PMID- 37504543
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231102
IS  - 2308-3425 (Electronic)
IS  - 2308-3425 (Linking)
VI  - 10
IP  - 7
DP  - 2023 Jul 5
TI  - Metabolic Approaches for the Treatment of Dilated Cardiomyopathy.
LID - 10.3390/jcdd10070287 [doi]
LID - 287
AB  - In dilated cardiomyopathy (DCM), where the heart muscle becomes stretched and 
      thin, heart failure (HF) occurs, and the cardiomyocytes suffer from an energetic 
      inefficiency caused by an abnormal cardiac metabolism. Although underappreciated 
      as a potential therapeutic target, the optimal metabolic milieu of a failing 
      heart is still largely unknown and subject to debate. Because glucose naturally 
      has a lower P/O ratio (the ATP yield per oxygen atom), the previous studies using 
      this strategy to increase glucose oxidation have produced some intriguing 
      findings. In reality, the vast majority of small-scale pilot trials using 
      trimetazidine, ranolazine, perhexiline, and etomoxir have demonstrated enhanced 
      left ventricular (LV) function and, in some circumstances, myocardial energetics 
      in chronic ischemic and non-ischemic HF with a reduced ejection fraction (EF). 
      However, for unidentified reasons, none of these drugs has ever been tested in a 
      clinical trial of sufficient size. Other pilot studies came to the conclusion 
      that because the heart in severe dilated cardiomyopathy appears to be 
      metabolically flexible and not limited by oxygen, the current rationale for 
      increasing glucose oxidation as a therapeutic target is contradicted and 
      increasing fatty acid oxidation is supported. As a result, treating metabolic 
      dysfunction in HF may benefit from raising ketone body levels. Interestingly, 
      treatment with sodium-glucose cotransporter-2 inhibitors (SGLT2i) improves 
      cardiac function and outcomes in HF patients with or without type 2 diabetes 
      mellitus (T2DM) through a variety of pleiotropic effects, such as elevated ketone 
      body levels. The improvement in overall cardiac function seen in patients 
      receiving SGLT2i could be explained by this increase, which appears to be a 
      reflection of an adaptive process that optimizes cardiac energy metabolism. This 
      review aims to identify the best metabolic therapeutic approach for DCM patients, 
      to examine the drugs that directly affect cardiac metabolism, and to outline all 
      the potential ancillary metabolic effects of the guideline-directed medical 
      therapy. In addition, a special focus is placed on SGLT2i, which were first 
      studied and prescribed to diabetic patients before being successfully 
      incorporated into the pharmacological arsenal for HF patients.
FAU - Spoladore, Roberto
AU  - Spoladore R
AD  - Department of Cardiology, Heart Failure Clinic, Alessandro Manzoni Hospital, ASST 
      Lecco, 23900 Lecco, Italy.
FAU - Pinto, Giuseppe
AU  - Pinto G
AUID- ORCID: 0000-0003-2213-2955
AD  - IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy.
FAU - Daus, Francesca
AU  - Daus F
AD  - Post-Graduate School of Cardiovascular Medicine, Milan-Bicocca University, 20126 
      Milan, Italy.
FAU - Pezzini, Sara
AU  - Pezzini S
AD  - Post-Graduate School of Cardiovascular Medicine, Milan-Bicocca University, 20126 
      Milan, Italy.
FAU - Kolios, Damianos
AU  - Kolios D
AD  - Department of Clinical Cardiology, Heart Failure Clinic, IRCCS San Raffaele 
      Scientific Institute, 20132 Milan, Italy.
FAU - Fragasso, Gabriele
AU  - Fragasso G
AD  - Department of Clinical Cardiology, Heart Failure Clinic, IRCCS San Raffaele 
      Scientific Institute, 20132 Milan, Italy.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20230705
PL  - Switzerland
TA  - J Cardiovasc Dev Dis
JT  - Journal of cardiovascular development and disease
JID - 101651414
PMC - PMC10380730
OTO - NOTNLM
OT  - SGLT2 inhibitors
OT  - dilated cardiomyopathy
OT  - heart failure
OT  - metabolic therapy
OT  - myocardial energetics
COIS- The authors declare no conflict of interest.
EDAT- 2023/07/28 13:10
MHDA- 2023/07/28 13:11
PMCR- 2023/07/05
CRDT- 2023/07/28 09:03
PHST- 2023/05/31 00:00 [received]
PHST- 2023/06/25 00:00 [revised]
PHST- 2023/06/26 00:00 [accepted]
PHST- 2023/07/28 13:11 [medline]
PHST- 2023/07/28 13:10 [pubmed]
PHST- 2023/07/28 09:03 [entrez]
PHST- 2023/07/05 00:00 [pmc-release]
AID - jcdd10070287 [pii]
AID - jcdd-10-00287 [pii]
AID - 10.3390/jcdd10070287 [doi]
PST - epublish
SO  - J Cardiovasc Dev Dis. 2023 Jul 5;10(7):287. doi: 10.3390/jcdd10070287.