Cardiology Plus

RESEARCH ARTICLE
Year
: 2019  |  Volume : 4  |  Issue : 1  |  Page : 15--21

Right ventricular systolic function and cardiac resynchronization therapy


Lu Tang1, Nianwei Zhou1, Xue Gong1, Shengmei Qin2, Zhaohua Yang3, Zhenning Nie2, Shimo Dai2, Quan Li1, Yangang Su2, Cuizhen Pan1, Xianhong Shu1,  
1 Department of Echocardiography, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, Shanghai Institute of Medical Imaging, Fudan University, Shanghai, China
2 Department of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, Shanghai Institute of Medical Imaging, Fudan University, Shanghai, China
3 Department of Cardiac Surgery, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, Shanghai Institute of Medical Imaging, Fudan University, Shanghai, China

Correspondence Address:
Xianhong Shu
Department of Echocardiography, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, Shanghai Institute of Medical Imaging, Fudan University, Shanghai
China

Abstract

Objectives: The aim of this study was to investigate the influence of right ventricular (RV) dysfunction on the response to cardiac resynchronization therapy (CRT) and the impact of CRT on RV function in a beagle model of heart failure (HF). Methods: Twenty-one beagles were implanted with transvenous cardiac pacemakers and underwent rapid RV pacing for 2 weeks at 260 bpm to induce HF. Dogs were subsequently divided into three groups that were either treated with bi-ventricular pacing (CRT group) or untreated (control group and HF group). Echocardiographic images were acquired at baseline, before CRT, and 4 weeks after CRT. Results: Left ventricular systolic function and synchrony (left ventricular internal dimensions, left ventricular end systolic volume [LVESV], left ventricular ejection fraction [LVEF], septal-to-posterior wall motion delay [SPWMD], and aorta pre-ejection interval and the pulmonary artery pre-ejection interval [|APEI-PPEI|]) were significantly improved in the CRT group compared with the HF group. RV myocardial performance index (MPI) and pulmonary artery systolic pressure deteriorated with left ventricular dysfunction and improved after CRT. RV outflow ESV, standard deviation of time to minimum systolic volume (Tmsv), and Tmsv% decreased in the CRT group compared with the HF group. LVESV, LVEF, SPWMD, and |APEI-PPEI| were significantly different between responders and nonresponders, while there was no difference about RV functional parameters. Conclusions: RV function deteriorated with left ventricular dysfunction and improved after CRT. RV function did not significantly influence the response to CRT.



How to cite this article:
Tang L, Zhou N, Gong X, Qin S, Yang Z, Nie Z, Dai S, Li Q, Su Y, Pan C, Shu X. Right ventricular systolic function and cardiac resynchronization therapy.Cardiol Plus 2019;4:15-21


How to cite this URL:
Tang L, Zhou N, Gong X, Qin S, Yang Z, Nie Z, Dai S, Li Q, Su Y, Pan C, Shu X. Right ventricular systolic function and cardiac resynchronization therapy. Cardiol Plus [serial online] 2019 [cited 2021 Apr 16 ];4:15-21
Available from: https://www.cardiologyplus.org/text.asp?2019/4/1/15/255072


Full Text

 Introduction



It is well established that cardiac resynchronization therapy (CRT) improves left ventricular ejection fraction (LVEF) in patients with heart failure (HF).[1],[2] However, uncertainty exists both about the effects of CRT on right ventricular (RV) function and how RV dysfunction affects the response to CRT[3],[4],[5],[6],[7] because of the difficulty in measuring RV parameters and heterogeneity of patients involved in the research in measures such as drug therapy, complication, and experimental ethics. Furthermore, the lack of control groups in some studies makes it difficult to distinguish treatment effects from the natural history of the disease.

