Postinfluenza Cardiac Tamponade: A Review of Published Case Reports

Abstract

Increased vaccination rates and better understanding of influenza virus infection and clinical presentation have improved the disease’s overall prognosis. However, influenza can cause life-threatening complications such as cardiac tamponade, which has only been documented in case reports. We searched PubMed/Medline and SCOPUS and EMBASE through December 2021 and identified 25 case reports on echocardiographically confirmed cardiac tamponade in our review of influenza-associated cardiac tamponade. Demographics, clinical presentation, investigations, management, and outcomes were analyzed using descriptive statistics. Among 25 cases reports [19 adults (47.6 ±15.12) and 6 pediatric (10.1 ± 4.5)], 15 (60%) were females and 10 (40%) were male patients. From flu infection to the occurrence of cardiac tamponade, the average duration was 7±8.5 days. Fever (64%), weakness (40%), dyspnea (24%), cough (32%), and chest pain (32%) were the most prevalent symptoms. Hypertension, diabetes, and renal failure were most commonly encountered comorbidities. Sinus tachycardia (11 cases, 44%) and ST-segment elevation (7 cases, 28%) were the most common ECG findings. Fourteen cases (56%) reported complications, the most common being hypotension (24%), cardiac arrest (16%), and acute kidney injury (8%). Mechanical circulatory/respiratory support was required for 14 cases (56%), the most common being intubation (9 cases, 64%). Outcomes included recovery in 88% and death in 3 cases. With improving vaccination rates, pericardial tamponade remains an infrequently encountered complication following influenza virus infection. The complicated cases appear within the first week of diagnosis, of which nearly half suffer from concurrent complications including cardiac arrest or acute kidney injury. Majority of patients recovered with timely diagnoses and therapeutic interventions.

Introduction

Influenza causes enormous public health burdens around the world each year. From 2010 through 2020, the CDC estimates that influenza infection caused 12000–61000 fatalities, 140000–810000 hospitalizations, and 9–45 million illnesses [1]. Influenza is one of the most common and serious viral respiratory infections, posing a significant healthcare burden. Influenza causes a variety of symptoms that usually resolve spontaneously, with just a few consequences. However, sometimes it may lead to pulmonary complications like a respiratory failure. Besides pulmonary complications, influenza infection can also lead to extrapulmonary complications including myocarditis and encephalitis [2]. Increased cardiovascular mortality has been documented among older patients visiting emergency rooms during flu season, indicating that influenza infection is directly linked to cardiovascular death and is reported to result in temporary and reversible heart malfunction [3], fulminant myocarditis, and dilated cardiomyopathy [4, 5]. Influenza infection has also been linked to a range of cardiovascular complications like pericarditis, cardiac tamponade, ventricular arrhythmias, and sudden cardiac death [5].

Although most patients with influenza infections recover because of advances in diagnoses and treatment over the previous decade, severe complications such as cardiac tamponade can have life-threatening implications and increase overall healthcare costs. Cardiac tamponade has been a known life-threatening condition, and among the numerous etiologies, the postviral compilation is one of them [6]. With the increasing number of case reports suggesting influenza-related cardiac tamponade, it has become essential to understand the demographic and clinical characteristics and subsequent management strategies to curtail mortality in these high-risk patients. Therefore, considering a lack of aggregated data in existing literature, we aimed to systematically review the occurrence of cardiac tamponade in patients with influenza virus infection in this report.

Methods

We comprehensively searched for case reports and case series using different keyword combinations using influenza, flu, cardiac tamponade, and tamponade in PubMed/Medline, Web of Science, SCOPUS, and Google Scholar from inception till December 2021.

Our search using these keywords yielded a total of 180 results [PubMed 54, Scopus 60, EMBASE 66], of which 23 articles with 25 unique case reports were selected based on abstract/full-text screening and removal of duplicates [7–29]. Only articles published in English were considered for the final analysis.

Age, sex, underlying comorbidities, therapies needed, and results were all curated. Categorical data were presented as absolute values and percentages, whereas continuous variables were given as averages and standard deviations. Microsoft Excel was used for data extraction and descriptive analysis. Since the data included in this review were deidentified and already available in the publicly accessible databases, the IRB review was not mandatory.

