Early survival after acute myocardial infarction with ST-segment elevation: What could be improved? Insights from France PCI French registry.

Early mortality post-ST-segment elevation myocardial infarction (STEMI) in France remains high. The multicentre France Percutaneous Coronary Intervention Registry includes every patient undergoing coronary angiography in France. We analyzed the prevalence and impact of unmodifiable and modifiable risk factors on 30-day survival in patients experiencing STEMI. Patients admitted for STEMI between 01/2014 and 12/2016 were included in the analysis. Patients with nonobstructive coronary artery disease, with cardiogenic shock or cardiac arrest without STEMI, were excluded. Prehospital, clinical and procedural data were collected prospectively by the cardiologist in the cath lab using medical reporting software. Information on outcomes, including mortality, was obtained by a dedicated research technician by phone calls or from medical records. Marginal Cox proportional hazards regression was used to test the predictive value for survival at 30 days in a multivariable analysis. Included were 2590 patients (74% men) aged 63 ± 14 years. During the first month, 174 patients (6.7%) died. After adjustment, unmodifiable variables significantly associated with reduced 30-day survival were: age > 80 years (prevalence 15%; hazard ratio [HR] 2.7; 95% confidence interval [CI] 1.5-4.7), chronic kidney disease (2%; HR 5.3; 95% CI 2.6-11.1), diabetes mellitus (14%; HR 1.6; 95% CI 1.0-2.5), anterior or circumferential electrical localization (39%; HR 2.0; 95% CI 1.4-2.9), and Killip class 2, 3, or 4 (7%; HR 3.4; 95% CI 1.9-5.9; 2%; HR 10.1; 95% CI 5.3-19.4; 4%; HR 18; 95% CI 10.8-29.8, respectively). Among modifiable variables, total ischemic time > 3 hours (68%; HR 1.8; 95% CI 1.1-3.0), lack of appropriate premedication (18%; HR 2.2; 95% CI 1.5-3.3), and post-PCI TIMI < 3 (6%; HR 4.9; 95% CI 3.2-7.6) were significantly associated with reduced 30-day survival. Most predictors of 30-day survival post-STEMI are unmodifiable, but outcomes might be improved by optimizing modifiable factors, most importantly ischemic time and appropriate premedication.

TAVR Patients Requiring Anticoagulation: Direct Oral Anticoagulant or Vitamin K Antagonist?

OBJECTIVES: Using French transcatheter aortic valve replacement (TAVR) registries linked with the nationwide administrative databases, the study compared the rates of long-term mortality, bleeding, and ischemic events after TAVR in patients requiring oral anticoagulation with direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs). BACKGROUND: The choice of optimal drug for anticoagulation after TAVR remains debated. METHODS: Data from the France-TAVI and FRANCE-2 registries were linked to the French national health single-payer claims database, from 2010 to 2017. Propensity score matching was used to reduce treatment-selection bias. Two primary endpoints were death from any cause (efficacy) and major bleeding (safety). RESULTS: A total of 24,581 patients who underwent TAVR were included and 8,962 (36.4%) were treated with OAC. Among anticoagulated patients, 2,180 (24.3%) were on DOACs. After propensity matching, at 3 years, mortality (hazard ratio [HR]: 1.37; 95% confidence interval [CI]: 1.12-1.67; P < 0.005) and major bleeding including hemorrhagic stroke (HR: 1.64; 95% CI: 1.17-2.29; P < 0.005) were lower in patients on DOACs compared with those on VKAs. The rates of ischemic stroke (HR: 1.32; 95% CI: 0.81-2.15; P = 0.27) and acute coronary syndrome (HR: 1.17; 95% CI: 0.68-1.99; P = 0.57) did not differ among groups. CONCLUSIONS: In these large multicenter French TAVR registries with an exhaustive clinical follow-up, the long-term mortality and major bleeding were lower with DOACs than VKAs at discharge. The present study supports preferential use of DOACs rather than VKAs in patients requiring oral anticoagulation therapy after TAVR.

