Impact of ventricular geometric pattern on cardiac remodeling after myocardial infarction

Abstracts

FUNDAMENTO: A relevância do padrão de geometria após o infarto do miocárdio não é conhecida. OBJETIVOS: Analisar a presença de diferentes padrões de geometria ventricular esquerda (VE) e seu impacto como preditor de remodelação em pacientes com infarto do miocárdio. MÉTODOS: Pacientes com infarto agudo anterior (n = 80) foram divididos de acordo com o padrão de geometria: normal (índice de massa [IMVE] normal e espessura relativa da parede [ERP] normal), remodelação concêntrica (IMVE normal e ERP aumentada), hipertrofia concêntrica (IMVE e ERP aumentadas) e hipertrofia excêntrica (IMVE aumentado e ERP normal). Após seis meses, foi repetido o ecocardiograma. RESULTADOS: Quatro pacientes foram a óbito. Dos sobreviventes, 41 apresentaram remodelação (R+), enquanto 39 não remodelaram (R-). Considerando-se o padrão geométrico, houve a seguinte distribuição: 24 pacientes com padrão normal, 13 com remodelação concêntrica, 29 com hipertrofia concêntrica e 14 com hipertrofia excêntrica. Os pacientes que remodelaram apresentaram maiores tamanhos de infarto analisados pelo pico da CPK (R+ = 4.610 (1.688 - 7.970), R- = 1.442 (775 - 4.247), p < 0,001) e da CK-MB (R+ = 441 (246 - 666), R- = 183 (101 - 465), p < 0,001), tendência a maior prevalência de remodelação concêntrica (R+ = 10, R- = 3, p = 0,08) e menor prevalência de hipertrofia excêntrica (R+ = 2, R- = 12, p = 0,006). Na análise de regressão multivariada, o tamanho do infarto foi preditor (OR = 1,01; p = 0,020) e a hipertrofia excêntrica foi fator protetor (OR = 0,189; p = 0,046) de remodelação ventricular após a oclusão coronariana. CONCLUSÃO: O padrão de geometria ventricular pode ter impacto no processo de remodelação em pacientes com infarto do miocárdio.

Remodelação Ventricular; Infarto do Miocárdio; Função Ventricular Esquerda; Hipertensão

Faculdade de Medicina de Botucatu - UNESP, Botucatu, SP - Brazil

Mailing Address

ABSTRACT

BACKGROUND: The relevance of left ventricular (LV) geometric pattern after myocardial infarction is not known.

OBJECTIVES: To analyze the presence of different LV geometric patterns and teir impact as a predictor of remodeling in patients with myocardial infarction.

METHODS: Patients with anterior acute myocardial infarction (n = 80) were divided according to the geometric pattern: normal (normal left ventricular mass index [LVMI] and normal relative wall thickness [RWT]), concentric remodeling (normal LVMI and increased RWT), concentric hypertrophy (increased LVMI and RWT) and eccentric hypertrophy (increased LVMI and normal RWT). After six months, echocardiographic assessment was repeated.

RESULTS: Four patients died. Of the survivors, 41 showed remodeling (R +), whereas 39 did not (R-). Considering the geometric pattern, the cases were distributed as follows: 24 patients with normal pattern, 13 with concentric remodeling, 29 with concentric hypertrophy and 14 with eccentric hypertrophy. Patients who showed remodeling had larger infarction sizes analyzed by peak CPK (R + = 4,610 (1,688-7,970), R- = 1,442 (775-4247), p <0.001) and CK-MB (R + = 441 (246 - 666), R- = 183 (101-465), p <0.001), trend towards higher prevalence of concentric remodeling (R+ = 10, R- = 3, p = 0.08) and lower prevalence of eccentric hypertrophy (R + = 2 R- = 12, p = 0.006). In the multivariate regression analysis, infarction size was a predictor (OR = 1.01, p = 0.020) and eccentric hypertrophy was a protective factor (OR = 0.189, p = 0.046) of ventricular remodeling after coronary occlusion.

CONCLUSION: The LV geometric pattern of can have an impact on the remodeling process in patients with myocardial infarction.

Keywords: Ventricular Remodeling; Myocardial Infarction; Ventricular Function, Left; Hypertension.

Introduction

After cardiac injury, molecular, cellular and interstitial alterations may occur in the heart, which will manifest clinically as alterations in heart architecture, mass, geometric pattern, function and size. This phenomenon is called cardiac remodeling^1,2 and plays a key role in the physiopathology of ventricular dysfunction that occurs in different models of cardiac injury^3,4.

