Epicardial fat volume is associated with primary coronary slow-flow phenomenon in patients with severe aortic stenosis undergoing transcatheter valve implantation.

BACKGROUND: Primary coronary slow flow (CSF) is defined as delayed opacification of the distal epicardial vasculature during coronary angiography in the absence of relevant coronary artery stenoses. Microvascular disease is thought to be the underlying cause of this pathology. Epicardial fat tissue (EFT) is an active endocrine organ directly surrounding the coronary arteries that provides pro-inflammatory factors to the adjacent tissue by paracrine and vasocrine mechanisms. The aim of the present study was to investigate a potential association between EFT and primary CSF and whether EFT can predict the presence of primary CSF. METHODS: Between 2016 and 2017, n = 88 patients with high-grade aortic stenosis who were planned for transcatheter aortic valve implantation (TAVI) were included in this retrospective study. EFT volume was measured by pre-TAVI computed tomography (CT) using dedicated software. The presence of primary CSF was defined based on the TIMI frame count from the pre-TAVI coronary angiograms. RESULTS: Thirty-nine of 88 TAVI patients had CSF (44.3%). EFT volume was markedly higher in patients with CSF (142 ml [IQR 107-180] vs. 113 ml [IQR 89-147]; p = 0.009) and was strongly associated with the presence of CSF (OR 1.012 [95%CI 1.002-1.021]; p = 0.014). After adjustment, EFT volume was still an independent predictor of CSF (OR 1.016 [95%CI 1.004-1.026]; p = 0.009). CONCLUSION: Primary CSF was independently associated with increased EFT volume. Further studies are needed to validate this finding and elucidate whether a causal relationship exists.

Incidence and pattern of urgent revascularization in acute coronary syndromes treated with ticagrelor or prasugrel.

BACKGROUND: The ISAR-REACT 5 trial compared the efficacy and safety of ticagrelor and prasugrel in patients with ACS managed invasively. The present study sought to investigate the impact of ticagrelor and prasugrel on the incidence and pattern of urgent revascularization in acute coronary syndromes (ACS) patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: This post-hoc analysis of the ISAR-REACT 5 trial included all ACS patients who underwent PCI. The primary endpoint for this analysis was the incidence of urgent revascularization at 12-month follow-up. Secondary outcome was the pattern of urgent revascularization procedures (namely, urgent target vessel/non-target vessel revascularization - TVR/NTVR). Among 3,377 ACS patients who underwent PCI, 1,676 were assigned to ticagrelor and 1,701 to prasugrel before PCI. After 12 months, the incidence of urgent revascularization was higher among patients assigned to ticagrelor as compared to prasugrel (6.8% vs. 5.2%; hazard ratio [HR] = 1.32, 95% confidence interval [CI] 1.00-1.75; p = 0.051), mostly attributable to significantly more urgent NTVR in the ticagrelor group (3.8% vs. 2.4%; HR = 1.62 [1.09-2.41]; p = 0.017). The risk of urgent TVR did not differ between treatment groups (3.3% vs. 3.0%; HR = 1.13 [0.77-1.65]; p = 0.546). CONCLUSIONS: In ACS patients treated with PCI, the cumulative rate of urgent revascularizations after 12 months is higher with ticagrelor compared to prasugrel, due to a significant increase in urgent revascularizations involving remote coronary vessels.

The role of Matrix Metalloproteinase-2 and Galectin-3 as predictive biomarkers for all-cause mortality in patients undergoing transfemoral transcatheter aortic valve implantation.

BACKGROUND: Currently available risk scores fail to accurately predict morbidity and mortality in patients with severe symptomatic aortic stenosis who undergo transcatheter aortic valve implantation (TAVI). In this context, biomarkers like matrix metalloproteinase-2 (MMP-2) and Galectin-3 (Gal-3) may provide additional prognostic information. METHODS: Patients with severe aortic stenosis undergoing consecutive, elective, transfemoral TAVI were included. Baseline demographic data, functional status, echocardiographic findings, clinical outcomes and biomarker levels were collected and analysed. RESULTS: The study cohort consisted of 89 patients (age 80.4 ± 5.1 years, EuroScore II 7.1 ± 5.8%). During a median follow-up period of 526 d, 28 patients (31.4%) died. Among those who died, median baseline MMP-2 (alive: 221.6 [170.4; 263] pg/mL vs. deceased: 272.1 [225; 308.8] pg/mL, p < 0.001) and Gal-3 levels (alive: 19.1 [13.5; 24.6] pg/mL vs. deceased: 25 [17.6; 29.5] pg/mL, p = 0.006) were higher than in survivors. In ROC analysis, MMP-2 reached an acceptable level of discrimination to predict mortality (AUC 0.733, 95% CI [0.62; 0.83], p < 0.001), but the predictive value of Gal-3 was poor (AUC 0.677, 95% CI [0.56; 0.79], p = 0.002). Kaplan-Meier and Cox regression analyses showed that patients with MMP-2 and Gal-3 concentrations above the median at baseline had significantly impaired long-term survival (p = 0.004 and p = 0.02, respectively). CONCLUSIONS: In patients with severe aortic stenosis undergoing transfemoral TAVI, MMP-2 and to a lesser extent Gal-3, seem to have additive value in optimizing risk prediction and streamlining decision-making.

