LETTERS FROM READERS

The importance of evaluating remodeling

La importancia de evaluar el remodelado

Juan A. Moukarzel 1 MTSAC, Joaquín Peirano 2, Mariana Daicz 2

1 Cardiology Department

2 Nuclear Medicine Department Sanatorio Mater Dei, Autonomous City of Buenos Aires

Correspondence: Juan A. Moukarzel, San Martín de Tours 2952, City of Buenos Aires. E-mail: juan.moukarzel@smdeil.com

Rev Argent Cardiol 2024;92:169-170. http://dx.doi.org/10.7775/rac.v92.i2.20762

 Adverse left ventricular remodeling is a myocardial maladaptive process characterized by morphological changes in the structure and shape of the chamber with subsequent impaired function.

It is a common cause of heart failure occurring in up to 30% of anterior infarctions and 17% of inferior infarctions, according to some series. (1)

From a pathophysiological perspective, the process involves a sequence that could be divided in two stag­es: an early acute stage in the site of acute myocardial infarction (AMI), and a second late stage of remod­eling at least a month after the event. The latter is po­tentially reversible and includes both structural and biochemical changes, occurs in sites other than site of infarction, and involves viable cardiomyocytes. (2)

As a result, noninfarcted remote myocardial tissue becomes hypertrophic and undergoes adaptive dilata­tion in response to increased wall stress; this is not necessarily the case in all infarctions and is not neces­sarily progressive. (3, 4)

The connection among extensive infarction, re­modeling, and the rate of cardiovascular events is well known. It has been interesting to read the article Left Ventricular Remodeling After Infarction: A Perspec­tive from Gated-Spect Myocardial Perfusion Imaging, where L. San Miguel et al. (5) evaluate risk factors associated with adverse remodeling after a non-exten­sive infarction. This model identifies diabetes as a risk factor independently associated with adverse remod­eling in less extensive infarctions.

While no clinical endpoints were evaluated, patho­physiological evidence supports this finding and iden­tifies diabetes as a factor related to adverse remod­eling.

As suggested by this article, gated-SPECT myo­cardial perfusion at rest is an accessible, less complex method with a shorter time of acquisition than mag­netic resonance imaging, and can be used to evaluate adverse remodeling through the association between necrotic burden and left ventricular ejection fraction.

While this is a retrospective work sensitive to potential unidentified confounders, it suggests, like many others, the importance of more aggressive treat­ment for heart failure in diabetic patients.

This information, together with other method-related aspects –such as AMI localization and degree of motility–, provide a wider view for clinical cardiolo­gists when considering other variables and, therefore, enable enhancement of the relevant treatment for the benefit of the patient.

REFERENCES

  1. Masci PG, Ganame J, Francone M, Desmet W, Lorenzoni V, Iacucci I, et al. Relationship between location and size of myocardial infarc­tion and their reciprocal influences on post-infarction left ventricular remodelling. Eur Heart J. 2011;32:1640-8. https://doi.org/10.1093/eurheartj/ehr064
  2. Sutton MG, Sharpe N. Left ventricular remodeling after myocardial infarction: pathophysiology and therapy. Circulation. 2000;101:2981- 8. https://doi.org/10.1161/01.CIR.101.25.2981
  3. Yalta K, Yilmaz MB, Yalta T, Palabiyik O, Taylan G, Zorkun C. Late Versus Early Myocardial Remodeling After Acute Myocardial Infarc­tion: A Comparative Review on Mechanistic Insights and Clinical Implications. J Cardiovasc Pharmacol Ther. 2020;25:15-26. https://doi.org/10.1177/1074248419869618
  4. Weber KT, Clark WA, Janicki JS, Shroff SG. Physiologic versus pathologic hypertrophy and the pressure-overloaded myocardium. J Cardiovasc Pharmacol. 1987;10 Suppl 6:S37-S50. https://doi.org/10.1097/00005344-198706106-00006
  5. San Miguel L, Brodsky L, Masoli OH. Remodelado del ventrículo iz­quierdo postinfarto: una mirada desde la perfusión miocárdica gated- SPECT. Rev Argent Cardiol 2024;92:15-20. https://doi.org/10.7775/rac.v92.i1.20724

AUTHORS’ REPLY

We deeply appreciate our colleagues’ interest in our article. As above stated, the association between di­abetes and left ventricular remodeling has been de­scribed in previous articles. Our report from a nuclear cardiology department database was our modest con­tribution and shows that SPECT myocardial perfu­sion imaging may provide valuable information on this subject. We believe that these concepts may spe­cially help colleagues who are unable to perform other more complex cardiologic images.

