Revisiting Secondary Dilative Cardiomyopathy
Abstract
1. Introduction
2. Epidemiology
3. Etiology
4. Secondary Dilated Cardiomyopathy
5. Toxic Cardiomyopathy
6. Chemotherapy-Induced Cardiomyopathy
- Oxidative Stress: Anthracyclines undergo redox cycling, producing reactive oxygen species (ROS) that overwhelm the heart’s antioxidant defenses, leading to lipid peroxidation, mitochondrial damage, and apoptosis of cardiomyocytes [35];
- Topoisomerase IIβ Inhibition: Doxorubicin interferes with topoisomerase IIβ in cardiomyocytes, causing DNA double-strand breaks and triggering cell death pathways [36];
- Mitochondrial Dysfunction: The accumulation of anthracyclines in mitochondria disrupts electron transport chains, leading to energy depletion and further ROS production [37].
- Trastuzumab: A monoclonal antibody targeting HER2 receptors, trastuzumab disrupts cardiomyocyte survival pathways, leading to reversible cardiac dysfunction [39];
- Cyclophosphamide: An alkylating agent that can cause endothelial damage, leading to hemorrhagic myocarditis and subsequent DCM [40];
- 5-Fluorouracil (5-FU): An antimetabolite associated with coronary vasospasm and myocardial ischemia, potentially leading to DCM [41];
- Bevacizumab: An anti-VEGF agent that can induce hypertension and thromboembolic events, contributing to cardiac dysfunction [42].
7. Myocarditis, Inflammatory Cardiomyopathies, and Dilative Cardiomyopathy
8. Peripartum Cardiomyopathy
9. Other Causes of Dilative Cardiomyopathy
9.1. Rheumatic Fever
9.2. Endocrine-Related Dilative Cardiomyopathy
9.3. Sarcoidosis
9.4. Dyssynchronopathy: Left Bundle Branch Block-Induced Cardiomyopathy
9.5. Atrial Fibrillation-Induced Dilated Cardiomyopathy
9.6. Premature Ventricular Complex-Induced Cardiomyopathy
10. Diagnosis
10.1. Anamnesis and Clinical Examination
10.2. Electrocardiogram (ECG)
10.3. Imaging
10.3.1. Echocardiography
10.3.2. Cardiac Magnetic Resonance Imaging (MRI)
10.3.3. Future Directions: Integrating Artificial Intelligence in Imaging
11. Therapy
11.1. Pharmacology
11.2. Surgery
11.3. Emerging Therapies
12. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Category | Details |
---|---|
Regional Prevalence | Higher in tropical/less developed regions (Briceno, Schuster et al., 2016 [16]) |
Contribution to Heart Failure | Represents 30–50% of DCM cases (Heymans, Lakdawala et al., 2023 [9]) |
Developed Countries—Common Causes | Linked to hypertension, coronary artery disease (Sivitz and Nagdev, 2012 [18]) |
Developing Countries—Common Causes | Infectious causes like Chagas disease prevalent in Latin America |
Hospitalized Patients | Accounts for 10–20% among hospitalized HF patients (Verdonschot and Heymans, 2023 [17]) |
Specific Risk Factors | Chemotherapy (e.g., anthracyclines), alcohol abuse, systemic inflammatory diseases, older age, male sex |
Nutritional Deficiencies | Vitamin D deficiency; example from Ethiopia (Moges, Shiferaw et al., 2017 [20]) |
Socioeconomic Disparities | Limited access to nutrition and healthcare in low-income communities (Moges, Shiferaw et al., 2017 [20]) |
Etiological Class | Definition | Common Causes | Diagnostic Tools | Estimated Incidence |
---|---|---|---|---|
Toxic | Cardiomyopathy resulting from exposure to harmful substances, including drugs, alcohol, and chemicals. | Anthracyclines (e.g., doxorubicin), alcohol, heavy metals, illicit drugs | History of toxin exposure, ECG, echocardiography, cardiac MRI | Common in cancer patients (up to 9% for anthracyclines); varies by exposure type |
Infectious | Myocardial damage due to viral, bacterial, or parasitic infections. | Coxsackievirus, Cytomegalovirus, Trypanosoma cruzi (Chagas disease) | Serology, cardiac MRI, endomyocardial biopsy | Significant in endemic areas (e.g., Chagas: 30% of infected individuals) |
Autoimmune | Cardiac inflammation and dysfunction due to immune system attacking the myocardium. | Systemic lupus erythematosus, sarcoidosis, post-viral immune activation | Autoantibodies, inflammatory markers, CMR, biopsy | Low to moderate; varies with underlying autoimmune disease prevalence |
Endocrine | Cardiomyopathy secondary to hormonal imbalances or deficiencies. | Hypothyroidism, hyperthyroidism, adrenal insufficiency | Hormonal panels (TSH, cortisol), echocardiography | Variable; hypothyroidism and adrenal insufficiency-induced DCM are rare but reversible |
Peripartum | DCM occurring during the last trimester of pregnancy or postpartum period. | Pregnancy-associated hormonal changes and oxidative stress | Echocardiography, BNP levels, clinical correlation with pregnancy | Incidence ranges from 1 in 1000 to 1 in 3000 live births globally |
Nutritional | Cardiomyopathy due to deficiency of key nutrients essential for cardiac function. | Vitamin D, selenium, calcium deficiencies; post-bariatric surgery malnutrition | Blood nutrient levels, echocardiography, clinical history | Rare; more frequent in low-resource settings and post-bariatric surgery patient |
