Relationship between functional capacity and diastolic function in early myocardial infarction

Correspondence to: Raquel Britto – Avenida Antonio Carlos, 6627 – CEP: 31370-901 – Belo Horizonte (MG), Brasil – E-mail: r3britto@gmail.com Presentation: Sept. 2012 – Accepted for publication: Mar. 2013 – Financing source: FAPEMIG – Proccess PPM-072-09 and CNPq 307597/2011-3 – Conflict of interest: nothing to declare – Approval at the Ethics Committee n. 0515.0.203.000-10. ABSTRACT | The myocardial infarction (MI) alters left ventricle diastolic function (LVDF) in different grades, which may reflect on functional capacity (FC). This study aimed to assess, in patients with recent MI, the relation between LVDF and FC evaluated by the distance covered during the six minute walking test (6MWT). Fifty-six uncomplicated MI inpatients were selected after discharge from the coronary care unit and submitted to tests. Statistic analyses were carried out considering all patients for correlations and groups according to the classification of LVDF to comparison. It was found correlation between lateral wave a’ (later diastole) and 6MWD (r=-0.320; p=0.023) and no difference between FC and LVDF between groups. Blood pressure and heart rate had physiologic responses. The correlation indicates that the impairment of early diastole expands the role of atrial contraction in CF, reinforcing the need for evaluation of these patients still in the hospital. The physiological responses related to the six minute walking test reinforce the feasibility of its use after recent MI.


INTRODUCTION
Myocardial infarction (MI) is defined by the total interruption of the coronary flow with consequent ischemia and myocardial necrosis 1 .In MI, the diastolic function (DF) of the left ventricle (LV) is rapidly altered 2,3 , since part of the diastole depends on energy [4][5][6] .DF of the LV is associated with functional capacity (FC) in different populations [7][8][9][10] , but it is little investigated in acute conditions 11 .
The six-minute walking test (6MWT) is a submaximal, reliable, practical and low cost test [12][13][14][15] to assess the FC of healthy subjects, as well as cardiac 16 and lung disease patients 17 .Its use in MI before hospital discharge is recent 18 and little discussed 19 .The evaluation of FC in the hospital assists risk stratification and medical therapeutics and, especially, the proper prescription of exercise [15][16][17][18][19][20] .
It is likely that patients with higher degree of diastolic dysfunction (reduced DF of the LV) present reduced FC, proportional to the severity.Thus, the main objective of this study was to assess the relation between FC and DF of the LV in patients after recent MI, and also to identify the behavior of physiological variables during the application of the 6MWT.

