Exercise capacity and N-terminal pro-brain natriuretic peptide levels with biventricular vs. right ventricular pacing for atrioventricular block: results from the PREVENT-HF German Substudy.

AIMS: Previous studies showed unfavourable effects of right ventricular (RV) pacing. Ventricular pacing (VP), however, is required in many patients with atrioventricular (AV) block. The PREVENT-HF study explored left ventricular (LV) remodelling during RV vs. biventricular (BIV) pacing in AV block without advanced heart failure. The pre-specified PREVENT-HF German Substudy examined exercise capacity and N-terminal pro-brain natriuretic peptide (NT-proBNP). METHODS AND RESULTS: Patients with expected VP ≥80% were randomized to RV or BIV pacing. Endpoints were peak oxygen uptake (pVO2), oxygen uptake at the anaerobic threshold (VO2AT), ventilatory efficiency (VE/VCO2), and logNT-proBNP. Considering crossover, intention to treat (ITT), and on-treatment (OT) analyses of covariance (ANCOVA) were performed. For exercise testing 44 (RV: 25, BIV: 19), and for NT-proBNP 53 patients (RV: 29, BIV: 24) were included. The ITT analysis revealed significant differences in pVO2 [ANCOVA effect 2.83 mL/kg/min, confidence interval (CI) 0.83-4.91, P = 0.007], VO2AT (ANCOVA effect 2.14 mL/min/k, CI 0.14-4.15, P = 0.03), and VE/VCO2 (ANCOVA effect -5.46, CI -10.79 to -0.13, P = 0.04) favouring BIV randomization. The significant advantage in pVO2 persisted in OT analysis, while VO2AT and VE/VCO2 showed trends favouring BIV pacing. LogNT-proBNP did not differ between groups. (ITT: ANCOVA effect 0.008, CI -0.40 to +0.41, P = 0.97; OT: ANCOVA effect -0.03, CI -0.44 to 0.30, P = 0.90). CONCLUSION: Our study suggests that BIV pacing produces better exercise capacity over 1 year compared with RV pacing in patients without advanced heart failure and AV block. In contrast, we observed no significant changes of NT-proBNP. Larger trials will allow appraising the clinical usefulness of BIV pacing in AV block. ClinicalTrials.gov Identifier: NCT00170326.

Relationship between the intensity of heparin anticoagulation and clinical outcomes in patients receiving glycoprotein IIb/IIIa inhibitors during primary percutaneous coronary intervention in acute myocardial infarction.

OBJECTIVES: We sought to determine the impact of the activated clotting time (ACT) in patients with ST elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) with unfractionated heparin (UFH) and a glycoprotein IIb/IIIa inhibitor (GPI). BACKGROUND: UFH+GPI is commonly used during primary PCI for STEMI. UFH anticoagulation is titrated with ACT. METHODS: Patients randomized to UFH+GPI in HORIZONS-AMI who underwent primary PCI are included (N = 1,624). Initial UFH bolus was 60 IU kg(-1) (target ACT: 200-250 sec). Patients were divided into three tertiles of peak ACT (cutoffs 240 and 298 sec). The 30-day rates of major and minor bleeding, major adverse cardiovascular events (MACE), and net adverse clinical events (NACE; MACE or major bleeding) were determined. RESULTS: Mortality at 30 days occurred in 2.2, 3.3, and 3.5% of patients in the low to high ACT tertiles, respectively (P(trend) = 0.22). Nor was the peak ACT significantly related to major bleeding, MACE or NACE. However, minor bleeding was increased in the highest ACT tertile (14.7% vs. 14.2% vs. 19.4%, P(trend) = 0.04). By multivariable analysis peak ACT was not significantly related to major bleeding, mortality, MACE, and NACE but was a significant independent predictor of minor bleeding (odds ratio = 1.027 [1.013, 1.042], P < 0.001, for each 10 sec increase in ACT). CONCLUSIONS: In patients undergoing primary PCI for STEMI treated with UFH+GPI, the peak procedural ACT achieved does not have a substantial effect on major bleeding, mortality, or MACE, although lower peak ACT is associated with less minor bleeding.

Impact of transfer for primary percutaneous coronary intervention on survival and clinical outcomes (from the HORIZONS-AMI Trial).

