Clinical trial NCT06002321: Right Ventricular Dysfunction in Chronic Heart Failure
Official title: Right Ventricular Dysfunction in Chronic Heart Failure: Clinical Laboratory and Echocardiographic Characteristics
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Chronic Heart Failure
Right Ventricular Dysfunction
Right Heart Failure
Lead sponsor: University of Siena
Sponsor class: OTHER
Collaborators: name: Italian Society of Cardiology
First posted: 2023-08-21
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All patients with chronic heart failure will be consecutively enrolled prospectively in different cities. The diagnosis will be made on the basis of the signs and symptoms of the disease associated with BNP and NT-proBNP levels. Patients will be classified according to the type of cardiac structure and remodeling defect and ejection fraction.

Brief summary: The goal of this multi center observational prospective study is to analyze the concordance between the signs and symptoms of RHF and echocardiographic features of RVD in patient with heart failure. The main questions it aims to answer are:

1. to assess the incidence of RVH and RVD in each HF subtypes.
2. to evaluate prognostic impact ( in terms of cardiovascular mortality and HF hospitalization) of different RVD patterns during a mean followup period of 3 years
3. To investigate the incidence of different RV maladaptation ( isolated RV dilatation, isolated Pulmonary hypertension, combined pattern) in each HF groups and the related outcome.

Participants will follow by direct check up visit and/or virtual visits every 6 months for a mean follow-up period of 3 years.

Detailed description: Right ventricular dysfunction (RVD) and pulmonary hypertension (PH) have been recognized as two important prognostic features in patients with left side heart failure (HF). Nevertheless literature does not distinguish between right heart failure (RHF) and RVD, and the two terms are indifferently employed to describe PH and impaired RV performance. This is a multicenter observational prospective study endorsed by the Italian Society of Cardiology that would analyse the concordance between the signs and symptoms of RHF and echocardiographic features of RVD. Therefore the right ventricle (RV) adaptation across different left ventricular ejection fraction (LVEF) values, is poorly investigated. According to the recent heart failure (HF) guidelines classified patients based on LVEF in HF with preserved ( HFpEF) mild reduced (HFmEF) and reduced LVEF ( HFrEF), the investigators would assess by seral clinical laboratory and detailed echocardiographic study all patients affected by chronic HF regardless LVEF threshold in stable condition and will follow by direct check up visit and/or virtual visits every 6 months for a mean follow-up period of 3 years. All clinical laboratory and echocardiographic data will be recorded in a web platform system accessible for all center included in the study The main aims of the study are; 1- to assess the incidence of RVH and RVD in each HF subtypes. 2- to evaluate prognostic impact ( in terms of cardiovascular mortality and HF hospitalization) of different RVD patterns during a mean followup period of 3 years 3- To investigate the incidence of different RV maladaptation ( isolated RV dilatation, isolated Pulmonary hypertension, combined pattern) in each HF groups and the related outcome. The investigators expect to find different RVD degree and severity according to the type of left HF and its severity. Additionally, by a serial multiparametric analysis of RV, it would be possible to establish the stage and type of RVD and consequent concordance with signs of RHF.

Eligibility criteria: Inclusion Criteria:

* All patients with a diagnosis of chronic heart failure made according to the recommendations of the ESC guidelines through the simultaneous presence of signs and symptoms of disease associated with BNP and NT proBNP levels \> 100 and 300 pg/ml respectively which are associated with a modest increase PAPS \> 30 mmHg with or without right ventricular dilatation.

Exclusion Criteria:

* Patients with dyspnea of non-cardiogenic origin, related to systemic respiratory diseases, pulmonary embolism, patients with primary pulmonary hypertension will be excluded.
* Patients with heart failure linked to primary valvular pathologies or infiltrative pathologies, secondary and on a genetic basis, patients diagnosed with acute heart failure in non-optimized therapy for at least 3 months will also be excluded. - Patients with systemic inflammatory neoplastic diseases, advanced liver and kidney diseases awaiting transplantation will be excluded.

