Tingfei Hu

Incomplete inhibition of thromboxane biosynthesis by acetylsalicylic acid: Determinants and effect on cardiovascular risk

Background— Incomplete inhibition of platelet thromboxane generation, as measured by elevated urinary 11-dehydro thromboxane B2 concentrations, has been associated with an increased risk of cardiovascular events. We aimed to determine the external validity of this association in aspirin-treated patients enrolled in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance (CHARISMA) trial and to determine whether there are any modifiable factors or interventions that lower urinary 11-dehydro thromboxane B2 concentrations that could thereby reduce cardiovascular risk. Methods and Results— Urinary 11-dehydro thromboxane B2 concentrations were measured in 3261 aspirin-treated patients at least 1 month after they had been randomly assigned to placebo or clopidogrel. Baseline urinary 11-dehydro thromboxane B2 concentrations in the highest quartile were associated with an increased risk of stroke, myocardial infarction, or cardiovascular death compared with the lowest quartile (adjusted hazard ratio 1.66, 95% CI 1.06 to 2.61, P=0.03). Increasing age, female sex, history of peripheral artery disease, current smoking, and oral hypoglycemic or angiotensin-converting enzyme inhibitor therapy were independently associated with higher urinary concentrations of 11-dehydro thromboxane B2, whereas aspirin dose ≥150 mg/d, history of treatment with nonsteroidal antiinflammatory drugs, history of hypercholesterolemia, and statin treatment were associated with lower concentrations. Randomization to clopidogrel (versus placebo) did not reduce the hazard of cardiovascular events in patients in the highest quartile of urinary 11-dehydro thromboxane B2 levels. Conclusions— In aspirin-treated patients, urinary concentrations of 11-dehydro thromboxane B2 are an externally valid and potentially modifiable determinant of stroke, myocardial infarction, or cardiovascular death in patients at risk for atherothrombotic events.

Cardiac implantable electronic device infections: Presentation, management, and patient outcomes

BACKGROUND Indications for cardiac implantable electronic devices (CIEDs) are increasing. Although CIED infections occur infrequently, the impact of this outcome is expected to be substantial. OBJECTIVE The purpose of this study was to the evaluate the outcome of patients undergoing removal of infected CIEDs. METHODS A retrospective study was conducted of all patients with proven or suspected infected CIEDs who were referred to the Cleveland Clinic for system removal from January 2002 through March 2007. RESULTS A total of 412 patients (age 68 +/- 15 years) were included in the study. The majority of patients (241 [59%]) presented with localized infection involving the device pocket. The remaining 171 patients (41%) presented with endovascular infection but no evidence of inflammation of the device pocket. Of the total 414 pathogens isolated, 366 (88%) were aerobic gram-positive organisms, of which 90% were Staphylococcus species, and almost half of these were methicillin resistant. In-hospital mortality was 4.6% (19 patients). Only 2 deaths were extraction related. One-year mortality was 17%. Among the total cohort, 8 (1.9%) patients had relapsing infection within the first year. Among patients who had device replacement during the same hospitalization, 6 (2.6%) had relapsing infections within 1 year of reimplantation; 5 of these patients had systemic symptoms and were bacteremic upon initial presentation. CONCLUSION CIED infections are most often caused by Staphylococcus species, half of which are methicillin resistant. Percutaneous lead and device removal along with antibiotic therapy are effective as primary interventions. The overall relapse rate is 1.9%, and the relapse rate among patients who had reimplantation during the same hospitalization is 2.6%.

The metabolic syndrome, its component risk factors, and progression of coronary atherosclerosis.

