Guy Proulx

A Randomized Study Comparing Same-Day Home Discharge and Abciximab Bolus Only to Overnight Hospitalization and Abciximab Bolus and Infusion After Transradial Coronary Stent Implantation

Background— Systematic use of coronary stents and optimized platelet aggregation inhibition has greatly improved the short-term results of percutaneous coronary interventions. Transradial percutaneous coronary interventions have been associated with a low risk of bleeding complications. It is unknown whether moderate- and high-risk patients can be discharged safely the same day after uncomplicated transradial percutaneous coronary interventions. Methods and Results— We randomized 1005 patients after a bolus of abciximab and uncomplicated transradial percutaneous coronary stent implantation either to same-day home discharge and no infusion of abciximab (group 1, n=504) or to overnight hospitalization and a standard 12-hour infusion of abciximab (group 2, n=501). The primary composite end point of the study was the 30-day incidence of any of the following events: death, myocardial infarction, urgent revascularization, major bleeding, repeat hospitalization, access site complications, and severe thrombocytopenia. The noninferiority of same-day home discharge and bolus of abciximab only compared with overnight hospitalization and abciximab bolus and infusion was evaluated. Two thirds of patients presented with unstable angina and ≈20% presented with high-risk acute coronary syndrome prior to the procedure. The incidence of the primary end point was 20.4% in group 1 and 18.2% in group 2 (P=0.017 for noninferiority) with a troponin T–based definition of myocardial infarction; the incidence of the primary end point was 11.1% in group 1 and 9.6% in group 2 (P=0.0004 for noninferiority) with a creatinine kinase myocardial band–based definition of myocardial infarction. No death occurred. Rate of major bleeding in both groups was extremely low at 0.8% and 0.2%, respectively. From 504 patients randomized in group 1, 88% were discharged home the same day. Conclusion— Our data suggest that same-day home discharge after uncomplicated transradial coronary stenting and bolus only of abciximab is not clinically inferior, in a wide spectrum of patients, to the standard overnight hospitalization and a bolus followed by a 12-hour infusion. This novel approach offers a safe strategy for same-day home discharge after uncomplicated coronary intervention.

Predicting Late Myocardial Recovery and Outcomes in the Early Hours of ST-Segment Elevation Myocardial Infarction : Traditional Measures Compared With Microvascular Obstruction, Salvaged Myocardium, and Necrosis Characteristics by Cardiovascular Magnetic Resonance

OBJECTIVES The aim of this study was to determine whether a very early imaging strategy improves the prediction of late systolic dysfunction and poor outcomes in ST-segment elevation myocardial infarction (STEMI) compared with traditional predictors. BACKGROUND Earlier prediction of poor outcomes after STEMI is desirable, because it will allow tailored therapy at the earliest possible time, when benefits might be greatest. METHODS One hundred and three patients with acute STEMI were studied by contrast-enhanced cardiovascular magnetic resonance within 12 h of primary angioplasty and at 6 months and followed >2 years. The primary end point was left ventricular (LV) dysfunction, whereas poor outcomes were a key secondary end point. RESULTS Traditional risk factors were only modest predictors of late LV dysfunction. Late gadolinium enhancement (LGE) volume maintained a stronger association to LV ejection fraction change than infarct transmurality, microvascular obstruction, or myocardial salvage during STEMI (p = 0.02). Multivariable logistic regression identified LGE volume during STEMI as the best predictor of late LV dysfunction (odds ratio: 1.36, p = 0.03). An LGE >or=23% of LV during STEMI accurately predicted late LV dysfunction (sensitivity 89%, specificity 74%). The LGE volume provided important incremental benefit for predicting late dysfunction (area under the curve = 0.92, p <or= 0.03 vs. traditional risk factors). Twenty-three patients developed poor outcomes (1 death, 2 myocardial infarctions, 5 malignant arrhythmias, 4 severe LV dysfunction <35%, 11 hospital stays for heart failure) over 2.6 +/- 0.9 years; LGE volume remained a strong independent predictor of poor outcomes, whereas LGE >or=23% carried a hazard ratio of 6.1 for adverse events (p < 0.0001). CONCLUSIONS During the hyperacute phase of STEMI, LGE volume provides the strongest association and incremental predictive value for late systolic dysfunction and discerns poor late outcomes.

