European Journal of Cardiovascular Medicine

Non-communicable diseases (NCDs) remain a global health burden, causing 68% of deaths worldwide, including 60% in India [1]. Among these, thyroid dysfunction (TD) is a significant endocrine disorder, affecting over 200 million people globally [2]. Hypothyroidism—marked by reduced thyroid hormone production—is highly prevalent and often underdiagnosed, despite its preventable nature when detected early [3]. Studies reveal a greater susceptibility among Indians [4,5], with a national prevalence of 10.95%, notably higher than that in the US (4.6%) and UK (2%) [7]. Factors like longstanding iodine deficiency and regional variations contribute to this trend [7,8], with older adults (46–54 years) being particularly affected [9]. Hypothyroidism’s impact extends to cardiovascular health, particularly left ventricular dysfunction (LVD). It leads to impaired cardiac contractility, increased vascular resistance, and diastolic dysfunction. Disturbances in lipid metabolism, endothelial function, and elevated atherosclerotic risk further compound cardiovascular compromise in these patients. Despite these risks, existing ACC/AHA guidelines for heart failure recognize thyroid dysfunction as an aggravating factor but lack detailed recommendations regarding TSH level variations and heart failure outcomes [10]. Hypothyroidism, primarily of thyroidal origin (>99.5%), may present as overt (high TSH, low T4) or subclinical (high TSH, normal T4) [11]. Given thyroid hormones' regulatory role across multiple organ systems, deficiency can produce wide-ranging symptoms depending on the patient’s age and disease duration [12]. Both overt and subclinical hypothyroidism have been linked to cardiovascular abnormalities—particularly diastolic dysfunction—with potential effects on systolic function remaining debatable [13].

This study aimed to evaluate left ventricular systolic and diastolic function in hypothyroid individuals to highlight the necessity of early detection and management. Timely intervention may prevent or limit irreversible cardiac changes, improve metabolic control, and reduce cardiovascular morbidity and mortality [14].

A cross-sectional observational study was conducted in the Department of Medicine, Mahatma Gandhi Medical College and Hospital, Jaipur, from April 2023 to September 2024, to assess left ventricular (LV) dysfunction in patients with hypothyroidism. Institutional Ethics Committee approval and informed consent were obtained prior to study initiation.

A total of 149 patients (18–65 years) with clinically and biochemically confirmed primary hypothyroidism were enrolled. Diagnosis was based on abnormal serum TSH, total T3, and total T4 levels. Exclusion criteria included secondary hypothyroidism, use of drugs affecting thyroid or cardiac function, systemic illnesses (e.g., diabetes, anemia, collagen vascular disease, known cardiac disease), other endocrine disorders, pregnancy, lactation, mental disability, critical illness, or refusal to consent.

All participants underwent detailed clinical evaluation and laboratory testing, including thyroid profile (TSH, T3, T4), complete blood count, ESR, CRP, liver and renal function tests, and serum electrolytes. Cardiac assessment included ECG and 2D echocardiography for LV systolic and diastolic function evaluation using ejection fraction (EF), E/A ratio, deceleration time, and isovolumic relaxation time. Systolic dysfunction was defined as EF <50%, and diastolic dysfunction was graded per standard guidelines. Additional investigations such as chest X-ray and arterial blood gas analysis were performed when required.

Data were analyzed using appropriate statistical software. Continuous variables were expressed as mean ± SD and compared using t-test or ANOVA, while categorical variables were analyzed using Chi-square or Fisher’s exact test. Correlation between hypothyroidism severity/duration and LV dysfunction was evaluated. A p-value <0.05 was considered significant.

A total of 149 patients were included, with 74 in the case group (hypothyroid patients) and 75 in the control group (euthyroid individuals). The mean age was 40.88 ± 13.57 years in cases and 41.84 ± 13.51 years in controls, with no statistically significant difference (P=0.32). Females predominated in both groups (case: 79.73%; control: 80.00%; P=0.11). The mean BMI was 23.34 ± 3.09 kg/m² in cases and 24.91 ± 2.99 kg/m² in controls (P=0.18).

Table: I Comparison of Demographic Characteristics, Diastolic Dysfunction Grades, and Vital Parameters Between Control and Case Groups

Clinical Profile

Symptoms were more prevalent in hypothyroid cases than controls: general weakness (20.27% vs. 5.33%), hoarseness (13.51% vs. 4.00%), muscle/joint pain (21.62% vs. 2.67%), constipation (16.22% vs. 1.33%), slow activity (14.86% vs. 1.33%), swelling of limbs (8.11% vs. 2.67%), cold intolerance (9.46% vs. 2.67%), and weight gain (10.81% vs. 4.00%). Cardiovascular symptoms such as chest pain (5.41% vs. 1.33%), breathlessness (13.51% vs. 2.67%), effort intolerance (13.51% vs. 1.33%), and palpitations (20.27% vs. 6.67%) were also significantly higher in the case group.

