Georgios Sideris

Outcome Impact of Coronary Revascularization Strategy Reclassification With Fractional Flow Reserve at Time of Diagnostic Angiography Insights From a Large French Multicenter Fractional Flow Reserve Registry

Background— There is no large report of the impact of fractional flow reserve (FFR) on the reclassification of the coronary revascularization strategy on individual patients referred for diagnostic angiography. Methods and Results— The Registre Français de la FFR (R3F) investigated 1075 consecutive patients undergoing diagnostic angiography including an FFR investigation at 20 French centers. Investigators were asked to define prospectively their revascularization strategy a priori based on angiography before performing the FFR. The final revascularization strategy, reclassification of the strategy by FFR, and 1-year clinical follow-up were prospectively recorded. The strategy a priori based on angiography was medical therapy in 55% and revascularization in 45% (percutaneous coronary intervention, 38%; coronary artery bypass surgery, 7%). Patients were treated according to FFR in 1028/1075 (95.7%). The applied strategy after FFR was medical therapy in 58% and revascularization in 42% (percutaneous coronary intervention, 32%; coronary artery bypass surgery, 10%). The final strategy applied differed from the strategy a priori in 43% of cases: in 33% of a priori medical patients, in 56% of patients undergoing a priori percutaneous coronary intervention, and in 51% of patients undergoing a priori coronary artery bypass surgery. In reclassified patients treated based on FFR and in disagreement with the angiography-based a priori decision (n=464), the 1-year outcome (major cardiac event, 11.2%) was as good as in patients in whom final applied strategy concurred with the angiography-based a priori decision (n=611; major cardiac event, 11.9%; log-rank, P=0.78). At 1 year, >93% patients were asymptomatic without difference between reclassified and nonreclassified patients (Generalized Linear Mixed Model, P=0.75). Reclassification safety was preserved in high-risk patients. Conclusion— This study shows that performing FFR during diagnostic angiography is associated with reclassification of the revascularization decision in about half of the patients. It further demonstrates that it is safe to pursue a revascularization strategy divergent from that suggested by angiography but guided by FFR.

Outcome Impact of Coronary Revascularization Strategy Reclassification With Fractional Flow Reserve at Time of Diagnostic Angiography

Background— There is no large report of the impact of fractional flow reserve (FFR) on the reclassification of the coronary revascularization strategy on individual patients referred for diagnostic angiography. Methods and Results— The Registre Français de la FFR (R3F) investigated 1075 consecutive patients undergoing diagnostic angiography including an FFR investigation at 20 French centers. Investigators were asked to define prospectively their revascularization strategy a priori based on angiography before performing the FFR. The final revascularization strategy, reclassification of the strategy by FFR, and 1-year clinical follow-up were prospectively recorded. The strategy a priori based on angiography was medical therapy in 55% and revascularization in 45% (percutaneous coronary intervention, 38%; coronary artery bypass surgery, 7%). Patients were treated according to FFR in 1028/1075 (95.7%). The applied strategy after FFR was medical therapy in 58% and revascularization in 42% (percutaneous coronary intervention, 32%; coronary artery bypass surgery, 10%). The final strategy applied differed from the strategy a priori in 43% of cases: in 33% of a priori medical patients, in 56% of patients undergoing a priori percutaneous coronary intervention, and in 51% of patients undergoing a priori coronary artery bypass surgery. In reclassified patients treated based on FFR and in disagreement with the angiography-based a priori decision (n=464), the 1-year outcome (major cardiac event, 11.2%) was as good as in patients in whom final applied strategy concurred with the angiography-based a priori decision (n=611; major cardiac event, 11.9%; log-rank, P=0.78). At 1 year, >93% patients were asymptomatic without difference between reclassified and nonreclassified patients (Generalized Linear Mixed Model, P=0.75). Reclassification safety was preserved in high-risk patients. Conclusion— This study shows that performing FFR during diagnostic angiography is associated with reclassification of the revascularization decision in about half of the patients. It further demonstrates that it is safe to pursue a revascularization strategy divergent from that suggested by angiography but guided by FFR.

