Review of Literature on COVID-19 and Associated Cardiac Dysfunction in Patients Aged 30 to 50 Years Old

Abstract

Emerging evidence suggests that COVID is associated with a wide range of cardiac abnormalities in patients aged 30–50 years, including individuals with no prior cardiovascular risk factors. This review synthesizes five contemporary studies to evaluate the nature, persistence, and clinical implications of post-COVID cardiac dysfunction. Diagnostic approaches used in these studies included cardiac magnetic resonance imaging (CMR), echocardiography, and exercise testing. The use of these testing methodologies revealed subclinical impairments, structural remodeling, and diminished functional capacity. Additionally, persistent inflammation and abnormal global longitudinal strain were also frequently observed, often in the absence of other symptoms or elevated biomarkers. Despite variations in methodology and sample demographics, the studies converged on the conclusion that COVID poses a threat to cardiac health. Limitations of these studies included small cohort sizes, limited follow-up, and heterogeneity in diagnostic protocols, underscoring the need for standardized longitudinal research. The overall conclusion emphasizes the importance of proactive diagnostic screening and tailored treatment strategies to mitigate long-term cardiovascular consequences in this population.

Introduction 

Background and Significance

The COVID-19 pandemic in 2020, which was caused by the virus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has played a significant role in reshaping the global public health landscape and has served as a testament to failures in current healthcare systems. Right after the peak of the pandemic, the majority of medical research and resources concentrated predominantly on acute management and the immediate complications of the disease. At the time, the acute effects of the disease were far more prominent and little was known about the virus’s effects after the clearance of the acute infection. However, as we have moved away from the peak of the pandemic, attention has slowly started to shift toward the long-term health consequences experienced by survivors of COVID-19. These health consequences are commonly referred to as post-acute sequelae of SARS-CoV-2 infection (PASC).¹ Emerging evidence indicates that having COVID with long-term symptoms can affect multiple organ systems, most notably the cardiovascular system.^2,3 

Among the wide range of COVID associated symptoms, cardiac complications have been of  particular interest to clinicians due to their potential longitudinal severity and subtle clinical presentation in COVID survivors. Conditions such as myocarditis, subclinical left ventricular dysfunction, and arrhythmias have been documented even among patients who initially experienced mild acute infections.^4,5 Given that cardiac dysfunction can significantly reduce quality of life and increase morbidity, understanding the mechanisms, and prognosis of COVID associated cardiac dysfunction is of significant clinical importance. 

Research Question and Objectives 

Considering the clinical significance and public health implications of the COVID-19 pandemic, this literature review synthesizes existing knowledge about cardiac dysfunction in patients infected with COVID. The study is specifically targeting adults 30 to 50 years old, a population that is not considered at-risk by public health standards but displays a significant incidence of cardiac anomaly post-COVID infection. Furthermore, the study primarily focuses on cardiac dysfunction diagnosed within the first year of diagnosis. Overall, the primary research question guiding this review is: 

In patients aged 30–50 years (P), does a diagnosis of COVID (I), compared to those without a COVID diagnosis (C), increase susceptibility to prominent cardiac dysfunction (O) within the first year of diagnosis (T)? 

By reviewing recent and relevant research on this topic, including systematic reviews and primary studies, this review seeks to clarify the extent and characteristics of cardiac impairment linked with COVID infection. This will help identify diagnostic challenges, outline implications for clinical practice, and present a timeline for future research on COVID infection and the subsequent development of Cardiac Comorbidities (ie. diabetes, hypertension, and renal failure) which develop as a result of heart failure. 

Methods 

This review of literature employed a systematic approach to source selection and appraisal, drawing information from contemporary peer-reviewed literature that directly addressed cardiac dysfunction in the context of COVID infection. Studies were selected based on their relevance to the guiding research question and the methodologies which were employed to assess and track cardiac abnormalities in post COVID populations. A particular emphasis was placed on the rigor and diversity of methodologies used to assess cardiac function.

