Karsten Tange Veien

Zotarolimus-eluting durable-polymer-coated stent versus a biolimus-eluting biodegradable-polymer-coated stent in unselected patients undergoing percutaneous coronary intervention (SORT OUT VI): a randomised non-inferiority trial

BACKGROUND New-generation drug-eluting coronary stents have reduced the risk of coronary events, especially in patients with complex disease or lesions. To what extent different stent platforms, polymers, and antiproliferative drugs affect outcomes, however, is unclear. We investigated the safety and efficacy of a third-generation stent by comparing a highly biocompatible durable-polymer-coated zotarolimus-eluting stent with a biodegradable-polymer-coated biolimus-eluting stent. METHODS This open-label, randomised, multicentre, non-inferiority trial was done at three sites across western Denmark. All patients who presented with stable coronary artery disease or acute coronary syndromes and at least one coronary artery lesion (more than 50% stenosis) from March, 2011, to August, 2012, were assessed for eligibility. Patients were randomly assigned in a 1:1 ratio to receive either the durable-polymer zotarolimus-eluting stent or the biodegradable-polymer biolimus-eluting stent. The primary endpoint was a composite of safety (cardiac death and myocardial infarction not clearly attributable to a non-target lesion) and efficacy (target-lesion revascularisation) at 12 months, analysed by intention to treat. The trial was powered to assess non-inferiority of durable-polymer zotarolimus-eluting stent compared with the biodegradable-polymer biolimus-eluting stent with a predetermined non-inferiority margin of 0·025. This trial is registered with ClinicalTrials.gov, number NCT01956448. FINDINGS Of 7103 screened, 1502 patients with 1883 lesions were assigned to receive the durable-polymer zotarolimus-eluting stent and 1497 patients with 1791 lesions to receive the biodegradable-polymer biolimus-eluting stent. 79 (5·3%) and 75 (5·0%) patients, respectively, met the primary endpoint (absolute risk difference 0·0025, upper limit of one-sided 95% CI 0·016%; p=0·004). The individual components of the primary endpoint did not differ significantly between stent types at 12 months. INTERPRETATION The durable-polymer-coated zotarolimus-eluting stent was non-inferior to the biodegradable-polymer-coated biolimus-eluting stent in unselected patients. FUNDING Medtronic Cardiovascular and Biosensors Interventional Technologies.

Randomized Comparison of a Biodegradable Polymer Ultrathin Strut Sirolimus-Eluting Stent With a Biodegradable Polymer Biolimus-Eluting Stent in Patients Treated With Percutaneous Coronary Intervention The SORT OUT VII Trial

Background—Coronary drug-eluting stents with biodegradable polymers have been designed to improve safety and efficacy. Methods and Results—The Scandinavian Organization for Randomized Trials With Clinical Outcome (SORT OUT) VII trial—a large-scale registry-based randomized, multicenter, single-blind, 2-arm, noninferiority trial—compared 2 biodegradable polymer drug-eluting stents: the thin-strut cobalt–chromium sirolimus-eluting Orsiro stent and the stainless steel biolimus-eluting Nobori stent in an all-comer patient population. The primary end point target lesion failure was a composite of cardiac death, myocardial infarction (not related to other than index lesion), or target lesion revascularization within 1 year, analyzed by intention to treat (noninferiority margin of 3.0%). Clinically driven event detection based on Danish registries was used. A total of 1261 patients were assigned to receive the sirolimus-eluting stent (1590 lesions) and 1264 patients to the biolimus-eluting stent (1588 lesions). At 1 year, the composite end point target lesion failure occurred in 48 patients (3.8%) in the sirolimus-eluting group and in 58 patients (4.6%) in the biolimus-eluting group (absolute risk difference, −0.78% [upper limit of 1-sided 95% confidence interval, 0.61%]; P<0.0001). Rates of definite stent thrombosis occurred in 5 (0.4%) of the sirolimus-eluting group compared with 15 (1.2%) biolimus-eluting stent–treated patients (rate ratio, 0.33; 95% confidence interval, 0.12–0.92; P=0.034), which largely was attributable to a lower risk of subacute definite stent thrombosis: 0.1% versus 0.6% (rate ratio, 0.12; 95% confidence interval, 0.02–1.00; P=0.05). Conclusions—The thin-strut sirolimus-eluting Orsiro stent was noninferior to the biolimus-eluting Nobori stent in unselected patients for target lesion failure at 1 year. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01879358.

