Inpatient cardiology consultation for COVID-19: What are cardiologists' diagnostic approaches?
Mitra Chitsazan1, Mandana Chitsazan2, Ahmad Amin1, Stephan Von Haehling3, Farah Naghashzadeh4, Meysam Khoshavi5, Mohammadreza Hoseinalizadeh6, Sara Amini1, Naghmeh Ziaie7, Sanaz Ghaffari8, Raana Asghari9, Afsaneh Amiri10, Tania Garfias-Macedo11, Majid Maleki1
1 Rajaie Cardiovascular, Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
2 Department of Medicine, Norwalk Hospital, Connecticut, United States
3 Department of Cardiology and Pneumology, University of Göttingen Medical Center, Heart Center, Göttingen, Germany
4 Department of Cardiology, National Research Institute of Tuberculosis and Lung Disease, Shahid Beheshti University of Medical Sciences, Tehran, Iran
5 Department of Cardiology, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
6 Department of Cardiology, Shariati Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
7 Department of Cardiology, Imam Reza Hospital, Shiraz University of Medical Sciences, Lar, Iran
8 Department of Cardiology, Babol University of Medical Sciences, Babol, Iran
9 Department of Cardiology, Velayat Hospital, Qazvin University of Medical Sciences, Qazvin, Iran
10 Department of Cardiology, Ahvaz Jundishapour University of Medical Sciences, Imam Khomeini Hospital, Ahvaz, Iran
11 Department of Cardiology and Pneumology, University of Göttingen Medical Center and German Center for Cardiovascular Research (DZHK), Partner Site Göttingen, Göttingen, Germany
Correspondence Address:
Dr. Ahmad Amin
Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Vali-Asr Ave, Niyayesh Blvd, Tehran
Iran
Source of Support: None, Conflict of Interest: None
DOI: 10.4103/rcm.rcm_45_21
Aim: Despite concerns about cardiovascular implications in coronavirus disease-2019 (COVID-19) patients, not all COVID-19 patients are visited by cardiologists and recommended to perform comprehensive cardiovascular assessments including measurement of biomarkers and echocardiography. We aimed to investigate the reasons for seeking cardiology care and to assess our cardiologists' diagnostic approaches to COVID-19 patients with potential cardiovascular involvement. Methods and Results: In this prospective, observational study, data of all consecutive COVID-19 patients admitted to six designated hospitals for COVID-19 in Iran in whom bedside cardiology consultation was requested were collected. A total of 148 patients including 105 (71%) males were included. The mean age was 57 ± 17 years. The most common reasons for cardiology consultation were dyspnea (56.7%), chest pain (12.8%), and suspected arrhythmias (10.8%). The most common comorbidities were hypertension (40.5%), diabetes mellitus (19.6%), and coronary heart disease (18.9%). A 12-lead electrocardiography (ECG) was obtained in all patients. Point-of-care ultrasonography or limited transthoracic echocardiography (TTE) was performed in 106 (71.6%) patients, and complete TTE was performed in 35 (23.4%) patients. Cardiac troponin was measured in 63 (42.6%) patients, and N-terminal pro B-type natriuretic peptide level was measured in 34 (23%) patients. Overall, 51 (34.5%) patients underwent invasive mechanical ventilation, inotropes were used in 29 (19.6%) patients, and 40 (27%) patients died. Conclusions: While preventing unnecessary investigations, the cardiologists should not overlook the lifesaving role of ubiquitous diagnostic modalities (such as ECG and TTE) in early detection and management of cardiac involvement in COVID-19.
Keywords: Cardiology consultation, coronavirus disease-2019, severe acute respiratory syndrome coronavirus 2
Mitra Chitsazan, Mandana Chitsazan and Ahmad Amin contributed equally.
IntroductionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, in the December 2019 and resulted in the coronavirus disease-2019 (COVID-19) pandemic.[1],[2]
Although severe pneumonia and subsequent acute respiratory distress syndrome (ARDS) are considered the predominant causes of mortality in patients with COVID-19, studies have shown that cardiac injury occurs in a considerable proportion of patients and is associated with poorer outcomes.[3],[4],[5],[6],[7] In addition, evidence suggests that patients with the previous history of cardiovascular diseases and/or cardiovascular risk factors have higher case fatality rates.[8],[9],[10]
However, despite these concerns about cardiovascular implications in patients with COVID-19, experts recommend against routine echocardiographic study and measurement of cardiac biomarkers in all patients, mainly due to the potential challenges in the interpretation of abnormal results and the risk of transmission of the virus to health-care professionals.[11],[12]
Since there is still no well-established clinical guideline determining the timing of cardiac consultation and indications of different cardiac tests, the decisions on timing and modalities of cardiovascular evaluation are made case-by-case at the discretion of physicians, which obviously may differ in different countries and hospitals.
