Obesity, which is defined as a body mass index (BMI) value of 30 kg/m2 or more, is a growing public health problem all around the world.[1] It is now becoming a global epidemic.[2] Due to a close relationship between obesity and several clinical conditions, including hypertension (HT),[3] diabetes mellitus (DM),[4] and atherosclerosis,[5] it is now accepted as one of the most common causes of mortality and morbidity. Over the past decades, our understanding of the pathophysiological outcomes of obesity for the cardiovascular system have advanced significantly.[6] Recent studies have shown that there is a strong association between obesity and hemodynamic changes that contribute to the impairment of ventricular function.[7] Obesity may lead to deterioration in cardiac functions, such as an increase in left ventricular (LV) mass, LV hypertrophy, and LV and left atrial (LA) dilatation.[8] In addition, it has been established that obesity is a risk factor for left-sided heart failure in both men and women.[9] Most studies analyzing the effect of obesity on heart functions have focused on the left side of the heart. Although there has been some research investigating the relationship between obesity and right heart functions, the underlying mechanism is still not understood. This study was an analysis of the effect of obesity on right heart functions and a comparison of the sensitivity and specificity of different echocardiographic modalities in the detection of right ventricular (RV) dysfunction. METHODS Study population and design In this observational cross-sectional study, subjects were selected from consecutive patients who were admitted to the hospital obesity outpatient clinic between March 7, 2019 and July 31, 2019. All of the patient medical data and medications were reviewed. Patients were excluded if there was a record of HT; DM; coronary artery disease (CAD); LV systolic dysfunction (LV ejection fraction 40 mmHg was considered pulmonary arterial HT). A total of 116 patients were included after applying the exclusion criteria. The patients enrolled in the study were divided into 4 groups according to a BMI calculation. Participants with a 19.990.55 was considered abnormal.[11] Measurements of 3 cardiac cycles were averaged for all of the right heart function parameters. Statistical analysis Statistical analyses were conducted with a commercially available software package (SPSS for Windows, Version 16.0; SPSS, Inc., Chicago, IL, USA). Parametric test data are expressed as mean±SD for continuous variables and as counts and percentages for categorical variables. Continuous variables of nonparametric test data are expressed as median (first quartile-third quartile). Differences were considered statistically significant at p0.55 and an R-IVA 0.55 or an R-IVA <3.5 cm/s2 . The area under the curve (AUC) for the BMI was 0.977 (95% CI: 0.947–1.007). A cut-off value of 30.45 kg/m2 for BMI was associated with 93.3% sensitivity and 94.3% specificity in the prediction of RV systolic dysfunction defined by the MPI. Moreover, the AUC for the BMI was 0.784 (95% CI: 0.676–0.892). A cut-off value of 30.50 kg/ m2 for the BMI was associated with 76.7% sensitivity and 72.3% specificity in the prediction of RV systolic dysfunction defined by R-IVA. Figure 1. Graphs illustrating (A) the significant difference in R-IVV between the OBG, the MOG, and the NWG, (B) the significant difference in the IVCT between the OWG, the OBG, the MOG, and the NWG, (C) the significant difference in the IVRT between the MOG and the NWG, and (D) the significant difference in the ET between the OBG, the MOG, and the NWG. ET: Ejection time; IVCT: Isovolumic contraction time, IVRT: Isovolumic relaxation time; R-IVV: Right ventricular myocardial velocity during isovolumic contraction; MOG: Morbidly obese group; NS: Nonsignificant; NWG: Normal weight group; OBG: Obese group; OWG: Overweight group. 