Etienne Puymirat

Prognostic Value of Fractional Flow Reserve: Linking Physiologic Severity to Clinical Outcomes

BACKGROUNDnFractional flow reserve (FFR) has become an established tool for guiding treatment, but its graded relationship to clinical outcomes as modulated by medical therapy versus revascularization remains unclear.nnnOBJECTIVESnThe study hypothesized that FFR displays a continuous relationship between its numeric value and prognosis, such that lower FFR values confer a higher risk and therefore receive larger absolute benefits from revascularization.nnnMETHODSnMeta-analysis of study- and patient-level data investigated prognosis after FFR measurement. An interaction term between FFR and revascularization status allowed for an outcomes-based threshold.nnnRESULTSnA total of 9,173 (study-level) and 6,961 (patient-level) lesions were included with a median follow-up of 16 and 14 months, respectively. Clinical events increased as FFR decreased, and revascularization showed larger net benefit for lower baseline FFR values. Outcomes-derived FFR thresholds generally occurred around the range 0.75 to 0.80, although limited due to confounding by indication. FFR measured immediately after stenting also showed an inverse relationship with prognosis (hazard ratio: 0.86, 95% confidence interval: 0.80 to 0.93; p < 0.001). An FFR-assisted strategy led to revascularization roughly half as often as an anatomy-based strategy, but with 20% fewer adverse events and 10% better angina relief.nnnCONCLUSIONSnFFR demonstrates a continuous and independent relationship with subsequent outcomes, modulated by medical therapy versus revascularization. Lesions with lower FFR values receive larger absolute benefits from revascularization. Measurement of FFR immediately after stenting also shows an inverse gradient of risk, likely from residual diffuse disease. An FFR-guided revascularization strategy significantly reduces events and increases freedom from angina with fewer procedures than an anatomy-based strategy.

Should patients with acute coronary disease be stratified for management according to their risk? Derivation, external validation and outcomes using the updated GRACE risk score

Objectives Risk scores are recommended in guidelines to facilitate the management of patients who present with acute coronary syndromes (ACS). Internationally, such scores are not systematically used because they are not easy to apply and some risk indicators are not available at first presentation. We aimed to derive and externally validate a more accurate version of the Global Registry of Acute Coronary Events (GRACE) risk score for predicting the risk of death or death/myocardial infarction (MI) both acutely and over the longer term. The risk score was designed to be suitable for acute and emergency clinical settings and usable in electronic devices. Design and setting The GRACE risk score (2.0) was derived in 32u2005037 patients from the GRACE registry (14 countries, 94 hospitals) and validated externally in the French registry of Acute ST-elevation and non-ST-elevation MI (FAST-MI) 2005. Participants Patients presenting with ST-elevation and non-ST elevation ACS and with long-term outcomes. Outcome measures The GRACE Score (2.0) predicts the risk of short-term and long-term mortality, and death/MI, overall and in hospital survivors. Results For key independent risk predictors of death (1u2005year), non-linear associations (vs linear) were found for age (p<0.0005), systolic blood pressure (p<0.0001), pulse (p<0.0001) and creatinine (p<0.0001). By employing non-linear algorithms, there was improved model discrimination, validated externally. Using the FAST-MI 2005 cohort, the c indices for death exceeded 0.82 for the overall population at 1u2005year and also at 3u2005years. Discrimination for death or MI was slightly lower than for death alone (c=0.78). Similar results were obtained for hospital survivors, and with substitutions for creatinine and Killip class, the model performed nearly as well. Conclusions The updated GRACE risk score has better discrimination and is easier to use than the previous score based on linear associations. GRACE Risk (2.0) performed equally well acutely and over the longer term and can be used in a variety of clinical settings to aid management decisions.

