Quantitative flow ratio versus fractional flow reserve for guiding percutaneous coronary intervention: design and rationale of the randomised FAVOR III Europe Japan trial.

Quantitative flow ratio (QFR) is a computation of fractional flow reserve (FFR) based on invasive coronary angiographic images. Calculating QFR is less invasive than measuring FFR and may be associated with lower costs. Current evidence supports the call for an adequately powered randomised comparison of QFR and FFR for the evaluation of intermediate coronary stenosis. The aim of the FAVOR III Europe Japan trial is to investigate if a QFR-based diagnostic strategy yields a non-inferior 12-month clinical outcome compared with a standard FFR-guided strategy in the evaluation of patients with intermediary coronary stenosis. FAVOR III Europe Japan is an investigator-initiated, randomised, clinical outcome, non-inferiority trial scheduled to randomise 2,000 patients with either 1) stable angina pectoris and intermediate coronary stenosis, or 2) indications for functional assessment of at least 1 non-culprit lesion after acute myocardial infarction. Up to 40 international centres will randomise patients to either a QFR-based or a standard FFR-based diagnostic strategy. The primary endpoint of major adverse cardiovascular events is a composite of all-cause mortality, any myocardial infarction, and any unplanned coronary revascularisation at 12 months. QFR could emerge as an adenosine- and wire-free alternative to FFR, making the functional evaluation of intermediary coronary stenosis less invasive and more cost-effective.

International randomized trial on the effect of revascularization or optimal medical therapy of chronic total coronary occlusions with myocardial ischemia - ISCHEMIA-CTO trial - rationale and design.

BACKGROUND: Chronic total occlusions (CTO) are frequent among patients with coronary artery disease. Revascularization with percutaneous coronary intervention (PCI) is safe and feasible in experienced hands. However, randomized data are needed to demonstrate symptomatic as well as prognostic effect of CTO-PCI compared to optimal medical therapy alone. METHODS: This trial aims to evaluate the effect of CTO PCI in patients with a CTO lesion and target vessel diameter ≥ 2.5 mm, and myocardial ischemia in the relevant territory. First, all patients are subjected to optimal medical therapy (OMT) for at least for 3 months and non-CTO lesions are managed according to guidelines. Subsequently, prior to randomization myocardial ischemia and quality of life (Seattle Questionnaire (SAQ)) is assessed. Patients are divided into two cohorts based on their SAQ score and randomized to either OMT alone or OMT and CTO-PCI. Cohort A is defined as Low- or asymptomatic patients with a quality-of-life score > 60 and/or CCS class < 2, and more than 10 % ischemia in the left ventricle (LV). Cohort B is symptomatic patients with a quality-of-life score < 60 or CCS class angina > 1 and at least ischemia in 5% of the LV. The primary end-point in cohort A is a composite of major adverse cardiac and cerebral events, hospitalization for heart failure and malignant ventricular arrhythmias. The primary endpoint in cohort B is difference in quality of life 6 months after randomization. IMPLICATIONS: This trial is designed to investigate if CTO-PCI improves QoL and MACCE. Both positive and negative outcome of the trial will affect future guidelines and recommendations on how to treat patients with CTO.

Temporal trends in characteristics and outcome of heart failure patients with and without significant coronary artery disease.

