Timing of Complete Revascularization with Multivessel PCI for Myocardial Infarction.

BACKGROUND: In patients with ST-segment elevation myocardial infarction (STEMI) with multivessel coronary artery disease, the time at which complete revascularization of nonculprit lesions should be performed remains unknown. METHODS: We performed an international, open-label, randomized, noninferiority trial at 37 sites in Europe. Patients in a hemodynamically stable condition who had STEMI and multivessel coronary artery disease were randomly assigned to undergo immediate multivessel percutaneous coronary intervention (PCI; immediate group) or PCI of the culprit lesion followed by staged multivessel PCI of nonculprit lesions within 19 to 45 days after the index procedure (staged group). The primary end point was a composite of death from any cause, nonfatal myocardial infarction, stroke, unplanned ischemia-driven revascularization, or hospitalization for heart failure at 1 year after randomization. The percentages of patients with a primary or secondary end-point event are provided as Kaplan-Meier estimates at 6 months and at 1 year. RESULTS: We assigned 418 patients to undergo immediate multivessel PCI and 422 to undergo staged multivessel PCI. A primary end-point event occurred in 35 patients (8.5%) in the immediate group as compared with 68 patients (16.3%) in the staged group (risk ratio, 0.52; 95% confidence interval, 0.38 to 0.72; P<0.001 for noninferiority and P<0.001 for superiority). Nonfatal myocardial infarction and unplanned ischemia-driven revascularization occurred in 8 patients (2.0%) and 17 patients (4.1%), respectively, in the immediate group and in 22 patients (5.3%) and 39 patients (9.3%), respectively, in the staged group. The risk of death from any cause, the risk of stroke, and the risk of hospitalization for heart failure appeared to be similar in the two groups. A total of 104 patients in the immediate group and 145 patients in the staged group had a serious adverse event. CONCLUSIONS: Among patients in hemodynamically stable condition with STEMI and multivessel coronary artery disease, immediate multivessel PCI was noninferior to staged multivessel PCI with respect to the risk of death from any cause, nonfatal myocardial infarction, stroke, unplanned ischemia-driven revascularization, or hospitalization for heart failure at 1 year. (Supported by Boston Scientific; MULTISTARS AMI ClinicalTrials.gov number, NCT03135275.).

Inflammatory state does not affect the antiplatelet efficacy of potent P2Y12 inhibitors in ACS.

Inflammation leads to atherosclerosis and acute coronary syndromes (ACS). We performed a prospective, observational study to assess association between the concentrations of inflammatory markers (high sensitivity C-reactive protein, hsCRP; high sensitivity interleukin6, hsIL-6; soluble CD40 ligand, sCD40 L) and platelet reactivity in 338 patients with ACS treated with ticagrelor and prasugrel. We also assessed whether hsCRP, hsIL-6, and sCD40 L are associated with standard inflammatory markers (white blood cell [WBC] and fibrinogen), and whether they differ according to patient diabetic status and pre-treatment with statins. Concentrations of hsCRP and concentrations of hsIL-6 and sCD40 L were assessed using turbidimetric assay and enzyme-linked immunosorbent assay, respectively. Platelet reactivity was measured using multiple electrode aggregometry. There was only a weak inverse correlation between hsIL-6 and platelet reactivity (r≤-0.125). In contrast, concentration of hsIL6 and hsCRP positively correlated with WBC and fibrinogen (r ≥ 0.199). Insulin-dependent diabetes mellitus (IDDM) was associated with higher concentration of hsIL-6 (p = .014), whereas pre-treatment with statins - with lower concentration of hsIL-6 (p = .035). In conclusion, inflammatory state does not affect the antiplatelet efficacy of potent P2Y12 inhibitors in the acute phase of ACS, confirming the safety and efficacy of potent P2Y12 inhibitors in patients with a high inflammatory burden.

Rationale and design of the MULTISTARS AMI Trial: A randomized comparison of immediate versus staged complete revascularization in patients with ST-segment elevation myocardial infarction and multivessel disease.