MATERIALS AND METHODS
Cross-sectional study that assessed volunteers diagnosed with MI with or without the elevation of the ST segment (MI CSST and MI SSST), uncomplicated, after discharge from the coronary unit and medical.MI was defined by: ischemic symptoms, elevated troponin and evaluation of electrocardiogram (ECG).MI CSST was characterized by the presence of SST in at least two consecutive derivations in ECG and MI SSST due to the absence of changes in the ECG or the presence of changes indicating ischemia, different from SST 21 .Patients higher than I in the Killip classification 22 were excluded (clinical signs of ventricular dysfunction), as well as those with persistent arrhythmias, myocardial ischemia at the ECG, instability of pressure levels, moderate to severe mitral valve insufficiency 23,24 or difficulties for walking.The patients were divided into groups according to the DF classification of the LV.The study was approved by the Research Ethics Committee of the institution (Report n. 0515.0.203.000-10), and all the volunteers signed the informed consent form.
• 6MWT.FC was assessed by means of distance walked in the 6MWT (6DW), according to the guidelines by the American Thoracic Society (ATS) 12 .
Heart rate (HR), blood pressure, saturation of peripheral oxygen (SpO 2 ), and perceived exertion were assessed before and after the test (at the end and after five minutes), by means of the cardio frequency meter (Polar®, FS2c, Finland), auscultatory method, wrist oximeter (Mindray®, PM50, China) and the modified Borg Scale 23 , respectively.HR and SpO 2 were monitored also during the performance of the test.6MWT was performed by the same examiner twice (due to the learning effect 12,13 ) on the same day, with rest interval 12,13 .The longest distance walked was considered.Signs and symptoms of exertional intolerance 12 and elevated HR, higher than 85% in relation to the estimated HR for the age, were used as criteria to interrupt the test 15 .• ECHO.The diastolic function (DF) of the left ventricle (LV) can be assessed by different parameters, such as the E/A ratio and the E/e' ratio 25,26 .The E and A waves refer to the blood flow in the mitral valve during early and late diastole, respectively.The e' wave and the a' wave represent, respectively, the myocardial displacement in the mitral ring during early and late diastole.The E/e' ratio has been the most used parameter to assess DF and LV, since it is less influenced by other physiological variables 25,26 .Examinations were performed by experienced echocardiographists who did not have access to clinical data.The echocardiography system Philips IE 33 (USA, 2010) was used, with a multifrequency transducer of 2 to 4 mHz to obtain bidimensional images of the M mode sometidos a los tests.Fue realizado el análisis estadístico considerando todos los pacientes y por grupos, de acuerdo a la clasificación de la FD del VI.Fue observada una correlación entre la onda a' lateral (referente a la diástole tardía) y la DTM6 (r=-0,320; p=0,023).Sin embargo, no hubo asociación entre la CF y la FD del VI en el análisis por grupos.La correlación entre la DTM6 y la onda a´ lateral indica asociación entre la diástole tardía y la CF en estos pacientes, sugiriendo una mayor contribución de la contracción auricular para la promoción del llenado del VI en esta población.Estos datos proporcionan una asignación adicional para la utilización del TM6 en la evaluación de la CF después de un IAM reciente.
and with pulsatile Doppler.Mitral inflow velocities were registered with the pulsatile Doppler in the apical four chamber cut, with a 5 mm sample volume of at the tip of the mitral leaflets.The velocities of early (E) and late (A) diastole were measured, and the E/A ratio was also calculated.A 2 mm sample volume was placed at the junction of the LV wall and the mitral ring, in the septal and lateral regions, for the tissue Doppler register, deriving the velocities during systole (s'), early diastole (e') and late diastole (a').
The left ventricular ejection fraction (LVEF) was calculated by the Simpson method 24 .The compromised systolic function was considered as LVEF <50% 27 .The DF of the LV was classified, according to the E/A ratio, as normal, abnormal diastolic relaxation (ADR), pseudonormal relaxation (PR) or restrictive (RE) 26 .The E/e' ratio was calculated to estimate LV filling pressures 26 .The E/e' ratio <8 is associated with normal LV filling pressures, and the E/e' ratio >13 is associated with high LV filling pressures in patients with normal LVEF, when the mean of septal and lateral e' was used for calculation 26 .

Statistical analysis
An assessment of normality of data distribution by the was conducted by the Kolmogorov-Smirnov test, ANOVA one-way and the least significant difference test or the χ 2 test, to compare between groups.Pearson or Spearman correlation was used to assess the relation between the 6MWT and the echocardiographic parameters.Data are presented as absolute frequency, percentage and mean ± deviation, considering α=5% as being significant.

RESULTS
Seventy-two patients were selected, and some of them were excluded: 3 due to compromised deambulation, 8 for not being submitted to ECHO during hospital stay, 4 for using another device, and 1 due to severe mitral dysfunction.Therefore, 56 subjects were included and their characteristics are presented in Table 1.Most patients (71.42%) underwent revascularization by means of thrombolysis (30.35%), angioplasty (64.28%) or both, before the performance of the 6MWT, and 53 (94.64%) were on beta blockers.The echocardiographic analysis (Table 2) showed that 18 patients (32.14%) had systolic dysfunction, and 47 (83.93%), diastolic dysfunction.Only 8 (14.28%) had high LV filling pressures; all of these presented with diastolic dysfunction, being 3 with PR and 5 with ADR.According to the classification of the DF of the LV, the following proportion was observed: normal FD: 16.07%(9 patients), ADR: 64.29% (36 patients), PR: 19.64% (11 patients) and RE: 0% (no patient).Therefore, three groups were considered for comparison (1 to 3).There was no statistical difference between the base characteristics of the groups (Table 1).However, as expected, differences were observed in echocardiographic variables (Table 2).
There was correlation (Figure 1) betwen the lateral a' wave and the 6MWT.There was no difference in the 6MWT in the analysis per group (Table 3).In the 6MWT, only one patient surpassed the defined HR limit.The others presented physiological behavior of the assessed variables (Table 3).