Results

Of 25 cases reviewed [19 adults (47.6 ± 15.12) and 6 pediatric (10.1 ± 4.5)], 15 (60%) were females, and 10 (40%) were male. Because none of the cases mentioned race, it was excluded from the analysis (Table 1). Most instances were recorded from the United States (48%), France (12%), Spain (12%), Korea, Japan, and Canada (7% each), with the rest coming from the United Kingdom, Poland, Italy, and Finland. Nineteen patients (76%) had influenza A, and six (16%) had influenza B. Four patients had received a flu vaccination. Of 19 adult cases, hypertension was noted in around 21% [4] and diabetes in around 16% [3] of cases whereas 3 patients were on hemodialysis.

Table 1.

Demographics, clinical characteristics, investigations/management, complications, and outcomes in influenza virus infection-associated pericardial tamponade

Author, year, country	Age, sex	Past medical history	Presenting symptoms	Days to develop cardiac tamponade	Influenza A/B	Antiviral therapy	Influenza vaccine	ECG findings	LVEF (%)	Peak troponin T (ng/ml)	Pericardiocentesis	Complication	Mechanical circulatory/respiratory support	Outcome at discharge/follow-up
Adult case reports
Schroff, 2021, USA	29,F	x	Flu-like illness, chest pain, abdominal pain, nausea, vomiting	15	B	O	No	Electrical alternans	x	x	Yes	x	x	Recovered
Arfaras-Melainis, 2020, USA	32,F	x	Flu-like illness, epigastric pain, orthopnea, cough	4	B	O	x	x	x	x	Yes	x	x	Recovered
Ganji, 2019, USA	66,F	HTN, DM, breast cancer (remission)	SOB, pleuritic chest pain, chills	14	A	No	No	Diffuse ST-segment elevation, PR segment depression in anterolateral leads	x	x	Yes	x	MRSA pericarditis	Recovered
Pandey, 2019, USA	57, M	HTN	Fever, muscle aches, chest pain	2	A	O	x	Sinus tachycardia	x	0.12	Yes	Shock	x	Recovered
Mendez, 2019, Spain	35, M	Cocaine and smoking	Flu-like illness, cough, chest pain	5	A	O	x	Sinus tachycardia	24-15	x	Yes	Myocarditis, cardiogenic shock	Intubation, ECMO, vasopressor	Recovered
Roto, , 2018, USA	57,F	x	Altered mental status, nausea, vomiting, mild cough, fever	7	B	x	x	Sinus tachycardia	x	x	Yes	Cardiac arrest	CPR, intubation	Death
Allyn, 2017, France	69,F	Horton disease	Weakness	23	A	O	Yes	x	30	0.397	Yes	Cardiogenic & hypovolemic shock, ARDS, AKI	ECMO	Recovered
Burke, 2017, USA	53, M	CML, GVHD	SOB, productive cough, rhinorrhea, congestion, fever, chills, weakness	7	A	O	Yes	x	x	x	Yes	PJP pneumonia	Intubation	Recovered
Leon, 2017, Spain	54,F	Diverticulitis, PBC	Generalized weakness, pain, fever, “cold” symptoms	7	A	No	No	Sinus tachycardia	37	0.312	Yes	Shock, AKI	Intubation	Recovered
