Predictors and 5-Year Clinical Outcomes of Pacemaker After TAVR: Analysis From the PARTNER 2 SAPIEN 3 Registries.

BACKGROUND: Conduction disturbances requiring a permanent pacemaker (PPM) are a frequent complication of transcatheter aortic valve replacement (TAVR) with few reports of rates, predictors, and long-term clinical outcomes following implantation of the third-generation, balloon-expandable SAPIEN 3 (S3) transcatheter heart valve (THV). OBJECTIVES: The aim of this study was to investigate the rates, predictors, and long-term clinical outcomes of PPM implantation following TAVR with the S3 THV. METHODS: The current study included 857 patients in the PARTNER 2 S3 registries with intermediate and high surgical risk without prior PPM, and investigated predictors and 5-year clinical outcomes of new PPM implanted within 30 days of TAVR. RESULTS: Among 857 patients, 107 patients (12.5%) received a new PPM within 30 days after TAVR. By multivariable analysis, predictors of PPM included increased age, pre-existing right bundle branch block, larger THV size, greater THV oversizing, moderate or severe annulus calcification, and implantation depth >6 mm. At 5 years (median follow-up 1,682.0 days [min 2.0 days, max 2,283.0 days]), new PPM was not associated with increased rates of all-cause mortality (Adj HR: 1.20; 95% CI: 0.85-1.70; P = 0.30) or repeat hospitalization (Adj HR: 1.22; 95% CI: 0.67-2.21; P = 0.52). Patients with new PPM had a decline in left ventricular ejection fraction at 1 year that persisted at 5 years (55.1 ± 2.55 vs 60.4 ± 0.65; P = 0.02). CONCLUSIONS: PPM was required in 12.5% of patients without prior PPM who underwent TAVR with a SAPIEN 3 valve in the PARTNER 2 S3 registries and was not associated with worse clinical outcomes, including mortality, at 5 years. Modifiable factors that may reduce the PPM rate include bioprosthetic valve oversizing, prosthesis size, and implantation depth.

Empagliflozin's role in reducing ventricular repolarization heterogeneity: insights into cardiovascular mortality decline from the EMPATHY-HEART trial.

BACKGROUND: The incidence of myocardial infarction (MI) and sudden cardiac death (SCD) is significantly higher in individuals with Type 2 Diabetes Mellitus (T2DM) than in the general population. Strategies for the prevention of fatal arrhythmias are often insufficient, highlighting the need for additional non-invasive diagnostic tools. The T-wave heterogeneity (TWH) index measures variations in ventricular repolarization and has emerged as a promising predictor for severe ventricular arrhythmias. Although the EMPA-REG trial reported reduced cardiovascular mortality with empagliflozin, the underlying mechanisms remain unclear. This study investigates the potential of empagliflozin in mitigating cardiac electrical instability in patients with T2DM and coronary heart disease (CHD) by examining changes in TWH. METHODS: Participants were adult outpatients with T2DM and CHD who exhibited TWH > 80 µV at baseline. They received a 25 mg daily dose of empagliflozin and were evaluated clinically including electrocardiogram (ECG) measurements at baseline and after 4 weeks. TWH was computed from leads V4, V5, and V6 using a validated technique. The primary study outcome was a significant (p < 0.05) change in TWH following empagliflozin administration. RESULTS: An initial review of 6,000 medical records pinpointed 800 patients for TWH evaluation. Of these, 412 exhibited TWH above 80 µV, with 97 completing clinical assessments and 90 meeting the criteria for high cardiovascular risk enrollment. Empagliflozin adherence exceeded 80%, resulting in notable reductions in blood pressure without affecting heart rate. Side effects were generally mild, with 13.3% experiencing Level 1 hypoglycemia, alongside infrequent urinary and genital infections. The treatment consistently reduced mean TWH from 116 to 103 µV (p = 0.01). CONCLUSIONS: The EMPATHY-HEART trial preliminarily suggests that empagliflozin decreases heterogeneity in ventricular repolarization among patients with T2DM and CHD. This reduction in TWH may provide insight into the mechanism behind the decreased cardiovascular mortality observed in previous trials, potentially offering a therapeutic pathway to mitigate the risk of severe arrhythmias in this population. TRIAL REGISTRATION: NCT: 04117763.