Prevention of Contrast-Induced Nephropathy With N-Acetylcysteine or Sodium Bicarbonate in Patients With ST-Segment–Myocardial Infarction A Prospective, Randomized, Open-Labeled Trial

Background—Contrast-induced nephropathy (CIN) is a serious condition in patients with ST-segment–elevation myocardial infarction treated with primary percutaneous coronary intervention. We compared the risk of acute CIN and the influence of preventive strategies in patients with ST-segment–elevation myocardial infarction undergoing primary percutaneous coronary intervention. Methods and Results—A total of 720 patients were randomized in the Prevention of Contrast-induced Nephropathy in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention (CINSTEMI) trial. Patients were randomly assigned in a 1:1:1:1 ratio to receive hydration with sodium chloride together with 1 of 4 prophylactic regimes (1) N-acetylcysteine (NAC), (2) sodium bicarbonate (NaHCO3) infusion, (3) NAC in combination with NaHCO3, or (4) hydration with sodium chloride infusion alone. Patients in cardiogenic shock were excluded. Acute CIN was defined as an increase in serum creatinine concentration >25% from the baseline value within a 3-day period. Overall, CIN occurred in 141 (21.9%) patients. The prevention treatment with NAC, NaHCO3, or the combined NAC and NaHCO3 did not reduce the rate of CIN significantly compared with hydration with intravenous sodium chloride infusion alone (20.1% versus 20.1% versus 20.8% versus 26.5%; P=NS). However, an increase in serum creatinine >25% from the baseline value to 30 day was significantly lower in patients treated with combined NAC and NaHCO3 (18.7% versus 19.1% versus 9.2% versus 21.3%; P=0.033). Conclusions—Treatment with NAC or NaHCO3 did not reduce the rate of acute CIN significantly. Combined treatment with NAC and NaHCO3 may reduce the risk of renal dysfunction after 30 days. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01160627.

High mortality among heart failure patients treated with antidepressants

BACKGROUND This study was designed to assess whether pharmacologically treated depression was associated with increased mortality risk in systolic heart failure (SHF) patients. METHODS Patients (n=3346) with SHF (left ventricular ejection fraction ≤ 0.45) and primarily New York Heart Association (NYHA) classes II-III (78%) were recruited from a clinical database used in 20 heart failure clinics in Denmark. The association between pharmacologically treated depression identified by at least one prescription of an antidepressant and mortality risk was evaluated. RESULTS Follow-up time was 540 days (range: 30-1600 days). 539 patients died. For 243 patients (7%) an antidepressant had been prescribed at least once. In a Cox Proportional Hazard Model, pharmacologically treated depression was associated with a 49% increased mortality risk (Hazard ratio: 1.49, 95% confidence interval: 1.03-2.16) after adjustment for traditional confounders. Three months after the baseline visit in the heart failure clinic, these patients received lower doses of beta-blockers than patients without antidepressant therapy (p=0.006). Female sex (p<0.001) and NYHA classes III-IV (p=0.007) were associated with the prescription of an antidepressant. CONCLUSIONS Our analyses suggest that pharmacologically treated depression is associated with a 49% increased mortality risk, and that these high-risk patients receive lower doses of beta-blockers than patients with no antidepressant therapy.

Effect of Ischemic Postconditioning During Primary Percutaneous Coronary Intervention for Patients With ST-Segment Elevation Myocardial Infarction: A Randomized Clinical Trial

Importance Ischemic postconditioning of the heart during primary percutaneous coronary intervention (PCI) induced by repetitive interruptions of blood flow to the ischemic myocardial region immediately after reopening of the infarct-related artery may limit myocardial damage. Objective To determine whether ischemic postconditioning can improve the clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). Design, Setting, And Participants In this multicenter, randomized clinical trial, patients with onset of symptoms within 12 hours, STEMI, and thrombolysis in myocardial infarction (TIMI) grade 0-1 flow in the infarct-related artery at arrival were randomized to conventional PCI or postconditioning. Inclusion began on March 21, 2011, through February 2, 2014, and follow-up was completed on February 2, 2016. Analysis was based on intention to treat. Interventions Patients were randomly allocated 1:1 to conventional primary PCI, including stent implantation, or postconditioning performed as 4 repeated 30-second balloon occlusions followed by 30 seconds of reperfusion immediately after opening of the infarct-related artery and before stent implantation. Main Outcome and Measures A combination of all-cause death and hospitalization for heart failure. Results During the inclusion period, 1234 patients (975 men [79.0%] and 259 women [21.0%]; mean [SD] age, 62 [11] years) underwent randomization in the trial. Median follow-up was 38 months (interquartile range, 24-58 months). The primary outcome occurred in 69 patients (11.2%) who underwent conventional primary PCI and in 65 (10.5%) who underwent postconditioning (hazard ratio, 0.93; 95% CI, 0.66-1.30; P = .66). The hazard ratios were 0.75 (95% CI, 0.49-1.14; P = .18) for all-cause death and 0.99 (95% CI, 0.60-1.64; P = .96) for heart failure. Conclusions and Relevance Routine ischemic postconditioning during primary PCI failed to reduce the composite outcome of death from any cause and hospitalization for heart failure in patients with STEMI and TIMI grade 0-1 flow at arrival. Trial Registration clinicaltrials.gov Identifier: NCT01435408