In the present study, we aimed to investigate the reasons for seeking cardiology care and to assess the diagnostic approach of our cardiologists to COVID-19 patients with potential cardiovascular involvement, mainly through evaluating the cardiology tests they perform on suspected patients.
MethodsStudy participants
From November 25, 2020, to March 5, 2021, we prospectively enrolled 148 consecutive patients with confirmed diagnosis of COVID-19 in whom the attending physicians had requested a bedside cardiology consultation. Diagnosis of COVID-19 was confirmed in all patients with a positive result for SARS-CoV-2 on real-time reverse transcriptase-polymerase chain reaction assay, using a nasopharyngeal swab. There were no specific exclusion criteria. The Institutional Review Board at Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences (Tehran, Iran), approved the study, and written informed consent was obtained from all participants or their guardians.
Data collection
We collected patients' baseline characteristics including routine laboratory parameters, cardiac biomarkers, electrocardiography (ECG), and cardiac imaging studies. Patients were followed until death, discharge, or until the database was censored on August 2020.
For this study, a standard or complete transthoracic echocardiography (TTE) refers to an echocardiographic examination in which all of the following eight parameters were assessed by the cardiologists: left atrial size, left ventricular (LV) end-diastolic size, LV ejection fraction (LVEF), LV diastolic function, right ventricular (RV) end-diastolic size, RV function, systolic pulmonary artery pressure (sPAP), valvular function, and the presence of pericardial effusion. Point-of-care ultrasonography (POCUS) and limited TTE were defined when cardiologists have investigated only gross abnormalities in the LV/RV size and function, the valvular function, or the presence of pericardial effusion.
Statistical analysis
Categorical data are expressed as number (percentages) while continuous data are expressed as mean standard deviation or median (interquartile range [IQR]) values. Since N-terminal pro B-type natriuretic peptide (NT-proBNP) level was not normally distributed, the correlation between NT-proBNP level and LVEF and sPAP was assessed using Spearman's correlation coefficient. Data were analyzed using the Statistical Package for the Social Sciences (SPSS) version 25.0 (IBM Armonk, New York, USA).
ResultsPatient characteristics
A total of 148 patients with COVID-19, including 105 males (71%), in whom a cardiology consultation was requested were included in this prospective study. The mean age was 57 ± 17 years (range: 16–89 years). The majority of patients had history of hypertension (40.5%), diabetes (19.6%), and coronary heart disease (18.9%).
The most common reasons for requesting cardiology consultation were dyspnea (new, rapidly deteriorating or out-of-proportion to lung involvement) (84 [56.7%] patients), chest pain (19 [12.8%] patients), and suspected arrhythmias (16 [10.8%] patients). A comprehensive list of reasons for cardiology consultation is shown in [Table 1]. The most common comorbidities were hypertension (60 [40.5%] patients), diabetes mellitus (29 [19.6%] patients), and coronary heart disease (28 [18.9] patients). The baseline characteristics are represented in [Table 2].
Cardiovascular testing
Electrocardiogram
A 12-lead ECG was obtained in all patients. The majority of patients were in sinus rhythm (133 patients, 89.9%), and arrhythmias were seen in 22 patients (10.1%). The most common abnormal heart rhythms were atrial fibrillation (7 [4.7%] patients), frequent premature ventricular contractions (5 [3.4%]), and atrioventricular blocks (4 [2.7%] patients). ST segment elevation and depression were seen in 6 (4%) and 18 (12.2%) patients; respectively. The ECG findings are shown in [Table 3].
Cardiac imaging
In 7 (4.7%) patients, no cardiac imaging was performed. POCUS or limited TTE to investigate for gross abnormalities in cardiac function was performed in 106 (71.6%) patients. Complete TTE was performed in 35 (23.4%) patients.
The mean LVEF was 44% ± 12%, and 49 (34.8%) patients had an LVEF of ≤40%. Among 105 patients in whom LV diastolic function was assessed, only 24 patients (22.9%) had normal LV diastolic function and the majority of patients had impaired LV myocardial relaxation.
RV dilatation and RV dysfunction were seen in 11 (18.3%) and 16 (16%) patients, respectively. Mean sPAP was 28 ± 9.5 mmHg, and 14 (14%) patients had an elevated sPAP of >35 mmHg.
A mild pericardial effusion was detected in 9 (6%) patients.
The results of POCUS and TTE findings are presented in [Table 4].
Cardiac biomarkers
Cardiac troponin was measured in 63 (42.6%) patients; 38 (60.3%) of them had positive cardiac troponin levels. NT-proBNP level was measured in 34 (23%) patients; 33 (97%) of them had an elevated NT-proBNP level (median [IQR]: 3000 [786.5–8161] pg/mL). NT-proBNP level was positively correlated with sPAP (rho = 0.40, P = 0.02) and inversely correlated with LVEF (rho = −0.43, P = 0.01). Measurement of troponin and NT-proBNP levels has been requested by the cardiologists as part of their diagnostic approach.
