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Biomedical subjects

Dean J Kereiakes

Publications and source records attributed to Dean J Kereiakes.

At least 19 recordsLinked to original sources
PubMed2006

Microvolt T-wave alternans identifies patients with ischemic cardiomyopathy who benefit from implantable cardioverter-defibrillator therapy.

OBJECTIVES: This study sought to assess whether implantable cardioverter-defibrillators (ICDs) have different mortality benefits among patients with ischemic cardiomyopathy who screen negative and non-negative (positive and indeterminate) for microvolt T-wave alternans (MTWA). BACKGROUND: Microvolt T-wave alternans has been proposed as an effective tool for risk stratification. However, no studies have examined whether ICD benefits differ by MTWA group. METHODS: We developed a prospective cohort of 768 patients with ischemic cardiomyopathy (left ventricular ejection fraction < or =35%) and no prior sustained ventricular arrhythmia, of which 392 (51%) received ICDs. The mean follow-up time was 27 +/- 12 months. Propensity scores for ICD implantation based on the variables most likely to influence defibrillator implantation were developed for each MTWA cohort. Multivariable Cox analyses that controlled for propensity score, demographics, and clinical variables evaluated the degree to which ICDs decreased mortality risk for each MTWA group. RESULTS: We identified 514 (67%) patients with a non-negative MTWA test result. After multivariable adjustment, ICDs were associated with lower all-cause mortality in MTWA-non-negative patients (hazard ratio [HR] 0.45, 95% confidence interval [CI] 0.27 to 0.76, p = 0.003) but not in MTWA-negative patients (HR 0.85, 95% CI 0.33 to 2.20, p = 0.73) (for interaction, p = 0.04), with the mortality benefit in MTWA-non-negative patients largely mediated through arrhythmic mortality reduction (HR 0.30, 95% CI 0.13 to 0.68, p = 0.004). The number needed to treat with an ICD for 2 years to save 1 life was 9 among MTWA-non-negative patients and 76 among MTWA-negative patients. CONCLUSIONS: In patients with ischemic cardiomyopathy and no prior history of ventricular arrhythmia, mortality reduction with ICD implantation differs by MTWA status, with implications for risk stratification and health policy.

Aged↗
PubMed2006

The influence of peripheral arterial disease on outcomes: a pooled analysis of mortality in eight large randomized percutaneous coronary intervention trials.

OBJECTIVES: We aimed to evaluate clinical outcomes among peripheral arterial disease (PAD) patients following percutaneous coronary intervention (PCI). BACKGROUND: A significant proportion of patients with coronary artery disease undergoing PCI have concomitant PAD, which may be associated with worse outcomes. METHODS: We performed a pooled analysis of 8 randomized PCI trials. We included multicenter PCI trials that compared antiplatelet therapies (EPIC, EPILOG, EPISTENT, RAPPORT, CAPTURE, IMPACT-II, TARGET, and CREDO) and had baseline PAD status recorded. Multivariable analyses were performed with stepwise logistic regression for 7- and 30-day outcomes and Cox regression for 6-month and 1-year events. RESULTS: In our pooled analysis of 19,867 patients undergoing PCI, 1,602 (8.1%) were previously diagnosed with PAD. Patients with PAD had higher incidences of 7-day death (1.0% vs. 0.4%; p < 0.001) or myocardial infarction (MI) (6.8% vs. 5.6%; p = 0.047), 30-day death (1.7% vs. 0.7%; p < 0.001) or MI (7.4% vs. 6.1%; p = 0.05), 6-month death (4.2% vs. 1.5%; p < 0.001) or MI (9.1%, vs. 7.7%; p = 0.048), and 1-year death (5.0% vs. 2.1%; p < 0.001). There was a trend toward higher major bleeding risk with PAD (4.8% vs. 3.9%; p = 0.06). With multivariable analyses, PAD remains a significant predictor of mortality at 30 days (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.03 to 2.70; p = 0.039), 6 months (HR 1.76, 95% CI 1.31 to 2.37; p < 0.001), and 1 year (HR 1.46, 95% CI 1.08 to 1.96; p = 0.013). CONCLUSIONS: The presence of PAD is associated with higher rates of post-PCI death and MI, and is an independent predictor of short- and long-term mortality.

Angioplasty, Balloon, Coronary↗
PubMed2006

Clinical guidelines and practice: in search of the truth.

