Improved Utilization of Serial Testing Without Increased Admissions after Implementation of High-Sensitivity Troponin I: a Controlled Retrospective Cohort Study.

BACKGROUND: Guidelines recommend high-sensitivity cardiac troponin (hs-cTn) for diagnosis of myocardial infarction. Use of hs-cTn is increasing across the U.S., but questions remain regarding clinical and operational impact. Prior studies have had methodologic limitations and yielded conflicting results. OBJECTIVE: To evaluate the impact of transitioning from conventional cardiac troponin (cTn) to hs-cTn on test and resource utilization, operational efficiency, and patient safety. DESIGN: Retrospective cohort study in two New York City hospitals during the months before and after transition from conventional cTn to hs-cTn at Hospital 1. Hospital 2 served as a control. PARTICIPANTS: Consecutive emergency department (ED) patients with at least one cTn test resulted. INTERVENTION: Multifaceted hs-cTn intervention bundle, including a 0/2-h diagnostic algorithm for non-ST-elevation myocardial infarction, an educational bundle, enhancements to the electronic medical record, and nursing interventions to facilitate timed sample collection. MAIN MEASURES: Primary outcomes included serial cTn test utilization, probability of hospital admission, ED length of stay (LOS), and among discharged patients, probability of ED revisit within 72 h resulting in hospital admission. Multivariable regression models adjusted for age, sex, temporal trends, and interhospital differences. KEY RESULTS: The intervention was associated with increased use of serial cTn testing (adjusted risk difference: 48 percentage points, 95% CI: 45-50, P < 0.001) and ED LOS (adjusted geometric mean difference: 50 min, 95% CI: 50-51, P < 0.001). There was no significant association between the intervention and probability of admission (adjusted relative risk [aRR]: 0.99, 95% CI: 0.89-1.1, P = 0.81) or probability of ED revisit within 72 h resulting in admission (aRR: 1.1, 95% CI: 0.44-2.9, P = 0.81). CONCLUSIONS: Implementation of a hs-cTn intervention bundle was associated with an improvement in serial cTn testing, a neutral effect on probability of hospital admission, and a modest increase in ED LOS.

Systematic Review for the 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society.

BACKGROUND: Although large randomized clinical trials have found that primary prevention use of an implantable cardioverter-defibrillator (ICD) improves survival in patients with cardiomyopathy and heart failure symptoms, patients who receive ICDs in practice are often older and have more comorbidities than patients who were enrolled in the clinical trials. In addition, there is a debate among clinicians on the usefulness of electrophysiological study for risk stratification of asymptomatic patients with Brugada syndrome. AIM: Our analysis has 2 objectives. First, to evaluate whether ventricular arrhythmias (VAs) induced with programmed electrostimulation in asymptomatic patients with Brugada syndrome identify a higher risk group that may require additional testing or therapies. Second, to evaluate whether implantation of an ICD is associated with a clinical benefit in older patients and patients with comorbidities who would otherwise benefit on the basis of left ventricular ejection fraction and heart failure symptoms. METHODS: Traditional statistical approaches were used to address 1) whether programmed ventricular stimulation identifies a higher-risk group in asymptomatic patients with Brugada syndrome and 2) whether ICD implantation for primary prevention is associated with improved outcomes in older patients (>75 years of age) and patients with significant comorbidities who would otherwise meet criteria for ICD implantation on the basis of symptoms or left ventricular function. RESULTS: Evidence from 6 studies of 1138 asymptomatic patients were identified. Brugada syndrome with inducible VA on electrophysiological study was identified in 390 (34.3%) patients. To minimize patient overlap, the primary analysis used 5 of the 6 studies and found an odds ratio of 2.3 (95% CI: 0.63-8.66; P=0.2) for major arrhythmic events (sustained VAs, sudden cardiac death, or appropriate ICD therapy) in asymptomatic patients with Brugada syndrome and inducible VA on electrophysiological study versus those without inducible VA. Ten studies were reviewed that evaluated ICD use in older patients and 4 studies that evaluated unique patient populations were identified. In our analysis, ICD implantation was associated with improved survival (overall hazard ratio: 0.75; 95% confidence interval: 0.67-0.83; P<0.001). Ten studies were identified that evaluated ICD use in patients with various comorbidities including renal disease, chronic obstructive pulmonary disease, atrial fibrillation, heart disease, and others. A random effects model demonstrated that ICD use was associated with reduced all-cause mortality (overall hazard ratio: 0.72; 95% confidence interval: 0.65-0.79; P<0.0001), and a second "minimal overlap" analysis also found that ICD use was associated with reduced all-cause mortality (overall hazard ratio: 0.71; 95% confidence interval: 0.61-0.82; P<0.0001). In 5 studies that included data on renal dysfunction, ICD implantation was associated with reduced all-cause mortality (overall hazard ratio: 0.71; 95% confidence interval: 0.60-0.85; P<0.001).

