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Alteration of left ventricular global longitudinal function by 2D-strain in a group of Cameroonians heart failure patients with a preserved ejection fraction.

 

Altération de la fonction longitudinale globale du ventricule gauche en strain bidimensionnel chez un groupe de patients camerounais insuffisants cardiaques avec une fraction d’éjection préservée.

 

 

AP MENANGA1,2, CN NGANOU-GNINDJIO1,3*, TC NGO NGUE4, DL TIWA MELI1, G SADEU WAFEU1, S KINGUE1,2

 

 

RESUME

 

 

Contexte et objectifs : L'altération de la fonction globale longitudinale du ventricule gauche a été décrite comme un outil de diagnostic chez les patients insuffisants cardiaque avec une fraction d'éjection préservée. Sa fréquence et ses déterminants restent inexplorés dans la population africaine. L’objectif général de notre travail était d'évaluer la fréquence de fraction d’éjection du ventricule gauche altérée par la méthode de 2D Strain, dans une population camerounaise de patients atteints d'insuffisance cardiaque à fraction d’éjection préservée ainsi que les facteurs y associés.

Méthodes : Nous avons mené une étude observationnelle d'une durée de cinq mois dans les services de cardiologie des hôpitaux central et général de Yaoundé, au Cameroun. Les patients adultes atteints d'insuffisance cardiaque avec fraction d'éjection du ventricule gauche préservée ont été inclus, avec une collecte de données sur les variables sociodémographiques, les facteurs de risque cardiovasculaire et le profil clinique. L’évaluation de la fraction d'éjection du ventricule gauche a été faite par la méthode de Simpson Biplan et la méthode de 2D-strain.

Résultats : Au total, 30 patients ont été inclus, dont 11 (37 %) étaient des hommes et l'âge médian était de 64 (25e-75e percentiles : 55 - 71,8) ans. La fraction d'éjection ventriculaire gauche (FEVG) moyenne était de 62 % (59 - 70,3). La fonction longitudinale du VG variait de -23 à -7% avec une valeur moyenne de -15,5 (-19,3 à-11,8). Dans l'ensemble, 67 % (IC à 95 % : 50-83) des patients présentaient un strain longitudinal global altéré. La FEVG selon la méthode de Simpson était significativement plus basse chez les patients avec un strain global altéré que chez ceux avec un strain global normal (p = 0,039). Aucun autre facteur sociodémographique ou clinique n'était significativement associé à l'atteinte du strain global.

Conclusion : L’altération de la fonction longitudinale globale ventriculaire gauche semble fréquente dans chez les patients insuffisants cardiaques avec une fraction d'éjection du ventricule gauche préservée, suggérant une dysfonction systolique myocardique méconnue chez ces patients.

 

 

MOTS CLES

Insuffisance cardiaque à fraction d’éjection préservée; Déformation longitudinale globale; Échocardiographie bidimensionnelle ; Cameroun.

 

 

 

SUMMARY

 

 

Background and aims: Altered Left ventricular global longitudinal strain (LVGLS) has been described as a diagnostic tool in heart failure with persevered ejection fraction patients (HFpEF). Its frequency and correlates remain unexplored in an African population. We aimed to assess the prevalence of LVGLS impairment in a Cameroonian population of HFpEF patients and factors associated with this impairment.

Methods: We conducted a cross-sectional study of a five-month duration in the cardiology units of Central and General Hospitals in Yaoundé, Cameroon. Adult patients with heart failure with preserved ejection fraction were included, with data collection on sociodemographic variables, cardiovascular risk factors and clinical profiles. Cardiac ultrasound was used to assess the left ventricular ejection fraction by Simpson Biplane and 2D global longitudinal strain.

Results: 30 patients were included, with 11 (37%) being male and median age being 64 (Min: 53, Max: 73) years. The median left ventricular ejection fraction (LVEF) was 62% (59–70.3). The LV GLS ranged from -23 to -7%, with a median value of -15.5 (-19.3 to-11.8). Overall, 67% (95% CI: 50 - 83) of patients had altered global longitudinal strain. LVEF was significantly lower in patients with altered LV GLS than those with normal LV GLS (p = 0.039). No other sociodemographic or clinical factor was significantly associated with LV GLS impairment.

Conclusion: Left ventricular global longitudinal strain impairment seems frequent in heart failure with persevered ejection fraction patients despite preserved left ventricular global ejection fraction, suggesting unrecognized myocardial systolic dysfunction in these patients.