Accordingly, to investigate the relationship between CRT and RV, we studied a canine model combining rapid pacing-induced HF with CRT.[8],[9] The rapid pacing-induced HF in developing dilated cardiomyopathy (DCM) model has been commonly used due to its simplicity and convenience. HF was induced by 2 weeks of rapid pacing. The modifications utilized in this study are summarized in [Figure 1].{Figure 1}

Echocardiography is the most widely used method in the assessment of RV systolic function for its high availability and reproducibility.[10],[11] Two-dimensional (2D) echocardiography was mainly used in the assessment of RV regional systolic function in the longitudinal direction in previous studies.[12],[13],[14] However, the complete RV structure is difficult to display in one 2D view with the inflow and outflow sections perpendicular to each other.[15],[16] Real-time 3D echocardiography (RT3DE) is a novel echocardiographic method with the advantage of displaying the 3D anatomy of the right ventricle despite its irregular chamber shape, reflecting the effect of both longitudinal and transverse movements on RV systolic function simultaneously.[17] This advantage makes it superior to conventional 2D methods in RV functional assessment. Thus, the purposes of the present study were to assess RV function before and after CRT with RT3DE and to explore the relationship between RV functional parameters and CRT.

 Methods



Animals and groups

Twenty-four beagles aged 1.4 ± 0.5 years and weighing 14.8 ± 3.1 kg (Shanghai Jiagan biological Technology Company, Shanghai, China; Licence No. SCXK-Shanghai 2010–0028) were assigned to three groups: control group (n = 4), HF group (n = 8), and CRT group (n = 12). Experiments were performed using both male and female beagles at random. All animal experiments were approved by the Animal Care and Use Committee of Fudan University (Shanghai, China) in compliance with the “Guide for the Care and Use of Laboratory Animals” published by the National Academy Press (NIH Publication No. 85–23, revised 1996).

Surgical procedures

The beagles were fasted for 6 h and sedated with 3% pentobarbital sodium 30 mg/kg, and if necessary, intravenously injected succinylcholine 10 mg/kg to relax their muscles. All animals were intubated and mechanically ventilated with oxygen and underwent electrocardio monitoring before and during surgery. To better simulate the DCM model with complete left bundle branch block (LBBB), all dogs underwent left bundle branch ablation and implantation of a pacemaker in the supraclavicular area. Under the guidance of X line, an RV lead (CAPSURE SENSE 4074, Medtronic, USA) was sutured in the RV apex and a J type lead (MEMBRANE EX 1474K, Medtronic, USA) was sutured in the right atria (RA) appendage. Intracardiac electrograms were performed to ensure the electrodes were in the endocardium of the RA and RV. Appropriate lead position was acceptable for R-wave sensing above 10 mV and pacing threshold <2 V at 0.5 ms. The RV lead was connected with a single chamber pacemaker ventricular port (Medtronic 8626), without pacing. Beagles in the CRT group had their chests opened, allowing for an epicardial lead (CAPSUREEPI 4965, Medtronic, USA) sutured to the surface of left ventricular lateral wall and had a piece of myocardial tissue taken out for examination with a light and electron microscope. Then, all leads were connected to the CRT pacemaker (INSYNC III8042, Medtronic, USA). Pacing was initiated in the CRT group only. After 4 weeks of pacing, animals receiving CRT were further divided into two subgroups on the basis of their response to CRT. The LVEF of dogs in the HF group was spontaneously improved and peaked at 49.6% by 4 weeks. Thus, LVEF >49.6% was considered as a positive response to CRT after 4 weeks of resynchronization therapy in the CRT group. Animals in CRT group were then classified as “responders” or “nonresponders” to the biventricular treatment [Figure 1].

Pacemaker program

The animals were allowed a 1-week period recovery from the effect of surgery; following that pacing was started. The electrocardiogram (ECG) was taken after the program. The HF and CRT group opened Medtronic program, entered the program interface, and set the parameters of Brady. After 2 weeks of pacing, the CRT group changed the pacemaker.

Observation indicators

Baseline characteristics

The operation success rate and exposure time were observed. The respiratory, heart rate, activity, and urine volume were observed, and the following symptoms of lethargy, decreased activity, fluid retention, or tachypnea were defined as clinical HF.

Myocardial microscopic evaluation

After rapid RV pacing for 2 weeks, LV anterior wall cardiac samples were obtained. Some were stained with hematoxylin and eosin (HE) to assess myofilament, and the others were used for electron microscopy to image mitochondria in the HF group.