About half of patients with acute ST-segment elevation myocardial infarction (STEMI) present with multivessel coronary artery disease (MVD). Recent evidence supports complete revascularization in these patients. However, optimal timing of non-culprit lesion revascularization in STEMI patients is unknown because dedicated randomized trials on this topic are lacking. STUDY DESIGN: The MULTISTARS AMI trial is a prospective, international, multicenter, randomized, two-arm, open-label study planning to enroll at least 840 patients. It is designed to investigate whether immediate complete revascularization is non-inferior to staged (within 19-45 days) complete revascularization in patients in stable hemodynamic conditions presenting with STEMI and MVD and undergoing primary percutaneous coronary intervention (PCI). After successful primary PCI of the culprit artery, patients are randomized in a 1:1 ratio to immediate or staged complete revascularization. The primary endpoint is a composite of all-cause death, non-fatal myocardial infarction, ischemia-driven revascularization, hospitalization for heart failure, and stroke at 1 year. CONCLUSIONS: The MULTISTARS AMI trial tests the hypothesis that immediate complete revascularization is non-inferior to staged complete revascularization in stable patients with STEMI and MVD.

Ticagrelor and prasugrel are independent predictors of improved long-term survival in ACS patients.

AIM: To investigate the long-term clinical benefit of dual antiplatelet therapy with potent P2Y12 inhibitors compared to clopidogrel in patients with acute coronary syndrome (ACS). METHODS: In this prospective multicenter observational study, we enrolled 708 patients with ACS treated with clopidogrel (n = 137), ticagrelor (n = 260) or prasugrel (n = 311). Major adverse cardiac events (MACE; over 1 year) and long-term mortality (median: 5.6 years; interquartile range [IQR] 4.9-6.5 years) were assessed. Multiple electrode aggregometry (MEA) was used to measure adenosine diphosphate (ADP)- and arachidonic acid (AA)-induced platelet aggregation. RESULTS: Type of P2Y12 inhibitor emerged as an independent predictor of long-term mortality and MACE: patients treated with potent platelet inhibitors prasugrel or ticagrelor were at lower risk for long-term mortality (adjusted hazard ratio [HR] = 0.44; 95% CI: 0.22-0.92; P = .028) or MACE (adjusted HR = 0.38; 95% CI: 0.20-0.73; P = .004) than those treated with clopidogrel independent from clinical risk factors. In contrast, the efficacy of clopidogrel decreased with increasing severity of ACS: platelet aggregation was 37% higher in patients with ST segment elevation myocardial infarction (STEMI) and 25% higher in patients with non-ST elevation myocardial infarction (non-STEMI) compared to patients with unstable angina (P = .039). Patients with diabetes achieved less potent ADP- and AA-induced platelet inhibition under clopidogrel, compared to patients without diabetes (P = .045; P = .030, respectively). CONCLUSION: In the setting of ACS, treatment with ticagrelor or prasugrel reduced long-term mortality and 1-year MACE as compared to clopidogrel.

Impact of anemia on long-term outcomes after percutaneous coronary intervention for chronic total occlusion.

OBJECTIVES: A single-centre, observational study was performed in order to investigate the relationship between anemia and outcomes after percutaneous coronary intervention (PCI) for chronic total occlusion (CTO). BACKGROUND: Anemia has been identified as adverse predictor in patients with coronary artery disease undergoing coronary revascularization. Data on the impact of anemia on outcomes in patients undergoing PCI for CTO lesions are lacking. METHODS: A total of 1,964 patients undergoing CTO PCI were stratified according to the presence/absence of anemia (hemoglobin of <13 g/dl for men and <12 g/dl for women). The primary endpoint was all-cause mortality. Median follow-up was 2.6 (interquartile range 1.1-3.1) years. RESULTS: Of the 1,964 patients, 297 (15.1%) had anemia. Anemic as compared to nonanemic patients had and an increased all-cause mortality (27.9% versus 9.1%, P < 0.001), and associations remained significant after multivariable adjustments (adjusted HR 2.26, 95% CI 1.71-2.98, P < 0.001). All-cause mortality decreased with increasing hemoglobin tertiles (T1: 18.6%, T2: 8.6%, T3: 8.2%, log rank P < 0.001). Procedural success was associated with reduced all-cause mortality both in anemic (21.8% versus 47.2%, adjusted HR 0.59, 95% CI 0.37-0.93, P = 0.02) and nonanemic patients (7.8% versus 16.3%, adjusted HR 0.64, 95% CI 0.42-0.98, P = 0.02, interaction P = 0.69). CONCLUSIONS: Although anemia is associated with an increased all-cause mortality in patients undergoing CTO PCI, the survival benefit associated with successful CTO recanalization is maintained.