 

 

 

KEY WORDS

Heart failure with preserved ejection fraction; Global longitudinal strain; 2D-Echocardiography; Cameroon.

 

 

 

1. Internal medicine and specialities department, Faculty of Medicine and Biomedical Sciences, University of Yaoundé 1, Cameroon

2. Internal medicine department, Yaoundé General Hospital, Cameroon

3. Cardiology department, Yaoundé Central Hospital, Cameroon

4. Faculté des Sciences de la Santé, Université des Montagnes, Cameroon

 

Adresse pour correspondance

Dr Nganou-Gnindjio CN, Senior lecturer,

Faculty of Medicine and biomedical Sciences, University of Yaoundé 1;

PO. Box: 1364 Yaoundé-Cameroon;

Email: This email address is being protected from spambots. You need JavaScript enabled to view it.

 

 

INTRODUCTION

 

 

Heart failure (HF) is a global public health problem affecting about 26 million people worldwide, with a higher mortality rate than bowel, breast or prostate cancer[1]. HF accounts for 9.4 to 42.5% of all general internal medicine admissions in sub-Saharan Africa and 25.6 to 30% of admissions in the cardiology unit[2].

The proportion of HF with preserved ejection fraction (HFpEF) among patients worldwide ranges from 30 to 75%, with variations explained at least in part by differences in the definition of HFpEF[3]. Recent data suggest that the 2-year mortality rate is significantly lower in HFpEF than in heart failure with reduced ejection fraction (HFrEF). However, unlike HFrEF, there is currently no treatment that can reduce the mortality rate of patients with HFpEF[3]. Previously considered as “diastolic heart failure”, it has been shown that abnormalities in HFpEF are not limited to diastolic function. Other cardiac abnormalities include reduced cardiac output reserve, atrial fibrillation, and coronary artery disease. In contrast, non-cardiac abnormalities include reduced vasodilation, arterial stiffness, ventilatory dysfunction,  skeletal  myopathy,  activation  of  the  autonomic  nervous  system,  and  renal  dysfunction[4].

Diagnostic criteria and diagnostic tools for HFpHF have considerably evolved since 2007 when The Heart Failure Association (HFA) of the European Society of Cardiology (ESC) published a consensus statement on ‘How to diagnose diastolic heart failure[5]. The global longitudinal strain (GLS), which assesses subclinical systolic dysfunction, is a potentially useful diagnostic tool to evaluate left ventricular (LV) systolic properties[6]. Altered GLS predicts HF hospitalization, cardiovascular death, or cardiac arrest and is correlated with invasive LV stiffness measurements and serum natriuretic peptides (NP) levels[7]. GLS is a rapidly and reproducible non-invasive method; it is a more quantitative and objective measure of cardiac function. However, speckle-tracking echocardiography is not commonly used in an African context, and data on GLS impairment in African HFpEF patients is very limited. We assessed the prevalence and correlation of LV GLS impairment in a Cameroonian population of HFpEF patients.

 

 

 

MATERIALS AND METHODS

 

Study population

 

From January 2019 to June 2019, we conducted a cross-sectional study at the cardiology units of Yaoundé Central and General Hospitals in Cameroon. We selected 76 participants (inpatients and outpatients) with clinical signs of heart failure (dyspnoea, orthopnoea, paroxysmal nocturnal dyspnoea, rales, third heart sound (s3), and/or leg oedema) by non-exhaustive consecutive sampling. After obtaining informed consent, an echocardiography was performed on all participants to evaluate left ventricular ejection fraction (LVEF) using biplane Simpson’s disc method and perform strain analysis.

We excluded 46 patients with rhythm disorders and/or heart failure (according to Framingham criteria), LVEF < 40% (HFrEF), renal dysfunction, or myocardial infarction. A total number of 30 patients with heart failure signs and/or symptoms and EF > 50% (HFpEF) were included. Sociodemographic data, cardiovascular risk factors and clinical data were collected from patients and their health records.

 

Echocardiographic analysis

 

Transthoracic echocardiography was performed using a Philips IE33 system (Phillips Medical Systems, Andover, MA, USA) equipped with an X5-1 xMATRIX array transducer,1 to 5 MHz frequency with a second harmonic, a two-dimensional mode (2D), a TM mode, a Doppler mode (pulsed, continuous and colour) and software for analysis of the global longitudinal systolic function which is QLAB 9 (quantification of cardiac motion; Phillips Medical Systems).

