Right Ventricular Function in Ischemic or Idiopathic Dilated Cardiomyopathy

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1 Circ J 2008; 72: Right Ventricular Function in Ischemic or Idiopathic Dilated Cardiomyopathy Despina G. Parcharidou, MD; Georgios Giannakoulas, MD*; Georgios K. Efthimiadis, MD; Haralambos Karvounis, MD; Klio N. Papadopoulou, MD; Emmanouella Dalamanga, MD; Ioannis Styliadis, MD; Georgios E. Parcharidis, MD Background Differentiation between ischemic (ICM) and dilated cardiomyopathy (DCM) has important therapeutic implications because the former may benefit from coronary revascularization. The aim of this study was to investigate right ventricular (RV) function using tissue Doppler echocardiography (TDE) and compare the TDE parameters of the RV among patients with ICM and DCM. Methods and Results Forty-two patients with ICM and 40 patients with DCM were studied with conventional echocardiography and TDE. The 2 groups did not differ in terms of New York Heart Association class, left ventricular ejection fraction and pharmacological treatment. Patients with ICM had higher pulmonary artery systolic pressure (44.4 mmhg vs 34.7 mmhg, p=0.006) and lower tricuspid annular motion systolic (RV Sa 0.06 m/s vs 0.09m/s, p<0.0001), and diastolic velocities (RV Ea 0.05m/s vs 0.07m/s, p=0.0003, RV Aa 0.075m/s vs 0.11m/s, p=0.0016). They also exhibited a higher ratio of early transtricuspid filling velocity to early diastolic velocity of the tricuspid annulus (RV E/Ea 8.2 vs 5.7, p=0.0008). Age, pulmonary artery systolic pressure and tricuspid Sa were significant independent predictors of the diagnosis of ICM. Conclusions RV dysfunction is more pronounced in patients with ICM than in patients with DCM. The RV TDE parameters can be used to complement clinical and conventional echocardiographic findings in the assessment of patients with ICM and DCM. (Circ J 2008; 72: ) Key Words: Idiopathic dilated cardiomyopathy; Ischemic cardiomyopathy; Right ventricle; Tissue Doppler echocardiography Chronic heart failure (CHF) has emerged as the most prevalent cause of mortality, morbidity and hospitalization in industrialized countries over the past years. 1 Despite the advances in medical and invasive treatment of CHF, its incidence is expected to rise in the future because of improved survival rates following acute myocardial infarction (MI), which is the principal etiology of CHF in>70% of patients. 2 Traditionally, great emphasis was put on evaluation of the various etiologic factors of this syndrome. Differentiation between ischemic cardiomyopathy (ICM) and idiopathic dilated cardiomyopathy (DCM) has important therapeutic implications because the former may gain substantial benefit from coronary revascularization. 3 Conventional echocardiography is commonly used for the evaluation of left ventricular (LV) and right ventricular (RV) function, but does not provide detailed information about myocardial systolic and diastolic properties in the regional segments. Tissue Doppler echocardiography (TDE) is a promising ultrasonographic technique that quantitatively measures the velocity of the myocardium in systole and (Received July 5, 2007; revised manuscript received September 10, 2007; accepted September 28, 2007) First Cardiology Department, AHEPA General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece, *Adult Congenital Heart Centre, and Centre for Pulmonary Hypertension, Royal Brompton Hospital, London, UK Mailing address: Georgios Giannakoulas, MD, AHEPA General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece. giannak@med.auth.gr All rights are reserved to the Japanese Circulation Society. For permissions, please cj@j-circ.or.jp diastole. 