Lucas San Miguel MTSAC

N-acetyl Cysteine and Post-infarction Remodeling

N-acetil cisteína y remodelado post infarto

María Florencia Pérez 1, 2, Juan Manuel Pérez 3, Joaquín Pérez 1

1 Department of Cardiology, Fundación Favaloro, Autonomous City of Buenos Aires

2 Cardiac Imaging Fellowship, Fundación Favaloro, Autonomous City of Buenos Aires

3 Hemodynamics Unit, Fundación Favaloro, Autonomous City of Buenos Aires

Correspondence: María Florencia Pérez, Soler 3700, Ciudad de Buenos Aires. E-mail: mfperez@ffavaloro.org

Rev Argent Cardiol 2024;92:170-171. http://dx.doi.org/10.7775/rac.v92.i2.20763

Ischemic cardiomyopathy is the main cause of world­wide mortality. Despite progress in the strict control of risk factors and in anti-ischemic and antithrombot­ic treatment, patients suffering from acute myocardi­al infarction (AMI) present with a worse prognosis. A concept supporting the unfavorable outcome of these patients is cardiac remodeling following the irrevers­ible loss of cardiac muscle, with the resulting increase in the risk of heart failure and sudden death. (1)

Pathophysiologically, during AMI there is an in­crease of oxidative stress, triggered by the over pro­duction of oxygen-derived free radicals (2) which are deleterious for the cardiomyocytes and lead to a re­duction of their viability, greater hypertrophy, and ventricular remodeling. (3)

In their interesting study, M Rodriguez et al. used an experimental AMI model in rabbits with the aim of reducing this oxidative stress by increasing anti­oxidant species, through N-acetyl cysteine (NAC) ad­ministration in animals with AMI induced by ligation of the left coronary artery. (4) N-acetyl cysteine is a precursor of cysteine, an amino acid catabolized by gamma-glutamyl cysteine synthetase producing glu­tathione, the main endogenous antioxidant system of the organism against oxidative stress. (5)

After a 28-day follow-up period, the AMI group treated with NAC significantly reduced non-infarcted zone thinning, left ventricular (LV) dilation, the in­crease of LV diastolic pressure and ejection fraction impairment.

The results of this study support the importance of targeting post AMI ventricular remodeling and sug­gest that antioxidant therapy, as NAC administration, could provide significant benefits to improve the prog­nosis of patients, with a favorable effect in the initial stages of cardiac remodeling. However, studies in hu­mans, applicable to the general population, as well as randomized clinical trials, are necessary to extend this knowledge and reproduce these results.

These findings highlight the need to continue the research in this field to develop new therapeutic strat­egies that benefit the affected population.

REFERENCES

  1. Roberts CS, Maclean D, Maroko P, Kloner RA. Early and late remodeling of the left ventricle after myocardial infarction. Am J Cardiol 1984;54:407-10.
  2. Tsutsui H, Kinugawa S, Matsushima S. Oxidative stress and heart failure. Am J Physiol Heart Circ Physiol 2011;301:H2181-90. https://doi.org/10.1152/ajpheart.00554.2011
  3. Li W, Kennedy D, Shao Z, Wang X, Kamdar AK, Weber M, et al. Paraoxonase 2 prevents the development of heart failure. Free Radic Biol Med 2018;121:117-26. https://doi.org/10.1016/j.freerad­biomed.2018.04.583
  4. Rodriguez M, Pidal G, Buzzano O, Damonte M, Lago N, Lightowler C, et al. La administración de N-acetilcisteína atenúa el remodelado postinfarto de miocardio. Rev Argent Cardiol 2024;92:28-34. https://doi.org/10.7775/rac.es.v92.i1.20726
  5. Cho S, Hazama M, Urata Y, Goto S, Horiuchi S, Sumikawa K, et al. Protective rol of glutathione synthesis in response to oxidized low density lipoprotein in human vascular endothelial cells. Free Rad Biol Med 1999;26:589-602. https://doi.org/10.1016/S0891-5849(98)00232-9

AUTHORS’ REPLY

On behalf of the research team, I wish to express our most sincere thanks to Drs. María Florencia Pérez, Juan Manuel Pérez and Joaquín Pérez, for their in­terest and thorough and valuable comments on our study: Administration of N-acetylcysteine Attenuates Post-Myocardial Infarction Remodeling. Their obser­vations and analysis enrich our publication.

As mentioned in the article, post myocardial infarction remodeling refers to the structural changes that take place in the heart after a myocardial infarction (MI), affecting its geometry. In its chronic evolution, it pro­vokes progressive functional impairment and heart failure, significantly affecting patient quality of life and increasing the long-term risk of adverse events. Management of ventricular remodeling includes strat­egies to reduce the working load of the heart, improve the contractile function and prevent complications. However, even with available therapeutic resources, an unfavorable outcome occurs in a high number of patients. Therefore, it is necessary to develop new strategies to modify this harmful situation.

Oxidative stress increasingly emerges as a pathophys­iological mechanism of myocardial injury, involved in different pathological processes. Recent experimental animal and clinical studies, have pointed out that dur­ing post MI remodeling and heart failure, oxidative stress due greater oxygen-derived free radical produc­tion plays a key role, in both early as late stages. The search for alternative therapies that decrease myo­cardial damage caused by oxidative stress have led to consider N-acetylcysteine as an antioxidant agent. Its use as such in other medical areas is a very active field of research. Though studies in the cardiovascular area are scarce, the results are promising.

The search for new therapeutic resources can start knowing the mechanisms involved in the development and/or maintenance of pathological processes, as at­tempted in our study. Unfortunately, this type of work usually goes unnoticed or does receive careful atten­tion. However, preclinical findings frequently set the foundations for future clinical progress and improved patient care.

As expressed by Dr. Pérez et al., human studies are necessary to confirm our results and benefit the af­fected population. Nevertheless, their comment endorsing the importance of targeting ventricular remodeling after an acute myocardial infarction en­courages us to persist in a more detailed study of this field and to continue exploring the afore-mentioned and new strategies.

Manuel Rodríguez MTSAC

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