Optical Coherence Tomography Guided Percutaneous Coronary Intervention With Nobori Stent Implantation in Patients With Non–ST-Segment–Elevation Myocardial Infarction (OCTACS) Trial Difference in Strut Coverage and Dynamic Malapposition Patterns at 6 Months

Background—Incomplete strut coverage has been documented an important histopathologic morphometric predictor for later thrombotic events. This study sought to investigate whether optical coherence tomography (OCT)–guided percutaneous coronary intervention with Nobori biolimus-eluting stent implantation in patients with non–ST-segment–elevation myocardial infarction would provide improved strut coverage at 6 months in comparison with angiographic guidance only. Methods and Results—One hundred patients were randomized 1:1 to either OCT-guided or angio-guided Nobori biolimus-eluting stent implantation. Postprocedure OCT was performed in all patients. In the OCT-guided group, prespecified criteria indicating additional intervention were related to (1) stent underexpansion, (2) strut malapposition, (3) edge dissection(s), and (4) residual stenosis at the distal or proximal reference segment(s). A final OCT was performed in case of reintervention. Six-month OCT follow-up was available in 85 patients. Twenty-three (46%) OCT-guided patients had additional postdilation or stenting. The percentage of acutely malapposed struts was substantially lower in the OCT-guided group (3.4% [interquartile range, 0.3–7.6] versus 7.8% [interquartile range, 2.3–19.4]; P<0.01). At 6-month follow-up, the OCT-guided group had a significantly lower proportion of uncovered struts; 4.3% [interquartile range, 1.2–9.8] versus 9.0% [interquartile range, 5.5–14.5], P<0.01. Furthermore, OCT-guided patients had significantly more completely covered stents: 17.5% versus 2.2%, P=0.02. The percentages of malapposed struts and struts being both uncovered and malapposed at follow-up were comparable between groups. Conclusions—OCT-guided optimization of Nobori biolimus-eluting stent implantation improves strut coverage at 6-month follow-up in comparison with angiographic guidance alone. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT02272283.

Prevention of atrial fibrillation in patients with aortic valve stenosis with candesartan treatment after aortic valve replacement

BACKGROUND Accumulating data has suggested that treatment with Angiotensin-II receptor antagonists can prevent the new onset of atrial fibrillation (AF). The aim of this study was to evaluate whether treatment with candesartan on top of conventional treatment could prevent new onset AF in patients with aortic valve stenosis (AS) after aortic valve replacement. METHODS AND RESULTS The study was a single centre, consecutive; investigator initiated study using a prospective randomised blinded endpoint design. 91 patients with severe AS without known AF scheduled for aortic valve replacement (AVR) were randomised to candesartan 32 mg once daily on top of conventional treatment or conventional therapy immediately after AVR. Patients were examined with ECG 3, 6, 9 and 12 months after surgery, and Holter-ECG analysis after 3 and 12 months. Primary endpoint was episode of AF with a duration exceeding 30s, on the ECG or Holter-ECG and/or patients hospitalised due to AF. 14 patients developed new onset AF during follow up. AF-free survival was significantly higher (94% vs 74%, p=0.02) in patients treated with candesartan. CONCLUSION In patients with symptomatic severe AS undergoing AVR, treatment with candesartan may prevent the new onset of atrial fibrillation.