For this reason, we seek to identify variables associated with the remodeling process that could stratify the risk of cardiovascular events. Among these indices, the left ventricular (LV) geometric pattern is particularly significant.

It has been observed in hypertensive patients that pressure overload can result in different geometric patterns. Using the LV mass index (LVMI) and relative wall thickness (RWT) as echocardiographic variables, the patients were divided into four different geometric patterns: normal (normal LVMI and normal RWT), concentric remodeling (normal LVMI and increased RWT), concentric hypertrophy (increased LVMI and increased RWT) and eccentric hypertrophy (increased LVMI and normal RWT). In this model, the concentric hypertrophy pattern was predictive of cardiovascular events⁵.

One must consider, however, that the importance of cardiac remodeling pattern after acute myocardial infarction remains to be clarified. Thus, the objective of the present study was to analyze the presence of different left ventricular (LV) geometric patterns and their impact as predictors of remodeling in patients with myocardial infarction of the anterior wall.

Methods

Design

This was a prospective observational study, carried out in the coronary care unit of our institution. Consecutive patients of both sexes that had the first episode of anterior wall AMI from December 2008 to July 2010 were included. The diagnosis of anterior wall AMI was established by history of chest pain lasting longer than 20 minutes and the presence of ST-segment elevation in at least two contiguous precordial leads (V1-V4) or the presence of new complete left bundle-branch block at electrocardiogram. Exclusion criteria were the presence of congenital heart disease, significant primary valvular disease, atrial fibrillation, inadequate circumstances to undergo the first echocardiogram during hospitalization, inadequate echocardiographic window, cancer, autoimmune disease, chronic renal failure (creatinine clearance < 30 mL/min), liver failure and chronic therapy with immunosuppressant agents.

The study protocol was approved by the Ethics Committee of our institution, and patients were enrolled after signing the free and informed consent form. During hospitalization, patients were evaluated daily and submitted to the first echocardiogram; follow-up duration after hospital discharge was six months, and at that time, patients underwent clinical reassessment and a new echocardiogram.

Clinical variables

Data related to patient clinical profiles were obtained from medical history and physical examination on admission. Blood samples were obtained according to the coronary care unit routine. Electrolytes, renal function and blood count were measured on admission and blood glucose and lipids were measured in samples obtained after a 12-hour fast. The levels of total creatine phosphokinase (CPK) and MB isoenzyme (CK-MB) were evaluated at baseline and every six hours until their levels started to decrease. Two troponin I measurements were performed (at baseline and 90 minutes after patient arrival).

Clinical variables, risk factors, prescription drugs and other definitions used in this study were similar to the variables used in other clinical studies^6-8.

Echocardiographic assessment

LV morphological and functional assessment was performed by echocardiography. The examinations were performed by three echocardiographists blinded to patients' clinical characteristics and treatment. Echocardiograms were performed in-hospital and six months after the AMI by the same examiner. In our service, the interobserver variability is < 5% for one-dimensional and < 10% for two-dimensional measurements and Doppler-derived time variables; the intraobserver variability is < 5% for all variables.

The examinations were performed in Philips HDI-5000 equipment according to the standard technique⁹. LV mass was calculated by the formula M = 0.8 x [1.04 x (IVS thickness + thickness of PW + LV diastolic diameter)³ - (LV diastolic diameter) ³] + 0.6, where IVS is the interventricular septum thickness and PW is the LV posterior wall. The mass was corrected for body surface area for LVMI.

The relative wall thickness (RWT) was calculated by the formula RWT = 2x PW thickness / LVDD, where LVDD is the left ventricular diastolic diameter.

Regarding the geometric pattern, the LVMI was considered increased when > 115 g/m² and RWT was considered increased when > 0.42¹⁰. Patients were divided according to the geometric pattern: normal (normal LVMI and normal RWT), concentric remodeling (normal LVMI and increased RWT), concentric hypertrophy (increased LVMI and RWT) and eccentric hypertrophy (increased LVMI and normal RWT).

Ventricular remodeling was defined as an increase of at least 15% in LV systolic and/or diastolic volume detected between the first and second echocardiography¹¹.

Statistical analysis

Continuous variables are shown as mean and standard deviation or median and 25% and 75% percentiles in case of non-normal distribution. The proportional variables were analyzed by Chi-square test or Fisher's test for comparison between groups. Continuous variables were tested for normality; continuous variables with normal distribution were compared by Student's t test (comparisons between two groups) and ANOVA, while non-normal continuous variables were compared by Mann-Whitney test (comparisons between two groups) and Kruskal-Wallis test.