INCREASED EXPOSURE TO X-RAYS DURING CORONARY ANGIOGRAPHY AND PERCUTANEOUS CORONARY INTERVENTIONS ASSOCIATED WITH FRACTIONAL FLOW RESERVE MEASUREMENT AND ENDOCORONARY IMAGING TECHNIQUES.

Growing use of fractional flow reserve (FFR) and intracoronary imaging techniques by optical coherence tomography or intravascular ultrasound has raised concerns about additional exposure during coronary angiography and percutaneous coronary interventions (PCIs). Using data from the prospective CRAC-France PCI Prospective Multicentre registry, we sought to evaluate the effect of these new techniques on the radiation dose to patients undergoing coronary procedures. Data on Kerma Area Product (PKA), total air kerma (KAr) and fluoroscopy time from 42 182 coronary procedures were retrospectively compared, using multivariable linear regression, according to whether they included FFR and intracoronary imaging. In coronary angiography, FFR was associated with longer fluoroscopy time and higher PKA (21.0 vs. 18.9 Gy.cm2) and KAr (372 vs. 299 mGy) (all p < 0.001). Intracoronary imaging was associated with longer fluoroscopy time, higher contrast volume (both p < 0.001), lower PKA (18.3 vs. 19.0 Gy.cm2, p = 0.02) and similar KAr. In PCI, FFR was associated with a moderate increase in KAr (682 vs. 626 mGy, p < 0.01) but not PKA (35.9 vs. 33.7 Gy.cm2, p = 0.34). For intracoronary imaging, there were no differences between groups, except for contrast volume. Increased patient exposure associated with FFR and intracoronary imaging is moderate in diagnostic coronary angiography and minimal or none in PCI, provided optimization techniques are used. It should not be a limitation on the use of these techniques given the important additional information they provide.

Organophosphorus diisopropylfluorophosphate (DFP) intoxication in zebrafish larvae causes behavioral defects, neuronal hyperexcitation and neuronal death.

With millions of intoxications each year and over 200,000 deaths, organophosphorus (OP) compounds are an important public health issue worldwide. OP poisoning induces cholinergic syndrome, with respiratory distress, hypertension, and neuron damage that may lead to epileptic seizures and permanent cognitive deficits. Existing countermeasures are lifesaving but do not prevent long-lasting neuronal comorbidities, emphasizing the urgent need for animal models to better understand OP neurotoxicity and identify novel antidotes. Here, using diisopropylfluorophosphate (DFP), a prototypic and moderately toxic OP, combined with zebrafish larvae, we first showed that DFP poisoning caused major acetylcholinesterase inhibition, resulting in paralysis and CNS neuron hyperactivation, as indicated by increased neuronal calcium transients and overexpression of the immediate early genes fosab, junBa, npas4b, and atf3. In addition to these epileptiform seizure-like events, DFP-exposed larvae showed increased neuronal apoptosis, which were both partially alleviated by diazepam treatment, suggesting a causal link between neuronal hyperexcitation and cell death. Last, DFP poisoning induced an altered balance of glutamatergic/GABAergic synaptic activity with increased NR2B-NMDA receptor accumulation combined with decreased GAD65/67 and gephyrin protein accumulation. The zebrafish DFP model presented here thus provides important novel insights into the pathophysiology of OP intoxication, making it a promising model to identify novel antidotes.

OCT and CMR for the Diagnosis of Patients Presenting With MINOCA and Suspected Epicardial Causes.