Impact of Access Site on Periprocedural Bleeding and Cerebral and Coronary Events in High-Bleeding-Risk Percutaneous Coronary Intervention: Findings from the RIVA-PCI Trial.

INTRODUCTION: The preference for using transradial access (TRA) over transfemoral access (TFA) in patients requiring percutaneous coronary intervention (PCI) is based on evidence suggesting that TRA is associated with less bleeding and fewer vascular complications, shorter hospital stays, improved quality of life, and a potential beneficial effect on mortality. We have limited study data comparing the two access routes in a patient population with atrial fibrillation (AF) undergoing PCI, who have a particular increased risk of bleeding, while AF itself is associated with an increased risk of thromboembolism. METHODS: Using data from the RIVA-PCI registry, which includes patients with AF undergoing PCI, we analyzed a high-bleeding-risk (HBR) cohort. These patients were predominantly on oral anticoagulants (OAC) for AF, and the PCI was performed via radial or femoral access. Endpoints examined were in-hospital bleeding (BARC 2-5), cerebral events (TIA, hemorrhagic or ischemic stroke) and coronary events (stent thrombosis and myocardial infarction). RESULTS: Out of 1636 patients, 854 (52.2%) underwent TFA, while 782 (47.8%) underwent the procedure via TRA, including nine patients with brachial artery puncture. The mean age was 75.5 years. Groups were similar in terms of age, sex distribution, AF type, cardiovascular history, risk factors, and comorbidities, except for a higher incidence of previous bypass surgeries, heart failure, hyperlipidemia, and chronic kidney disease (CKD) with a glomerular filtration rate (GFR) < 60 ml/min in the TFA group. No clinically relevant differences in antithrombotic therapy and combinations were present at the time of PCI. However, upon discharge, transradial PCI patients had a higher rate of triple therapy, while dual therapy was preferred after transfemoral procedures. Radial access was more frequently chosen for non-ST-segment elevation myocardial infarction (NSTEMI) and unstable angina pectoris (UAP) cases (NSTEMI 26.6% vs. 17.0%, p < 0.0001; UAP 21.5% vs. 14.5%, p < 0.001), while femoral access was more common for elective PCI (60.3% vs. 44.1%, p < 0.0001). No differences were observed for ST-segment elevation myocardial infarction (STEMI). Both groups had similar rates of cerebral events (TFA 0.2% vs. TRA 0.3%, p = 0.93), but the TFA group had a higher incidence of bleeding (BARC 2-5) (4.2% vs. 1.5%, p < 0.01), mainly driven by BARC 3 bleeding (1.5% vs. 0.4%, p < 0.05). No significant differences were found for stent thrombosis and myocardial infarction (TFA 0.2% vs. TRA 0.3%, p = 0.93; TFA 0.4% vs. TRA 0.1%, p = 0.36). CONCLUSIONS: In HBR patients with AF undergoing PCI for acute or chronic coronary syndrome, the use of TRA might be associated with a decrease in in-hospital bleeding, while not increasing the risk of embolic or ischemic events compared to femoral access. Further studies are required to confirm these preliminary findings.

Patient-Reported Long-Term Outcome of Balloon Pulmonary Angioplasty for Inoperable CTEPH.