The associations between the geometric pattern and remodeling after myocardial infarction were analyzed by multivariate logistic regression analysis. The statistical package SigmaStat for Windows release 3.5 (Systat Software Inc. - San Jose, CA - USA) was used for the analyses. The level of significance was set at 5% for all tests.

Results

During the study period, 90 consecutive patients were evaluated. Of these, three patients did not agree to participate, three patients had atrial fibrillation, and four patients died within six months. Therefore, our sample consisted of 80 patients.

Regarding the remodeling process, 41 patients had remodeling (R +), whereas 39 patients did not (R-). Patients' clinical characteristics are shown in Table 1. It can be observed that the infarction size was higher in patients who progressed to remodeling.

Regarding the geometric pattern, 24 patients had a normal pattern (N), 13 had concentric remodeling (CR), 29 had concentric hypertrophy (CH) and 14 had eccentric hypertrophy (EH). Patient geometric pattern in relation to the remodeling process is shown in Table 2. It can be observed that patients with remodeling showed a tendency toward a higher prevalence of concentric remodeling (R+ = 10 +, R- = 3, p = 0.08) and lower prevalence of eccentric hypertrophy (R + = 2, R- = 12, p = 0.006).

Considering the association between LV geometric pattern and function, patients with eccentric hypertrophy showed lower ejection fraction than patients with concentric hypertrophy (N = 0.48 ± 0.08, CR = 0.48 ± 0.10 , CH = 0.49 ± 0.10, EH = 0.40 ± 0.09, p = 0.026). There were no other differences.

Regarding the association between the geometric pattern and the treatment used, no differences were observed between the groups, particularly with medications of which properties attenuate remodeling (Table 3).

In the multivariate regression analysis, infarction size was a predictor and eccentric hypertrophy was a protective factor for ventricular remodeling after coronary occlusion (Table 4).

Discussion

The identification of cardiac remodeling predictors can help the therapeutic management after myocardial infarction and, therefore, has been the subject of experimental^12-15 and clinical^6,7 studies. Considering the lack of information on the relevance of the remodeling pattern in the acute myocardial infarction model, the aim of the study was to analyze the presence of different remodeling patterns and their association with ventricular function in this model.

The first aspect to be considered is the presence of different geometric patterns. In cases of hypertension, the four different geometric patterns are explained by the different physiopathological mechanisms for hypertension, with different hemodynamic patterns. Thus, the geometric pattern would depend on the degree of vasoconstriction, intensity of neurohumoral factor activation and presence of volume overload¹⁶. Verna et al., in an analysis of the VALIANT Echocardiographic Study¹⁰ in the myocardial infarction model, observed the four geometric patterns in patients with left ventricular dysfunction after myocardial infarction: concentric hypertrophy (12.6%), eccentric hypertrophy (18.6%) concentric remodeling (18.2%) and normal pattern (50.6%). In this study, the different geometric patterns are attributed to the different comorbidities shown by patients, such as arterial hypertension.

In our study, patients with anterior wall myocardial infarction also had the four geometric patterns, which could be explained by different clinical characteristics. However, in experimental models, mice with myocardial infarction and exposed to cigarette smoke also showed different geometric patterns^17,18. Considering that the animals had the same characteristics (strain, age, gender, origin, acclimatization conditions) and no comorbidities, these findings suggest that animals with the same characteristics respond differently when exposed to the same offending agent.

Another important aspect is that different authors have shown that the remodeling process may have prognostic implications. Thus, in patients with hypertension, the concentric hypertrophy pattern has been associated with increased risk of cardiovascular events when compared to other geometric patterns¹⁹.

Other studies have suggested that concentric remodeling is associated with increased risk of cardiovascular events^20-24. On the other hand, the geometric pattern was not associated with worse prognosis in other studies^25-27, indicating that the relevance of the remodeling pattern in hypertensive patients remains a controversial issue. In patients with acute myocardial infarction, the LVMI, RWT and concentric hypertrophy geometric pattern were independent predictors of death¹⁰. We are not aware of studies that evaluated the relevance of geometric patterns as predictors of remodeling in the acute myocardial infarction model.