OBJECTIVES: Among all patients presenting with myocardial infarction with nonobstructive coronary arteries (MINOCA), epicardial causes may be suspected when there is a correlation between electrocardiogram (ECG) changes and regional wall motion abnormalities (WMAs). We evaluated the diagnostic yield of intravascular optical coherence tomography (OCT) and cardiac magnetic resonance (CMR) in this specific setting. BACKGROUND: OCT is able to identify different morphologic features of coronary plaques that are well known causes of MINOCA. Furthermore, CMR has become the gold standard for detection of myocardial infarction in the setting of MINOCA. METHODS: In a prospective 2-center study, consecutive patients with MINOCA including ECG features of ischemia associated with corresponding WMAs underwent OCT and CMR. RESULTS: Forty patients (mean age: 50 ± 11 years, 62.5% male, 32.5% with ST-segment elevation) were enrolled. Coronary arteries were normal on coronary angiography in 10 patients (25%); 18 patients (45%) presented minimal lumen irregularities, whereas the remaining 12 patients (30%) showed mild to moderate (≥30% but <50%) coronary lesions. Plaque rupture, eruptive calcific nodule, plaque erosion, lone thrombus, and spontaneous coronary artery dissection were found in 14 (35%), 1 (2.5%), 12 (30%), 3 (7.5%), and 2 (5%) patients, respectively. Acute myocardial infarction was evident at CMR in 31 of 40 patients (77.5%). Twenty-three patients (57.5%) had a substrate and/or diagnosis supported by both techniques with an evident relationship between the findings obtained by the 2 techniques. By coupling OCT with CMR, a substrate and/or diagnosis was found in 100% of cases. CONCLUSIONS: OCT coupled with CMR can provide a clear substrate and/or diagnosis in the vast majority of patients presenting with MINOCA including ECG features of ischemia associated with corresponding WMAs.

Balloon-Expandable Versus Self-Expanding Transcatheter Aortic Valve Replacement: A Propensity-Matched Comparison From the FRANCE-TAVI Registry.

BACKGROUND: No randomized study powered to compare balloon expandable (BE) with self expanding (SE) transcatheter heart valves (THVs) on individual end points after transcatheter aortic valve replacement has been conducted to date. METHODS: From January 2013 to December 2015, the FRANCE-TAVI nationwide registry (Registry of Aortic Valve Bioprostheses Established by Catheter) included 12 141 patients undergoing BE-THV (Edwards, n=8038) or SE-THV (Medtronic, n=4103) for treatment of native aortic stenosis. Long term mortality status was available in all patients (median 20 months; interquartile range, 14 to 30). Patients treated with BE-THV (n=3910) were successfully matched 1:1 with 3910 patients treated with SE-THV by using propensity score (25 clinical, anatomical, and procedural variables) and by date of the procedure (within 3 months). The first coprimary outcome was ≥ moderate occurrence of paravalvular regurgitation or in-hospital mortality, or both. The second coprimary outcome was 2-year all-cause mortality. RESULTS: In propensity-matched analyses, the incidence of the first coprimary outcome was higher with SE-THV (19.8%) compared with BE-THV (11.9%; relative risk, 1.68 [95% CI, 1.46-1.91]; P<0.0001). Each component of the outcome was also higher in patients receiving SE-THV: ≥ moderate paravalvular regurgitation (15.5% versus 8.3%; relative risk, 1.90 [95% CI, 1.63-2.22]; P<0.0001) and in hospital mortality (5.6% versus 4.2%; relative risk, 1.34 [95% CI, 1.07-1.66]; P=0.01). During follow up, all cause mortality occurred in 899 patients treated with SE-THV (2-year mortality, 29.8%) and in 801 patients treated with BE-THV (2-year mortality, 26.6%; hazard ratio, 1.17 [95% CI, 1.06-1.29]; P=0.003). Similar results were found using inverse probability of treatment weighting using propensity score analysis. CONCLUSION: The present study suggests that use of SE-THV was associated with a higher risk of paravalvular regurgitation and higher in-hospital and 2-year mortality compared with use of BE-THV. These data strongly support the need for a randomized trial sufficiently powered to compare the latest generation of SE-THV and BE-THV. CLINICAL TRIAL REGISTRATION: https://www.clinicaltrials.gov. Unique identifier: NCT01777828.

Assessment of Long-Term Structural Deterioration of Transcatheter Aortic Bioprosthetic Valves Using the New European Definition.