Value of post-resuscitation electrocardiogram in the diagnosis of acute myocardial infarction in out-of-hospital cardiac arrest patients

BACKGROUND Diagnosis of acute myocardial infarction (AMI) in out-of-hospital cardiac arrest (OHCA) patients is important because immediate coronary angiography with coronary angioplasty could improve outcome in this setting. However, the value of acute post-resuscitation electrocardiographic (ECG) data for the detection of AMI is debatable. METHODS We assessed the diagnostic characteristics of post-resuscitation ECG changes in a retrospective single centre study evaluating several ECG criteria of selection of patients undergoing AMI, in order to improve sensitivity, even at the expense of specificity. Immediate post resuscitation coronary angiogram was performed in all patients. AMI was defined angiographically using coronary flow and plaque morphology criteria. RESULTS We included 165 consecutive patients aged 56 (IQR 48-67) with sustained return of spontaneous circulation after OHCA between 2002 and 2008. 84 patients had shockable, 73 non-shockable and 8 unknown initial rhythm; 36% of the patients had an AMI. ST-segment elevation predicted AMI with 88% sensitivity and 84% specificity. The criterion including ST-segment elevation and/or depression had 95% sensitivity and 62% specificity. The combined criterion including ST-segment elevation and/or depression, and/or non-specific wide QRS complex and/or left bundle branch block provided a sensitivity and negative predictive value of 100%, a specificity of 46% and a positive predictive value of 52%. CONCLUSION In patients with OHCA without obvious non-cardiac causes, selection for coronary angiogram based on the combined criterion would detect all AMI and avoid the performance of the procedure in 30% of the patients, in whom coronary angiogram did not have a therapeutic role.

Biological efficacy of twice daily aspirin in type 2 diabetic patients with coronary artery disease

BACKGROUND Diabetes is associated with a high rate of events after acute coronary syndrome and percutaneous coronary intervention despite aspirin treatment. Once daily aspirin might not provide 24-hour stable biological efficacy in patients with diabetes. We compared the biological efficacy of the same daily dose of aspirin given either once (OPD) or divided twice per day in a population of diabetic patients with previous coronary artery disease. METHODS Ninety-two consecutive diabetic patients with at least 1 criteria of time-dependent aspirin efficacy, elevated high-sensibility C-reactive protein (hs-CRP), fibrinogen, platelet count, or active smoking were prospectively included. Consecutive patients were randomly treated with 150-mg aspirin daily given either OPD (150 mg in the morning) or twice per day (75 mg in the morning and 75 mg in the evening) in a crossover study. The main outcome was platelet reactivity to arachidonic acid (0.5 mg/mL) measured by light transmission aggregometry at trough level before morning aspirin intake. RESULTS Mean maximum aggregation intensity triggered by arachidonic acid was 19.7% ± 15.4% on OPD and 11.9% ± 10.4% on twice per day (P < .0001). Biological resistance (maximum aggregation intensity ≥20%) was observed in 42% of patients on OPD and 17% on twice per day (P < .001). Of the 39 patients with biological resistance on OPD, 24 (62%) overcame resistance on twice per day. Of the 16 resistant on twice per day, only 1 patient (6%) overcame resistance on OPD. Results were concordant with global evaluation of platelet reactivity by Platelet Function Analyzer-100. A better twice per day efficacy was independent of clopidogrel cotreatment. CONCLUSION In a population of diabetic patients with coronary artery disease and a high risk of time-dependent aspirin resistance, aspirin divided twice per day can significantly decrease the rate of biological loss of efficacy at trough level.

Role of cardiac troponin in the diagnosis of acute myocardial infarction in comatose patients resuscitated from out-of-hospital cardiac arrest.

