The Assessment of Left Ventricular Function in Patients with and without Left Ventricular Systolic Dysfunction by the Resting Versus Peak Exercise Left Ventricular Ejection Fraction-An Observational Study

Dr Ayesha Mohammed Abdul Raoof ¹*, Dr Abdullah Ansari ² 

1 Department of Internal Medicine, Adam hospital, Ministry of Health, Sultanate of Oman.

2 Department of Internal Medicine (Cardiology Unit ), Nizwa hospital, Ministry of Health, Sultanate of Oman

*Correspondence to: Dr Ayesha Mohammed Abdul Raoof, Department of Internal Medicine, Adam hospital, Ministry of Health, Sultanate of Oman.

Copyright

© 2024 Dr Ayesha Mohammed Abdul Raoof. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Received: 10 April 2024                      

Published: 01 October 2024

DOI:  https://doi.org/10.5281/zenodo.13892660

Abstract

Background: Ejection fraction (EF) is widely used as a measure of systolic function. However, it doesn’t correlate well with exercise tolerance and other measures of peak cardiac output. Present study was conducted to compare resting ejection fraction and peak exercise left ventricular ejection fraction as a measure of left ventricular function and correlate it with peak exercise capacity, symptom class and morbidity index in patients with and without left ventricular systolic dysfunction.

Material and Methods:  Baseline and peak exercise LV dimensions, stroke volume and cardiac output were measured in patients who were referred for stress echocardiography (treadmill or dobutamine stress testing). We analysed the relationship between exercise capacity, symptom class, morbidity index and LVH with change in LV dimensions during rest and exercise. In addition, we also analysed the change in LV dimensions in young adults, elderly hypertensives and patients of ischemic or dilated cardiomyopathy with exercise.

Results: Exercise time and the maximal achieved workload were similar between elderly hypertensives and low resting EF patients (total exercise time ≈ 6 and half minutes and MWL≈ 8 METS in both the groups) but were significantly impaired in patient groups compared with young adults (total exercise time ≈ 10 minutes and MWL≈ 11 METS). At peak exercise, young adults and patients with HFrEF (Low EF) showed no change in LVedD, but there was a significant decrease in peak exercise LVedD (43.33 mm to 39.04 mm) in patients with HFpEF. Stroke volume increased in healthy adults (from 60.95 ml to 74.11 ml) and patients with HFrEF (from 53.55 ml to 60.20 ml) but showed no change in patients with HFpEF (52.25 ml at rest, 51.75 ml at peak exercise). Increase in peak exercise cardiac output was 2.9-fold in healthy adults, 2.5-fold in HFrEF, and 2.1-fold in elderly hypertensives.

Conclusion: Resting ejection fraction in young patients with past infarctions reflects increased end-diastolic volume with normal resting stroke volume; it is not due to systolic dysfunction. Elderly hypertensive patients fail to grow their ventricle by eccentric hypertrophy and they have systolic dysfunction, with impaired contractile reserve and little augmentation of systolic ejection during stress and severe worsening of abnormalities of relaxation during stress, with decrease in ventricular end-diastolic dimension, unlike healthy individuals and young patients with low EF. Therefore, normal resting echocardiography does not preclude the presence of significant functional abnormalities on exercise that can contribute to symptoms in patients with HFpEF. LVEF is a flawed measure of contractility and normal resting LVEF does not imply normal LV systolic function.

Introduction

Ejection fraction (EF) is widely used as a measure of systolic function. However, it doesn’t correlate well with exercise tolerance and other measures of peak cardiac output.

 Ejection fraction is the LV stroke volume expressed as a percentage of the end-diastolic volume. There is no ideal measure of myocardial contractility despite extensive investigation. By default, because it is relatively easy to measure and to understand, the LV ejection fraction has maintained its position as the most commonly used index. In patients with HFpEF, ejection fraction can be preserved or even be supranormal if the end-diastolic volume is significantly reduced. Thus, accurate measurement and reporting of global LV systolic function should include not just ejection fraction but also the volumes, LV end-diastolic or end-systolic, which reflect the remodeling process. Similar findings are seen with normal ageing and the typical precursors of heart failure with a normal ejection fraction such as hypertension, diabetes, and ischemia. There appears to be a spectrum of abnormalities of systolic function from the truly normal to systolic heart failure with heart failure with a normal ejection fraction occupying an intermediate position [1].

LVEF is recognized to be a poor measure of contractility because of its sensitivity to load and chamber remodeling1. Cardiac output may be adequate at rest in heart disease. Abnormalities may be present only during stress. Stroke volume, cardiac output, and their augmentation during stress or exercise are biologically relevant measures of systolic function, whereas ejection fraction is a mathematical calculation and correlate with prognosis but is not a measure of LV function. A normal LVEF does not imply normal LV function [2].

In order for the left ventricle to function as an effective pump, it must not only be able to empty but also to fill without requiring an elevated left atrial pressure. Furthermore, the stroke volume must be able to increase in response to stress, such as exercise, without much increase in left atrial pressure [3].