AIMS: Ischaemic coronary artery disease (CAD) remains the leading cause of mortality globally due to sudden death and heart failure (HF). Invasive coronary angiography (CAG) is the gold standard for evaluating the presence and severity of CAD. Our objective was to assess temporal trends in CAG utilization, patient characteristics, and prognosis in HF patients undergoing CAG at a national level. METHODS AND RESULTS: We used data from the Swedish Coronary Angiography and Angioplasty Registry. Data on all patients undergoing CAG for HF indication in Sweden between 2000 and 2018 were collected and analysed. Long-term survival was estimated with multivariable Cox proportional hazards regression adjusted for differences in patient characteristics. In total, 22 457 patients (73% men) with mean age 64.2 ± 11.3 years were included in the study. The patients were increasingly older with more comorbidities over time. The number of CAG specifically for HF indication increased by 5.5% per calendar year (P < 0.001). No such increase was seen for indications angina pectoris and ST-elevation myocardial infarction. A normal CAG or non-obstructive CAD was reported in 63.2% (HF-NCAD), and 36.8% had >50% diameter stenosis in one or more coronary arteries (HF-CAD). The median follow-up time was 3.6 years in HF-CAD and 5 years in HF-NCAD. Age and sex-adjusted survival improved linearly by 1.3% per calendar year in all patients. Compared with HF-NCAD, long-term mortality was higher in HF-CAD patients. The risk of death increased with the increasing severity of CAD. Compared with HF-NCAD, the risk estimate in patients with a single-vessel disease was higher [hazard ratio (HR) 1.3; 95% confidence interval (CI) 1.20-1.41; P < 0.001], a multivessel disease without the involvement of left main coronary artery (HR 1.72; 95% CI 1.58-1.88; P < 0.001), and with left main disease (HR 2.02; 95% CI 1.88-2.18; P < 0.001). The number of HF patients undergoing revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) increased by 7.5% (P < 0.001) per calendar year. The majority (53.4%) of HF-CAD patients were treated medically, while a minority (46.6%) were referred for revascularization with PCI or CABG. Compared with patients treated with PCI, the proportion of patients treated medically or with CABG decreased substantially (P < 0.001). CONCLUSIONS: Over 18 years, the number of patients with HF undergoing CAG has increased substantially. Expanded utilization of CAG increased the number of HF patients treated with percutaneous coronary intervention and coronary artery bypass surgery. Long-term survival improved in all HF patients despite a steady increase of elderly patients with comorbidities.

Long-term mortality in patients with ischaemic heart failure revascularized with coronary artery bypass grafting or percutaneous coronary intervention: insights from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR).

AIMS: To compare coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) for treatment of patients with heart failure due to ischaemic heart disease. METHODS AND RESULTS: We analysed all-cause mortality following CABG or PCI in patients with heart failure with reduced ejection fraction and multivessel disease (coronary artery stenosis >50% in ≥2 vessels or left main) who underwent coronary angiography between 2000 and 2018 in Sweden. We used a propensity score-adjusted logistic and Cox proportional-hazards regressions and instrumental variable model to adjust for known and unknown confounders. Multilevel modelling was used to adjust for the clustering of observations in a hierarchical database. In total, 2509 patients (82.9% men) were included; 35.8% had diabetes and 34.7% had a previous myocardial infarction. The mean age was 68.1 ± 9.4 years (47.8% were >70 years old), and 64.9% had three-vessel or left main disease. Primary designated therapy was PCI in 56.2% and CABG in 43.8%. Median follow-up time was 3.9 years (range 1 day to 10 years). There were 1010 deaths. Risk of death was lower after CABG than after PCI [odds ratio (OR) 0.62; 95% confidence interval (CI) 0.41-0.96; P = 0.031]. The risk of death increased linearly with quintiles of hospitals in which PCI was the preferred method for revascularization (OR 1.27, 95% CI 1.17-1.38, Ptrend < 0.001). CONCLUSION: In patients with ischaemic heart failure, long-term survival was greater after CABG than after PCI.

Association of Pretreatment With P2Y12 Receptor Antagonists Preceding Percutaneous Coronary Intervention in Non-ST-Segment Elevation Acute Coronary Syndromes With Outcomes.