BACKGROUND Troponin is a major diagnostic criterion of acute myocardial infarction (AMI) but in out-of-hospital cardiac arrest (OHCA) patients, its diagnostic value may be altered by cardiopulmonary resuscitation. METHODS Single-centre study assessing the diagnostic characteristics of troponin for AMI diagnosis in consecutive patients resuscitated from OHCA between 2002 and 2008 with coronary angiogram (CA) performed on admission. Patients with obvious non-cardiac cause of OHCA, unsustained or absent return of spontaneous circulation were excluded. AMI was defined on CA by the presence of acute occlusion or critical stenosis with intracoronary fresh thrombus easily crossed by an angioplasty wire. Troponin concentration was recorded once on admission and once 6-12h after the OHCA. RESULTS A total of 163 patients aged 56 (median) years (interquartile range (IQR) 48-65) was included, all comatose. Most prevalent initial OHCA rhythms were ventricular fibrillation (49%) and asystole (41%). AMI was diagnosed on coronary angiogram in 37% of the patients. Median troponin concentration on admission was 1.7 (0.3-10)ngml(-1) and sensitivity for AMI diagnosis was 72% and specificity 75% for a 2.5ngml(-1) cut-off. A combined criterion comprising ST elevation and troponin >2.5ngml(-1) had a sensitivity of 93% and specificity of 64%. Six to twelve hours after the OHCA, median troponin concentration was 7.6ngml(-1) (1.4-47.5), sensitivity was 84% and specificity 84% for a 14.5ngml(-1) cut-off. CONCLUSION Troponin I has a good diagnostic value for AMI diagnosis in OHCA patients. In combination with ST elevation, troponin I on admission achieves a very high sensitivity.

Drug-eluting stents in elderly patients with coronary artery disease (SENIOR): a randomised single-blind trial

BACKGROUND Elderly patients regularly receive bare-metal stents (BMS) instead of drug-eluting stents (DES) to shorten the duration of double antiplatelet therapy (DAPT). The aim of this study was to compare outcomes between these two types of stents with a short duration of DAPT in such patients. METHODS In this randomised single-blind trial, we recruited patients from 44 centres in nine countries. Patients were eligible if they were aged 75 years or older; had stable angina, silent ischaemia, or an acute coronary syndrome; and had at least one coronary artery with a stenosis of at least 70% (≥50% for the left main stem) deemed eligible for percutaneous coronary intervention (PCI). Exclusion criteria were indication for myocardial revascularisation by coronary artery bypass grafting; inability to tolerate, obtain, or comply with DAPT; requirement for additional surgery; non-cardiac comorbidities with a life expectancy of less than 1 year; previous haemorrhagic stroke; allergy to aspirin or P2Y12 inhibitors; contraindication to P2Y12 inhibitors; and silent ischaemia of less than 10% of the left myocardium with a fractional flow reserve of 0·80 or higher. After the intended duration of DAPT was recorded (1 month for patients with stable presentation and 6 months for those with unstable presentation), patients were randomly allocated (1:1) by a central computer system (blocking used with randomly selected block sizes [two, four, eight, or 16]; stratified by site and antiplatelet agent) to either a DES or similar BMS in a single-blind fashion (ie, patients were masked), but those assessing outcomes were masked. The primary outcome was to compare major adverse cardiac and cerebrovascular events (ie, a composite of all-cause mortality, myocardial infarction, stroke, or ischaemia-driven target lesion revascularisation) between groups at 1 year in the intention-to-treat population, assessed at 30 days, 180 days, and 1 year. This trial is registered with ClinicalTrials.gov, number NCT02099617. FINDINGS Between May 21, 2014, and April 16, 2016, we randomly assigned 1200 patients (596 [50%] to the DES group and 604 [50%] to the BMS group). The primary endpoint occurred in 68 (12%) patients in the DES group and 98 (16%) in the BMS group (relative risk [RR] 0·71 [95% CI 0·52-0·94]; p=0·02). Bleeding complications (26 [5%] in the DES group vs 29 [5%] in the BMS group; RR 0·90 [0·51-1·54]; p=0·68) and stent thrombosis (three [1%] vs eight [1%]; RR 0·38 [0·00-1·48]; p=0·13) at 1 year were infrequent in both groups. INTERPRETATION Among elderly patients who have PCI, a DES and a short duration of DAPT are better than BMS and a similar duration of DAPT with respect to the occurrence of all-cause mortality, myocardial infarction, stroke, and ischaemia-driven target lesion revascularisation. A strategy of combination of a DES to reduce the risk of subsequent repeat revascularisations with a short BMS-like DAPT regimen to reduce the risk of bleeding event is an attractive option for elderly patients who have PCI. FUNDING Boston Scientific.