BACKGROUND: Balloon pulmonary angioplasty (BPA) is a promising interventional treatment for inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Evidence in favor of BPA is growing, but long-term data remain scarce. The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) is validated for the assessment of patients with pulmonary hypertension within three domains: symptoms, activity, and quality of life (QoL). The aim of the present study was to evaluate the long-term effects of BPA on these domains in patients with inoperable CTEPH. METHODS: Between March 2014 and August 2019, technically inoperable patients with target lesions for BPA were included in this prospective, observational study. CAMPHOR scores were compared between baseline (before the first BPA) and 6 months after the last intervention and also for scores assessed at annual follow-ups. RESULTS: A total of 152 patients had completed a full series of BPA interventions and a 28 (interquartile range [IQR]: 26-32) week follow-up. Further follow-up assessments including the CAMPHOR score were performed 96 (IQR: 70-117) weeks, 178 (IQR: 156-200) weeks, and 250 (IQR: 237-275) weeks after the last intervention. From baseline to the last follow-up, CAMPHOR scores for symptoms, activity, and QoL improved from 9 (IQR: 6-14) to 3 (IQR: 0-9) (p < 0.001), 8 (IQR: 5-12) to 4 (IQR: 2-8) (p < 0.001), and 5 (IQR: 2-9) to 1 (IQR: 0-5) (p < 0.001). CONCLUSION: BPA leads to long-lasting, significant improvement of symptoms, physical capacity, and QoL in inoperable CTEPH patients.

Coronary Angiography After Out-of-Hospital Cardiac Arrest Without ST-Segment Elevation: One-Year Outcomes of a Randomized Clinical Trial.

Importance: Myocardial infarction is a frequent cause of out-of-hospital cardiac arrest (OHCA). The long-term effect of early coronary angiography on patients with OHCA with possible coronary trigger but no ST-segment elevation remains unclear. Objective: To compare the clinical outcomes of early unselective angiography with the clinical outcomes of a delayed or selective approach for successfully resuscitated patients with OHCA of presumed cardiac origin without ST-segment elevation at 1-year follow-up. Design, Setting, and Participants: The TOMAHAWK trial was a multicenter, international (Germany and Denmark), investigator-initiated, open-label, randomized clinical trial enrolling 554 patients between November 23, 2016, to September 20, 2019. Patients with stable return of spontaneous circulation after OHCA of presumed cardiac origin but without ST-segment elevation on the postresuscitation electrocardiogram were eligible for inclusion. A total of 554 patients were randomized to either immediate coronary angiography after hospital admission or an initial intensive care assessment with delayed or selective angiography after a minimum of 24 hours. All 554 patients were included in survival analyses during the follow-up period of 1 year. Secondary clinical outcomes were assessed only for participants alive at 1 year to account for the competing risk of death. Interventions: Early vs delayed or selective coronary angiography and revascularization if indicated. Main Outcomes and Measures: Evaluations in this secondary analysis included all-cause mortality after 1 year, as well as severe neurologic deficit, myocardial infarction, and rehospitalization for congestive heart failure in survivors at 1 year. Results: A total of 281 patients were randomized to the immediate angiography group and 273 to the delayed or selective group, with a median age of 70 years (IQR, 60-78 years). A total of 369 of 530 patients (69.6%) were male, and 268 of 483 patients (55.5%) had a shockable arrest rhythm. At 1 year, all-cause mortality was 60.8% (161 of 265) in the immediate angiography group and 54.3% (144 of 265) in the delayed or selective angiography group without significant difference between the treatment strategies, trending toward an increase in mortality with immediate angiography (hazard ratio, 1.25; 95% CI, 0.99-1.57; P = .05). For patients surviving until 1 year, the rates of severe neurologic deficit, myocardial infarction, and rehospitalization for congestive heart failure were similar between the groups. Conclusions and Relevance: This study found that a strategy of immediate coronary angiography does not provide clinical benefit compared with a delayed or selective invasive approach for patients 1 year after resuscitated OHCA of presumed coronary cause and without ST-segment elevation. Trial Registration: ClinicalTrials.gov Identifier: NCT02750462.

Optimal medical therapy improves outcomes in patients with diabetes mellitus and acute myocardial infarction.

AIMS: We aimed to explored the association between the use of optimal medical therapy (OMT) in patients with myocardial infarction (AMI) and diabetes mellitus (DM) and clinical outcomes. METHODS: Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome (BleeMACS) is an international registry that enrolled participants with acute coronary syndrome followed up for at least 1 year across 15 centers from 2003 to 2014. Baseline characteristics and endpoints were analyzed. RESULTS: Among 3095 (23.2%) patients with AMI and DM, 1898 (61.3%) received OMT at hospital discharge. OMT was associated with significantly reduced mortality (4.3% vs. 10.8%, p < 0.001), re-AMI (4.4% vs. 8.1%, p < 0.001), and composite endpoint of death/re-AMI (8.0% vs. 17.6%, p < 0.001). No difference was observed among regions. Propensity score matching confirmed that OMT significantly associated with lower mortality. After adjusting for confounding variables, OMT, drug-eluting stents, and complete revascularization were independent protective factors of 1-year mortality, whereas left ventricular ejection fraction and age were risk factors. CONCLUSIONS: Guideline-recommended OMT was prescribed at suboptimal frequencies with geographic variations in this worldwide cohort. OMT can improve long-term clinical outcomes in patients with DM and AMI. CLINICAL TRIAL REGISTRATION: NCT02466854 June 9, 2015.

