1. Introduction

The intricate relationship between mental health and cardiovascular health has been a subject of considerable research interest over the past few decades. Bipolar disorder, a mental health condition characterized by extreme mood swings, has been particularly noted for its association with various cardiovascular risks.[1] Despite increasing recognition of this association, the specific impact of bipolar disorder on myocardial function, particularly in terms of myocardial strain as assessed by echocardiography, remains poorly explored. This research gap forms the crux of our study, which aims to deepen the cardiac implications of bipolar disorder.[1]

Cardiovascular diseases are among the leading causes of morbidity and mortality worldwide, and their intersection with psychiatric conditions such as bipolar disorder presents a complex clinical challenge.[1] Studies have shown that patients with bipolar disorder have an increased risk of developing cardiovascular diseases, which can be attributed to a combination of lifestyle factors, the psychiatric condition itself, and the side effects of psychiatric medications.[2] However, the understanding of how bipolar disorder affects cardiac structure and function in different phases—depressive, manic, and euthymic, remains limited.

Research in this area has focused predominantly on the broader aspects of cardiovascular risk, such as the prevalence of traditional risk factors such as hypertension, diabetes, and dyslipidemia in individuals with bipolar disorder.[3] There has been less emphasis on the direct assessment of cardiac function using advanced techniques such as echocardiography, particularly in terms of myocardial strain. Myocardial deformation, a parameter that provides information on cardiac muscle deformation during the cardiac cycle, is an important indicator of myocardial function and has been associated with various cardiac pathologies.[4]

The primary objective of this study is to fill this research gap by investigating myocardial strain patterns in patients diagnosed with bipolar disorder during different phases of their illness compared to healthy controls. This objective is driven by the hypothesis that bipolar disorder, with its varying emotional and physiological stresses in different phases, may have distinct impacts on cardiac function.

By employing a cross-sectional study design and using echocardiographic measures, particularly focusing on global longitudinal strain (GLS), this study aims to ascertain whether there are significant differences in myocardial strain between individuals in different phases of bipolar disorder. This approach is expected to provide a more nuanced understanding of the cardiac implications of this mental health condition, beyond what is known from traditional cardiovascular risk assessments.[5]

In addition to exploring the primary association between bipolar phases and myocardial strain, this study also aims to examine the potential effects of bipolar medications on cardiac function. Given that many psychiatric medications have known cardiovascular effects, understanding their impact on myocardial strain could have significant clinical implications for the management of bipolar disorder.[6]

In summary, this study addresses a critical gap in the current understanding of bipolar disorder. Using a focus on myocardial strain through an echocardiographic assessment, it aims to provide valuable information on the cardiac health of individuals with bipolar disorder. The findings of this study are anticipated to contribute to a more comprehensive approach to managing bipolar disorder, considering both mental and cardiac health, and could potentially inform clinical guidelines and therapeutic strategies.[7]

2. Methods 2.1. Study design and setting

This cross-sectional study will be conducted at the Dursun Odabaş Medical Centre, Psychiatry Clinic of Van Yüzüncü Yl University. The objective is to evaluate electrocardiographic (ECG) and echocardiographic (Echo) findings in patients diagnosed with bipolar disorder during different phases of their illness compared to healthy controls.

2.2. Participants

The study will enroll 200 participants: 50 in a depressive phase, 50 in a manic phase, 50 in an euthymic phase of bipolar disorder, and 50 healthy volunteers. The inclusion criteria for the bipolar group include patients aged 20 to 50 years, diagnosed with bipolar disorder, and with no known history of cardiac disease. The control group will consist of people who match the age and gender distribution of the patient group but without a history of psychiatric or cardiac disorders.

2.3. Data collection

Participants will undergo routine physical examinations and laboratory tests during their outpatient visits. Subsequently, they will be referred for an ECG and echocardiographic evaluation. Data collection will focus on ECG abnormalities (such as arrhythmias and ischemic changes), echocardiographic parameters (including systolic and diastolic functions), and myocardial strain patterns. Additionally, a physical examination will include an assessment of chest shape and posture to evaluate their potential impact on echocardiographic findings. The effects of bipolar medication on ECG and Echo findings will also be assessed.

