Stephane Fournier

Circadian variations of ischemic burden among patients with myocardial infarction undergoing primary percutaneous coronary intervention

BACKGROUND Several parameters of cardiovascular physiology and pathophysiology exhibit circadian rhythms. Recently, a relation between infarct size and the time of day at which it occurs has been suggested in experimental models of myocardial infarction. The aim of this study is to investigate whether circadian rhythms could cause differences in ischemic burden in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). METHODS In 353 consecutive patients with STEMI treated by PPCI, time of symptom onset, peak creatine kinase (CK), and follow-up at 30 days were obtained. We divided 24 hours into 4 time groups based on time of symptom onset (00:00-05:59, 06:00-11:59, 12:00-17:59, and 18:00-23:59). RESULTS There was no difference between the groups regarding baseline patients and managements characteristics. At multivariable analysis, there was a statistically significant difference between peak CK levels among patients with symptom onset between 00:00 and 05:59 when compared with peak CK levels of patients with symptom onset in any other time group (mean increase 38.4%, P < .05). Thirty-day mortality for STEMI patients with symptom onset occurring between 00:00 and 05:59 was significantly higher than any other time group (P < .05). CONCLUSION This study demonstrates an independent correlation between the infarct size of STEMI patients treated by PPCI and the time of the day at which symptoms occurred. These results suggest that time of the day should be a critical issue to look at when assessing prognosis of patients with myocardial infarction.

Myocardial infarct size and mortality depend on the time of day-a large multicenter study.

Background Different studies have shown circadian variation of ischemic burden among patients with ST-Elevation Myocardial Infarction (STEMI), but with controversial results. The aim of this study was to analyze circadian variation of myocardial infarction size and in-hospital mortality in a large multicenter registry. Methods This retrospective, registry-based study was based on data from AMIS Plus, a large multicenter Swiss registry of patients who suffered myocardial infarction between 1999 and 2013. Peak creatine kinase (CK) was used as a proxy measure for myocardial infarction size. Associations between peak CK, in-hospital mortality, and the time of day at symptom onset were modelled using polynomial-harmonic regression methods. Results 6,223 STEMI patients were admitted to 82 acute-care hospitals in Switzerland and treated with primary angioplasty within six hours of symptom onset. Only the 24-hour harmonic was significantly associated with peak CK (p = 0.0001). The maximum average peak CK value (2,315 U/L) was for patients with symptom onset at 23:00, whereas the minimum average (2,017 U/L) was for onset at 11:00. The amplitude of variation was 298 U/L. In addition, no correlation was observed between ischemic time and circadian peak CK variation. Of the 6,223 patients, 223 (3.58%) died during index hospitalization. Remarkably, only the 24-hour harmonic was significantly associated with in-hospital mortality. The risk of death from STEMI was highest for patients with symptom onset at 00:00 and lowest for those with onset at 12:00. Discussion As a part of this first large study of STEMI patients treated with primary angioplasty in Swiss hospitals, investigations confirmed a circadian pattern to both peak CK and in-hospital mortality which were independent of total ischemic time. Accordingly, this study proposes that symptom onset time be incorporated as a prognosis factor in patients with myocardial infarction.

Five-Year Outcomes with PCI Guided by Fractional Flow Reserve

BACKGROUND We hypothesized that fractional flow reserve (FFR)–guided percutaneous coronary intervention (PCI) would be superior to medical therapy as initial treatment in patients with stable coronary artery disease. METHODS Among 1220 patients with angiographically significant stenoses, those in whom at least one stenosis was hemodynamically significant (FFR, ≤0.80) were randomly assigned to FFR‐guided PCI plus medical therapy or to medical therapy alone. Patients in whom all stenoses had an FFR of more than 0.80 received medical therapy and were entered into a registry. The primary end point was a composite of death, myocardial infarction, or urgent revascularization. RESULTS A total of 888 patients underwent randomization (447 patients in the PCI group and 441 in the medical‐therapy group). At 5 years, the rate of the primary end point was lower in the PCI group than in the medical‐therapy group (13.9% vs. 27.0%; hazard ratio, 0.46; 95% confidence interval [CI], 0.34 to 0.63; P<0.001). The difference was driven by urgent revascularizations, which occurred in 6.3% of the patients in the PCI group as compared with 21.1% of those in the medical‐therapy group (hazard ratio, 0.27; 95% CI, 0.18 to 0.41). There were no significant differences between the PCI group and the medical‐therapy group in the rates of death (5.1% and 5.2%, respectively; hazard ratio, 0.98; 95% CI, 0.55 to 1.75) or myocardial infarction (8.1% and 12.0%; hazard ratio, 0.66; 95% CI, 0.43 to 1.00). There was no significant difference in the rate of the primary end point between the PCI group and the registry cohort (13.9% and 15.7%, respectively; hazard ratio, 0.88; 95% CI, 0.55 to 1.39). Relief from angina was more pronounced after PCI than after medical therapy. CONCLUSIONS In patients with stable coronary artery disease, an initial FFR‐guided PCI strategy was associated with a significantly lower rate of the primary composite end point of death, myocardial infarction, or urgent revascularization at 5 years than medical therapy alone. Patients without hemodynamically significant stenoses had a favorable long‐term outcome with medical therapy alone. (Funded by St. Jude Medical and others; FAME 2 ClinicalTrials.gov number, NCT01132495.)

