There is growing evidence that COVID-19 can cause cardiovascular complications. However, there are limited data on the characteristics and importance of atrial arrhythmia (AA) in patients hospitalized with COVID-19. Data from 1,029 patients diagnosed with of COVID-19 and admitted to Columbia University Medical Center between March 1, 2020 and April 15, 2020 were analyzed. The diagnosis of AA was confirmed by 12 lead electrocardiographic recordings, 24-hour telemetry recordings and implantable device interrogations. Patients’ history, biomarkers and hospital course were reviewed. Outcomes that were assessed were intubation, discharge and mortality. Of 1,029 patients reviewed, 82 (8%) were diagnosed with AA in whom 46 (56%) were new-onset AA 16 (20%) recurrent paroxysmal and 20 (24%) were chronic persistent AA. Sixty-five percent of the patients diagnosed with AA (n=53) died. Patients diagnosed with AA had significantly higher mortality compared with those without AA (65% vs 21%; p < 0.001). Predictors of mortality were older age (Odds Ratio (OR)=1.12, [95% Confidence Interval (CI), 1.04 to 1.22]); male gender (OR=6.4 [95% CI, 1.3 to 32]); azithromycin use (OR=13.4 [95% CI, 2.14 to 84]); and higher D-dimer levels (OR=2.8 [95% CI, 1.1 to 7.3]). In conclusion, patients diagnosed with AA had 3.1 times significant increase in mortality rate versus patients without diagnosis of AA in COVID-19 patients. Older age, male gender, azithromycin use and higher baseline D-dimer levels were predictors of mortality.
The Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome Coronavirus 2 (SARS-CoV2) has affected millions across different ethnicities and countries in the past few months since its emergence from Wuhan, China. COVID-19 mostly presents as a respiratory tract infection with different levels of severity. The more severe form of acute respiratory distress requires hospital admission and advanced treatments. There is increasing evidence of associated cardiovascular complications from mild myocardial injuries to more severe forms of myocarditis. However, there is limited data on arrhythmic presentations including atrial arrhythmias (AA) in COVID-19. In this study, the incidence, characteristics and outcomes in patients with AA admitted to hospital with COVID-19 were investigated.
Methods
The study included 1029 COVID-19 patients who were 18 years of age or older admitted to the Columbia University’s 3 affiliated hospitals between March 1, 2020 and April 15, 2020. All baseline data including patients’ demographics, co-morbidities, laboratory results, electrocardiographic (ECG) recordings and hospital course were extracted from the electronic medical records. The initial laboratory results for inflammatory markers, coagulation values, myocardial stretch and injury were collected at the time or near the time of admission.
Medication history prior to admission as well as during hospital course were obtained. Hydroxychloroquine and azithromycin usage during admission for treatment of COVID-19 were also included. Hydroxychloroquine dosing regimen at our institution was an initial loading dose of 600 mg x 2 for 1 day, followed by 400 mg daily for 4 more days. Azithromycin was given with an initial dose of 500 mg for one day, followed by 250 mg daily for 4 additional days.
Patients with atrial fibrillation (AF) or flutter (new or pre-existing) were anticoagulated with intravenous heparin (53%) or direct oral anticoagulants (34%) or low molecular weight heparin (7%) or warfarin (6%). This study was approved by the Columbia University Irving Medical Center Institutional Review Board. All patients included in the study had a positive result for SARS-CoV-2 on real time polymerase -chain- reaction testing on pharyngeal or nasal cavity swabs.
AA and its subtype of AF, atrial flutter and supraventricular tachycardia (long or short RP) were diagnosed using three sources: 12 lead ECGs, 24-hour telemetry recordings or implantable device interrogations. The diagnosis of AA was confirmed and verified by two board certified cardiac electrophysiologists who reviewed all ECGs, telemetry recordings and device interrogation reports. The AA patterns of presentation were divided into 3 patterns: new-onset, recurrent paroxysmal AA and chronic persistent AA. New-onset AA including AF was defined as newly diagnosed AA at the time of hospital admission or during the hospital course. The onset of arrhythmia and history of prior AA were verified by reviewing the patient history, ECGs, telemetry recording and device interrogation reports. Recurrent paroxysmal AA was defined as patients with prior history of AA with recurrence at the time of admission. Patients who were chronically in AA before and during the current admission were classified as chronic persistent AA. In patients with new-onset AA, the exact time to the onset of AA was established by reviewing the ECGs, progress reports as well as daily vital sign recordings. All AA lasted longer than 6 minutes.
Hospitalization outcomes were assessed by reviewing the patient’s electronic health records. The outcomes were divided into four groups: (1) died by any cause, (2) still admitted and intubated, (3) still admitted but not intubated, (4) discharged from hospital. The cause of death was divided into arrhythmic and non-arrhythmic based on the review of death notes and telemonitoring recordings. Follow-up continued through April 23, 2020.