In response to external demands the myocardium undergoes adaptive changes. This process has been termed cardiac plasticity and changes at the cellular and macroscopic levels have been documented under various environmental conditions[4]. The most common and best understood cardiac adaptation is concentric left ventricular remodelling, which most commonly develops in response to pressure overload due to hypertension and aortic stenosis [5,6].

The adaptive changes that occur with endurance exercise and deconditioning are not as well understood but have been described in the exercise physiology literature [7-9]. Adaptive eccentric remodelling with left ventricular chamber enlargement is well documented in endurance athletes such as long-distance cyclists [7]. Extreme physical inactivity induced by bed rest or zero-gravity conditions in healthy subjects has been demonstrated to rapidly reduce left ventricular chamber volumes and mass [8,9].

Although population or disease-based studies provide interesting structural insights into the remodelling of the left ventricle they typically do not directly relate left ventricular dimensions and cardiac output to exercise capacity. Moreover, patients with markedly reduced myocardial contractility at rest (ischemic or dilated cardiomyopathy), but with good residual contractile reserve, have a favourable exercise capacity. On the other hand, patients with mildly abnormal myocardial contractility at rest, but reduced contractile reserve have a poor exercise capacity [10].

Therefore, I proposed to study comparison of resting ejection fraction and peak exercise left ventricular ejection fraction as a measure of left ventricular function and correlate it with peak exercise capacity, symptom class and morbidity index in patients with and without left ventricular systolic dysfunction.

Aim and Objective:

• Resting ejection fraction versus peak exercise ejection fraction as a measure of left ventricular function as assessed by peak exercise capacity, symptom class and morbidity index.

 

Materials and Methods

Study Area

The study was conducted at a tertiary care hospital.

Study Population

All patients with age more than 18 years who fulfilled the inclusion and exclusion criteria and presented to the echocardiographic laboratory for physical or dobutamine echocardiography were enrolled as cases.

Sample Size

As there were no previous studies on this subject, so we had proposed to do a pilot study with a minimum of 50 patients, including at least half in symptom class 2 or 3, and also a minimum of 10 patients with resting ejection fraction below 50%.

Study Design

It was a prospective, observational study. The present study compared resting ejection fraction and peak exercise ejection fraction as a measure of left ventricular function and correlated it with peak exercise capacity, symptom class and morbidity index.

Time Frame

Jan 2022 to Dec 2022

Inclusion Criteria

• All patients aged 18 years and above referred for stress echocardiography to our laboratory were screened for inclusion.

 

Exclusion Criteria

• Patients with stress induced ischemia, or those who were already known to have significant coronary obstructions.
• Patients with atrial fibrillation or other persistent arrhythmia.
• Patients with significant mitral or aortic valvular disease.
• When echo visualization was suboptimal due to poor echo window.

 

Methodology

Data on age, sex, BMI, co-morbidities, clinical diagnosis, and NYHA class was collected. An informed consent was obtained from all patients enrolled for study for their will to undergo stress echocardiography using GE vivid E-9 and Philips CX50 echocardiography machines. Patients were kept fasting for at least 4 hours prior to stress test and they were advised to avoid tea, coffee and smoking 4 hours prior to stress echocardiography.

Patients were subjected to treadmill stress test using standardized Bruce protocol. Images were obtained both at rest and at peak exercise following recommended guidelines. Patients who were unable to exercise underwent pharmacological stress echocardiography using intravenous dobutamine which was delivered using an infusion pump starting at 5mcg/kg/min which was stepwise increased to 10, 20 & 40 mcg/kg/min every 3 minutes. If even after this dose, 85% of age-predicted maximum heart rate was not achieved then atropine in divided doses of 0.25-0.5mg to a maximum of 1 mg was given to achieve target heart rate. Images were obtained at baseline, low dose and peak dose of dobutamine [20,21].

Resting heart rate and resting LV dimensions by M-mode echocardiography were measured. Resting ejection fraction and resting stroke volume was calculated using Teichholz formula [22]. Resting Cardiac output was calculated by multiplying resting stroke volume by the resting heart rate.  Peak heart rate and peak exercise LV dimensions were measured. From these measurements, LV ejection fraction, stroke volume and cardiac output at peak exercise were calculated.

Change in LV end-diastolic dimension (ΔLVedD), change in LV end-systolic dimension (ΔLVesD), change in left ventricular ejection fraction (ΔLVEF) and change in stroke volume (ΔStroke volume) at peak stress (i.e. peak stress value minus resting value) was also calculated.

Peak exercise capacity was calculated from total exercise time (measured in minutes) and maximum workload (measured as METS). One "metabolic equivalent" (MET) is equated with the resting metabolic rate (≈ 3.5ml of O2/kg/min) [23].