Importance: Pretreatment of patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) with P2Y12 receptor antagonists is a common practice despite the lack of definite evidence for its benefit. Objective: To investigate the association of P2Y12 receptor antagonist pretreatment vs no pretreatment with mortality, stent thrombosis, and in-hospital bleeding in patients with NSTE-ACS undergoing percutaneous coronary intervention (PCI). Design, Setting, and Participants: This cohort study used prospective data from the Swedish Coronary Angiography and Angioplasty Registry of 64 857 patients who underwent procedures between 2010 and 2018. All patients who underwent PCI owing to NSTE-ACS in Sweden were stratified by whether they were pretreated with P2Y12 receptor antagonists. Associations of pretreatment with P2Y12 receptor antagonists with the risks of adverse outcomes were investigated using instrumental variable analysis and propensity score matching. Data were analyzed from March to June 2019. Exposures: Pretreatment with P2Y12 receptor antagonists. Main Outcomes and Measures: The primary end point was all-cause mortality within 30 days. Secondary end points were 1-year mortality, stent thrombosis within 30 days, and in-hospital bleeding. Results: In total, 64 857 patients (mean [SD] age, 64.7 [10.9] years; 46 809 [72.2%] men) were included. A total of 59 894 patients (92.4%) were pretreated with a P2Y12 receptor antagonist, including 27 867 (43.7%) pretreated with clopidogrel, 34 785 (54.5%) pretreated with ticagrelor, and 1148 (1.8%) pretreated with prasugrel. At 30 days, there were 971 deaths (1.5%) and 101 definite stent thromboses (0.2%) in the full cohort. Pretreatment was not associated with better survival at 30 days (odds ratio [OR], 1.17; 95% CI, 0.66-2.11; P = .58), survival at 1 year (OR, 1.34; 95% CI, 0.77-2.34; P = .30), or decreased stent thrombosis (OR, 0.81; 95% CI, 0.42-1.55; P = .52). However, pretreatment was associated with increased risk of in-hospital bleeding (OR, 1.49; 95% CI, 1.06-2.12; P = .02). Conclusions and Relevance: This cohort study found that pretreatment of patients with NSTE-ACS with P2Y12 receptor antagonists was not associated with improved clinical outcomes but was associated with increased risk of bleeding. These findings support the argument that pretreatment with P2Y12 receptor antagonists should not be routinely used in patients with NSTE-ACS.

Ticagrelor is Not Superior to Clopidogrel in Patients With Acute Coronary Syndromes Undergoing PCI: A Report from Swedish Coronary Angiography and Angioplasty Registry.

Background Ticagrelor reduces ischaemic end points in acute coronary syndromes. However, outcomes of ticagrelor versus clopidogrel in real-world patients with acute coronary syndromes treated with percutaneous coronary intervention (PCI) remain unclear. We sought to examine whether treatment with ticagrelor is superior to clopidogrel in unselected patients with acute coronary syndromes treated with PCI. Methods and Results We used data from SCAAR (Swedish Coronary Angiography and Angioplasty Registry) for PCI performed in Västra Götaland County, Sweden. The database contains information about all PCI performed at 5 hospitals (∼20% of all data in SCAAR). All procedures between January 2005 and January 2015 for unstable angina/non‒ST-segment‒elevation myocardial infarction and ST-segment‒elevation myocardial infarction were included. We used instrumental variable 2-stage least squares regression to adjust for confounders. The primary combined end point was mortality or stent thrombosis at 30 days, secondary end points were mortality at 30 days and 1-year, stent thrombosis at 30 days, in-hospital bleeding, in-hospital neurologic complications and long-term mortality. A total of 15 097 patients were included in the study of which 2929 (19.4%) were treated with ticagrelor. Treatment with ticagrelor was not associated with a lower risk for the primary end point (adjusted odds ratio [aOR], 1.20; 95% CI, 0.87-1.61; P=0.250). Estimated risk of death at 30 days (aOR, 1.18; 95% CI, 0.88-1.64; P=0.287) and at 1-year (aOR, 1.28; 95% CI, 0.86-1.64; P=0.556) was not different between the groups. The risk of in-hospital bleeding was higher with ticagrelor (aOR, 2.88; 95% CI, 1.53-5.44; P=0.001). Conclusions In this observational study, treatment with ticagrelor was not superior to clopidogrel in patients with acute coronary syndromes treated with PCI.

PROspective evaluation of coronary FLOW reserve and molecular biomarkers in patients with established coronary artery disease the PROFLOW-trial: cross-sectional evaluation of coronary flow reserve.