Incidence and predictors of hemodynamic compromise due to high-grade AV block after TAVI.

Background: High-grade AV block (HAVB) is the most frequent adverse event after transcatheter aortic valve implantation (TAVI). In rare cases, HAVB is associated with hemodynamic compromise (HC) followed by syncope or application of cardiopulmonary resuscitation (CPR), but data on this severe complication are scarce. The aim of the present study was to investigate the incidence and predictors of HC due to HAVB in patients undergoing TAVI. Methods: In this retrospective analysis of 4,602 TAVI cases between 2010 and 2022, 466 developed HAVB. Baseline characteristics and procedural and postprocedural findings were compared for patients with HC versus those without. Univariate and multivariable regression analyses were used to investigate independent predictors of HC. Results: Forty-nine of 466 patients (10.5%) had HC due to HAVB after TAVI. Patients with HC had a longer hospital stay [10 (8-13) vs. 13 (9-18) days; p < 0.001], more frequent peripheral artery disease (PAD) (28.6% vs. 15.1%; p = 0.016), and lower hemoglobin levels [11.8 (±) vs. 12.5 (±) g/dl; p = 0.006]. In the HC group, HAVB onset post-TAVI was delayed compared with the non-HC group [2 (1-4) vs. 1 (0-3) days; p < 0.001]. Before HAVB onset, patients in the HC group more frequently developed post-TAVI delirium [18 (4.6%) vs. 11 (25.0%); p < 0.001]. In univariate regression analysis, PAD, hemoglobin, procedural time, contrast agent volume, and post-TAVI delirium were significant predictors of HC. After adjustment, only post-TAVI delirium and contrast agent volume remained independent predictors [OR 3.22 (95% CI: 1.05-9.89); p = 0.042 and OR: 1.01 (95% CI: 1.0-1.01); p = 0.04, respectively]. Conclusion: HC due to HAVB after TAVI occurred in over 10% of cases. Development of post-TAVI delirium and contrast agent volume are independent predictors of this severe complication.

Fibroblast growth factor 23 as a biomarker of right ventricular dysfunction in pulmonary hypertension.

BACKGROUND: Fibroblast growth factor 23 (FGF-23) has been associated with left ventricular hypertrophy (LVH) and heart failure. However, its role in right ventricular (RV) remodeling and RV failure is unknown. This study analyzed the utility of FGF-23 as a biomarker of RV function in patients with pulmonary hypertension (PH). METHODS: In this observational study, FGF-23 was measured in the plasma of patients with PH (n = 627), dilated cardiomyopathy (DCM, n = 59), or LVH with severe aortic stenosis (n = 35). Participants without LV or RV abnormalities served as controls (n = 36). RESULTS: Median FGF-23 plasma levels were higher in PH patients than in healthy controls (p < 0.001). There were no significant differences between PH, DCM, and LVH patients. Analysis across tertiles of FGF-23 levels in PH patients revealed an association between higher FGF-23 levels and higher levels of NT-proBNP and worse renal function. Furthermore, patients in the high-FGF-23 tertile had a higher pulmonary vascular resistance (PVR), mean pulmonary artery pressure, and right atrial pressure and a lower cardiac index (CI) than patients in the low tertile (p < 0.001 for all comparisons). Higher FGF-23 levels were associated with higher RV end-diastolic diameter and lower tricuspid annular plane systolic excursions (TAPSE) and TAPSE/PASP. Receiver operating characteristic analysis revealed FGF-23 as a good predictor of RV maladaptation, defined as TAPSE < 17 mm and CI < 2.5 L/min/m2. Association of FGF-23 with parameters of RV function was independent of the glomerular filtration rate in regression analysis. CONCLUSION: FGF-23 may serve as a biomarker for maladaptive RV remodeling in patients with PH.

Outcomes After Early Postoperative Myocardial Infarction Due to Graft Failure in Patients Undergoing Coronary Artery Bypass Grafting.

