Markku Eskola

Percutaneous coronary angioplasty versus coronary artery bypass grafting in treatment of unprotected left main stenosis (NOBLE): a prospective, randomised, open-label, non-inferiority trial

BACKGROUND Coronary artery bypass grafting (CABG) is the standard treatment for revascularisation in patients with left main coronary artery disease, but use of percutaneous coronary intervention (PCI) for this indication is increasing. We aimed to compare PCI and CABG for treatment of left main coronary artery disease. METHODS In this prospective, randomised, open-label, non-inferiority trial, patients with left main coronary artery disease were enrolled in 36 centres in northern Europe and randomised 1:1 to treatment with PCI or CABG. Eligible patients had stable angina pectoris, unstable angina pectoris, or non-ST-elevation myocardial infarction. Exclusion criteria were ST-elevation myocardial infarction within 24 h, being considered too high risk for CABG or PCI, or expected survival of less than 1 year. The primary endpoint was major adverse cardiac or cerebrovascular events (MACCE), a composite of all-cause mortality, non-procedural myocardial infarction, any repeat coronary revascularisation, and stroke. Non-inferiority of PCI to CABG required the lower end of the 95% CI not to exceed a hazard ratio (HR) of 1·35 after up to 5 years of follow-up. The intention-to-treat principle was used in the analysis if not specified otherwise. This trial is registered with ClinicalTrials.gov identifier, number NCT01496651. FINDINGS Between Dec 9, 2008, and Jan 21, 2015, 1201 patients were randomly assigned, 598 to PCI and 603 to CABG, and 592 in each group entered analysis by intention to treat. Kaplan-Meier 5 year estimates of MACCE were 29% for PCI (121 events) and 19% for CABG (81 events), HR 1·48 (95% CI 1·11-1·96), exceeding the limit for non-inferiority, and CABG was significantly better than PCI (p=0·0066). As-treated estimates were 28% versus 19% (1·55, 1·18-2·04, p=0·0015). Comparing PCI with CABG, 5 year estimates were 12% versus 9% (1·07, 0·67-1·72, p=0·77) for all-cause mortality, 7% versus 2% (2·88, 1·40-5·90, p=0·0040) for non-procedural myocardial infarction, 16% versus 10% (1·50, 1·04-2·17, p=0·032) for any revascularisation, and 5% versus 2% (2·25, 0·93-5·48, p=0·073) for stroke. INTERPRETATION The findings of this study suggest that CABG might be better than PCI for treatment of left main stem coronary artery disease. FUNDING Biosensors, Aarhus University Hospital, and participating sites.

Randomized Comparison of Final Kissing Balloon Dilatation Versus No Final Kissing Balloon Dilatation in Patients With Coronary Bifurcation Lesions Treated With Main Vessel Stenting The Nordic-Baltic Bifurcation Study III

Background— It is unknown whether the preferred 1-stent bifurcation stenting approach with stenting of the main vessel (MV) and optional side branch stenting using drug-eluting stents should be finalized by a kissing balloon dilatation (FKBD). Therefore, we compared strategies of MV stenting with and without FKBD. Methods and Results— We randomized 477 patients with a bifurcation lesion to FKBD (n=238) or no FKBD (n=239) after MV stenting. The primary end point was major adverse cardiac events: cardiac death, non–procedure-related index lesion myocardial infarction, target lesion revascularization, or stent thrombosis within 6 months. The 6-month major adverse cardiac event rates were 2.1% and 2.5% (P=1.00) in the FKBD and no-FKBD groups, respectively. Procedure and fluoroscopy times were longer and more contrast media was needed in the FKBD group than in the no-FKBD group. Three hundred twenty-six patients had a quantitative coronary assessment. At 8 months, the rate of binary (re)stenosis in the entire bifurcation lesion (MV and side branch) was 11.0% versus 17.3% (P=0.11), in the MV was 3.1% versus 2.5% (P=0.68), and in the side branch was 7.9% versus 15.4% (P=0.039) in the FKBD versus no-FKBD groups, respectively. In patients with true bifurcation lesions, the side branch restenosis rate was 7.6% versus 20.0% (P=0.024) in the FKBD and no-FKBD groups, respectively. Conclusions— MV stenting strategies with and without FKBD were associated with similar clinical outcomes. FKBD reduced angiographic side branch (re)stenosis, especially in patients with true bifurcation lesions. The simple no-FKBD procedures resulted in reduced use of contrast media and shorter procedure and fluoroscopy times. Long-term data on stent thrombosis are needed. Clinical Trial Registration— URL: http://clinicaltrials.gov. Unique identifier: NCT00914199.