Influence of ezetimibe in addition to high-dose atorvastatin therapy on plaque composition in patients with ST-segment elevation myocardial infarction assessed by serial ☆: Intravascular ultrasound with iMap: the OCTIVUS trial

BACKGROUND The aim of this study was to examine the influence of ezetimibe in addition to atorvastatin on plaque composition in patients with first-time ST-segment Elevation Myocardial Infarction treated with primary percutaneous intervention. METHODS Eighty-seven patients were randomized (1:1) to ezetimibe 10mg or placebo in addition to Atorvastatin 80mg. Intravascular ultrasound with iMap was performed at baseline and after 12months in a non-infarct-related artery. Primary endpoint was change in necrotic core (NC). Secondary endpoints were total atheroma volume (TAV) and percentage atheroma volume (PAV). RESULTS NC did not change significantly: ezetimibe group 24.9 (11.9, 51.3) mm3 to 24.9 (15.3, 54.5) mm3, p=0.76, placebo group 29.4 (16.3, 78.5) mm3 to 32.0 (16.0, 88.7) mm3, p=0.30, (p=0.35 between groups). TAV was reduced in the ezetimibe group only: ezetimibe (200.0 (135.6, 311.9) mm3 to 189.3 (126.4, 269.1) mm3, p<0.001) compared to placebo group (218.4 (163.5, 307.9) mm3 to 212.2 (149.9, 394.8) mm3, p=0.07) (p=0.56 between groups). PAV was reduced in the ezetimibe group only (40.1±8.6% to 39.2±9.0%, p=0.036) compared to placebo group (43.3±9.4% to 42.2±10.7%, p=0.07), p=0.91 between groups. CONCLUSIONS Ezetimibe in addition to atorvastatin therapy did not influence NC content, but was associated with regression of coronary atherosclerosis.

Single-centre experience with the Impella CP, 5.0 and RP in 109 consecutive patients with profound cardiogenic shock

Rationale: Short-term mechanical circulatory support is increasingly used in the management of cardiogenic shock, but data from controlled studies are sparse. Thus, real-life data on complication rates and predictors of adverse outcome are important. Objective: The objective of this study was to analyse the experience with Impella devices in the management of profound cardiogenic shock. Methods and results: A retrospective study of 109 consecutive patients with severe shock after myocardial infarction, acute heart failure, or cardiac surgery. Possible device-related complications were registered and predictors of death while on Impella support and within 180 days were identified. In 79 patients (72%) cardiogenic shock was caused by myocardial infarction, acute heart failure in 16 (15%) and post-cardiotomy shock in 14 patients (13%). Thirty-five patients (32%) were comatose after cardiac arrest and in seven, the Impella was placed during chest compression. Mean age was 62±12 years, mean arterial pressure was 57±13 mmHg, pH 7.19±0.17 and lactate 7.5±5.7 mmol/l (range 1.8–30.0 mmol/l) at placement. During Impella therapy, 26 patients (28%) died among patients with myocardial infarction or acute heart failure. Of data available prior to placement lactate (hazard ratio 1.14, 95% confidence interval 1.04–1.25, P=0.004) was the only predictor of death on support. During support, five patients (5%) developed leg ischaemia requiring intervention. Bleeding from the Impella insertion site was seen in 14 patients (13%). Conclusion: Impella treatment is feasible in profound cardiogenic shock at an acceptable rate of complications. Despite an aggressive approach to restore cardiac output, mortality was high. Besides the severity of lactic acidosis there were no strong predictors of early death.

Percutaneous right ventricular assist device in sepsis due to right ventricular failure and pulmonary hypertension.

Pulmonary hypertension can cause right ventricular pressure overload, and with increased demands of cardiac output, there is a risk of acute right ventricular (RV) failure. In general, increased number of patients with acute heart failure are managed with percutaneous mechanical circulatory support. We report a case of profound cardiogenic shock due to acute right heart failure and sepsis, which was managed with the use of a percutaneous isolated right ventricular coaxial assist device. A 37-year-old, obese, female patient was diagnosed with mixed connective tissue disease (MCTD) 14 months prior to this hospital admission. She suffered from fatigue, arthralgia, NYHA functional class 3 dyspnea, anemia, skin manifestations, and nausea with vomiting which in periods occurred up to 10 times a day. Gastroscopy revealed no macroscopic pathology of either the esophagus or the stomach, other than a small diaphragmatic hernia. Echocardiography performed 2 weeks before this admission, which showed a moderately dilated right ventricle (RV) with preserved systolic function, along with normal left ventricular function. Right heart catheterization at that time revealed an increased pulmonary vascular resistance of 4.3 Wood Units. High-resolution chest CT showed no signs thromboembolic disease. The patient was hospitalized with pneumonia 14 days after the above cardiac evaluation, and her clinical status rapidly progressed to severe septic shock. Echocardiography showed severe RV failure and tricuspid regurgitation with poor filling of a hyperdynamic left ventricle. There was no clinical improvement in response to fluid, inotropes (levosimendan, adrenaline), and vasopressor (norepinephrine). She rapidly developed profound lactic acidosis and severe hypotension. Right heart catheterization