Five-Year Survival in Patients With ST-Segment–Elevation Myocardial Infarction According to Modalities of Reperfusion Therapy The French Registry on Acute ST-Elevation and Non–ST-Elevation Myocardial Infarction (FAST-MI) 2005 Cohort

Background— Although primary percutaneous coronary intervention (pPCI) is the preferred reperfusion method for ST-segment–elevation myocardial infarction, it remains difficult to implement in many areas, and fibrinolytic therapy is still widely used. Methods and Results— We assessed 5-year mortality in patients with ST-segment–elevation myocardial infarction from the French Registry of Acute ST-Elevation or Non-ST Elevation Myocardial Infarction (FAST-MI) 2005 according to use and type of reperfusion therapy. Of 1492 patients with ST-segment–elevation myocardial infarction with a first call ⩽12 hours from onset, 447 (30%) received fibrinolysis (66% prehospital; 97% with subsequent angiography, 84% with subsequent PCI), 583 (39%) had pPCI, and 462 (31%) received no reperfusion. Crude 5-year survival was 88% for the fibrinolytic-based strategy, 83% for pPCI, and 59% for no reperfusion. Adjusted hazard ratios for 5-year death were 0.73 (95% confidence interval, 0.50–1.06) for fibrinolysis versus pPCI, 0.57 (95% confidence interval, 0.36–0.88) for prehospital fibrinolysis versus pPCI, and 0.63 (95% confidence interval, 0.34–0.91) for fibrinolysis versus pPCI beyond 90 minutes of call in patients having called ⩽180 minutes from onset. In propensity score–matched populations, however, survival rates were not significantly different for fibrinolysis and pPCI, both in the whole population (88% lysis, 85% pPCI) and in the population seen early (87% fibrinolysis, 85% pPCI beyond 90 minutes from call). Conclusions— In a real-world setting, on a nationwide scale, a pharmaco-invasive strategy constitutes a valid alternative to pPCI, with 5-year survival at least equivalent to that of the reference reperfusion method. Clinical Trial Registration— URL: www.clinicaltrials.gov. Unique identifier: NCT00673036.

Use of Invasive Strategy in Non–ST-Segment Elevation Myocardial Infarction Is a Major Determinant of Improved Long-Term Survival: FAST-MI (French Registry of Acute Coronary Syndrome)

OBJECTIVESnThis study sought to assess the impact of invasive strategy (IS) versus a conservative strategy (CS) on in-hospital complications and 3-year outcomes in patients with non-ST-segment elevation myocardial infarction (NSTEMI) from the FAST-MI (French Registry of Acute Coronary Syndrome).nnnBACKGROUNDnResults from randomized trials comparing IS and CS in patients with NSTEMI are conflicting.nnnMETHODSnOf the 3,670 patients in FAST-MI, which included patients with acute myocardial infarction (within 48 h) over a 1-month period in France at the end of 2005, 1,645 presented with NSTEMI.nnnRESULTSnOf the 1,645 patients analyzed, 80% had an IS. Patients in the IS group were younger (67 ± 12 years vs. 80 ± 11 years), less often women (29% vs. 51%), and had a lower GRACE (Global Registry of Acute Coronary Events) risk score (137 ± 36 vs. 178 ± 34) than patients treated with CS. In-hospital mortality and blood transfusions were significantly more frequent in patients with CS versus IS (13.1% vs. 2.0%, 9.1% vs. 4.6%). Use of IS was associated with a significant reduction in 3-year mortality and cardiovascular death (17% vs. 60%, adjusted hazard ratio [HR]: 0.44, 95% confidence interval [CI]: 0.35 to 0.55 and 8% vs. 36%, adjusted HR: 0.37, 95% CI: 0.27 to 0.50). After propensity score matching (181 patients per group), 3-year survival was significantly higher in patients treated with IS.nnnCONCLUSIONSnIn a real-world setting of patients admitted with NSTEMI, the use of IS during the initial hospital stay is an independent predictor of improved 3-year survival, regardless of age. (French Registry of Acute Coronary Syndrome [FAST-MI]; NCT00673036).