Articles were retrieved from prominent scientific databases, particularly PubMed, ScienceDirect, and Google Scholar. The primary search terms used during the research phase were "long COVID,” “cardiac dysfunction,” “myocarditis,” “CMR,” and “cardiovascular outcomes.” Inclusion criteria for the review included peer-reviewed primary research or systematic reviews published within the last five years focusing on the examination of cardiac function in post-COVID patients aged 30–50 years. Preference was given to studies utilizing advanced diagnostic methodologies such as cardiac magnetic resonance imaging (CMR), echocardiography, and electrocardiography. These tools were chosen for their ability to detect a wide spectrum of cardiac dysfunction, including subtle or subclinical abnormalities that may not present through routine clinical assessments. 

The selected literature also emphasized populations not traditionally considered at risk for cardiac disease, such as individuals without significant cardiac stress. This allowed for a more precise delineation of COVID-associated cardiac dysfunction independent of other cardiovascular risk factors. 

Critical appraisal of the studies was performed using the CASP checklists for systematic reviews and cohort studies. These tools were used to assess each article's validity, methodological quality, and relevance. Articles lacking sufficient follow-up, failing to clearly define cardiac endpoints, or focusing exclusively on elderly or high-risk populations were excluded. The resulting five studies, which comprises one systematic review and four primary studies serve as the foundation used for the synthesis and discussion which follow in the review of literature. 

Results 

Subclinical Cardiac Dysfunction in COVID 

Several primary studies have unveiled the prevalence of subclinical cardiac impairment in patients with a COVID diagnosis. This was particularly highlighted in the Marwick et al.’s large observational study with unique matched controls from the pre-pandemic era as a source of comparison. When subjected to Duke Activity Status Index (DASI) and a six-minute walk test, the COVID group showed significantly higher rates of subclinical left ventricular systolic dysfunction.⁵ This was particularly emphasized in reduced global longitudinal strain (GLS), with 34% having GLS <18% and 13% falling below 16%, compared to 15% and 8% in the control group, respectively.⁵ In addition, there were subtle structural changes in cardiac tissue including LV mass and minimal hypertrophy; however, diastolic parameters remained largely unchanged. Minimal hypertrophy suggests minimal enlargement or inflammation of cardiac cells. This indicates that despite changes in cardiac pathology, there are no real surface level indicators of cardiac stress. The lack of early surface level indicators may allow for subtle cardiac changes to transform into irreversible damage and cause severe impingements to one's quality of life. 

Similarly, the study conducted by Wojtowicz et al. revealed that 54% of patients from the TRICITY-CMR trial exhibited signs of non-ischemic myocardial injury, such as late gadolinium enhancement (LGE) and increased native T1 values, while maintaining normal cardiac biomarkers.² The severity of the non-ischemic myocardial injury is emphasized by the 8.3 % of trial participants who were found to meet the criteria for active myocarditis.² Despite the differences in testing methodology, approach, and demographics, the results presented by Wojtowicz et al. align with those seen in Marwick et al’s study. In both studies, patients exhibited varying signs of subclinical cardiac abnormalities (elevated T1 Values, reduced GLS strain, LV Mass, and active Myocarditis) while simultaneously presenting with normal diastolic parameters and and normal levels of biomarkers troponin and NT-proBNP. 

Despite the strong evidence of subtle structural changes presented by Marwick et al.’s study, it is important to note that RV strain could only be measured in a limited subset, and findings may not generalize to populations outside Australia, where most participants had the Omicron variant and were vaccinated.⁵ However, the study design used in the Trinity CMR Trial allows for a broader conclusion that COVID is associated with subtle structural changes in cardiac tissue. When viewed together, the two studies provide concrete support for structural and pathological changes in cardiac tissue associated with COVID infection. 