Efficacy and safety of direct oral anticoagulants in patients with atrial fibrillation and chronic kidney disease.

BACKGROUND: Direct oral anticoagulants (DOACs) are effective alternatives to warfarin for stroke prevention in patients with atrial fibrillation (AF) including patients with CKD III. However, data on patient outcomes with DOACs for advanced CKD are limited, while warfarin use is controversial. METHODS: A retrospective study of patients with AF using DOACs and CKD stages III-V was conducted. The primary outcomes were stroke or systemic embolism and major bleeding while on DOAC therapy among CKD IV and V patients. Rates of outcomes from the DOAC trials and from previous studies of warfarin in CKD were referenced. RESULTS: Of 316 patients reviewed, 152 were included with mean CrCl of 38.8 mL/min. Stroke and systemic embolism occurred at a rate of 1.17 per 100 person-years, with no significant difference between CKD IV/V and CKD III (P = .567). Rates were comparable to DOAC use from the DOAC trials, and lower than rates in studies of warfarin in CKD IV/V patients. There was a nonstatistically significant trend toward increased major bleeding in CKD IV/V patients. Rates of major bleeding in CKD III to V subjects were comparable to published rates for warfarin users with similar levels of renal impairment. CONCLUSIONS: In our study, DOACs appeared to be as efficacious and safe in CKD IV and V as in CKD III. In addition, DOACs appeared to be more effective than, and as safe as warfarin when compared with reference studies of patients with advanced CKD. Our findings support the use of DOACs for thromboembolism prevention in patients with advanced CKD and AF.

Management and clinical outcomes of acute cardiac tamponade complicating electrophysiologic procedures: a single-center case series.

BACKGROUND: Cardiac perforation with tamponade is an infrequent occurrence during an electrophysiologic procedure. The customary approach to management includes volume resuscitation followed by pericardiocentesis. Such a procedure, however, is not without its own risk, especially when performed emergently. We hypothesized that some patients experiencing this type of complication can be managed successfully in a conservative fashion, without the need for an additional invasive procedure. METHODS: We retrospectively analyzed the clinical outcomes and echocardiographic features of 33 consecutive patients who experienced this complication during cardiac electrophysiology (EP) procedures performed at our institution from 1988 to 2007. Nineteen patients (58%) were managed conservatively with intravenous fluids and vasopressors (Group A). Fourteen patients (42%) were managed invasively with pericardiocentesis (Group B). RESULTS: The mean systolic blood pressure at diagnosis did not differ between the two groups (64 vs 71 mmHg, P = 0.134). The mean lengths of hospitalization (4.7 vs 4.9 days, P = 0.75) and survival to hospital discharge (100% in both groups) were also similar. A large pericardial effusion (>or=2 cm) was seen predominantly among Group B patients. There was a statistically significant temporal trend toward managing this type of complication invasively (P = 0.038). CONCLUSION: Among patients who experience cardiac perforation as an acute complication of EP procedure, there appears to be a role for conservative management in a subset of patients who do not have echocardiographic evidence of a large effusion and who respond well to initial stabilizing measures consisting of fluids and vasopressors.

FIGO stage IIIC endometrial carcinoma: prognostic factors and outcomes.