Data from randomized clinical trials, non-randomized studies, and registries, as well as expert panel consensus are appropriately weighted and woven into the context of clinical practice guidelines. Recent guidelines for the care of patients with ischemic heart disease have emphasized both risk stratification and early coronary angiography with revascularization of patients with high-risk indicators. Advances in our understanding of the pathogenesis of acute coronary syndromes and the dynamics of therapeutic innovation (improvement in catheter-based technologies and adjunctive pharmacotherapy) mandate the timely update and revision of practice guidelines. We believe that the weight of evidence remains clearly in support of an early invasive treatment strategy based on risk stratification. Arguments regarding treatment strategy (invasive vs. conservative) are misguided, and greater focus should be placed on improving the treatment-risk paradox demonstrated in clinical practice as well as on strategies to enhance current guideline compliance and utilization. Interest exists in establishing regional centers of excellence for care of patients with acute ischemic heart disease, analogous to the regionalized approach already established for patients with trauma or stroke. This approach is supported by data that demonstrate an inverse relationship between both institutional and operator procedural volumes and mortality, as well as by existing constraints in resources such as specialized nurses and subspecialty-trained physicians. It is appropriate at this time to briefly review specific aspects of the American College of Cardiology/American Heart Association practice guidelines and the current process of care for acute ischemic heart disease.

Acute Disease↗
PubMed2006

Periprocedural and late consequences of overlapping Cypher sirolimus-eluting stents: pooled analysis of five clinical trials.

OBJECTIVES: The purpose of this research was to determine the relative safety and efficacy of multiple (> or =2) overlapping Cypher sirolimus-eluting stents (SES) (Johnson & Johnson, New Brunswick, New Jersey). BACKGROUND: Overlapping coronary stents are common. The periprocedural and late clinical and angiographic consequences of overlapped coronary stents are not clearly defined, particularly for drug-eluting stents. METHODS: All patients enrolled into five clinical trials of the SES were analyzed. Three of these trials were prospective randomized comparisons of the SES to the bare-metal stent (BMS), and two were prospective non-randomized trials of SES-treated patients with historical controls. All clinical and angiographic outcomes in overlap-stent-treated patients were compared by stent type and with single-stent-treated patients for the same stent device. RESULTS: In all, 575 patients with stent overlap (337 SES, 238 BMS) and 1,162 patients with single stents (697 SES, 465 BMS) were analyzed. Stent overlap was associated with a greater late lumen loss in stent and more frequent angiographic restenosis regardless of stent type. Among overlap-stent-treated patients, the SES provided similar magnitude of restenosis benefit as observed for single-stent-treated patients. Overlapped SES was not associated with an increase in myocardial infarction. CONCLUSIONS: The strategy of SES overlap, when required, is both safe and efficacious in reducing restenosis with no increase in the incidence of myocardial infarction or major adverse cardiovascular events, when compared with a bare metal coronary stent prosthesis.

Angioplasty, Balloon, Coronary↗
PubMed2006

Prognostic utility of microvolt T-wave alternans in risk stratification of patients with ischemic cardiomyopathy.

OBJECTIVES: The purpose of this study was to assess if microvolt T-wave alternans (MTWA) is an independent predictor of mortality in patients with ischemic cardiomyopathy. BACKGROUND: Microvolt T-wave alternans has been proposed as an effective tool for identifying high-risk patients with ischemic cardiomyopathy who are likely to benefit from implantable cardioverter-defibrillator (ICD) therapy. However, earlier studies have been limited in their ability to control for baseline differences between MTWA-negative and -non-negative (positive and indeterminate) patients. METHODS: We enrolled 768 consecutive patients with ischemic cardiomyopathy (left ventricular ejection fraction < or =35%) and no prior history of ventricular arrhythmia. All patients underwent baseline MTWA testing and were classified as MTWA negative or non-negative. Multivariable Cox regression analyses, stratified by ICD status, were used to determine the association between MTWA testing and mortality after adjusting for demographic, clinical, and treatment differences between MTWA-negative and -non-negative patients. RESULTS: We identified 514 (67%) patients with a non-negative MTWA test. After multivariable adjustment, a non-negative MTWA test was associated with a significantly higher risk for all-cause (stratified hazard ratio [HR] = 2.24 [95% confidence interval 1.34 to 3.75]; p = 0.002) and arrhythmic mortality (stratified HR = 2.29 [1.00 to 5.24]; p = 0.049) but not for nonarrhythmic mortality (stratified HR = 1.77 [0.84 to 3.74]; p = 0.13). In subgroup analyses, a non-negative MTWA test was also associated with a higher risk for all-cause mortality in patients with ejection fractions < or =30% (stratified HR = 2.10 [1.18 to 3.73]; p = 0.01) and after excluding those with indeterminate MTWA tests (stratified HR = 2.08 [1.18 to 3.66]; p = 0.01). CONCLUSIONS: Microvolt T-wave alternans is a strong and independent predictor of all-cause and arrhythmic mortality in patients with ischemic cardiomyopathy.