Usefulness of Coronary Fractional Flow Reserve Measurements in Guiding Clinical Decisions in Intermediate or Equivocal Left Main Coronary Stenoses

The objectives of this study were to evaluate the usefulness of fractional flow reserve (FFR) measurements to guide the clinical decision in patients with intermediate left main coronary artery (LMCA) stenosis and to determine the predictors of major adverse cardiac events (MACE) -- cardiac death, myocardial infarction, coronary revascularization -- in such cases; 142 consecutive patients with intermediate LMCA stenosis (mean percent diameter stenosis 42 +/- 13%) were included. All patients underwent FFR measurement after intracoronary administration of adenosine at a dose > or =30 microg. The clinical decisions were based on FFR as follows: coronary revascularization was recommended if FFR was <0.75, medical treatment if FFR was >0.80, and individualized decision based on additional clinical data if FFR was between 0.75 and 0.80. Mean FFR was 0.81 +/- 0.09 after the administration of 176 +/- 99 microg of adenosine. Based on FFR results, 60 patients (42%) underwent coronary revascularization, and 82 patients (58%) received medical treatment. At 14 +/- 11 months follow-up, the incidence of MACE related to the LMCA stenosis was 13% in the medical treatment group and 7% in the revascularization group (p = 0.27). The incidence of cardiac death or myocardial infarction was 6% in the medical treatment group and 7% in the revascularization group (p = 0.70). In the medical treatment group, with MACE had received a lower dose of intracoronary adenosine (86 +/- 57 vs 167 +/- 102 microg; odds ratio 1.39 for each decrease of 30 microg of intracoronary adenosine, 95% confidence interval 1.02 to 1.89) and more frequently had diabetes (55% vs 21%; odds ratio 4.40, 95% confidence interval 1.17 to 16.42). In conclusion, FFR measurement is helpful in guiding the decision whether to revascularize patients with intermediate LMCA stenosis. However, patients with diabetes remain at higher risk, and higher doses than previously recommended of intracoronary adenosine might have to be used in the evaluation of LMCA stenosis.

Comparison of Plaque Sealing With Paclitaxel-Eluting Stents Versus Medical Therapy for the Treatment of Moderate Nonsignificant Saphenous Vein Graft Lesions: The Moderate VEin Graft LEsion Stenting With the Taxus Stent and Intravascular Ultrasound (VELETI) Pilot Trial

Background— The presence of moderate saphenous vein graft (SVG) lesions is a major predictor of cardiac events late after coronary artery bypass grafting. We determined the effects of sealing moderate nonsignificant SVG lesions with paclitaxel-eluting stents (PES) on the prevention of SVG atherosclerosis progression. Methods and Results— Patients with at least 1 moderate SVG lesion (30% to 60% diameter stenosis) were randomized either to stenting the moderate SVG lesion with a PES (n=30, PES group) or to medical treatment alone (n=27, medical treatment group). Patients had an angiographic and intravascular ultrasound evaluation of the SVG at baseline and at 12-month follow-up. The primary end points were (1) the ultrasound SVG minimal lumen area at follow-up and (2) the changes in ultrasound atheroma volume in an angiographically nondiseased SVG segment. Mean time from coronary artery bypass grafting was 12±6 years, and mean low-density lipoprotein cholesterol level was 73±31 mg/dL. A total of 70 moderate SVG lesions (39±7% diameter stenosis) were evaluated. Significant disease progression occurred in the medical treatment group at the level of the moderate SVG lesion (decrease in minimal lumen area from 6.3±3.0 to 5.6±3.1 mm2; P<0.001), leading to a severe flow-limiting lesion or SVG occlusion in 22% of the patients compared with none in the PES group (P=0.014). In the PES group, mean minimal lumen area increased (P<0.001) from 6.1±2.2 to 8.6±2.9 mm2 at follow-up (P=0.001 compared with the medical treatment group at 12 months). There were no cases of restenosis or stent thrombosis. No significant atherosclerosis progression occurred at the nonstented SVG segments. At 12-month follow-up, the cumulative incidence of major adverse cardiac events related to the target SVG was 19% in the medical treatment group versus 3% in the PES group (P=0.091). Conclusions— Stenting moderate nonsignificant lesions in old SVGs with PES was associated with a lower rate of SVG disease progression and a trend toward a lower incidence of major adverse cardiac events at 1-year follow-up compared with medical treatment alone, despite very low low-density lipoprotein cholesterol values. This pilot study supports further investigation into the role of plaque sealing in SVGs. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT002289835.

