Mechanisms and Definitions of Periprocedural Myocardial Infarction in the Era of Modern Revascularization.

One of the most frequent complications following coronary revascularization is cardiac myonecrosis characterized by an elevation of cardiac biomarkers, particularly with the implementation of high-sensitivity cardiac troponin. In the last decades, various definitions of periprocedural myocardial injury and infarction have been proposed, based on different cardiac biomarkers, various thresholds, and the need for additional ischemic features. In this review, we aim at providing insights on the mechanisms involved in periprocedural myocardial injury and infarction following percutaneous coronary intervention or coronary artery bypass grafting, the strengths and limitations of the available definitions and their clinical implications. We also provide an updated description of preventive strategies that have been evaluated in randomized controlled trials to avoid these complications as well as patient-level and lesion-level risk factors to better anticipate and rebalance the indication for coronary revascularization and plan adequate post-procedure monitoring.

Changes in absolute coronary flow and microvascular resistance during exercise in patients with ANOCA.

BACKGROUND: Whether saline-induced hyperaemia captures exercise-induced coronary flow regulation remains unknown. AIMS: Through this study, we aimed to describe absolute coronary flow (Q) and microvascular resistance (Rµ) adaptation during exercise in participants with angina with non-obstructive coronary artery disease (ANOCA) and to explore the correlations between saline- and exercise-derived coronary flow reserve (CFR) and microvascular resistance reserve (MRR). METHODS: Rµ, Q, CFR and MRR were assessed in the left anterior descending artery using continuous thermodilution with saline infusion at 10 mL/min (rest), 20 mL/min (hyperaemia) and finally at a 10 mL/min infusion rate during stress testing with a dedicated supine cycling ergometer. An incremental workload of 30 watts every two minutes was applied. A saline-derived CFR (CFRsaline) cutoff <2.5 was used to identify coronary microvascular dysfunction (CMD). RESULTS: CFRsaline-defined CMD was observed in 53.3% of the participants (16/30). While cycling, these patients less of an ability to increase Q (7 [interquartile range [IQR] 30.5-103.0] vs 21 [IQR 5.8-45.0] mL/min/30 watts; p=0.01) due to a smaller decrease of Rµ (109 {IQR 32-286} vs 202 [IQR 102-379] Wood units [WU]/30 watts; p<0.01) as compared with the group with normal CFRsaline. In the overall population, CFRsaline and exercise-derived CFR (CFRexercise) were 2.70±0.90 and 2.85±1.54, respectively, with an agreement classification of 83.3%. A good correlation between saline and exercise techniques for both CFR (r=0.73; p<0.0001) and MRR (r=0.76; p<0.0001) was observed. Among participants with normal CFRsaline, 28.7% (4/14) had an impaired CFRexercise <2.5 at the peak of exercise due to a moderate and late decrease of Rµ. CONCLUSIONS: Saline-induced hyperaemia provided a valid surrogate for exercise physiology independently of the absolute level of CFR and MRR, although exercise provided more granularity to evaluate adaptation among participants with exercise-related CMD.

Ten-year trends in characteristics, management and outcomes of patients admitted with cardiogenic shock in the ACTION-SHOCK cohort.

BACKGROUND: The ACTION-SHOCK registry offers a decade-long perspective on patients admitted with cardiogenic shock (CS). AIMS: To assess trends in the management and outcomes of patients with CS over 10 years. METHODS: Trends in the characteristics, management and outcomes of patients with CS admitted into the cardiac intensive care unit of Pitié-Salpêtrière hospital from 2011 to 2020 were analysed. Short-term outcomes included in-hospital mortality, heart transplantation or ventricular assist device. Long-term outcomes were all-cause death or readmission for acute heart failure at 1 year. RESULTS: Over a 10-year period, data from 700 patients with CS (median [interquartile range] age 61 [50-72] years; 73% of men) were analysed. The proportion of CS related to acute myocardial infarction decreased (from 45% in 2011-2012 to 27% in 2019-2020) while the proportions related to chronic coronary syndrome (18% to 23%) and non-ischaemic cardiomyopathies (37 to 51%) increased (P<0.01). The use of rescue extracorporeal membrane oxygenation remained stable (19 to 14%) and intra-aortic balloon pump use decreased (22% to 7%) (P<0.01). In-hospital mortality remained stable (27 to 29%) as did the proportions of patients discharged after transplantation (17 to 14%) or with a durable ventricular assist device (2 to 4%). Among patients discharged alive, death or readmission for acute heart failure at 1 year remained high (37 to 47%). CONCLUSION: CS remained associated with a poor prognosis over the last decade. There are significant unmet needs in the management strategies of patients with CS.

