Sex Differences in Outcomes of Tetralogy of Fallot Patients With Implantable Cardioverter-Defibrillators.

BACKGROUND: Women with congenital heart disease at high risk for sudden cardiac death have been poorly studied thus far. OBJECTIVES: The aim of this study was to assess sex-related differences in patients with tetralogy of Fallot (TOF) and implantable cardioverter-defibrillators (ICDs). METHODS: Data were analyzed from the DAI-T4F (French National Registry of Patients With Tetralogy of Fallot and Implantable Cardioverter Defibrillator) cohort study, which has prospectively enrolled all patients with TOF with ICDs in France since 2010. Clinical events were centrally adjudicated by a blinded committee. RESULTS: A total of 165 patients (mean age 42.2 ± 13.3 years) were enrolled from 40 centers, including 49 women (29.7%). Among the 9,692 patients with TOF recorded in the national database, the proportion of women with ICDs was estimated to be 1.1% (95% CI: 0.8%-1.5%) vs 2.2% (95% CI: 1.8%-2.6%) in men (P < 0.001). The clinical profiles of patients at implantation, including the number of risk factors for ventricular arrhythmias, were similar between women and men. During a median follow-up period of 6.8 years (IQR: 2.5-11.4 years), 78 patients (47.3%) received at least 1 appropriate ICD therapy, without significant difference in annual incidences between women (12.1%) and men (9.9%) (HR: 1.22; 95% CI: 0.76-1.97; P = 0.40). The risk for overall ICD-related complications was similar in women and men (HR: 1.33; 95% CI: 0.81-2.19; P = 0.30), with 24 women (49.0%) experiencing at least 1 complication. CONCLUSIONS: Our findings suggest that women with TOF at high risk for sudden cardiac death have similar benefit/risk balance from ICD therapy compared with men. Whether ICD therapy is equally offered to at-risk women vs men warrants further evaluation in TOF as well as in other congenital heart disease populations. (French National Registry of Patients With Tetralogy of Fallot and Implantable Cardioverter Defibrillator [DAI-T4F]; NCT03837574).

Lack of early etiologic investigations in young sudden cardiac death.

BACKGROUND: Since majority of sudden cardiac arrest (SCA) victims die in the intensive care unit (ICU), early etiologic investigations may improve understanding of SCA and targeted prevention. METHODS: In this prospective, population-based registry all SCA admitted alive across the 48 hospitals of the Paris area were enrolled. We investigated the extent of early etiologic work-up among young SCD cases (<45 years) eventually dying within the ICU. RESULTS: From May 2011 to May 2018, 4,314 SCA patients were admitted alive. Among them, 3,044 died in ICU, including 484 (15.9%) young patients. SCA etiology was established in 233 (48.1%) and remained unexplained in 251 (51.9%). Among unexplained (compared to explained) cases, coronary angiography (17.9 vs. 49.4%, P < 0.001), computed tomography scan (24.7 vs. 46.8%, P < 0.001) and trans-thoracic echocardiography (31.1 vs. 56.7%, P < 0.001) were less frequently performed. Only 22 (8.8%) patients with unexplained SCD underwent all three investigations. SCDs with unexplained status decreased significantly over the 7 years of the study period (from 62.9 to 35.2%, P = 0.005). While specialized TTE and CT scan performances have increased significantly, performance of early coronary angiography did not change. Autopsy, genetic analysis and family screening were performed in only 48 (9.9%), 5 (1.0%) and 14 cases (2.9%) respectively. CONCLUSIONS: More than half of young SCD dying in ICU remained etiologically unexplained; this was associated with a lack of early investigations. Improving early diagnosis may enhance both SCA understanding and prevention, including for relatives. Failure to identify familial conditions may result in other preventable deaths within these families.

Characteristics and factors associated to patients discharging from hospital without an implantable cardioverter defibrillator after out-of-hospital cardiac arrest.