Intracoronary compared to intravenous Abciximab and high-dose bolus compared to standard dose in patients with ST-segment elevation myocardial infarction undergoing transradial primary percutaneous coronary intervention: a two-by-two factorial placebo-controlled randomized study.

Platelet aggregation inhibition (PAI) of > or =95% has been associated with improved outcomes after percutaneous coronary intervention (PCI) and glycoprotein IIb/IIIa inhibitor treatment. A greater thrombotic burden in acute ST-segment elevation myocardial infarction (STEMI) might require higher doses and/or intracoronary delivery of glycoprotein IIb/IIIa inhibitors to achieve optimal PAI. Using a 2 x 2 factorial placebo-controlled design, 105 patients with STEMI who had been referred for primary PCI within 6 hours of symptom onset were randomized to intracoronary (IC) or intravenous (IV) delivery of an abciximab bolus at a standard dose (0.25 mg/kg) or high dose (> or =0.30 mg/kg) of abciximab. The primary end point was PAI measured at 10 minutes after the bolus of abciximab. Secondary end points included the acute and 6-month outcomes using angiographic parameters, cardiac biomarkers, cardiovascular magnetic resonance imaging, and clinical end points. At 10 minutes after the bolus, the proportion of patients with > or =95% PAI was not different between the IC and IV groups (53% vs 54%, p = 1.00) nor between the high-dose and standard-dose bolus groups (56% vs 51%, p = 0.70). Acutely, the angiographic myocardial blush grades, peak release of cardiac biomarkers, necrosis size, myocardial perfusion, and no reflow as assessed by magnetic resonance imaging, and clinical end points were similar between the groups and did not suggest a benefit for IC compared to IV or high-dose versus standard-dose bolus of abciximab. No increase occurred in bleeding complications with the high-dose bolus or IC delivery. The clinical, angiographic and cardiac magnetic resonance imaging outcomes at 6 and 12 months were similar between the 4 groups. In conclusion, in patients with STEMI presenting with symptom onset <6 hours and undergoing transradial primary PCI, PAI remained suboptimal, despite a higher dose bolus of abciximab. A higher dose bolus or IC delivery of abciximab bolus was not associated with improved acute or late results compared to the standard IV dosing and administration.

Comparison of medical treatment and coronary revascularization in patients with moderate coronary lesions and borderline fractional flow reserve measurements

Objectives: (1) To evaluate the clinical outcomes of patients with moderate coronary lesions and borderline fractional flow reserve (FFR) measurements (between 0.75 and 0.80), comparing those who underwent coronary revascularization (CR) to those who had medical treatment (MT), and (2) to determine the predictive factors of major adverse cardiac events (MACE) at follow‐up. Methods: A total of 107 consecutive patients (mean age 62 ± 10 years) with at least one moderate coronary lesion (mean percent diameter stenosis 47 ± 12%) evaluated by coronary pressure wire with FFR measurement between 0.75 and 0.80 (mean 0.77 ± 0.02) were included in the study. MACE [CR, myocardial infarction (MI), cardiac death) and the presence of angina were evaluated at follow‐up. Results: Sixty‐three patients (59%) underwent CR and 44 patients (41%) had MT, with no clinical differences between groups. At a mean follow‐up of 13 ± 7 months, MACE related to the coronary lesion evaluated by FFR were higher in the MT group compared with CR group (23% vs. 5%, P = 0.005). Most MACE consisted of CRs, with no differences between groups in MI and cardiac death rate at follow‐up. Both MT and FFR measurements in an artery supplying a territory with previous MI were independent predictive factors of MACE at follow‐up, respectively (hazard ratio 5.2, 95% CI 1.4–18.9, P = 0.01; hazard ratio 4.1, 95% CI 1.1–15.3, P = 0.03). The presence of angina at follow‐up was more frequent in the MT group compared with the CR group (41% vs. 9%, P = 0.002). Conclusions: In patients with moderate coronary lesions and borderline FFR measurements deferral of revascularization was associated with a higher rate of MACE (CR) and a higher prevalence of angina at follow‐up, especially in those with previous MI in the territory evaluated by FFR. Further prospective randomized studies should confirm whether or not an FFR cut‐off point of 0.80 instead of 0.75 would be more appropriate for deferring CR in these cases.