Favourable 5-year postdischarge survival of comatose patients resuscitated from out-of-hospital cardiac arrest, managed with immediate coronary angiogram on admission:

Aims: On-admission coronary angiogram (CA) with angioplasty (percutaneous coronary intervention, PCI) may improve survival in patients resuscitated from out-of-hospital cardiac arrest (OHCA), but long-term survival data are scarce. We assessed long-term survival in OHCA patients managed with on-admission CA and PCI if indicated and compared survival rates in patients with/without acute coronary syndrome (ACS). Methods: Retrospective single-centre study including patients aged ≥18 years resuscitated from an OHCA without noncardiac cause, with sustained return of spontaneous circulation, undergoing on-admission CA with PCI if indicated. ACS was diagnosed angiographically. Survival was recorded at hospital discharge and at 5-year follow up. Survival probability was estimated by Kaplan–Meier survival curves. Results: A total of 300 comatose patients aged 56 years (IQR 48–67 years) were included, 36% with ST-segment elevation. All had on-admission CA; 31% had ACS. PCI was attempted in 91% of ACS patients and was successful in 93%. Hypothermia was performed in 84%. Survival to discharge was 32.3%. After discharge, 5-year survival was 81.7±5.4%. Survival from admission to 5 years was 26.2±2.8%. ACS patients had better survival to discharge (40.8%) compared with non-ACS patients (28.5%, p=0.047). After discharge, 5-year survival was 92.2±5.4% for patients with ACS and 73.4±8.6% without ACS (hazard ratio, HR, 2.7, 95% CI 0.8–8.9, p=0.1). Survival from admission to 5 years was 37.4±5.2% for ACS patients, 20.7±3.0%, for non-ACS patients (HR 1.5, 95% CI 1.12–2.0, p=0.0067). Conclusions: OHCA patients undergoing on-admission CA had a very favourable postdischarge survival. Patients with OHCA due to ACS had better survival to discharge at 5-year follow up than patients with OHCA due to other causes.

Usefulness of subcutaneous nitrate for radial access

Objectives: We made the hypothesis that adjunction of nitrate to lidocaine for local anesthesia may facilitate accessibility of radial access. Background: Transradial approach is associated with a clear decrease in the rate of access bleeding when compared with femoral approach. The diffusion of this technique remains limited due to the small size and the spastic profile of this artery. Methods: Eighty‐four consecutive patients undergoing coronary procedures using radial approach were randomly assigned between two types of local anesthesia (double blind): 5 ml lidocaine (group L)—5 ml lidocaine + 0.5 mg dinitrate isosorbide (group LN). The primary endpoint was the duration of radial puncture (from beginning of local anesthesia to sheath insertion) and the total number of punctures. Results: Sixty‐two men and 22 women (mean age 59 ± 8 y.o.) were included. Mean ± SEM access duration was 3:33 ± 3:11 min in group L when compared with 2:26 ± 1:20 min in group LN (P < 0.05). Mean number of puncture was 1.50 ± 1.0 in group L when compared with 1.16 ± 0.5 in group LN (P = 0.05). There were no differences between two groups concerning pain score during anesthesia and sheath insertion. There was no difference between two groups concerning the rate of hypotensive and vagal reactions. Radial spasm occurred in four patients in group L and only one in the group LN. Conclusion: Local anesthesia using lidocaine plus nitrate is feasible and improves the accessibility of radial access.

Influence of α-stat and pH-stat blood gas management strategies on cerebral blood flow and oxygenation in patients treated with therapeutic hypothermia after out-of-hospital cardiac arrest: a crossover study.