BACKGROUND: Survivors of myocardial infarction (MI) are at high risk of new major adverse cardiovascular events (MACE). Coronary flow reserve (CFR) is a strong and independent predictor of MACE. Understanding the prevalence of impaired CFR in this patient group and identifying risk markers for impaired CFR are important steps in the development of personalized and targeted treatment for high-risk individuals with prior MI. METHODS: PROFLOW is a prospective, exploratory, cross-sectional open study. We used information from the SCAAR (Swedish Coronary Angiography and Angioplasty Registry) to identify high-risk patients with a history of type-1 MI. We measured CFR non-invasively in a left anterior descending artery (LAD) using transthoracic Doppler echocardiography. Coronary flow velocity was measured at rest and at maximal flow after induction of hyperemia by intravenous infusion of adenosine (140 µg/kg/min). Independent predictors of CFR were assessed with multiple linear regression. RESULTS: We included 619 patients. The median age was 69 (IQR 65-73), and 114 (18.4%) were women. Almost one-half of the patients, 285 (46.0%) had the multi-vessel disease, and 147 (23.7%) were incompletely revascularized. The majority were on optimal standard treatment eg ASA (93.1%), statins (90.0%), ACEI/ARB (82.6%) and beta-blockers (80.8%). The majority, 547 (88.4%) had no angina pectoris, and 572 (92.2%) were in NYHA class I. Evaluation of CFR was possible in 611 (98.7%) patients. Mean CFR was 2.74 (±0.79 (mean ± SD)). A substantial number of patients (39.7%) had CFR ≤2.5. In a multiple linear regression model age, dyslipidemia, smoking, hypertension, body mass index, incomplete revascularization, and treatment with angiotensin receptor blockers were independent predictors of CFR. CONCLUSION: In this high-risk group of patients with prior MI, the prevalence of impaired CFR was high. Further risk stratification with CFR in addition to traditional cardiovascular risk factors may improve predictive accuracy for future MACE in this patient population.

Pretreatment with P2Y12 receptor antagonists in ST-elevation myocardial infarction: a report from the Swedish Coronary Angiography and Angioplasty Registry.

AIMS: Pretreatment of patients with ST-elevation myocardial infarction (STEMI) with P2Y12 receptor antagonists is supported by guidelines and is a common practice despite the lack of definite evidence for its benefit. METHODS AND RESULTS: Using data from the Swedish Coronary Angiography and Angioplasty Registry on procedures between 2005 and 2016, we stratified all patients who underwent primary percutaneous coronary intervention due to STEMI in Sweden by whether or not they were pretreated with P2Y12 receptor antagonists. We investigated associations between pretreatment with P2Y12 receptor antagonists and the risk of adverse outcomes using propensity score-adjusted mixed-effects logistic regression, which accounted for clustering of patients within hospitals. The primary endpoint was all-cause death within 30 days. Secondary endpoints were infarct-related artery (IRA) occlusion, 30-day stent thrombosis, in-hospital bleeding, neurological complications, and cardiogenic shock. In total, 44 804 patients were included. They were treated with clopidogrel (N = 26 136, 58.3%), ticagrelor (N = 15 792, 35.3%), or prasugrel (N = 2352, 5.3%); 37 840 (84.5%) were pretreated, and 30 387 (67.8%) had IRA occlusion. At 30 days, there were 2488 (5.6%) deaths and 267 (0.6%) stent thrombosis. Pretreatment was not associated with better survival at 30 days [odds ratio (OR) 1.08, 95% confidence interval (CI) 0.95-1.24; P = 0.313], reduced IRA occlusion (OR 0.98, 95% CI 0.92-1.05; P = 0.608), decreased stent thrombosis (OR 0.99, 95% CI 0.69-1.43; P = 0.932), higher risk of in-hospital bleeding (OR 1.05, 95% CI 0.89-1.26; P = 0.526), or neurological complications (OR 0.72, 95% CI 0.43-1.21; P = 0.210). CONCLUSION: Pretreatment of STEMI patients with P2Y12 receptor antagonists was not associated with improved clinical outcomes.

Value of the SYNTAX Score in ST-Elevation Myocardial Infarction Patients With a Concomitant Chronic Total Coronary Occlusion(from the EXPLORE Trial).