Electrocardiographic classification of acute coronary syndromes: a review by a committee of the International Society for Holter and Non-Invasive Electrocardiology.

The electrocardiogram (ECG) remains the most immediately accessible and widely used diagnostic tool for guiding emergency treatment strategies. The ECG recorded during acute myocardial ischemia is of diagnostic, therapeutic, and prognostic significance. In patients with myocardial ischemia as a result of decreased blood supply, the initial 12-lead ECG typically shows (1) predominant ST-segment elevation (STE) as part of STE acute coronary syndrome (STE-ACS), or (2) no predominant STE, that is, non-STE ACS (NSTE-ACS). Patients with predominant STE are classified as having either aborted myocardial infarction (MI) or ST-elevation MI (STEMI) based on the absence or presence of biomarkers of myocardial necrosis. The MI may be aborted either by spontaneous or therapeutic reperfusion of the ischemic myocardium before development of myocardial cell necrosis. NSTE-ACS patients are classified as having either unstable angina or NSTE-MI, based also on the absence or presence of biomarkers of mycardial necrosis. The information obtained from the 12-lead ECG at presentation should be complemented by repeated ECGs especially during symptoms indicative of ischemia and, if applicable, by comparing the findings with reference ECGs. Also, continuous ECG recording in a coronary care setting, including the comparison of ECGs with and without pain, adds to the information gained at patient presentation. In this article, mechanisms of ischemic ECG changes and the ECG patterns recorded in both STE-ACS and NSTE-ACS are described. ECG patterns of NSTE-ACS, which include ST depression, negative T wave, and even normal ECG, need to be better defined in future studies to correlate them with the severity and extent of ischemia and to explore to what extent they are explained by acute active ischemia or represent consequences of ischemia. One of the aims of this article is to propose a classification of the ECG patterns encountered in different clinical scenarios of ACS. How these patterns will aid in guiding the diagnostic and therapeutic process is discussed.

Pregnancy‐associated plasma protein A: A biomarker in acute ST‐elevation myocardial infarction (STEMI)

Background. Elevated circulating levels of pregnancy‐associated plasma protein A (PAPP‐A), a novel marker of atherosclerotic plaque instability, are associated with increased risk of future cardiac events in patients with acute coronary syndromes (ACS). However, little is known of the kinetics or clinical significance of circulating PAPP‐A after plaque rupture in acute ST‐elevation myocardial infarction (STEMI). Aim. To evaluate the 48‐hour release of pregnancy‐associated plasma protein A (PAPP‐A) and its association with 12‐month outcome in patients with acute ST‐elevation myocardial infarction (STEMI). Methods. Sixty‐two consecutive STEMI patients were included (40 men and 22 women, median age 67.5 years (range 34–84)), of whom 54 (87.1%) received reperfusion therapy. PAPP‐A was measured at admission and 6–12, 24 and 48 hours thereafter. In 14 patients, samples were obtained also at 1, 2 and 4 hours. Results. There was an early peak of circulating PAPP‐A during the first 12 hours from symptom onset, followed by rapid normalization. A second, late PAPP‐A elevation was noticed in 20/62 patients (32.3%). Admission PAPP‐A >10.0 mIU/L (highest tertile) was associated (P = 0.049) with increased 12‐month risk of cardiovascular death or non‐fatal myocardial infarction. Moreover, the combination of failed early reperfusion together with late PAPP‐A elevation was strongly (7/13 versus 10/49 patients, P = 0.016) associated with adverse outcome. Admission PAPP‐A did not correlate with admission C‐reactive protein or cardiac troponin I. Conclusions. PAPP‐A is elevated early in STEMI and then declines rapidly, a pattern consistent with release from the ruptured plaque. The variability of PAPP‐A kinetics at 48 hours reflects the success of reperfusion. This study also shows that PAPP‐A may have prognostic value in STEMI.

PR depression is useful in the differential diagnosis of myopericarditis and ST elevation myocardial infarction.

Background: Deviation of the PR segment is a common but often ignored ECG finding in acute myopericarditis, but seems to be rare in the acute phase of ST elevation myocardial infarction (STEMI). Since rapid bedside differential diagnosis of acute myopericarditis and STEMI is essential, we decided to assess the diagnostic power of PR depressions in patients presenting with ST elevations in the emergency room.