Continuous variables are presented as mean ± SD. Categorical variables are reported as frequencies and percentages. Shapiro-Wilk test was performed to assess the normality of distribution for continuous variables. Skewed continuous variables were log-transformed for greater symmetry of distribution. Linear regression was used for determining statistically significant differences across continuous variables. Pearson’s or Fisher’s exact chi square testing were used for analysis of categorical variables. Predictors of mortality in patients with AA were determined using multivariable logistic regression models. In the first model, the association between the clinical risk factors and the outcome of death was examined. The second model examined the relationship between the biomarkers and outcome of death. A 2-sided p value of < 0.05 was considered statistically significant. Statistical analyses were performed using STATA version 11 (College Station, Texas).
Results
Among the 1029 patients who were admitted with COVID-19, 82 (8%) patients were diagnosed with AA, including 46 (4.5%) patients without prior history of AA (new-onset) ( Figure 1 ). The mean age of the 1,029 patients was 63.6 ± 17.4. The mean age of patients with AA was 76 ± 13 and was significantly higher than the mean age of patients without AA (62.4 ± 17.3; p < 0.001). The male to female ratio was similar between the two groups (43% female in AA vs 42% female in non AA, p = 0.9). Hispanic and/or Latino patients constituted nearly 50% of patients with no significant differences across different patterns of AA (p = 0.8).
Of 82 patients with AA, arrhythmia was present at the time of admission in 44 (54%) patients. The rest of the patients were diagnosed on average 3 to 4 days after hospital admission date. Of the 82 patients, 62 (76%) were diagnosed with AF, 13 (16%) patients were diagnosed with atrial flutter (typical flutter based on ECG) and 7 (8%) were found to have supraventricular tachycardia (5 with long RP and 2 with short RP tachycardia) ( Table 1 ). ECGs of the 5 patients with long RP tachycardia showed different p wave morphology than sinus with positive polarity in inferior leads, strongly favoring focal atrial tachycardia. New-onset AA was seen in 46 (56%) of the patients. Recurrent paroxysmal and chronic persistent were diagnosed in 16 (20%) and 20 (24%) patients, respectively ( Table 1 ). New-onset AA patients were significantly younger than the two other patterns, and also had higher BMIs (p < 0.05). Patients with new-onset AA less often had a history of heart failure and coronary artery disease compared with recurrent and chronic persistent AA patients (p < 0.05). Thirteen (16%) patients had a history of pacemaker and defibrillator implanted among whom a significant number (86%) had a history of AA prior to admission (p <0.05). One patient had a history of MAZE surgery and another patient had history of pulmonary vein isolation.
| Variables | All AA (n = 82) | New-onset AA (n = 46) | Recurrent Paroxysmal AA (n = 16) | Chronic Persistent AA (n = 20) | p value for subtypes |
|---|---|---|---|---|---|
| Age (years) | 76±13 | 71±13 | 82±8 | 81±13 | 0.002 |
| Men | 47 (57%) | 27 (58%) | 7 (44%) | 13 (65%) | 0.8 |
| Hispanic | 39 (48%) | 21 (46%) | 10 (63%) | 8 (40%) | 0.8 |
| White | 32 (39%) | 18 (39%) | 6 (37%) | 8 (40%) | |
| Black | 7 (8%) | 3 (6%) | 4 (20%) | ||
| Asian | 4 (5%) | 4 (9%) | |||
| Body mass index (kg/m 2 ) | 29±7 | 31±8 | 30±5 | 26±4 | 0.011 |
| Diabetes mellitus | 42 (51%) | 25 (55%) | 10 (63%) | 7 (35%) | 0.23 |
| Hypertension | 69 (84%) | 36 (78%) | 16 (100%) | 17 (85%) | 0.1 |
| Heart failure | 23 (28%) | 8 (17%) | 8 (50%) | 7 (35%) | 0.03 |
| Coronary artery disease | 29 (35%) | 11 (23%) | 8 (50%) | 10 (50%) | 0.04 |
| CKD/ESRD | 17 (20%) | 10 (22%) | 3 (19%) | 4 (20%) | 1 |
| Prior asthma/COPD | 13 (16%) | 8 (17%) | 4 (25%) | 1 (5%) | 0.22 |
| Prior PPM/ICD | 13 (16%) | 2 (4%) | 6 (37%) | 5 (25%) | 0.002 |
| Atrial arrhythmia Type Atrial fibrillation | 62 (76%) | 0 (65%) | 13 (81%) | 19 (95%) | 0.03 |
| Typical Atrial flutter | 13 (16%) | 9 (20%) | 3 (19%) | 1 (5%) | 0.3 |
| SVT | 7 (8%) | 7 (15%) | 0 | 0 | |
| Medications | |||||
| Hydroxychloroquine | 47 (58%) | 34 (74%) | 7 (44%) | 6 (30%) | 0.002 |
| Azithromycin | 36 (44%) | 24 (52%) | 9 (56%) | 3 (15%) | 0.009 |
| Amiodarone use | 29 (41%) | 26 (56%) | 2 (12.5%) | 1 (5%) | < 0.001 |
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