Cardiovascular Complications With Delivery Hospitalizations in Patients With Pulmonary Hypertension: A Nationwide Study From 2011 to 2020.

BACKGROUND: Pregnancy in patients with pulmonary hypertension (PH) is associated with a heightened risk of medical complications including right heart failure, pulmonary edema, and arrhythmias. Our study investigated the association between PH and these complications during delivery. METHODS AND RESULTS: The National Inpatient Sample was used to identify delivery hospitalizations from 2011 to 2020. Multivariable logistic regression was performed to study the association of PH with the primary outcomes of in-hospital medical and obstetric complications. A total of 37 482 207 delivery hospitalizations in women ≥18 years of age were identified, of which 9593 patients had PH. Pregnant patients with PH had higher incidence of complications during delivery including preeclampsia/eclampsia, arrhythmias, and pulmonary edema among others, compared with those without PH. Pregnant patients with PH also had a higher incidence of in-hospital mortality compared with those without PH (0.51% versus 0.007%). In propensity-matched analyses, PH was still significantly associated with a higher risk of in-hospital mortality (odds ratio [OR], 5.02 [95% CI, 1.82-13.90]; P=0.001), pulmonary edema (OR, 9.11 [95% CI, 6.34-13.10]; P<0.001), peripartum cardiomyopathy (OR, 1.85 [95% CI, 1.37-2.50]; P<0.001), venous thromboembolism (OR, 12.60 [95% CI, 6.04-26.10]; P<0.001), cardiac arrhythmias (OR, 6.11 [95% CI, 4.97-7.53]; P<0.001), acute kidney injury (OR, 3.72 [95% CI, 2.86-4.84]; P<0.001), preeclampsia/eclampsia (OR, 2.24 [95% CI, 1.95-2.58]; P<0.001), and acute coronary syndrome (OR, 2.01 [95% CI, 1.06-3.80]; P=0.03), compared with pregnant patients without PH. CONCLUSIONS: Delivery hospitalizations in patients with PH are associated with a high risk of mortality, pulmonary edema, peripartum cardiomyopathy, venous thromboembolism, arrhythmias, acute kidney injury, preeclampsia/eclampsia, and acute coronary syndrome.

Lack of Prognostic Value of T-Wave Alternans for Implantable Cardioverter-Defibrillator Benefit in Primary Prevention.

BACKGROUND: New methods to identify patients who benefit from a primary prophylactic implantable cardioverter-defibrillator (ICD) are needed. T-wave alternans (TWA) has been shown to associate with arrhythmogenesis of the heart and sudden cardiac death. We hypothesized that TWA might be associated with benefit from ICD implantation in primary prevention. METHODS AND RESULTS: In the EU-CERT-ICD (European Comparative Effectiveness Research to Assess the Use of Primary Prophylactic Implantable Cardioverter-Defibrillators) study, we prospectively enrolled 2327 candidates for primary prophylactic ICD. A 24-hour Holter monitor reading was taken from all recruited patients at enrollment. TWA was assessed from Holter monitoring using the modified moving average method. Study outcomes were all-cause death, appropriate shock, and survival benefit. TWA was assessed both as a contiguous variable and as a dichotomized variable with cutoff points <47 µV and <60 µV. The final cohort included 1734 valid T-wave alternans samples, 1211 patients with ICD, and 523 control patients with conservative treatment, with a mean follow-up time of 2.3 years. TWA ≥60 µV was a predicter for a higher all-cause death in patients with an ICD on the basis of a univariate Cox regression model (hazard ratio, 1.484 [95% CI, 1.024-2.151]; P=0.0374; concordance statistic, 0.51). In multivariable models, TWA was not prognostic of death or appropriate shocks in patients with an ICD. In addition, TWA was not prognostic of death in control patients. In a propensity score-adjusted Cox regression model, TWA was not a predictor of ICD benefit. CONCLUSIONS: T-wave alternans is poorly prognostic in patients with a primary prophylactic ICD. Although it may be prognostic of life-threatening arrhythmias and sudden cardiac death in several patient populations, it does not seem to be useful in assessing benefit from ICD therapy in primary prevention among patients with an ejection fraction of ≤35%.