Aged↗
PubMed2006

Safety and tolerability of serial home infusions of nesiritide for advanced heart failure.

Although the therapeutic strategy of serial 6-hour intravenous infusions of nesiritide for advanced chronic heart failure (HF) is currently under investigation, frequent hospital or clinic visits may present logistical challenges for many patients with HF. Therefore, a pilot study was conducted to evaluate the safety and tolerability of serial nesiritide infusions administered at home in this patient population. Twenty patients with advanced HF were enrolled into a protocol for the administration of 12 weekly intravenous infusions of nesiritide (2 microg/kg bolus, 0.01 microg/kg/min for 6 hours) at home. Blood samples and weights were obtained weekly, and clinical assessments were made at 4 and 12 weeks. During the 12-week study period, there were 3 deaths unrelated to nesiritide therapy. Six patients required >or=1 hospitalization for HF. Two of 204 infusions resulted in symptomatic hypotension, and there were no adverse renal events. Mean body weight decreased at week 4 but returned to baseline by week 12. Antibodies to nesiritide were not detected in any patient. In conclusion, serial home infusions of nesiritide in patients with advanced HF appear to be safe and well tolerated, but the efficacy of this therapeutic strategy requires definition in a larger, randomized trial.

Aged↗
PubMed2006

Two-year outcomes after sirolimus-eluting stent implantation: results from the Sirolimus-Eluting Stent in de Novo Native Coronary Lesions (SIRIUS) trial.

OBJECTIVES: The purpose of this study was to examine the two-year clinical outcomes in patients enrolled in the Sirolimus-Eluting Stent in De Novo Native Coronary Lesions (SIRIUS) study. BACKGROUND: The SIRIUS study was a double-blinded randomized study which demonstrated that sirolimus-eluting stents (SES) significantly improved angiographic results (at 8 months) and clinical outcomes (at 9 and 12 months) compared with bare-metal stents (BMS). METHODS: Patients with de novo native coronary artery lesions randomized to either SES (533 patients) or control BMS (525 patients) were followed for two years. RESULTS: Between one and two years, there were infrequent additional clinical events that were equally distributed between the sirolimus and control groups. After two years, target lesion revascularization was 5.8% and 21.3% in SES and control patients, respectively (p < 0.001), and major adverse cardiovascular events and target vessel failure rates were 10.1% versus 24.4% and 12.0% versus 26.7%, respectively (p < 0.0001 for both). There were no differences in death, myocardial infarction, and stent thrombosis between the two groups. CONCLUSIONS: Clinical outcomes two years after implantation of SES continue to demonstrate significant reduction in the need for repeat target lesion (and vessel) revascularization compared with BMS without evidence for either disproportionate late restenosis or late stent thrombosis.

Coronary Angiography↗
PubMed2006

Paclitaxel-eluting stents vs vascular brachytherapy for in-stent restenosis within bare-metal stents: the TAXUS V ISR randomized trial.