4 Traditionally, the principal target of the cardiologist is the evaluation of the LV function, with little interest in the RV. In spite of the fact that several recent studies have used the TDE technique in the assessment of RV function in various clinical conditions, 5,6 the literature on the RV and its impact on the pathophysiologic processes is limited. However, there is a growing body of evidence that RV function is a powerful predictor of mortality in patients with CHF. 7 We hypothesized that ICM and DCM differ in terms of RV function. Thus, the aim of our study was to investigate the RV function in patients with ICM and DCM using pulsed wave TDE and to compare the TDE parameters of the RV among the patients with ischemic and idiopathic dilated causes of LV dysfunction. Methods Study Population We prospectively studied 82 consecutive patients with CHF who had undergone an echocardiographic examination at the AHEPA Hospital (Thessaloniki, Greece). CHF was defined as the presence of heart failure symptoms plus a dilated (>55 mm in end-diastolic diameter) LV with a depressed (<40%) ejection fraction of uncertain origin. The inclusion criteria were: (a) good quality echocardiographic imaging of tricuspid and mitral annular motion, (b) adequate tricuspid valve regurgitation Doppler signal in order to assess pulmonary artery systolic pressure, (c) sinus rhythm on electrocardiography (ECG), and (d) stable clinical condition. The following were considered as exclusion criteria:

2 Right Ventricular TDI in CHF atrial fibrillation, recent (<3 months) MI, unstable angina, severe hypertension ( 170/100 mmhg), and cases in which the entity of coronary artery disease was felt to be disproportionately mild to explain the severity of LV dysfunction. We also investigated 32 healthy control subjects who were divided into 2 groups, age and sex-matched with the ICM and DCM patients. All patients underwent diagnostic cardiac catheterization, coronary angiography and left ventriculography using the Judkins technique. DCM was defined as a heart muscle disease of unknown cause, so that diagnosis was made when other causes of cardiac failure were excluded (coronary or hypertensive heart disease, amyloid or sarcoid heart disease, hemochromatosis). Coronary-induced heart failure was recognized when myocardial damage was attributable to severe coronary artery disease. Forty-two patients with significant coronary artery disease, defined as 70% or greater diameter stenosis in 1 or more of the major coronary arteries, had coronary-induced heart failure (ICM group) and 40 patients had idiopathic DCM (DCM group). Thirty-nine of the patients in the ICM group had a history of previous MI, 22 patients had undergone coronary artery bypass surgery and 21 percutaneous transluminal coronary angioplasty. In the same group there were 38 patients with 3-vessel disease, 3 with 2-vessel disease and 1 patient with 1-vessel disease. Based on ECG and the patients medical files, and after excluding the 27 patients with left bundle brunch block, we identified the location of previous MI as anterior or anteroseptal in 12 patients, lateral in 2 and inferior in 3 patients. No patient had a history of RV involvement after inferior MI. Finally, in 3 patients we could not identify the site of myocardial injury by the abovementioned criteria. The mean interval between cardiac catheterization and the echocardiographic study was 44±28 months, and from coronary artery bypass surgery to the echocardiographic study 38±22 months. Informed consent was given by all patients comprising the study population before enrollment. The study complied with the Declaration of Helsinki and was approved by the Ethical Committee on Human Research of AHEPA Hospital. Echocardiography A complete echocardiographic study was performed for each patient and control subject using a standard commercial ultrasound machine (Vivid 7, GE Vingmed, Horten, Norway) with a MHz phased array transducer. All images were saved digitally