Advanced cardiovascular imaging and procedures
Coronary angiography with/without angioplasty was performed in five patients. Computed tomography (CT) pulmonary angiography was performed in two patients for suspected pulmonary emboli.
Outcome
Overall, 51 (34.5%) patients underwent invasive mechanical ventilation, inotropes were used in 29 (19.6%) patient, and 40 (27%) patients died.
DiscussionAlthough the lungs are the primary site of involvement in COVID-19, a growing body of evidence indicates that cardiac involvement occurs in up to one-third of patients;[3],[4],[5],[6] and the presence of cardiac injury has been associated with worse outcome.[3],[6],[13]
Possible pathophysiologic mechanisms for cardiac involvement in COVID-19 include acute myocarditis, myocardial injury due to cytokine storm, hypoxic injury, coronary spasm, microthrombi formation, direct endothelial or vascular injury, acute myocardial infarction type I (due to atherosclerotic plaque rupture triggered by the infection) or Type II (due to imbalanced oxygen demand and supply), exacerbation of chronic heart failure, and impaired myocardial relaxation.[14],[15],[16],[17],[18]
In the present observational study, we evaluated our physician's current attitude toward cardiovascular concerns in COVID-19 and investigated their current diagnostic approaches by assessing how much detailed and extensive cardiovascular workups they perform in patients at high risk of cardiac injury from COVID-19. For these purposes, first, we reviewed patients' baseline characteristics and indications for requesting a cardiology consultation. We found that dyspnea of new-onset, rapidly deteriorating, or out-of-proportion to lung involvement, as shown by chest radiography and CT findings, was the main indication that encouraged physicians to call for a bedside cardiology consultation. Chest pain, arrhythmias, suspected cardiogenic shock, and peripheral edema were the other most frequent reasons which prompted a need for cardiology consultation. However, 12 (8.1%) patients had not presented with alarming evidence of cardiac involvement by COVID-19, and cardiac consultation was requested for providing a throughout assessment solely based on a previous medical history of cardiovascular diseases.
Consistent with previous studies, the most common comorbidities seen in our study population were hypertension, diabetes, and coronary heart disease.[5],[6],[7],[19] It has been shown that patients with cardiac injury had higher rates of comorbidities, including hypertension, coronary heart disease diabetes, and chronic kidney disease.[3]
In the next step, we assessed cardiologists' diagnostic approach to possible cardiac involvement in COVID-19. A 12-lead ECG was the initial test that was requested in all patients, irrespective of indication for consultation. In a study by Shi et al.[3] among 82 patients with cardiac injury, ECG examination has been performed in only 22 (26.8%) patients after admission. Although might have been overlooked in previous studies, the ECG examination provided valuable information in the cardiac evaluation of our COVID-19 patients, which ultimately helped decide for the next diagnostic and/or management strategy. Cardiac arrhythmias were seen in 22 (10%) patients who then received appropriate treatment. The ST-T change abnormalities consistent with myocardial ischemia and/or necrosis, such as T wave depression and inversion, ST segment depression or elevation, poor R progression, and Q waves, were seen in 48 (32.5%) patients. A prolonged QT was detected in 16 (10.8%) patients.
Our results also showed that except in 7 (4.7%) patients, cardiologists have been decided for a cardiovascular imaging test after the initial ECG examination. POCUS or limited TTE was performed in the majority of patients (106 patients, 71.6%) to evaluate gross abnormalities in ventricular sizes and function, valvular function, and the presence of pericardial effusion. In 35 (23.6%) patients, a complete TTE was performed to thoroughly assess cardiac function. Of note, due to the risk of medical staff contamination, routine echocardiography is not recommended for all COVID-19 patients.[12]
Although only eight patients had previous history of congestive heart failure, 49 patients had a LVEF of ≤40% on imaging studies. There are limited data on the pathophysiology of systolic dysfunction in COVID-19 patients; however, it seems that myocardial dysfunction secondarily to COVID-19 mostly result from hypoxia, cytokine-related myocardial impairment, or an imbalance between oxygen supply and demand in susceptible patients (such as those with ischemic heart diseases), rather than being a consequence of direct injury of myocardium by the virus. Impaired myocardial relaxation, ranging from increases in cardiac filling pressures to symptomatic heart failure with preserved ejection fraction, also might occur in COVID-19 patients.[15],[20] Consistently, among 105 patients in whom LV diastolic function has been assessed, impaired myocardial relaxation was seen in 81 patients. In a retrospective study on 110 hospitalized COVID-19 patients, RV dilatation was seen in 32 (31%) of patients and was strongly associated with in-hospital mortality.[21] In our study, RV size and function were assessed in 60 and 100 patients, and RV dilatation and RV dysfunction were seen in 11 (18.3%) and 16 (16%) patients, respectively. sPAP was measured in 99 patients; 14% of them had a sPAP of >35 mmHg on echocardiographic examination.
