Cardiovascular disease development in COVID-19 patients admitted to a tertiary medical centre in Iran

Cardiovascular diseases (CVDs) have been reported to occur in a significant number of patients diagnosed with coronavirus disease 2019 (COVID-19). We report our experience regarding the occurrence of symptomatic and asymptomatic CVDs in COVID-19 patients. In this cross-sectional study, 690 COVID-19 patients were included. Cardiovascular consultation had been requested for all of the patients based on their primary clinical examination, vital signs, and electrocardiogram (ECG). Additionally, 2D transthoracic echocardiography (TTE), and myocardial injury serum biomarkers assays (creatine phosphokinase-MB [CPK-MB] and cardiac troponins [cTn]) were measured once. Manifestations of CVDs, such as chest pain, abnormal serum markers, unstable angina, myocardial infarction (MI), myocarditis, and new-onset hypertension, were documented. The most common symptom was left hemithorax and interscapular pain (317 patients, 46%). New-onset high systolic and diastolic blood pressures were seen in 67 patients (10%). Unstable angina, MI, and myocarditis were, respectively, diagnosed in 20 (2.8%), five (0.7%), and 12 (1.7%) patients. On TTE, pericardial effusion was diagnosed in 139 patients (31.1%). The most common abnormal ECG changes seen were regarding the T-wave, including flat T-wave (148 cases, 21.4%) and inverted T-wave (141 cases, 20.4%). Serum cTn levels were positive or weekly positive in 17 cases (7.4%). The incidence rate of cardiovascular involvements was high in COVID-19 patients.

Introduction

In late 2019, the first case of a patient with pneumonia of unknown cause was reported in Wuhan, China. The disease, called coronavirus disease 2019 (COVID-19), spread rapidly and caused a pandemic. The virus that causes this infection is called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).¹

Besides respiratory tract disease, which is considered the main and most common clinical manifestation of COVID-19, other systems, including the cardiovascular system, could also be affected. Factors, such as tissue hypoxia, which results as the pneumonia progresses, and inflammation of the vessel walls, have been suggested as a main contributing mechanism for myocardial injury in these patients.^2-4 SARS-CoV-2 binds to cells expressing viral receptors, particularly to angiotensin-converting enzyme 2 (ACE2).⁵ ACE2 is an important factor in regulating cardiac function and is expressed in various tissues like the kidneys, heart, and lung. One study reported that when ACE2 is destroyed, severe left ventricle dysfunction develops in mice models.^5,6

Cardiovascular disease (CVD) is an important cause of morbidity in COVID-19 patients. The prevalence of CVD varies from 4% to 14% of COVID-19 individuals.^7–9 These comprise a wide range of manifestations from asymptomatic rise in myocardial injury biomarkers to symptomatic ischemic heart disease, myocardial injury, arrythmias, heart failure, newly developed hypertension, and cardiogenic shock.^10,11 The investigators have estimated the case fatality rate (CFR) of COVID-19 to be lower for patients without any comorbidity compared with those with CVDs.¹²

We decided to determine the incident rate of CVD induced by COVID-19 in hospitalised patients. Since CVDs can have adverse effects on the prognosis of COVID-19 patients, basic knowledge about the prevalence of CVDs is necessary.

Method

Study population and design

In this cross-sectional study, a total of 2,100 COVID-19 patients were assessed with 690 COVID-19 patients who had a cardiovascular consultation requested for them from March to September 2020. The patients referred to the hospital were hospitalised in the infectious ward during the first seven days of onset of the disease. All the patients were visited by only two infection experts. COVID-19 treatment regimen was based on World Health Organisation (WHO) guidelines.¹³ The diagnosis of the infection was made by reverse transcription polymerase chain reaction (RT-PCR) using nasopharyngeal swab specimens. Electrocardiogram (ECG), vital signs, and clinical examination were performed for all admitted patients. Then, if there were any cardiovascular signs/symptoms, such as chest pain, ECG changes, and unexplainable shortness of breath, board-certified cardiologists would visit the patients and review the medical records. Since we decided to investigate CVDs as the result of COVID-19 infection, we excluded those with previously diagnosed CVDs (n=63). However, hypertensive patients were eligible to be included.

