Metal Stent Implantation
Gregg W. Stone, MD; Stephen G. Ellis, MD; Antonio Colombo, MD; Keith D. Dawkins, MD; Eberhard Grube, MD; Donald E. Cutlip, MD; Mark Friedman, MD; Donald S. Baim, MD; Joerg Koglin, MD

Background— Drug-eluting stents compared with bare metal stents (BMS) may increase late stent thrombosis (ST), although an accompanying increase in the rates of death and myocardial infarction (MI) has not been observed. We hypothesized that the prevention of restenosis-related adverse events by drug-eluting stents might offset some or all of the excess risk from ST.

Methods and Results— We analyzed a pooled patient-level database from 4 prospective, double-blind trials in which 3445 patients were randomized to paclitaxel-eluting stents or BMS. The occurrence of death or MI within 7 days of ST or target lesion revascularization was assessed. With a median follow-up of 3.2 years, ST occurred in 34 patients (1.0%), 31 (91.1%) of whom sustained death or MI within 7 days. Target lesion revascularization was performed in 425 patients (12.3%), 15 (3.5%) of whom died or had MI within 7 days. ST occurred in 14 BMS and 20 paclitaxel-eluting stent patients, resulting in 12 and 19 deaths or MIs within 7 days, respectively. Target lesion revascularization was performed in 290 BMS and 135 paclitaxel-eluting stent patients, resulting in 11 and 4 deaths or MI events within 7 days, respectively. In total, 23 patients in both the BMS and paclitaxel-eluting stents groups died or had an MI event within 7 days of either ST or target lesion revascularization.

Conclusions— ST, although infrequent, results in a high incident rate of death and MI, whereas the more frequent occurrence of target lesion revascularization is associated with a finite but lower rate of death and MI. The marked reduction in restenosis with drug-eluting stents compared with BMS may counterbalance the potential excess risk from late ST with drug-eluting stents.

Key Words: mortality • myocardial infarction • restenosis • stent • thrombosis

Valvular Heart Disease

7、B-Type Natriuretic Peptide in Low-Flow, Low-Gradient Aortic Stenosis
Relationship to Hemodynamics and Clinical Outcome: Results From the Multicenter Truly or Pseudo-Severe Aortic Stenosis (TOPAS) Study
Jutta Bergler-Klein, MD; Gerald Mundigler, MD; Philippe Pibarot, DVM, PhD; Ian G. Burwash, MD; Jean G. Dumesnil, MD; Claudia Blais, MSc; Christina Fuchs, MD; Dania Mohty, MD, MSc; Rob S. Beanlands, MD; Zeineb Hachicha, MD; Nicole Walter-Publig, MD; Florian Rader, MD; Helmut Baumgartner, MD

Background— The prognostic value of B-type natriuretic peptide (BNP) is unknown in low-flow, low-gradient aortic stenosis (AS). We sought to evaluate the relationship between AS and rest, stress hemodynamics, and clinical outcome.

Methods and Results— BNP was measured in 69 patients with low-flow AS (indexed effective orifice area <0.6 cm2/m2, mean gradient 40 mm Hg, left ventricular ejection fraction 40%). All patients underwent dobutamine stress echocardiography and were classified as truly severe or pseudosevere AS by their projected effective orifice area at normal flow rate of 250 mL/s (effective orifice area 1.0 cm2 or >1.0 cm2). BNP was inversely related to ejection fraction at rest (Spearman correlation coefficient rs=–0.59, P<0.0001) and at peak stress (rs=–0.51, P<0.0001), effective orifice area at rest (rs=–0.50, P<0.0001) and at peak stress (rs=–0.46, P=0.0002), and mean transvalvular flow (rs=–0.31, P=0.01). BNP was directly related to valvular resistance (rs=0.42, P=0.0006) and wall motion score index (rs=0.36, P=0.004). BNP was higher in 29 patients with truly severe AS versus 40 with pseudosevere AS (median, 743 pg/mL [Q1, 471; Q3, 1356] versus 394 pg/mL [Q1, 191 to Q3, 906], P=0.012). BNP was a strong predictor of outcome. In the total cohort, cumulative 1-year survival of patients with BNP 550 pg/mL was only 47±9% versus 97±3% with BNP <550 (P<0.0001). In 29 patients who underwent valve replacement, postoperative 1-year survival was also markedly lower in patients with BNP 550 pg/mL (53±13% versus 92±7%).

Conclusions— BNP is significantly higher in truly severe than pseudosevere low-gradient AS and predicts survival of the whole cohort and in patients undergoing valve replacement.