Primary outcomes:
measure: Different patterns of RVD in chronic heart failure.
timeFrame: 6 months.
measure: Analyze the incidence and prevalence of RVD and RHF.
timeFrame: 6 months.
measure: Compare the clinical signs of right heart failure with the echocardiographic signs of RVD.
timeFrame: 6 months.
Secondary outcomes:
measure: Define the incidence of RVD.
timeFrame: 6 months.
measure: Investigate a correlation between the different parameters.
timeFrame: 6 months.
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Centro Cardiologico Monzino
state: Milano
city: Fisciano
country: Italy
facility: Department of Medicine, Surgery and Dentistry, Università di Salerno
state: Salerno
city: Foggia
country: Italy
facility: SC Universitaria di Cardiologia - UTIC Policlinico Riuniti Foggia
city: Messina
country: Italy
facility: Department of Clinical and Experimental Medicine, Operativee Unit of Cardiology, University of Messina
city: Milano
country: Italy
facility: Ospedale Sant'Agostino Milano
city: Napoli
country: Italy
facility: Department of Translational Medical Sciences, CIRCET
city: Napoli
country: Italy
facility: Department of Translational Medical Sciences, Federico II University, CIRCET
city: Napoli
country: Italy
facility: Heart Failure Unit, Department of Cardiology, AORN dei Colli-Monaldi
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo - Pavia UOC Cardiologia 1
city: Perugia
country: Italy
facility: S. Maria della Misericordia Hospital
city: Potenza
country: Italy
facility: SC Cardiologia, Azienda Ospedaliera Ospedale San Carlo Potenza
city: Roma
country: Italy
facility: Cardiology, Department of Clinica, Internal, Anesthesiology and Cardiovascular Scienses, Sapienza.
city: Roma
country: Italy
facility: Cardiology, Department of Clinica, Internal, Anesthesiology and Cardiovascular Scienses.
city: Siena
country: Italy
facility: Unità di Malattie Cardiovascolari, Dipartimento Cardio-Toraco-Vascolare AOUS, Università degli Studi, Siena.
Study officials:
affiliation: Unità di Malattie Cardiovascolari, Dipartimento Cardio-Toraco-Vascolare AOUS, Siena
name: Alberto Palazzuoli, MD
role: STUDY_DIRECTOR
References:
citation: Furey SA 3rd, Zieske HA, Levy MN. The essential function of the right ventricle. Am Heart J. 1984 Feb;107(2):404-10. doi: 10.1016/0002-8703(84)90402-2. No abstract available.
citation: Poels EM, da Costa Martins PA, van Empel VP. Adaptive capacity of the right ventricle: why does it fail? Am J Physiol Heart Circ Physiol. 2015 Apr 15;308(8):H803-13. doi: 10.1152/ajpheart.00573.2014. Epub 2015 Feb 13.
citation: Haddad F, Doyle R, Murphy DJ, Hunt SA. Right ventricular function in cardiovascular disease, part II: pathophysiology, clinical importance, and management of right ventricular failure. Circulation. 2008 Apr 1;117(13):1717-31. doi: 10.1161/CIRCULATIONAHA.107.653584. No abstract available.
citation: Meyer P, Filippatos GS, Ahmed MI, Iskandrian AE, Bittner V, Perry GJ, White M, Aban IB, Mujib M, Dell'Italia LJ, Ahmed A. Effects of right ventricular ejection fraction on outcomes in chronic systolic heart failure. Circulation. 2010 Jan 19;121(2):252-8. doi: 10.1161/CIRCULATIONAHA.109.887570. Epub 2010 Jan 4.
citation: Voelkel NF, Gomez-Arroyo J, Abbate A, Bogaard HJ. Mechanisms of right heart failure-A work in progress and a plea for failure prevention. Pulm Circ. 2013 Jan;3(1):137-43. doi: 10.4103/2045-8932.109957. No abstract available.
citation: Markel TA, Wairiuko GM, Lahm T, Crisostomo PR, Wang M, Herring CM, Meldrum DR. The right heart and its distinct mechanisms of development, function, and failure. J Surg Res. 2008 May 15;146(2):304-13. doi: 10.1016/j.jss.2007.04.003. Epub 2007 Nov 26.
citation: Ghio S, Acquaro M, Agostoni P, Ambrosio G, Carluccio E, Castiglione V, Colombo D, D'Alto M, Delle Grottaglie S, Dini FL, Emdin M, Fortunato M, Guaricci AI, Jacoangeli F, Marra AM, Paolillo S, Papa S, Scajola LV, Correale M, Palazzuoli A. Right heart failure in left heart disease: imaging, functional, and biochemical aspects of right ventricular dysfunction. Heart Fail Rev. 2023 Jul;28(4):1009-1022. doi: 10.1007/s10741-022-10276-0. Epub 2022 Nov 16.