`To analyze the impact of additional coronary artery disease, quantified by the SYNTAX (SYNergy between PCI with TAXus and cardiac surgery) score, on left ventricular ejection fraction (LVEF) and long-term outcomes in a cohort of ST-elevated myocardial infarction (STEMI) patients with a concomitant chronic total coronary occlusion (CTO). A total of 302 STEMI patients were randomized to percutaneous coronary intervention of a CTO (CTO PCI) (n = 148) or conservative CTO treatment (n = 154). SYNTAX scores were calculated by an independent corelab (Cardialysis BV, Rotterdam) at two time-points: (1) at baseline, and (2) after primary PCI in the conservative CTO arm and after CTO PCI in the invasive arm (named 'discharge SYNTAX score'). The population was divided in two groups (below or equal to the median SYNTAX score preprimary PCI, or above the median). At 4-month follow-up, the LVEF was significantly lower in patients in the group with a SYNTAX score above the group median (42.8% vs 48.5%, p = 0.001), and the SYNTAX score was an independent predictor for LVEF at 4 months (ß-0.151 (SE 0.068), p = 0.028). In the group with a SYNTAX score above the group median the mortality rate was higher (10.1% vs 3.9%, p = 0.025), and there was a trend towards a higher MACE rate (15.4% vs 8.5%, p = 0.063). In conclusion, in this sub-analysis of the EXPLORE trial we observed a worse LVEF and a higher mortality rate for patients with a SYNTAX score above the median. We found that the SYNTAX score is an independent negative predictor for LVEF and an independent positive predictor for LVEDV at 4-month follow-up.

Bivalirudin versus Heparin Monotherapy in Myocardial Infarction.

BACKGROUND: The comparative efficacy of various anticoagulation strategies has not been clearly established in patients with acute myocardial infarction who are undergoing percutaneous coronary intervention (PCI) according to current practice, which includes the use of radial-artery access for PCI and administration of potent P2Y12 inhibitors without the planned use of glycoprotein IIb/IIIa inhibitors. METHODS: In this multicenter, randomized, registry-based, open-label clinical trial, we enrolled patients with either ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) who were undergoing PCI and receiving treatment with a potent P2Y12 inhibitor (ticagrelor, prasugrel, or cangrelor) without the planned use of glycoprotein IIb/IIIa inhibitors. The patients were randomly assigned to receive bivalirudin or heparin during PCI, which was performed predominantly with the use of radial-artery access. The primary end point was a composite of death from any cause, myocardial infarction, or major bleeding during 180 days of follow-up. RESULTS: A total of 6006 patients (3005 with STEMI and 3001 with NSTEMI) were enrolled in the trial. At 180 days, a primary end-point event had occurred in 12.3% of the patients (369 of 3004) in the bivalirudin group and in 12.8% (383 of 3002) in the heparin group (hazard ratio, 0.96; 95% confidence interval [CI], 0.83 to 1.10; P=0.54). The results were consistent between patients with STEMI and those with NSTEMI and across other major subgroups. Myocardial infarction occurred in 2.0% of the patients in the bivalirudin group and in 2.4% in the heparin group (hazard ratio, 0.84; 95% CI, 0.60 to 1.19; P=0.33), major bleeding in 8.6% and 8.6%, respectively (hazard ratio, 1.00; 95% CI, 0.84 to 1.19; P=0.98), definite stent thrombosis in 0.4% and 0.7%, respectively (hazard ratio, 0.54; 95% CI, 0.27 to 1.10; P=0.09), and death in 2.9% and 2.8%, respectively (hazard ratio, 1.05; 95% CI, 0.78 to 1.41; P=0.76). CONCLUSIONS: Among patients undergoing PCI for myocardial infarction, the rate of the composite of death from any cause, myocardial infarction, or major bleeding was not lower among those who received bivalirudin than among those who received heparin monotherapy. (Funded by the Swedish Heart-Lung Foundation and others; VALIDATE-SWEDEHEART ClinicalTrialsRegister.eu number, 2012-005260-10 ; ClinicalTrials.gov number, NCT02311231 .).

Hypertension is associated with increased mortality in patients with ischaemic heart disease after revascularization with percutaneous coronary intervention - a report from SCAAR.