in raw-data format to magnetooptical disks for offline analysis. Standard 2-dimensional and color-flow Doppler images were obtained in all patients using the parasternal long-axis and apical views. M-mode traces were recorded at a speed of 50 mm/s. The RV and LV diameters were measured according to the recommendations of the American Society of Echocardiography, and the LV ejection fraction was calculated using the biplane method according to the modified Simpson s rule. 8 For the evaluation of RV diastolic function the peak early transtricuspid filling velocity (E), peak late transtricuspid filling velocity (A) and their ratio (E/A) were recorded. The transtricuspid diastolic flow tracing was imaged in the apical 4-chamber view using pulsed Doppler echocardiography with the sample volume sited at the tips of the tricuspid leaflets. Measurements were averaged from 3 end-expiratory cycles at a sweep speed of 100mm/s. Pulmonary artery systolic pressures were estimated by calculating the systolic pressure gradient between the RV and the right atrium by 239 the maximum velocity of the tricuspid regurgitant jet using the modified Bernoulli equation and then adding to this value an estimated right atrial pressure based on the size of the inferior vena cava and the change in the caliber of this vessel with respiration. 9 Valvular regurgitation severity was graded according to the guidelines of the American Society of Echocardiography. 10 The same ultrasound machine was used to acquire spectral pulsed tissue Doppler data using high-frequency acquisition. The imaging angle was adjusted to ensure a parallel alignment of the beam with the myocardial segment of interest. Filters were set to exclude high-frequency signals. Gains were minimized to allow for a clear tissue signal with minimal background noise. From the standard apical 4-chamber view, resting tissue Doppler velocities within a 5 10mm 2 sample volume were derived for the mitral septal and lateral annular sites and for the tricuspid annulus at the place of attachment of the anterior leaflet of the tricuspid valve. Peak systolic (Sa), early diastolic (Ea) and late diastolic (Aa) motion velocities were measured offline for each subject. Isovolumetric relaxation time (IVRT) was measured as the period ranging from the end of the systolic wave to the onset of the early diastolic wave and the isovolumic contraction time (IVCT) was measured as the time from the Q wave of the ECG to the beginning of the systolic wave in the TDE spectrum. All TDE measurements were performed by 2 experienced operators who were unaware of the clinical data. The intra- and interobserver variabilities of the tissue Doppler imaging parameters were determined in 10 randomly selected recordings twice by the same observer and once each by 2 independent observers. Intra- and interobserver variabilities of tissue Doppler imaging amounted to <5%. Statistical Analysis Continuous data are expressed as mean ± SD or median (25 75 th percentile) based on whether they have a normal distribution or not. Accordingly, comparisons between continuous variables were tested by unpaired t-test or Mann- Whitney U test. Categorical data are presented as absolute values and percentages, and comparisons were tested by Fisher exact test. Because the values of RV Sa, Ea, Aa and E/Ea did not have a normal distribution, the values were subjected to a logarithmic transformation. Multivariate logistic regression analysis was used to assess the relationship between the probability of diagnosis of ICM rather than DCM and the clinical and echocardiographic variables. Sensitivity, specificity, and receiver-operator characteristic (ROC) curves were calculated to measure the performance of Sa, Ea, Aa and E/Ea in the diagnosis of ICD. Sensitivity was defined as TP/(TP+FN) 100 and specificity as TN/(TN+ FP) 100, where