OBJECTIVES: Investigate the clinicopathologic characteristics, nodal distribution, and postoperative treatment of patients with FIGO stage IIIC endometrial carcinoma and determine patterns of recurrence and survival. METHODS: A retrospective review of 85 patients who underwent surgical staging with lymph node dissection at a single institution between 1979 and 2005 was performed. Data collected from patient charts included demographics, treatment, recurrence and survival. Variables were compared using the log-rank and X2 tests, and multivariate analysis was performed. RESULTS: Of 1487 patients who underwent surgical staging for endometrial cancer, 104 (7.0%) were diagnosed with stage IIIC disease and 85 of these were analyzed. Stage was determined by positive pelvic lymph nodes (PLN) in 54 patients, and positive para-aortic lymph nodes (PaLN)+/-PLN in 31 patients. With a median follow up of 50 months, 5-year overall survival (OS) was 61.3%, recurrence-free survival (RFS) was 58.0%, and disease-specific survival (DSS) was 71.9%. Median OS, RFS and DSS were 131 months, 131 months, and not attained, respectively. Five-year OS and RFS with positive PaLN were 48.8% and 44.4% respectively, compared to 69.7% and 65.6% with positive PLN only. On multivariate analysis, age, non-endometrioid histology, and >50% invasion were significantly associated with OS; age and non-endometrioid histology were associated with RFS. Disease recurred in 21 patients (24.7%): 15 distant, 4 abdominal, 1 para-aortic, and 1 pelvic. Disease recurred outside the field of radiation in all patients. CONCLUSIONS: Endometrial cancer patients with FIGO stage IIIC had a 5-year OS of 61.3%, a RFS of 58.0% and a DSS of 71.9% in this series. Because of the high proportion of distant sites of recurrence (71.4%), recurrence outside the radiation field (100%), and mortality after recurrence (86.3%), multimodality therapy should be considered.

Multidetector row computed tomography for identification of left atrial appendage filling defects in patients undergoing pulmonary vein isolation for treatment of atrial fibrillation: comparison with transesophageal echocardiography.

BACKGROUND: Advances in multidetector computed tomography (MDCT) technology now permit three-dimensional cardiac imaging with high spatial and temporal resolution. Historically, transesophageal echocardiography (TEE) has been the gold standard for assessment of the left atrial appendage (LAA) in patients with atrial fibrillation and other atrial arrhythmias. Findings on TEE, including demonstration of LAA thrombus and dense nonclearing spontaneous echocardiographic contrast (SEC), predict future fatal and nonfatal thromboembolic events. OBJECTIVE: The purpose of this study was to compare the diagnostic performance of 64-detector row MDCT in detecting LAA thrombus and dense nonclearing SEC as identified by TEE in patients undergoing pulmonary vein isolation for treatment of atrial fibrillation. METHODS: A total of 72 consecutive patients (69.4% male; mean age 56.1 +/- 10.3 years) underwent both MDCT and TEE for evaluation of the LAA (median intertest interval 0 days, interquartile range 0-5 days). MDCT assessment of the LAA was performed by two methods: (1) comparison of Hounsfield unit (HU) densities in the LAA apex to the ascending aorta (AscAo) in the same axial plane and (2) nonquantitative visual identification of a filling defect in the LAA. TEE evaluation of the LAA included identification of echodense intracavitary masses in the LAA as well as pulsed-wave Doppler interrogation of the LAA ostium. RESULTS: Patients with LAA thrombus or dense nonclearing SEC by TEE exhibited significantly lower LAA/AscAo HU ratios than patients who did not (0.82 +/- 0.22 vs 0.39 +/- 0.19, P <.001). LAA/AscAo HU cutoff ratios < or = 0.75 correlated to LAA thrombus or dense nonclearing SEC by TEE, with 100% sensitivity, 72.2% specificity, 28.6% positive predictive value, and 100% negative predictive value. HU ratios < or = 0.75 were associated with pulsed-wave Doppler velocities <50 cm/s of the LAA ostium (P <.001). In multivariable analysis, LAA/AscAo HU ratio < or = 0.75 remained a robust predictor of LAA thrombus or dense nonclearing SEC by TEE (P <.001). In contrast, MDCT identification of TEE-identified LAA thrombus or dense nonclearing SEC by visual detection of LAA filling defects resulted in lower sensitivity (50%) and negative predictive value (95.1%). CONCLUSION: Current-generation MDCT successfully identifies LAA thrombus and dense nonclearing SEC with high sensitivity and moderate specificity. Importantly, LAA/AscAo HU ratios >0.75 demonstrate 100% negative predictive value for exclusion of LAA thrombus or dense nonclearing SEC. These results suggest that in patients undergoing pulmonary vein isolation procedures, MDCT examinations that demonstrate LAA/AscAo HU ratios >0.75 may preclude the need for preprocedural TEE.

Precipitation of ventricular fibrillation by intravenous diltiazem and metoprolol in a young patient with occult Wolff-Parkinson-White syndrome.