Influence of socioeconomic factors on delays, management and outcome amongst patients with acute myocardial infarction undergoing primary percutaneous coronary intervention.

AIMS The outcome after primary percutaneous coronary intervention (pPCI) for ST-elevation myocardial infarction (STEMI) is strongly affected by time delays. In this study, we sought to identify the impact of specific socioeconomic factors on time delays, subsequent STEMI management and outcomes in STEMI patients undergoing pPCI, who came from a well-defined region of the French part of Switzerland. METHOD AND RESULTS A total of 402 consecutive patients undergoing pPCI for STEMI in a large tertiary hospital were retrospectively studied. Symptom-to-first-medical-contact time was analysed for the following socioeconomic factors: level of education, origin and marital status. Main exclusion criteria were: time delay beyond 12 hours, previous treatment with fibrinolytic agents or patients immediately referred for coronary artery bypass graft surgery. Therefore, 222 patients were finally included. At 1 year, there was no difference in mortality between the different socioeconomic groups. Furthermore, there was no difference in management characteristics between them. Symptom-to-first-medical-contact time was significantly longer for patients with a low level of education, Swiss citizens and unmarried patients, with median differences of 23 minutes, 18 minutes and 13 minutes, respectively (p <0.05). Nevertheless, no difference was found regarding in-hospital management and clinical outcome. CONCLUSION This study demonstrates that symptom-to-first-medical-contact time is longer amongst people with a lower educational level, Swiss citizens and unmarried people. Because of the low mortality rate in general, these differences in delays did not affect clinical outcomes. Still, tertiary prevention measures should particularly focus on these vulnerable populations.

Angiography versus Hemodynamics to Predict the Natural History of Coronary Stenoses: A FAME 2-Substudy

Background: Among patients with documented stable coronary artery disease and in whom no revascularization was performed, we compared the respective values of angiographic diameter stenosis (DS) and fractional flow reserve (FFR) in predicting natural history. Methods: The present analysis included the 607 patients from the FAME 2 trial (Fractional Flow Reserve Versus Angiography in Multivessel Evaluation 2) in whom no revascularization was performed. FFR varied from 0.20 to 1.00 (average 0.74±0.16), and DS (by quantitative coronary analysis) varied from 8% to 98% (average 53±15). The primary end point, defined as vessel-oriented clinical end point (VOCE) at 2 years, was a composite of prospectively adjudicated cardiac death, vessel-related myocardial infarction, vessel-related urgent, and not urgent revascularization. The stenoses were divided into 4 groups according to FFR and %DS values: positive concordance (FFR⩽0.80; DS≥50%), negative concordance (FFR>0.80; DS<50%), positive mismatch (FFR⩽0.80; DS<50%), and negative mismatch (FFR>0.80; DS≥50%). Results: The rate of VOCE was highest in the positive concordance group (log rank: X2=80.96; P=0.001) and lowest in the negative concordance group. The rate of VOCE was higher in the positive mismatch group than in the negative mismatch group (hazard ratio, 0.38; 95% confidence interval, 0.21–0.67; P=0.001). There was no significant difference in VOCE between the positive concordance and positive mismatch groups (FFR⩽0.80; hazard ratio, 0.77; 95% confidence interval, 0.57–1.09; P=0.149) and no significant difference in rate of VOCE between the negative mismatch and negative concordance groups (FFR>0.80; hazard ratio, 1.89; 95% confidence interval, 0.96–3.74; P=0.067). Conclusions: In patients with stable coronary disease, physiology (FFR) is a more important determinant of the natural history of coronary stenoses than anatomy (DS). Clinical Trial Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT01132495.Background —Among patients with documented stable coronary artery disease (CAD) and in whom no revascularization was performed, we compared the respective values of angiographic diameter stenosis (DS) and of fractional flow reserve (FFR) in predicting natural history. Methods —The present analysis included the 607 patients from the Fractional flow reserve versus angiography in multivessel evaluation 2 (FAME 2) trial in whom no revascularization was performed. FFR varied from 0.20 to 1.00 (average 0.74 ± 0.16) and DS (by QCA) varied from 8% to 98% (average 53 ± 15). The primary end point, defined as VOCE (Vessel oriented clinical endpoint) at 2 years, was a composite of prospectively adjudicated cardiac death, vessel-related myocardial infarction, vessel-related urgent and not urgent revascularization. The stenoses were divided into 4 groups according to FFR and %DS values: Positive Concordance (PC: FFR≤0.80; DS≥50%); Negative Concordance (NC: FFR>0.80; DS 0.80; DS≥50%). Results —The rate of VOCE was highest in the PC group (Log Rank: X 2 =80.96; p=0.001), and lowest in the NC group. The rate of VOCE was higher in the PM group than in the NM group (H.R. 0.38, 95% C.I. 0.21 - 0.67; p=0.001). There was no significant difference in VOCE between the PC and the PM (both groups with FFR≤0.80, H.R. 0.77, 95% C.I. 0.57 - 1.09; p=0.149) and no significant difference in rate of VOCE between the NM and NC (both groups with FFR>0.80, H.R. 1.89, 95% C.I. 0.96 - 3.74; p=0.067). Conclusions —In patients with stable coronary disease, physiology (FFR) is a more important determinant of the natural history of coronary stenoses than anatomy (DS). Clinical Trial Registration —URL: https://clinicaltrials.gov Unique Identifier: NCT01132495.