Grading distribution revealed that all controls (100%) were Grade 0. Among cases, 78.38% were Grade 0, 13.51% Grade 1, 6.76% Grade 2, and 1.35% Grade 3. The mean duration of illness increased with disease grade: Grade 0 (2.97 ± 0.74 years), Grade 1 (3.1 ± 0.94 years), Grade 2 (4.2 ± 0.75 years), and Grade 3 (6.0 ± 0.00 years). The overall mean illness duration was 3.11 ± 0.89 years.

Thyroid Function and Vital Parameters

The mean TSH level was significantly higher in cases (8.95 ± 3.05 mIU/L) versus controls (2.9 ± 1.18 mIU/L) (P=0.01). No significant differences were noted in T3 (cases: 1.46 ± 0.32 ng/mL; controls: 1.97 ± 0.61 ng/mL; P=0.22) or T4 levels (cases: 10.3 ± 2.34 μg/dL; controls: 8.91 ± 2.04 μg/dL; P=0.7). Vital signs, including heart rate (cases: 79.82 ± 5.38 bpm; controls: 82.65 ± 5.42 bpm; P=0.21), systolic BP (cases: 120.72 ± 6.34 mmHg; controls: 118.23 ± 8.58 mmHg; P=0.44), and diastolic BP (cases: 76.95 ± 5.35 mmHg; controls: 79.33 ± 4.63 mmHg; P=0.09), showed no significant differences.

Table: II Comparison of Thyroid Profile Between Control and Case Groups

Table: III Comparison of Left Ventricular (LV) Dimensions and Mass Between Control and Case Groups

Left Ventricular Systolic Function

Conventional systolic function parameters, including ejection fraction (EF), stroke volume, shortening fraction, and MAPSE, showed no significant differences. However, tissue Doppler imaging revealed significantly reduced systolic velocities in cases: lateral s′ (6.47 ± 1.09 cm/s) vs. controls (8.32 ± 1.72 cm/s) (P=0.01), and septal s′ (5.98 ± 0.99 cm/s) vs. controls (8.17 ± 1.52 cm/s) (P=0.01), indicating impaired longitudinal systolic function.

Table: IV Comparison of Left Ventricular (LV) Systolic Function Between Control and Case Groups

Left Ventricular Diastolic Function

Cases exhibited significantly altered diastolic parameters compared to controls: lower E wave velocity (65.95 ± 7.17 cm/s vs. 76.2 ± 8.75 cm/s; P=0.01), higher A wave velocity (70.2 ± 8.44 cm/s vs. 60.85 ± 7.92 cm/s; P=0.01), and reduced E/A ratio (0.96 ± 0.16 vs. 1.27 ± 0.21; P=0.04). E wave deceleration time was prolonged in cases (179.45 ± 22.56 ms) compared to controls (156.39 ± 25.64 ms; P=0.01). The E/e′ ratio was significantly lower in cases (7.73 ± 1.21) versus controls (9.44 ± 1.98; P=0.01). Other diastolic indices, including tissue Doppler e′ and a′ velocities, and LAVI, showed no significant intergroup differences.

Table: V Comparison of Left Ventricular (LV) Diastolic Function Parameters Between Control and Case Groups

Left Ventricular Dysynchrony

There were no significant differences in LV dysynchrony parameters such as IVRT (cases: 94.02 ± 12.73 ms; controls: 92.6 ± 13.13 ms; P>0.05), FT, ET, T-IVT, and Tei index between the groups.

Table:6 Comparison of Left Ventricular (LV) Desynchrony Parameters Between Control and Case Groups

The present hospital-based observational study on left ventricular (LV) dysfunctions in hypothyroid patients provided valuable insights into the subtle yet progressive cardiac alterations associated with thyroid hormone deficiency. Hypothyroidism is a common endocrine disorder that exerts significant effects on the cardiovascular system, often leading to subclinical myocardial dysfunction before manifesting as overt heart disease. The evaluation of both systolic and diastolic LV functions in these patients facilitated early detection of cardiac involvement, emphasizing the importance of prompt therapeutic intervention to prevent further deterioration.

In this study, the mean age of the control group was 41.84 ± 13.51 years, while that of the case group was 40.88 ± 13.57 years (P = 0.32), indicating a comparable age distribution. Gender distribution was also similar in both groups, with a higher proportion of females, consistent with the known female predominance in thyroid disorders [15]. The mean BMI was slightly higher in the control group compared to the case group, but this difference was not statistically significant (P = 0.18) [16].