For all included patients, cardiologists performed daily cardiovascular examinations. Besides the primary ECG recorded, more may have been ordered according to cardiologist opinion. Additionally, serum markers of myocardial injury (creatine phosphokinase-MB [CPK-MB] and cardiac troponin [cTn]), 2D transthoracic echocardiography (TTE) were measured once. However, they might be measured up to three times based on cardiologist’s opinion.

Data items

The basic data gathered included age, gender, systolic blood pressure (SBP), diastolic blood pressure (DBP), abnormal ECG findings, hospitalisation duration, serum myocardial injury markers, and abnormal TTE findings.

Procedures

Blood pressure (BP) measurements were performed by an experienced nurse. Mean value of BP measurements of right and left arms was recorded at admission until three days after hospitalisation. Then we used the mean of BP. TTE was performed by a cardiologist with 10 years of experience (General Electric set model VIVID S6). The Sansure RT-PCR kit was used for diagnosis of COVID-19 (Sansure Co., China). A nasopharyngeal swab was taken for RT-PCR. The RT-PCR tests positive when both genes (N and RD-RP) are recognised. If a patient’s RT-PCR results were suspicious, we repeated the RT-PCR.

Definitions

High blood pressure was defined as SBP ≥130 mmHg and/or DBP ≥80 mmHg.¹⁴ A low SBP was defined as SBP <90 mmHg.¹⁵ Abnormal ECG and TTE findings were recognised according to the American Heart Association (AHA) guidelines.^16,17 Serum CPK-MB levels <25 UI/L and troponin levels <0.06 µg/L were defined as the normal range.¹⁸ Seventh Version of the Novel Coronavirus Pneumonia Diagnosis and Treatment Guidance from National Health Commission of China were used for severity definition of COVID-19.¹⁹

Statistical analysis

Data were analysed by SPSS software version 22 (IBM, USA). Descriptive indices including frequency, percentage, mean and its standard deviation (SD) were used to express data. In order to compare binary data between the groups, the Chi-squared test was used. The independent t-test was used to compare continuous data between the groups. A p value <0.05 was considered statistically significant.

Ethics

This project was approved by the Ethical Committee of Shahroud University of Medical Sciences, Shahroud, Iran (IR.SHMU.REC.1398.160). The study was conducted according to the guidelines of the Declaration of Helsinki. Informed consent was waived by the committee as no intervention was done. An informed consent is routinely obtained from the patients at our hospital upon admission to receive medical care and diagnostic procedures.

Results

The study included 690 patients with COVID-19 infection (379 males) with a mean ± SD age of 58.81 ± 17.25 years. The mean hospitalisation duration was 7.8 days. The most common symptom was left hemithorax and interscapular clearly burning and briefly depressing chest pain (n=317, 46%) that was associated with shortness of breath. On the physical examination, the most common sign was new-onset high SBP and DBP (67 patients, 10%) and tachycardia at rest (43 patients, 7.6%). Also, 83 (12%) patients were receiving antiplatelets before contracting COVID-19. The prevalence of mild, moderate, severe, and critical patients was 40%, 37%, 18%, and 5%, respectively.

The incidence rate of CVD varied from 0.7% (five patients) to 31.1% (139 patients), respectively, for MI and pericardial effusion. Unstable angina was present in 2.8% (20 patients) and myocarditis in 1.7% (12 patients). Also, prevalence of abnormal CPK-MB and positive troponin were 9.3% (n=64) and 7.4% (n=17), respectively.

Flat T-wave (148 patients, 21.4%), sinus tachycardia at rest (90 patients, 13%), and bradycardia (78 patients, 11.3%) were the most common abnormal ECG findings. Thirteen patients (1.9%) had new atrial fibrillation (AF). Other non-sinus rhythms were not detected. In addition, the incidence rate of premature atrial contractions (PAC) and premature ventricular contractions (PVC) were 1.6% (11 patients) and 1.6% (11 patients), respectively (table 1).

A total of 367 patients (64.9%) had hypertension. Although 57 (10%) patients were found to have new-onset hypertension, the incidence rates of new-onset high SBP and high DBP were 10% (67 patients) and 7.3% (49 patients), respectively. High SBP (10.3% vs. 9.8%) and high DBP (7.7% vs. 7.2%) were more common in women. Mean SBP was 132.4 ± 11.6 mmHg. The incidence rate of hypotension was very rare (table 2).

