Periprocedural Bleeding and 1-Year Outcome After Percutaneous Coronary Interventions Appropriateness of Including Bleeding as a Component of a Quadruple End Point

ObjectivesThe aim of the study was to investigate the relationship between bleeding within the 30 days after percutaneous coronary interventions (PCI) and 1-year mortality and to assess the appropriateness of inclusion of the periprocedural bleeding in a quadruple composite end point to assess PCI outcome.BackgroundPeriprocedural bleeding is one of the most frequent complications of PCI.MethodsThis study included 5,384 patients from 4 randomized placebo-controlled trials on the value of abciximab after pre-treatment with 600 mg of clopidogrel: ISAR-REACT, -SWEET, -SMART-2, and –REACT-2. Bleeding—defined according to the Thrombolysis In Myocardial Infarction criteria—included all bleeding events within 30 days after enrollment. The primary end point was 1-year mortality.ResultsIn the 4 trials, within the first 30 days there were 42 deaths (0.8%), 314 myocardial infarctions (MIs) (5.8%), 52 urgent revascularizations (1.0%), and 215 bleeding complications (4.0%). Mortality at 1 year was 3.6% (n = 197). A Cox proportional hazards model revealed that the 30-day occurrence of bleeding (hazard ratio [HR] 2.96, 95% confidence interval [CI] 1.96 to 4.48; p < 0.001), MI (HR 2.29, 95% CI 1.52 to 3.46; p < 0.001) and urgent revascularization (HR 2.49, 95% CI 1.16 to 5.35; p = 0.019) independently predicted 1-year mortality. The c statistic was 0.79 for bleeding, 0.78 for MI, and 0.78 for urgent revascularization, demonstrating a comparable discriminatory power of these adverse events for predicting 1-year mortality.ConclusionsOur study demonstrates a strong relationship between the 30-day frequency of bleeding and 1-year mortality after PCI and supports the inclusion of periprocedural bleeding in a 30-day quadruple end point for the assessment of outcome after PCI

Impact of Coronary Anatomy and Stenting Technique on Long-Term Outcome After Drug-Eluting Stent Implantation for Unprotected Left Main Coronary Artery Disease

ObjectivesThis study sought to evaluate the impact of anatomic and procedural variables on the outcome of the unprotected left main coronary artery (uLMCA) itself after drug-eluting stent (DES) implantation.BackgroundThere is a controversial debate regarding when and how to perform percutaneous coronary intervention (PCI) for an uLMCA stenosis.MethodsThis analysis is based on a randomized study of 607 patients undergoing PCI for uLMCA, randomized 1:1 to receive paclitaxel- or sirolimus-eluting stents. We evaluated the impact of the SYNTAX score, uLMCA anatomy, and stenting technique on in-stent restenosis (ISR), target lesion revascularization (TLR), and the 3-year outcomes.ResultsThe 3-year cardiac mortality rate was 5.8%; 235 (39%) patients had a true bifurcation lesion (TBL), and the median SYNTAX score was 27. TBL was associated with a higher need for multiple stents (72% vs. 37%, p < 0.001). TBL was a significant predictor of ISR (23% vs. 14%, p = 0.008) and for TLR (18% vs. 9%, p < 0.001). The need for multiple stents was a predictor of ISR (22% vs. 13%, p = 0.005) and for TLR (16% vs. 9%, p = 0.005). Culotte stenting showed better results compared with T-stenting for ISR (21% vs. 56%, p = 0.02) and for TLR (15% vs. 56%, p < 0.001). We observed a significant association between uLMCA-TLR and SYNTAX scores (9.2% for scores ≤22, 14.9% for scores 23 to 32, and 13.0% for scores ≥33, p = 0.008).ConclusionsPCI of uLMCA lesions with DES is safe and effective out to 3 years. TBL and multiple stents were independent predictors for ISR. In the multivariate analysis, independent predictors for TLR were TBL, age, and EuroSCORE (European System for Cardiac Operative Risk Evaluation). (Drug-Eluting-Stents for Unprotected Left Main Stem Disease [ISAR-LEFT-MAIN]; NCT00133237