Ischemic Burden in ST Elevation Myocardial Infarction and Circadian Rhythms

To the Editor: We read the recent publication by Ammirati et al1 with interest. It analyzed a cohort of 1099 patients in Italy, Scotland, and China to confirm results of Suarez-Barrientos et al,2 Reiter et al,3 and our own study.4 The authors of these 3 recent publications showed statistically significant relationships between the time of symptom onset and the size of ST-segment–elevation myocardial infarction in terms of peak creatine kinase. Both Reiter et al and our team found a higher vulnerability to ischemia in patients with symptom onset occurring at night (between midnight and 6:00 am). In their study, Ammirati et al concluded that they were unable to reproduce our results or draw similar conclusions. However, we feel that their methodology failed to adequately …

Diagnostic Contribution of Cardiac Magnetic Resonance in Patients with Acute Coronary Syndrome and Culprit-Free Angiograms

Background In spite of robust knowledge about underlying ischemic myocardial damage, acute coronary syndromes (ACS) with culprit-free angiograms raise diagnostic concerns. The present study aimed to evaluate the additional value of cardiac magnetic resonance (CMR) over commonly available non-CMR standard tests, for the differentiation of myocardial injury in patients with ACS and non-obstructed coronary arteries. Material/Methods Patients with ACS, elevated hs-TnT, and a culprit-free angiogram were prospectively enrolled into the study between January 2009 and July 2013. After initial evaluation with standard tests (ECG, echocardiography, hs-TnT) and provisional exclusion of acute myocardial infarction (AMI) in coronary angiogram, patients were referred for CMR with the suspicion of myocarditis or Takotsubo cardiomyopathy (TTC). According to the result of CMR, patients were reclassified as having myocarditis, AMI, TTC, or non-injured myocardium as assessed by late gadolinium enhancement. Results Out of 5110 patients admitted with ACS, 75 had normal coronary angiograms and entered the study; 69 of them (92%) were suspected for myocarditis and 6 (8%) for TTC. After CMR, 49 patients were finally diagnosed with myocarditis (65%), 3 with TTC (4%), 7 with AMI (9%), and 16 (21%) with non-injured myocardium. The provisional diagnosis was changed or excluded in 23 patients (31%), with a 9% rate of unrecognized AMI. Conclusions The study results suggest that the evaluation of patients with ACS and culprit-free angiogram should be complemented by a CMR examination, if available, because the initial work-up with non-CMR tests leads to a significant proportion of misdiagnosed AMI.