AIMS: Guidelines recommend that in the absence of reversible cause for sudden cardiac arrest (SCA), implantable cardioverter defibrillator (ICD) should be performed to prevent further fatal event. We sought to describe the frequency and characteristics of patients discharged from the hospital without ICD after the SCA in the daily practice. METHODS AND RESULTS: From 2011 to 2018, all SCAs related to a cardiac cause admitted alive across the 48 hospitals of Great Paris Area were prospectively enrolled. Two investigators thoroughly reviewed each medical report to ensure accuracy of the assigned diagnosis towards identifying the cause of SCA and ICD implantation. Out of the 4314 SCA admitted alive at hospital admission, 1064 cardiac-related SCA survivors were discharged alive from hospital, including 356 patients (33.5%) with an ICD and 708 (66.5%) without. The principal underlying cause of SCA among those discharged without an ICD was acute coronary syndrome (ACS; 602, 85%), chronic coronary artery disease (41, 5.8%), structural non-ischaemic heart disease (48, 6.8%), and non-structural heart disease (17, 2.4%). Among ACS-related SCA, 93.8% (602/642) discharged without an ICD. The unique factor associated with non-ICD implantation in the setting of ACS was immediate coronary angioplasty (odds ratio 4.22, 95% confidence interval 1.86-9.30, P < 0.001). CONCLUSION: Two-thirds of SCA survivors were discharged without an ICD, mainly in the setting of ACS. The unique factor associated with non-ICD implantation among ACS was immediate coronary angioplasty emphasizing the fact that ACS definition must be precise since associated with ICD implantation or not.

Evolution of Incidence, Management, and Outcomes Over Time in Sports-Related Sudden Cardiac Arrest.

BACKGROUND: Major efforts have been made to reduce the burden of sports-related sudden cardiac arrest (SrSCA). The extent to which the incidence, management, and outcomes changed over time has not been investigated. OBJECTIVES: The purpose of this study was to assess temporal trends in SrSCA incidence, management, and survival. METHODS: Using data from the French National Institute of Health and Medical Research, we evaluated the evolution of incidence, prehospital management, and survival at hospital discharge of SrSCA among subjects aged 18 to 75 years, over 6 successive 2-year periods between 2005 and 2018. RESULTS: Among the 377 SrSCA, 20 occurred in young competitive athletes (5.3%), whereas 94.7% occurred in middle-aged recreational sports participants. Comparing the last 2-year to the first 2-year period, SrSCA incidence remained stable (6.24 vs 7.00 per million inhabitants/y; P = 0.51), with no significant differences in patients' mean age (46.6 ± 13.8 years vs 51.0 ± 16.4 years; P = 0.42), sex (men 94.7% vs 95.2%; P = 0.99), and history of heart disease (12.5% vs 15.9%; P = 0.85). However, frequency of bystander cardiopulmonary resuscitation and public automated external defibrillator use increased significantly (34.9% vs 94.7%; P < 0.001 and 1.6% vs 28.8%; P = 0.006, respectively). Survival to hospital discharge improved steadily, reaching 66.7% in the last study period compared with 23.8% in the first (P < 0.001). CONCLUSIONS: Incidence of SrSCA remained relatively stable over time, suggesting a need for improvement in screening strategies. However, major improvements in on-field resuscitation led to a 3-fold increase in survival, underlining the value of public education in basic life support that should serve as an example for SCA in general.

Temporal Trends of Out-of-Hospital Cardiac Arrests Without Resuscitation Attempt by Emergency Medical Services.

BACKGROUND: Significant improvements in survival from out-of-hospital cardiac arrest (OHCA) have been reported; however, these are based only on data from OHCA in whom resuscitation is initiated by emergency medical services (EMS). We aimed to assess the characteristics and temporal trends of OHCA without resuscitation attempt by EMS. METHODS: Prospective population-based study between 2011 and 2016 in the Greater Paris area (6.7 million inhabitants). All cases of OHCA were included in collaboration with EMS units, 48 different hospitals, and forensic units. RESULTS: Among 15 207 OHCA (mean age 70.7±16.9 years, 61.6% male), 5486 (36.1%) had no resuscitation attempt by EMS. Factors that were independently associated with increase in likelihood of no resuscitation attempt included: age of patients (odds ratio, 1.06 per year [95% CI, 1.05-1.06], P<0.001), female sex (odds ratio, 1.21 [95% CI, 1.10-1.32], P=0.002), OHCA at home location (odds ratio, 3.38 [95%CI, 2.86-4.01], P<0.001), and absence of bystander (odds ratio, 1.94 [95% CI, 1.74-2.16], P<0.001). Overall, the annual number of OHCA increased by 9.1% (from 2923 to 3189, P=0.028). This increase was related to an increase of the annual number of OHCA without resuscitation attempt by EMS by 26.3% (from 993 to 1253, P=0.012), while the annual number of OHCA with resuscitation attempt by EMS did not significantly change (from 1930 to 1936, P=0.416). Considering only cases with resuscitation attempt, survival rate at hospital discharge increased (from 7.3% to 9.5%, P=0.02). However, when considering all OHCA, survival improvement did not reach statistical significance (from 4.8% to 5.7%, P=0.17). CONCLUSIONS: We demonstrated an increase of the total number of OHCA related to an increase of the number of OHCA without resuscitation attempt by EMS. This increasing proportion of OHCA without resuscitation attempt attenuates improvement in survival rates achieved in EMS-treated patients.

