key: cord-0836518-yyjdg6kb authors: Abrams, Mark P.; Wan, Elaine Y.; Waase, Marc P.; Morrow, John P.; Dizon, Jose M.; Yarmohammadi, Hirad; Berman, Jeremy P.; Rubin, Geoffrey A.; Kushnir, Alexander; Poterucha, Timothy J.; Elias, Pierre A.; Rubin, David A.; Ehlert, Frederick; Biviano, Angelo; Uriel, Nir; Garan, Hasan; Saluja, Deepak title: Clinical and cardiac characteristics of COVID‐19 mortalities in a diverse New York City Cohort date: 2020-10-20 journal: J Cardiovasc Electrophysiol DOI: 10.1111/jce.14772 sha: 306500c624e9d5e0c5949ac3eefb8b0b0853a3f8 doc_id: 836518 cord_uid: yyjdg6kb INTRODUCTION: Electrocardiographic characteristics in COVID‐19‐related mortality have not yet been reported, particularly in racial/ethnic minorities. METHODS AND RESULTS: We reviewed demographics, laboratory and cardiac tests, medications, and cardiac rhythm proximate to death or initiation of comfort care for patients hospitalized with a positive SARS‐CoV‐2 reverse‐transcriptase polymerase chain reaction in three New York City hospitals between March 1 and April 3, 2020 who died. We described clinical characteristics and compared factors contributing toward arrhythmic versus nonarrhythmic death. Of 1258 patients screened, 133 died and were enrolled. Of these, 55.6% (74/133) were male, 69.9% (93/133) were racial/ethnic minorities, and 88.0% (117/133) had cardiovascular disease. The last cardiac rhythm recorded was VT or fibrillation in 5.3% (7/133), pulseless electrical activity in 7.5% (10/133), unspecified bradycardia in 0.8% (1/133), and asystole in 26.3% (35/133). Most 74.4% (99/133) died receiving comfort measures only. The most common abnormalities on admission electrocardiogram included abnormal QRS axis (25.8%), atrial fibrillation/flutter (14.3%), atrial ectopy (12.0%), and right bundle branch block (11.9%). During hospitalization, an additional 17.6% developed atrial ectopy, 14.7% ventricular ectopy, 10.1% atrial fibrillation/flutter, and 7.8% a right ventricular abnormality. Arrhythmic death was confirmed or suspected in 8.3% (11/133) associated with age, coronary artery disease, asthma, vasopressor use, longer admission corrected QT interval, and left bundle branch block (LBBB). CONCLUSIONS: Conduction, rhythm, and electrocardiographic abnormalities were common during COVID‐19‐related hospitalization. Arrhythmic death was associated with age, coronary artery disease, asthma, longer admission corrected QT interval, LBBB, ventricular ectopy, and usage of vasopressors. Most died receiving comfort measures. Since the first cluster of cases in Wuhan, China, 1 the 2019 novel coronavirus (SARS-CoV-2) has rapidly spread to pandemic proportions, affecting the United States since January 19, 2020 in Washington DC with the first case of the resultant clinical syndrome, Since that time, New York City has become an epicenter of disease with 197 351 total cases, 51 380 hospitalizations, and 21 362 deaths resulting from confirmed or probable SARS-CoV-2 infection as of May 27, 2020. 3 Initial findings from the Chinese cohorts described acute respiratory distress syndrome (ARDS), myocardial injury, and death in 4.3%-15%. [4] [5] [6] Findings from a large cohort of patients in the New York City and its surrounding suburbs recently reported a death rate of 21%. 7 Older age, racial and ethnic minority status, pre-existing cardiovascular disease (CVD), and secondary infections have been associated with increased mortality. 8, 9 Studies describing the cardiac rhythm most proximate to death in COVID-19 patients have reported ventricular tachycardia (VT) or ventricular fibrillation (VF) in approximately 6% with the majority having asystole or pulseless electrical activity (PEA), consistent with respiratory failure or massive pulmonary embolism as the primary cause of death. [10] [11] [12] However, the specific electrocardiogram (ECG) and rhythm changes that develop in those that die of COVID-19 have not been reported. Additionally, although myocardial injury as defined by elevated serum troponin has been seen in those with arrhythmic death, other contributing factors have yet to be reported. 12 The present study investigated demographics, comorbidities, and electrocardiographic characteristics of a large cohort of hospitalized patients in the New York-Presbyterian Hospital Network in New York City who died from complications of COVID-19. We also performed an exploratory analysis assessing the frequency and associated factors of arrhythmic death. Demographics, comorbidities, laboratory findings, medication records, ECGs, echocardiograms, and telemetry recordings were reviewed manually. Assessed comorbidities included CVD (hypertension, hyperlipidemia, heart failure with preserved or reduced ejection fraction [EF]), coronary artery disease (CAD), valvular heart disease, and atrial fibrillation (AF), diabetes mellitus (DM), body mass index (BMI), chronic obstructive pulmonary disease (COPD), asthma, and Stage 3-5 chronic kidney disease (CKD). Laboratory values analyzed included potassium, calcium, bicarbonate, glucose, creatinine, arterial pH, arterial pCO 2 , arterial lactate, high-sensitivity troponin T (hs-TpnT), N-terminal pro-B type natriuretic peptide (NT-pro-BNP), interleukin-6 (IL-6), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), ferritin, and Cause of death was categorized as either arrhythmic or nonarrhythmic based on telemetry strips, ECGs, and hospital documentation. The authors were not blinded to arrhythmic or nonarrhythmic death during chart review and reading of ECGs. Arrhythmic deaths were adjudicated by a second investigator. Confirmed arrhythmic death was defined as sudden death due to documented tachyarrhythmia or bradyarrhythmia. Bradyarrhythmias were only considered arrhythmic death when not judged to be secondary to hypoxic respiratory failure. When cardiac rhythm was not recorded, documented sudden death without other