All echocardiographic analyses were performed by a single experienced operator blinded to other patients’ characteristics and outcomes. LV longitudinal strain assessment was performed in the apical 4-chamber, 3-chamber, and 2-chamber views. For speckle tracking, the endocardial border was manually traced in end-systole. The integrity of speckle tracking was visually ascertained. In the case of insufficient tracking, manual correction of the endocardial tracing was attempted, and if still unsatisfactory, the participant was excluded from the study.  The longitudinal strain was calculated as the change in length divided by the original size of the speckle pattern over the cardiac cycle and expressed as a percentage; longitudinal myocardial lengthening was represented as positive strain and shortening as negative strain. Global longitudinal strain for the entire LV was averaged from the results of 18 segmental peak systolic strains. Normal LV GLS was defined as ≤ -18%, based on previous literature where normal LV GLS ranged from -15.9 to - 22.1%[8].

 

Statistical analysis

 

Data were analyzed using the IBM Corp. Released 2015. IBM SPSS Statistics for Windows, Version 23.0. Armonk, NY: IBM Corp. The results were expressed as counts and percentages for qualitative variables, median and 25th-75th percentile (Q1-Q3) for quantitative variables. Groups comparisons used Fisher exact test and Mann-Whitney U-test.  The odds ratio (OR) and the 95% confidence interval (95% CI) were calculated from age and sex-adjusted logistic regression to assess the association between altered LV GLS and potential correlates. A P-value less than 0.05 was considered statistically significant.

 

Ethical considerations

 

Ethical clearance

 

(N°2019/209/UDM/PR/CIE) was obtained from the Ethics Committee of the Université des Montagnes. Administrative authorization was obtained from studies sites. Informed consent was obtained from the participant before inclusion, and the investigation conforms with the principles outlined in the Declaration of Helsinki[9].

 

 

RESULTS

 

 

Of the 30 patients included, 19 (63%) were female, and 11 (37%) were male, with a median (Q1-Q3) age of 64 (55 – 71.8) years. Hypertension (90%), physical inactivity (80%), and obesity (50%) were the most frequent cardiovascular risk factors. At diagnosis of LVHF, 21 patients (70%) were dyspneic, and 7 (23%) patients had lower limb oedema. Other socio-demographic and clinical characteristics are described in Table 1.

Data from echocardiographic assessments are displayed in Table 1. The median (Q1-Q3) value of LVEF was 62% (59 – 70.3) with a minimum of 50% and a maximum of 74%, and 11 (37%) patients had at least one valvulopathy. LV GLS ranged from – 24 % to – 7%, with a median value (Q1-Q3) of -15.5 % (-19.3 to-11.8). The prevalence of LV GLS impairment was 67% (95% CI: 50 - 83).

After adjustment for age and gender, LVEF was significantly (p = 0.039) higher in patients with normal LV GLS (66%) compared to those with altered GLS (60%). As shown in Table I, there was no other significantly associated factor to altered GLS in our sample.  

 

 

DISCUSSION

 

 

Heart failure with preserved left ventricular ejection fraction represents 40 to 50% of heart failure in general [7]. In this study, we examined the presence of LV GLS in a population of patients with well-profiled, objectively defined HFpEF and assessed for associations of LV GLS with other baseline characteristics.

We observed that 67% of heart failure patients with normal LVEF had altered GLS, which is similar to Adam D. DeVore et al. in 2018, who also found an altered GLS in 65% of patients with normal LVEF[6]. The high rate of systolic dysfunction shown by LV GLS impairment can be explained because, although the left ventricular ejection fraction is the most commonly used and accepted measure for systolic function, it is highly dependent on the load and relatively insensitive to minor left ventricle abnormalities. In addition, the ejection fraction only explores a single type of myocardial fibres (radial myocardial fibres). These fibres are less sensitive than GLS to left ventricle systolic function abnormalities[10].

LV GLS impairment. A similar result was found by Bshiebish et al. in Iraqi patients with HFpEF; there was a negative correlation between the two variables[11]. Indeed, altered LV GLS was a predictor of HF decompensation in stable outpatients with LV systolic dysfunction and may play the same role in patients with HFpEF[12]. Furthermore, GLS impairment was independently associated with mortality and a composite endpoint of mortality or rehospitalization at 30 days in HFpEF patients [13]. GLS measurement may provide incremental information for early detection of LVEF reduction and assessment of the prognosis of these patients. The lack of association between selected attributes and LV GLS in our study should be interpreted in the context of our small sample size and accordingly limited statistical power. In previous studies, a higher proportion of abnormal LV GLS was observed in men with chronic HFpEF. However, the clinical manifestation of HF and past medical history was similar between patients with normal and abnormal LV GLS [13].