BACKGROUND: Early graft failure (EGF) after coronary artery bypass grafting (CABG) occurs in up to 12% of grafts, but is often clinically unapparent. EGF may result in perioperative myocardial infarction with consequently increased mortality. The aim of the present study was to analyze the incidence of clinically apparent EGF in patients undergoing CABG and the influence on mortality. METHODS: We analyzed outcomes of consecutive patients undergoing CABG from January 2015 to December 2018 with respect to postoperative emergency coronary angiography (CAG) due to suspected EGF and 30-day mortality. Patients with CAG-documented EGF were matched to patients without EGF to examine predictors of mortality. RESULTS: The analysis included 5638 patients undergoing CABG. Eighty-six patients (1.5%) underwent emergency CAG due to suspected EGF. Clinically apparent EGF was observed in 61 of these patients (70.9%), whereas 14 (16.3%) had a culprit lesion in a native coronary artery. The majority of patients (n = 45; 52.3%) were treated with percutaneous coronary intervention and 31 (36%) underwent re-do CABG. The remaining patients were treated conservatively. The 30-day mortality rate of suspected EGF patients undergoing CAG was 22.4% (n = 19), which was higher than the mortality rate of 2.8% overall (P<.001); this remained higher after matching the EGF patients with the control group (11 [20.4%] vs 2 [4.0%]; P=.02). CONCLUSION: Emergency CAG after CABG is rare and is primarily carried out in patients with EGF. The 30-day mortality rate of these patients is high, and EGF is an independent predictor of mortality. Perioperative CAG with subsequent treatment is mandatory in these patients.

Current status of antithrombotic therapy and in-hospital outcomes in patients with atrial fibrillation undergoing percutaneous coronary intervention in Germany.

BACKGROUND: Little is known about current patterns of antithrombotic therapy in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) in clinical practice in Germany. METHODS: The RIVA-PCI is a prospective, non-interventional, multicenter study with follow-up until hospital discharge including consecutive patients with AF undergoing PCI. RESULTS: Between January 2018 and March 2020, 1636 patients (elective in 52.6%, non-ST elevation acute coronary syndrome [NSTE-ACS] in 39.3%, ST-elevation myocardial infarction in 8.2%) from 51 German hospitals were enrolled in the study. After PCI a dual antithrombotic therapy (DAT) consisting of OAC and a P2Y12 inhibitor was given to 66.0%, triple antithrombotic therapy (TAT) to 26.0%, dual antiplatelet therapy to 5.5%, and a mono-therapy to 2.5% of the patients. Non-vitamin K antagonist oral anticoagulants (NOACs) were given to 82.4% and vitamin K antagonists to 11.5% of the patients. In-hospital events included death in 12 cases (0.7%), myocardial infarction, stent thrombosis, and ischemic stroke in four (0.2%) patients each, while 2.8% of patients had bleeding complications. The recommended durations for DAT or TAT at discharge were 1 month (1.5%), 3 months (2.1%), 6 months (43.1%), and 12 months (45.6%), with a 6-month course of DAT (47.7%) most often recommended after elective PCI and a 12-month course of DAT (40.1%) after ACS. CONCLUSION: The preferred therapy after PCI in patients with AF is DAT with a NOAC and clopidogrel. In-hospital ischemic and bleeding events were rare. The recommended durations for combination therapy vary considerably.

Rivaroxaban in Patients With Atrial Fibrillation Who Underwent Percutaneous Coronary Intervention in Clinical Practice.

Little is known about the efficacy and safety of rivaroxaban in patients with atrial fibrillation (AF) who underwent percutaneous coronary intervention (PCI) in clinical practice. We therefore conducted a prospective observational study to determine the rate of ischemic, embolic, and bleeding events in patients with AF and PCI treated with rivaroxaban in a real-world experience. The RIVA-PCI ("rivaroxaban in patients with AF who underwent PCI") (clinicaltrials.gov NCT03315650) is a prospective, noninterventional, multicenter study with a follow-up until 14 months, including patients with AF who underwent PCI discharged with rivaroxaban. Between January 2018 and March 2020, 700 patients with PCI treated with rivaroxaban (elective in 50.1%, non-ST-elevation acute coronary syndrome 43.0%, ST-elevation myocardial infarction in 6.9%) were enrolled at 51 German hospitals. After PCI, a dual antithrombotic therapy consisting of rivaroxaban and a P2Y12 inhibitor was administered in 70.7% and triple antithrombotic therapy in 27.9%, respectively. Follow-up information could be obtained in 695 patients (99.3%). Rivaroxaban has been stopped prematurely in 21.6% of patients. Clinical events under rivaroxaban during the 14-month follow-up compared with those observed in the PIONEER-AF PCI trial included cardiovascular death (2.0% % vs 2.0%), myocardial infarction (0.9% vs 3.0%), stent thrombosis (0.2% vs 0.8%), stroke (1.3% vs 1.3%), International Society on Thrombosis and Haemostasis major (4.2% vs 3.9%), and International Society on Thrombosis and Haemostasis nonmajor clinically relevant bleeding (15.3% vs 12.9%). Therefore, in this real-world experience, rivaroxaban in patients with AF who underwent PCI is associated with ischemic and bleeding event rates comparable with those observed in the randomized PIONEER-AF PCI trial.