Burden of cardiac arrhythmias in patients with acute myocardial infarction and their impact on hospitalization outcomes: insights from China acute myocardial infarction (CAMI) registry.

BACKGROUND: The coexistence of cardiac arrhythmias in patients with acute myocardial infarction (AMI) usually exhibits poor prognosis. However, there are few contemporary data available on the burden of cardiac arrhythmias in AMI patients and their impact on in-hospital outcomes. METHODS: The present study analyzed data from the China Acute Myocardial Infarction (CAMI) registry involving 23,825 consecutive AMI patients admitted to 108 hospitals from January 2013 to February 2018. Cardiac arrhythmias were defined as the presence of bradyarrhythmias, sustained atrial tachyarrhythmias, and sustained ventricular tachyarrhythmias that occurred during hospitalization. In-hospital outcome was defined as a composite of all-cause mortality, cardiogenic shock, re-infarction, stroke, or heart failure. RESULTS: Cardiac arrhythmia was presented in 1991 (8.35%) AMI patients, including 3.4% ventricular tachyarrhythmias, 2.44% bradyarrhythmias, 1.78% atrial tachyarrhythmias, and 0.73% ≥2 kinds of arrhythmias. Patients with arrhythmias were more common with ST-segment elevation myocardial infarction (83.3% vs. 75.5%, P < 0.001), fibrinolysis (12.8% vs. 8.0%, P < 0.001), and previous heart failure (3.7% vs. 1.5%, P < 0.001). The incidences of in-hospital outcomes were 77.0%, 50.7%, 43.5%, and 41.4%, respectively, in patients with ≥ 2 kinds of arrhythmias, ventricular tachyarrhythmias, bradyarrhythmias, and atrial tachyarrhythmias, and were significantly higher in all patients with arrhythmias than those without arrhythmias (48.9% vs. 12.5%, P < 0.001). The presence of any kinds of arrhythmia was independently associated with an increased risk of hospitalization outcome (≥ 2 kinds of arrhythmias, OR 26.83, 95%CI 18.51-38.90; ventricular tachyarrhythmias, OR 8.56, 95%CI 7.34-9.98; bradyarrhythmias, OR 5.82, 95%CI 4.87-6.95; atrial tachyarrhythmias, OR4.15, 95%CI 3.38-5.10), and in-hospital mortality (≥ 2 kinds of arrhythmias, OR 24.44, 95%CI 17.03-35.07; ventricular tachyarrhythmias, OR 13.61, 95%CI 10.87-17.05; bradyarrhythmias, OR 7.85, 95%CI 6.0-10.26; atrial tachyarrhythmias, OR 4.28, 95%CI 2.98-6.16). CONCLUSION: Cardiac arrhythmia commonly occurred in patients with AMI might be ventricular tachyarrhythmias, followed by bradyarrhythmias, atrial tachyarrhythmias, and ≥ 2 kinds of arrhythmias. The presence of any arrhythmias could impact poor hospitalization outcomes. REGISTRATION: Clinical Trial Registration: Identifier: NCT01874691.

Arrhythmias and ion channelopathies causing sudden cardiac death in Hispanic/Latino and Indigenous populations.