TTE findings showed that 139 patients (31.1%) had pericardial effusion. Most effusions were at the posterior side of the left ventricle (LV) with less frequent cases around the right atrium. None of the patients had massive pericardial effusion. Ninety-seven patients (21.7%) had LV regional wall motion abnormalities (RWMA), of which global hypokinesia was the most common pattern, followed by the inferior wall hypokinesia. LV ejection fraction (EF) had decreased to values lower than 55% in 95 patients. Table 3 shows TTE findings of the patients.

Discussion

Based on the obtained findings, the least frequent CVD was MI. This was diagnosed in just 0.7% of patients. The most common CVD was pericardial effusion detected in 31.1% of patients.

Although the most concerning complication of COVID-19 is acute respiratory distress syndrome (ARDS), involvement of other organs is not uncommon. Previous studies have noted myocardial injury and increased troponin levels as a major cause of morbidity in COVID-19 patients.^20,21

Wang et al. described the clinical characteristics of 138 hospitalised COVID-19 patients at a university hospital in Wuhan, China.²² They reported elevated serum troponin I levels in 10 patients (7.2%). In addition, 23 patients (16.7%) were found to have arrhythmia. Also, Lippi et al. reported that the incidence rate of myocardial injuries was 8–12%.²³ Angeli et al.²⁴ reported that about one-quarter (26%) of 50 patients with COVID-19 pneumonia developed new ECG abnormalities during hospitalisation. Atrial fibrillation was detected in 6% of patients and brady-tachy syndrome in 2% of patients. However, we observed a much higher proportion of patients to have abnormal ECG changes (68.4%). A review study declared QT prolongation might be found in 13% of COVID-19 patients, which is higher than our findings.²⁵ However, this difference might be caused by the type of medications that were used for patients. Another systematic review suggested that the incidence rate of arrhythmia was 1.9%, which was similar to the incidence rate of arrhythmia in our study.²⁶ In another study, 11 patients (46%) with significant myocardial injury and increased troponin levels were found to have RWMA on TTE.²⁷ However, in our study, the prevalence of LV-RWMA was 21.7%. A retrospective study from China suggested that heart failure might be found in 24% of COVID-19 patients.²⁸ Another study with larger sample size reported a similar percentage of heart failure among COVID-19 patients.²⁹ Besides, the incidence rate of decreased LVEF was 21.2%.

Yu et al. showed that the prevalence of tachycardia and bradycardia in their study was 71.9% and 14.9%.³⁰ Also, the prevalence of hypotension in their study was 50.4%, which was higher than our finding (3.4%). However, it might be caused by their cut-off point for the definition of hypotension (SBP <100 mmHg), which is higher than ours (SBP <90 mmHg).

A few studies reported the prevalence of hypertension among COVID-19 patients in China and the USA as 30.5% and 49.7%, respectively.^20,31 We found the prevalence of high SBP was 64.9% (367 patients) and the prevalence of new-onset high SBP was 10% (67 patients). Some patients were diagnosed to have unstable angina, MI, and myocarditis. A reduction in oxygen supply, severe lung failure, and the cytokine storm could lead to myocardial dysfunction. Moreover, such complications can be attributed to decreased ACE2 activity in the heart. Some researchers reported that ACE expression decreased in the hearts of SARS-infected mice. The presence of SARS-CoV in seven hearts of human autopsies and the association with myocardial injury and decreased expression of myocardial ACE2 protein have been observed in some studies.³²

We had some limitations. This study was conducted in a single centre. However, it should be noted that the hospital where the patients had been admitted is one of the major hospitals providing medical services to the city.

Conclusion

Based on our findings, the prevalence of CVDs was high in COVID-19 patients. These findings highlight the importance of close monitoring of admitted COVID-19 patients during their hospitalisation.

Key messages

• Based on our findings, the prevalence of cardiovascular disease (CVD) was high in COVID-19 patients
• The least frequent CVD was myocardial infarction (MI), just 0.7% of patients, while the most common CVD was pericardial effusion detected in 31.1% of patients
• Our findings highlight the importance of close monitoring of COVID-19 patients for development of cardiac diseases during hospitalisation

Conflicts of interest

None declared.

Funding

The current study was supported by Shahroud University of Medical Sciences (grant number: 98126). The fund was absorbed in order to collect data.

Study approval

This project was approved by the Ethical Committee of Shahroud University of Medical Sciences, Shahroud, Iran (IR.SHMU.REC.1398.160).

Acknowledgement

We would like to thank the Vice-Chancellor of Research for their cooperation in collection of data.

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