In this sense, one should consider that the cardiac remodeling process after myocardial infarction is well characterized. In infarcted hearts, the ventricle loses its normal elliptical form after the expansion, taking on a spherical shape. With this new format, there is increased wall tension, with significantly greater increase during diastole than in systole. It is believed that the increased stress stimulates sarcomere replication, preferably in series. Therefore, larger ventricular cavities in the acute phase of myocardial infarction would be stimulate subsequent ventricular dilatation, which clinically characterizes the cardiac remodeling process after myocardial infarction^1,2,4,28. Our study, however, did not confirm this theory. Differently from what was expected, the presence of eccentric dilation in the early phase was a protective factor for the occurrence of remodeling after six months of coronary occlusion. An important aspect to be considered is that the mechanisms responsible for this phenomenon remain to be investigated.

Finally, we must consider that different therapeutic strategies can modulate the remodeling process after infarction. Among them, reperfusion therapy, angiotensin-converting enzyme inhibitors, beta-blockers and aldosterone antagonists are significant in clinical practice.

Thus, the treatment used during the recovery phase may be a confounding factor in studies that assess the remodeling process after infarction. However, we must emphasize that in our study, there were no differences in treatment among patients who progressed or not with remodeling or between patients with different geometric patterns. Thus, this finding has two implications. First, the process of remodeling remains a frequent event after anterior wall myocardial infarction, although adequately treated. Additionally, it can be inferred that the treatment did not influence our results on the relevance of the geometric pattern as a determinant of remodeling in this model.

In conclusion, the ventricular geometry pattern can have an impact on the remodeling process in patients with myocardial infarction of the anterior wall.