18 16 14 12 10 8 6 4 2 0 NWG NS OWG p=0.0001 p=0.0001 OBG MOG R-IVV (cm/s) A B 70 60 50 40 30 20 10 0 NWG OWG NS NS p=0.014 p=0.020 p=0.001 OBG MOG IVCT (ms) 80 70 60 50 40 30 20 10 0 NWG OWG p=0.002 OBG MOG NS NS IVRT (ms) 300 250 200 150 100 50 0 NWG NS OWG p=0.014 p=0.0001 OBG MOG ET (ms) C D Table 3. Multivariate binary logistic regression analysis for right ventricular dysfunction defined by R-IVA Variables B value SE OR 95% CI p Right atrium diameter 0.001 0.097 1.001 0.827–1.211 0.994 Right ventricle diameter -0.086 0.116 0.917 0.731–1.151 0.456 Systolic pulmonary arterial pressure 0.114 0.050 1.121 1.016–1.236 0.241 Body mass index 0.191 0.061 1.211 1.074–1.366 0.002 CI: Confidence interval; OR: Odds ratio; SE: Standard error. Obesity and right heart 599 DISCUSSION In the present study, we investigated the effect of obesity on right heart functions. Our results revealed that the diameter of the right heart chamber and right heart functional deterioration were significantly increased with obesity. The BMI value was found to be an independent risk factor for RV dysfunction. In addition, the MPI was found to be more sensitive and specific than the R-IVA in detecting RV systolic dysfunction. Figure 2. Graphs showing the correlation between (A) the RA diameter and the BMI, (B) the RV diameter and the BMI, (C) the MPI and the BMI, and (D) the R-IVA and the BMI. BMI: Body mass index; MPI: Myocardial performance index; RA: Right atrium; R-IVA: Right ventricular isovolumic acceleration; RV: Right ventricle. A C B D 45.0 1.00 40.0 7.00 40.0 0.80 35.0 6.00 35.0 30.0 5.00 30.0 0.60 25.0 4.00 25.0 0.40 20.0 3.00 20.0 0.20 15.0 1.00 2.00 20.0 20.0 20.0 20.0 30.0 30.0 30.0 30.0 BMI BMI BMI BMI RA diameter MPI RV diameter R-IVA 40.0 40.0 40.0 40.0 50.0 50.0 50.0 50.0 60.0 60.0 60.0 60.0 Table 4. Multivariate binary logistic regression analysis for right ventricular dysfunction defined by MPI Variables B value SE OR 95% CI p Right atrium diameter 0.227 0.352 1.255 0.629–2.504 0.520 Right ventricle diameter -0.334 0.381 0.716 0.339–1.513 0.382 Systolic pulmonary arterial pressure 0.253 0.170 1.288 0.922–1.799 0.137 Body mass index 0.662 0.196 1.939 1.320–2.850 <0.001 CI: Confidence interval; OR: Odds ratio; SE: Standard error. 600 Turk Kardiyol Dern Ars The World Health Organization defines obesity as abnormal or excessive fat accumulation that represents a risk to health. The increasing prevalence of obesity is alarming because it is a risk factor for several chronical diseases, including HT, DM, CAD, dyslipidemia, insulin resistance, metabolic syndrome, and cancer.[12–15] Numerous metabolic steps are involved in the uptake, transport, and storage of lipids and there are a number of different factors that contribute to dyslipidemia seen in patients with obesity. These factors include greater delivery of free fatty acids to the liver from increased total and visceral adiposity, insulin resistance, and a pro-inflammatory state induced by macrophages infiltrating fat tissue.[16] Gruzdeva et al.[17] observed that in obese patients, increased free fatty acids, pro-inflammatory cytokines (interleukin 1, interleukin 6, tumor necrosis factor alpha) and leptin caused irreversible changes (i.e., dyslipidemia, insulin resistance) in the body. Clinically, dyslipidemia caused by obesity typically consists of increased TG, decreased HDL, and normal or slightly increased LDL.[18] It has been established that the greater the increase in the BMI, the greater the abnormalities in lipid levels.[19] In our study, we also found that the TG level was significantly higher in the OWG, the OBG, and the MOG, and that the HDL level was significantly lower in the MOG compared with the NWG. However, we found a significant correlation only between the TG level and the BMI. The correlation between HDL and the BMI was statistically nonsignificant, which might be due to the small size of the patient group. As a result of hemodynamic, metabolic, and neurohormonal alterations, obesity may cause LV and RV morphological changes. Barbossa et al.[20] postulated that expanded intravascular volume and elevated vascular resistance present in obesity could cause ventricular hypertrophic remodeling and diastolic dysfunction. Controversially, Alpert et al.