BACKGROUND: The prognostic role of hypertension on long-term survival after percutaneous coronary intervention (PCI) is limited and inconsistent. We hypothesize that hypertension increases long-term mortality after PCI. METHODS: We analyzed data from SCAAR (Swedish Coronary Angiography and Angioplasty Registry) for all consecutive patients admitted coronary care units in Sweden between January 1995 and May 2013 and who underwent PCI due to ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI)/unstable angina (UA) or stable angina pectoris. We used Cox proportional-hazards regression for statistical modelling on complete-case data as well as on imputed data sets. We used interaction test to evaluate possible effect-modulation of hypertension on risk estimates in several pre-specified subgroups: age categories, gender, diabetes, smoking and indication for PCI (STEMI, NSTEMI/UA and stable angina). RESULTS: During the study period, 175,892 consecutive patients underwent coronary angiography due to STEMI, NSTEMI/UA or stable angina. 78,100 (44%) of these had hypertension. Median follow-up was 5.5 years. After adjustment for differences in patient's characteristics, hypertension was associated with increased risk for mortality (HR 1.12, 95% CI 1.09-1.15, p < .001). In subgroup analysis, risk was highest in patients less than 65 years, in smokers and in patients with STEMI. The risk was lowest in patients with stable angina (p < .001 for interaction test). CONCLUSION: Hypertension is associated with higher mortality in patients with STEMI, NSTEMI/UA or stable angina who are treated with PCI.

Low socioeconomic status of a patient's residential area is associated with worse prognosis after acute myocardial infarction in Sweden.

INTRODUCTION: Previous studies have established a relationship between socioeconomic status (SES) and survival in coronary heart disease. Acute cardiac care in Sweden is considered to be excellent and independent of SES. We studied the influence of area-level socioeconomic status on mortality after hospitalization for acute myocardial infarction (AMI) between 1995 and 2013 in the Gothenburg metropolitan area, which has little over 800,000 inhabitants and includes three city hospitals. METHODS: Data were obtained from the SWEDEHEART registry (Swedish Websystem for Enhancement of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) and the Swedish Central Bureau of Statistics for patients hospitalized for ST-elevation myocardial infarction (STEMI) and non-STEMI in the city of Gothenburg in Western Sweden. The groups were compared using Cox proportional hazards regression and logistic regression. RESULTS: 10,895 (36% female) patients were hospitalized due to AMI during the study period. Patients residing in areas with lower SES had higher rates of smoking and diabetes (P<0.001), and were also at increased risk of developing complications, including heart failure and cardiogenic shock (P<0.05). Living in an area with lower SES associated with increased risk of dying after an AMI also in models adjusted for risk factors (P<0.05). CONCLUSION: Also in a country with strong egalitarian traditions, lower SES associates with worse prognosis after AMI, an association that persists after adjustments for differences in traditional cardiovascular risk factors.

Chronic total occlusions in Sweden--a report from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR).

INTRODUCTION: Evidence for the current guidelines for the treatment of patients with chronic total occlusions (CTO) in coronary arteries is limited. In this study we identified all CTO patients registered in the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) and studied the prevalence, patient characteristics and treatment decisions for CTO in Sweden. METHODS AND RESULTS: Between January 2005 and January 2012, 276,931 procedures (coronary angiography or percutaneous coronary intervention) were performed in 215,836 patients registered in SCAAR. We identified all patients who had 100% luminal diameter stenosis known or assumed to be ≥ 3 months old. After exclusion of patients with previous coronary artery bypass graft (CABG) surgery or coronary occlusions due to acute coronary syndrome, we identified 16,818 CTO patients. A CTO was present in 10.9% of all coronary angiographies and in 16.0% of patients with coronary artery disease. The majority of CTO patients were treated conservatively and PCI of CTO accounted for only 5.8% of all PCI procedures. CTO patients with diabetes and multivessel disease were more likely to be referred to CABG. CONCLUSION: CTO is a common finding in Swedish patients undergoing coronary angiography but the number of CTO procedures in Sweden is low. Patients with CTO are a high-risk subgroup of patients with coronary artery disease. SCAAR has the largest register of CTO patients and therefore may be valuable for studies of clinical importance of CTO and optimal treatment for CTO patients.

Contemporary overview and clinical perspectives of chronic total occlusions.

Chronic total occlusions (CTOs) are often detected on diagnostic coronary angiograms, but percutaneous coronary intervention (PCI) for CTO is currently infrequently performed owing to high technical difficulty, perceived risk of complications, and a lack of randomized data. However, successful CTO-PCI can significantly increase a patient's quality of life, improve left ventricular function, reduce the need for subsequent CABG surgery, and possibly improve long-term survival. A number of factors must be taken into account for the selection of patients for CTO-PCI, including the extent of ischaemia surrounding the occlusion, the level of myocardial viability, coronary location of the CTO, and probability of procedural success. Moreover, in patients with ST-segment elevation myocardial infarction, a CTO in a noninfarct-related artery might lead to an increase in infarct area, increased end-diastolic left ventricular pressure, and decreased left ventricular function, which are all associated with poor clinical outcomes. In this Review, we provide an overview of the anatomy and histopathology of CTOs, perceived benefits of CTO-PCI, considerations for patient selection for this procedure, and a summary of emerging techniques for CTO-PCI.