DISCUSSION
This study indicates that: 1) the correlation between the 6MWT and the lateral a' wave (late diastole), even if with low magnitude, suggests a greater contribution of the atrial contraction for the LV filling; 2) there is no difference in the 6MWT in groups with different DF of the LV; and 3) no adverse physiological response to the 6MWT was found in the assessed patients.The diastole is divided into isovolumetric relaxation, early diastole, diastasis and late diastole (atrial contraction) 26 .In the MI, the early diastolic relaxation is the first stage to be altered, since it is a process that depends on energy 17,[4][5][6] , thus generating more dependency on atrial contraction to promote ventricular filling 28 .This can be observed in ECHO by the increased velocity of the A wave of the mitral flow.Such change consists of the first stage of diastolic dysfunction: the ADR, which is common in the early stage of most heart conditions 25,29 .
The lateral a' wave presented higher values (9.19±3.04)than the mean of the national population (7.3±1.5) 30, and was inversely correlated with FC.In patients with with ADR and normal LV filling pressures, the a' wave is related to the systolic function of the left atrium 31 .According to Nagueh et al (2001), the compromised early diastolic relaxation increases the left atrial preload, leading to the increased muscle contraction, by the frank-Starling mechanism, which results in the increased a' wave velocity.
The found correlation can be related to the regions that are most compromised by the MI.Since the anterior and septal regions presented with compromised mobility for most subjects, the other regions can present with hyperkinesias as an attempt to attenuate the compromise of the ventricular function 32 .This compensation mechanism may have increased the velocity of the lateral a' wave.Therefore, this study, despite the low correlation magnitude, draws attention to the need for the early assessment of FC, especially among subjects who present with these echocardiographic characteristics, and also to the need for additional studies.Echocardiography is a routine procedure for these patients, being little explored from the functional capacity point of view.
According to ATS 12 , the recent MI (up to 30 days) is a contraindication to perform the 6MWT; however, there is no evidence to prove such restriction 19 .On the contrary, the test is widely used in conditions of reduced FC, such as heart failure 16 .Besides, the 6MWT has been used with patients with recent MI, without intercurrences, in other studies 18,19 .The early assessment of FC guides the prescription of physical exercise in cardiac rehabilitation 15,20 , thus contributing for the return to activities 33 and the improvement in quality of life 34 .
Concerning the absence of 6MWT differences between groups with different DF of the LV, the type II error cannot be put aside, since the sample size was not calculated due to the absence of a clinically important reference in previous studies.Besides, the uneven number of patients per group and the lack of details on the used medication point to the need for new studies with the same focus.
In conclusion, even though no differences were observed between the groups with different degrees of DF, the found correlation indicates that the compromised early diastole increases the role of atrial contraction in the FC, reinforcing the need to assess these patients in the hospital.The physiological response to the 6MWT reinforces the viability of its use after recent MI.

Figure 1 .
Figure 1.Graphic representation of the Spearman correlation between the distance walked in 6 minutes (6DW) and a' lateral velocity with (left) and without outlier (right)

Table 1 .
Characteristics of subjectsValues expressed as absolute frequency and percentage (%) or mean±standard deviation (age and BMI).No significant differences were observed between the grouops by the ANOVA or the χ 2 test.
DF: diastolic function; ADR: abnormal diastolic relaxation; PR: pseudonormal relaxation; BMI: body mass index; FH ACD: family history of atherosclerosis coronary disease; SAH: systemic arterial hypertension; DM: diabetes mellitus; MI EST: myocardial infarction with elevated ST segment; MI WEST: myocardial infarction without elevated ST segment; RV: right ventricle