MRI findings in patients with acute coronary syndrome and unobstructed coronary arteries

PURPOSE:The underlying diagnosis in patients with acute coronary syndrome (ACS) and unobstructed coronary arteries remains a diagnostic challenge. We analyzed the value of magnetic resonance imaging (MRI) in this clinical setting.METHODS:A total of 213 patients with ACS and unobstructed coronary arteries underwent MRI within a median of 2 days after initial presentation. Clinical, laboratory, and MRI data were analyzed. A consensus diagnosis was established for each case by an independent panel after reviewing the individual clinical, laboratory, and MRI data. Standardized interviews to determine patient outcomes were carried out after a median follow-up of 24 months. Clinical events were defined as a composite of death, stroke, myocardial infarction or recurrence of Takotsubo syndrome (TTS), new onset of heart failure with a left ventricular ejection fraction (LVEF) <30%, and occurrence of a new left ventricular thrombus formation.RESULTS:Final diagnoses included acute myocardial infarction (AMI) (40%), acute myocarditis (24%) and TTS (33%). In 3% of patients, nonspecific findings lead to an indeterminate diagnosis. Patients with TTS showed a significantly impaired LVEF during the index event (50% vs. 60% in AMI and 60% in myocarditis, P = 0.001). The extent of myocardial edema was most pronounced in patients with TTS (13.4%±11.4 vs. 4.6%±7.9 in AMI and 1.8%±2.7 in myocarditis, P < 0.001). TTS patients had the highest event rate (16.9%).CONCLUSION:Our study emphasizes the diagnostic utility of timely MRI in patients with ACS and unobstructed coronary arteries. We found a high prevalence of TTS patients, who had poorer outcomes compared with patients with a final diagnosis of AMI or myocarditis

Serum insulin-like growth factor-1 and its binding protein-7: potential novel biomarkers for heart failure with preserved ejection fraction

BACKGROUND: Insulin-like growth factor binding protein-7 (IGFBP-7) modulates the biological activities of insulin-like growth factor-1 (IGF-1). Previous studies demonstrated the prognostic value of IGFBP-7 and IGF-1 among patients with systolic heart failure (HF). This study aimed to evaluate the IGF1/IGFBP-7 axis in HF patients with preserved ejection fraction (HFpEF). METHODS: Serum IGF-1 and IGFBP-7 levels were measured in 300 eligible consecutive patients who underwent comprehensive cardiac assessment. Patients were categorized into 3 groups including controls with normal diastolic function (n = 55), asymptomatic left ventricular diastolic dysfunction (LVDD, n = 168) and HFpEF (n = 77). RESULTS: IGFBP-7 serum levels showed a significant graded increase from controls to LVDD to HFpEF (median 50.30 [43.1-55.3] vs. 54.40 [48.15-63.40] vs. 61.9 [51.6-69.7], respectively, P < 0.001), whereas IGF-1 levels showed a graded decline from controls to LVDD to HFpEF (120.0 [100.8-144.0] vs. 112.3 [88.8-137.1] vs. 99.5 [72.2-124.4], p < 0.001). The IGFBP-7/IGF-1 ratio increased from controls to LVDD to HFpEF (0.43 [0.33-0.56] vs. 0.48 [0.38-0.66] vs. 0.68 [0.55-0.88], p < 0.001). Patents with IGFB-7/IGF1 ratios above the median demonstrated significantly higher left atrial volume index, E/E’ ratio, and NT-proBNP levels (all P ≤ 0.02). CONCLUSION: In conclusion, this hypothesis-generating pilot study suggests the IGFBP-7/IGF-1 axis correlates with diastolic function and may serve as a novel biomarker in patients with HFpEF. A rise in IGFBP-7 or the IGFBP-7/IGF-1 ratio may reflect worsening diastolic function, adverse cardiac remodeling, and metabolic derangement