2.4. Echocardiographic and electrocardiographic assessment

Conventional 2-dimensional tissue speckle tracking echocardiography will be used to evaluate cardiac structure and function. Parameters such as left ventricular internal diameters, ejection fraction, and GLS will be evaluated. An ECG will be performed to identify any cardiac rhythm abnormalities and changes in cardiac rhythm due to bipolar medications.

2.5. Statistical analysis

Statistical comparisons between groups (manic, depressive, euthymic, and control) will be performed using appropriate statistical tests (e.g., ANOVA and chi-square tests) depending on the data distribution. The aim is to determine whether there are significant differences in ECG and echocardiographic findings between these groups. The relationship between phases of bipolar disorder and myocardial strain will be particularly examined.

2.6. Ethical considerations

The study protocol will be reviewed and approved by the Institutional Review Board of Van Yüzüncü Yl University. Informed consent will be obtained from all participants.

3. Results

This cross-sectional study, conducted at the Dursun Odabaş Medical Centre, the Psychiatry Clinic of Van Yüzüncü Yl University, aimed to evaluate electrocardiographic (ECG) and echocardiographic (Echo) findings in patients diagnosed with bipolar disorder during various phases of their illness compared to healthy controls.

The primary result of this study highlighted significant variations in echocardiographic parameters between the different groups. Most notably, GLS was found to be highest in the manic phase (21.51) and lowest in the healthy control group (19.0), indicating potential alterations in myocardial strain in bipolar disorder (Table 3).

Further analysis revealed differences in the E/A ratio of the mitral valve between groups, with the manic phase showing the highest ratio (1.21), suggesting altered diastolic function in this phase compared to others (Table 1).

Table 1 - Comparative view of echocardiographic parameters in different phases of bipolar disorder and healthy control. Measurement Depression Manic Euthymic Healthy control Global longitudinal strain 20.25 21.51 20.75 19.0 Mitral valve E/A ratio 1.16 1.21 1.20 1.1

Comprehensive echocardiographic evaluations revealed significant differences in various parameters, including left ventricular (LA) size, interventricular septum thickness (IVS), and ejection fraction, among others. These differences were particularly evident when comparing the depressive, manic, and euthymic phases of bipolar disorder with healthy controls, indicating specific cardiac structural and functional changes associated with each phase of the disorder (Table 2).

Table 2 - Comparative echocardiographic parameters across different phases of bipolar disorder and healthy control. Measurement Depression Manic Euthymic Healthy control Global longitudinal strain 20.25 21.51 20.75 19.0 Mitral valve E/A ratio 1.16 1.21 1.20 1.1 Left atrium (LA) 3.165 3.115 3.245 3.0 Interventricular septum thickness (IVS) 0.905 0.8925 0.9175 0.9 Posterior wall thickness (PW) 0.950 0.9375 0.930 0.9 Left ventricular end-diastolic diameter (LVDD) 4.715 4.5825 4.860 4.5 Left ventricular end-systolic diameter (LVSD) 2.9125 2.795 2.9425 2.8 Ejection fraction (EF) 58.675 59.350 57.750 60.0 Pulmonary artery pressure 12.40 13.90 12.35 12.0 Tricuspid annular plane systolic excursion 2.055 2.185 2.095 2.1 Early atrial velocity 0.6125 0.590 0.650 0.6 Mitral E velocity 0.7925 0.790 0.800 0.8 Mitral A velocity (MİT.A) 0.7075 0.6975 0.7075 0.7 E/A Ratio 1.120 1.133 1.131 1.1 Isovolumetric relaxation time 81.925 77.900 79.175 80.0 Deceleration time 147.000 148.575 144.300 150.0 Mitral lateral E′ 12.475 13.450 12.1025 12.5 Mitral lateral A′ 11.425 11.125 11.080 11.0 Mitral septal E′ 10.575 11.000 10.7525 10.5 Mitral septal A′ 10.175 9.775 10.175 10.0 Tricuspid lateral E′ 11.475 11.825 11.475 11.5 Tricuspid lateral A′ 14.050 14.875 13.275 14.0 Tricuspid lateral S′ 17.450 16.450 18.305 17.5

Demographic and clinical characteristics of the participants were also analyzed. The study groups, consisting of individuals in the manic, euthymic, and depressive phases of bipolar disorder, as well as healthy controls, showed varied age ranges, gender distributions, and clinical histories. This demographic variability provided a comprehensive background to understand the impact of bipolar disorder on cardiac function (Table 3).