Euro Heart Survey 2009 Snapshot: Regional variations in presentation and management of patients with AMI in 47 countries

Aims: Detailed data on patients admitted for acute myocardial infarction (AMI) on a European-wide basis are lacking. The Euro Heart Survey 2009 Snapshot was designed to assess characteristics, management, and hospital outcomes of AMI patients throughout European Society of Cardiology (ESC) member countries in a contemporary ‘real-world’ setting, using a methodology designed to improve the representativeness of the survey. Methods: Member countries of the ESC were invited to participate in a 1-week survey of all patients admitted for documented AMI in December 2009. Data on baseline characteristics, type of AMI, management, and complications were recorded using a dedicated electronic form. In addition, we used data collected during the same time period in national registries in Sweden, England, and Wales. Data were centralized at the European Heart House. Results: Overall, 4236 patients (mean age 66±13 years; 31% women) were included in the study in 47 countries. Sixty per cent of patients had ST-segment elevation myocardial infarction, with 50% having primary percutaneous coronary intervention and 21% fibrinolysis. Aspirin and thienopyridines were used in >90%. Unfractionated and low-molecular-weight heparins were the most commonly used anticoagulants. Statins, beta-blockers, and angiotensin-converting enzyme inhibitors were used in >80% of the patients. In-hospital mortality was 6.2%. Regional differences were observed, both in terms of population characteristics, management, and outcomes. Conclusions: In-hospital mortality of patients admitted for AMI in Europe is low. Although regional variations exist in their presentation and management, differences are limited and have only moderate impact on early outcomes.

β blockers and mortality after myocardial infarction in patients without heart failure: multicentre prospective cohort study

Objective To assess the association between early and prolonged β blocker treatment and mortality after acute myocardial infarction. Design Multicentre prospective cohort study. Setting Nationwide French registry of Acute ST- and non-ST-elevation Myocardial Infarction (FAST-MI) (at 223 centres) at the end of 2005. Participants 2679 consecutive patients with acute myocardial infarction and without heart failure or left ventricular dysfunction. Main outcome measures Mortality was assessed at 30 days in relation to early use of β blockers (≤48 hours of admission), at one year in relation to discharge prescription, and at five years in relation to one year use. Results β blockers were used early in 77% (2050/2679) of patients, were prescribed at discharge in 80% (1783/2217), and were still being used in 89% (1230/1383) of those alive at one year. Thirty day mortality was lower in patients taking early β blockers (adjusted hazard ratio 0.46, 95% confidence interval 0.26 to 0.82), whereas the hazard ratio for one year mortality associated with β blockers at discharge was 0.77 (0.46 to 1.30). Persistence of β blockers at one year was not associated with lower five year mortality (hazard ratio 1.19, 0.65 to 2.18). In contrast, five year mortality was lower in patients continuing statins at one year (hazard ratio 0.42, 0.25 to 0.72) compared with those discontinuing statins. Propensity score and sensitivity analyses showed consistent results. Conclusions Early β blocker use was associated with reduced 30 day mortality in patients with acute myocardial infarction, and discontinuation of β blockers at one year was not associated with higher five year mortality. These findings question the utility of prolonged β blocker treatment after acute myocardial infarction in patients without heart failure or left ventricular dysfunction. Trial registration Clinical trials NCT00673036.

A Pre-Hospital Extracorporeal Cardio Pulmonary Resuscitation (ECPR) strategy for treatment of refractory out hospital cardiac arrest: an observational study and propensity analysis.

BACKGROUNDnOut of hospital cardiac arrest (OHCA) mortality rates remain very high with poor neurological outcome in survivors. Extracorporeal cardiopulmonary resuscitation (ECPR) is one of the treatments of refractory OHCA. This study used data from the mobile intensive care unit (MOICU) as part of the emergency medical system of Paris, and included all consecutive patients treated with ECPR (including pre-hospital ECPR) from 2011 to 2015 for the treatment of refractory OHCA, comparing two historical ECPR management strategies.nnnMETHODSnWe consecutively included refractory OHCA patients. In Period 1, ECPR was indicated in selected patients after 30min of advanced life support; in- or pre-hospital implementation depended on estimated transportation time and ECPR team availability. In Period 2, patient care relied on early ECPR initiation after 20min of resuscitation, stringent patient selection, epinephrine dose limitation and deployment of ECPR team with initial response team. Primary outcome was survival with good neurological function Cerebral Performance Category score (CPC score) 1 and 2 at ICU discharge or day 28.nnnFINDINGSnA total of 156 patients were included. (114 in Period 1 and 42 in Period 2). Baseline characteristics were similar. Mean low-flow duration was shorter by 20min (p<0.001) in Period 2. Survival was significantly higher in Period 2: 29% vs 8% (P<0.001), as confirmed by the multivariate analysis and propensity score. When combining stringent patient selection with an aggressive strategy, the survival rate increased to 38%. Pre-hospital ECPR implementation in itself was not an independent predictor of improved survival, but it was part of the strategy in Period 2.nnnINTERPRETATIONnOur data suggest that ECPR in specific settings in the management of refractory OHCA is feasible and can lead to a significant increase in neurological intact survivors. These data, however, need to be confirmed by a large RCT.