[21] reported that impaired systolic function in patients with obesity occurs only in the presence of coexisting heart disease or other risk factors, and that the duration of obesity may be a contributing influence. Most of the previous studies regarding heart function and obesity have been dedicated to the left heart. Hence, scientific data and knowledge of the right heart chambers regarding subjects such as function, morphology, adaptation to loading are still behind what we know for the left heart. Labombarda et al.[22] demonstrated that RV dimensions were enlarged in obese children compared with healthy controls. In another study, Jing et Figure 3. Receiver operating characteristic curve analysis of the performance of the BMI for diagnosing right ventricular dysfunction defined by (A) the MPI and (B) the R-IVA. BMI: Body mass index; MPI: Myocardial performance index; R-IVA: Right ventricular isovolumic acceleration. A B Sensitivity 0.8 0.6 0.4 0.2 0.0 0.0 0.2 0.4 0.6 0.8 1.0 1.0 1 - Specificity MPI Sensitivity 0.8 0.6 0.4 0.2 0.0 0.0 0.2 0.4 0.6 0.8 1.0 1.0 1 - Specificity R-IVA Obesity and right heart 601 al.[23] found that obese/overweight children revealed evidence of RV remodeling. Mahfouz et al.,[24] however, observed no changes in RV dimensions. In addition, Shaimaa et al.[25] showed that weight reduction surgery significantly improved right heart function. In our study, we also observed that the RA and RV diameters were significantly increased with obesity. We also demonstrated that the RA and RV diameters were positively correlated with the BMI. Although various studies have been conducted to investigate the relationship between RV contractile function and different clinical conditions, the relationship between obesity and RV function, especially in the healthy adult population, has not been sufficiently examined. Kowalik et al.[26] showed that overweight status/obesity in adult patients with corrected congenital heart diseases was associated with RV systolic dysfunction. Alhamshari et al.[27] noted that obese patients had better RV systolic function at the time of acute myocardial infarction compared with the nonobese, and that after 2 years of follow-up, the obese patients were less likely to have developed new-onset right heart failure. Furthermore, Serrano-Ferrer et al.[28] reported that RV systolic dysfunction in metabolic syndrome patients, which could be related to obesity-induced changes, was probably not permanent and was modifiable with a healthy diet and physical activity. In our study, we analyzed the RV systolic function of otherwise healthy patients. We found that the R-IVA was significantly lower and the MPI was significantly higher in the OWG, the OBG, and the MOG compared with the NWG. Moreover, the R-IVA and the MPI were significantly correlated with the BMI. We also analyzed the individual effects of all of the parameters used in the calculation of the R-IVA and the MPI. The results showed that a decrease in the R-IVA with obesity was a result of the decrease in the R-IVV. The AcT was not significantly affected by the BMI value. When the MPI was examined, all of the parameters used to calculate the MPI were significantly changed. There is significantly less myocardial tissue in the RV compared with the LV. Hence, the compensation capability of the RV is more limited. In our opinion, this makes the RV more susceptible to any condition affecting the RV, even at the cellular level. This is why RV systolic functional deterioration seems to affect the peak tissue velocity at the very beginning. This subclinical functional deterioration of the RV also decreases the ET and increases the time needed to counterbalance trans-chamber gradients during isovolumic contraction and relaxation periods. This makes it possible to detect RV functional deterioration even at the subclinical stage using the appropriate echocardiographic techniques. Due to relative volume independence, the IVA is considered a reliable index of global contractility to analyze the systolic function of both ventricles.