Catheter-based measurements of absolute coronary blood flow and microvascular resistance feasibility, safety, and reproducibility in humans

Background— The principle of continuous thermodilution can be used to calculate absolute coronary blood flow and microvascular resistance (R). The aim of the study is to explore the safety, feasibility, and reproducibility of coronary blood flow and R measurements as measured by continuous thermodilution in humans. Methods and Results— Absolute coronary flow and R can be calculated by thermodilution by infusing saline at room temperature through a dedicated monorail catheter. The temperature of saline as it enters the vessel, the temperature of blood and saline mixed in the distal part of the vessel, and the distal coronary pressure were measured by a pressure/temperature sensor-tipped guidewire. The feasibility and safety of the method were tested in 135 patients who were referred for coronary angiography. No significant adverse events were observed; in 11 (8.1%) patients, bradycardia and concomitant atrioventricular block appeared transiently and were reversed immediately on interruption of the infusion. The reproducibility of measurements was tested in a subgroup of 80 patients (129 arteries). Duplicate measurements had a strong correlation both for coronary blood flow (&rgr;=0.841, P<0.001; intraclass correlation coefficient=0.89, P<0.001) and R (&rgr;=0.780, P<0.001; intraclass correlation coefficient=0.89, P<0.001). In Bland–Altman plots, there was no significant bias or asymmetry. Conclusions— Absolute coronary blood flow (in L/min) and R (in mm Hg/L/min or Wood units) can be safely and reproducibly measured with continuous thermodilution. This approach constitutes a new opportunity for the study of the coronary microcirculation.

Interosseous artery collaterals and their support to ulno-palmar arch: A case report and a review of the literature

Article history: Received 3 June 2015 Accepted 20 June 2015 Available online 27 June 2015 (Glidesheath, Terumo, Somerset, NJ) instead of a brachial access to perform coronary angiography. We also performed a right forearm arteriography (Fig. 1), which demonstrated an efficient collateralization from interosseous anterior branch to distal radial artery. The access site was managed with verapamil 5 mg and heparin 5000 UI. The coronary angiography showed a sub-occlusive restenosis of the RCA treated with a DES. At the end of the procedure, the 6 French ulnar sheath was A 65 year-old woman, with known hypertension, dyslipidemia, and positive family history of coronary artery disease and conservatively treated for an aorto-iliac occlusive disease, was admitted in September 2014 in our institution with angina (CCS 2) and a positive non-invasive test suggests myocardial ischemia in the inferior wall of the left ventricle. Diagnostic suspicion of a right coronary artery (RCA) restenosis indicated an invasive coronary artery assessment. Patient clinical history starts 7 months before with an acute anterior non-ST-segment Elevation Myocardial Infarction. Coronary angiography, performed through a right trans-radial access (TRA) evidenced a sub-occlusive mid-LAD stenosis and a significant stenosis on the RCA. The patient was successfully treated by a PCI on the proximal left anterior descending (LAD)with drug eluting stent (DES) implantation. After a short and uneventful hospitalization, she was discharged. One month later, the patient was readmitted to undergo a stage procedure on the RCA due to ventricular inferior wall ischemia evidence. Arterial pulse evaluation showed a probably iatrogenic right radial arterial occlusion (RAO). Therefore, in the context of the aorto-iliac occlusive disease, a left TRA was chosen. Coronary angiography confirmed the good result of the LAD stenting and the RCA stenosis was treated with PCI and Bare Metal Stent (BMS) implantation. The procedure was uneventful and the patient was discharged the following day. Prior to coronary artery angiography, during September 2014 hospitalization, pulse examination was performed with a bilateral radial artery occlusion evidence. Despite a highly abnormal reverse modified Allen test which would have contraindicated a wrist access, the pulseoxymetry evaluation (right thumb) recorded a C pattern [1] suggesting the presence of an efficient blood flow to ulno-palmar arch. We then

Real-Life Fractional Flow Reserve

Article, see p 2241 Rare are the approaches that have changed our understanding of coronary artery disease as has fractional flow reserve (FFR). After extensive animal and human validation work and hypothesis-generating observational studies,1 larger randomized trials with a superiority design have reshaped our therapeutic strategies in stable coronary artery disease and, albeit to a lesser extent, of acute coronary syndromes. In a nutshell: (1) stenoses with an FFR >0.80 do not benefit from revascularization, not even the nonculprit vessels in patients with acute coronary syndromes2,3; (2) patients with ≤1 stenosis with an FFR ≤0.80 are better off with contemporary percutaneous coronary intervention than with medical therapy4; (3) the angiographic 50% diameter stenosis is a battered standard to define coronary artery disease, risk stratify patients, or guide therapy5,6; (4) performing FFR during diagnostic angiography modifies about half of the revascularization decisions7; and (5) there is a risk continuum for FFR over the entire range of stenosis severity.8,9 Therefore, one might wonder what an observational database could add to this knowledge. The results of the IRIS-FFR registry (Interventional Cardiology Research Incooperation Society Fractional Flow Reserve) published in this issue of Circulation 10 …