Hypothyroid patients exhibited a higher prevalence of clinical symptoms such as general weakness, constipation, hoarseness of voice, cold intolerance, and weight gain, consistent with classical manifestations of reduced metabolic activity [17]. Cardiovascular symptoms, including chest pain, breathlessness, effort intolerance, and palpitations, were also significantly more common among hypothyroid individuals [18].

Echocardiographic assessment revealed that while all control participants had normal LV function (Grade 0), a spectrum of diastolic dysfunction was observed among hypothyroid cases, with 21.62% demonstrating Grades 1 to 3 dysfunction [19]. Early myocardial involvement in hypothyroidism has been previously documented, even in the absence of overt clinical symptoms [15].

A progressive increase in disease duration corresponded with worsening grades of LV dysfunction, from 2.97 years in Grade 0 to 6.0 years in Grade 3 patients. Chronic thyroid hormone deficiency has been implicated in cumulative myocardial alterations contributing to this trend [20].

TSH levels were markedly elevated in the case group, with 36.49% exhibiting values >10 mIU/L. Although many of these patients remained in Grade 0, higher dysfunction grades were exclusive to the case group and more prevalent in those with elevated TSH, suggesting a correlation between TSH levels and myocardial involvement [15,18].

Vital signs, including heart rate, systolic blood pressure, and diastolic blood pressure, did not significantly differ between groups, reflecting preserved hemodynamic stability in hypothyroid patients despite early myocardial changes [17].

A significant elevation in serum TSH levels was observed among hypothyroid patients compared to controls (8.95 ± 3.05 mIU/L vs. 2.9 ± 1.18 mIU/L, P = 0.01), while serum T3 and T4 levels did not differ significantly. This finding aligns with the understanding that TSH elevation precedes overt changes in circulating thyroid hormones in early thyroid dysfunction [15,21].

LV mass index was significantly increased in the case group (41.38 ± 11.13 g/m².⁷) compared to controls (38.35 ± 2.06 g/m².⁷; P = 0.04), indicating early myocardial remodelling. Despite this, absolute LV mass was lower in the case group but did not reach statistical significance (P = 0.09). Other structural parameters remained comparable between groups, suggesting early-stage myocardial involvement without established hypertrophy [15,22,23].

Conventional echocardiographic measures of systolic function, such as ejection fraction, stroke volume, and MAPSE, showed no significant differences. However, tissue Doppler imaging (TDI) revealed significantly reduced lateral s′ and septal s′ velocities in hypothyroid patients, reflecting subclinical impairment in longitudinal systolic function—an early marker of myocardial dysfunction [24-28].

Assessment of diastolic function demonstrated significant alterations in hypothyroid patients, including reduced E wave velocity (65.95 ± 7.17 cm/s vs. 76.2 ± 8.75 cm/s; P = 0.01), increased A wave velocity (70.2 ± 8.44 cm/s vs. 60.85 ± 7.92 cm/s; P = 0.01), and a lower E/A ratio (0.96 ± 0.16 vs. 1.27 ± 0.21; P = 0.04), indicating early diastolic dysfunction. Prolonged deceleration time (179.45 ± 22.56 ms vs. 156.39 ± 25.64 ms; P = 0.01) and altered E/e′ ratios were also observed, consistent with impaired myocardial relaxation [23,29].

Other parameters such as IVRT, LAVI, and T-IVT did not differ significantly, indicating the absence of advanced structural remodeling. These findings highlight the utility of TDI in detecting subclinical myocardial changes in hypothyroid patients, supporting its role in early cardiovascular risk assessment [].

In conclusion, this study underscores the importance of routine cardiac evaluation in hypothyroid patients, particularly using sensitive imaging modalities like TDI, to detect early myocardial involvement. The results emphasize the potential benefit of early intervention to mitigate the progression of cardiac dysfunction in this population.

This study demonstrates that hypothyroidism, even in its early stages, adversely affects left ventricular function, primarily causing diastolic dysfunction marked by impaired relaxation and delayed filling. While global systolic function appeared preserved, tissue Doppler imaging detected subtle systolic impairment through reduced s′ velocities. A positive correlation was observed between higher TSH levels, longer disease duration, and worsening cardiac function, including increased left ventricular mass index. Hypothyroid patients also exhibited more frequent cardiovascular symptoms such as fatigue, chest discomfort, and palpitations. These findings highlight the need for routine cardiac evaluation in hypothyroid patients to enable early detection and intervention, potentially preventing progression to overt cardiac disease.

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