Despite methodological differences, all studies support the theme that measurable yet asymptomatic cardiac dysfunction remains prevalent among COVID patients. Holistically, these findings stress the importance of sensitive imaging tools in identifying cardiac dysfunction in populations which have a history of COVID-19 infection. This provides a bridge to the next section, which explores how these subclinical changes may evolve structurally over time. 

Persistent Inflammation and Structural Remodeling 

While subclinical dysfunction may appear benign on the surface, a growing body of research suggests it could mark the early stages of persistent myocardial inflammation and structural remodeling of cardiac tissue. In a study by Roca-Fernandez et al., 534 adults were recruited at random from a community setting that had many cases of persistent post-COVID symptoms and were screened using cardiac magnetic resonance (CMR) imaging with multiple parameters.³ As a result the study identified that 55% of participants who had cardiac abnormalities at six months continued to exhibit signs of myocardial inflammation and reduced left ventricular function after one year.³Coupled with this, there were also structural changes, such as elevated T1 values and persistent GLS abnormalities.³ These findings are consistent with those of Marwick et al. and Wojtowicz et al. as they indicate chronic structural changes without the presence of elevated cardiac biomarkers. The core difference in Roca et al.’s study is the longitudinal nature of her study model, which allows for the tracking of cardiac dysfunction long after initial infection.³ The findings primarily highlight the persistent nature of COVID associated inflammation and structural remodeling. 

Despite the strong results supporting the incidence of long term cardiac injury, the study’s applicability to the general population is limited by the study cohort's lack of ethnic diversity. Furthermore, the study's reliance on non-contrast imaging may lead to the underrepresentation of some structural changes in cardiac vasculature. To elaborate, the usage of primarily non-contrast imaging makes it harder to detect occlusions in smaller cardiac vessels, potentially underrepresenting some cardiac abnormalities. Despite the limitations of the study, it accomplishes its primary purpose of uncovering the true extent of longitudinal cardiac inflammation and structural remodeling. 

Furthermore, Krishna et al.’s systematic review bolsters these observations by highlighting a sustained pro-inflammatory state and endothelial dysfunction as potential drivers of continued cardiac remodeling.¹Interestingly, while both Roca-Fernandez et al. and Krishna et al. point to chronic inflammation, only Roca-Fernandez offers longitudinal imaging evidence that captures the persistence of these changes over time. In contrast, Wojtowicz et al., confirms inflammation via CMR, but is limited due follow-up imaging occurring at only a single point in time.² The use of CMR helps establish a baseline level of remodeling after COVID infection, however, the lack of follow-up imaging prevents analysis of the evolution of COVID associated cardiac remodeling. Evidence of baseline cardiac remodeling highlights the importance of long-term monitoring as cardiac remodeling coincides with rapid changes in cardiac anatomy and electrophysiology. These changes in physiology and anatomy directly correlate with increased risk of certain cardiac arrhythmias. 

The findings of these studies, however, are dissimilar to the results of Marwick et al. who identified functional cardiac deficits, but did not report persistent structural abnormalities on imaging, suggesting that not all post-COVID cardiac symptoms are the result of anatomical restructuring.⁵ Anatomical restructuring of the heart tissue is the result of damage caused by COVID infection and can result in the reshaping of the heart’s chambers and valves. These contrasting findings point to a possible decoupling between symptomatic experience and measurable structural pathology in post-COVID populations. The persistence of inflammation may be one factor that links structural remodeling to autonomic dysfunction, tying this theme to the next section that examines cardiovascular functional capacity of post COVID patients. 

Impaired Functional Capacity and Quality of Life 

In addition to structural and subclinical dysfunction, COVID has been associated with decreased functional capacity, including reduced exercise tolerance and quality of life. Marwick et al. found that patients with abnormal GLS were significantly more likely to report impaired functional capacity and perform poorly on objective treadmill exercise testing.⁵ This correlation suggests that subtle cardiac abnormalities may translate into meaningful physical limitations, even in the absence of traditional heart failure symptoms. 