BACKGROUND: The durability of transcatheter aortic bioprosthetic valves is a crucial issue, but data are scarce, especially beyond 5 years of follow-up. We aimed to assess long-term (7 years) structural valve deterioration (SVD) and bioprosthetic valve failure of transcatheter aortic bioprosthetic valves. METHODS AND RESULTS: Consecutive patients with at least 5-year follow-up available undergoing transcatheter aortic valve implantation from April 2002 to December 2011 in 5 French centers were included. Incidence of SVD and bioprosthetic valve failure were defined according to newly standardized criteria of the European Association of Percutaneous Cardiovascular Interventions/European Society of Cardiology/European Association for Cardio-Thoracic Surgery and reported as cumulative incidence function to account for the competing risk of death. One thousand four hundred three consecutive patients were included with a mean age of 82.6±7.5 years and with a mean logistic EuroSCORE (European System for Cardiac Operative Risk Evaluation) of 21.3±7.5%. A balloon-expandable valve was used in 83.7% of cases. Survival rates were 83.5% (95% CI, 81.4%-85.5%) and 18.6% (95% CI, 15.3%-21.8%) at 1 and 7 years, respectively. Median duration of follow-up was 3.9 years. Bioprosthetic valve failure occurred in 19 patients with a 7-year cumulative incidence of 1.9% (95% CI, 1.4%-2.4%). SVD occurred in 49 patients (moderate, n=32; severe, n=17) with a 7-year cumulative incidence of moderate and severe SVD of 7.0% (95% CI, 5.6%-8.4%) and 4.2% (95% CI, 2.9%-5.5%), respectively. Five patients had aortic valve reintervention (1.0%; 95% CI, 0.4%-1.6%) including 1 case of surgical aortic valve replacement and 4 redo-transcatheter aortic valve implantation. The incidences of SVD and bioprosthetic valve failure were not significantly different between balloon and self-expandable prostheses. CONCLUSIONS: The long-term assessment of transcatheter aortic bioprosthetic valves durability is limited by the poor survival of our population beyond 5 years. Further studies are warranted, particularly in younger and lower-risk patients.

Temporal Trends in Transcatheter Aortic Valve Replacement in France: FRANCE 2 to FRANCE TAVI.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is standard therapy for patients with severe aortic stenosis who are at high surgical risk. However, national data regarding procedural characteristics and clinical outcomes over time are limited. OBJECTIVES: The aim of this study was to assess nationwide performance trends and clinical outcomes of TAVR during a 6-year period. METHODS: TAVRs performed in 48 centers across France between January 2013 and December 2015 were prospectively included in the FRANCE TAVI (French Transcatheter Aortic Valve Implantation) registry. Findings were further compared with those reported from the FRANCE 2 (French Aortic National CoreValve and Edwards 2) registry, which captured all TAVRs performed from January 2010 to January 2012 across 34 centers. RESULTS: A total of 12,804 patients from FRANCE TAVI and 4,165 patients from FRANCE 2 were included in this analysis. The median age of patients was 84.6 years, and 49.7% were men. FRANCE TAVI participants were older but at lower surgical risk (median logistic European System for Cardiac Operative Risk Evaluation [EuroSCORE]: 15.0% vs. 18.4%; p < 0.001). More than 80% of patients in FRANCE TAVI underwent transfemoral TAVR. Transesophageal echocardiography guidance decreased from 60.7% to 32.3% of cases, whereas more recent procedures were increasingly performed in hybrid operating rooms (15.8% vs. 35.7%). Rates of Valve Academic Research Consortium-defined device success increased from 95.3% in FRANCE 2 to 96.8% in FRANCE TAVI (p < 0.001). In-hospital and 30-day mortality rates were 4.4% and 5.4%, respectively, in FRANCE TAVI compared with 8.2% and 10.1%, respectively, in FRANCE 2 (p < 0.001 for both). Stroke and potentially life-threatening complications, such as annulus rupture or aortic dissection, remained stable over time, whereas rates of cardiac tamponade and pacemaker implantation significantly increased. CONCLUSIONS: The FRANCE TAVI registry provided reassuring data regarding trends in TAVR performance in an all-comers population on a national scale. Nonetheless, given that TAVR indications are likely to expand to patients at lower surgical risk, concerns remain regarding potentially life-threatening complications and pacemaker implantation. (Registry of Aortic Valve Bioprostheses Established by Catheter [FRANCE TAVI]; NCT01777828).