Primary percutaneous coronary intervention (PCI) is the preferred reperfusion strategy in patients with ST-segment elevation myocardial infarction (STEMI). We evaluated whether presentation of patients with STEMI to a noninterventional facility requiring transfer for primary PCI compared to direct admission to a PCI center has an impact on clinical outcomes. Of 3,602 patients enrolled in the multicenter, prospective HORIZONS-AMI trial, 988 (24.7%) were transferred for primary PCI and 2,614 were directly admitted to an interventional hospital. Clinical outcomes at 30 days and 1 year were evaluated. Median time to reperfusion in patients with transfer was 67 minutes longer compared to patients without transfer (272 vs 205 minutes, p <0.001), and first door-to-balloon time was 47 minutes longer (134 vs 87 minutes, p <0.001). At 30 days and 1 year there were no significant differences between patients with and without transfer in the rates of major adverse cardiac events (30 days 5.8% vs 5.4%, p = 0.68; 1 year 11.6% vs 12.0%, p = 0.74), major bleeding (30 days 7.3% vs 6.9%, p = 0.66; 1 year 7.9% vs 7.4%, p = 0.63), or mortality (30 days 2.6% vs 2.6%, p = 0.92; 1 year 4.0% vs 4.2%, p = 0.81). In transfer and nontransfer patients use of bivalirudin compared to unfractionated heparin plus glycoprotein IIb/IIIa inhibitor was associated with lower rates of bleeding, cardiac death, and net adverse clinical events. In conclusion, in the HORIZONS-AMI trial, 30-day and 1-year survival rates and clinical outcomes were comparable in patients with STEMI requiring and not requiring transfer for primary PCI.

Clinical and arrhythmic outcomes after implantation of a defibrillator for primary prevention of sudden death in patients with post-myocardial infarction cardiomyopathy: The Survey to Evaluate Arrhythmia Rate in High-risk MI patients (SEARCH-MI).

AIMS: To evaluate clinical and arrhythmic outcomes in post-infarction cardiomyopathy patients implanted with a defibrillator (ICD) for primary prevention of sudden death. METHODS AND RESULTS: The SEARCH-MI registry is a European multi-centre, prospective, observational study enrolling patients after myocardial infarction, chronic left ventricular dysfunction and an ICD implanted for primary prevention of sudden death. Data on 556 patients with at least one recorded follow-up are presented. Survey to Evaluate Arrhythmia Rate in High-risk MI (SEARCH-MI) patients were sicker than those enrolled in MADIT-II with higher New York Heart Association class and left bundle branch block. Total mortality was 10.4%. Close to one-third (30%) of patients experienced episodes of sustained ventricular arrhythmia. One-quarter (23%) received at least one appropriate therapy and 10% inappropriate therapy. Gender (25% males vs. 5% females, P = 0.0009) and history of non-sustained ventricular tachycardia (24% with vs. 18% without P = 0.037) were predictive of appropriate ventricular therapy. CONCLUSION: SEARCH-MI represents the current clinical management of post-MI patients with left ventricular dysfunction indicated to defibrillator implant for primary prevention. European routine clinical practice was influenced by landmark trials and guidelines which impacted on the implantation of cardiac resynchronization therapy in over 25% of such patients. Non-sustained ventricular tachycardia identifies subjects with a higher incidence of appropriate ICD therapy.

Systemic exposure of everolimus after stent implantation: a pharmacokinetic study.

OBJECTIVES: We evaluated the pharmacokinetics of the eluted everolimus by assessing systemic drug release and distribution of everolimus-eluting stents. BACKGROUND: Drugs eluted by a coronary stent might cause adverse events such as tumors, infections, or noncardiac death. The systemic exposure of the drugs is unknown because there are only limited data about pharmacokinetics of drug-eluting stents in humans. METHODS: Venous blood samples in a subset of 39 patients were drawn just before implantation of the first stent (baseline, 0-minute time point) and at 10 and 30 minutes and 1, 2, 4, 6, 12, 24, 36, 48, 72, 168, and 720 hours (30 days) after completion of implantation of the last stent. Whole blood concentrations of everolimus were determined using a sensitive validated high-performance liquid chromatography mass spectrometry/mass spectrometry method. RESULTS: The total dose of everolimus received by the patients ranged from 53 to 588 microg. The last time point up to which whole blood concentrations could be quantified ranged per patient from 4 to 720 hours after implantation of the last stent. Across all dose levels, individual T(max) values ranged from 0.13 and 2.17 hours; individual C(max) ranged from 0.14 to 2.79 ng/mL. CONCLUSION: This study confirms the limited exposure to the systemic circulation of the eluted drug with the use of the XIENCE V Everolimus-Eluting Coronary Stent System (Abbott Vascular, Santa Clara, CA). Therefore, a systemic cause of adverse events is unlikely.