Table 3 - Comparative analysis of demographic and clinical characteristics across different groups. Group Age range (yr) Gender distribution (M/F) Income level Disease duration (y) Hospitalization frequency ECT history Attack number Common medications Manic 18 to 56 25/25 Mixed 1 to 30 0 to 7 Yes/no 1 to 4+ Valproate, Lithium, Ketiapin Euthymic 18 to 65 25/25 Mixed 1 to 24 0 to 4+ Yes/no 0 to 4+ Olanzapine, Fluoxetine, Ketiapin Depressive 17 to 64 25/25 Mixed 1 to 25 0 to 4+ Yes/no 0 to 4+ Olanzapine, Valproate, Risperidone Healthy control 18 to 65 25/25 Mixed N/A N/A N/A N/A N/A

In conclusion, the study findings underscore the importance of cardiac monitoring in patients with bipolar disorder, as evident from the significant differences in ECG and Echo findings across different phases of the disorder compared to healthy controls. The relationship between phases of bipolar disorder and myocardial strain, in particular, warrants further investigation to understand the underlying mechanisms and potential clinical implications.

4. Discussion

This study embarked on a comprehensive analysis of echocardiographic strain, specifically myocardial tissue strain, in patients diagnosed with bipolar disorder in its various phases—depressive, manic, and euthymic compared to healthy controls. The main factor reveals a discernible variance in GLS values across different phases of bipolar disorder, suggesting a possible relationship between bipolar disorder and myocardial strain.[8]

In particular, the manic phase of bipolar disorder exhibited the highest GLS values, in contrast to the conventional understanding of myocardial function in psychiatric conditions.[9] This deviation from expected norms raises questions about the underlying cardiac adaptations or stressors in bipolar disorder during its different phases. Such findings highlight the need for cardiac monitoring in bipolar patients, as these variations may have significant clinical implications.[8]

An important consideration in interpreting these results is the potential influence of extrinsic factors, such as chest shape conformation, on GLS values in different stages of bipolar syndrome. It is plausible that the observed reduced GLS value in the depressive state could be related to extrinsic cardiac compression exerted by a concave-shaped chest wall or posture. Conversely, in the manic phase, the chest might be more expanded, with no evidence of cardiac compression, leading to higher GLS magnitude. This perspective is supported by findings in the literature that explore the influence of chest conformation on cardiac function.[10]

Compared to others, the literature on cardiac function in bipolar disorder is sparse. Previous studies have focused primarily on general cardiac health or the impact of psychiatric medications on cardiac function. However, our study delves deeper, scrutinizing myocardial strain, a parameter not been extensively explored in this population.[11] The elevated GLS values in manic phases align with some reports suggesting increased cardiac stress during acute psychiatric episodes but contradict others that find no significant cardiac change during different bipolar phases.[12]

The observed echocardiographic variations, particularly elevated GLS during manic episodes, could be attributable to multiple factors. These include physiological stress, altered autonomic nervous system functioning, or even the impact of medications used during these phases.[13] In light of this, future research should consider the potential impact of physical factors, such as chest shape, on these echocardiographic findings. The bipolar disorder itself, characterized by mood swings and emotional stress, could impose a physiological burden on the heart, manifesting itself in altered myocardial strain patterns.[14]

An additional aspect to consider is the possible influence of extrinsic determinants on GLS magnitude in bipolar disorder, particularly how chest shape conformation may affect echocardiographic outcomes. The reduced GLS value observed in the depressive state could be, in part, a result of extrinsic cardiac compression from a concave-shaped chest wall or posture. This extrinsic factor might lead to a misleading interpretation of intrinsic myocardial dysfunction. Conversely, during the manic phase, an expanded chest conformation, possibly due to different postures or physiological states, might contribute to the higher GLS magnitude observed. These considerations underscore the importance of accounting for physical factors that could influence cardiac imaging results.[15]