BACKGROUND The mechanism that confers adverse cardiovascular prognosis in patients with the metabolic syndrome (MetS) remains unclear. We sought to investigate the association of MetS and its component risk factors with progression of coronary atherosclerosis. METHODS We performed a systematic review of 3459 patients who participated in 7 clinical trials that monitored coronary atheroma progression with intravascular ultrasonography. Patients with or without MetS were compared with regard to clinical characteristics, coronary atheroma burden at baseline, and change on serial evaluation. Relationships between plaque progression (> or =5% increase in percent atheroma volume [PAV]), MetS, and its component risk factors were investigated. RESULTS The metabolic syndrome was highly prevalent and was associated with greater progression of PAV (+0.51% +/- 0.23% vs +0.23% +/- 0.24%; P = .003). Multivariable analysis showed that MetS was associated with a greater likelihood of undergoing progression of PAV (adjusted odds ratio [OR], 1.25; 95% confidence interval [CI], 1.05-1.48; P = .01). When the individual components were used in the model instead of MetS, hypertriglyceridemia (OR, 1.26; 95% CI, 1.06-1.49; P = .008) and a body mass index of 30 or higher (1.18, 1.00-1.40; P = .05) predicted progression of PAV. However, after adjusting for its individual components, MetS was no longer an independent predictor (OR, 1.04; 95% CI, 0.79-1.37; P = .79). CONCLUSION Although accelerated disease progression is observed in the setting of MetS, this is owing to the presence of individual component risk factors rather than to the presence of the syndrome itself.

Prognostic Value of Electrocardiographic Measurements Before and After Cardiac Resynchronization Device Implantation in Patients With Heart Failure due to Ischemic or Nonischemic Cardiomyopathy

Postimplant QRS narrowing may predict clinical response after cardiac resynchronization therapy (CRT), but identification of nonresponders remains difficult. We studied the predictive value of electrocardiographic characteristics for mortality or cardiac transplantation in patients after CRT. Patients who had electrocardiograms available for review from before and after CRT device implantation were identified from a clinical database. Bivariate and multivariate Cox regression analyses were performed for the end point of death or transplantation. Of 337 patients (age 65+/-12 years, 76% men, left ventricular ejection fraction 22+/-12%, pre-QRS 175+/-30 ms), 84 died and 7 underwent transplantation during a follow-up of 27+/-15 months. Variables predictive of death or transplantation included QRS increase after CRT (45% vs 32%, p=0.03), older age, higher New York Heart Association class, lower left ventricular ejection fraction, and higher tertile of postimplant QRS (p=0.04), but not preimplant rhythm, QRS duration, or QRS morphology. After adjusting for confounding variables, independent predictors of mortality were older age (hazard ratio [HR] 1.03, 95% confidence interval [CI] 1.00 to 1.05, p=0.04), lack of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (HR 2.17, 95% CI 1.16 to 4.08, p<0.02), and longer postimplant QRS by tertile (HR 1.50, 95% CI 1.09 to 2.05, p=0.01). In conclusion, wider QRS after CRT device implantation is an independent predictor of mortality or transplantation. In patients with increased QRS durations despite CRT, closer follow-up or reassessment for alternative management strategies may be warranted.

Long-term outcomes and clinical predictors for pacemaker-requiring bradyarrhythmias after cardiac transplantation: Analysis of the UNOS/OPTN cardiac transplant database

BACKGROUND Pacemaker-requiring bradyarrhythmias after cardiac transplantation are common, and rarely can lead to sudden cardiac death. Prior outcomes studies have been limited to single-center data. OBJECTIVE This study sought to define the long-term outcomes and clinical predictors for pacemaker-requiring bradyarrhythmias in the cardiac transplant population. METHODS This study used multivariable analysis of the United Network for Organ Sharing/Organ Procurement and Transplantation Network (UNOS/OPTN) database of sequential U.S. cardiac transplant recipients from 1997 to 2007 stratified by postoperative bradyarrhythmias requiring a pacemaker. The primary end point was all-cause mortality. RESULTS Among 35,987 cardiac transplant recipients (age 46.1 ± 18.3 years, 76% male, 22% bicaval technique) with a follow-up of 6.3 ± 4.7 years, pacemaker-requiring bradyarrhythmias occurred in 3,940 patients (10.9%). Pacemaker recipients demonstrated improved survival (median 8.0 years vs. 5.2 years, P < .001), decreased 5-year mortality (13.8% vs. 17.7%, P < .001), and overall crude mortality (42.9% vs. 45.9%, P < .001). Multivariable propensity-score-adjusted analysis demonstrated improved survival among pacemaker recipients (adjusted hazard ratio 0.84, 95% confidence interval [CI] 0.80 to 0.88, P < .001) after adjustment for donor/recipient age, UNOS listing status, donor heart ischemic time, surgical technique, graft rejection, and other common comorbidities. The bicaval surgical technique was strongly protective against a postoperative pacemaker requirement (odds ratio [OR] 0.33, 95% CI 0.29 to 0.36, P < .001) in multivariable analysis. Among the other variables studied, only increasing donor age (OR 1.04, 95% CI 1.00 to 1.09, P < .001) and recipient age (OR 1.09, 95% CI 1.0 to 1.12, P < .001) were associated with a permanent pacemaker requirement. CONCLUSION Cardiac transplant recipients with pacemaker-requiring bradyarrhythmias have an excellent long-term prognosis. Increased mortality in the nonpacemaker group merits further investigation. Biatrial surgical technique and increasing donor/recipient age are associated with postoperative pacemaker requirement.