An unusual cause of myocardial ischemia: Compression of a left internal mammary artery grafting to the left anterior descending artery by a pacemaker lead.

An 83-year-old patient, with prior history of coronary artery disease treated by coronary-artery bypass graft with left internal mammary artery (LIMA) to the left anterior descending artery (2001) and angioplasty of the right coronary artery (2012) and prior pacemaker through left subclavian vein (2014), was referred to coronary angiography for an anterior silent ischemia. It found no evolving lesion on the native coronary artery network (compared with 2012 review) but revealed an external compression of the LIMA bridge by the pacemaker lead. Conservative treatment was chosen rather than explantation and reimplantation of stimulus material or LIMA angioplasty. .

The appropriate and justified use of medical radiation in cardiovascular imaging: a position document of the ESC Associations of Cardiovascular Imaging, Percutaneous Cardiovascular Interventions and Electrophysiology.

The benefits of cardiac imaging are immense, and modern medicine requires the extensive and versatile use of a variety of cardiac imaging techniques. Cardiologists are responsible for a large part of the radiation exposures every person gets per year from all medical sources. Therefore, they have a particular responsibility to avoid unjustified and non-optimized use of radiation, but sometimes are imperfectly aware of the radiological dose of the examination they prescribe or practice. This position paper aims to summarize the current knowledge on radiation effective doses (and risks) related to cardiac imaging procedures. We have reviewed the literature on radiation doses, which can range from the equivalent of 1-60 milliSievert (mSv) around a reference dose average of 15 mSv (corresponding to 750 chest X-rays) for a percutaneous coronary intervention, a cardiac radiofrequency ablation, a multidetector coronary angiography, or a myocardial perfusion imaging scintigraphy. We provide a European perspective on the best way to play an active role in implementing into clinical practice the key principle of radiation protection that: 'each patient should get the right imaging exam, at the right time, with the right radiation dose'.

Brain and neck tumors among physicians performing interventional procedures.

Physicians performing interventional procedures are chronically exposed to ionizing radiation, which is known to pose increased cancer risks. We recently reported 9 cases of brain cancer in interventional cardiologists. Subsequently, we received 22 additional cases from around the world, comprising an expanded 31 case cohort. Data were transmitted to us during the past few months. For all cases, where possible, we endeavored to obtain the baseline data, including age, gender, tumor type, and side involved, specialty (cardiologist vs radiologist), and number of years in practice. These data were obtained from the medical records, interviews with patients, when possible, or with family members and/or colleagues. The present report documented brain and neck tumors occurring in 31 physicians: 23 interventional cardiologists, 2 electrophysiologists, and 6 interventional radiologists. All physicians had worked for prolonged periods (latency period 12 to 32 years, mean 23.5 ± 5.9) in active interventional practice with exposure to ionizing radiation in the catheterization laboratory. The tumors included 17 cases (55%) of glioblastoma multiforme (GBM), 2 astrocytomas (7%), and 5 meningiomas (16%). In 26 of 31 cases, data were available regarding the side of the brain involved. The malignancy was left sided in 22 (85%), midline in 1, and right sided in 3 operators. In conclusion, these results raise additional concerns regarding brain cancer developing in physicians performing interventional procedures. Given that the brain is relatively unprotected and the left side of the head is known to be more exposed to radiation than the right, these findings of disproportionate reports of left-sided tumors suggest the possibility of a causal relation to occupational radiation exposure.

Interventional cardiologists and risk of radiation-induced cataract: results of a French multicenter observational study.