We report the case of a young man who presented with a rapid, narrow-complex atrial fibrillation. A few hours after being administered intravenous metoprolol and diltiazem for rate control, he developed intermittent ventricular preexcitation on the electrocardiogram (ECG) and experienced ventricular fibrillation, from which he was successfully defibrillated. A subsequent electrocardiogram in sinus rhythm demonstrated previously unknown Wolff-Parkinson-White pattern. A left lateral accessory pathway was successfully ablated. Wolff-Parkinson-White syndrome should be included in the differential diagnosis when a young patient presents with atrial fibrillation, even if the ventricular complexes on the ECG are not preexcited.

Atrial fibrillation and chronic kidney disease: A review of options for therapeutic anticoagulation to reduce thromboembolism risk.

Atrial fibrillation and chronic kidney disease (CKD) commonly occur together, which poses a therapeutic dilemma due to increased risk of both systemic thromboembolism and bleeding. Chronic kidney disease also has implications for medication selection. The objective of this review is to evaluate the options for anticoagulation for thromboembolism prevention in patients with atrial fibrillation and chronic kidney disease. We searched PubMed for studies of patients with atrial fibrillation and CKD on warfarin or a direct oral anticoagulant (DOAC) for thromboembolism prevention through January 1 2018, in addition to evaluating major trials evaluating DOACs and warfarin use as well as society guidelines. For patients with mild to moderate chronic kidney disease, primarily observational data supports the use of warfarin, and high quality trial data and meta-analyses support the use and possible superiority of DOACs. For patients with severe chronic kidney disease, there are limited data on warfarin which supports its use, and data for DOACs is limited primarily to pharmacologic studies which support dose reductions but lack information on patient outcomes. For patients with end-stage renal disease, studies on warfarin are conflicting, but the majority suggest a lack of benefit and possible harm; studies in DOACs are very limited, but apixaban is the least renally cleared and may be both safe and effective. In conclusion, warfarin or DOACs may be used based on the degree of severity of chronic kidney disease, but further study in needed in patients with end-stage renal disease.

Decreased Rates of Inpatient Hypoglycemia Following Implementation of an Automated Tool in the Electronic Medical Record for Identifying Root Causes.

OBJECTIVE: The objective was to identify root causes of hypoglycemia on medicine inpatient units using an automated tool. Data collected will guide educational interventions aimed at improving patient care and safety by decreasing rates of hypoglycemia. METHODS: A survey was conducted among RNs to identify risk factors for hypoglycemia. Survey data were used to create a hypoglycemia root cause survey tool in the EMR. RNs were prompted to utilize the tool when blood glucose (BG) < 70 mg/dL. Once the most common modifiable cause of hypoglycemia was identified, an educational intervention for safe and effective use of insulin was launched. This strategy was designed to empower the care team to reduce the insulin dose when appropriate to prevent future hypoglycemic episodes. RESULTS: BG data were compared from March and April in 2016 and 2017. Rates of hypoglycemia (BG < 70 mg/dL) decreased from 2.3% to 1.5%; BG values in target range (70-180 mg/dL) increased from 59.4% to 65.7%; hyperglycemia (BG > 180 mg/dL) decreased from 38.3% to 32.8% (all P values < .001). The number of patients with recurrent hypoglycemia (3 or more episodes) decreased from 5.7% to 2.2% ( P = .044). CONCLUSIONS: The two most frequent modifiable causes of hypoglycemia (insulin and nutrition) were identified by an RN survey and confirmed by chart review. A targeted educational intervention addressing safe and effective insulin dosing resulted in a significant decrease in both hypoglycemia and recurrent hypoglycemia. This was associated with an improvement in overall glycemic control. Ongoing clinician education regarding insulin and nutrition accompanied by discussions between RNs and prescribers to address hypoglycemic events in real-time could continue to lower the rate of occurrence.

Systematic Review for the 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society.