Coronary dominance and prognosis in patients with chronic total occlusion treated with percutaneous coronary intervention.

AIM: The prognostic value of coronary artery dominance pattern in patients with chronic total occlusions (CTO) is unknown. The aim of this study was to assess the influence of coronary vessel dominance on short and long-term outcomes in patients undergoing percutaneous coronary intervention (PCI) for CTO. METHODS AND RESULTS: Our study population consisted of 2002 consecutive patients (17% females, mean age 65.2 ± 10.7 years) who underwent PCI of at least one coronary CTO lesion at our center between 01/2005 and 12/2013. Based on the origin of the posterior descending coronary artery, coronary circulation was categorised into left, right, and balanced coronary dominance. Right coronary dominance (RD) was present in 88% (n = 1759), left coronary dominance (LD) in 7% (n = 136), and balanced coronary dominance (BD) in 5% (n = 107) of the study population. After a median follow-up duration of 2.6 years [interquartile range 1.1-3.1 years] all-cause mortality was significantly higher in patients with LD as compared with RD and BD (log rank = 0.001). Accordingly, the presence of a LD system was identified as a significant predictor for all-cause mortality (adjusted HR 1.7, 95% CI: 1.2-2.6, P = .007) and major adverse cardiac events (MACE) (adjusted HR 1.4, 95% CI: 1.1-1.8, P = 0.02). CONCLUSION: Our data suggest that LD is an independent predictor of increased all-cause death and MACE in patients with CTO. Therefore, assessment of coronary vessel dominance by angiography may contribute to risk stratification in these patients.

Culotte stenting vs. TAP stenting for treatment of de-novo coronary bifurcation lesions with the need for side-branch stenting: the Bifurcations Bad Krozingen (BBK) II angiographic trial.

AIMS: In percutaneous coronary intervention for de-novo coronary bifurcation lesions, the optimal technique for provisional side-branch stenting is still a matter of debate. We tested whether in this setting culotte stenting reduces the incidence of restenosis as compared with T-and-protrusion (TAP) stenting. METHODS AND RESULTS: This trial included 300 patients with a coronary bifurcation lesion requiring a side-branch stent. Patients were randomly assigned to culotte stenting or TAP stenting using drug-eluting stents in a 1:1 fashion. Primary endpoint was maximal per cent diameter stenosis of the bifurcation lesion at 9-month angiographic follow-up. As clinical endpoints we assessed target lesion re-intervention (TLR) and target lesion failure (composite of cardiac death, target vessel myocardial infarction, and TLR).Angiographic follow-up was available in 91% of the patients. After culotte stenting, the maximum per cent diameter stenosis in the treated bifurcation lesion was 21 ± 20% as compared with 27 ± 25% after TAP stenting (P = 0.038). The respective corresponding binary restenosis rates were 6.5 and 17% (P = 0.006). The 1-year incidence of TLR was 6.0% after culotte stenting vs. 12.0% after T-stenting (P = 0.069). Target lesion failure occurred in 6.7% of the culotte group and in 12.0% of the TAP group (P = 0.11). Only one patient of the culotte group incurred a definite stent thrombosis during 1-year follow-up. CONCLUSIONS: Compared with the TAP stenting, culotte stenting was associated with a significantly lower incidence of angiographic restenosis.

Longitudinal compression of the platinum-chromium everolimus-eluting stent during coronary implantation: predisposing mechanical properties, incidence, and predictors in a large patient cohort.