Riociguat and balloon pulmonary angioplasty improve prognosis in patients with inoperable chronic thromboembolic pulmonary Hypertension.

BACKGROUND: The combination of riociguat and interventional balloon pulmonary angioplasty (BPA) is currently used to treat patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). The aim of the present study was to evaluate the impact of this combination therapy on the prognosis of inoperable CTEPH patients by comparing the long-term survival rates of patients undergoing combination therapy with riociguat and BPA with those of inoperable patients from the first international CTEPH registry who did not receive specific treatment. METHODS: Between March 2014 and August 2019, 138 technically inoperable patients were included in the present prospective, observational cohort study when they were treated with riociguat and BPA at a single CTEPH referral center. Long-term survival of this cohort was compared using propensity score matching with that of inoperable patients recruited between 2007 and 2009 in the first international CTEPH registry. Kaplan-Meier methods were used to evaluate differences in outcomes. RESULTS: Whereas the survival rate in the historical group was 84.6% in the first year, 76.6% in the second, 68.5% in the third, and 58.5% in the fifth year after diagnosis, implementation of riociguat/BPA led to survival rates of 100%, 96.7%, 92.9%, and 90% in the respective follow-up periods. In a comparison of 83 well-matched pairs from the 2 cohorts, survival was markedly better in the group treated with riociguat and BPA than in the historical cohort (HR = 0.145, 95% CI 0.05, 0.421). CONCLUSION: The combination of riociguat and BPA for the treatment of inoperable CTEPH is associated with excellent 5-year survival rates.

Antithrombotic Strategy in Secondary Prevention for High-Risk Patients with Previous Acute Coronary Syndrome: Overlap between the PEGASUS Eligibility and the COMPASS Eligibility in a Large Multicenter Registry.

BACKGROUND: Patients with previous acute coronary syndrome (ACS) are at high risk of recurrent adverse cardiovascular events. Recently, prolonged dual antiplatelet therapy (DAPT) and oral anticoagulation therapy (OAT) have been shown to reduce recurrent ischemic events to the expense of an increase in bleeding events. The number of patients potentially eligible for these therapies in real life remains to be determined. METHODS: Among ACS patients from five registries and one randomized controlled trial, we assessed the proportion of patients eligible for the PEGASUS strategy only and the proportion of patients eligible for the COMPASS strategy only, and set out the proportion of patients with an overlap between the strategies. FINDINGS: Among the 10,048 evaluable patients, we found that 5373 (53.4%) were eligible for the PEGASUS strategy and 3841 (38.2%) were eligible for the COMPASS strategy, with a group of 3444 (34.4%) overlapping between the two strategies. The number of patients eligible for the PEGASUS strategy only was 1929 (19.2%) and the number eligible for the COMPASS strategy only was 397 (4.0%); 4278 (42.6%) were eligible for neither a PEGASUS strategy nor a COMPASS strategy. INTERPRETATION: In a large cohort of ACS patients, one in three patients was eligible for either a prolonged DAPT with ticagrelor 60 mg and low-dose aspirin or a dual pathway inhibition approach with rivaroxaban 2.5 mg and low-dose aspirin.

Exercise MR-proANP unmasks latent right heart failure in CTEPH.

OBJECTIVE: The present study was designed to investigate the dynamics of right atrial pressure (RAP) and mid-regional pro-atrial natriuretic peptide (MR-proANP) during physical exercise in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and to determine whether these parameters might serve as a tool to measure exercise-dependent atrial stress as an indicator of right heart failure. METHODS: This prospective observational cohort study included 100 CTEPH patients who underwent right heart catheterization during physical exercise (eRHC). Blood samples for MR-proANP measurement were taken prior, during, and after eRHC. MR-proANP levels were correlated to RAP levels at rest, at peak exercise (eRAP), and during recovery. RAP at rest ≤7 mmHg was defined as normal and eRAP >15 mmHg as suggestive of right heart failure. RESULTS: During eRHC mean RAP increased from 6 mmHg (standard deviation, SD 4) to 16 mmHg (SD 7; p < 0.001). MR-proANP levels and dynamics correlated with RAP at rest (rs = 0.61; p < 0.001) and at peak exercise (rs = 0.66; p < 0.001). Logistic regression analysis revealed the peak MR-proANP level (B = 0.058; p = 0.004) and the right atrial area (B = 0.389; p < 0.001) to be associated with eRAP dynamics. A peak MR-proANP level ≥139 pmol/L (AUC = 0.81) and recovery level ≥159 pmol/L (AUC = 0.82) predicted an eRAP >15 mmHg. Physical exercise unmasked right heart failure in 39% of patients with normal RAP at rest; these patients were also characterized by a more distinct increase in MR-proANP levels (p = 0.005) and higher peak (p < 0.001) and recovery levels (p < 0.001). CONCLUSIONS: RAP and MR-proANP dynamics unmask manifest and latent right heart failure in CTEPH patients.