Temporal course of microvascular obstruction after myocardial infarction assessed by MRI

PURPOSEWe aimed to analyze the extent of microvascular obstruction (MO) after the index event compared with the follow-up at a median of three months.METHODSWe identified 31 patients with MO after primary percutaneous coronary intervention of acute myocardial infarction by cardiac magnetic resonance imaging. The initial examination was performed after the index event, and 27 patients had the follow-up exam after a median of three months (interquartile range, 2–4 months). In addition, we examined 10 patients without MO after transmural myocardial infarction, as a control group.RESULTSMO disappeared in 23 of 27 patients (85%) in the follow-up and transformed into transmural late gadolinium enhancement. In patients with persistent MO, mean MO size decreased from 2.25% to 1.25%. In patients with MO, mean infarct size decreased significantly from 20.8% to 14.7% (P < 0.001). In the control group, mean infarct size decreased from 12.7% to 10.5% in the follow-up scan (P = 0.137).CONCLUSIONMO is significantly reduced during the follow-up after acute myocardial infarction

Statin effect on thrombin inhibitor effectiveness during percutaneous coronary intervention: a post-hoc analysis from the ISAR-REACT 3 trial

Objective: To determine whether statin therapy influences the efficacy of thrombin inhibitor bivalirudin or unfractionated heparin (UFH) during PCI. Setting and patients: The post-hoc analysis of the ISAR-REACT 3 Trial included 4,570 patients: 3,106 patients were on statin therapy and 1,464 patients were not on statin therapy at the time of PCI procedure. Main outcome measures: The primary outcome of this analysis was the 30-day composite of death, myocardial infarction, target vessel revascularization (TVR) or major bleeding. Results: The primary outcome occurred in 7.9% patients (n=246) in the statin group versus 9.8% (n=143) in the non-statin group (P=0.036). There was an interaction in univariate (P=0.028) and multivariable (P=0.026) analysis between pre-PCI statin therapy and the type of antithrombotic therapy regarding myocardial infarction. In the statin group, bivalirudin significantly reduced the incidence of major bleeding (2.6 vs. 4.3%, P=0.013) with no significant difference in the incidence of myocardial infarction (4.9 vs. 5.2%; P=0.73) compared with UFH. In the non-statin group, bivalirudin was inferior to UFH regarding the incidence of myocardial infarction (7.1 vs. 4.1%, P=0.013), yet major bleeding remained lower among bivalirudin-treated patients (4.0 vs. 5.2%, P=0.25). Conclusion: This post-hoc analysis suggests the existence of an interaction between statin therapy before PCI and antithrombotic therapy during PCI. Patients receiving bivalirudin therapy at the time of PCI showed less periprocedural myocardial infarction when on pre-PCI statin therapy which has to be investigated in further studie

Single Center Retrospective Analysis of Conventional and Radial TIG Catheters for Transradial Diagnostic Coronary Angiography

Current guidelines favor the radial approach for coronary angiography. Therefore, specialty radial diagnostic catheters were designed to engage both coronary arteries with a single device. However, it is unclear if single catheters are superior to conventional catheters. A retrospective analysis was performed of consecutive right radial coronary angiographies to determine catheter use, fluoroscopy time, radiation dosage, and consumption of contrast. Procedures were performed with a single TIG catheter or conventional catheters (CONV). Procedures with coronary artery bypass grafts or ventricular angiographies were excluded. 273 transradial procedures were performed successfully. 95 procedures were performed with CONV and 178 procedures with a TIG. Crossover to additional catheters was higher in TIG (15.2%) compared to CONV (5.3%, p=0.02). Fluoroscopy time was comparable between CONV and TIG, without crossover (2.2±1.2 min versus 2.3±1.2 min; n.s.), however, greater in the case of crossover for CONV (5.8±0.7) and TIG (7.6±3.0; p=0.0001). Radiation dosage was similar in CONV and the TIG, without crossover (1419±1075, cGy∗cm2 versus 1690±1138; n.s.), however, greater for CONV (2374±620) and TIG (3733±2281, p=0.05) with crossover. Overall, the amount of contrast was greater in TIG (56±13 mL) versus CONV (48±3 mL; p=0.0003). CONV femoral catheters may be the primary choice for radial approach