Sidhu, 2016, Canada	22, F	Alcohol and cocaine use	Fever, nausea, vomiting, myalgia, fatigue	7	A	O	x	Sinus tachycardia, low voltage limb leads	x	x	Yes	x	x	Recovered
Youn, 2016, Korea	34 M	x	Fever, chills, malaise	3	A	Antiviral treatment	x	Normal sinus	x	x	Yes	x	x	Recurrent pericardial effusion, primary pericardial synovial sarcoma
Buzon, 2015, France	57,F	COPD, TTS-10 years ago	Pulmonary edema, fever	5	A	O	No	ST-segment elevation in V3, V4, V5	30	0.52 μg/ml	Yes	Cardiogenic shock	Intubation	Recovered
Martín-Lázaro, 2013, Spain	62, M	HTN, DM, Obesity	Respiratory failure, altered sensorium, dyspnea, malaise, asthenia, anorexia	42 (6 weeks flu-like)	A	O	x	Low voltage, sinus rhythm, old RBBB	40	0.03 ng/dl	Yes	x	Noninvasive ventilatory support	Recovered
Horai, 2010, Japan	24, M	Head injury, Schizophrenia, SLE	Fever	x	B	Z	x	x	x	x	Yes	Acute circulatory and respiratory failure	Intubation	Recovered
Laurila, 2005, Finland	41, F	x	Fever, headache, sore throat, myalgia, fatigue, abdominal pain, lower back pain	5	A	x	x	Sinus tachycardia, low-voltage QRS, diffuse ST-segment depression	x	x	Yes	Septic shock, ileus	Mechanical ventilation	Recovered
Nwizu, 2004, USA	53,F	x	Cold, malaise, generalized weakness, nausea, body ache	6	B	x	x	Sinus tachycardia, diffuse ST-segment elevation	x	x	Yes	x	x	Recovered
Osanloo, 1979 (1), USA	51, M	Diabetic glomerulosclerosis (on HD)	Chest pain, dyspnea	1	A	x	x	x	x	x	Yes	x	x	Recovered
Osanloo, 1979 (2), USA	68, M	AF, ESRD (on HD)	Chest pain, dyspnea	10	A	x	x	x	x	x	Yes	x	x	Recovered
Osanloo, 1979 (3), USA	41, M	HTN, malignant nephrosclerosis (on HD)	Fever, chills, cough, chest pain	1	A	x	x	x	x	x	Yes	x	x	Recovered
Pediatric case reports
Lefeuvre, 2018, France	14,F	x	Fever, SOB, tachypnea, abdominal pain	2	A	x	x	x	x	x	No	Cardiac arrest	External defibrillator, intubation	Death
Morparia, 2018, USA	4,M	Mild intermittent asthma	High fever, right-sided chest pain	2	B	O	Yes (5months ago)	x	x	x	Yes	MRSA pleural effusion	x	Recovered
Ito, 2015, Japan	9, F	Asthma	Fever and cough	4	A	Z, P	Yes	ST-segment elevation in V3-V6	47.2	10.3	Yes	x	Intubation	Recovered
Chaluvadi, 2011, USA	6, F	x	Cough, diarrhea, fever	5	A	O	No	x	x	x	No	Cardiac arrest, pulmonary hemorrhage, MRSA septic shock, ischemic, hemorrhagic stroke	Intubation and ECMO	Recovered with right-sided hemiparesis
Puzelli, 2010, Italy	11, F	x	Fever, cough, vomiting, dizziness	36 hours	A	x	x	Sinus tachycardia with diffuse ST-segment elevation	20-30	4.24	No	Metabolic lactic acidosis, heart failure	CPR	Death
Mamas, 2007, UK	17, F	x	Flu-like illness, dizziness, fever	3	A	x	x	Sinus tachycardia, inferior ST-segment elevation, diffuse anterolateral T wave inversion	x	x	Yes	Shock	x	Recovered