Additionally, Roca-Fernandez et al. extended these findings by demonstrating that persistent cardiac inflammation was associated with reduced oxygen uptake (VO2 max) at one-year follow-up, providing a physiological basis for reported fatigue and dyspnea.³ While the findings of Roca-Fernandez et al. and Marwick et al. reach the similar conclusions, it is important to note the differences in their methodologies, as differences in assessment modalities complicate interpretation. While Marwick et al. utilized exercise treadmill testing, Roca-Fernandez relied on cardiopulmonary exercise testing (CPET), which may provide a more nuanced understanding of exertional limitations.^3,5 This distinction underscores the need for standardized evaluation methods in COVID research. The variation in outcomes also highlights the broader challenge of correlating imaging abnormalities with functional outcomes, a theme that intersects with both subclinical dysfunction and persistent inflammation. 

Xie et al. add further weight to these concerns through a large-scale cohort analysis showing that COVID-19 survivors had an elevated risk of developing heart failure, dysrhythmias, and other cardiac events that can manifest in impaired physical performance and quality of life.⁴ Particularly it was noted that the hazard ratio for myocarditis was 5.38, and for heart failure, it is 1.72, even among patients who were never hospitalized during the acute phase of their infections.⁴ These ratios are computed by comparing the incidence of myocarditis and heart failure respectively between the COVID survivors group and the two control groups used in the study. A hazard ratio greater than one is indicative of a higher incidence rate of myocarditis and heart failure in the COVID survivors group.  Overall, the studies presented show a strong association between the incidence of COVID infection and inflammatory, structural, and functional cardiac dysfunction. However, more research is needed to establish a more reliant methodology to predict COVID associated cardiovascular dysfunction. 

Discussion 

The purpose of this review was to determine whether individuals aged 30–50 years with COVID exhibit increased susceptibility to cardiac dysfunction within the first year of infection. Overall,  the five studies assessed in this review agree that COVID with prolonged symptoms is associated with both subclinical 

and functional cardiac abnormalities in populations without traditional cardiovascular risk factors. 

The findings present concrete support for the integration of more advanced diagnostic methods in post-COVID evaluations. While subclinical dysfunction may remain asymptomatic, it has the potential to evolve into more serious cardiovascular complications. The widespread use of tools such as cardiac magnetic resonance imaging (CMR) and global longitudinal strain (GLS) measurements can enhance early detection of myocardial injury associated with COVID infection, enabling proactive intervention before irreversible damage occurs. 

The findings also underscore the need to re-evaluate post-COVID care protocols. Current symptom-based assessments may overlook patients with underlying cardiac issues, which may not be screened for in any traditional cardiac screening methodologies. Hence, developing standardized screening strategies, particularly for younger patients who may not present typical risk factors, could significantly improve long-term outcomes. Tailored treatment plans based on imaging and functional assessments could help prevent progression to overt heart failure or arrhythmias. 

Ensuring that COVID infection does not decrease the longevity of younger populations can be best established by focusing on the hidden markers of COVID related cardiac dysfunction. The use of advanced imaging and functional tests like stress-tests coupled with EKGs can uncover subtle changes in cardiac electrophysiology. Furthermore, investing in studies targeted toward younger populations with no cardiac dysfunction at the time of COVID infection, will help reduce COVID related morbidity and will contribute to decreases in Disability Adjusted Life Years (DALY) and Years of Potential Life Lost (YPLL). 

The studies analyzed exhibited important strengths in diagnostic platforms used. The use of advanced imaging techniques such as CMR allowed for detailed visualization of myocardial tissue, uncovering subtle yet clinically relevant changes. Longitudinal designs, such as those employed by Roca-Fernandez et al., provided critical insights into the persistence of cardiac dysfunction over time. These methodological strengths should inform future study designs, emphasizing the need for consistency, diversity, and longer follow-up periods.