TP is true positive, FN is false negative, TN is true negative, and FP is false positive. The ROC curve was constructed by plotting the sensitivity on the ordinate as a function of the false-positive rate (1 specificity) for all possible cutoff values of the diagnostic test. This method allowed us to perform multiple tests across a wide range of cutoffs and to decide the optimum cutoff (ie, minimal false-negative and false-positive cases), suggesting the best accuracy of the RV TDE indices to discriminate between ICM and DCM patients. A p value <0.05 was regarded as statistically significant. SPSS version 12.0 (SPSS Inc, Chicago, IL, USA) and S-Plus 6.0 (Insightful Corp, Seattle, WA, USA) were used for all analyses.

3 240 PARCHARIDOU D G et al. Table 1 Demographical and Clinical Characteristics of the Study Subjects Parameter DCM Control group 1 ICM Control group 2 (n=40) (n=16) (n=42) (n=16) p value Age (years) 49.9± ± ± ±9.8 < M/F 29/11 12/4 39/3 15/ NYHA class (I, II/III, IV) 16/24 14/28 NS LBBB Arterial hypertension NS Hyperlipidemia NS Diabetes mellitus NS Smoking NS Medications Aspirin 8 7 NS Clopidogrel 0 1 NA -blockers NS ACEIs/ARBs NA Spironolactone/eplerenone NS Diuretics NS Digoxin 9 9 NA Statins 5 30 < Values are mean ± SD. DCM, dilated cardiomyopathy; ICM, ischemic cardiomyopathy; NYHA, New York Heart Association; LBBB, left bundle branch block; NA, not applicable; ACEIs, angiotensin enzyme inhibitors; ARBs, angiotensin-receptor blockers. Table 2 Conventional Echocardiographic Parameters of the Study Subjects Parameter DCM Control group 1 ICM Control group 2 (n=40) (n=16) (n=42) (n=16) p value* LV end-diastolic diameter (cm) 6.9± ± ± ±0.3 NS LV ejection fraction (%) 29.3±8 63.6± ± ±2.9 NS Left atrium diameter (mm) 44±7 34±2.6 44±6 35.2±2.8 NS RV end-diastolic diameter (cm) 2.6± ± ± ±0.1 NS RV area change (%) 31.7±9.9 45±3 28.5± ±3.8 NS Pulmonary artery systolic pressure (mmhg) 34.7 ( ) 21.7± ( ) 23.1± Tricuspid E (m/s) 0.47± ±0.1*** 0.47± ±0.1*** NS A (m/s) 0.44± ± ± ±0.11 NS E/A 1.12± ±0.46*** 1.16± ±0.31 NS DT (ms) 188.2± ±26** 207.7± ±25.1 NS Values are mean±sd or median (25 75 th percentile). *Comparison between DCM and ICM groups; **p<0.05 vs DCM in Control group 1 and vs ICM in Control group 2; ***p<0.01 vs DCM in Control group 1 and vs ICM in Control group 2; p<0.001 vs DCM in Control group 1 and vs ICM in Control group 2. LV, left ventricular; RV, right ventricular; DT, deceleration time. Other abbreviations see in Table 1. Table 3 Tissue Doppler Echocardiography of the Study Subjects Parameter DCM Control group 1 ICM Control group 2 (n=40) (n=16) (n=42) (n=16) p value* Mitral septal Sa (m/s) 0.04 ( ) 0.08±0.02*** 0.03 ( ) 0.07±0.01*** 0.03 Ea (m/s) 0.04 ( ) 0.08±0.02*** 0.03 ( ) 0.07±0.02*** Aa (m/s) 0.06 ( ) 0.09±0.03*** 0.03 ( ) 0.1±0.02*** E/Ea 17.7 ( ) 9.3±1.4*** 24.9 ( ) 9.9±1.3*** Mitral lateral Sa (m/s) 0.04 ( ) 0.09±0.02*** 0.04 ( ) 0.09±0.01*** NS Ea (m/s) 0.05 ( ) 0.1±0.03*** 0.05 ( ) 0.09±0.01*** NS Aa (m/s) 0.05 ( ) 0.11±0.03*** 0.04 ( ) 0.12±0.02*** NS E/Ea 17.1± ±1.4*** 19.7± ±1.8*** NS Tricuspid Sa (m/s) 0.09 ( ) 0.1 ( )** 0.06 ( ) 0.1 ( )*** < Ea (m/s) 0.07 ( ) 0.11±0.02** 0.05 ( ) 0.1±0.02*** Aa (m/s) 0.11 ( ) 0.07 ( )** 0.07 ( ) 0.09 ( ) Ea/Aa 0.71 ( ) 1.62±0.67*** 0.66 (0.48 1) 1.31±0.5*** NS E/Ea 5.7 ( ) 5.75± ( ) 5.94±1.98*** IVRT (ms) 68.2± ( ) 68.5± ±10.6 NS IVCT (ms) 91.3± ±15.4** 91± ±14.45** NS Values are mean±sd or median (25 75 th percentile). *Comparison between DCM and ICM groups; **p<0.01 vs DCM in Control group 1 and vs ICM in Control group 2; ***p<0.001 vs DCM in Control group 1 and vs ICM in Control group 2. Sa, peak systolic myocardial velocity; Ea, peak early diastolic myocardial velocity; Aa, peak late diastolic myocardial velocity; IVRT, isovolumetric relaxation time; IVCT, isovolumic contraction time. Other abbreviations see in Table 1.