x not available, F female, M male, HTN hypertension, DM diabetes mellitus, CML chronic myeloid leukemia, GVHD graft versus host disease, PBC primary biliary cholangitis, COPD chronic obstructive pulmonary disease, TTS takotsubo cardiomyopathy, SLE systemic lupus erythematosus, HD hemodialysis, O oseltamivir, Z zanamivir, P peramivir, RBBB right bundle branch block, MRSA methicillin-resistant staphylococcus aureus, ARDS acute respiratory distress syndrome, AKI acute kidney injury, PJP Pneumocystis jirovecii

From flu infection to cardiac tamponade, the average period was 7±8.5 days. Fever (64%), weakness (40%), dyspnea (24%), cough (32%), and chest pain (32%) were the most prevalent symptoms. On physical examination, three cases displayed pulsus paradoxus; three displayed pericardial friction rub, two showed pleural friction rub, and seven presented jugular venous distension. A chest X-ray of nine cases demonstrated cardiomegaly. Sinus tachycardia (11 cases, 44%) and ST-segment elevation (7 cases, 28%) were the most common ECG findings. Echocardiography, in all cases, confirmed cardiac tamponade.

Of 25 cases, 14 cases (56%) reported complications, the most common being hypotension (24%), cardiac arrest (16%), and acute kidney injury (8%). Mechanical circulatory/ respiratory support was required for 14 cases (56%), the most common being intubation (9 cases, 64%). The outcomes were reported as either recovery or death. Eighty-eight percent recovered successfully with three reported deaths. One patient had cardiopulmonary arrest, and the autopsy showed cardiac tamponade; the second patient had associated acute respiratory distress syndrome and asystolic cardiac arrest while third the patient who died had complications including metabolic lactic acidosis and heart failure.

Discussion

Influenza being a self-limiting infection usually resolves without any intervention. Morbidity and mortality, on the other hand, have only been reported in high-risk populations. Pericardial involvement can proceed to pericarditis, which can lead to cardiac tamponade and sudden cardiac death. There is a recent report reviewing 75 case reports on myopericarditis associated with influenza infections [30]. However, the contemporary large-scale data on the incidence of pericardial effusion and tamponade with influenza infection are currently unavailable.

Both adults (mean 48 years) and pediatric patients (mean 10 years) were found to be affected by postinfluenza cardiac tamponade in this systematic review of 25 cases. The majority of the individuals in our study developed tamponade within a week of contracting influenza. Patients infected with strain A had a higher rate of tamponade than patients infected with strain B. Even though there was no clear gender difference in adult patients, girls under the age of 18 were diagnosed with tamponade more frequently than boys. Quandelacy et al. conducted a retrospective analysis using aggregated regional and national level data from 1997 to 2007 to better understand the causes of influenza-related death [31]. According to the study, influenza-related cardiovascular problems and mortality were particularly high in older patients and those with underlying heart disorders. Similarly, our analysis revealed that half of the patients (40%) with cardiac tamponade had one or more underlying comorbidities, with hypertension being the most common in adults and asthma in the pediatric age group. Sellers et al. discussed the hidden burden of extrapulmonary complications associated with influenza virus infection including cardiac manifestations. However, the association of cardiovascular comorbidities remains understudied on a large scale in relation to pericardial diseases following influenza virus infection [2]. Furthermore, 3 patients were on hemodialysis and 4 patients had autoimmune/immunocompromised states during the presentation. Data pertaining to the autoimmune or multisystem disorders affecting the course and outcomes of influenza-related pericardial complications remain limited.

When compared to the current literature on influenza-related cardiovascular problems, our review has a few noteworthy findings. There have been studies that show influenza immunization reduces cardiovascular mortality. Naghavi et al. found that immunization against the influenza virus was related to a 67 percent reduction in the incidence of cardiovascular problems in a case-control study of 233 patients [32]. Even though the studies have shown vaccination reduces symptoms and death [33], we discovered that only one-fourth of the patients in our study were vaccinated. This could explain why these reported cases might have experienced life-threatening consequences such as cardiac tamponade [34]. This further reinforces the importance for the timely vaccinations especially amid rising fears of new viral strains and possibly multistrain respiratory illnesses.

Echocardiography was acknowledged as a diagnostic tool for cardiac tamponade [35], and all the patients had tamponade diagnosed on echocardiogram. A particular pattern of changes was difficult to characterize since changes in the ECG, chest X-ray, CT scan thorax, and Troponin-T were not uniformly recorded in all patients. On EKG, sinus tachycardia and new ST-elevation changes not ascribed to acute myocardial infarction were reported frequently.

Eighty-eight percent of the patients survived. Antiviral medications were given to 14 of the 25 cases. Oseltamivir was the most often used antiviral. There is little evidence to support the use of antivirals as a prophylactic treatment for postinfluenza cardiac problems. There are ongoing studies evaluating the long-term effects of anti-influenza vaccination reducing acute cardiovascular events that can further pave the way to effectively control fatalities related to tamponade.