Meta-analysis of randomized trials on drug-eluting stents vs. bare-metal stents in patients with acute myocardial infarction

Aims To compare the efficacy and safety of drug-eluting stents vs. bare-metal stents in patients with acute ST-segment elevation myocardial infarction. Methods and results We performed a meta-analysis of eight randomized trials comparing drug-eluting stents (sirolimus-eluting or paclitaxel-eluting stents) with bare-metal stents in 2786 patients with acute ST-segment elevation myocardial infarction. All patients were followed up for a mean of 12.0-24.2 months. Individual data were available for seven trials with 2476 patients. The primary efficacy endpoint was the need for reintervention (target lesion revascularization). The primary safety endpoint was stent thrombosis. Other outcomes of interest were death and recurrent myocardial infarction. Drug-eluting stents significantly reduced the risk of reintervention, hazard ratio of 0.38 (95% CI, 0.29-0.50), P < 0.001. The overall risk of stent thrombosis: hazard ratio of 0.80 (95% CI, 0.46-1.39), P = 0.43; death: hazard ratio of 0.76 (95% CI, 0.53-1.10), P = 0.14; and recurrent myocardial infarction: hazard ratio of 0.72 (95% CI, 0.48-1.08, P = 0.11) was not significantly different for patients receiving drug-eluting stents vs. bare-metal stents. Conclusion The use of drug-eluting stents in patients with acute ST-segment elevation myocardial infarction is safe and improves clinical outcomes by reducing the risk of reintervention compared with bare-metal stent

Selective Attenuation of Norepinephrine Release and Stress-Induced Heart Rate Increase by Partial Adenosine A1 Agonism

The release of the neurotransmitter norepinephrine (NE) is modulated by presynaptic adenosine receptors. In the present study we investigated the effect of a partial activation of this feedback mechanism. We hypothesized that partial agonism would have differential effects on NE release in isolated hearts as well as on heart rate in vivo depending on the genetic background and baseline sympathetic activity. In isolated perfused hearts of Wistar and Spontaneously Hypertensive Rats (SHR), NE release was induced by electrical stimulation under control conditions (S1), and with capadenoson 6 · 10−8 M (30 µg/l), 6 · 10−7 M (300 µg/l) or 2-chloro-N6-cyclopentyladenosine (CCPA) 10−6 M (S2). Under control conditions (S1), NE release was significantly higher in SHR hearts compared to Wistar (766+/−87 pmol/g vs. 173+/−18 pmol/g, p<0.01). Capadenoson led to a concentration-dependent decrease of the stimulation–induced NE release in SHR (S2/S1 = 0.90±0.08 with capadenoson 6 · 10−8 M, 0.54±0.02 with 6 · 10−7 M), but not in Wistar hearts (S2/S1 = 1.05±0.12 with 6 · 10−8 M, 1.03±0.09 with 6 · 10−7 M). CCPA reduced NE release to a similar degree in hearts from both strains. In vivo capadenoson did not alter resting heart rate in Wistar rats or SHR. Restraint stress induced a significantly greater increase of heart rate in SHR than in Wistar rats. Capadenoson blunted this stress-induced tachycardia by 45% in SHR, but not in Wistar rats. Using a [35S]GTPγS assay we demonstrated that capadenoson is a partial agonist compared to the full agonist CCPA (74+/−2% A1-receptor stimulation). These results suggest that partial adenosine A1-agonism dampens stress-induced tachycardia selectively in rats susceptible to strong increases in sympathetic activity, most likely due to a presynaptic attenuation of NE release