OBJECTIVES: To assess the longitudinal compression behavior of platinum-chromium everolimus-eluting stents, evaluate frequency of inadvertent longitudinal compression during percutaneous intervention, and define patient- and lesion-related predictors of this complication. BACKGROUND: Platinum-chromium stents of Element family have unique design features to improve flexibility that may, however, impair longitudinal stability. Incidence of longitudinal stent compression during implantation and predictors for this complication are not well understood. METHODS: Five contemporary stent platforms were longitudinally compressed in a bench test experiment, and spring constant, yield force, and ultimate strength were calculated from force-strain curves. We also evaluated all coronary cases treated with an Element stent from January 1, 2010, to October 31, 2011, for documented longitudinal compression. We compared baseline characteristics and periprocedural data between patients with and without longitudinal stent compression and assessed predictors for this event by multiple logistic regression models. RESULTS: Yield force and ultimate strength were significantly lower for the Element compared with all other tested stents. In 20 patients (1.4%) and 20 lesions (0.7%) from 1,392 cases with 2,839 atherosclerotic lesions longitudinal stent compression was reported. Ostial segments, number of stents, and the presence of a bifurcation were significant predictors (adjusted odds ratios [95% confidence intervals]: 8.33 [3.30-21.28], 1.57 [1.01-2.45], 3.57 [1.36-9.35], respectively). CONCLUSION: The Element stent exhibits the lowest overall longitudinal strength compared with four contemporary platforms. Longitudinal compression of the Element stent is a rare complication and occurs more frequently in ostial or bifurcation lesions and with multiple stents.

Prognostic Value of Different Levels of Uric Acid in Patients with Coronary Chronic Total Occlusion Undergoing Percutaneous Coronary Intervention.

Recent data suggest that uric acid (UA) might be an independent predictor of clinical outcomes following percutaneous coronary intervention (PCI). The predictive value of uric acid in patients undergoing PCI for chronic total occlusions (CTO) is unknown. We included patients with CTO who underwent PCI at our center in 2005 and 2012, with available uric acid levels before angiography. Subjects were divided into groups according to uric acid tertiles (<5.5 mg/dL, 5.6-6.9 mg/dL, and >7.0 mg/dL), and outcomes were compared among the groups. Out of the 1963 patients (mean age 65.2 ± 11 years), 34.7% (n = 682) had uric acid concentrations in the first tertile, 34.3% (n = 673) in the second tertile, and 31% (n = 608) in the third tertile. Median follow-up was 3.0 years. Uric acid levels in the first tertile were associated with significantly lower all-cause mortality, as compared to the third tertile, with an adjusted hazard ratio (HR) of 0.67 (95% confidence interval (CI): 0.49 to 0.92; p = 0.012). No significant differences regarding all-cause mortality were found between patients in the first and second tertiles (HR: 0.96 [95% CI: 0.71 to 1.3; p = 0.78]). High levels of uric acid emerged as an independent predictor of all-cause mortality in patients with chronic total occlusion treated with PCI. Hence, uric acid levels should be incorporated into the risk assessment of patients with CTO.

New ECG algorithms with improved accuracy for prediction of culprit vessel in inferior ST-segment elevation myocardial infarction.

BACKGROUND: In addition to diagnosing acute myocardial infarction (MI), the electrocardiogram (ECG) may also predict the culprit coronary artery. We aimed to assess the diagnostic accuracy of ECG algorithms predicting the occluded vessel in inferior ST-segment elevation myocardial infarction (STEMI). METHODS: This retrospective cohort study included 300 consecutive patients with inferior STEMI undergoing acute coronary angiography. A new method based on the summation of ST-segment deviations in multiple leads from the first 12-lead-ECG was used to develop algorithms to discriminate between right coronary artery (RCA) and circumflex artery (CX) occlusion. Additionally, older algorithms were reassessed. RESULTS: The RCA was occluded in 235 patients (78%) and the CX in 65 (22%). ST-segment deviations differed significantly between RCA and CX occlusions in leads I, III, aVR, aVL, aVF and V1. ST-segment deviations in lead I showed the highest discriminatory ability of a single lead (area under the receiver operating curve [AUC]=0.77). The summation of multiple leads further increased the discriminatory ability ("III-II+aVF+aVR+V1:" AUC=0.86; "III-II-I+aVF+V1:" AUC=0.85). The best binary algorithm "III-II-I+aVF+V1>0.1 mV" classified 86% of cases correctly and was better than the best old algorithm (83.3%). The simpler algorithm "III+aVR+V1≥0.1 mV" still predicted 85.0% correctly. All algorithms had higher sensitivities for RCA than for CX detection and performed better in right-dominant anatomy. CONCLUSIONS: A new approach summating multiple ST-segment deviations generated ECG algorithms with higher diagnostic accuracy to predict the occluded vessel in inferior STEMI compared to previous studies. These algorithms may facilitate earlier risk stratification for patients at risk of postinfarct complications.