A Primary Prevention Clinical Risk Score Model for Patients With Brugada Syndrome (BRUGADA-RISK).

OBJECTIVES: The goal of this study was to develop a risk score model for patients with Brugada syndrome (BrS). BACKGROUND: Risk stratification in BrS is a significant challenge due to the low event rates and conflicting evidence. METHODS: A multicenter international cohort of patients with BrS and no previous cardiac arrest was used to evaluate the role of 16 proposed clinical or electrocardiogram (ECG) markers in predicting ventricular arrhythmias (VAs)/sudden cardiac death (SCD) during follow-up. Predictive markers were incorporated into a risk score model, and this model was validated by using out-of-sample cross-validation. RESULTS: A total of 1,110 patients with BrS from 16 centers in 8 countries were included (mean age 51.8 ± 13.6 years; 71.8% male). Median follow-up was 5.33 years; 114 patients had VA/SCD (10.3%) with an annual event rate of 1.5%. Of the 16 proposed risk factors, probable arrhythmia-related syncope (hazard ratio [HR]: 3.71; p < 0.001), spontaneous type 1 ECG (HR: 3.80; p < 0.001), early repolarization (HR: 3.42; p < 0.001), and a type 1 Brugada ECG pattern in peripheral leads (HR: 2.33; p < 0.001) were associated with a higher risk of VA/SCD. A risk score model incorporating these factors revealed a sensitivity of 71.2% (95% confidence interval: 61.5% to 84.6%) and a specificity of 80.2% (95% confidence interval: 75.7% to 82.3%) in predicting VA/SCD at 5 years. Calibration plots showed a mean prediction error of 1.2%. The model was effectively validated by using out-of-sample cross-validation according to country. CONCLUSIONS: This multicenter study identified 4 risk factors for VA/SCD in a primary prevention BrS population. A risk score model was generated to quantify risk of VA/SCD in BrS and inform implantable cardioverter-defibrillator prescription.

Long-Term Follow-Up of Patients With Tetralogy of Fallot and Implantable Cardioverter Defibrillator: The DAI-T4F Nationwide Registry.

BACKGROUND: Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease, and sudden cardiac death represents an important mode of death in these patients. Data evaluating the implantable cardioverter defibrillator (ICD) in this patient population remain scarce. METHODS: A Nationwide French Registry including all patients with tetralogy of Fallot with an ICD was initiated in 2010 by the French Institute of Health and Medical Research. The primary time to event end point was the time from ICD implantation to first appropriate ICD therapy. Secondary outcomes included ICD-related complications, heart transplantation, and death. Clinical events were centrally adjudicated by a blinded committee. RESULTS: A total of 165 patients (mean age, 42.2±13.3 years, 70.1% males) were included from 40 centers, including 104 (63.0%) in secondary prevention. During a median (interquartile range) follow-up of 6.8 (2.5-11.4) years, 78 (47.3%) patients received at least 1 appropriate ICD therapy. The annual incidence of the primary outcome was 10.5% (7.1% and 12.5% in primary and secondary prevention, respectively; P=0.03). Overall, 71 (43.0%) patients presented with at least 1 ICD complication, including inappropriate shocks in 42 (25.5%) patients and lead dysfunction in 36 (21.8%) patients. Among 61 (37.0%) patients in primary prevention, the annual rate of appropriate ICD therapies was 4.1%, 5.3%, 9.5%, and 13.3% in patients with, respectively, 0, 1, 2, or ≥3 guidelines-recommended risk factors. QRS fragmentation was the only independent predictor of appropriate ICD therapies (hazard ratio, 3.47 [95% CI, 1.19-10.11]), and its integration in a model with current criteria increased the 5-year time-dependent area under the curve from 0.68 to 0.81 (P=0.006). Patients with congestive heart failure or reduced left ventricular ejection fraction had a higher risk of nonarrhythmic death or heart transplantation (hazard ratio, 11.01 [95% CI, 2.96-40.95]). CONCLUSIONS: Patients with tetralogy of Fallot and an ICD experience high rates of appropriate therapies, including those implanted in primary prevention. The considerable long-term burden of ICD-related complications, however, underlines the need for careful candidate selection. A combination of easy-to-use criteria including QRS fragmentation might improve risk stratification. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03837574.