Telephone contact to improve adherence to dual antiplatelet therapy after drug-eluting stent implantation

Background Many patients delay or interrupt dual antiplatelet therapy (DAT) after drug-eluting stent (DES) implantation, which increases the risk of stent thrombosis and death. Objective To test the hypothesis that simple telephone contact made by nurses would improve adherence to and persistence of DAT. Design Randomised controlled trial. Patients and intervention A total of 300 patients (mean±SD 64±10 years, 73% male) were recruited immediately after DES implantation performed between June 2009 and June 2010. The last patient recruited reached the 1-year follow-up time point in June 2011. Patients were randomised to one of two groups: intervention, with four telephone follow-ups, versus a control group. In the intervention group, phone calls were made within 7 days of the DES implantation and at 1, 6 and 9 months to support drug adherence. Control patients were followed as per usual clinical practice. Pharmacy data were collected to assess drug prescription filling and refill. Setting Tertiary care university cardiovascular centre and community. Main outcome measures The primary end point was the proportion of days covered with aspirin and clopidogrel over the year after discharge as assessed by pharmacy refill data. Secondary outcome measures included persistence of aspirin and clopidogrel treatment, defined as no gaps longer than 14 days during follow-up. Results Most patients (73%) underwent DES implantation in the context of an acute coronary syndrome. All patients had drug insurance cover, either from the public plan (59%) or through private plans (41%). Complete pharmacy follow-up data were available for 96% of the cohort. At 12 months, median scores (25th–75th centile) for adherence to aspirin and clopidogrel were 99.2% (97.5–100%) and 99.3% (97.5–100%), respectively, in the intervention group compared with 90.2% (84.2–95.4%) and 91.5% (85.1–96.0%), respectively, in the control group (p<0.0001 for aspirin and clopidogrel). Patients in the intervention group were significantly more persistent in the aspirin and clopidogrel treatment than those in the control group. For clopidogrel, 87.2% of patients in the intervention group were still persistent at 12 months compared with only 43.1% in the control group (p<0.0001). Conclusions A simple approach of four telephone calls to patients after DES implantation significantly improved 1-year drug adherence to near-perfect scores. Persistence of DAT was also significantly improved by the intervention.

Effects of chronic sildenafil use on pulmonary hemodynamics and clinical outcomes in heart transplantation.

BACKGROUND Elevated pulmonary vascular resistance (PVR) in heart transplant (HT) candidates is associated with poor survival after HT. This study assessed the effect of peri-operative sildenafil administration on pulmonary hemodynamics and clinical outcomes in patients with advanced heart failure who were considered high-risk for HT because of elevated PVR and transpulmonary gradient (TPG). METHODS The study included 119 consecutive patients who underwent HT between 2004 and 2011. Fifteen patients (Group A) had severe pulmonary hypertension (PH), defined as mean pulmonary pressure (MPAP)>25 mm Hg and PVR>2.5 Wood units (WU), and/or TPG>12 mm Hg after vasodilator test or the continuous administration of inotropics drugs, and 104 patients (Group B) were without severe PH. Group A received sildenafil therapy. Pulmonary hemodynamics were evaluated before HT with and without sildenafil therapy. Right catheterization was performed early after HT with sildenafil therapy and late after HT without sildenafil. Survival after HT was compared between the groups. RESULTS The sildenafil dosage was 109±42 mg/day during 163±116 days before HT. After sildenafil therapy MPAP, PVR, and TPG decreased from 43.9±12.5 to 33.4±5.8 mm Hg, 5.0±1.1 to 3.0±1.6 WU, and 17.3±3.2 to 10.2±4.1 mm Hg, respectively (p<.01). All patients underwent successful HT. Sildenafil dosage was 140±70 mg/day for 43±45 days after HT. There were no differences in PVR and TPG with sildenafil therapy early after HT and without sildenafil 6 months after HT. Survival after HT was similar between the groups. CONCLUSION Sildenafil therapy before and after HT in patients with severe PH is associated with improved pulmonary hemodynamics and successful HT, without an increase in post-HT mortality.