Ticagrelor vs Clopidogrel for Complex Percutaneous Coronary Intervention in Chronic Coronary Syndrome.

BACKGROUND: Whether ticagrelor in chronic coronary syndrome patients undergoing complex percutaneous coronary intervention (PCI) can prevent cardiovascular events is unknown. OBJECTIVES: The authors sought to evaluate outcomes of complex PCI and the efficacy of ticagrelor vs clopidogrel in stable patients randomized in the ALPHEUS (Assessment of Loading with the P2Y12 inhibitor ticagrelor or clopidogrel to Halt ischemic Events in patients Undergoing elective coronary Stenting) trial. METHODS: All PCI procedures were blindly reviewed and classified as complex if they had at least 1 of the following criteria: stent length >60 mm, 2-stent bifurcation, left main, bypass graft, chronic total occlusion, use of atherectomy or guiding catheter extensions, multiwire technique, multiple stents. The primary endpoint was a composite of type 4a or b myocardial infarction (MI) and major myocardial injury during the 48 hours after PCI. We compared the event rates according to the presence or not of complex PCI criteria and evaluated the interaction with ticagrelor or clopidogrel. RESULTS: Among the 1,866 patients randomized, 910 PCI (48.3%) were classified as complex PCI. The primary endpoint was more frequent in complex PCI (45.6% vs 26.6%; P < 0.001) driven by higher rates of type 4 MI and angiographic complications (12.2% vs 4.8 %; P < 0.001 and 19.3% vs 8.6%; P < 0.05, respectively). The composite of death, MI, and stroke at 48 hours (12.7% vs 5.1 %; P < 0.05) and at 30 days (13.4% vs 5.3%; P < 0.05) was more frequent in complex PCI. No interaction was found between PCI complexity and the randomized treatment for the primary endpoint (Pinteraction = 0.47) nor the secondary endpoints. CONCLUSIONS: In chronic coronary syndrome, patients undergoing a complex PCI have higher rates of periprocedural and cardiovascular events that are not reduced by ticagrelor as compared with clopidogrel.

Ticagrelor vs Clopidogrel in Clopidogrel-Naive Patients With Chronic Coronary Syndrome.

BACKGROUND: Whether ticagrelor may reduce periprocedural myocardial necrosis after elective percutaneous coronary intervention (PCI) in patients with and without chronic clopidogrel therapy is unclear. OBJECTIVES: This study sought to compare ticagrelor vs clopidogrel in patients with and without chronic clopidogrel therapy before undergoing elective PCI. METHODS: In this prespecified analysis of the ALPHEUS (Assessment of Loading With the P2Y12 Inhibitor Ticagrelor or Clopidogrel to Halt Ischemic Events in Patients Undergoing Elective Coronary Stenting) trial, patients were defined as clopidogrel(+) and clopidogrel(-) according to the presence and absence of clopidogrel treatment for ≥7 days before PCI, respectively. The primary endpoint was the composite of PCI-related myocardial infarction and major injury as defined by the third and fourth universal definition 48 hours after PCI. RESULTS: A total of 1,882 patients were included, 805 (42.7%) of whom were clopidogrel(+). These patients were older, had more comorbidities, and had more frequent features of complex PCI. The primary endpoint was less frequently present in clopidogrel(-) compared to clopidogrel(+) patients (32.8% vs 40.0%; OR: 0.73; 95% CI: 0.60-0.88), but no significant differences were reported for the risk of death, myocardial infarction, stroke, or transient ischemic attack at 48 hours or 30 days. Ticagrelor did not reduce periprocedural myocardial necrosis or the risk of adverse outcomes, and there was no significant interaction regarding the presence of chronic clopidogrel treatment. CONCLUSIONS: Clopidogrel-naive patients presented less periprocedural complications compared to clopidogrel(+) patients, a difference related to a lower risk profile and less complex PCI. The absence of clopidogrel at baseline did not affect the absence of a difference between ticagrelor and clopidogrel in terms of PCI-related complications supporting the use of clopidogrel as the standard of care in elective PCI in patients with or without chronic clopidogrel treatment.

Restrictive vs Liberal Blood Transfusions for Patients With Acute Myocardial Infarction and Anemia by Heart Failure Status: An RCT Subgroup Analysis.