Radiotherapy in Patients With a Cardiac Implantable Electronic Device.

Recently, the Heart Rhythm Society published recommendations on management of patients with cardiac implantable electronic device (CIED) who require radiotherapy (RT). We aimed to report the experience of a teaching hospital, and discuss our practice in the context of recently published guidelines. We identified all consecutive CIED recipients (12,736 patients) who underwent RT between March 2006 and June 2017. Among them, 90 (1%) patients (78.2 ± 10 years, 73% male) had a CIED: 82 pacemakers and 8 implantable cardioverter-defibrillators. Two patients required CIED extraction prior to RT for ipsilateral breast cancer (no device replacement in 1 patient). Four patients (5%) were considered at high-risk, 35 (39%) at intermediate-risk, and the remaining 50 (56%) at low-risk for CIED dysfunction. Overall, only a minority of patients followed recommended local protocol during RT delivery (31%) and during follow-up (56%). CIED malfunction was detected in 5 patients (6%), mainly back-up mode resetting (80%), with 4 (including 3 pelvic cancer location) patients initially classified as being at intermediate-risk and 1 at low-risk. Four out of the 5 patients with CEID malfunction had received neutron producing beams. In conclusion, our findings underline the lack of rigorous monitoring of patients undergoing RT (though CIED malfunction appears to be rare and relatively benign in nature), and emphasize the interest of considering neutron producing beam for risk stratification as recommended in recent guidelines. Optimization of patient's management requires a close collaboration between both CIED clinicians and radiation oncologists, and more systematic remote CIED monitoring may be helpful.

Out-of-hospital cardiac arrest during the COVID-19 pandemic in Paris, France: a population-based, observational study.

BACKGROUND: Although mortality due to COVID-19 is, for the most part, robustly tracked, its indirect effect at the population level through lockdown, lifestyle changes, and reorganisation of health-care systems has not been evaluated. We aimed to assess the incidence and outcomes of out-of-hospital cardiac arrest (OHCA) in an urban region during the pandemic, compared with non-pandemic periods. METHODS: We did a population-based, observational study using data for non-traumatic OHCA (N=30 768), systematically collected since May 15, 2011, in Paris and its suburbs, France, using the Paris Fire Brigade database, together with in-hospital data. We evaluated OHCA incidence and outcomes over a 6-week period during the pandemic in adult inhabitants of the study area. FINDINGS: Comparing the 521 OHCAs of the pandemic period (March 16 to April 26, 2020) to the mean of the 3052 total of the same weeks in the non-pandemic period (weeks 12-17, 2012-19), the maximum weekly OHCA incidence increased from 13·42 (95% CI 12·77-14·07) to 26·64 (25·72-27·53) per million inhabitants (p<0·0001), before returning to normal in the final weeks of the pandemic period. Although patient demographics did not change substantially during the pandemic compared with the non-pandemic period (mean age 69·7 years [SD 17] vs 68·5 [18], 334 males [64·4%] vs 1826 [59·9%]), there was a higher rate of OHCA at home (460 [90·2%] vs 2336 [76·8%]; p<0·0001), less bystander cardiopulmonary resuscitation (239 [47·8%] vs 1165 [63·9%]; p<0·0001) and shockable rhythm (46 [9·2%] vs 472 [19·1%]; p<0·0001), and longer delays to intervention (median 10·4 min [IQR 8·4-13·8] vs 9·4 min [7·9-12·6]; p<0·0001). The proportion of patients who had an OHCA and were admitted alive decreased from 22·8% to 12·8% (p<0·0001) in the pandemic period. After adjustment for potential confounders, the pandemic period remained significantly associated with lower survival rate at hospital admission (odds ratio 0·36, 95% CI 0·24-0·52; p<0·0001). COVID-19 infection, confirmed or suspected, accounted for approximately a third of the increase in OHCA incidence during the pandemic. INTERPRETATION: A transient two-times increase in OHCA incidence, coupled with a reduction in survival, was observed during the specified time period of the pandemic when compared with the equivalent time period in previous years with no pandemic. Although this result might be partly related to COVID-19 infections, indirect effects associated with lockdown and adjustment of health-care services to the pandemic are probable. Therefore, these factors should be taken into account when considering mortality data and public health strategies. FUNDING: The French National Institute of Health and Medical Research (INSERM).