BACKGROUND: Although large randomized clinical trials have found that primary prevention use of an implantable cardioverter-defibrillator (ICD) improves survival in patients with cardiomyopathy and heart failure symptoms, patients who receive ICDs in practice are often older and have more comorbidities than patients who were enrolled in the clinical trials. In addition, there is a debate among clinicians on the usefulness of electrophysiological study for risk stratification of asymptomatic patients with Brugada syndrome. AIM: Our analysis has 2 objectives. First, to evaluate whether ventricular arrhythmias (VAs) induced with programmed electrostimulation in asymptomatic patients with Brugada syndrome identify a higher risk group that may require additional testing or therapies. Second, to evaluate whether implantation of an ICD is associated with a clinical benefit in older patients and patients with comorbidities who would otherwise benefit on the basis of left ventricular ejection fraction and heart failure symptoms. METHODS: Traditional statistical approaches were used to address 1) whether programmed ventricular stimulation identifies a higher-risk group in asymptomatic patients with Brugada syndrome and 2) whether ICD implantation for primary prevention is associated with improved outcomes in older patients (>75 years of age) and patients with significant comorbidities who would otherwise meet criteria for ICD implantation on the basis of symptoms or left ventricular function. RESULTS: Evidence from 6 studies of 1138 asymptomatic patients were identified. Brugada syndrome with inducible VA on electrophysiological study was identified in 390 (34.3%) patients. To minimize patient overlap, the primary analysis used 5 of the 6 studies and found an odds ratio of 2.3 (95% CI: 0.63-8.66; p=0.2) for major arrhythmic events (sustained VAs, sudden cardiac death, or appropriate ICD therapy) in asymptomatic patients with Brugada syndrome and inducible VA on electrophysiological study versus those without inducible VA. Ten studies were reviewed that evaluated ICD use in older patients and 4 studies that evaluated unique patient populations were identified. In our analysis, ICD implantation was associated with improved survival (overall hazard ratio: 0.75; 95% confidence interval: 0.67-0.83; p<0.001). Ten studies were identified that evaluated ICD use in patients with various comorbidities including renal disease, chronic obstructive pulmonary disease, atrial fibrillation, heart disease, and others. A random effects model demonstrated that ICD use was associated with reduced all-cause mortality (overall hazard ratio: 0.72; 95% confidence interval: 0.65-0.79; p<0.0001), and a second "minimal overlap" analysis also found that ICD use was associated with reduced all-cause mortality (overall hazard ratio: 0.71; 95% confidence interval: 0.61-0.82; p<0.0001). In 5 studies that included data on renal dysfunction, ICD implantation was associated with reduced all-cause mortality (overall hazard ratio: 0.71; 95% confidence interval: 0.60-0.85; p<0.001).

Systematic review for the 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society.

BACKGROUND: Although large randomized clinical trials have found that primary prevention use of an implantable cardioverter-defibrillator (ICD) improves survival in patients with cardiomyopathy and heart failure symptoms, patients who receive ICDs in practice are often older and have more comorbidities than patients who were enrolled in the clinical trials. In addition, there is a debate among clinicians on the usefulness of electrophysiological study for risk stratification of asymptomatic patients with Brugada syndrome. AIM: Our analysis has 2 objectives. First, to evaluate whether ventricular arrhythmias (VAs) induced with programmed electrostimulation in asymptomatic patients with Brugada syndrome identify a higher risk group that may require additional testing or therapies. Second, to evaluate whether implantation of an ICD is associated with a clinical benefit in older patients and patients with comorbidities who would otherwise benefit on the basis of left ventricular ejection fraction and heart failure symptoms. METHODS: Traditional statistical approaches were used to address 1) whether programmed ventricular stimulation identifies a higher-risk group in asymptomatic patients with Brugada syndrome and 2) whether ICD implantation for primary prevention is associated with improved outcomes in older patients (>75 years of age) and patients with significant comorbidities who would otherwise meet criteria for ICD implantation on the basis of symptoms or left ventricular function. RESULTS: Evidence from 6 studies of 1138 asymptomatic patients were identified. Brugada syndrome with inducible VA on electrophysiological study was identified in 390 (34.3%) patients. To minimize patient overlap, the primary analysis used 5 of the 6 studies and found an odds ratio of 2.3 (95% CI: 0.63-8.66; p=0.2) for major arrhythmic events (sustained VAs, sudden cardiac death, or appropriate ICD therapy) in asymptomatic patients with Brugada syndrome and inducible VA on electrophysiological study versus those without inducible VA. Ten studies were reviewed that evaluated ICD use in older patients and 4 studies that evaluated unique patient populations were identified. In our analysis, ICD implantation was associated with improved survival (overall hazard ratio: 0.75; 95% confidence interval: 0.67-0.83; p<0.001). Ten studies were identified that evaluated ICD use in patients with various comorbidities including renal disease, chronic obstructive pulmonary disease, atrial fibrillation, heart disease, and others. A random effects model demonstrated that ICD use was associated with reduced all-cause mortality (overall hazard ratio: 0.72; 95% confidence interval: 0.65-0.79; p<0.0001), and a second "minimal overlap" analysis also found that ICD use was associated with reduced all-cause mortality (overall hazard ratio: 0.71; 95% confidence interval: 0.61-0.82; p<0.0001). In 5 studies that included data on renal dysfunction, ICD implantation was associated with reduced all-cause mortality (overall hazard ratio: 0.71; 95% confidence interval: 0.60-0.85; p<0.001).