BACKGROUND: Red blood cell transfusion can cause fluid overload. We evaluated the interaction between heart failure (HF) at baseline and transfusion strategy on outcomes in acute myocardial infarction (AMI). METHODS: We used data from the randomized REALITY trial. HF was defined as history of HF or Killip class > 1 at randomization. Primary outcome was major adverse cardiovascular events (MACE): composite of all-cause death, nonrecurrent AMI, stroke, or emergency revascularization prompted by ischemia at 30 days. RESULTS: Among 658 randomized patients, 311 (47.3%) had HF. Patients with HF had higher rates of MACE at 30 days and 1 year and higher rates of nonfatal new-onset HF. There was no interaction between HF and effect of randomized assignment on the primary outcome or nonfatal new-onset HF. A liberal transfusion strategy was associated with increased all-cause death at 30 days and at 1 year in patients with HF (Pinteraction = 0.009 and P = 0.049, respectively). The main numerical difference in cause of death between restrictive and liberal strategies was death by HF at 30 days (4 vs 11). CONCLUSIONS: HF is frequent in patients with AMI and anemia and is associated with higher risk of MACE (including all-cause death) and nonfatal new-onset HF. Although there was no interaction of HF with effect of transfusion strategy on MACE, a liberal transfusion strategy was associated with higher all-cause death that appears driven by a higher risk of early death caused by HF. CLINICAL TRIAL REGISTRATION: NCT02648113.

Flecainide to prevent atrial arrhythmia after patent foramen ovale closure, Rationale and design of the randomized AFLOAT study.

INTRODUCTION: Atrial arrhythmia is the most common complication of patent foramen ovale (PFO) closure. The real incidence of post-PFO closure atrial arrhytmia and whether this complication can be prevented is unknown. METHODS/DESIGN: The Assessment of Flecainide to Lower the PFO closure risk of Atrial fibrillation or Tachycardia (AFLOAT) trial is a prospective, national, multicentre, randomized, open-label, superiority trial with a blind evaluation of all the endpoints (PROBE design). A total of 186 patients are randomized in a 1:1:1 ratio immediately after PFO closure to receive Flecainide (150 mg per day in a single sustained-release (SR) dose) for 6 months (Group 1), Flecainide (150 mg per day in a single SR dose) for 3 months (Group 2), or no additional treatment (standard of care) for 6 months (Group 3). The primary endpoint is the percentage of patients with at least one episode of symptomatic or asymptomatic atrial arrhythmia episode (≥30 s) recorded within 3 months after PFO closure on long-term monitoring with an insertable cardiac monitor. Whether 3 months of treatment is sufficient compared to 6 months will be analysed as a secondary objective of the study. CONCLUSION: AFLOAT is the first trial to test the hypothesis that a short treatment with oral Flecainide can prevent the new-onset of atrial arrhythmia after PFO closure. CLINICAL TRIAL REGISTRATION: NCT05213104 (clinicaltrials.gov).

SYNERGY-Everolimus-Eluting Stent With a Bioabsorbable Polymer in ST-Elevation Myocardial Infarction: CLEAR SYNERGY OASIS-9 Registry.

Our objective was to evaluate the clinical effectiveness of the SYNERGY stent (Boston Scientific Corporation, Marlborough, Massachusetts) in patients with ST-elevation myocardial infarction (STEMI). The only drug-eluting stent approved for treatment of STEMI by the Food and Drug Administration is the Taxus stent (Boston Scientific) which is no longer commercially available, so further data are needed. The CLEAR (Colchicine and spironolactone in patients with myocardial infarction) SYNERGY stent registry was embedded into a larger randomized trial of patients with STEMI (n = 7,000), comparing colchicine versus placebo and spironolactone versus placebo. The primary outcome for the SYNERGY stent registry is major adverse cardiac events (MACE) as defined by cardiovascular death, recurrent MI, or unplanned ischemia-driven target vessel revascularization within 12 months. We estimated a MACE rate of 6.3% at 12 months after primary percutaneous coronary intervention for STEMI based on the Thrombectomy vs percutaneous coronary intervention alone in STEMI (TOTAL) trial. Success was defined as upper bound of confidence interval (CI) to be less than the performance goal of 9.45%. Overall, 733 patients were enrolled from 8 countries with a mean age 60 years, 19.4% diabetes mellitus, 41.3% anterior MI, and median door-to-balloon time of 72 minutes. The MACE rate was 4.8% (95% CI 3.2 to 6.3%) at 12 months which met the success criteria against performance goal of 9.45%. The rates of cardiovascular death, recurrent MI, or target vessel revascularization were 2.7%, 1.9%, 1.0%, respectively. The rates of acute definite stent thrombosis were 0.3%, subacute 0.4%, late 0.4%, and cumulative stent thrombosis of 1.1% at 12 months. In conclusion, the SYNERGY stent in STEMI performed well and was successful compared with the performance goal based on previous trials.