Chemotherapy-Induced | Cardiac dysfunction secondary to antineoplastic treatments leading to systolic impairment and ventricular dilation. | Anthracyclines, trastuzumab, cyclophosphamide, ICIs, 5-FU, bevacizumab | Cardiac MRI, biomarkers (troponin, BNP), echocardiography (strain imaging), clinical monitoring | Up to 9% in patients receiving anthracyclines; varies by agent and patient risk factors |
Dyssynchronopathy (LBBB-Induced DCM) | Cardiomyopathy due to electromechanical dyssynchrony from left bundle branch block (LBBB), reversible with resynchronization. | Isolated LBBB, post-surgical conduction block | ECG, echocardiography with dyssynchrony analysis, cardiac MRI | Subset of heart failure with reduced EF; improves with CRT in selected patients |
AF-Induced DCM | Tachycardia-induced cardiomyopathy due to persistent atrial fibrillation. | Chronic uncontrolled AF | ECG, Holter monitoring, echocardiography | Up to 25% of patients with AF-related heart failure show LV recovery with rhythm control |
VES-Induced DCM | Cardiomyopathy due to high burden of ventricular ectopic beats; reversible after arrhythmia control. | Frequent monomorphic PVCs (>10,000/day), idiopathic or structural | ECG, Holter, echocardiography, electrophysiological study | ~5% of patients with high PVC burden may develop reversible DCM |
Imaging Technique | Strengths | Limitations |
---|---|---|
Transthoracic Echocardiography (TTE) | Widely available, non-invasive, real-time assessment of cardiac function and chamber size | Operator-dependent, limited by poor acoustic windows, limited tissue characterization |
Cardiac Magnetic Resonance (CMR) | High-resolution imaging, tissue characterization (e.g., fibrosis), accurate volume, and EF measurements | Costly, limited availability, contraindications in patients with metal implants or severe renal dysfunction |
Cardiac CT | Excellent for coronary artery visualization and calcium scoring; quick scan times | Radiation exposure, less informative for functional assessment, limited soft tissue detail |
Nuclear Imaging | Assesses perfusion, metabolism, and receptor expression; useful for specific causes like sarcoidosis | Radiation exposure, lower spatial resolution, limited availability, expensive |
Therapy | Indications | Benefits | Limitations |
---|---|---|---|
Thyroid Hormone Replacement (Levothyroxine) | DCM due to hypothyroidism | Reduces LV size, improves ejection fraction, and may reverse DCM | Requires careful hormone monitoring and dose adjustment |
Glucocorticoid Therapy (Corticosteroids) | DCM due to adrenal insufficiency | Can result in full cardiac function recovery | Diagnosis of adrenal insufficiency may be delayed or missed |
Anticoagulation Therapy | Presence of ventricular thrombi or high thromboembolic risk | Reduces thromboembolic complications, improves prognosis | Risk of bleeding; requires monitoring of coagulation status |
ACE Inhibitors and Beta-Blockers | Heart failure symptoms and blood pressure control in DCM | Improves symptoms, reduces mortality in heart failure | Does not address the underlying cause of secondary DCM directly |
Surgical Procedure | Indications | Strengths | Limitations |
---|---|---|---|
Mitral valve repair | Mitral insufficiency due to DCM | Improves ejection fraction, limits heart failure symptoms | Surgical risks are not suitable for all patients |
Aortic valve replacement | Aortic stenosis leading to DCM | Restores cardiac function, lowers all-cause mortality | Invasive, requires thorough assessment for suitability |
Heart transplant | End-stage heart failure unresponsive to other treatments | Improves survival and quality of life in end-stage DCM | Limited donor availability, immune suppression required |
Catheter ablation | Atrial fibrillation/frequent PVCs | May restore sinus rhythm and reduce long-term chances of ischemic events | Surgical risks are not suitable for all patients |
Cardiac resynchronization therapy (CRT) | Dyssynchronopathy due to LBBB | Restores normal electrical conduction, improves EF | Surgical risks, not suitable for all patients |
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Kundnani, N.R.; Di Luca, F.; Meche, V.; Sharma, A.; Popa, M.-D.; Nicula-Neagu, M.; Voinescu, O.R.; Iacob, M.; Duda-Seiman, D.-M.; Dragan, S.R. Revisiting Secondary Dilative Cardiomyopathy. Int. J. Mol. Sci. 2025, 26, 4181. https://doi.org/10.3390/ijms26094181
Kundnani NR, Di Luca F, Meche V, Sharma A, Popa M-D, Nicula-Neagu M, Voinescu OR, Iacob M, Duda-Seiman D-M, Dragan SR. Revisiting Secondary Dilative Cardiomyopathy. International Journal of Molecular Sciences. 2025; 26(9):4181. https://doi.org/10.3390/ijms26094181
Chicago/Turabian StyleKundnani, Nilima Rajpal, Federico Di Luca, Vlad Meche, Abhinav Sharma, Mihaela-Diana Popa, Marioara Nicula-Neagu, Oana Raluca Voinescu, Mihai Iacob, Daniel-Marius Duda-Seiman, and Simona Ruxanda Dragan. 2025. "Revisiting Secondary Dilative Cardiomyopathy" International Journal of Molecular Sciences 26, no. 9: 4181. https://doi.org/10.3390/ijms26094181
APA StyleKundnani, N. R., Di Luca, F., Meche, V., Sharma, A., Popa, M.-D., Nicula-Neagu, M., Voinescu, O. R., Iacob, M., Duda-Seiman, D.-M., & Dragan, S. R. (2025). Revisiting Secondary Dilative Cardiomyopathy. International Journal of Molecular Sciences, 26(9), 4181. https://doi.org/10.3390/ijms26094181