Diabetes and Lipid Accumulationand Heart Transplant

NCT03546062 | Completed Results

• 1 other identifier: DCM-AHEAD
• Study Type: observational
• Target: 177
• Locations: 1 country
• Sites: 2

Brief Summary

Idiopathic dilated cardiomyopathy (IDC) is defined by the presence of left ventricular systolic dysfunction in the absence of an abnormal loading condition or significant coronary artery disease. IDC is the main cause of end-stage heart failure (HF) and is responsible for half of all heart transplants (HTx). Endocrine disorders, including diabetes, are known to be associated with IDC. Diabetes mellitus (DM), which is present in 75% of patients with idiopathic IDC, is an independent risk factor for the development of heart failure and death in IDC. Therefore, DM can exacerbate the need for HTx, in addition, diabetic patients are less suitable for HTx and DM remains an independent risk factor for death even after HTx. Recent studies have revealed the presence of diabetic cardiomyopathy, a condition of myocardial dysfunction without coronary artery disease. This term was introduced for the first time by Rubler et al. in 1972 which highlighted patients with diabetes and congestive heart failure with normal coronary arteries. The pathophysiological mechanisms through which diabetes affects the development and progression of diabetic heart disease are not known. Therefore, the purpose of our study will be to evaluate, in the explanted diabetic heart, the presence of possible cellular alterations attributable to the diabetic disease. Furthermore, the progression of these lesions in the transplanted heart in diabetic patients will be evaluated.

Conditions

Diabetes Mellitus; Heart Failure

Outcome Measures

Primary Outcomes (1)

• Myocyte Lipid Accumulation as Oil Red-O Positive Biopsie

  Authors will evaluate myocyte lipid accumulation as Oil Red-O positive biopsie after heart transplant at follow up.

  12 months.

Study Arms (3)

T2DM patients treated by HTx

Authors will include a population of T2DM patients with advanced heart failure and treated by heart transplant. 41 patients recluted from January 2015

Other: patients treated by HTx

T2DM Metformin treated by HTx

Authors will include a population of T2DM patients with advanced heart failure and treated by heart transplant in metformin therapy. 35 patients recluted from January 2015

Other: patients treated by HTx

Non-diabetic patients treated by HTx

Authors will include a population of non-diabetic patients with advanced heart failure treated by heart transplant. 82 patients recluted from January 2015

Other: patients treated by HTx

Interventions

patients treated by HTx OTHER

From removed and frozen hearts, authors will conduct a tissue and molecular analysis of possible mechanisms T2DM linked.

Non-diabetic patients treated by HTx; T2DM Metformin treated by HTx; T2DM patients treated by HTx

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Two main groups according to whether patients did or did not have pre-transplantation diabetes. Patients with DM for at least 6 months before HTX, with optimal glycemic control (HbA1c \<7.0), BMI \<30kg/m2, without severe secondary end-organ disease will be included. Patients with endomyocardial biopsy specimens consistent with ISHLT Grade 2R considered positive for rejection, increased T4/T8 ratio, positive IgM and/or IgG Cytomegalovirus antibodies, and with post-HTX diabetes will be excluded.

You may qualify if:

• type 2 diabetes mellitus (T2DM);
• heart failure in III/IV NYHA class
• patients with clear indication to receive heart transplantation (HTx).

You may not qualify if:

• aged \< 18 years
• aged \>75 years
• non T2DM diagnosis
• controindication to receive HTx.

Sponsors & Collaborators

• University of Campania Luigi Vanvitelli: lead

Study Sites (2)

Celestino Sardu

Naples, 80138, Italy

Location

Raffaele Marfella

Naples, 80138, Italy

Location

Related Publications (3)

• Marfella R, D'Onofrio N, Mansueto G, Grimaldi V, Trotta MC, Sardu C, Sasso FC, Scisciola L, Amarelli C, Esposito S, D'Amico M, Golino P, De Feo M, Signoriello G, Paolisso P, Gallinoro E, Vanderheyden M, Maiello C, Balestrieri ML, Barbato E, Napoli C, Paolisso G. Glycated ACE2 reduces anti-remodeling effects of renin-angiotensin system inhibition in human diabetic hearts. Cardiovasc Diabetol. 2022 Aug 5;21(1):146. doi: 10.1186/s12933-022-01573-x.

  PMID: 35932065 DERIVED

• Marfella R, D'Onofrio N, Trotta MC, Sardu C, Scisciola L, Amarelli C, Balestrieri ML, Grimaldi V, Mansueto G, Esposito S, D'Amico M, Golino P, Signoriello G, De Feo M, Maiello C, Napoli C, Paolisso G. Sodium/glucose cotransporter 2 (SGLT2) inhibitors improve cardiac function by reducing JunD expression in human diabetic hearts. Metabolism. 2022 Feb;127:154936. doi: 10.1016/j.metabol.2021.154936. Epub 2021 Nov 18.

  PMID: 34801581 DERIVED

• Marfella R, Amarelli C, Cacciatore F, Balestrieri ML, Mansueto G, D'Onofrio N, Esposito S, Mattucci I, Salerno G, De Feo M, D'Amico M, Golino P, Maiello C, Paolisso G, Napoli C. Lipid Accumulation in Hearts Transplanted From Nondiabetic Donors to Diabetic Recipients. J Am Coll Cardiol. 2020 Mar 24;75(11):1249-1262. doi: 10.1016/j.jacc.2020.01.018.

  PMID: 32192650 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

The patients received in the past heart transplant. In the removed and frizzed hearts authors will extract portions of septal wall. From this tissue authors will analyze inflammatory markers and microRNAs involved in the progression of cardiac disease.

MeSH Terms

Conditions

Diabetes Mellitus; Heart Failure

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Heart Diseases; Cardiovascular Diseases

Limitations and Caveats

Our real life study is not multi-center study and thus we need to extend our observations to a larger cohort of randomized patients. Second, immunosuppressive therapy by per se could affect molecular mechanisms of DMCM.

Results Point of Contact

• Title: Raffaele Marfella
• Organization: Università degli studi della Campania "luigi Vanvitelli"

raffaele.marfella@unicampania.it

+390815665110

Study Officials

• Raffaele Marfella, MD

  Università della Campania Luigi Vanvitelli

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: primary investigator

Study Record Dates

• First Submitted: May 22, 2018
• First Posted: June 6, 2018
• Study Start: January 1, 2010
• Primary Completion: January 1, 2018
• Study Completion: May 1, 2018
• Last Updated: April 20, 2023
• Results First Posted: April 20, 2023

Record last verified: 2023-04

Locations

IT (2)