The limited literature and increasing interest in studies on cardiac electrophysiology, explicitly focusing on cardiac ion channelopathies and sudden cardiac death in diverse populations, has prompted a comprehensive examination of existing research. Our review specifically targets Hispanic/Latino and Indigenous populations, which are often underrepresented in healthcare studies. This review encompasses investigations into genetic variants, epidemiology, etiologies, and clinical risk factors associated with arrhythmias in these demographic groups. The review explores the Hispanic paradox, a phenomenon linking healthcare outcomes to socioeconomic factors within Hispanic communities in the United States. Furthermore, it discusses studies exemplifying this observation in the context of arrhythmias and ion channelopathies in Hispanic populations. Current research also sheds light on disparities in overall healthcare quality in Indigenous populations. The available yet limited literature underscores the pressing need for more extensive and comprehensive research on cardiac ion channelopathies in Hispanic/Latino and Indigenous populations. Specifically, additional studies are essential to fully characterize pathogenic genetic variants, identify population-specific risk factors, and address health disparities to enhance the detection, prevention, and management of arrhythmias and sudden cardiac death in these demographic groups.

Predictors of mortality and burden of arrhythmias in endstage heart failure.

BACKGROUND: Heart failure (HF) is a significant cause of morbidity and mortality in the United States, contributing to approximately 1 in 8 deaths. Individuals with end-stage HF (eHF) experience debilitating symptoms leading to poor quality of life (QoL). METHODS: We used the ICD-10 code for eHF (I5084) from the National Inpatient Sample (NIS) (2016-2020) to identify all patients with eHF. We used a multivariable logistic regression model to adjust for confounders and estimate the mortality probability in each arrhythmia cohort. Our primary outcome was in-hospital mortality risk in each group. A p-value of 0.05 was deemed significant. RESULTS: There were 22,703 hospitalizations with eHF (mean age 67 years ±16). Men represented 66.5 % (15,091) of the population. In this cohort, 59 % (13,018) were Caucasians, 27.2 % (6,017) were Blacks, 8.7 % (1,924) were Hispanics, and 2.9 % (505) were Asians. Of these individuals, 50.4 % (11,434) had atrial fibrillation (AFIB). The majority of the arrhythmia subgroups had independent associations with mortality, with adjusted odds ratio (aOR) for VFIB 5.8 (4.6-7.1), AFIB 4.3 (3.9-4.5), SVT 1.9 (1.6-2.4), and VT 1.2 (1.1-1.4), p < 0.0001, each. CONCLUSION: This analysis revealed that approximately half of the hospitalized population with end-stage heart failure are burdened with atrial fibrillation. Ventricular and atrial fibrillation, supraventricular tachycardia, and ventricular tachycardia each carried an independent mortality risk, with ventricular fibrillation having the highest risk.

Pacemaker-Related Factors and Outcomes of Fontan Patients　- Impact of Paced QRS Duration.

BACKGROUND: Permanent pacemaker (PPM) implantation has been identified as a risk factor for morbidity and mortality after Fontan operation. This study investigated the factors associated with outcomes in patients with Fontan physiology who underwent PPM implantation.Methods and Results: We retrospectively reviewed 508 patients who underwent Fontan surgery at Asan Medical Center between September 1992 and August 2022. Of these patients, 37 (7.3%) received PPM implantation. Five patients were excluded, leaving 32 patients, of whom 11 were categorized into the poor outcome group. Poor outcomes comprised death, heart transplantation, and "Fontan failure". Clinical, Fontan procedure-related, and PPM-related factors were compared between the poor and good outcome groups. Ventricular morphology, Fontan procedure-associated factors, pacing mode, high ventricular pacing rate, and time from first arrhythmia to PPM implantation did not differ significantly between the 2 groups. However, the poor outcome group exhibited a significantly longer mean paced QRS duration (P=0.044). Receiver operating characteristic curve analysis revealed a paced QRS duration cut-off value of 153 ms with an area under the curve of 0.73 (P=0.035). CONCLUSIONS: A longer paced QRS duration was associated with poor outcomes, indicating its potential to predict adverse outcomes among Fontan patients.