Various definitions have been used to characterize cardiac injury in COVID-19 patients. The most widely used definition is an elevated cardiac troponin level above the 99th percentile of upper reference limit.[3],[4],[6] Several studies have shown elevated cardiac troponin levels, particularly high-sensitivity cardiac troponins, in many patients with COVID-19.[3],[4],[5],[6] Elevated cardiac troponin level has also been linked to increased severity of COVID-19 disease and worse outcomes.[3],[6],[22],[23],[24] However, it is worth noting that elevated cardiac troponin levels might not be specific to cardiac injury, as elevated cardiac troponin levels have been shown in critically ill patients[25],[26] and patients with ARDS of other causes,[27],[28],[29] sepsis, or systemic inflammatory response syndrome.[30] In addition, cardiac involvement in COVID-19 does not always occur as a form of direct cardiac myocyte injury with a subsequent rise in troponin level. Given all these findings into consideration, initially, some experts recommended against the routine measurement of cardiac troponin level to detect cardiac injury in COVID-19 and advised to restrict cardiac troponin measurement to patients in whom a diagnosis of acute myocardial infarction is being considered on clinical grounds.[11] However, considering strong prognosticator significance of cardiac troponin level in severe COVID-19 diseases, more recent studies recommended troponin measurement in hospitalized COVID-19 patients to optimize risk stratification.[31],[32] In our study, cardiac troponin has been requested in 63 patients, in whom 38 (60%) patients showed a positive troponin level. This troponin measurement has been made as part of our cardiologists' diagnostic approach and not as a routine risk assessment process.
Natriuretic peptides are hormones that are mainly released from the heart in response to increased myocardial wall stress.[33] Several studies have demonstrated elevated BNP or NT-proBNP levels in COVID-19 patients, and an elevated NT-proBNP level has been associated with worse outcomes in patients with severe COVID-19.[34],[35] It seems that both systolic dysfunction and impaired myocardial relaxation might be involved in the pathogenesis of elevated BNP levels in COVID-19 patients. However, elevated NT-proBNP has been reported in patients with acute lung injury and ARDS even in the absence of clinical findings of heart failure.[36],[37],[38],[39],[40],[41] This might be explained by the myocardial injury caused by hypoxia, elevated pulmonary pressure, or circulating inflammatory cytokines. Considering the high frequency and lack of specificity, experts prohibited routine measurement of NT-proBNP level in all COVID-19 patients.[11] In our study, NT-proBNP was measured in 34 patients, of which 33 patients had an elevated NT-proBNP level. In addition, higher NT-proBNP level was significantly associated with lower LVEF and higher sPAP.
Our study has some limitations. First, we had a relatively small sample size, and the interpretation of our results might be limited by including cardiologists from a few designated hospitals for COVID-19 in Iran. However, we enrolled patients from six different cities in Iran in an attempt to represent the most common approaches used throughout the country. Second, due to the risk of contamination, all questionnaires were filled out by the cardiologists themselves, rather than the research personnel. This resulted in missing data on some baseline characteristics of the participants. Third, we only assessed reasons for requesting cardiology consultation and the diagnostic approach of our cardiologists to COVID-19 patients. We did not assess the final cardiovascular diagnoses made by the cardiologists and how cardiologists' diagnoses could have effectively altered treatment strategies and/or prognosis of patients. Therefore, the significance of cardiovascular abnormalities in determining the degree of cardiac contribution to the clinical manifestations and outcome of COVID-19 patients cannot be reliably concluded from our study. Of note, our study did not evaluate the diagnostic or prognostic significance of cardiac biomarkers (including cardiac troponin and natriuretic peptides) in hospitalized patients with COVID-19. Thus, we could not make conclusions regarding the role of these cardiac biomarkers in determining the etiology, severity, and/or prognosis of cardiac involvement in COVID-19 patients.
ConclusionsAll abnormalities in ECG and echocardiographic examinations should not be considered new findings and attributed to COVID-19 since many patients with previous cardiac abnormalities might also have concomitant COVID-19 infection. Consequently, it seems reasonable for cardiologists to consider the risk of contamination as well as a cost–benefit ratio when requesting for cardiology tests. While preventing unnecessary investigations which may not significantly alter the management strategies or patients' outcome, the lifesaving role of these ubiquitous diagnostic modalities in early detection and management of cardiac involvement in COVID-19 should not be overlooked.
Ethical clearance
The ethics committee of Rajaie Cardiovascular Medical and Research Center, Tehran, Iran approved the study protocol.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
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