Feasibility and repeatability of optical coherence tomography measurements of pre-stent thrombus burden in patients with STEMI treated with primary PCI

AIMS Intracoronary thrombus is disrupted by stent deployment and confounded by the development of intrastent plaque prolapse. This study aims at investigating the feasibility and repeatability of thrombus quantification prior to stent implantation using optical coherence tomography (OCT) in ST-segment elevation myocardial infarction (STEMI) patients. METHODS AND RESULTS Patients were enrolled in an OCT substudy of the TOTAL trial (a randomized trial of routine aspiration ThrOmbecTomy with PCI vs. PCI ALone in patients with STEMI undergoing primary PCI) of aspiration thrombectomy or percutaneous coronary intervention (PCI) alone in primary PCI (PPCI) of STEMI. Using OCT, thrombus burden (TB) and other measures of pre- and post-stent atherothrombus were analysed over the arterial segment defined by the final stent length. Feasibility was 86.2% (25/29 patients) for both pre- and post-stent OCT imaging. Altogether, 8111 OCT cross-sections were analysed. In Bland-Altman analyses of inter-observer variation (n = 25), the mean pre-stent TB was 8.76% for Observer 1 and 8.97% for Observer 2 (limits of agreement -2.6 to 2.2%). In Bland-Altman analyses of intra-observer variation (n = 15), the mean pre-stent TB was 8.06% for the first and 7.35% for the second round of analysis by Observer 1 (limits of agreement -1.72 to 3.15%). There was a good correlation between pre-stent TB and pre-stent quadrants with thrombus/mm (r = 0.97), but only modest correlation between pre-stent TB and post-stent atherothrombotic burden (ATB; r = 0.54). CONCLUSIONS Measurement of pre-stent TB by OCT during the PPCI of STEMI is feasible and highly repeatable. Pre-stent TB is only modestly correlated with post-stent ATB, which indicates that pre-stent measurements might be of additional value when assessing the TB in STEMI.

Efficacy and safety of the Lotus Valve System for treatment of patients with severe aortic valve stenosis and intermediate surgical risk: Results from the Nordic Lotus-TAVR registry

BACKGROUND Transcatheter aortic valve replacement (TAVR) has become an established therapeutic option for patients with symptomatic, severe aortic valve stenosis (AS) who are ineligible or at high risk for conventional valvular surgery. In Northwestern Europe, the TAVR technology is also increasingly used to treat patients with an intermediate risk profile. METHODS AND RESULTS The study was designed as an independent Nordic multicenter registry of intermediate risk patients treated with the Lotus Valve System (Boston Scientific, MA, USA; N=154). Valve Academic Research Consortium (VARC)-defined device success was obtained in 97.4%. A Lotus Valve was successfully implanted in all patients. There was no valve migration, embolization, ectopic valve deployment, or TAV-in-TAV deployment. The VARC-defined combined safety rate at 30days was 92.2%, with a mortality rate of 1.9% and stroke rate of 3.2%. The clinical efficacy rate after 30days was 91.6% - only one patient had moderate aortic regurgitation. When considering only those patients in the late experience group (N=79), the combined safety and clinical efficacy rates were 93.7% and 92.4%, respectively. The pacemaker implantation rate was 27.9% - this rate was 12.8% in case of a combined implantation depth <4mm and a device/annulus ratio<1.05. CONCLUSIONS The present study demonstrates the efficacy and safety of the repositionable, retrievable Lotus Valve System in intermediate risk patients with AS. The VARC-defined device success rate was 97.4% with a 30-day patient safety and clinical efficacy rate of more than 90%. Less than moderate aortic regurgitation was obtained in 99.4% of patients.