CONTEXT: Restenosis within bare-metal stents is often treated with repeat percutaneous coronary intervention, although subsequent recurrence rates are high, with vascular brachytherapy (VBT) affording the best results. The effectiveness of drug-eluting stents in this setting has not been established. OBJECTIVE: To investigate the safety and efficacy of the polymer-based, slow-release paclitaxel-eluting stent in patients with restenotic lesions after prior stent implantation in native coronary arteries. DESIGN, SETTING, AND PATIENTS: Prospective, multicenter, randomized trial conducted between June 6, 2003, and July 16, 2004, at 37 North American academic and community-based institutions in 396 patients with in-stent restenosis of a previously implanted bare-metal coronary stent (vessel diameter, 2.5-3.75 mm; lesion length, < or =46 mm). INTERVENTIONS: Patients were randomly assigned to undergo angioplasty followed by VBT with a beta source (n = 201) or paclitaxel-eluting stent implantation (n = 195). Clinical and angiographic follow-up at 9 months was scheduled in all patients. MAIN OUTCOME MEASURE: Ischemia-driven target vessel revascularization at 9 months. RESULTS: Diabetes mellitus was present in 139 patients (35.1%). Median reference vessel diameter was 2.65 mm and median lesion length was 15.3 mm. In the VBT group, new stents were implanted in 22 patients (10.9%) and in the paclitaxel-eluting stent group, multiple stents were required in 57 patients (29.2%), with median stent length of 24 mm. Follow-up at 9 months was complete in 194 patients in the VBT group and 191 patients in the paclitaxel-eluting stent group (96.5% and 97.9%, respectively). For VBT and paclitaxel-eluting stents, respectively, the number of events and 9-month rates for ischemic target lesion revascularization were 27 (13.9%) vs 12 (6.3%) (relative risk [RR], 0.45; 95% confidence interval [CI], 0.24-0.86; P = .01); for ischemic target vessel revascularization, 34 (17.5%) vs 20 (10.5%) (RR, 0.60; 95% CI, 0.36-1.00; P = .046); and for overall major adverse cardiac events, 39 (20.1%) vs 22 (11.5%) (RR, 0.57; 95% CI, 0.35-0.93; P = .02), with similar rates of cardiac death or myocardial infarction (10 [5.2%] vs 7 [3.7%]; RR, 0.71; 95% CI, 0.28-1.83; P = .48) and target vessel thrombosis (5 [2.6%] vs 3 [1.6%]; RR, 0.61; 95% CI, 0.15-2.50; P = .72). Angiographic restenosis at 9 months was 31.2% (53 of 170 patients) with VBT and 14.5% (25 of 172 patients) with paclitaxel-eluting stents (RR, 0.47; 95% CI, 0.30-0.71; P<.001). CONCLUSION: Treatment of bare-metal in-stent restenotic lesions with paclitaxel-eluting stents rather than angioplasty followed by VBT reduces clinical and angiographic restenosis at 9 months and improves event-free survival. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00287573.

Aged↗
PubMed2006

Initial experience with an intravenous P2Y12 platelet receptor antagonist in patients undergoing percutaneous coronary intervention: results from a 2-part, phase II, multicenter, randomized, placebo- and active-controlled trial.

BACKGROUND: Platelet-initiated acute thrombosis and coronary embolization are fundamental in the pathophysiology of complications during percutaneous coronary intervention (PCI). Cangrelor (formerly AR-C69931MX) is a novel, rapidly acting, intravenous, specific antagonist of platelet aggregation via binding to the adenosine diphosphate (ADP) P2Y12 receptor subtype. The primary aims of this study were to assess the initial safety and pharmacodynamics of cangrelor in patients undergoing PCI. METHODS: In part 1, patients undergoing PCI were randomized to an 18- to 24-hour of either placebo, 1-, 2-, or 4-microg/kg per minute cangrelor in addition to aspirin and heparin beginning before PCI. In part 2, patients were randomized to receive either cangrelor (4 microg/kg per minute) or abciximab before PCI. The primary end point was the composite incidence of major and minor bleeding through 7 days. Secondary end points included the occurrence of major adverse coronary events (death, MI, and unplanned repeat coronary intervention) through 30 days plus ex vivo platelet aggregation and bleeding times. RESULTS: Two hundred patients (3 dosage groups and placebo) were studied in part 1, and 199 additional patients were then randomized in the second part, comparing 1 dose of cangrelor and abciximab. Combined major and minor bleeding occurred in 13% of those receiving cangrelor and in 8% in those randomized to placebo (P = non significant [NS]) during part 1 and in 7% receiving cangrelor compared with 10% randomized to abciximab (P = NS), during part 2. The 30-day composite incidence of adverse cardiac events was similar between those receiving cangrelor and those receiving abciximab during part 2 (7.6% vs 5.3%, respectively, P = NS). Mean inhibition of ex vivo platelet aggregation in response to 3 micromol/L ADP at steady state was 100% for both cangrelor 4 microg/kg per minute and abciximab groups in part 2. After termination of infusion, platelet aggregation returned to baseline response more rapidly with cangrelor compared with abciximab. There was a trend toward longer bleeding time prolongation and lower platelet count with abciximab compared with cangrelor. CONCLUSIONS: This initial experience with intravenous cangrelor during PCI suggests an acceptable risk of bleeding and adverse cardiac events while achieving rapid, reversible inhibition of platelet aggregation via competitive binding to the ADP P2Y12 platelet receptor with less prolongation of bleeding time then the glycoprotein IIb/IIIa receptor antagonist abciximab.

Abciximab↗
PubMed2006

Platelet activation and progression to complications.