Markers of ventricular repolarization and overall mortality in sleep disordered breathing.

INTRODUCTION: Variability and prolongation of ventricular repolarization - measured by changes in QT interval and QT variability are independently associated with ventricular arrhythmias, sudden death, and mortality but such studies did not examine the role of sleep-disordered breathing. We aimed to determine whether sleep-disordered breathing moderated the association between measures of ventricular repolarization and overall mortality. METHODS: Eight hundred participants were randomly selected from each of the following four groups in the Sleep Heart Health Study: mild, moderate, severe or no sleep disordered breathing (n = 200 each). Overnight electrocardiograms were analyzed for QTc duration and QT variability (standard deviation of QT intervals, normalized QT interval variance and the short-term interval beat-to-beat QT variability). Cox proportional hazards penalized regression modeling was used to identify predictors of mortality. RESULTS: Eight hundred of 5600 participants were randomly selected. The participants (68 ± 10 years; 56.8% male) were followed for an average of 8.2 years during which time 222 (28.4%) died. QTc, SDQT, and QTVN were associated with the presence of SDB (p = 0.002, p = 0.014, and p = 0.024, respectively). After adjusting for covariates, the presence of sleep-disordered breathing did not moderate the association between QTc length, QT variability and mortality (p > 0.05). CONCLUSION: Sleep-disordered breathing was associated with some measures of ventricular repolarization. However, sleep-disordered breathing was not an effect modifier for the relationship between QTc and QT variability and mortality.

The best QT correction formula in a non-hospitalized population: the Fasa PERSIAN cohort study.

BACKGROUND: QT interval as an indicator of ventricular repolarization is a clinically important parameter on an electrocardiogram (ECG). QT prolongation predisposes individuals to different ventricular arrhythmias and sudden cardiac death. The current study aimed to identify the best heart rate corrected QT interval for a non-hospitalized Iranian population based on cardiovascular mortality. METHODS: Using Fasa PERSIAN cohort study data, this study enrolled 7071 subjects aged 35-70 years. Corrected QT intervals (QTc) were calculated by the QT interval measured by Cardiax® software from ECGs and 6 different correction formulas (Bazett, Fridericia, Dmitrienko, Framingham, Hodges, and Rautaharju). Mortality status was checked using an annual telephone-based follow-up and a minimum 3-year follow-up for each participant. Bland-Altman, QTc/RR regression, sensitivity analysis, and Cox regression were performed in IBM SPSS Statistics v23 to find the best QT. Also, for calculating the upper and lower limits of normal of different QT correction formulas, 3952 healthy subjects were selected. RESULTS: In this study, 56.4% of participants were female, and the mean age was 48.60 ± 9.35 years. Age, heart rate in females, and QT interval in males were significantly higher. The smallest slopes of QTc/RR analysis were related to Fridericia in males and Rautaharju followed by Fridericia in females. Thus, Fridericia's formula was identified as the best mathematical formula and Bazett's as the worst in males. In the sensitivity analysis, however, Bazett's formula had the highest sensitivity (23.07%) among all others in cardiac mortality. Also, in the Cox regression analysis, Bazett's formula was better than Fridericia's and was identified as the best significant cardiac mortality predictor (Hazard ratio: 4.31, 95% CI 1.73-10.74, p value = 0.002). CONCLUSION: Fridericia was the best correction formula based on mathematical methods. Bazett's formula despite its poorest performance in mathematical methods, was the best one for cardiac mortality prediction. Practically, it is suggested that physicians use QTcB for a better evaluation of cardiac mortality risk. However, in population-based studies, QTcFri might be the one to be used by researchers.

Validation of Corrected and Dispersed QT as Predictors of Adverse Outcomes in Acute Cardiotoxicities.