 

 

IMITATIONS TO STUDY

 

 

This study has some limitations. The main weakness of this study is its small sample size.  Nevertheless, our study has the advantage of being one of the pioneers aiming to evaluate the systolic function of patients with HFpEF in our context since the latter remains a scientific enigma.

 

 

CONCLUSION

 

 

Abnormal left ventricular systolic function is frequent in two out of three patients in our study population, objectively defined HFpEF by routine echocardiography. It would be important to track down an alteration in the function of the left ventricle in this population by the 2D strain method, which would require additional training for dedicated staff and capacity building for the technical platform in our context.

 

 

List of abbreviation

ESC: European Society of Cardiology

GLS: global longitudinal strain

HF: Heart failure

HFA: Heart Failure Association

HFpEF: with preserved ejection fraction

HFrEF: heart failure with reduced ejection fraction

LV GLS: Left ventricular global longitudinal strain

LVEF: left ventricular ejection fraction

NP: natriuretic peptides

 

Table 1

 Factors associated with altered LVGLS in heart failure patients

with a preserved ejection fraction

 

 

Characteristics

Overall

altered LV GLS

Normal LV GLS

aOR (95% CI)

Adjusted p-value

n

 

 

 

 

 

Age, years*

64 (55 – 71.8)

63 (53 – 73)

66 (59 – 72)

/

0.390

Male sex, n (%)

11 (36.7)

  7 (35)

4 (40)

0.7 (0.1 – 3.6)

0.695

Symptoms at diagnosis

 

 

 

 

 

Dyspnoea, n (%)

21 (70)

16 (80)

5 (50)

3.6 (0.7 – 19.5)

0.139

Palpitation, n (%)

  2 (6.7)

  1 (5)

1 (10)

0.6 (0.03 – 12.3)

0.630

Lower limb oedema, n (%)

  7 (23.3)

  3 (15)

4 (40)

0.3 (0.05 – 1.7)

0.164

NYHA’ stages

 

 

 

 

 

StageI, n (%)

  3 (10)

  2 (10)

1 (10)

1.4 (0.09 – 18.9)

0.817

Stage II, n (%)

14 (46.7)

  8 (40)

6 (60)

0.1 (0.01 – 1.3)

0.078

Stage III, n (%)

13 (43.3)

10 (50)

3 (30)

4.5 (0.6 – 34.1)

0.145

Hypertension, n (%)

27 (90)

18 (90)

9 (90)

0.7 (0.05 – 10.3)

0.815

Diabetes, n (%)

  3 (10)

  2 (10)

1 (10)

0.9 (0.08 – 12.2)

0.971

Ever smoked, n (%)

  1 (3.3)

  1 (5)

0 (0)

NA

>0.999

Inactivity, n (%)

24 (80)

16 (80)

8 (80)

1.1 (0.1 – 7.7)

0.953

Obesity, n (%)

15 (50)

12 (60)

3 (30)

4 (0.6 – 26.7)

0.152

BMI, Kg/m2*

30.2 (26.4 – 36.3)

31.6 (26.5 – 37.1)

27.5 (26.1 – 32.3)

/

0.398

LVEF, %*

62 (59 – 70.3)

60.5 (55.5 –    66.5)

66.5 (61.8 – 71.8)

/

0.039

Valvulopathy, n (%)

11 (36.7)

8 (40)

3 (30)

1.9 (0.4 – 10.5)

0.450

aOR: Odd Ratios adjusted for age and gender; BMI: body mass index; LV GLS, left ventricular global longitudinal strain; LVEF, left ventricular

    ejection fraction; NA, Not Applicable; NYHA, New York heart Association.

    *Quantitative parameters are expressed as median (Q1 – Q3).

 

REFERENCES

 

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3. Harper AR, Patel HC, Lyon AR. Heart failure with preserved ejection fraction. Clin Med. 2018;18:s249.

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7. Pieske B, Tschöpe C, de Boer RA, Fraser AG, Anker SD, Donal E, et al. How to diagnose heart failure with preserved ejection fraction: the HFA–PEFF diagnostic algorithm: a consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC). Eur Heart J. 2019;40:3297317.

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