Rationale and design of the FRENch CoHort of myocardial Infarction Evaluation (FRENCHIE) study.

BACKGROUND: Despite major advances in prevention and treatment, cardiovascular diseases - particularly acute myocardial infarction - remain a leading cause of death worldwide and in France. Collecting contemporary data about the characteristics, management and outcomes of patients with acute myocardial infarction in France is important. AIMS: The main objectives are to describe baseline characteristics, contemporary management, in-hospital and long-term outcomes of patients with acute myocardial infarction hospitalized in tertiary care centres in France; secondary objectives are to investigate determinants of prognosis (including periodontal disease and sleep-disordered breathing), to identify gaps between evidence-based recommendations and management and to assess medical care costs for the index hospitalization and during the follow-up period. METHODS: FRENCHIE (FRENch CoHort of myocardial Infarction Evaluation) is an ongoing prospective multicentre observational study (ClinicalTrials.gov Identifier: NCT04050956) enrolling more than 19,000 patients hospitalized for acute myocardial infarction with onset of symptoms within 48hours in 35 participating centres in France since March 2019. Main exclusion criteria are age<18 years, lack of health coverage and procedure-related myocardial infarction (types 4a and 5). Detailed information was collected prospectively, starting at admission, including demographic data, risk factors, medical history and treatments, initial management, with prehospital care pathways and medication doses, and outcomes until hospital discharge. The follow-up period (up to 20 years for each patient) is ensured by linking with the French national health database (Système national des données de santé), and includes information on death, hospital admissions, major clinical events, healthcare consumption (including drug reimbursement) and total healthcare costs. FRENCHIE is also used as a platform for cohort-nested studies - currently three randomized trials and two observational studies. CONCLUSIONS: This nationwide large contemporary cohort with very long-term follow-up will improve knowledge about acute myocardial infarction management and outcomes in France, and provide a useful platform for nested studies and trials.

Three-Year Outcomes With Fractional Flow Reserve-Guided or Angiography-Guided Multivessel Percutaneous Coronary Intervention for Myocardial Infarction.

BACKGROUND: In patients with multivessel disease with successful primary percutaneous coronary intervention for ST-segment-elevation myocardial infarction, the FLOWER-MI trial (Flow Evaluation to Guide Revascularization in Multivessel ST-Elevation Myocardial Infarction) showed that a fractional flow reserve (FFR)-guided strategy was not superior to an angiography-guided strategy for treatment of noninfarct-related artery lesions regarding the 1-year risk of death from any cause, myocardial infarction, or unplanned hospitalization leading to urgent revascularization. The extension phase of the trial was planned using the same primary outcome to determine whether a difference in outcomes would be observed with a longer follow-up. METHODS: In this multicenter trial, we randomly assigned patients with ST-segment-elevation myocardial infarction and multivessel disease with successful percutaneous coronary intervention of the infarct-related artery to receive complete revascularization guided by either FFR (n=586) or angiography (n=577). RESULTS: After 3 years, a primary outcome event occurred in 52 of 498 patients (9.40%) in the FFR-guided group and in 44 of 502 patients (8.17%) in the angiography-guided group (hazard ratio, 1.19 [95% CI, 0.79-1.77]; P=0.4). Death occurred in 22 patients (4.00%) in the FFR-guided group and in 23 (4.32%) in the angiography-guided group (hazard ratio, 0.96 [95% CI, 0.53-1.71]); nonfatal myocardial infarction in 23 (4.13%) and 14 (2.56%), respectively (hazard ratio, 1.63 [95% CI, 0.84-3.16]); and unplanned hospitalization leading to urgent revascularization in 21 (3.83%) and 18 (3.36%; hazard ratio, 1.15 [95% CI, 0.61-2.16]), respectively. CONCLUSIONS: Although event rates in the trial were lower than expected, in patients with ST-segment-elevation myocardial infarction undergoing complete revascularization, an FFR-guided strategy did not have a significant benefit over an angiography-guided strategy with respect to the risk of death, myocardial infarction, or urgent revascularization up to 3 years. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02943954.