Echocardiography

Echocardiography was performed using a commercially available system (Philips Medical Systems) at baseline, after 2 weeks of pacing, and at the conclusion of pacing at 4 weeks (6 weeks from baseline). Conventional left and RV echocardiographic parameters were evaluated using criteria standardized by the American Society of Echocardiography.[17] All the echocardiographic measurements were made during normal sinus rhythm. RT3DE was performed in all subjects after a 2D examination using an iE33 ultrasound machine with an X5-1 matrix-array transducer. RV3DE images were acquired in a full-volume set in the apical four-chamber view. The acquisition of RV3DE images was conducted twice, with a time interval of 5 min, and the acquired images were stored on a compact disc. Postprocessing of RT3DE images was performed using a TomTec workstation with 4D analysis software (Echo View, TomTec Imaging Systems GmbH, Munich, Germany). The software analyzed RT3DE images in a semiautomatic way. With the observer manually tracing end-diastolic and end-systolic frames in the sagittal, four-chamber, and coronal views obtained from RT3DE images, the software automatically traced the RV inner border during one heart cycle, recording RV chamber volume changes, calculating RV global end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and EF, and developing an immediate report. At the same time, the 3D chamber of the right ventricle was divided into three parts, the inflow, body, and outflow compartments, on the basis of the RV surface landmarks automatically by the software [Figure 2]. These landmarks were defined at 50% of the distance between the point of the tricuspid annulus, the apical point, and the point of the pulmonary annulus. We converted the digital record of RV regional volumes over one heart cycle into a spreadsheet to form a volume-time curve. The maximum and minimum values of regional volumes were detected as regional EDV and ESV. Regional SV and EF were then calculated as the difference and the percentage change of EDV and ESV, respectively. We analyzed the digital record of RV regional volumes over one heart cycle, and then got RV regional time to minimum systolic volume (Tmsv), Tmsv corrected by heart rate (Tmsv%) and standard deviations (SDs) of Tmsv and Tmsv% in three RV segments. A single reader performed all interpretations of the echocardiographic findings and was blinded to the pacing assignment of the animals.{Figure 2}

Statistical analysis

All data are expressed in mean ± SD. Statistical analyses were performed using SPSS v19.0 software package (SPSS, Inc., Chicago, IL, USA). Comparison between groups was performed with the t or t-test for measurement data. A probability value <0.05 was considered statistically significant.

 Results



Baseline characteristics

These modifications utilized in this study are summarized in [Figure 1]. Twenty-four beagles underwent device implantation without surgical complications. Two beagles in HF group died of severe HF and one in the CRT group died of infection. The success rate was 87.5% (21/24). The beagles in the HF group had signs of overt HF such as lethargy, decreased activity, or tachypnea. ECG after ablation showed LBBB with wide QRS duration. HE staining showed that myocardial of HF beagles had small vascular congestion, myofilament thinning, and disorganization compared to control animals. Electron microscopy showed that HF beagles' mitochondria were swollen and the number of mitochondria had decreased compared to control animals [Figure 3]. Using these measures, we determined that the canine model of HF was successful.{Figure 3}

Comparison of two-dimensional-echocardiographic parameters of left ventricular and right ventricular between the three groups

The 2D echocardiographic parameters of LV and RV are presented in [Table 1]. LVEF and myocardial performance index (MPI) showed a significant increase in the CRT group than in the HF group by 4 weeks after the initiation of biventricular pacing (P < 0.05). Left ventricular internal dimension systole at end-diastole, left ventricular ESV (LVESV), septal-to-posterior wall motion delay (SPWMD), the absolute difference of the aorta pre-ejection interval and the pulmonary artery pre-ejection interval (|APEI-PPEI|), and pulmonary artery systolic pressure (PASP) were significantly decreased in the CRT group compared to the HF group by 4 weeks after the initiation of biventricular pacing (ALL P < 0.05).{Table 1}

Comparison three-dimensional-right ventricular parameters between the three groups

RT3DE images of the right ventricle were successfully analyzed in 20 of the 21 baseline (95.2%), 18 of the 21 before CRT (85.7%), and 17 of the 21 CRT (81.0%). RT3DE parameters regarding RV regional systolic function and dyssynchrony are summarized in [Table 2]. Outflow ESV (7.2 ± 4.1 ml vs. 4.4 ± 2.1 ml), SD of Tmsv (30.9 ± 24.6 ms vs. 8.0 ± 7.3 ms), and Tmsv% (0.07 ± 0.05 vs. 0.02 ± 0.01) were significantly decreased in the CRT group than in the HF group by 4 weeks after the initiation of biventricular pacing (ALL P < 0.05).{Table 2}