Platelets localize, amplify, and sustain the coagulant response at an injury site and release procoagulant platelet-derived microparticles. Abnormalities in platelet size and function may be present in acute coronary syndromes and following percutaneous coronary intervention (PCI). Platelet functional assessment prior to PCI is a predictor for the subsequent occurrence of adverse clinical events. Trials of glycoprotein IIb-IIIa inhibitors as adjunctive pharmacotherapy for PCI show that the magnitude of platelet inhibition achieved by therapy correlates with the degree of clinical benefit observed. In general, optimal periprocedural outcomes require high levels of platelet inhibition. Combined administration of antiplatelet therapies may produce additive or synergistic inhibition of platelet-mediated thrombosis.

Acute Disease↗
PubMed2006

Anterior mitral valve leaflet aneurysm due to infective endocarditis detected by cardiac magnetic resonance imaging.

We report a case of mitral valve aneurysm in a 30-year-old man presenting with fatigue, malaise, and fever 10 weeks after emergent aortic valve replacement for endocarditis. The transthoracic echocardiogram demonstrated perivalvular aortic regurgitation, but no abscess cavity was defined. Cardiac magnetic resonance imaging (MRI) revealed a mitral valve leaflet aneurysm. Both aortic and mitral valves were replaced with mechanical prostheses. Pathology of the excised mitral valve showed a focally hemorrhagic aneurysm of the anterior leaflet with myxoid degeneration and focal calcification. Early diagnosis and intervention are important to treat this rare, potentially fatal complication of aortic valve endocarditis. Cardiac MRI provided an accurate and useful preoperative diagnostic evaluation.

Abscess↗
PubMed2006

Early revascularization and ACC/AHA guideline-compliant medical management improve left ventricular function and short-term prognosis in patients presenting with acute myocardial infarction and severe left ventricular dysfunction.

BACKGROUND: Myocardial infarction (MI) complicated by severe left ventricular (LV) dysfunction is associated with significant morbidity and mortality. The natural history of this population with contemporary revascularization and guideline-based medical therapies is poorly defined. We sought to determine the impact of contemporary treatment strategies on LV function and prognosis in patients with MI and severe LV dysfunction. METHODS: Consecutive MI patients were prospectively followed as part of an ongoing internal database. The current report comprises 75 patients with first MI and severe LV systolic dysfunction (EF less than or equal to 3%). Initial demographic and clinical data were collected during hospitalization and at 1-, 3- and 6-month follow up. RESULTS: Patients were 71% male, 36% diabetic and 51% had prior coronary disease with a mean (+/- SD) age of 65 +/- 14 years. The average hospital stay was 5.7 days for ST-elevation (CPK range 424 to 5,250) and 2.4 days for non-ST-elevation MI (CPK range 175 to 705). Revascularization in-hospital was performed in 87% of patients (62 percutaneous, 3 surgical). At hospital discharge, treatment included beta-blockers (84%), ACE-inhibitors (73%), statins (81%), aspirin (88%) and clopidogrel (84%). Mean (+/- SD) LVEF was 25.7 +/- 5.9% in hospital, 36.6 +/- 11.8% by 1 to 3 months (p < 0.01), and 37.6 +/- 9.3% at 6 months (p < 0.01). By 1 to 3 months, 63% had improved LVEF, 24% were unchanged and 14% were worse. One patient died in the hospital and 3 died by 6-month follow up (mortality 5.3%). CONCLUSION: A strategy of early revascularization combined with guideline-based medical management favorably impacts LV function and short-term prognosis in MI patients with severe LV systolic dysfunction. With contemporary treatment strategies, the majority (> 60%) of patients demonstrate improvement in LVEF and mortality is low (5.3%).

Aged↗
PubMed2006

Therapeutic goals for effective platelet inhibition: a consensus document.

Clopidogrel combined with aspirin is the mainstay of antiplatelet therapy for patients who present with acute coronary syndromes as well as following either bare metal or drug-eluting stent placement. Limitations of clopidogrel therapy include the relatively long time course required to achieve maximal inhibition of platelet aggregation, individual variability in response to its effect, the risk of bleeding during its administration, and the irreversible nature of P2Y12 receptor binding, which leads to a prolonged time course for recovery of platelet function following discontinuation of clopidogrel. Several investigational P2Y12 receptor antagonists have pharmacological properties that may overcome some or all of these limitations. These novel agents such as prasugrel, AZD6140, and cangrelor are in advanced stages of clinical development for potential use in patients with coronary artery disease.

Consensus Statements as Topic↗