Acute Myocardial Infarction: Changes in Patient Characteristics, Management, and 6-Month Outcomes Over a Period of 20 Years in the FAST-MI Program (French Registry of Acute ST-Elevation or Non-ST-elevation Myocardial Infarction) 1995 to 2015

Background: ST-segment–elevation myocardial infarction (STEMI) and non–ST-segment–elevation myocardial infarction (NSTEMI) management has evolved considerably over the past 2 decades. Little information on mortality trends in the most recent years is available. We assessed trends in characteristics, treatments, and outcomes for acute myocardial infarction in France between 1995 and 2015. Methods: We used data from 5 one-month registries, conducted 5 years apart, from 1995 to 2015, including 14u2009423 patients with acute myocardial infarction (59% STEMI) admitted to cardiac intensive care units in metropolitan France. Results: From 1995 to 2015, mean age decreased from 66±14 to 63±14 years in patients with STEMI; it remained stable (68±14 years) in patients with NSTEMI, whereas diabetes mellitus, obesity, and hypertension increased. At the acute stage, intended primary percutaneous coronary intervention increased from 12% (1995) to 76% (2015) in patients with STEMI. In patients with NSTEMI, percutaneous coronary intervention ⩽72 hours from admission increased from 9% (1995) to 60% (2015). Six-month mortality consistently decreased in patients with STEMI from 17.2% in 1995 to 6.9% in 2010 and 5.3% in 2015; it decreased from 17.2% to 6.9% in 2010 and 6.3% in 2015 in patients with NSTEMI. Mortality still decreased after 2010 in patients with STEMI without reperfusion therapy, whereas no further mortality gain was found in patients with STEMI with reperfusion therapy or in patients with NSTEMI, whether or not they were treated with percutaneous coronary intervention. Conclusions: Over the past 20 years, 6-month mortality after acute myocardial infarction has decreased considerably for patients with STEMI and NSTEMI. Mortality figures continued to decline in patients with STEMI until 2015, whereas mortality in patients with NSTEMI appears stable since 2010.

Épidémiologie des syndromes coronaires aigus en France et en Europe

Resume L’incidence annuelle des hospitalisations pour infarctus en France peut etre estimee entre 60 000 et 65 000 cas ; en prenant en compte les angors instables, on peut ainsi evaluer a 80 000 a 100 000 le nombre de cas de syndromes coronaires aigus, auxquels il convient d’ajouter les cas de mort subite extra-hospitaliere d’origine ischemique. Au niveau europeen, on note un gradient nord-sud et surtout est-ouest, avec une incidence d’evenements coronaires nettement plus elevee dans les pays d’Europe centrale et de l’est. L’incidence des infarctus semble cependant en nette diminution, et des evaluations recentes nord-americaines montrent un recul de plus de 50 % en 10 ans des infarctus avec sus-decalage de ST. En parallele, la prise en charge des syndromes coronaires aigus s’est amelioree et la mortalite au stade aigu a considerablement baisse. L’ensemble explique la baisse spectaculaire de la mortalite cardio-vasculaire, observee en France comme dans la plupart des pays europeens au cours des 25 dernieres annees. Toutefois, les syndromes coronaires aigus restent des accidents graves, avec une morbi-mortalite a moyen terme elevee, et qui necessite la poursuite des efforts therapeutiques dans ce domaine.

Fractional flow reserve: concepts, applications and use in France in 2010.

Fractional flow reserve (FFR) is emerging as a useful clinical tool for assessing the functional significance of coronary atherosclerosis. As opposed to anatomical approaches, physiological measurements (particularly pressure-derived FFR) assess the function of the coronary circulation and offer the possibility of ad hoc treatment. The use of FFR is still limited in France because there is no financial support. The present review will focus on coronary pressure-derived FFR.