Cardiopulmonary Long-Term Sequelae in Patients after Severe COVID-19 Disease.

We aimed to identify cardiopulmonary long-term effects after severe COVID-19 disease as well as predictors of Long-COVID in a prospective registry. A total of 150 consecutive, hospitalized patients (February 2020 and April 2021) were included six months post hospital discharge for a clinical follow-up. Among them, 49% experienced fatigue, 38% exertional dyspnea and 75% fulfilled criteria for Long-COVID. Echocardiography detected reduced global longitudinal strain (GLS) in 11% and diastolic dysfunction in 4%. Magnetic resonance imaging revealed traces of pericardial effusion in 18% and signs of former pericarditis or myocarditis in 4%. Pulmonary function was impaired in 11%. Chest computed tomography identified post-infectious residues in 22%. Whereas fatigue did not correlate with cardiopulmonary abnormalities, exertional dyspnea was associated with impaired pulmonary function (OR 3.6 [95% CI: 1.2-11], p = 0.026), reduced GLS (OR 5.2 [95% CI: 1.6-16.7], p = 0.003) and/or left ventricular diastolic dysfunction (OR 4.2 [95% CI: 1.03-17], p = 0.04). Predictors of Long-COVID included length of in-hospital stay (OR: 1.15 [95% CI: 1.05-1.26], p = 0.004), admission to intensive care unit (OR cannot be computed, p = 0.001) and higher NT-proBNP (OR: 1.5 [95% CI: 1.05-2.14], p = 0.026). Even 6 months after discharge, a majority fulfilled criteria for Long-COVID. While no associations between fatigue and cardiopulmonary abnormalities were found, exertional dyspnea correlated with impaired pulmonary function, reduced GLS and/or diastolic dysfunction.

Plasma Trimethylamine-N-Oxide Is an Independent Predictor of Long-Term Cardiovascular Mortality in Patients Undergoing Percutaneous Coronary Intervention for Acute Coronary Syndrome.

To investigate the association of liver metabolite trimethylamine N-oxide (TMAO) with cardiovascular disease (CV)-related and all-cause mortality in patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention. Our prospective observational study enrolled 292 patients with ACS. Plasma concentrations of TMAO were measured during the hospitalization for ACS. Observation period lasted seven yr in median. Adjusted Cox-regression analysis was used for prediction of mortality. ROC curve analysis revealed that increasing concentrations of TMAO levels assessed at the time point of ACS significantly predicted the risk of CV mortality (c-index=0.78, p < 0.001). The cut-off value of >4 µmol/L, labeled as high TMAO level (23% of study population), provided the greatest sum of sensitivity (85%) and specificity (80%) for the prediction of CV mortality and was associated with a positive predictive value of 16% and a negative predictive value of 99%. A multivariate Cox regression model revealed that high TMAO level was a strong and independent predictor of CV death (HR = 11.62, 95% CI: 2.26-59.67; p = 0.003). High TMAO levels as compared with low TMAO levels were associated with the highest risk of CV death in a subpopulation of patients with diabetes mellitus (27.3 vs. 2.6%; p = 0.004). Although increasing TMAO levels were also significantly associated with all-cause mortality, their estimates for diagnostic accuracy were low. High TMAO level is a strong and independent predictor of long-term CV mortality among patients presenting with ACS.

Non-Vitamin K Oral Anticoagulants (NOAC) Versus Vitamin K Antagonists (VKA) for Atrial Fibrillation with Elective or Urgent Percutaneous Coronary Intervention: A Meta-Analysis with a Particular Focus on Combination Type.