ECG Diagnosis and Classification of Acute Coronary Syndromes

In acute coronary syndromes, the electrocardiogram (ECG) provides important information about the presence, extent, and severity of myocardial ischemia. At times, the changes are typical and clear. In other instances, changes are subtle and might be recognized only when ECG recording is repeated after changes in the severity of symptoms. ECG interpretation is an essential part of the initial evaluation of patients with symptoms suspected to be related to myocardial ischemia, along with focused history and physical examination. Patients with ST‐segment elevation on their electrocardiogram and symptoms compatible with acute myocardial ischemia/infarction should be referred for emergent reperfusion therapy. However, it should be emphasized that a large number of patients may have ST‐elevation without having acute ST‐elevation acute coronary syndrome, while acute ongoing transmural ischemia due to an abrupt occlusion of an epicardial coronary artery may occur in patients with ST‐elevation less than the thresholds defined by the guidelines. Up‐sloping ST‐segment depression with positive T waves is increasingly recognized as a sign of regional subendocardial ischemia associated with severe obstruction of the left anterior descending coronary artery. Widespread ST‐segment depression, often associated with inverted T waves and ST‐segment elevation in lead aVR during episodes of chest pain, may represent diffuse subendocardial ischemia caused by severe coronary artery disease. In case of hemodynamic compromise, urgent coronary angiography has been increasingly recommended for these patients.

Early clinical outcome of aortic transcatheter valve-in-valve implantation in the Nordic countries.

OBJECTIVE Transcatheter valve-in-valve implantation has emerged as an option, in addition to reoperative surgical aortic valve replacement, to treat failed biologic heart valve substitutes. However, the clinical experience with this approach is still limited. We report the comprehensive experience of transcatheter valve-in-valve implantation in the Nordic countries from May 2008 to January 2012. METHODS A total of 45 transcatheter aortic valve-in-valve implantations were performed during the study period in 11 centers. The mean age of the patients was 80.6 years (range, 61-91), 26 were male and 19 were female, and the mean EuroSCORE, EuroSCORE II, and Society of Thoracic Surgeons score was 35.4, 16.3, and 14.6, respectively. The type of failure was stenosis and combined in 58% (mean and peak aortic valve gradient, 77 and 45 mm Hg, respectively) and regurgitation in 42% of cases. The SAPIEN/XT (Edwards LifeSciences, Irvine, Calif) and CoreValve (Medtronic Inc, Minneapolis, Minn) system was used in 33 and 12 cases, respectively. The access route was transapical in 25, transfemoral in 17, transaortic in 2, and subclavian in 1 case. The mean follow-up was 14.4 months. The periprocedural and postoperative outcomes were assessed using the Valve Academic Research Consortium criteria. RESULTS No intraprocedural mortality occurred. The technical success rate was 95.6% (1 second valve implantation, 1 conversion to open surgery). The all-cause 30-day mortality was 4.4% (1 cardiac-related and 1 aspiration pneumonia). The major complications within 30 days included stroke in 2.2%, periprocedural myocardial infarction in 4.4%, and major vascular complication in 2.2% of patients. At 1 month, all but 1 patient had either no or mild paravalvular leakage, with a mean and peak valve gradient of 17 mm Hg (range, 4-38) and 30 mm Hg (range, 7-68), respectively. The mean gradient was greater than 20 mm Hg in 17% of patients and remained unchanged at 12 months. The 1-year survival was 88.1%. CONCLUSIONS Transcatheter valve-in-valve implantation is widely performed, albeit in small numbers, in most centers in the Nordic countries. The short-term results were excellent in this high-risk patient population, demonstrating a low incidence of device- or procedure-related complications. However, a considerable number of patients were left with suboptimal systolic valve performance with unknown long-term effects, warranting close surveillance after transcatheter valve-in-valve implantation.

Prognostic implications of intraventricular conduction delays in a general population: The Health 2000 Survey

Abstract Aims. We examined the prognostic impact of eight different intraventricular conduction delays (IVCD) in the standard electrocardiogram (ECG) in a community cohort. Methods and results. Data were collected from 6299 Finnish individuals. During a mean 8.2 years (interquartile range 8.1 to 8.3) of follow-up 640 subjects died (10.2%); 277 (4.4%) were cardiovascular deaths. For both sexes, all-cause and cardiovascular mortality was higher in subjects with IVCD than in those without. In Cox regression analysis after adjustment for age and gender, the hazard ratio for cardiovascular mortality for non-specific IVCD was 4.25 (95% confidence interval [CI] 1.95–9.26, P < 0.0001) and for left bundle branch block (LBBB) 2.11 (95% CI 1.31–3.41, P = 0.002). Right bundle branch block (RBBB) was not related to additional mortality, while incomplete RBBB (IRBBB) presented a hazard ratio of 2.24 (95% CI 1.064–4.77, P = 0.036). Conclusions. In the general population, non-specific IVCD, LBBB, and IRBBB were associated with increased relative risk for all-cause and cardiovascular mortality. RBBB did not have an impact on cardiovascular mortality either in subjects with or without previous heart disease.