Right and left ventricular outflow tract tachycardias: evidence for a common electrophysiologic mechanism.

INTRODUCTION: "Idiopathic" ventricular arrhythmias most often arise from the right ventricular outflow tract (RVOT), although arrhythmias from the left ventricular outflow tract (LVOT) are also observed. While previous work has elucidated the mechanism and electropharmacologic profile of RVOT arrhythmias, it is unclear whether those from the LVOT share these properties. The purpose of this study was to characterize the electropharmacologic properties of RVOT and LVOT arrhythmias. METHODS AND RESULTS: One hundred twenty-two consecutive patients (61 male; 50.9 +/- 15.2 years) with outflow tract arrhythmias comprise this series, 100 (82%) with an RVOT origin, and 22 (18%) with an LVOT origin. The index arrhythmia was similar: sustained ventricular tachycardia (VT) (RVOT = 28%, LVOT = 36%), nonsustained VT (RVOT = 40%, LVOT = 23%), and premature ventricular complexes (RVOT = 32%, LVOT = 41%) (P = 0.32). Cardiac magnetic resonance imaging and microvolt T-wave alternans results (normal/indeterminate) were also comparable. In addition, 41% with RVOT foci and 50% with LVOT foci were inducible for sustained VT (P = 0.48), and induction of VT was catecholamine dependent in a majority of patients in both groups (66% and 73%; RVOT and LVOT, respectively; P = 1.0). VT was sensitive to adenosine (88% and 78% in the RVOT and LVOT groups, respectively, P = 0.59) as well as blockade of the slow-inward calcium current (RVOT = 70%, LVOT = 80%; P = 1.00) in both groups. CONCLUSIONS: Electrophysiologic and pharmacologic properties, including sensitivity to adenosine, are similar for RVOT and LVOT arrhythmias. Despite disparate sites of origin, these data suggest a common arrhythmogenic mechanism, consistent with cyclic AMP-mediated triggered activity. Based on these similarities, these arrhythmias should be considered as a single entity, and classified together as "outflow tract arrhythmias."

Association between factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T mutations and events of the arterial circulatory system: a meta-analysis of published studies.

BACKGROUND: The association between the inherited gene mutations of factor V, prothrombin, and homocysteine metabolism and venous thromboembolic events is accepted widely; however, their influence on the arterial circulatory system remains controversial. METHODS: We performed a MEDLINE search to identify published case-control and cohort studies correlating the factor V Leiden, prothrombin (PT) G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T (TT genotype) mutations with myocardial infarction, ischemic stroke, or peripheral vascular disease. Studies were included only when they adhered to specific diagnostic criteria for ischemic events and met the published methodological criteria. Odds ratios (ORs) with accompanying 95% CIs were calculated for each mutation and clinical end points with a random-effects model (DerSimonian and Laird method). RESULTS: The association between inherited gene mutations and arterial ischemic events was modest: factor V Leiden mutation (OR, 1.21; 95% CI, 0.99-1.49), PT G20210A mutation (OR, 1.32; 95% CI, 1.03-1.69), and MTHFR TT mutation (OR, 1.20; 95% CI, 1.02-1.41). Subgroup analyses of younger patients (<55 years old) and of women revealed slightly stronger associations overall. CONCLUSIONS: Genetic abnormalities specific to factor V, prothrombin,and homocysteine metabolism increase the risk for myocardial infarction and ischemic stroke, particularly among younger patients and women. Because the overall association is only modest, screening studies should be limited to carefully selected patient populations. The individual propensity for arterial and venous thrombosis is likely influenced by differing local mechanisms, systemic mechanisms, or both.