Since pericardial tamponade can lead to fatal outcomes, it is essential to understand the characteristic signs of tamponade, including pulsus paradoxus, right atrial, and right ventricle diastolic collapse as the intrapericardial pressure exceeds the intracardiac pressure. Previous studies have reported that a few patients with cardiac tamponade will not have dyspnea, tachycardia, elevated jugular venous pressure, or cardiomegaly on chest radiograph; however, a pulsus paradoxus >10 mm Hg among patients with a pericardial effusion helps differentiate those with cardiac tamponade from those without [36]. Circulatory compromises that led to hypoperfusion problems were treated with pericardiocentesis, mechanical or circulatory support measures, and ECMO among the cases included in our review. Pericardiocentesis has shown to reduce recurrent pericardial complications in earlier reports [37]. Three patients who died reported to have associated complications including heart failure, acute respiratory distress syndrome, metabolic acidosis, and asystolic cardiac arrest. Two of the three patients who died did not receive pericardiocentesis, which is noteworthy enough to warrant pericardiocentesis in influenza-related tamponade.

There are a few limitations of this review. These cases span several years rather than a single season. As a result, adjusting the strain could affect the outcome and severity of complications. Due to the small sample size, commenting on the burden of any issues and the outcome was difficult. Because there was no uniform reporting, some data was missing from case to case. We were unable to locate any cases from underdeveloped countries, making it difficult to speculate on how changes in healthcare infrastructure would affect the outcome. Laboratory parameters were not reported in all case reports.

These are some of the recommendations that would help physicians to effectively screen and manage high-risk patients based on this review of published cases-

1. ECG may show signs of pericarditis. However, patients might just present with sinus tachycardia which was noted in most of our cases around 42% (8). Despite lack of typical ECG changes of pericarditis or cardiac tamponade, a high suspicion of pericardial tamponade should be considered on clinical basis in patients diagnosed positive for influenza with concomitant comorbidities and medical history.

2. Low QRS voltage is typical for pericardial tamponade; however, its absence should not exclude the diagnosis based on our review.

3. Reported cases did not mention any culture and cytology of pericardial fluids obtained during pericardiocentesis which could help in deciding any other underlying cause and help in management of these cases.

4. Consistent to literature, timely diagnoses and drainage of the pericardial fluid, preferably by needle pericardiocentesis performed in most cases, yielded excellent outcomes. Two of the three patients who died did not receive pericardiocentesis, which is noteworthy in our review.

5. Impact of frequently encountered comorbidities such as hypertension, diabetes, and renal failure needs further evaluation on influenza virus infection-associated pericardial complications and fatal outcomes.

6. There always remain high risk of developing shock, organ hypoperfusion leading to renal failure, and cardiac arrest as short-term compilations in these patients for which clinicians should remain highly vigilant as they could potentiate the risk of poor outcome. This has become more important given the nature of upcoming new virus strains and expectedly growing infectivity.

7. Future studies are warranted to evaluate the protective role of vaccination on long term to curb severe cardiovascular complications and improve outcomes.

Conclusion

Pericardial tamponade is one of the life-threatening disease and a rare complication of influenza infection. The complicated cases appear within the first week of diagnosis, more frequently from influenza type A strain, of which nearly half suffer from concurrent complications including cardiac arrest or acute kidney injury. Majority of patients recovered with timely diagnoses and therapeutic intervention. With the rising fear of coinfections with COVID-19 and influenza in upcoming flu seasons, it is essential to be cognizant of this potentially rare but fatal cardiovascular complication of influenza virus infection.

Authors’ Contributions

RD, SS, JR, VI, and JS conducted the literature search, study screening and selection, and data extraction. RD, AJ, JR, VI, and JS performed the statistical analysis; RD, AJ, SS, JS, UM, and BR contributed to writing this manuscript; RD, AJ, UM, BR, GK, and RS provided feedback and modified/edited this manuscript.

Data Availability

All data generated or analyzed during this study are included in this published article.

Code Availability

Not applicable.

Declarations

Ethics Approval

Since the data included in this review were deidentified and already available in the publicly accessible databases, the IRB review was not mandatory. This review was in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

Competing Interests

The authors declare no competing interests.