BACKGROUND: Interventional cardiologists (ICs) are exposed to X-rays and may be at risk to develop cataract earlier than common senile cataract. Excess risk of posterior subcapsular cataract, known as radiation-induced, was previously observed in samples of ICs from Malaysia, and Latin America. The O'CLOC study (Occupational Cataracts and Lens Opacities in interventional Cardiology) was performed to quantify the risk at the scale of France. METHODS: This cross-sectional multicenter study included an exposed group of ICs from different French centers and an unexposed control group of non-medical workers. Individual information was collected about cataract risk factors and past and present workload in catheterization laboratory. All participants had a clinical eye examination to classify the lens opacities (nuclear, cortical, or posterior subcapsular) with the international standard classification LOCS III. RESULTS: The study included 106 ICs (mean age = 51 ± 7 years) and 99 unexposed control subjects (mean age = 50 ± 7 years). The groups did not differ significantly in the prevalence of either nuclear or cortical lens opacities (61% vs. 69% and 23% vs. 29%, respectively). However, posterior subcapsular lens opacities, were significantly more frequent among ICs (17% vs. 5%, p=0.006), for an OR=3.9 [1.3-11.4]. The risk increased with duration of activity but no clear relationship with workload was observed. However, the risk appeared lower for regular users of protective lead glasses (OR=2.2 [0.4-12.8]). CONCLUSIONS: ICs, in France as elsewhere, are at high risk of posterior subcapsular cataracts. Use of protective equipment against X-rays, in particular lead glasses, is strongly recommended to limit this risk.

Eye lens radiation exposure to interventional cardiologists: a retrospective assessment of cumulative doses.

Radiation dose to the eye lens is a crucial issue for interventional cardiologists (ICs) who are exposed during the procedures they perform. This paper presents a retrospective assessment of the cumulative eye lens doses of ICs enrolled in the O'CLOC study for Occupational Cataracts and Lens Opacities in interventional Cardiology. Information on the workload in the catheterisation laboratory, radiation protection equipment, eye lens dose per procedure and dose reduction factors associated with eye-protective equipment were considered. For the 129 ICs at an average age of 51 who had worked for an average period of 22 years, the estimated cumulative eye lens dose ranged from 25 mSv to more than 1600 mSv; the mean ± SD was 423 ± 359 mSv. After several years of practice, without eye protection, ICs may exceed the new ICRP lifetime eye dose threshold of 500 mSv and be at high risk of developing early radiation-induced cataracts. Radiation protection equipment can reduce these doses and should be used routinely.

Understanding and Minimising Occupational Radiation in the Catheterisation Laboratory with PISAX and the ACIST CVi® Contrast Delivery System.

This paper provides an overview of radiation exposure and its associated risks in the cardiac catheterisation laboratory (cath lab), as well as strategies to minimise radiation exposure for operators, cath lab staff and patients. The benefits of using a mobile 2 mm lead equivalent radiation shield (PISAX) and adoption of an automated contrast injection system (the ACIST CVi® Contrast Delivery System) are discussed, and the potential advantages of their combination are reviewed.

Brain tumours among interventional cardiologists: a cause for alarm? Report of four new cases from two cities and a review of the literature.

AIMS: Interventional cardiologists who work in cardiac catheterisation laboratories are exposed to low doses of ionising radiation that could pose a health hazard. DNA damage is considered to be the main initiating event by which radiation damage to cells results in development of cancer. METHODS AND RESULTS: We report on four interventional cardiologists, all with brain malignancies in the left hemisphere. In a literature search, we found five additional cases and thus present data on six interventional cardiologist and three interventional radiologists who were diagnosed with brain tumours. All worked for prolonged periods with exposure to ionising radiation in the catheterisation laboratory. CONCLUSIONS: In interventional cardiologists and radiologists, the left side of the head is known to be more exposed to radiation than the right. A connection to occupational radiation exposure is biologically plausible, but risk assessment is difficult due to the small population of interventional cardiologists and the low incidence of these tumours. This may be a chance occurrence, but the cause may also be radiation exposure. Scientific study further delineating occupational risks is essential. Since interventional cardiologists have the highest radiation exposure among health professionals, major awareness of radiation safety and training in radiological protection are essential and imperative, and should be used in every procedure.