BACKGROUND: Our study aims to perform a meta-analysis of benefits and risks associated with the use of non-vitamin K oral anticoagulants (NOAC) versus vitamin K antagonists (VKA) in patients with a percutaneous coronary intervention (PCI) with a particular focus on the combination type: dual vs. dual antithrombotic therapy (DAT: NOAC + single antiplatelet therapy (SAPT) vs. DAT: VKA + SAPT), dual vs. triple antithrombotic therapy (DAT: NOAC + SAPT vs. TAT: VKA + dual antiplatelet therapy (DAPT)) or triple vs. triple antithrombotic therapy (TAT: NOAC+DAPT vs. TAT: VKA+DAPT). METHODS: PubMed, EMBASE, and Cochrane databases were searched to identify randomized controlled trials comparing antithrombotic regimens. Four randomized studies (n = 10.969; PIONEER AF-PCI, RE-DUAL PCI, AUGUSTUS, and ENTRUST-AF PCI) were included. The primary outcome was the composite of major bleeding defined by the International Society on Thrombosis and Hemostasis (ISTH) and clinically relevant bleeding requiring medical intervention (CRNM). Secondary outcomes included all-cause mortality, major adverse cardiovascular events (MACE), myocardial infarction (MI), stroke, and stent thrombosis (ST). RESULTS: Combination strategies with NOACs were associated with reduced risk of major bleeding events across different combination strategies as compared to VKA, with the most significant risk reduction when DAT was compared with TAT, namely DAT with NOAC + SAPT was associated with a 37% relative risk reduction (RRR) of major bleeding events as compared to TAT with VKA + DAPT (RR 0.63; 95% CI, 0.50-0.80). The reduction of major bleeding risks is a class effect of NOACs. Combination strategies of NOACs vs. VKAs resulted in a comparable risk of MACE, MI, stroke, ST, or death. CONCLUSIONS: Antithrombotic combinations of NOACs (as DAT or TAT) are safer than VKAs with respect to bleeding risk and result in a satisfactory efficacy with no increase of ischemic or thrombotic events in patients undergoing PCI.

von Willebrand Factor Predicts Mortality in ACS Patients Treated with Potent P2Y12 Antagonists and is Inhibited by Aptamer BT200 Ex Vivo.

BACKGROUND: von Willebrand factor (VWF) is crucial for arterial thrombosis and its plasma levels are increased in acute coronary syndromes (ACSs). The effects of conventional platelet inhibitors are compromised by elevated VWF under high shear rates. BT200 is a third-generation aptamer that binds and inhibits the A1 domain of human VWF. This article aims to study whether VWF is a predictor of mortality in ACS patients under potent P2Y12 blocker therapy and to examine the effects of a VWF inhibiting aptamer BT200 and its concentrations required to inhibit VWF in plasma samples of patients with ACS. METHODS: VWF activity was measured in 320 patients with ACS, and concentration effect curves of BT200 were established in plasma pools containing different VWF concentrations. RESULTS: Median VWF activity in patients was 170% (interquartile range % confidence interval [CI]: 85-255) and 44% of patients had elevated (> 180%) VWF activity. Plasma levels of VWF activity predicted 1-year (hazard ratio [HR]: 2.68; 95% CI: 1.14-6.31; p < 0.024) and long-term (HR: 2.59; 95% CI: 1.10-6.09) mortality despite treatment with potent platelet inhibitors (dual-antiplatelet therapy with aspirin and prasugrel or ticagrelor). Although half-maximal concentrations were 0.1 to 0.2 µg/mL irrespective of baseline VWF levels, increasing concentrations (0.42-2.13 µg/mL) of BT200 were needed to lower VWF activity to < 20% of normal in plasma pools containing increasing VWF activity (p < 0.001). CONCLUSION: VWF is a predictor of all-cause mortality in ACS patients under contemporary potent P2Y12 inhibitor therapy. BT200 effectively inhibited VWF activity in a target concentration-dependent manner.

Left Main Coronary Artery Disease and Outcomes after Percutaneous Coronary Intervention for Chronic Total Occlusions.