4 Right Ventricular TDI in CHF 241 Fig 1. Regional right ventricular systolic and diastolic parameters measured by tissue Doppler echocardiography in a patient with ischemic cardiomyopathy (Left panel) and another with idiopathic dilated cardiomyopathy (Right panel). Note the reduced tricuspid systolic and diastolic velocities in the patient with ischemic cardiomyopathy. Table 4 Multivariate Logistic Regression Analysis for Prediction of Diagnosis of ICM and Age and Echocardiographic Data of 82 Patients With Chronic Heart Failure Variable coefficient RR (CI) p value Age ( ) Pulmonary artery systolic pressure (1 1.1) 0.05 LnSa of tricuspid annulus ( ) RR, relative risk; CI, confidence interval; LnSa, natural logarithm of peak systolic myocardial velocity. Other abbreviation see in Table 1. Table 5 Sensitivity and Specificity of the Different RV Tissue Doppler Indices for Identification of Ischemic Aetiology in Patients With DCM Variable Sensitivity Specificity p value Sa % ( ) 57.5% ( ) Ea % ( ) 72.5% ( ) Aa % ( ) 67.5% ( ) E/Ea % ( ) 50% ( ) Values are percentage. 95%CI shown in parentheses. Abbreviations see in Tables 1 4. Results Of 128 patients admitted with a clinical diagnosis of CHF, 82 met the inclusion criteria for the study; 30 patients were excluded for non-sinus rhythm, 2 for severe hypertension, 1 for unstable angina, 3 for disproportionately mild entity of coronary artery disease to explain the severity of LV dysfunction, 6 for unstable condition, 3 for low quality echocardiographic imaging of tricuspid and/or mitral annular motion, and 1 patient for inadequate tricuspid valve regurgitation Doppler signal in order to assess pulmonary artery systolic pressure. The demographic and clinical characteristics of the 2 groups and controls are shown in Table 1. ICM and DCM patients were comparable for cardiovascular risk factors, functional class severity and drug treatment, except statin therapy. Tables 2 and 3 show the respective standard echocardiographic and pulsed Doppler tissue imaging measurements of the study groups. Systolic and diastolic TDE myocardial velocities were significantly lower in patients with LV dysfunction than in healthy control subjects. There were no differences between the 2 patient groups for LV ejection fraction and RV end-diastolic diameter. Both groups were comparable regarding the frequency of mitral regurgitation: mitral regurgitation grade IV (2 patients in ICM group vs 1 patient in DCM group), grade III (9 patients vs 8 patients) and grade I and II (29 patients vs 33 patients). The same occurred for the frequency of tricuspid regurgitation (grade IV/III 4 patients in ICM group vs 3 patients in DCM group, grade II 12 and 10 patients, respectively, and grade I 26 and 27 patients, respectively). Patients with ICM had more severe pulmonary hypertension and significantly lower systolic and diastolic velocities of mitral and tricuspid annular motion (Fig 1). By multivariate logistic regression analysis, age (p=0.0002), pulmonary artery systolic pressure (p=0.05), and lnsa of the tricuspid annulus (p=0.003) were the only variables independently associated with the probability of a diagnosis of ICM rather than DCM (Table 4). The sensitivity and specificity of the several RV tissue Doppler indices for identification of ischemic etiology in patients with DCM are shown in Table5. Values of the ratio of peak early transtricuspid filling velocity (E) to peak early diastolic velocity of the tricuspid annulus (Ea) 5.25 exhibited higher sensitivity (88.1%) and a peak early diastolic annular velocity 5cm/s a higher specificity (72.5%) for predicting ischemic etiology in patients with LV dysfunction (Fig 2). Discussion The present study compared RV systolic and diastolic

5 242 PARCHARIDOU D G et al. Fig 2. Receiver-operating characteristic curves for prediction of ischemic etiology in patients with dilated cardiomyopathy. (A) Tricuspid E/Ea ratio, (B) tricuspid Ea. Sens, sensitivity; Spec, specificity; PV+, positive predictive value; PV, negative predictive value; Ea, peak early diastolic myocardial velocity. function by TDE method in patients with severe ICM and DCM. Functional class severity, LV ejection fraction and the degree of mitral regurgitation were similar in the 2 groups. Patients with ICM exhibited significantly lower systolic and diastolic velocities of tricuspid and mitral septal annular motion and a higher ratio of peak early transtricuspid filling velocity to peak early diastolic velocity of the tricuspid annulus compared with patients with DCM. Interestingly, the tricuspid Sa was found to be a significant predictor of the cause of cardiomyopathy independent of the influence of age, gender, presence of left bundle branch block and other RV and LV echocardiographic parameters. We also found that of the TDE indices of the right ventricle, the tricuspid E/Ea presented a higher sensitivity, and the tricuspid Ea had a higher specificity, for the differentiation of ICM from DCM patients. Tissue Doppler imaging allows quantitative assessment of the motion of the myocardium, and is particularly useful in quantifying both regional and global LV and RV longaxis function. 