Metabolic Approaches for the Treatment of Dilated Cardiomyopathy
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 mil...
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| Format: | Article |
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MDPI AG
2023-07-01
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| Series: | Journal of Cardiovascular Development and Disease |
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| Online Access: | https://www.mdpi.com/2308-3425/10/7/287 |
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| author | Roberto Spoladore Giuseppe Pinto Francesca Daus Sara Pezzini Damianos Kolios Gabriele Fragasso |
| author_facet | Roberto Spoladore Giuseppe Pinto Francesca Daus Sara Pezzini Damianos Kolios Gabriele Fragasso |
| author_sort | Roberto Spoladore |
| collection | DOAJ |
| description | 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. |
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| format | Article |
| id | doaj.art-8042646588884cf088e75c4da5237292 |
| institution | Directory Open Access Journal |
| issn | 2308-3425 |
| language | English |
| last_indexed | 2024-03-11T00:58:46Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Cardiovascular Development and Disease |
| spelling | doaj.art-8042646588884cf088e75c4da52372922023-11-18T19:50:08ZengMDPI AGJournal of Cardiovascular Development and Disease2308-34252023-07-0110728710.3390/jcdd10070287Metabolic Approaches for the Treatment of Dilated CardiomyopathyRoberto Spoladore0Giuseppe Pinto1Francesca Daus2Sara Pezzini3Damianos Kolios4Gabriele Fragasso5Department of Cardiology, Heart Failure Clinic, Alessandro Manzoni Hospital, ASST Lecco, 23900 Lecco, ItalyIRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, ItalyPost-Graduate School of Cardiovascular Medicine, Milan-Bicocca University, 20126 Milan, ItalyPost-Graduate School of Cardiovascular Medicine, Milan-Bicocca University, 20126 Milan, ItalyDepartment of Clinical Cardiology, Heart Failure Clinic, IRCCS San Raffaele Scientific Institute, 20132 Milan, ItalyDepartment of Clinical Cardiology, Heart Failure Clinic, IRCCS San Raffaele Scientific Institute, 20132 Milan, ItalyIn 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.https://www.mdpi.com/2308-3425/10/7/287dilated cardiomyopathyheart failuremetabolic therapymyocardial energeticsSGLT2 inhibitors |
| spellingShingle | Roberto Spoladore Giuseppe Pinto Francesca Daus Sara Pezzini Damianos Kolios Gabriele Fragasso Metabolic Approaches for the Treatment of Dilated Cardiomyopathy Journal of Cardiovascular Development and Disease dilated cardiomyopathy heart failure metabolic therapy myocardial energetics SGLT2 inhibitors |
| title | Metabolic Approaches for the Treatment of Dilated Cardiomyopathy |
| title_full | Metabolic Approaches for the Treatment of Dilated Cardiomyopathy |
| title_fullStr | Metabolic Approaches for the Treatment of Dilated Cardiomyopathy |
| title_full_unstemmed | Metabolic Approaches for the Treatment of Dilated Cardiomyopathy |
| title_short | Metabolic Approaches for the Treatment of Dilated Cardiomyopathy |
| title_sort | metabolic approaches for the treatment of dilated cardiomyopathy |
| topic | dilated cardiomyopathy heart failure metabolic therapy myocardial energetics SGLT2 inhibitors |
| url | https://www.mdpi.com/2308-3425/10/7/287 |
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