Impact of Final Activated Clotting Time After Transradial Coronary Stenting With Maximal Antiplatelet Therapy

The optimal value of activated clotting time (ACT) during percutaneous coronary intervention (PCI) with unfractionated heparin remains controversial. No data are available on the relation between the ACT at the end of the procedure (final ACT) and the clinical outcomes after transradial PCI and maximal antiplatelet therapy. By dividing the final ACT values in tertiles, we analyzed the ischemic and bleeding events in 1,234 consecutive patients with acute coronary syndrome recruited in the EArly Discharge after Transradial Stenting of CoronarY Arteries (EASY) trial. All patients were pretreated with aspirin and clopidogrel. After radial sheath insertion, patients received 70 IU/kg unfractionated heparin. Abciximab was given before the first balloon inflation. The median final ACT value was 312 seconds (interquartile range 279 to 344). At 30 days, the rate of major adverse cardiac events, including death, myocardial infarction, and target vessel revascularization, from the lower to upper tertiles was 4%, 4%, and 2%, respectively (p = 0.16), and the rate of major bleeding was 2%, 1% and 0.7%, respectively (p = 0.20). During the 3 years of follow-up, the incidence of myocardial infarction was less in the tertile with the greatest ACT value (>330 seconds) than in the other 2 tertiles (4%, 8%, and 8%, respectively; p = 0.038). Troponin-T and creatine kinase-MB release after PCI indicated that the effect was related to periprocedural myonecrosis protection. After adjustment for baseline and procedural differences, a final ACT of >330 seconds remained associated with a 47% relative reduction in myocardial infarction (odds ratio 0.53, 95% confidence interval 0.29 to 0.93, p = 0.024). Death and target vessel revascularization remained similar in all tertiles for < or =3 years. In conclusion, with the combination of aspirin, clopidogrel pretreatment, and abciximab, a final ACT value of >330 seconds appears protective against peri-PCI myonecrosis, and this benefit was maintained for < or =3 years. With a transradial approach and maximal antiplatelet therapy, greater ACT values did not correlate with an increased risk of bleeding.

Assessment of Dyspnea in Acute Decompensated Heart Failure Insights from ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) on the Contributions of Peak Expiratory Flow

OBJECTIVES This study hypothesized that peak expiratory flow rate (PEFR) would increase with acute heart failure (AHF) treatment over the first 24 h, related to a Dyspnea Index (DI) change and treatment effect. BACKGROUND Dyspnea is a key symptom and clinical trial endpoint in AHF, yet objective assessment is lacking. METHODS In a clinical trial substudy, 421 patients (37 sites) underwent PEFR testing at baseline, 1, 6, and 24 h after randomization to nesiritide or placebo. DI (by Likert scale) was collected at hours 6 and 24. RESULTS Patients were median age 70 years, and 34% were female; no significant differences between nesiritide or placebo patients existed. Median baseline PEFR was 225 l/min (interquartile range [IQR]: 160 to 300 l/min) and increased to 230 l/min (2.2% increase; IQR: 170 to 315 l/min) by hour 1, 250 l/min (11.1% increase; IQR: 180 to 340 l/min) by hour 6, and 273 l/min (21.3% increase; IQR: 200 to 360 l/min) by 24 h (all p < 0.001). The 24-h PEFR change related to moderate or marked dyspnea improvement by DI (adjusted odds ratio: 1.04 for each 10 l/min improvement [95% confidence interval (CI): 1.07 to 1.10]; p < 0.01). A model incorporating time and treatment over 24 h showed greater PEFR improvement after nesiritide compared with placebo (p = 0.048). CONCLUSIONS PEFR increases over the first 24 h in AHF and could serve as an AHF endpoint. Nesiritide had a greater effect than placebo on PEFR, and this predicted patients with moderate/marked improvement in dyspnea, thereby providing an objective metric for assessing AHF. (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure [ASCEND-HF]; NCT00475852).