Acute cardiovascular poisoning is a major cause of adverse outcomes in poisoning emergencies. The prognostic validity of corrected QT (QTc) and dispersed QT (QTd) in these outcomes is still limited. The present study aimed to determine the risk factors of mortality, adverse cardiovascular events (ACVE), and intensive care unit (ICU) admission in patients with acute cardiovascular toxicities and assess the validity of QTc and QTd intervals in predicting these outcomes. This study was conducted on adult patients admitted to Tanta University Poison Control Center with a history of acute cardiotoxic drugs or toxins exposure. The demographic and toxicological data of patients were recorded. Clinical examination, routine laboratory investigations, ECG grading, and measurement of QTc and QTd were performed. The patients were grouped according to their adverse outcomes. Among the included patients, 51 (31.48%) patients died, 61 (37.65%) patients had ACVE, and 68 (41.98%) patients required ICU admission. The most common cause of poisoning is aluminum phosphide, followed by cholinesterase inhibitors. QTd and QTdc showed no significant difference among outcome groups. The best cut-off values of QTc to predict mortality, ACVE, and ICU admission were > 491.1 ms, > 497.9 ms, and ≥ 491.9 ms, respectively. The derived cut-off QTc values were independent predictors for all adverse outcomes after adjusting for poison type, serum HCO3, and pulse. The highest odds ratios for all adverse outcomes were observed in aluminum phosphide poisoning and low HCO3 < 18 mmol/L. Thus, serum HCO3 and QTc interval should be monitored for acute cardiotoxicities, especially in aluminum phosphide and cholinesterase inhibitors poisoning.

Relationship between impaired repolarization parameters and poor cardiovascular clinical outcomes in patients with potentially serious coronary artery anomalies.

BACKGROUND: Congenital coronary artery anomalies (CCAAs) have the potential for life-threatening complications, including malignant ventricular arrhythmias and sudden cardiac death (SCD). In this study, we aimed to evaluate the relationship between impaired repolarization parameters and poor cardiovascular clinical outcomes in patients with potentially serious CCAAs. METHODS: This retrospective study included 85 potentially serious CCAA patients (mean age: 54.7 ± 13.6 years; male:44) who were diagnosed with conventional and coronary computed tomography angiography (CCTA). All patients underwent transthoracic echocardiography and 12-lead surface electrocardiography. Cardiac events were defined as sustained ventricular tachycardia or fibrillation, syncope, cardiac arrest and SCD. RESULTS: The presence of interarterial course (IAC) was confirmed by CCTA in 37 (43.5%) patients. During a median follow-up time of 24 (18-50) months, a total of 11 (12.9%) patients experienced cardiac events. The presence of IAC was significantly more frequent and Tp-e interval, Tp-e/QTc ratio and frontal QRS/T angle (fQRSTa) were significantly greater in patients with poor clinical outcomes. Moreover, the presence of IAC, high Tp-e/QTc ratio and high fQRSTa were found to be independent predictors of poor clinical outcomes and decreased long-term cardiac event-free survival in these patients. A net reclassification index was +1.0 for the Tp-e/QTc ratio and +1.3 for fQRSTa which were confirmable for additional predictability of these repolarization abnormalities. CONCLUSION: Impaired repolarization parameters, including wider fQRSTa, prolonged Tp-e interval, and increased Tp-e/QTc ratio, and IAC may be associated with poor cardiovascular clinical outcomes in potentially serious CCAA patients.

Determinants of worse prognosis in patients with cardiac resynchronization therapy defibrillators. Are ventricular arrhythmias an adjunctive risk factor?