Does the timing of treatment with intra-aortic balloon counterpulsation in cardiogenic shock due to ST-elevation myocardial infarction affect survival?

BACKGROUND: Intra-aortic balloon pump (IABP) counterpulsation and primary percutaneous coronary intervention (PCI) are standard treatment modalities in cardiogenic shock (CS) complicating acute myocardial infarction. The aim of this study was to investigate the impact of the timing of IABP treatment start in relation to PCI procedure. METHODS: Data were obtained from the SCAAR registry (Swedish Coronary Angiography and Angioplasty Registry) about 139 consecutive patients with CS due to ST-elevation myocardial infarction (STEMI) who received IABP treatment. The patients were hospitalized at Sahlgrenska University Hospital, Gothenburg, during 2004-2008. The cohort was divided into the two groups: group (A) in whom IABP treatment started before start of PCI (n = 72) and group (B) in whom IABP treatment started after PCI treatment (n = 67). The primary endpoint was 30-day mortality. Propensity score (PS) adjusted Cox proportional hazards regression was used to analyze predictors of 30-day mortality. RESULTS: Mean age was 66.5 ± 12 and 28% were women. All patients have received IABP treatment 30 min before or 30 min after primary PCI. 63% had diabetes and 28% had hypertension. 16% were active tobacco smokers. The mortality rate at 30 days was 38%. IABP treatment commenced before or after PCI was not an independent predictor of mortality (P = 0.72). CONCLUSION: In this non-randomized trial the treatment with insertion of IABP before primary PCI in patients with CS due to STEMI is not associated with a more favorable outcome as compared with IABP started after primary PCI.

Clinical and procedural characteristics associated with higher radiation exposure during percutaneous coronary interventions and coronary angiography.

BACKGROUND: We aim to study the clinical and procedural characteristics associated with higher radiation exposure in patients undergoing percutaneous coronary interventions (PCIs) and coronary angiography. METHODS AND RESULTS: Our present study included all coronary angiography and PCI procedures in 5 PCI centers in the Western part of Sweden, between January 1, 2008, and January 19, 2012. The radiation exposure and clinical data were collected prospectively in these 5 PCI centers in Sweden as part of the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). A prediction model was made for the radiation exposure (dose-area product) expressed in Gy·cm(2). A total of 20 669 procedures were included in the present study, consisting of 9850 PCI and 10 819 coronary angiography procedures. In multivariable analyses, body mass index (ß=1.04; confidence interval [CI], 1.04-1.04; P<0.001); history of coronary artery bypass graft surgery (ß=1.32; CI, 1.28-1.32; P<0.001); 2, 3, or 4 treated lesions (2 treated lesions: ß=1.95; CI, 1.84-2.03; P<0.001; 3 treated lesions: ß=2.34; CI, 2.16-2.53; P<0.001; and 4 treated lesions: ß=2.83; CI, 2.53-3.16; P<0.001); and chronic total occlusion lesions (ß=1.39; CI, 1.31-1.48; P<0.001) were associated with the highest radiation exposure. After adjusting for procedural complexity, radial access route was not associated with increased radiation exposure (ß=1.00; CI, 0.98-1.03; P=0.67). CONCLUSIONS: In the largest study population to assess radiation exposure, we found that high body mass index, history of coronary artery bypass graft surgery, number of treated lesions, and chronic total occlusions were associated with the highest patient radiation exposure. Radial access site was not associated with higher radiation exposure when compared with femoral approach.

Electrophysiological effects of lysophosphatidylcholine on HL-1 cardiomyocytes assessed with a microelectrode array system.