Comparisons between responders and nonresponders in the cardiac resynchronization therapy group

Since the LVEF of dogs in the HF group was spontaneously improved after rapid RV pacing and peaked at 49.6% by 4 weeks after the pacemaker was turned off, we defined LVEF >49.6% as the cutoff point for distinguishing the responders or nonresponders to CRT. Six dogs (54.5%) in the CRT group were found to be effectively treated by the therapy, and the other five canines were designated nonresponders. As expected, LVESV (33.2 ± 5.1 ml vs. 26.8 ± 3.4 ml), LVEF (40.9% ± 3.2% vs. 31.6% ± 5.8%), SPWMD (137.1 ± 35.1 ms vs. 83.7 ± 41.2 ms), and |APEI-PPEI| (28.4 ± 13.7 ms vs. 15.8 ± 11.4 ms) differed significantly between the responders and nonresponders before CRT (ALL, P < 0.05), whereas no significant differences in RV parameters were observed [Figure 4].{Figure 4}

Three-dimensional-right ventricular reproducibility

Intraobserver coefficients of variation for body EF, outflow EF, inflow EF, global EF, and the SDs of Tmsv and Tmsv% were 16% ± 18%, 17% ± 19%, 8% ± 8%, 8% ± 7%, 7% ± 9%, and 7% ± 7%, respectively. Corresponding interobserver coefficients of variation were 16% ± 13%, 26% ± 26%, 16% ± 11%, 9% ± 9%, 8% ± 7%, and 8% ± 6%, respectively.

 Discussion



The main results of our study were that CRT seems to have no significant acute effect on RVEF and only improvement in MPI and RV dyssynchrony, which improved to a lesser extent than LVEF. Furthermore, RV function at baseline was less likely to affect response to CRT. To the best of our knowledge, this is the first large-animal study using RTSDE that has determined the relationship between RV function and the outcome of CRT. Furthermore we also considered the impact of biventricular pacing on RV regional systolic function.

Improvement in right ventricular function by cardiac resynchronization therapy

CRT might be expected to improve RV function by lowering left atrial and pulmonary artery pressures due to improvements in LV function and mitral regurgitation.[18],[19],[20] However, pacing leads might interfere with tricuspid valve function and RV apical pacing might impair RV function.[21],[22] We identified no significant acute improvement in right heart function with CRT when compared to the HF group; however, MPI was slightly improved and may have indicated subtle changes in RV systolic function, in contrast to several,[23],[24] but not all,[20],[25] observational studies. PASP was significantly decreased in the CRT group. MPI is a new, sensitive parameter for ventricular contractile function that has been evaluated in a variety of experimental and clinical settings.[26] Several studies[19],[27],[28] have shown that small changes in contractile function can be detected by measuring MPI, while changes in preload and afterload within the physiological range did not affect this parameter.

In our study, RV dyssynchrony was significantly improved after CRT when compared to the HF group. There may be mechanisms that influence RV function and remodeling following CRT implantation. It was established that electrical resynchronization by CRT reduces LBBB-induced dyssynchrony seen between the two ventricles and also intraventricular dyssynchrony within the left ventricle.[29] Rajagopalan[20] postulated that CRT may improve the coordination of the contractility of the right ventricle, which translates to functional improvement.

Baseline right ventricular function and response to cardiac resynchronization therapy

The effect of RV function on CRT has not been well studied, partially owing to difficulty in measuring this parameter. In the current study, RV function at baseline was less likely to affect the response to CRT and in contrast to Damy,[22] did not diminish the prognostic benefits of CRT. However, several observational studies[5],[6],[30] have suggested that patients with RV dysfunction receive less prognostic benefit from CRT. The problem with observational studies is that they are unable to distinguish between outcome with treatment and response to it. RV ejection fraction is an imperfect measure of RV systolic function as it is dependent on loading conditions and thus affected by volume status, pulmonary pressure, and tricuspid regurgitation, none of which were specifically evaluated in these studies. These factors were well balanced in our study.

The precise interplay between RV function and CRT is not fully understood. Our proposed mechanism for the beneficial effects of CRT on RV function is ventricular reverse remodeling. A decline in ventricular volumes and improvement of systolic function might improve RV filling and thereby improve RV systolic function. In clinical settings, the development of RV systolic dysfunction in HF has various causes. But to understand the precise mechanisms still requires further investigation.