Lastly, future research should prioritize longitudinal cohort studies that integrate clinical outcomes, biomarker analysis, and imaging data to better understand the trajectory and mechanisms of COVID-induced cardiac dysfunction. By refining diagnostic and therapeutic strategies, healthcare systems can better address the evolving cardiovascular burden posed by the pandemic. 

Conclusion 

This review of literature has demonstrated a strong association between COVID infection and various forms of cardiac dysfunction in individuals aged 30–50 years. Across the studies examined, subclinical myocardial impairment, persistent myocardial inflammation, and reduced exercise capacity were consistently documented in patients. These findings are significant as they highlight potential long-term consequences in a demographic not traditionally considered at high risk for cardiovascular complications. 

The implications of these results extend beyond academic or scientific interest. Clinicians must be equipped with advanced diagnostic tools and must possess a novel understanding of COVID’s cardiovascular effects. Strategies such as incorporating cardiac magnetic resonance imaging (CMR) and global longitudinal strain (GLS) into routine assessments may allow for earlier identification of at-risk patients and more personalized treatment interventions. 

Limitations within the current body of research, including small sample sizes, lack of standardized diagnostic protocols, and limited diversity in participant populations, hinders the  generalizability of findings from this body of literature. Ongoing research is essential to clarify the long-term trajectory of cardiac dysfunction in patients infected with COVID and to develop evidence-based guidelines for diagnosis, monitoring, and treatment. With consistent methodology and broader patient representation, future studies can build on these foundational insights to improve outcomes for affected individuals. 

None of the sources reviewed disclosed any conflicts of interest, contributing to the credibility and objectivity of the findings presented here.

About the Author: Surya Balamurugan

The author chose to write this literature review to analyze the cardiovascular impacts of COVID-19 on populations generally considered "not at-risk." By examining the specific mechanisms through which SARS-CoV-2 alters cardiac structure and physiology, the author aims to highlight how better screening protocols and treatments can be developed. Furthermore, they suggest that gaining insight into how subtle viral changes can have profound effects on long-term health will provide better preparedness for future pandemics. Ultimately, the author intends to continue applying the principles of microbiology to the field of medicine as they pursue a career as a physician.

Author’s Note

This review was written to inform the medical community about the prevalence of cardiac dysfunction in patients. The research question was aimed at addressing an increasingly prevalent and neglected long-term pathology which primarily affects men and women aged 30-50 years old. Furthermore, this review advocates for the development of new testing protocols to test for early stage cardiac dysfunction in patients with a history of COVID infection. Overall, the review brings attention to pertinent medical issues which can be addressed using new diagnostic and treatment protocols.

References

1. Krishna BA, Metaxaki M, Sithole N, et al. Cardiovascular disease and COVID-19: a systematic review. IJC Heart Vasc. 2024;54:101482. doi:10.1016/j.ijcha.2024.101482

2. Wojtowicz D, Dorniak K, Ławrynowicz M, et al. Cardiac magnetic resonance findings in patients recovered from COVID-19 pneumonia and presenting with persistent cardiac symptoms: the TRICITY-CMR Trial. Biology (Basel). 2022;11(12):1848. doi:10.3390/biology11121848 

3. Roca-Fernandez A, Wamil M, Telford A, et al. Non-invasive evaluation of cardiopulmonary symptoms in post-acute sequelae of SARS-CoV-2 infection. Open Heart. 2023;10:e002241. doi:10.1136/openhrt-2022-002241 

4. Xie Y, Xu E, Bowe B, Al-Aly Z. Long-term cardiovascular outcomes of COVID-19. Nat Med. 2022;28(3):583-590. doi:10.1038/s41591-022-01689-3 

5. Marwick TH, Wexler N, Smith J, et al. Cardiac function and functional capacity in patients with long COVID: a comparison to propensity-matched community controls. J Am Soc Echocardiogr. 2025;38(1):16-23. doi:10.1016/j.echo.2024.09.006