Objectives:In patients treated with therapeutic hypothermia after out-of-hospital cardiac arrest, two blood gas management strategies are used regarding the PaCO2 target: &agr;-stat or pH-stat. We aimed to compare the effects of these strategies on cerebral blood flow and oxygenation. Design:Prospective observational single-center crossover study. Setting:ICU of University hospital. Patients:Twenty-one therapeutic hypothermia–treated patients after out-of-hospital cardiac arrest more than 18 years old without history of cerebrovascular disease were included. Interventions:Cerebral perfusion and oxygenation variables were compared in &agr;-stat (PaCO2 measured at 37°C) versus pH-stat (PaCO2 measured at 32–34°C), both strategies maintaining physiological PaCO2 values: 4.8–5.6 kPa (36–42 torr). Measurements and Main Results:Bilateral transcranial middle cerebral artery flow velocities using Doppler and jugular vein oxygen saturation were measured in both strategies 18 hours (14–23 hr) after the return of spontaneous circulation. Pulsatility and resistance indexes and cerebral oxygen extraction were calculated. Data are expressed as median (interquartile range 25–75) in &agr;-stat versus pH-stat. No differences were found in temperature, arterial blood pressure, and oxygenation between &agr;-stat and pH-stat. Significant differences were found in minute ventilation (p = 0.006), temperature-corrected PaCO2 (4.4 kPa [4.1–4.6 kPa] vs 5.1 kPa [5.0–5.3 kPa], p = 0.0001), and temperature-uncorrected PaCO2 (p = 0.0001). No differences were found in cerebral blood velocities and pulsatility and resistance indexes in the overall population. Significant differences were found in jugular vein oxygen saturation (83.2% [79.2–87.6%] vs 86.7% [83.2–88.2%], p = 0.009) and cerebral oxygen extraction (15% [11–20%] vs 12% [10–16%], p = 0.01), respectively. In survivors, diastolic blood velocities were 25 cm/s (19–30 cm/s) versus 29 cm/s (23–35 cm/s) (p = 0.004), pulsatility index was 1.10 (0.97–1.18) versus 0.94 (0.89–1.05) (p = 0.027), jugular vein oxygen saturation was 79.2 (71.1–81.8) versus 83.3% (76.6–87.8) (p = 0.033), respectively. However, similar results were not found in nonsurvivors. Conclusions:In therapeutic hypothermia–treated patients after out-of-hospital cardiac arrest at physiological PaCO2, &agr;-stat strategy increases jugular vein blood desaturation and cerebral oxygen extraction compared with pH-stat strategy and decreases cerebral blood flow velocities in survivors.

Early coronary revascularization improves 24h survival and neurological function after ischemic cardiac arrest. A randomized animal study.

BACKGROUND Survival after out-of-hospital cardiac arrest (OHCA) remains poor. Acute coronary obstruction is a major cause of OHCA. We hypothesize that early coronary reperfusion will improve 24h-survival and neurological outcomes. METHODS Total occlusion of the mid LAD was induced by balloon inflation in 27 pigs. After 5min, VF was induced and left untreated for 8min. If return of spontaneous circulation (ROSC) was achieved within 15min (21/27 animals) of cardiopulmonary resuscitation (CPR), animals were randomized to a total of either 45min (group A) or 4h (group B) of LAD occlusion. Animals without ROSC after 15min of CPR were classified as refractory VF (group C). In those pigs, CPR was continued up to 45min of total LAD occlusion at which point reperfusion was achieved. CPR was continued until ROSC or another 10min of CPR had been performed. Primary endpoints for groups A and B were 24-h survival and cerebral performance category (CPC). Primary endpoint for group C was ROSC before or after reperfusion. RESULTS Early compared to late reperfusion improved survival (10/11 versus 4/10, p=0.02), mean CPC (1.4±0.7 versus 2.5±0.6, p=0.017), LVEF (43±13 versus 32±9%, p=0.01), troponin I (37±28 versus 99±12, p=0.005) and CK-MB (11±4 versus 20.1±5, p=0.031) at 24-h after ROSC. ROSC was achieved in 4/6 animals only after reperfusion in group C. CONCLUSIONS Early reperfusion after ischemic cardiac arrest improved 24h survival rate and neurological function. In animals with refractory VF, reperfusion was necessary to achieve ROSC.