Evaluating Adherence to Guideline-Directed Medical Therapy in Patients With Advanced Heart Failure

A Prospective Observational, Multi-Center, Real-World Pharmacological Study Evaluating Adherence to Guideline-Directed Medical Therapy Using the Four-Pillar Strategy in Patients with Advanced Heart Failure. Patients will be managed according to routine clinical practice, and no additional treatments are required as part of participation in this study.

As this is an observational study, data on the pharmacological therapies taken by the patients according to routine clinical practice will be recorded, without any modification resulting from participation in the present study. The medications are therefore in the patients' possession and are taken orally according to medical prescription, in accordance with the dosages and indications provided in the package leaflet.

In particular, GDMT consists of a combination of four classes of medications, which each patient may receive: one renin-angiotensin-aldosterone system drug, one beta-blocker, one mineralcorticoid receptor antagonist and one SGLT2 Inhibitor.

• GDMT (Drug), also known as beta-blocker, mineralcorticoid receptor antagonist, SGLT2 inhibitor, renin-angiotensin-aldosterone system drug: Percentage of patients receiving GDMT in advanced heart failure
• Quality of life questionnaire (Other): Absoute Quality of life questionnaire scores (SF 36 questionnaire and EqVAS scale, both validated in Italian language

Primary outcomes

• assess the adherence to guideline-directed medical therapy in patients with advanced heart failure [3 months, 6 months, 1 year, 2 years, 5 years]: Percentage of patients receiving GDMT in advanced heart failure

Secondary outcomes

• assess the level of quality of life in patients under study [3 months, 6 months, 1 year, 2 years, 5 years]: Absoute Quality of life questionnaire scores (short form 36, SF 36, questionnaire and EuroQol Visual Analogue Scale, EqVAS scale, both validated in Italian language). Scored on a 0-100 scale, where higher scores indicate better health.

Sex: All, ages: 18 Years to 75 Years

Inclusion Criteria:

1. Age > 18 and < 75 years
2. Heart failure with left ventricular ejection fraction ≤ 35%
3. Persistent symptoms of heart failure, New York Heart Association class III or IV
4. Requirement for high-dose diuretic therapy, specifically Furosemide > 50 mg/day orally as per routine clinical practice
5. At least one of the following additional indicators of severity or refractoriness:
6. need for progressive escalation of diuretics,
7. intolerance to optimized medical therapy,
8. persistence of symptoms despite advanced treatments such as (but not limited to) cardiac resynchronization therapy (CRT-D)and/or MitraClip
9. Ability and willingness to provide written informed consent for participation and for the processing of clinical data for research purposes

Exclusion Criteria:

1. Age ≤ 18 years or ≥ 75 years
2. Left ventricular ejection fraction > 35%
3. Mild or absent symptoms (New York Heart Association class I-II)
4. Good response to optimized conventional guideline-directed medical therapy
5. Extreme frailty or severe non-reversible disability, or psychiatric or cognitive disorders preventing adherence to follow-up
6. Pregnant or breastfeeding women

• European Society of Cardiology Heart Failure Long-Term Registry (ESC-HF-LT): 1-year follow-up outcomes and differences across regions. Eur J Heart Fail. 2017 Mar;19(3):438. doi: 10.1002/ejhf.772. No abstract available. PMID 28251778
• Adamo M, Gardner RS, McDonagh TA, Metra M. The 'Ten Commandments' of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2022 Feb 10;43(6):440-441. doi: 10.1093/eurheartj/ehab853. No abstract available. PMID 34922348
• Tannenbaum C, Ellis RP, Eyssel F, Zou J, Schiebinger L. Sex and gender analysis improves science and engineering. Nature. 2019 Nov;575(7781):137-146. doi: 10.1038/s41586-019-1657-6. Epub 2019 Nov 6. PMID 31695204
• Piano per l'applicazione e la diffusione della medicina di genere - Ministero della Salute, 2021.
• Regolamento (UE) 2017/745 sui dispositivi medici.
• Regione Lombardia. Deliberazione della Giunta Regionale n. XI/3522 del 5 agosto 2020. "Indicazioni e requisiti per l'ulteriore efficientamento organizzativo della rete cardiovascolare regionale". Milano: Regione Lombardia; 2020.Regolamento (UE) 2016/679 del Parlamento Europeo e del Consiglio del 27 aprile 2016 (GDPR).
• SAGER Guidelines - Sex and Gender Equity in Research.
• Baksh G, Haydo M, Frazier S et al Improving Utilization of Guideline-Directed Medical Therapy for Heart Failure J Nurse Pract 2024;20:105108
• Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, Fang JC, Fedson SE, Fonarow GC, Hayek SS, Hernandez AF, Khazanie P, Kittleson MM, Lee CS, Link MS, Milano CA, Nnacheta LC, Sandhu AT, Stevenson LW, Vardeny O, Vest AR, Yancy CW; ACC/AHA Joint Committee Members. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022 May 3;145(18):e895-e1032. doi: 10.1161/CIR.0000000000001063. Epub 2022 Apr 1. PMID 35363499

• Anna Maria Scandroglio, MD, Principal investigator, IRCCS Ospedale San Raffaele