Limitations

We relied on a clinically relevant large animal model. Therefore, the number of subjects per group (especially the nonresponder subgroup in CRT group) was by necessity limited when compared to rodent studies. RT3DE is limited by sector width, which might affect imaging of the entire RV free wall. The comparison of real-time 3D echocardiographic regional systolic function data with a reference method was not performed. Further investigation will be needed to evaluate the association between RV function and CRT in other HF model. As with any other animal study, our preclinical findings will require validation in humans before they can be appropriately translated to clinical applications.

 Conclusions



Our study indicates that CRT improves left-sided systolic function to a greater extent than right-sided systolic function, which seems logical from a mechanistic synchronism point of view. Baseline RV function seems to have no impact on response to CRT, but this parameter needs to be further explored before clinical applications. The challenge remains in finding a parameter that accurately evaluates RV function as predictivity of response to CRT.

Financial support and sponsorship

This study was supported by grant 81200170, 81371576 from National Nature Science Foundation of China, grant 124119a7702 from Science Committee Funds of Shanghai.

Conflicts of interest

There are no conflicts of interest.

References

1Abraham WT, Fisher WG, Smith AL, Delurgio DB, Leon AR, Loh E, et al. Cardiac resynchronization in chronic heart failure. N Engl J Med 2002;346:1845-53.
2Cleland JG, Daubert JC, Erdmann E, Freemantle N, Gras D, Kappenberger L, et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med 2005;352:1539-49.
3Bilge AK, Ozben B, Ozyigit T, Acar D, Hunerel D, Adalet K, et al. Assessment of early changes in the segmental functions of the left and the right ventricles after biventricular pacing in heart failure: A study with tissue Doppler imaging. Angiology 2008;59:179-84.
4Donal E, Vignat N, De Place C, Leray E, Crocq C, Mabo P, et al. Acute effects of biventricular pacing on right ventricular function assessed by tissue Doppler imaging. Europace 2007;9:108-12.
5Scuteri L, Rordorf R, Marsan NA, Landolina M, Magrini G, Klersy C, et al. Relevance of echocardiographic evaluation of right ventricular function in patients undergoing cardiac resynchronization therapy. Pacing Clin Electrophysiol 2009;32:1040-9.
6Burri H, Domenichini G, Sunthorn H, Fleury E, Stettler C, Foulkes I, et al. Right ventricular systolic function and cardiac resynchronization therapy. Europace 2010;12:389-94.
7Fazio S, Carlomagno G. The importance of tricuspid regurgitation and right ventricular overload in ICD/CRT recipients: Beside the left, beyond the left. Pacing Clin Electrophysiol 2011;34:1181-4.
8Chakir K, Depry C, Dimaano VL, Zhu WZ, Vanderheyden M, Bartunek J, et al. Galphas-biased beta2-adrenergic receptor signaling from restoring synchronous contraction in the failing heart. Sci Transl Med 2011;3:100ra88.
9Chakir K, Daya SK, Aiba T, Tunin RS, Dimaano VL, Abraham TP, et al. Mechanisms of enhanced beta-adrenergic reserve from cardiac resynchronization therapy. Circulation 2009;119:1231-40.
10Rudski LG, Lai WW, Afilalo J, Hua L, Handschumacher MD, Chandrasekaran K, 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.
11Sato T, Tsujino I, Ohira H, Oyama-Manabe N, Yamada A, Ito YM, et al. Validation study on the accuracy of echocardiographic measurements of right ventricular systolic function in pulmonary hypertension. J Am Soc Echocardiogr 2012;25:280-6.
12López-Candales A, Rajagopalan N, Gulyasy B, Edelman K, Bazaz R. Differential strain and velocity generation along the right ventricular free wall in pulmonary hypertension. Can J Cardiol 2009;25:e73-7.
13Fukuda Y, Tanaka H, Sugiyama D, Ryo K, Onishi T, Fukuya H, et al. Utility of right ventricular free wall speckle-tracking strain for evaluation of right ventricular performance in patients with pulmonary hypertension. J Am Soc Echocardiogr 2011;24:1101-8.
