Discussion
ICD shock negatively affects patients’ quality of life, causes adverse outcomes, is associated with higher mortality rates,9and is the most critical cause of rehospitalization in patients with ICDs. This study revealed a significant increase in hospitalizations due to ICD shock during the peak period of SARS-CoV-2 infection compared with the rates in the same period in the past, suggesting a possible correlation between SARS-CoV-2 infection and ICD shock. Therefore, it is essential to understand the causes of ICD shock in patients with ICDs following SARS-CoV-2 infection to provide targeted treatment and prevent adverse events upon admission.
With the increase in the number of SARS-CoV-2-infected patients and the accumulation of clinical data, the development of significant cardiovascular complications after infection has become more apparent.3,14–19 The current view is that SARS-CoV-2 infection triggers a range of cardiovascular manifestations through multiple mechanisms.16,20–24 However, owing to the lack of related reports, the mechanism through which patients with ICDs become more susceptible to shocks following SARS-CoV-2 infection remains unknown. A previous multicenter study reported a significant increase in ICD shock among those with such devices during the COVID-19 outbreak in the United States.12 Two other single-center studies reported no increase in ventricular arrhythmic events, although deaths were observed in patients with ICDs during the peak of the pandemic in Italy in 2020.25,26 However, these studies evaluated ICD shocks using continuous remote monitoring systems and did not determine whether patients experiencing them were infected with SARS-CoV-2; therefore, the correlation between ICD shock and SARS-CoV-2 infection requires further investigation.
In this study, we analyzed data from seven patients who were admitted to our hospital for ventricular arrhythmias or ICD shocks within 3–20 days after SARS-CoV-2 infection. We analyzed their program and clinical data and observed that they shared specific characteristics that may have driven the development of ventricular arrhythmias or ICD shocks after SARS-CoV-2 infection. Most patients exhibited elevated troponin levels, suggesting the development of myocardial damage post-infection, which has been suggested to be a cause of ICD-induced shocks.14,27 A higher incidence of malignant ventricular arrhythmias has been reported in patients with severe left ventricular dysfunction and coronary artery disease.28,29 Among these seven patients, six were implanted with ICDs or CRT-Ds for ischemic cardiomyopathy and were prone to malignant arrhythmias. SARS-CoV-2 infection can disrupt the oxygen supply equilibrium and cause a cytokine storm, further damaging cardiomyocytes, and the development of malignant arrhythmias increases the likelihood of ICD shock. In addition, SARS-CoV-2 can directly damage cardiomyocytes by downregulating angiotensin-converting enzyme 2 (ACE2) receptors and interfering with ACE2-associated signaling pathways.30 It should be noted that these six patients had not experienced sustained VT or recurrent ICD shocks prior to infection, suggesting that SARS-CoV-2 infection may play a role in ICD shock as a potential arrhythmia trigger.
Decreased potassium and calcium concentrations may represent another mechanism underlying ICD shock development after SARS-CoV-2 infection. Most of the patients developed electrolyte imbalances post-infection, mainly in the form of reduced potassium and calcium ion levels, possibly due to a fever-induced increase in sweating post-infection, or insufficient potassium and calcium ion intake due to decreased appetite. Decreased calcium ion concentrations can induce arrhythmias by affecting ion channel functions and the difference in potential between the interior and exterior of myocardial cells.31Clinically, hypokalemia is a common cause of arrhythmogenesis, and severe hypokalemia can lead to life-threatening ventricular arrhythmias. In addition, hypokalemia and hypocalcemia can prolong the QT interval, inducing the development of malignant arrhythmias. In this study, six patients exhibited QT interval prolongation (> 440 ms) (mean QT interval: 460 ± 46 ms; range: 386–536 ms). All patients exhibited varying degrees of HF symptom exacerbation after SARS-CoV-2 infection, and NT-proBNP levels significantly exceeded the normal range upon admission. We speculate that the exacerbation of HF due to SARS-CoV-2 infection may be another important factor leading to ICD shock. The current view is that an acute increase in cardiac load can cause cardiomyocyte stretching, altering myocardial electrical activity and leading to the development of various types of arrhythmias.32 We believe that myocardial injury and electrolyte imbalances caused by infection are the leading causes of HF exacerbation in these patients. Furthermore, most patients did not continue to take their anti-HF medications regularly after the infection, out of concern for Safety, which may be another cause of the acute exacerbation of HF in these patients.
Previous studies have shown that secondary prevention and ICD implantation are risk factors for the development of malignant arrhythmias.33 However, the total number of shocks administered was significantly higher in the patients who received ICDs for primary prevention than in those who received them for secondary prevention (68 vs. 12, respectively). This suggests that SARS-CoV-2 infection plays a dominant role in the induction of ICD shock. AF is a predictor of inappropriate shocks,34,35 and patients with SARS-CoV-2 infection are more susceptible to AF during the acute and late recovery phases.36,37 It can be hypothesized that SARS-CoV-2 infection increases the AF load, serving as another possible factor contributing to inappropriate shocks in these patients.
Three of the seven patients in this study experienced ventricular electrical storms post-infection, and these patients did not experience the reoccurrence of arrhythmias following the administration of antiarrhythmic drugs and the removal of the triggers. We suggest that SARS-CoV-2 infection can cause malignant arrhythmias through various mechanisms such as myocardial damage, electrolyte disturbances, QT interval prolongation, HF aggravation, and AF induction of AF; most of these malignant arrhythmias can be terminated by ICD shock, preventing mortality and demonstrating the value of ICDs in preventing SCD. Simultaneously, because ICD shock is associated with higher mortality,9 the frequency of programmed follow-up should be increased during the COVID-19 pandemic. Post-infection, follow-up of patients can be conducted by telephone for timely clinical evaluation and guidance on medications. If necessary, patients should be admitted to the hospital as early as possible to eliminate the triggers of arrhythmia and minimize the likelihood of ICD shock. In the present study, none of the patients experienced further ICD shock after the removal of the aforementioned triggers.
It is important to note, however, that this study included only seven patients; therefore, more extensive clinical studies are needed to confirm these findings.