identified cause was considered suspected arrhythmic death. Patients with confirmed or suspected arrhythmic death were categorized in the arrhythmic group. Nonarrhythmic death was defined as death due to other than arrhythmic causes or as the initiation of comfort care measures only. Continuous data were assessed for normality using the Shapiro-Wilks test. Normally distributed data is presented as mean ± SD and non-normally distributed data as median with interquartile range. Two analyses were performed in accordance with our methods: a descriptive analysis of the entire cohort and a comparative analysis investigating clinical and electrocardiographic factors related to arrhythmic death. Demographics and hospitalization characteristics of the 133 patient deaths that occurred during the study period are summarized in the last ECG recorded before death (n = 82) are presented in Figure 1 and Table 3 . Certain ECG diagnoses excluded the ability to make other Note: Baseline data on demographics and hospitalizations of the total cohort as well as divided between those who died of arrhythmic death or not with p values for comparison. Median with interquartile ranges are provided for non-normally distributed data. ECG differences between the two groups are outlined in There were no significant differences between QT, QTc, or QTf among those given hydroxychloroquine (n = 75) or not (n = 58), be- The overall baseline EF was normal. There were no differences between patients with arrhythmic versus non-arrhythmic death, although those with arrhythmic death had few baseline echocardiograms limiting comparison (see Table 1 ). There were no significant differences in admission laboratory tests between the arrhythmic and nonarrhythmic death groups. Those who died of arrhythmias did have significantly higher minimum NTpro-BNP levels (7220 vs. 964 pg/ml; p = .026) and significantly higher minimum ferritin levels (1456 vs. 529 ng/ml; p = .038) during hospitalization, but no significant difference in maximums (Table S1 ). Pooled electrocardiogram (ECG) comparison at baseline, admission, and before death. Comparisons between the total cohort, arrhythmic death cohort, and nonarrhythmic death cohort for heart rate, PR interval, QRS duration, QT interval, QTc interval, and QTf interval among baseline, admission, and final ECGs. Longer QTc and QTf intervals were associated with arrhythmic death. Statistically significant differences are annotated with p values. Other comparisons were not statistically significant. Normally distributed data as assessed by the Shapiro-Wilks test were reported as a mean with SD. Non-normally distributed data were reported as a median with interquartile range (IQR). Unpaired comparisons were assessed by the Student t test or the Mann-Whitney U test, as applicable. All p values are two-tailed progression of the disease in many patients. 13 The relatively low rates of intubation and mechanical ventilation were likely a result of the implementation of palliative care teams to the emergency department to discuss patients' goals of care at the time of presentation, thus avoiding unwanted invasive ventilator support. showed that new AF was associated with increased 90-day mortality (43% vs. 19%) among patients with ARDS, but the mechanism remains unclear. 19 However, a much higher incidence of atrial arrhythmias has been noted in COVID-19-infected patients requiring mechanical ventilation (17.7% vs. 1.9%), which may be a marker for severity of illness. 20 As systemic inflammation has been associated with the development of AF and severe COVID-19 infection has been associated with a marked inflammatory state, this could explain our findings. 21 Admission laboratory tests were generally revealing for a critically ill population with elevated creatinine, hs-TpnT, NT-pro-BNP, and inflammatory markers. Compared with limited laboratory data available in previously published laboratory data of nonsurvivors of Although not statistically significant, the trend toward increased arrhythmic deaths among non-Hispanic Blacks could be supported by a genetic susceptibility to sudden death among African Americans with COVID-19. 30 The paired analysis ECG data suggest a progressive increase in a catecholaminergic state, as would be expected in a severely ill population. Catecholamines were likely to be higher in the arrhythmia group, which was more likely to receive mechanical ventilation and exogenous catecholamines, previously shown to be associated with arrhythmias, 31 Prolonged QT interval is known to be associated with arrhythmic death and corrected QT intervals were longer in the arrhythmic group on admission, but no longer so before death. 33 The QTc and QTf interval differences between groups may represent a predisposition to malignant arrhythmias due to underlying CVD or LBBB, which was more frequent in the arrhythmic group. 34 Hospital operations have been significantly altered resulting from the COVID-19 crisis, as previously documented. 35 To mitigate the risk of spread, performance of diagnostic testing including assessments for structural heart disease and ECGs after admission was limited and not standardized. In those without baseline ECGs, the chronicity of newly F I G U R E 3 Paired comparison of QT Intervals in patients receiving hydroxychloroquine, azithromycin, and both. This paired comparison demonstrates no significant differences in QT, QTc, or QTf intervals between admission and the last electrocardiogram before death in patients receiving hydroxychloroquine, azithromycin, and both. Normally distributed data as assessed by the Shapiro-Wilks test were reported as a mean with SD. Non-normally distributed data were reported as a median with interquartile range (IQR). Paired comparisons were performed using a paired Student's t test or a Wilcoxon signed-rank test. 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