14Gurudevan SV, Malouf PJ, Kahn AM, Auger WR, Waltman TJ, Madani M, et al. Noninvasive assessment of pulmonary vascular resistance using Doppler tissue imaging of the tricuspid annulus. J Am Soc Echocardiogr 2007;20:1167-71.
15Haddad F, Hunt SA, Rosenthal DN, Murphy DJ. Right ventricular function in cardiovascular disease, part I: Anatomy, physiology, aging, and functional assessment of the right ventricle. Circulation 2008;117:1436-48.
16Ho SY, Nihoyannopoulos P. Anatomy, echocardiography, and normal right ventricular dimensions. Heart 2006;92 Suppl 1:i2-13.
17Lang RM, Badano LP, Tsang W, Adams DH, Agricola E, Buck T, et al. EAE/ASE recommendations for image acquisition and display using three-dimensional echocardiography. J Am Soc Echocardiogr 2012;25:3-46.
18D'Andrea A, Salerno G, Scarafile R, Riegler L, Gravino R, Castaldo F, et al. Right ventricular myocardial function in patients with either idiopathic or ischemic dilated cardiomyopathy without clinical sign of right heart failure: Effects of cardiac resynchronization therapy. Pacing Clin Electrophysiol 2009;32:1017-29.
19Aksoy H, Okutucu S, Aytemir K, Kaya EB, Tulumen E, Evranos B, et al. Improvement in right ventricular systolic function after cardiac resynchronization therapy correlates with left ventricular reverse remodeling. Pacing Clin Electrophysiol 2011;34:200-7.
20Rajagopalan N, Suffoletto MS, Tanabe M, Miske G, Thomas NC, Simon MA, et al. Right ventricular function following cardiac resynchronization therapy. Am J Cardiol 2007;100:1434-6.
21Miranda RI, Nault M, Simpson CS, Michael KA, Abdollah H, Baranchuk A, et al. The right ventricular septum presents the optimum site for maximal electrical separation during left ventricular pacing. J Cardiovasc Electrophysiol 2012;23:370-4.
22Damy T, Ghio S, Rigby AS, Hittinger L, Jacobs S, Leyva F, et al. Interplay between right ventricular function and cardiac resynchronization therapy: An analysis of the CARE-HF trial (Cardiac resynchronization-heart failure). J Am Coll Cardiol 2013;61:2153-60.
23Guendouz S, Rappeneau S, Nahum J, Dubois-Randé JL, Gueret P, Monin JL, et al. Prognostic significance and normal values of 2D strain to assess right ventricular systolic function in chronic heart failure. Circ J 2012;76:127-36.
24Donal E, Thibault H, Bergerot C, Leroux PY, Cannesson M, Thivolet S, et al. Right ventricular pump function after cardiac resynchronization therapy: A strain imaging study. Arch Cardiovasc Dis 2008;101:475-84.
25Bleeker GB, Schalij MJ, Nihoyannopoulos P, Steendijk P, Molhoek SG, van Erven L, et al. Left ventricular dyssynchrony predicts right ventricular remodeling after cardiac resynchronization therapy. J Am Coll Cardiol 2005;46:2264-9.
26Dalsgaard M, Snyder EM, Kjaergaard J, Johnson BD, Hassager C, Oh JK, et al. Isovolumic acceleration measured by tissue Doppler echocardiography is preload independent in healthy subjects. Echocardiography 2007;24:572-9.
27Toyono M, Harada K, Tamura M, Yamamoto F, Takada G. Myocardial acceleration during isovolumic contraction as a new index of right ventricular contractile function and its relation to pulmonary regurgitation in patients after repair of tetralogy of Fallot. J Am Soc Echocardiogr 2004;17:332-7.
28Schattke S, Knebel F, Grohmann A, Dreger H, Kmezik F, Riemekasten G, et al. Early right ventricular systolic dysfunction in patients with systemic sclerosis without pulmonary hypertension: A Doppler tissue and speckle tracking echocardiography study. Cardiovasc Ultrasound 2010;8:3.
29Schwarz K, Singh S, Dawson D, Frenneaux MP. Right ventricular function in left ventricular disease: Pathophysiology and implications. Heart Lung Circ 2013;22:507-11.
30Cappelli F, Cristina Porciani M, Ricceri I, Perrotta L, Ricciardi G, Pieragnoli P, et al. Tricuspid annular plane systolic excursion evaluation improves selection of cardiac resynchronization therapy patients. Clin Cardiol 2010;33:578-82.