Complications of balloon pulmonary angioplasty for inoperable chronic thromboembolic pulmonary hypertension: Impact on the outcome.

BACKGROUND: Balloon pulmonary angioplasty (BPA) is an emerging interventional treatment for inoperable chronic thromboembolic pulmonary hypertension (CTEPH) that targets subsegmental branches of the pulmonary artery. As the reported complication rates are high, the aim of the present study was to evaluate the effects of certain complications on the outcome after treatment. METHODS: From March 2014 to December 2019, a total of 235 patients with inoperable CTEPH underwent BPA. Of these patients, 140 were included who completed a follow-up examination 6 months after the last intervention; another 2 patients deceased due to complications of BPA. RESULTS: A high baseline pulmonary vascular resistance (PVR) >6.6 WU correlated with a higher rate of complications (mostly pulmonary artery perforations). Wire perforation during BPA did not correlate with worse outcome in terms of PVR reduction. The complication rate per intervention decreased from 21% to 14% during the 5 year period of the study. CONCLUSIONS: Complications are frequently observed in BPA, but the mortality rate is very low in expert centers. Importantly, the occurrence of complications does not portend a worse outcome.

CILP1 as a biomarker for right ventricular dysfunction in patients with ischemic cardiomyopathy.

The aim of this study was to evaluate the cartilage intermediate layer protein 1 (CILP1) as a biomarker of right ventricular dysfunction in patients with ischemic cardiomyopathy (ICM). CILP1 plasma concentrations were measured in 98 patients with ICM and 30 controls without any cardiac abnormalities. All participants underwent cardiac magnetic resonance imaging. Median CILP1 concentrations were higher in ICM than in controls. In the tertile analysis, low right ventricular ejection fraction (RVEF) and high right ventricular end-systolic volume index and N-terminal pro-brain natriuretic peptide (NT-proBNP) were associated with higher CILP1 levels in ICM. However, there were no associations between CILP1 concentrations and left ventricular (LV) parameters in this group. In receiver-operating characteristic (ROC) analysis CILP1 was a good predictor of RVEF < 40% with an optimal cut-off value of 3545 pg/ml in ICM, whereas it was not predictive of LV ejection fraction (LVEF) < 40% (area under the curve [AUC] = 0.57) There was no significant difference between the ROC curves of CILP1 (AUC = 0.72) and NT-proBNP (AUC = 0.77) for RVEF < 40% (p = 0.42). In multivariable regression analysis, RVEF was the only independent predictor of elevated CILP1. CILP1 and LVEF were the only independent predictors of RVEF < 40% in ICM. Our analysis demonstrates the potential role of CILP1 as a novel cardiac biomarker of prognostically relevant RV dysfunction in patients with ICM.

Effects of renin-angiotensin system inhibitor type and dosage on survival after transcatheter aortic valve implantation.

AIMS: The objective of the study was to determine the effect of renin-angiotensin system inhibitors (RASI) on the survival of subgroups of patients with aortic stenosis after transcatheter aortic valve implantation (TAVI) and to assess the impact of types and dosages of RASI on outcomes. METHODS AND RESULTS: This single-centre, retrospective analysis included 2862 patients (n = 2227 with RASI and n = 635 without RASI) after successful TAVI. Propensity score matching established comparable patient populations (n = 625 per group). Survival was analysed by Kaplan-Meier curves and Cox regression and was corrected for baseline, procedural, and medical parameters. Self-reported adherence to RASI therapy 3 months after hospital discharge was 94%. Three-year all-cause mortality rates were 12.3% and 20.2% for patients with or without RASI, respectively (log-rank <0.001). In the matched study populations, mortality rates were 14.2% vs. 20.0% (log-rank <0.03). RASI was particularly beneficial in patients with ejection fraction <40% [adjusted hazard ratio (HR) and 95% confidence interval 0.50 (0.29-0.87)], EuroScore II ≥4% [HR 0.47 (0.35-0.65)], or low-flow, low-gradient aortic stenosis [HR 0.53 (0.31-0.93)] who were also on beta-blockers and statins. An association between discharge dosage and survival was observed, with HR 0.75 (0.58-0.96) and 0.57 (0.44-0.72) for patients on <50% and ≥50% target dose, respectively. Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) reduced mortality rates similarly (13.9% vs. 9.8%, log-rank 0.103). CONCLUSIONS: The beneficial association between RASI after TAVI and improved survival during follow-up is particularly evident in high-risk patients and may be dose dependent. No superiority was noted in the effectiveness of ACEI or ARB.