Low rates of immediate coronary angiography among young adults resuscitated from sudden cardiac arrest.

AIM: Coronary artery disease (CAD) has recently been emphasized as a major cause of sudden cardiac arrest (SCA) in young adults. We aim to assess the rate of immediate coronary angiography performance in young patients resuscitated from SCA. METHODS: From May 2011 to May 2017, all cases of out-of-hospital SCA aged 18-40 years alive at hospital admission were prospectively included in 48 hospitals of the Great Paris area. Cardiovascular causes of SCA were centrally adjudicated, and management including immediate coronary angiography performance was assessed. RESULTS: Out of 3579 SCA admitted alive, 409 (11.4%) patients were under 40 years of age (32.3 ± 6.2 years, 69.7% males), with 244 patients having a definite cause identified. Among those, CAD accounted for 72 (29.5%) cases, of which 64 (88.9%) were acute coronary syndromes. The rate of immediate coronary angiography was only 41.7% compared to 65.1% among those ≥40-years (P < 0.001). During the study period, while the rate of immediate coronary angiography increased from 60.5% to 70.3% (P < 0.001) in patients aged ≥40 years, the rate in patients aged less than 40 years remained stable (43.5% to 45.3%, P = 0.795). Patients younger than 40 years were significantly less likely to undergo immediate coronary angiography (OR = 0.34, 95% CI: 0.25-0.47), although early angiography was associated with survival at hospital discharge (OR = 2.68, 95% CI: 1.21-6.00). CONCLUSION: CAD is the first cause of SCA in young adults aged less than 40 years. The observed low rates of immediate coronary angiography suggest a missed opportunity for early intervention.

Does occurrence during sports affect sudden cardiac arrest survival?

OBJECTIVES: A higher survival rate was observed in Sudden Cardiac Arrest (SCA) occurring during sports activities, although the underlying mechanisms remain unclear. We tested the hypothesis that better initial management, rather than sports per se, may account for the observed better outcomes during sports activities. METHODS: Data was taken between May 2011 and March 2016 from a prospective ongoing registry that includes all SCA in Paris and suburbs (6.7 million inhabitants). Sports-related SCA (i.e. SCA occurring during sport activities or within one hour of cessation of the activity) were identified. RESULTS: Over the study period, 13,400 SCA occurred, of which 154 were sports-related (median age: 51.2 years, 96.1% males). At discharge, sports activity was associated with an 8-times higher survival rate (39.7% vs. 5.1%, P < 0.001). Logistic regression showed that after considering potential confounders, including age, gender, SCA location, witness presence, time to response, and initial shockable rhythm, occurrence of SCA during sports was associated with a higher survival rate (OR 1.77, 95% CI 1.14-2.74, P = 0.01). However, after further adjustment for initial basic life support, i.e. bystander CPR and AED use, there was no association between sports setting and survival at hospital discharge (OR 1.43, 95% CI 0.91-2.23, P = 0.12). CONCLUSION: Sports-related SCA is a rare event, with an 8-times higher survival rate compared to non-sports-related SCA. Better initial management, including bystander CPR and AED use, rather than sports per se, mainly accounts this difference. This highlights the major importance of population education to basic life support in improving SCA outcome.