[29] Furthermore, a number of studies have documented that the MPI is independent of heart rate, arterial pressure, and preload, which also makes it a reliable contractility index.[30] In our study, we also analyzed the predictive accuracy of the BMI in RV systolic dysfunction. At nearly the same BMI levels, the predictive value of the MPI was higher than the R-IVA. The accuracy of the MPI to predict RV systolic dysfunction was greater than that of the R-IVA. Limitations The major limitation of our study was the relatively small sample size. The study may also have been affected by the cross-sectional, single-center design. Although 3-dimensional echocardiographic examination and strain study is more sensitive and specific for right heart functional evaluation, they could not be performed for this study due to technical difficulties. Conclusion In this study, we concluded that obesity significantly affected right heart functions and that there was a significant correlation between the degree of obesity and right heart functional deterioration. Additionally, the BMI value was an independent risk factor for RV systolic dysfunction and could be used alone to predict RV systolic dysfunction. Furthermore, the MPI was found to be more sensitive and specific than the RIVA in detecting RV dysfunction. Financial disclosure: This research received no specific grant from any funding agency, commercial or not-forprofit sectors. Ethical standards: Approval was granted by the local ethics committee (TUEK 03.03.2019/01-06). Peer-review: Externally peer-reviewed. Conflict-of-interest: None. Authorship contributions: Concept: M.Z.; Design: M.Z., M.S.A.; Supervision: M.Z.; Materials: M.Z., M.S.A.; Data: M.Z., M.S.A.; Analysis: M.Z.; Literature search: M.Z., 602 Turk Kardiyol Dern Ars M.S.A.; Writing: M.Z.; Critical revision: M.Z. REFERENCES 1. Cornier MA, Després JP, Davis N, Grossniklaus DA, Klein S, Lamarche B, et al. Assessing adiposity. A scientific statement from the American Heart Association. Circulation 2011;124:1996–2019. [CrossRef] 2. Engeland A, Bjørge T, Søgaard AJ, Tverdal A. Body mass index in adolescence in relation to total mortality: 32-year follow up of 227,000 Norwegian boys and girls. Am J Epidemiol 2003;157:517–23. [CrossRef] 3. Higgins M, Kannel W, Garrison R, Pinsky J, Stokes J. Hazards of obesity--the Framingham experience. Acta Med Scand Suppl 1988;723:23–36. [CrossRef] 4. Ma RC, Chan JC. Type 2 diabetes in East Asians: similarities and differences with populations in Europe and the United States. Ann N Y Acad Sci 2013;1281:64–91. [CrossRef] 5. Ortega FB, Lavie CJ, Blair SN. Obesity and Cardiovascular Disease. Circ Res 2016;118:1752–70. [CrossRef] 6. Badimon L, Bugiardini R, Cenko E, Judit Cubedo, Maria Dorobantu, Dirk J. Duncker, et al. Position paper of the European Society of Cardiology-working group of coronary pathophysiology and microcirculation: obesity and heart disease. Eur Heart J 2017;38:1951–8. [CrossRef] 7. Alpert MA, Karthikeyan K, Abdullah O, Ghadban R. Obesity and Cardiac Remodeling in Adults: Mechanisms and Clinical Implications. Prog Cardiovasc Dis 2018;61:114–23. [CrossRef] 8. Kenchaiah S, Evans JC, Levy D, Peter WF Wilson, Emilia J Benjamin, Larson SD, et al. Obesity and the risk of heart failure. N Engl J Med 2002;347:305–13. [CrossRef] 9. Alpert MA, Lavie CJ, Agrawal H, Owan T. Obesity and heart failure: epidemiology, pathophysiology, clinical manifestations, and management. Transl Res 2014;164:345–56. [CrossRef] 10. Maryam S, Maryam E, Majid M, Hooman B, Fatemeh P, Nasim N. Normal Reference Values of Tissue Doppler Imaging Parameters for Right Ventricular Function in Young Adults: a Population-Based Study. Research in Cardiovascular Medicine 2013;2:160–6. [CrossRef] 11. Lawrence G. Rudski, Wyman W. Lai, Jonathan Afilalo, Lanqi Hua, Mark D. Handschumacher, Krishnaswamy Chandrasekaran, et al. Guidelines for the Echocardiographic Assessment of the Right Heart in Adults: A Report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. J Am Soc Echocardiogr 2010;23:685–713. [CrossRef] 12. Björntorp P. Metabolic implications of body fat distribution. Diabetes Care 1991;14:1132–43. [CrossRef] 13. Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJ. The global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet 2006;367:1747–57. [CrossRef] 14. Aune D, Sen A, Norat T. Body Mass Index, Abdominal Fatness, and Heart Failure Incidence and Mortality: A Systematic Review and Dose-Response Meta Analysis of Prospective Studies. Circulation 2016;133:639–49. [CrossRef] 15. Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 2008;371:569–78. [CrossRef] 16. Xiao C, Satya D, Morgantini C, Hegele RA, Gary F Lewis. Pharmacological Targeting of the Atherogenic Dyslipidemia Complex: The Next Frontier in CVD Prevention Beyond Lowering LDL Cholesterol. Diabetes 2016;65:1767–78. [CrossRef] 17. Gruzdeva O, Borodkina D, Uchasova E, Dyeleva Y, Olga B. Localization of fat depots and cardiovascular risk. Lipids Health Dis 2018;17:218. [CrossRef] 18. Klop B, Elte JW, Cabezas MC. Dyslipidemia in Obesity: Mechanisms and Potential Targets. Nutrients 2013;5:1218–40 19. Bays HE, Toth PP, Kris-Etherton PM, Abate N, Aronne LJ, Brown WV, et al. Obesity, adiposity, and dyslipidemia: A consensus statement from the National Lipid Association. J Clin Lipidol 2013;7:304–83. [CrossRef] 20. Barbosa MM, Beleigoli AM, de Fatima Diniz M, Freire CV, Ribeiro AL, Nunes MC. Strain imaging in morbid obesity: insights into subclinical ventricular dysfunction. Clin Cardiol 2011;34:288–93. [CrossRef] 21. Alpert MA, Omran J, Mehra A, Ardhanari S. Impact of obesity and weight loss on cardiac performance and morphology in adults. Prog Cardiovasc Dis 2014;56:391–400. [CrossRef] 22. Labombarda F, Zangl E, Dugue AE, Bougle D, Pellissier A, Ribault V, et al. Alterations of left ventricular myocardial strain in obese children. Eur Heart J Cardiovasc Imaging 2013;14:668–76. [CrossRef] 23. Jing L, Pulenthiran A, Nevius CD, Mejia–Spiegeler A, Suever JD, Wehner GJ, et al. Impaired right ventricular contractile function in childhood obesity and its association with right and left ventricular changes: a cine DENSE cardiac magnetic resonance study. J Cardiovasc Magn Reson 2017;19:49. 24. Mahfouz RA, Dewedar A, Abdelmoneim A, Hossein EM. Aortic and pulmonary artery stiffness and cardiac function in children at risk for obesity. Echocardiography 2012;29:984– 9. [CrossRef] 25. Mostafa SA. Impact of obesity and surgical weight reduction on cardiac remodeling. Indian Heart J 2018;70:S224–S8. 26. Kowalik E, Klisiewicz A, Biernacka EK, Hoffman P. Assessment of systemic right ventricular function in adult overweight and obese patients with congenitally corrected transposition of the great arteries. Kardiol Pol 2017;75:462–9. 27. Alhamshari YS, Alnabelsi T, Mulki R, Cepeda-Valery B, Figueredo VM, Romero-Corral A. Right ventricular function measured by TAPSE in obese subjects at the time of acute myocardial infarction and 2year outcomes. Int J Cardiol 2017;232:181–5. [CrossRef] Obesity and right heart 603 28. Serrano-Ferrer J, Walther G, Crendal E, Vinet A, Dutheil F, Naughton G, et al. Right ventricle free wall mechanics in metabolic syndrome without type-2 diabetes: effects of a 3-month lifestyle intervention program. Cardiovasc Diabetol 2014;13:116. [CrossRef] 29. Vogel M, Schmidt MR, Kristiansen SB, Cheung M, White PA, Sorensen K, et al. Validation of the myocardial acceleration during isovolumic contraction as a novel index of right ventricular contractility: comparison with ventricular pressure-volume relations in an animal model. Circulation 2002;105:1693–9. [CrossRef] 30. Poulsen S, Nielsen J, Andersen H. The influence of heart rate on the Doppler-derived myocardial performance index. J Am Soc Echocardiogr 2000;13:379–84. [CrossRef] Keywords: Isovolumic acceleration; myocardial performance index; obesity; right ventricle. Anahtar sözcükler: izovolumetrik akselerasyon; myokard performans indeksi; obezite; sağ ventrikül.