Morbidity index was calculated by modified Cardiac index which was derived by modifying the CAD specific index 24 and included 10 risk factors-

a. Current smoking which was divided into mild and moderate to severe depending upon whether the number of pack-years smoked (pack-year is calculated by multiplying the number of packs of cigarettes smoked per day by the number of years the person has smoked) was less than or more than 5 and was given a score of 1 & 2 respectively.

b. Hypertension was divided into mild (mild LVH), moderate (moderate LVH) and severe (severe LVH) and was given a score of 1, 2 and 3 respectively.

c. Diabetes mellitus was divided into mild (less than 5 years), moderate (more than 5 years) and severe (more than 5 years with sequelae) and was given a score of 1, 2 and 3 respectively.

d. Clinical atherosclerotic event included old CVA, old CAD, post PCI and post CABG and was given a score of 2.

e. Peripheral vascular disease was given a score of 2 as it is associated with severe atherosclerosis.

f. Chronic obstructive pulmonary disease was given a score of 2.

g. Chronic kidney disease was divided into mild to moderate (those without dialysis) and severe (those on dialysis) and was given a score of 2 and 5 respectively.

h.Malignancy was divided into non-metastatic and metastatic and was given a score of 2 and 4 respectively.

i.Miscellaneous morbidities (those not included in above like rheumatoid arthritis, osteoarthritis, hypothyroidism, peptic ulcer disease) were divided into mild to moderate (without complications) and severe (with complications) and were given a score of 1 and 2 respectively.

j.In addition for each decade more than 40 years of age, a score of 1 was added to the above score.

• Symptom class was defined according to NYHA classification which places patients in one of four categories based on how much they are limited during physical activity [25].

 

NYHA Class	Patient Symptoms
I	Patients with cardiac disease but without resulting limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea, or anginal pain.
II	Patients with cardiac disease resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain.
III	Patients with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes fatigue, palpitation, dyspnea, or anginal pain.
IV	Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of heart failure or the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.

Ordinary effort is that of the person himself as regard his previous effort tolerance and usual life style.

To see the relationship between exercise capacity, symptom class, morbidity index and LVH with LV dimensions, we selected patients from the study group on the basis of-

- Poor exercise capacity versus excellent exercise capacity - poor exercise capacity was defined as the inability to exercise more than 6 minutes as compared to excellent exercise capacity which was defined as the ability to exercise more than or equal to 9 minutes according to standard Bruce treadmill protocol.

- NYHA Class 0-I versus NYHA Class II-III.

- Low morbidity index versus high morbidity index- low morbidity index was defined as morbidity index less than 6 and high morbidity index was defined as morbidity index more than equal to 6.

- LVH versus without LVH - inclusion criteria for LVH patients was an increase in wall thickness (>12mm regardless of gender)[22].

In order to gain insight into the relationship of young adults, elderly hypertensives and patients of ischemic or dilated cardiomyopathy with the LV dimensions, we divided the study group into-

A.Young-those with age <60 years with normal resting LVEF (LVEF>50%) along with a total exercise time more than or equal to 9 minutes when subjected to standard Bruce treadmill stress testing or a morbidity index less than or equal to 3  in case of Dobutamine stress testing.

B. Old-those with age >60 years with normal resting LVEF (LVEF>50%) and a morbidity index more than or equal to 6 or presence of LVH.

C. Low EF-those with resting LVEF<50% irrespective of age.

Statistical Methods

- Statistical correlation of resting measurements and peak exercise measurements was done with peak exercise time and with NYHA symptom class in patients who underwent exercise echocardiography. In patients who underwent dobutamine stress echocardiography, we correlated resting and peak stress measurements with morbidity index. In addition, statistical correlation of resting and peak stress measurements was done between young adults (Young), elderly hypertensives (Old) and ischemic or dilated cardiomyopathy (Low EF) patients.

- Data contained both continuous and categorical variables. Therefore, mean with SD for continuous and frequency with proportions was used for their presentation. Student‘t’ or Mann-Whitney ‘U’ test was used for the quantitative variables with two independent groups and Chi-square/Fisher’s test was used for statistical significance between qualitative variables. The oneway analysis of variance (ANOVA) was used for the three group comparisons and the Dunnett’s (2-sided) t test and Tukey’s HSD (honest significant difference) were performed to explore the significant pair(s) in the multiple comparison tests. The two sided p value less than 0.05 considered as statistical significant. Data was entered and coded in MS Excel (version 7). The statistical software IBM PASW (Version 22.0) was used for entire data analysis.

Ethical Considerations

The Research Ethics Committee of the Hospital reviewed and approved the study protocol.

Observation:

A total of 93 patients, with or without heart muscle disease were enrolled for stress testing in our study over a one year study period.

58 patients underwent treadmill stress testing using Bruce protocol and 35 patients underwent Dobutamine stress testing.

The results of the study are tabulated as follows:

Age (years)	No. of patients (n=93)	%
≤50	24	25.8
50-69	51	54.8
≥70	18	19.4

MEAN ± SD AGE = 57 ± 14 

Table 1: Age Distribution of study group (n=93)

74.2% (n=69) of the patients in our study were aged 50 years or above with 19.4% (n=18) aged more than 70 years of age. The mean age of study population was 57 years (Table 1, Figure 1).

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