BACKGROUND: Sudden death due to malignant ventricular arrhythmias is the most important cause of death in acute myocardial infarction. Improved knowledge about the pathophysiology underlying these arrhythmias is essential in the search for new anti-arrhythmic strategies. Lysophosphatidylcholine (LPC), a hydrolysis product of (membrane) phospholipid degradation, is one of the most potent pro-arrhythmic substances that accumulate in the human heart during myocardial ischemia. The aim of this study was to set up and validate an in vitro experimental system for studies on the effects of LPC on electrophysiological parameters in beating cardiomyocytes. METHODS AND RESULTS: Spontaneously beating HL-1 cardiomyocytes were cultured on multielectrode array microchips for three days for the recording of electrical activities in the form of field potentials (FP). FPs were recorded at baseline and after addition of 2, 4, 8, 12, 16, 20, and 24 µM of LPC to the cell medium (n=9). We found that LPC could induce rapid effects on electrical parameters in the HL-1 cells. The overall half-maximal effective concentration (EC(50)) of LPC was around 12 µM. The beating rate and peak-peak amplitude of FP thus decreased at concentrations ≥ 12 µM and were inversely proportional to increased LPC concentration. The duration of FP was significantly prolonged with LPC above 12 µM and was concentration-dependent. LPC delayed signal propagation, an effect which was mimicked by blocking gap junctions with heptanol and attenuated by pre-treatment with isoprenaline and atropine. Finally, asynchronous activity was induced by LPC at >12 µM. CONCLUSIONS: LPC induced prompt and pronounced electrophysiological alterations that may underlie its observed pro-arrhythmic properties. Our in vitro model with HL-1 cells and microelectrode array system may be a useful tool for preclinical studies of electrophysiological effects of various pathophysiological concepts.

Effects of doxorubicin on myocardial expression of apolipoprotein-B.

OBJECTIVE: Doxorubicin (DOX) is an effective antitumour agent against a variety of human malignancies but is associated with deleterious side effects, including myocardial damage and heart failure. Myocardial apoB-containing lipoprotein (apoB) is upregulated post myocardial infarction and has been shown to be cardioprotective in this setting by unloading excessive lipid. The aim of this study was to investigate whether apoB expression is increased also in DOX-induced heart failure and whether apoB overexpression protects the heart in DOX-induced myocardial injury. DESIGN: Cardiac function and energy metabolism was studied in mice and rats 24 hours after intraperitoneally administered DOX. RESULTS: We found that the content of apoB was decreased in rat myocardium 24 hours after DOX injection. In contrast, apoB content was increased in the infarcted myocardium of rats 24 hours post ischemia-reperfusion. Moreover, transgenic mice overexpressing apoB had better cardiac function and lower intracellular lipid accumulation compared to wild type mice 24 hours post DOX. CONCLUSIONS: Our findings indicate that depression of the myocardial apoB system may contribute to DOX-induced cardiac injury and that overexpression of apoB is protective, not only in ischemically damaged myocardium, but also in DOX-induced heart failure.

Aqueous fish extract increases survival in the mouse model of cytostatic toxicity.

BACKGROUND: Treatment of cancer patients with anthracycline antibiotic doxorubicin (DOX) may be complicated by development of acute and chronic congestive heart failure (CHF), malignant arrhythmias and death. The aim of this study was to test whether an aqueous low molecular weight (LMW) extract from cod muscle decreases acute mortality in the mouse model of acute CHF caused by DOX. METHODS: A LMW fraction (<500 Da) of the aqueous phase of cod light muscle (AOX) was used for treatment of male BALB/c mice (approximately 25 g, n = 70). The animals were divided into four groups, DOX + AOX (n = 20), DOX + saline (NaCl) (n = 30), NaCl + AOX (n = 10) and NaCl only (n = 10). Echocardiography was performed in the separate subgroups (DOX treated n = 6 and controls n = 6) to verify the presence and the grade of acute CHF. The cod extract was delivered by subcutaneously implanted osmotic minipumps over the period of 2 weeks. High-dose injection of DOX was administered to randomly selected animals. The animals received single intraperitoneal injection of DOX (25 mg/kg) and were followed over two weeks for mortality. RESULTS: Mortality rate was 68% lower (p < 0.05) in the mice treated with the extract. The analyses of cod extract have shown strong antioxidative effect in vitro. CONCLUSION: The aqueous LMW cod muscles extract decreases mortality in the mouse model of DOX induced acute CHF. This effect may be mediated by cardioprotection through antioxidative mechanisms.