Clopidogrel and aspirin versus aspirin alone for the prevention of stroke in patients with a history of atrial fibrillation: subgroup analysis of the CHARISMA randomized trial.

Background: Aspirin offers modest reduction in stroke in patients with atrial fibrillation. Whether combination of aspirin with clopidogrel offers additional protection is unclear. Methods: Post-hoc subgroup analysis of 593 participants with a history of atrial fibrillation in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) randomized trial testing clopidogrel 75 mg per day plus aspirin (75–162 mg per day) vs. aspirin alone in patients with stable cardiovascular disease or multiple cardiovascular risk factors. Results: Mean patient age was 70 years, 78% were men, and hypertension, heart failure and diabetes were present in 78, 20 and 44%, respectively. During a median follow-up of 2.3 years, stroke (ischemic and hemorrhagic) occurred in 15 of 298 assigned to clopidogrel plus aspirin and in 14 of 285 given aspirin alone (hazard ratio, HR, 1.03, 95% CI 0.49–2.1). There was no difference in all-cause mortality (HR 1.1, 95% CI 0.6–1.9) or in the composite of stroke, myocardial infarction, or vascular death (HR = 1.2, 95% CI 0.7–2.0). Severe/fatal extracranial hemorrhage occurred in 6 patients with combination vs. 3 with aspirin alone. Conclusions: This post-hoc subgroup analysis does not support the use of this combination over aspirin alone in patients with a history of atrial fibrillation pending results of ongoing larger randomized trials.

Comparison of Rates of Progression of Coronary Atherosclerosis in Patients With Diabetes Mellitus Versus Those With the Metabolic Syndrome

Diabetes mellitus (DM) and metabolic syndrome (MS) are associated with adverse cardiovascular outcomes. However, the extent and progression of coronary atherosclerosis for these conditions have not been directly compared. Three thousand four hundred fifty-nine patients with coronary artery disease underwent serial evaluation of atheroma burden by intravascular ultrasound. Patients with DM, MS, or neither diagnosis were compared with regard to plaque burden, progression, and arterial remodeling. Among the 3 groups, patients with MS had the largest number of individual cardiovascular risk factors. Patients with DM demonstrated more extensive atherosclerosis burden with a greater percent atheroma volume compared to patients with MS or those with neither diagnosis (40.3 +/- 9.0%, 37.6 +/- 8.9%, and 38.1 +/- 9.1%, p <0.001) and total atheroma volume (198.3 +/- 85.9, 190.7 +/- 85.0, and 186.3 +/- 79.1 mm(3), p = 0.05). MS compared to neither diagnosis was accompanied by expansion of the external elastic membrane (501.3 +/- 174.3 vs 484.4 +/- 160.7 mm(3), p = 0.02), whereas DM was associated with lumen constriction (290.6 +/- 111.7 vs 298.1 +/- 105.5 mm(3), p <0.0001). On serial evaluation, DM, but not MS, was associated with greater progression of percent atheroma volume compared to neither diagnosis (+0.8 +/- 0.3, +0.3 +/- 0.2, and +0.1 +/- 0.2%, p <0.0001) and total atheroma volume (-1.0 +/- 1.8, -3.3 +/- 1.8, and -4.0 +/- 1.8 mm(3), p = 0.001). Meeting criteria for MS was not associated with greater disease progression in patients with DM. In conclusion, despite having fewer individual risk factors, DM is associated with greater plaque progression and more constrictive remodeling than MS. This finding highlights the deleterious effects of DM on the arterial wall independent of its associated metabolic abnormalities.