AIMS: Cardiac resynchronization therapy (CRT) is indicated in patients with systolic heart failure (HF), severe left ventricle (LV) dysfunction and interventricular dyssynchrony.In prospective observational research, we aimed to evaluate whether CRT-induced LV reverse remodelling and occurrence of ventricular arrhythmias (VT/VF) independently contribute to prognosis in patients with CRT defibrillators (CRT-D). METHODS: In 95 Italian cardiological centres, after a screening period of 6 months, patients were categorized according to VT/VF occurrence and CRT response, defined as LV end-systolic volume relative reduction >15% or LV ejection fraction absolute increase >5%. The main endpoint was death or HF hospitalizations. RESULTS: Among 1308 CRT-D patients (80% male, mean age 66 years), at 6 months, follow-up 71% were identified as CRT responders and 12% experienced appropriate VT/VF detections. The main endpoint was significantly and independently associated with previous myocardial infarction, New York Heart Association Class, VT/VF occurrence and with CRT response. CRT nonresponder patients who suffered VT/VF in the screening period had a risk of death or HF hospitalizations [HR = 7.82, 95% confidence interval (CI) = 3.95-15.48] significantly (P < 0.001) higher than CRT responders without VT/VF occurrence. This risk is mitigated without VT/VF occurrence (HR = 3.47, 95% CI = 2.03-5.91, P < 0.001) or in case of CRT response (HR = 3.11, 95% CI = 1.44-6.72, P = 0.004). CONCLUSION: Our data show that both CRT response and occurrence of VT/VF independently contribute to the risk of death or HF-related hospitalizations in CRT-D patients. Early VT/VF occurrence may be identified as a marker of disease severity than can be mitigated by CRT response both in terms of all-cause mortality and long-term VT/VF onset. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00147290 and NCT00617175.

Epinephrine before defibrillation in patients with shockable in-hospital cardiac arrest: propensity matched analysis.

OBJECTIVE: To determine the use of epinephrine (adrenaline) before defibrillation for treatment of in-hospital cardiac arrest due to a ventricular arrhythmia and examine its association with patient survival. DESIGN: Propensity matched analysis. SETTING: 2000-18 data from 497 hospitals participating in the American Heart Association's Get With The Guidelines-Resuscitation registry. PARTICIPANTS: Adults aged 18 and older with an index in-hospital cardiac arrest due to an initial shockable rhythm treated with defibrillation. INTERVENTIONS: Administration of epinephrine before first defibrillation. MAIN OUTCOME MEASURES: Survival to discharge; favorable neurological survival, defined as survival to discharge with none, mild, or moderate neurological disability measured using cerebral performance category scores; and survival after acute resuscitation (that is, return of spontaneous circulation for >20 minutes). A time dependent, propensity matched analysis was performed to adjust for confounding due to indication and evaluate the independent association of epinephrine before defibrillation with study outcomes. RESULTS: Among 34 820 patients with an initial shockable rhythm, 7054 (20.3%) were treated with epinephrine before defibrillation, contrary to current guidelines. In comparison with participants treated with defibrillation first, participants receiving epinephrine first were less likely to have a history of myocardial infarction or heart failure, but more likely to have renal failure, sepsis, respiratory insufficiency, and receive mechanical ventilation before in-hospital cardiac arrest (standardized differences >10% for all). Treatment with epinephrine before defibrillation was strongly associated with delayed defibrillation (median 4 minutes v 0 minutes). In propensity matched analysis (6569 matched pairs), epinephrine before defibrillation was associated with lower odds of survival to discharge (22.4% v 29.7%; adjusted odds ratio 0.69; 95% confidence interval 0.64 to 0.74; P<0.001), favorable neurological survival (15.8% v 21.6%; 0.68; 0.61 to 0.76; P<0.001) and survival after acute resuscitation (61.7% v 69.5%; 0.73; 0.67 to 0.79; P<0.001). The above findings were consistent in a range of sensitivity analyses, including matching according to defibrillation time. CONCLUSIONS: Contrary to current guidelines that prioritize immediate defibrillation for in-hospital cardiac arrest due to a shockable rhythm, one in five patients are treated with epinephrine before defibrillation. Use of epinephrine before defibrillation was associated with worse survival outcomes.