11 Concerning the RV, Vinereanu et al have demonstrated good reproducibility of acquiring and measuring tricuspid annular velocities, especially for the peak systolic velocity, which appeared to be the most clinically useful parameter. 12 Pulsed TDE has been evaluated in healthy adults in studies that assessed the TDE-derived RV transverse and longitudinal velocities, establishing normal reference values for adults at the level of the RV free wall 13 and of the lateral tricuspid annulus. 14 Of interest, both the regional diastolic RV Ea and Ea/Aa ratio show a downward trend with aging: RV Aa increases from middle age, whereas systolic Sa is independent of age. 14 TDE of the RV has also been studied in various pathological clinical conditions. 15,16 Focusing on the RV in CHF patients, whether the presence of RV dysfunction can be used as a tool to separate DCM from ischemic disease is of clinical interest. The presence of RV systolic dysfunction has been correlated with adverse hemodynamic and humoral responses and survival. 7 Therefore, it is highly important to evaluate RV function in patients with CHF. None of the methods currently employed to assess size and function of the RV (high-frequency thermodilution, contrast ventriculography, radionuclide ventriculography, echocardiography, and magnetic resonance imaging) has proven to be the gold standard for assessing RV function in these patients, so TDE has the potential to be a complementary modality in the study of RV pathology. Patients with CHF have significantly decreased systolic myocardial velocities of the mitral and tricuspid annulus compared with healthy controls. 17 In a study by Meluzin et al, a tricuspid systolic annular velocity <11.5cm/s predicted RV dysfunction with a sensitivity of 90% and a specificity of 85%. 18 The prognostic significance of TDE assessment of tricuspid annular motion was shown in a recently published study in which patients with Sa <10.8 cm/s exhibited worse survival than those having Sa >10.8 cm/s. 19 The early diastolic velocity is also reduced in patients with CHF compared with healthy controls for both mitral and tricuspid annuli. 17 Although previous studies have shown that DCM is characterized by more severe RV systolic dysfunction than ICM, to our knowledge there is no study in the literature comparing the RV diastolic function of the 2 entities. Furthermore, the discrepancy between our results and those of previous studies concerning RV systolic involvement may be multifactorial. The fact that in the study by La Vecchia et al only 74% of ICM patients had a history of previous MI and 84% had 3-vessel disease, whereas in the present study these percentages were 93% and 95%, respectively, may partially explain the discrepancy between the results. 20 Juillière et al recruited a smaller sample of patients and matched the 2 groups for mean pulmonary artery pressure. 21 Finally, in the retrospective study by Iskandrian et al, in which gated radionuclide angiography was used for RV performance evaluation, patients with DCM were older and did nor receive -blockers, whereas patients with ICM had a lower incidence of a documented previous MI (49%) and prevalence of 3-vessel disease (59%). 22 A study by Plewka et al compared the TDE parameters of the LV in the 2 groups and found that in patients with IVCT <115ms or IVRT >120ms the diagnosis of an ischemic cause of CHF was associated with sensitivity 82%, specificity 89%, positive predictive value 90%, negative predictive value 80% and accuracy 85%. 23 They also found that there were no significant differences between groups with DCM and ICM in mitral Sa and Aa, although mitral Ea was significantly lower in the ICM than in the DCM group, 23 a