References

• 1. Pfeffer MA, Braunwald E. Ventricular remodeling after myocardial infarction: experimental observations and clinical implications. Circulation. 1990;81(4):1161-72.
• 2. Cohn JN, Ferrari R, Sharpe N. Cardiac Remodeling - concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. Behalf of an International Forum on Cardiac Remodeling. J Am Coll Cardiol. 2000;35(3):569-82.
• 3. Swynghedaunw B. Molecular mechanisms of myocardial remodeling. Physiol Rev. 1999;79(1):215-62.
• 4. Zornoff LA, Paiva SA, Duarte DR, Spadaro J. Ventricular remodeling after myocardial infarction: concepts and clinical implications. Arq Bras Cardiol. 2009;92(2):150-64.
• 5. Ganau A, Devereux RB, Roman MJ, de Simone G, Pickering TG, Saba PS, et al. Patterns of left ventricular hypertrophy and geometric remodeling in essential hypertension. J Am Coll Cardiol. 1992;19(7):1550-8.
• 6. Cogni AL, Farah E, Minicucci MF, Azevedo PS, Okoshi K, Matsubara BB, et al. Waist circumference, but not body mass index, is a predictor of ventricular remodeling. Nutrition. 2013;29(1):122-6.
• 7. Farah E, Cogni AL, Minicucci MF, Azevedo PS, Okoshi K, Matsubara BB, et al. Prevalence and predictors of ventricular remodeling after anterior myocardial infarction in the era of modern medical therapy. Med Sci Monit. 2012;18(5):CR276-81.
• 8. Azevedo PS, Cogni AL, Farah E, Minicucci MF, Okoshi K, Matsubara BB, et al. Predictors of right ventricle dysfunction after anterior myocardial infarction. Can J Cardiol. 2012;28(4):438-42.
• 9. Lang RM, Bierig M, Devereaux RB, Flachskampf FA, Foster E, Pellikka PA, et al. Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr. 2005;18(12):1440-63.
• 10. Verma A, Meris A, Skali H, Ghali JK, Arnold JM, Bourgoun M, et al. Prognostic implications of left ventricular mass and geometry following myocardial infarction: the VALIANT (VALsartan In Acute myocardial iNfarcTion) Echocardiographic Study. JACC Cardiovasc Imaging. 2008;1(5):582-91.
• 11. Hung CL, Verma A, Uno H, Shin SH, Bourgoun M, Hassanein AH, et al. Longitudinal and circumferential strain rate, left ventricular remodeling and prognosis after myocardial infarction. J Am Coll Cardiol. 2010;56(22):1812-22.
• 12. Minicucci MF, Azevedo PS, Santos DF, Polegato BF, Santos PP, Okoshi K, et al. Echocardiographic predictors of ventricular remodeling after acute myocardial infarction in rats. Arq Bras Cardiol. 2011;97(6):502-6.
• 13. Minicucci MF, Azevedo PS, Martinez PF, Lima AR, Bonomo C, Guizoni DM, et al. Critical infarct size to induce ventricular remodeling, cardiac dysfunction and heart failure in rats. Int J Cardiol. 2011;151(2):242-3.
• 14. Zornoff LA, Paiva SA, Minicucci MF, Spadaro J. Experimental myocardium infarction in rats: analysis of the model. Arq Bras Cardiol. 2009;93(4):434-40.
• 15. Minicucci MF, Azevedo PS, Matsubara BB, Matsubara LS, Paiva SA, Zornoff LA. Association between sphericity, ventricular function and size of the infarction in rats. Arq Bras Cardiol. 2010;94(5):645-50.
• 16. Dávila DF, Donis JH, Odreman R, Gonzalez M, Landaeta A. Patterns of left ventricular hypertrophy in essential hypertension: should echocardiography guide the pharmacological treatment? Int J Cardiol. 2008;124(2):134-8.
• 17. Azevedo PS, Minicucci MF, Matsubara BB, Matsubara LS, Duarte DR, Paiva SA, et al. [Remodeling pattern and ventricular function in rats exposed to cigarette smoke]. Arq Bras Cardiol. 2010;94(2):209-12, 224-8, 212-5.
• 18. Minicucci MF, Azevedo PS, Ardisson LP, Okoshi K, Matsubara BB, Matsubara LS, et al. Relevance of the ventricular remodeling pattern in the model of myocardial infarction in rats. Arq Bras Cardiol. 2010;95(5):635-8.
• 19. Koren MJ, Devereux RB, Casale PN, Savage DD, Laragh JH. Relation of left ventricular mass and geometry to morbidity and mortality in uncomplicated essential hypertension. Ann Intern Med. 1991;114(5):345-52.
• 20. de Simone G, Kitzman DW, Chinali M, Oberman A, Hopkins PN, Rao DC, et al. Left ventricular concentric geometry is associated with impaired relaxation in hypertension: the HyperGEN study. Eur Heart J. 2005;26(10):1039-45.
• 21. Gardin JM, McClellan R, Kitzman D, Lima JA, Bommer W, Klopfenstein HS, et al. M-mode echocardiographic predictors of six-to-seven year incidence of coronary heart disease, stroke, congestive heart failure, and mortality in an elderly cohort. Am J Cardiol. 2001;87(9):1051-7.
• 22. Verdecchia P, Schillaci G, Borgioni C, Ciucci A, Battistelli M, Bartoccini C, et al. Adverse prognostic significance of concentric remodeling of the left ventricle in hypertensive patients with normal left ventricular mass. J Am Coll Cardiol. 1995;25(4):871-8.
• 23. Muiesan ML, Salvetti M, Monteduro C, Bonzi B, Paini A, Viola S, et al. Left ventricular concentric geometry during treatment adversely affects cardiovascular prognosis in hypertensive patients. Hypertension. 2004;43(4):731-8.
• 24. Pierdomenico SD, Lapenna D, Bucci A, Manente BM, Cuccurullo F, Mezzetti A. Prognostic value of left ventricular concentric remodeling in uncomplicated mild hypertension. Am J Hypertens. 2004;17(11):1035-9.
• 25. Verdecchia P, Schillaci G, Borgioni C, Ciucci A, Gattobigio R, Zampi I, et al. Prognostic value of left ventricular mass and geometry in systemic hypertension with left ventricular hypertrophy. Am J Cardiol. 1996;78(2):197-202.
• 26. Krumholz HM, Larson M, Levy D. Prognosis of left ventricular geometric patterns in the Framingham Heart Study. J Am Coll Cardiol. 1995;25(4):879-84.
• 27. Ghali JK, Liao Y, Cooper RS. Influence of left ventricular geometric patterns on prognosis in patients with or without coronary artery disease. J Am Coll Cardiol. 1998;31(7):1635-40.
• 28. Pfeffer JM, Finn PV, Zornoff LA, Pfeffer MA. Endothelin-A receptor antagonism during acute myocardial infarction in rats. Cardiovasc Drugs Ther. 2000;14(6):579-87.

Impact of ventricular geometric pattern on cardiac remodeling after myocardial infarction

Elaine Farah; Daniéliso R. Fusco; Paulo R. R. Okumoto; Marcos F. Minicucci; Paula S. Azevedo; Beatriz B. Matsubara; Katashi Okoshi; Siméia G. Zanati; Sergio A. R. Paiva; Leonardo A. M. Zornoff

Publication Dates

• Publication in this collection
  14 May 2013
• Date of issue
  June 2013

History

• Received
  29 Oct 2012
• Accepted
  13 Mar 2013
• Reviewed
  20 Jan 2012