citation: de Groote P, Millaire A, Foucher-Hossein C, Nugue O, Marchandise X, Ducloux G, Lablanche JM. Right ventricular ejection fraction is an independent predictor of survival in patients with moderate heart failure. J Am Coll Cardiol. 1998 Oct;32(4):948-54. doi: 10.1016/s0735-1097(98)00337-4.
citation: Gorter TM, van Veldhuisen DJ, Bauersachs J, Borlaug BA, Celutkiene J, Coats AJS, Crespo-Leiro MG, Guazzi M, Harjola VP, Heymans S, Hill L, Lainscak M, Lam CSP, Lund LH, Lyon AR, Mebazaa A, Mueller C, Paulus WJ, Pieske B, Piepoli MF, Ruschitzka F, Rutten FH, Seferovic PM, Solomon SD, Shah SJ, Triposkiadis F, Wachter R, Tschope C, de Boer RA. Right heart dysfunction and failure in heart failure with preserved ejection fraction: mechanisms and management. Position statement on behalf of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2018 Jan;20(1):16-37. doi: 10.1002/ejhf.1029. Epub 2017 Oct 16.
citation: Nagueh SF, Bhatt R, Vivo RP, Krim SR, Sarvari SI, Russell K, Edvardsen T, Smiseth OA, Estep JD. Echocardiographic evaluation of hemodynamics in patients with decompensated systolic heart failure. Circ Cardiovasc Imaging. 2011 May;4(3):220-7. doi: 10.1161/CIRCIMAGING.111.963496. Epub 2011 Mar 11.
citation: Sanz J, Sanchez-Quintana D, Bossone E, Bogaard HJ, Naeije R. Anatomy, Function, and Dysfunction of the Right Ventricle: JACC State-of-the-Art Review. J Am Coll Cardiol. 2019 Apr 2;73(12):1463-1482. doi: 10.1016/j.jacc.2018.12.076.
citation: Drazner MH, Hamilton MA, Fonarow G, Creaser J, Flavell C, Stevenson LW. Relationship between right and left-sided filling pressures in 1000 patients with advanced heart failure. J Heart Lung Transplant. 1999 Nov;18(11):1126-32. doi: 10.1016/s1053-2498(99)00070-4.
citation: Melenovsky V, Hwang SJ, Lin G, Redfield MM, Borlaug BA. Right heart dysfunction in heart failure with preserved ejection fraction. Eur Heart J. 2014 Dec 21;35(48):3452-62. doi: 10.1093/eurheartj/ehu193. Epub 2014 May 29.
citation: Bosch L, Lam CSP, Gong L, Chan SP, Sim D, Yeo D, Jaufeerally F, Leong KTG, Ong HY, Ng TP, Richards AM, Arslan F, Ling LH. Right ventricular dysfunction in left-sided heart failure with preserved versus reduced ejection fraction. Eur J Heart Fail. 2017 Dec;19(12):1664-1671. doi: 10.1002/ejhf.873. Epub 2017 Jun 8.
citation: Gorter TM, Hoendermis ES, van Veldhuisen DJ, Voors AA, Lam CS, Geelhoed B, Willems TP, van Melle JP. Right ventricular dysfunction in heart failure with preserved ejection fraction: a systematic review and meta-analysis. Eur J Heart Fail. 2016 Dec;18(12):1472-1487. doi: 10.1002/ejhf.630. Epub 2016 Sep 20.
citation: Guazzi M, Borlaug BA. Pulmonary hypertension due to left heart disease. Circulation. 2012 Aug 21;126(8):975-90. doi: 10.1161/CIRCULATIONAHA.111.085761. No abstract available.
citation: Konstam MA, Kiernan MS, Bernstein D, Bozkurt B, Jacob M, Kapur NK, Kociol RD, Lewis EF, Mehra MR, Pagani FD, Raval AN, Ward C; American Heart Association Council on Clinical Cardiology; Council on Cardiovascular Disease in the Young; and Council on Cardiovascular Surgery and Anesthesia. Evaluation and Management of Right-Sided Heart Failure: A Scientific Statement From the American Heart Association. Circulation. 2018 May 15;137(20):e578-e622. doi: 10.1161/CIR.0000000000000560. Epub 2018 Apr 12.
citation: Puwanant S, Priester TC, Mookadam F, Bruce CJ, Redfield MM, Chandrasekaran K. Right ventricular function in patients with preserved and reduced ejection fraction heart failure. Eur J Echocardiogr. 2009 Aug;10(6):733-7. doi: 10.1093/ejechocard/jep052. Epub 2009 May 13.
citation: Barilli M, Tavera MC, Valente S, Palazzuoli A. Structural and Hemodynamic Changes of the Right Ventricle in PH-HFpEF. Int J Mol Sci. 2022 Apr 20;23(9):4554. doi: 10.3390/ijms23094554.
citation: Dini FL, Pugliese NR, Ameri P, Attanasio U, Badagliacca R, Correale M, Mercurio V, Tocchetti CG, Agostoni P, Palazzuoli A; Heart Failure Study Group of the Italian Society of Cardiology. Right ventricular failure in left heart disease: from pathophysiology to clinical manifestations and prognosis. Heart Fail Rev. 2023 Jul;28(4):757-766. doi: 10.1007/s10741-022-10282-2. Epub 2022 Oct 26.