Valvular Heart Disease

8、Paradoxical Low-Flow, Low-Gradient Severe Aortic Stenosis Despite Preserved Ejection Fraction Is Associated With Higher Afterload and Reduced Survival
Zeineb Hachicha, MD; Jean G. Dumesnil, MD; Peter Bogaty, MD; Philippe Pibarot, DVM, PhD

Background— Recent studies and current clinical observations suggest that some patients with severe aortic stenosis on the basis of aortic valve area may paradoxically have a relatively low gradient despite the presence of a preserved left ventricular (LV) ejection fraction. The objective of the present study was to document the prevalence, potential mechanisms, and clinical relevance of this phenomenon.

Methods and Results— We retrospectively studied the clinical and Doppler echocardiographic data of 512 consecutive patients with severe aortic stenosis (indexed aortic valve area 0.6 cm2 · m–2) and preserved LV ejection fraction (50%). Of these patients, 331 (65%) had normal LV flow output defined as a stroke volume index >35 mL · m2, and 181 (35%) had paradoxically low-flow output defined as stroke volume index 35 mL · m–2. When compared with normal flow patients, low-flow patients had a higher prevalence of female gender (P<0.05), a lower transvalvular gradient (32±17 versus 40±15 mm Hg; P<0.001), a lower LV diastolic volume index (52±12 versus 59±13 mL · m–2; P<0.001), lower LV ejection fraction (62±8% versus 68±7%; P<0.001), a higher level of LV global afterload reflected by a higher valvulo-arterial impedance (5.3±1.3 versus 4.1±0.7 mm Hg · mL–1 · m–2; P<0.001) and a lower overall 3-year survival (76% versus 86%; P=0.006). Only age (hazard ratio, 1.04; 95% CI, 1.01 to 1.08; P=0.025), valvulo-arterial impedance >5.5 mm Hg · mL–1 · m–2 (hazard ratio, 2.6; 95% CI, 1.2 to 5.7; P=0.017), and medical treatment (hazard ratio, 3.3; 95% CI, 1.8 to 6.7; P=0.0003) were independently associated with increased mortality.

Conclusion— Patients with severe aortic stenosis may have low transvalvular flow and low gradients despite normal LV ejection fraction. A comprehensive evaluation shows that this pattern is in fact consistent with a more advanced stage of the disease and has a poorer prognosis. Such findings are clinically relevant because this condition may often be misdiagnosed, which leads to a neglect and/or an underestimation of symptoms and an inappropriate delay of aortic valve replacement surgery.

AHA Scientific Statement

9、Relevance of Genetics and Genomics for Prevention and Treatment of Cardiovascular Disease
A Scientific Statement From the American Heart Association Council on Epidemiology and Prevention, the Stroke Council, and the Functional Genomics and Translational Biology Interdisciplinary Working Group
Donna K. Arnett, PhD, FAHA, Chair; Alison E. Baird, MD, PhD; Ruth A. Barkley, PhD; Craig T. Basson, MD, FAHA; Eric Boerwinkle, PhD; Santhi K. Ganesh, MD; David M. Herrington, MD, FAHA; Yuling Hong, MD, PhD, FAHA; Cashell Jaquish, PhD; Deborah A. McDermott, MS; Christopher J. O’Donnell, MD, FAHA

Atherosclerotic cardiovascular disease (CVD) is a major health problem in the United States and around the world. Evidence accumulated over decades convincingly demonstrates that family history in a parent or a sibling is associated with atherosclerotic CVD, manifested as coronary heart disease, stroke, and/or peripheral arterial disease. Although there are several mendelian disorders that contribute to CVD, most common forms of CVD are believed to be multifactorial and to result from many genes, each with a relatively small effect working alone or in combination with modifier genes and/or environmental factors. The identification and the characterization of these genes and their modifiers would enhance prediction of CVD risk and improve prevention, treatment, and quality of care. This scientific statement describes the approaches researchers are using to advance understanding of the genetic basis of CVD and details the current state of knowledge regarding the genetics of myocardial infarction, atherosclerotic CVD, hypercholesterolemia, and hypertension. Current areas of interest and investigation—including gene–environment interaction, pharmacogenetics, and genetic counseling—are also discussed. The statement concludes with a list of specific recommendations intended to help incorporate usable knowledge into current clinical and public health practice, foster and guide future research, and prepare both researchers and practitioners for the changes likely to occur as molecular genetics moves from the laboratory to clinic.

Key Words: AHA Scientific Statements • genetics • genomics • cardiovascular diseases