Access Route and Clinical Outcomes After Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome Undergoing Invasive Treatment Strategy.

BACKGROUND: Whether the access site influences the comparative efficacy and safety of ticagrelor and prasugrel in patients with acute coronary syndrome (ACS) undergoing invasive treatment strategy remains unstudied. METHODS: This post-hoc analysis included ACS patients undergoing invasive treatment via radial or femoral access and randomized to either ticagrelor or prasugrel in the ISAR-REACT 5 trial. The primary efficacy endpoint was the composite of death, myocardial infarction (MI) or stroke, safety endpoint was BARC 3 to 5 bleeding. Outcomes were assessed out to 12 months after randomization. RESULTS: Out of 4018 patients, 3984 underwent invasive treatment via radial or femoral access. 1479 had coronary angiography via radial access (ticagrelor, N = 748; prasugrel, N = 731) and 2505 via femoral access (ticagrelor, N = 1245; prasugrel, N = 1260). There was no interaction between access route and assignment to either ticagrelor or prasugrel regarding the primary efficacy or safety endpoints (P for interaction≥0.616). In the radial group, the primary efficacy endpoint (7.6% versus 5.8%, HR: 1.32 [0.88-1.97], P = 0.151) and the safety endpoint (4.3% versus 3.0%, HR: 1.36, [0.73-1.31], P = 0.300) were not statistically different in patients receiving either ticagrelor or prasugrel. In the femoral group, the primary efficacy endpoint occurred more frequently in patients assigned to ticagrelor as compared to prasugrel (10.3% versus 7.3%, HR: 1.44 [1.10-1.88], P = 0.006) without significant difference in terms of safety endpoint (6.4% versus 5.8%, HR: 1.14, [0.81-1.60], P = 0.470). CONCLUSIONS: In patients with ACS undergoing an invasive treatment strategy, the access route does not influence the comparative efficacy and safety of ticagrelor and prasugrel. CLINICAL TRIAL REGISTRATION: NCT01944800.

Safety and efficacy of different P2Y12 inhibitors in patients with acute coronary syndromes stratified by the PRAISE risk score: a multicentre study.

AIMS: To establish the safety and efficacy of different dual antiplatelet therapy (DAPT) combinations in patients with acute coronary syndrome (ACS) according to their baseline ischaemic and bleeding risk estimated with a machine learning derived model [machine learning-based prediction of adverse events following an acute coronary syndrome (PRAISE) score]. METHODS AND RESULTS: Incidences of death, re-acute myocardial infarction (re-AMI), and Bleeding Academic Research Consortium 3-5 bleeding with aspirin plus different P2Y12 inhibitors (clopidogrel or potent P2Y12 inhibitors: ticagrelor or prasugrel) were appraised among patients of the PRAISE data set grouped in four subcohorts: low-to-moderate ischaemic and bleeding risk; low-to-moderate ischaemic risk and high bleeding risk; high ischaemic risk and low-to-moderate bleeding risk; and high ischaemic and bleeding risk. Hazard ratios (HRs) for the outcome measures were derived with inverse probability of treatment weighting adjustment. Among patients with low-to-moderate bleeding risk, clopidogrel was associated with higher rates of re-AMI in those at low-to-moderate ischaemic risk [HR 1.69, 95% confidence interval (CI) 1.16-2.51; P = 0.006] and increased risk of death (HR 3.2, 1.45-4.21; P = 0.003) and re-AMI (HR 2.23, 1.45-3.41; P < 0.001) in those at high ischaemic risk compared with prasugrel or ticagrelor, without a difference in the risk of major bleeding. Among patients with high bleeding risk, clopidogrel showed comparable risk of death, re-AMI, and major bleeding vs. potent P2Y12 inhibitors, regardless of the baseline ischaemic risk. CONCLUSION: Among ACS patients with non-high risk of bleeding, the use of potent P2Y12 inhibitors is associated with a lower risk of death and recurrent ischaemic events, without bleeding excess. Patients deemed at high bleeding risk may instead be safely addressed to a less intensive DAPT strategy with clopidogrel.