citation: Schmeisser A, Rauwolf T, Groscheck T, Kropf S, Luani B, Tanev I, Hansen M, Meissler S, Steendijk P, Braun-Dullaeus RC. Pressure-volume loop validation of TAPSE/PASP for right ventricular arterial coupling in heart failure with pulmonary hypertension. Eur Heart J Cardiovasc Imaging. 2021 Jan 22;22(2):168-176. doi: 10.1093/ehjci/jeaa285.
citation: Guazzi M, Bandera F, Pelissero G, Castelvecchio S, Menicanti L, Ghio S, Temporelli PL, Arena R. Tricuspid annular plane systolic excursion and pulmonary arterial systolic pressure relationship in heart failure: an index of right ventricular contractile function and prognosis. Am J Physiol Heart Circ Physiol. 2013 Nov 1;305(9):H1373-81. doi: 10.1152/ajpheart.00157.2013. Epub 2013 Aug 30.
citation: Guazzi M, Dixon D, Labate V, Beussink-Nelson L, Bandera F, Cuttica MJ, Shah SJ. RV Contractile Function and its Coupling to Pulmonary Circulation in Heart Failure With Preserved Ejection Fraction: Stratification of Clinical Phenotypes and Outcomes. JACC Cardiovasc Imaging. 2017 Oct;10(10 Pt B):1211-1221. doi: 10.1016/j.jcmg.2016.12.024. Epub 2017 Apr 12.
citation: Gheorghiade M, Follath F, Ponikowski P, Barsuk JH, Blair JE, Cleland JG, Dickstein K, Drazner MH, Fonarow GC, Jaarsma T, Jondeau G, Sendon JL, Mebazaa A, Metra M, Nieminen M, Pang PS, Seferovic P, Stevenson LW, van Veldhuisen DJ, Zannad F, Anker SD, Rhodes A, McMurray JJ, Filippatos G; European Society of Cardiology; European Society of Intensive Care Medicine. Assessing and grading congestion in acute heart failure: a scientific statement from the acute heart failure committee of the heart failure association of the European Society of Cardiology and endorsed by the European Society of Intensive Care Medicine. Eur J Heart Fail. 2010 May;12(5):423-33. doi: 10.1093/eurjhf/hfq045. Epub 2010 Mar 30.
citation: McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Bohm M, Burri H, Butler J, Celutkiene J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A; ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021 Sep 21;42(36):3599-3726. doi: 10.1093/eurheartj/ehab368. No abstract available.
citation: Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, Flachskampf FA, Foster E, Goldstein SA, Kuznetsova T, Lancellotti P, Muraru D, Picard MH, Rietzschel ER, Rudski L, Spencer KT, Tsang W, Voigt JU. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2015 Jan;28(1):1-39.e14. doi: 10.1016/j.echo.2014.10.003.
citation: Rudski LG, Lai WW, Afilalo J, Hua L, Handschumacher MD, Chandrasekaran K, Solomon SD, Louie EK, Schiller NB. 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 Jul;23(7):685-713; quiz 786-8. doi: 10.1016/j.echo.2010.05.010. No abstract available.
citation: Harjola VP, Mebazaa A, Celutkiene J, Bettex D, Bueno H, Chioncel O, Crespo-Leiro MG, Falk V, Filippatos G, Gibbs S, Leite-Moreira A, Lassus J, Masip J, Mueller C, Mullens W, Naeije R, Nordegraaf AV, Parissis J, Riley JP, Ristic A, Rosano G, Rudiger A, Ruschitzka F, Seferovic P, Sztrymf B, Vieillard-Baron A, Yilmaz MB, Konstantinides S. Contemporary management of acute right ventricular failure: a statement from the Heart Failure Association and the Working Group on Pulmonary Circulation and Right Ventricular Function of the European Society of Cardiology. Eur J Heart Fail. 2016 Mar;18(3):226-41. doi: 10.1002/ejhf.478.
citation: Drazner MH, Rame JE, Stevenson LW, Dries DL. Prognostic importance of elevated jugular venous pressure and a third heart sound in patients with heart failure. N Engl J Med. 2001 Aug 23;345(8):574-81. doi: 10.1056/NEJMoa010641.
citation: Ghio S, Guazzi M, Scardovi AB, Klersy C, Clemenza F, Carluccio E, Temporelli PL, Rossi A, Faggiano P, Traversi E, Vriz O, Dini FL; all investigators. Different correlates but similar prognostic implications for right ventricular dysfunction in heart failure patients with reduced or preserved ejection fraction. Eur J Heart Fail. 2017 Jul;19(7):873-879. doi: 10.1002/ejhf.664. Epub 2016 Nov 17.
citation: Guazzi M, Naeije R. Pulmonary Hypertension in Heart Failure: Pathophysiology, Pathobiology, and Emerging Clinical Perspectives. J Am Coll Cardiol. 2017 Apr 4;69(13):1718-1734. doi: 10.1016/j.jacc.2017.01.051.