Routine upstream initiation vs deferred selective use of glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: the ACUITY Timing trial.

CONTEXT: In patients with moderate- and high-risk acute coronary syndromes (ACS) who undergo an early, invasive treatment strategy, current guidelines recommend administration of platelet glycoprotein IIb/IIIa (Gp IIb/IIIa) inhibitors, either upstream to all patients prior to angiography or deferred for selective use in the catheterization laboratory just prior to angioplasty. The preferred approach is undetermined. OBJECTIVE: To determine the optimal strategy for the use of Gp IIb/IIIa inhibitors in patients with moderate- and high-risk ACS undergoing an early, invasive treatment strategy. DESIGN: Prospective, randomized, open-label trial with 30-day clinical follow-up. SETTING: Four hundred fifty academic and community-based institutions in 17 countries. PATIENTS: A total of 9207 patients with moderate- and high-risk ACS undergoing an invasive treatment strategy. INTERVENTIONS: Patients were randomly assigned to receive either routine upstream (n=4605) or deferred selective (n=4602) Gp IIb/IIIa inhibitor administration, respectively. MAIN OUTCOME MEASURES: The primary outcome was assessment of noninferiority of deferred Gp IIb/IIIa inhibitor use compared with upstream administration for the prevention of composite ischemic events (death, myocardial infarction, or unplanned revascularization for ischemia) at 30 days, using a 1-sided alpha level of .025. Major secondary end points included noninferiority or superiority of major bleeding and net clinical outcomes (composite ischemia or major bleeding). RESULTS: Glycoprotein IIb/IIIa inhibitors were used more frequently (98.3% vs 55.7%, respectively) and for a significantly longer duration (median, 18.3 vs 13.1 hours; P<.001) in patients in the upstream group compared with the deferred group. Composite ischemia at 30 days occurred in 7.9% of patients assigned to deferred use compared with 7.1% of patients assigned to upstream administration (relative risk, 1.12; 95% confidence interval, 0.97-1.29; P = .044 for noninferiority; P = .13 for superiority); as such, the criterion for noninferiority was not met. Deferred use compared with upstream use resulted in reduced 30-day rates of major bleeding (4.9% vs 6.1%, respectively; P<.001 for noninferiority; P = .009 for superiority) and similar rates of net clinical outcomes (11.7% vs 11.7%; P<.001 for noninferiority; P = .93 for superiority). CONCLUSIONS: Among patients with moderate- and high-risk ACS undergoing an invasive treatment strategy, deferring the routine upstream use of Gp IIb/IIIa inhibitors for selective administration in the cardiac catheterization laboratory only to patients undergoing percutaneous coronary intervention resulted in a numerical increase in composite ischemia that, while not statistically significant, did not meet the criterion for noninferiority. This finding was offset by a significant reduction in major bleeding. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00093158.

One year clinical follow-up of the XIENCE V Everolimus-eluting stent system in the treatment of patients with de novo native coronary artery lesions: the SPIRIT II study.

AIMS: The SPIRIT II study randomised 300 patients in a ratio of 3:1 to receive either a XIENCE V or a TAXUS stent. The six month clinical and angiographic results have previously been reported. This paper presents the clinical follow-up of these patients to one year. METHODS AND RESULTS: As a continuation in the assessment of the safety and performance of the XIENCE V Everolimus-Eluting Coronary Stent System (EECSS) enrolled patients were requested to return for clinical follow-up one year following the procedure to assess the occurrence of ischaemia driven major adverse cardiac events (MACE).Of the 300 patients recruited at 28 sites in Europe, New Zealand and India, 223 were randomised to receive an EECSS stent and 77 a TAXUS paclitaxel eluting coronary stent system (PECSS). One-year clinical follow-up was obtained in 220 of the 223 patients in the EECSS group (98.7%) with one withdrawal prior to 180 days and two non-cardiac deaths (pulmonary malignancy and pneumonia) between six and 12 months, and in 76 of 77 (98.7%) PECSS group of patients (one patient had a missed 270-day and 1-year visit). Between six and 12 months there were no new occurrences of late stent thrombotic events in either group. There were no additional MACE events in the EECSS compared to, two, both ischaemia driven target lesion revascularisations (TLR) in the PECSS group. CONCLUSIONS: The clinical safety of the XIENCE V EECSS stent observed at six months was sustained at one year. There were no additional thrombotic or MACE events in the EECSS group. Although not a primary endpoint, there was a significant difference in MACE favouring the EECSS compared to PECSS (2.7% versus 9.2%, P=0.04).