6 Right Ventricular TDI in CHF finding that coincides with our results. We found significant differences of LV tissue Doppler velocities between the 2 entities only in the mitral septal site, not the lateral annular site, which could explain the greater impairment of RV performance in ICM patients. The perspective that CHF causes structural and functional changes that influence only the LV, while the RV remains unimpaired, is not reasonable. The 2 ventricles are anatomically united by their common blood supply, muscle fiber anatomy, interventricular septum and pericardium 24 and exhibit interdependence, as already demonstrated in other conditions such as arterial hypertension. 15 Systolic ventricular interdependence was found to be more pronounced in an experimental tachycardia-induced cardiomyopathy models in pigs than in normal hearts. 25 The overall RV function does not depend solely on the function of the right free wall, but also on septal contractility, which is irreversibly impaired in ICM. 7 It is known that RV function depends on afterload, resulting in its deterioration when pulmonary artery pressure is elevated, but this relationship may be dependent on the etiology of the cardiomyopathy. Only a weak inverse relationship was found for patients with DCM, whereas in ICM this relationship was much stronger given the same level of LV dysfunction. 20 This may indicate that the development of pulmonary hypertension is a sign of advanced disease resulting in RV dysfunction in ICM. In contrast, RV dysfunction observed in DCM may be the result of the myopathic process affecting the myocardium of both ventricles, rather than of pulmonary hypertension. Previous reports found that ICM is associated with more severe pulmonary hypertension and a higher mortality compared with DCM. 26 Patients with pulmonary artery hypertension exhibit reduced strain indices in the RV free wall compared with patients with normal pulmonary artery pressures, irrespective of whether RV systolic function is normal or reduced as assessed by echocardiography. 27,28 In our cohort, patients with ICM exhibited worse pulmonary hypertension than patients with DCM and that finding could explain the worse RV systolic and diastolic function in the former group. The differences in the performance of the RV between the 2 groups in the present study could also be explained by the anatomic arrangement of myocardial fibers. 29 The subepicardial myofibers are arranged mainly in a circumferential manner, parallel to the atrioventricular groove, and encircle the subpulmonary infundibulum. In contrast, the myofibers lying deeper than the subepicardium are longitudinally aligned, from apex to base and the subendocardial myofibers are similarly arranged. Contraction of the ventricle in the longitudinal axis is mainly caused by subendocardial fibers, 30 which are sensitive to ischemia. 31 Therefore, TDE velocity measurements in the free wall of the RV are affected in ICM. On the other hand, in DCM the dilatation of the RV might change the myofiber orientation, resulting in a more circumferential fiber arrangement. 243 Study Limitations One limitation of our study is that the 2 groups were not age- and sex-matched. Although gender differences do not seem to influence tricuspid annular or myocardial velocities measured in the free RV wall, the effect of age on the right wall velocities is controversial. 14 Nevertheless, our multivariate model showed that low RV Sa values were associated with the diagnosis of ICM independent of the influence of age. Although coordinated RV function depends on the contraction of myocardial fibers along both the long and short axes, myocardial velocities obtained by TDE in the apical 4-chambers reflect the movements of the myocardium only along the long axis. The contraction of ventricular circumferential fibers does not affect the myocardial velocities in this localization. This can lead to the idea that TDE does not accurately reflect global RV function. Because imaging of the RV is not technically easy, its assessment is not practical with echocardiography. Besides, it is accepted that mitral and tricuspid annulus changes are affected by the movement of the entire wall of the ventricle. 17 In conclusion, our study demonstrated that CHF is accompanied by RV dysfunction, which is more pronounced in ICM patients. TDE provides quantitative, reproducible and non-invasive analysis of RV function in patients with CHF. Peak systolic and diastolic tricuspid annular velocities and the ratio of peak early transtricuspid filling velocity to peak early diastolic velocity of the tricuspid annulus differ significantly in patients with ischemic and non-icm. Therefore, these parameters are complementary to clinical and conventional echocardiographic findings and facilitate the qualification for invasive procedures in patients with difficult-to-diagnose cardiomyopathy. Acknowledgments We are indebted to Kostantinos Tzanas for his contribution to the statistical analysis. There are no conflicts of interest or funding sources. References 1. Cleland JG, Khand A, Clark A. The heart failure epidemic: Exactly how big is it? Eur Heart J 2001; 22: Challapalli S, Bonow RO, Gheorghiade M. Medical management of heart failure secondary to coronary artery disease. Coron Artery Dis 1998; 9: Chaitman BR, Ryan TJ, Kronmal RA, Foster ED, Frommer PL, Killip T. 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