Although the study offers novel insights, it is not without limitations. The cross-sectional design restricts our ability to establish causality. Furthermore, reliance on echocardiographic parameters alone, without integrating biomarkers or more detailed cardiac imaging, could limit the comprehensiveness of our findings. The study sample size, although adequate, could be expanded in future research for more robust data.[8]

The generalizability of these findings to other populations or contexts remains cautious. The specific demographic and clinical characteristics of the study participants, drawn from a single medical center, might not represent the broader bipolar population. Furthermore, variations in treatment protocols in different regions might influence cardiac outcomes, which requires a cautious approach to extrapolating these results.[16]

Our study underscores the importance of cardiac monitoring in bipolar disorder, suggesting that evaluation of myocardial strain could become an integral part of the treatment of this condition. For future research, longitudinal studies are needed to observe these cardiac parameters over time and in bipolar phases. Clinically, these findings advocate for a more integrated approach to the treatment of bipolar disorder, which combines psychiatric and cardiac care. Policymakers may consider guidelines for regular cardiac evaluations in patients with bipolar disorder, especially during the manic phases.[17]

The implications of these findings are multiple. Clinically, they underscore the need for a more holistic approach to managing bipolar disorder, where cardiac monitoring, particularly echocardiographic evaluation of myocardial strain, becomes an integral part of the treatment and management strategy. This approach is crucial, especially considering the possible cardiac risks associated with bipolar disorder and its treatment.[18]

In terms of research, these findings open up new avenues to explore the pathophysiological mechanisms underlying the relationship between bipolar disorder and cardiac function. Future studies, particularly longitudinal ones, are essential to unravel the causal factors, the impact of medication, and the long-term cardiac implications of bipolar disorder. Such research could pave the way for more effective, customized interventions that address the psychiatric and cardiac aspects of this complex disorder.[19]

In conclusion, our study provides valuable information on the relationship between bipolar disorder and myocardial tissue deformation as evaluated by echocardiography. The key finding of this research is the evident variation in GLS values in different phases of bipolar disorder, with distinct differences observed compared to a healthy control group. This finding is pivotal as it not only reinforces the notion of tangible cardiac involvement in bipolar disorder, but also highlights the variability of this involvement in different phases of the illness.

The study results suggest that each phase of bipolar disorder, depressive, manic, and euthymic has its unique cardiac profile in relation to myocardial strain. This indicates that bipolar disorder, in its various manifestations, can exert differing levels of stress or impact cardiac function. It should be noted in particular the increased GLS observed during the manic phase, suggesting increased myocardial stress or altered cardiac function during this period.

Furthermore, our findings suggest a need for increased vigilance and potentially different management strategies during different phases of bipolar disorder. Variations in myocardial strain across different phases may require phase-specific monitoring and management protocols to mitigate potential cardiac risks.

In summary, our study contributes significantly to the growing body of evidence on the cardiac implications of bipolar disorder. It highlights the importance of comprehensive care that includes both mental and cardiac health, advocating for an integrated approach to managing patients with bipolar disorder. As we continue to explore this relationship, it is imperative that both clinicians and researchers remain aware of the intricate interplay between mental health and cardiac function, working collaboratively to improve outcomes for people with bipolar disorder.

Author contributions

Conceptualization: Ramazan Duz.

Data curation: Ramazan Duz.

Formal analysis: Ramazan Duz.

Funding acquisition: Ramazan Duz.

Investigation: Ramazan Duz.

Methodology: Ramazan Duz.

Project administration: Ramazan Duz.

Resources: Ramazan Duz.

Software: Ramazan Duz.

Supervision: Ramazan Duz.

Validation: Ramazan Duz.

Visualization: Ramazan Duz.

Writing—original draft: Ramazan Duz.

Writing—review & editing: Ramazan Duz.

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