BACKGROUND: Concomitant left main coronary artery (LMCA) disease in patients with chronic total occlusions (CTO) commonly results in referral for coronary artery bypass grafting, although the impact of LMCA in CTO patients remains largely unknown. Nevertheless, patient selection for percutaneous coronary intervention of CTOs (CTO-PCI) or alternative revascularization strategies should be based on precise evaluation of the coronary anatomy to anticipate those patients that most likely benefit from a procedure and not on strict adherence to perpetual clinical practice. Therefore, the aim of this study was to assess the impact of LMCA disease on long-term outcomes in patients undergoing percutaneous coronary intervention for CTO. METHODS: We enrolled 3860 consecutive patients undergoing PCI for at least one CTO lesion and investigated the predictive value of concomitant LMCA disease. All-cause mortality was defined as the primary study endpoint. RESULTS: We observed that LMCA disease is significantly associated with mortality. In the Cox regression analysis, we observed a crude hazard ratio (HR) 1.59 (95% confidence interval (CI) 1.23-2.04, p < 0.001) for patients with LMCA disease as compared to patients without. Results remained unchanged after bootstrap- or clinical confounder-based adjustment. CONCLUSION: LMCA disease is associated with excess mortality in CTO patients. Specifically, anatomical features such as CTO of the circumflex artery represent a high risk patient population.

Impact of treatment strategies on long-term outcome of CTO patients.

BACKGROUND: The percutaneous coronary intervention (PCI) for chronic total occlusions (CTO) remains debated. Therefore the aim of this large-scale observational multi-center registry was to compare the long-term outcome of CTO patients undergoing different therapeutic approaches comparing successful CTO revascularization either by PCI or coronary artery bypass graft (CABG), failed CTO-PCI and optimal medical therapy (OMT) alone. METHODS AND RESULTS: A total of 6630 CTO patients were enrolled from two high-volume centers to compare different treatment strategies. All procedures were performed by high-volume CTO operators in tertiary university hospital. Successful CTO-PCI was performed in 3906 patients, failed CTO-PCI in 1479 patients, 412 patients underwent CABG surgery and 833 patients were treated with OMT. During the 5-year follow-up period, 1019 (15%) patients died. Kaplan-Meier analysis unveiled a significantly improved long-term outcome for CTO patients undergoing revascularization either by PCI or by CABG compared to patients with failed CTO-PCI or OMT alone (log-rank P < 0.001). In the multivariate Cox-regression analysis successful CTO-PCI was associated with significantly improved long-term outcome compared to patients under OMT (adj. HR 0.39, 95%CI 0.33-0.45, P < 0.001) or CABG (adj. HR 0.68, 95%CI 0.53-0.86, P = 0.002) independent of clinical confounders encompassing age, BMI, diabetes, kidney function and left ventricular function. CONCLUSIONS: This study showed an improved long-term outcome for CTO revascularization compared to optimal medical therapy, independent from revascularization mode, with the highest survival rate in patients undergoing successful CTO-PCI.

An Extended Duration of the Pre-Operative Hospitalization is Associated with an Increased Risk of Healthcare-Associated Infections after Cardiac Surgery.

Nosocomial infections are a common complication in clinical practice with major impact on surgical success and patient outcome. The probability of nosocomial infections is rapidly increasing during hospitalization. Therefore, we investigated the impact of a prolonged pre-operative hospital stay on the development of post-operative infection. Within this prospective observational study, 200 patients scheduled for elective cardiac surgery were enrolled. Patients were followed during hospital admission and screened for the development of nosocomial infection. Logistic regression analysis was used to assess the impact of a prolonged pre-operative hospital stay on the development of infection. A total of 195 patients were suitable for the final analysis. We found a strong and direct association of the duration of pre-operative hospital stay and the number of patients developing infection (+23.5%; p = 0.006). Additionally, the length of patients' pre-operative hospital stay was independently associated with the development of post-operative nosocomial infection, with an adjusted OR per day of 1.38 (95%CI: 1.02-1.86; p = 0.036). A prolonged pre-operative hospital stay was significantly associated with the development of nosocomial infection after cardiac surgery. Those findings need to be considered in future clinical patient management in order to prevent unnecessary antibiotic use and potential harm to patients.

A Unifying Concept for the Quantitative Assessment of Secondary Mitral Regurgitation.

BACKGROUND: Diverging guideline definitions for the quantitative assessment of severe secondary mitral regurgitation (sMR) reflect the lacking link of the sMR spectrum to mortality and has introduced a source of uncertainty and continuing debate. OBJECTIVES: The current study aimed to define improved risk-thresholds specifically tailored to the complex nature of sMR that provide a unifying solution to the ongoing guideline-controversy. METHODS: This study enrolled 423 heart failure patients under guideline-directed medical therapy and assessed sMR by effective regurgitant orifice area (EROA), regurgitant volume (RegVol), and regurgitant fraction (RegFrac). RESULTS: Measures of sMR severity were consistently associated with 5-year mortality with a hazard ratio of 1.42 for a 1-SD increase (95% confidence interval [CI]: 1.25 to 1.63; p < 0.001) for EROA, 1.37 (95% CI: 1.20 to 1.56; p < 0.001) for RegVol, and 1.50 (95% CI: 1.30 to 1.73; p < 0.001) for RegFrac. Results remained statistically significant after bootstrap- or clinical confounder-based adjustment. Spline-curve analyses showed a linearly increasing risk enabling the ability to stratify into low-risk (EROA <20 mm2 and RegVol <30 ml), intermediate-risk (EROA 20 to 29 mm2 and RegVol 30 to 44 ml), and high-risk (EROA ≥30 mm2 and RegVol ≥45 ml) groups. In the intermediate-risk group, a RegFrac ≥50% as indicator for hemodynamic severe sMR was associated with poor outcome (p = 0.017). A unifying concept based on combined assessment of the EROA, the RegVol, and the RegFrac showed a significantly better discrimination compared with the currently established algorithms. CONCLUSIONS: Risk-based thresholds tailored to the pathophysiological concept of sMR provide a unifying solution to the ongoing guideline controversy. An algorithm based on the combined assessment of the unifying cutoffs for EROA, RegVol, and RegFrac improves risk prediction compared with currently established grading.

Stratified Approaches to Antiplatelet Therapies Based on Platelet Reactivity Testing.

Antiplatelet therapy with P2Y12 receptor inhibitors (clopidogrel, prasugrel, ticagrelor, cangrelor) is a cornerstone of medical therapy after percutaneous coronary interventions. Significant prevalence of high on-treatment platelet reactivity (HTPR) on clopidogrel treatment led to introduction of more potent P2Y12 inhibitors: prasugrel (a third generation thienopyridine), ticagrelor, and cangrelor (cyclopentyl-triazolo-pyrimidines). Nevertheless, more potent platelet inhibition and resulting low on-treatment platelet reactivity (LTPR) has led to increased risk of major bleeding events. These limitations resulted in a need for an individualized antiplatelet therapy approach. This review discusses the current role and future perspectives of diagnostic tools such as platelet function testing to optimize antiplatelet therapy with a focus on deescalating therapies to reduce bleeding risks.

Long-term results after PCI of unprotected distal left main coronary artery stenosis: the Bifurcations Bad Krozingen (BBK)-Left Main Registry.

AIMS: Percutaneous coronary intervention (PCI) of unprotected distal left main stenosis (UDLM) is increasingly performed as an alternative to surgical treatment. The optimal strategy for stenting in this setting is still a matter of debate. Therefore, this analysis investigated the long-term clinical outcome of a single- versus a double-stenting strategy for treatment of UDLM. METHODS AND RESULTS: From a large registry, 867 consecutive patients with UDLM undergoing either single or double stenting with drug-eluting stents (DES) were identified. Follow-up was up to 10 (median 3.1, interquartile range 1.1-5.3) years. Primary endpoint was MACE consisting of all-cause death, myocardial infarction, or target lesion re-intervention (TLR). Secondary clinical endpoints included these single endpoints and stent thrombosis. MACE occurred in 41.5% after single and in 49.0% after double stenting (P = 0.03). TLR was lower after single (17.4%) as compared to double stenting (27.2%; P < 0.01). Between single and double stenting, there were no significant differences for death (26.4 versus 23.3%; P = 0.31), death or myocardial infarction (29.1 versus 27.2%; P = 0.55), or definite/probable stent thrombosis (1.3 versus 2.1%; P = 0.42). CONCLUSIONS: Compared with single stenting, double stenting was associated with a significantly higher long-term risk of MACE. This was driven by a higher incidence of TLR, whereas the risk of death, MI, or stent thrombosis was similar between the two strategies.