November27, 2022

Abstract Volume: 4 Issue: 6 ISSN:

Baseline Characteristics and Outcome of Patients with Heart Failure and Preserved Ejection Fraction Included in an Algerian Cohort

Assia Haddad (MD)1,2, Mohamed Karim Guerchani (MD)3, Nadia Ould Bessi (MD) 4,
Dalila Djermane (MD)1,5, Omar Ait Mokhtar (MD, PhD)1,5, Hakim Himeur (MD,PhD)²,

Abdellaziz Dahou (MD, PhD)1, 6, Salim Benkhedda (MD, PhD)*1, 5.

1. Cardiology Oncology Research Collaborative Group. Faculty of medicine,

BENYOUCEF BENKHEDDA university of Algiers.

2. Mohamed Abderrahmani Specialized Hospital. Cardiac surgery department.

3. Mustapha Bacha University Hospital,;Epidemiology department.

4. Mustapha Bacha University Hospital; Pierre and Marie Cury Center, Biochemistry department.

5. Mustapha Bacha University Hospital. Cardiology department. Faculté de Médecine

BENYOUCEF BENKHEDDA university of Algiers

6. St Francis Hospital, The DeMatteis Center for Cardiac Research and Education, New York, USA

Corresponding Author’s: Dr. Abdellaziz Dahou (MD, PhD), St Francis Hospital, The DeMatteis Center for Cardiac Research and Education, New York, USA

Dr. Salim Benkhedda, (MD, PhD), Mustapha Bacha University Hospital. Cardiology department. Faculté de Médecine, BENYOUCEF BENKHEDDA university of Algiers

Copy Right: © 2022, Dr. Salim Benkhedda, MD, PhD, 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 Date: October 17, 2022

Published Date: November 01, 2022




Background: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous disease with a complex pathophysiology. Clinical presentation depends on comorbities and dominant etiology. This work aims to describe the baseline characteristics and outcome of an Algerian cohort of patients with HFpEF.

Patients and methods: A prospective observational study from April 2018 to April 2020, including patients aged 18 and over, referred to the echocardiography laboratory for HFpEF as defined according to the ESC 2016 criteria. Comprehensive Doppler echocardiography was performed at admission and levels of N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) and Growth Differenciation Factor 15 (GDF 15) were measured. The outcome of the study was a composite endpoint of death from any cause, rehospitalization for HF or stroke at 1 year. 

Results: 153 patients were enrolled. The mean age was 73 ±11 years, and 67%  were female. Patients were very frequently hypertensive (86%) and diabetic (64%) with a history of atrial fibrillation (46%), anemia (42.48%), chronic renal insinsufficiency (CRI) (38.56%), and obesity (35.76%). Among the echocardiographic parameters, left atrial dilatation was found in 80% of cases, Left ventricular hypertrophy (LVH) in 74% of cases and an E/é ratio > 13 in 69% of cases. Sixty-three percent of patients had an impaired global longitudinal strain (GLS < 16%) despite preserved LVEF (59% ±7%).

The median value of NT-proBNP was 1284 (Interquartile range [IQR]: 442-3109) with extremes ranging from 133 to 35000 pg/ml. The median value of Growth Differentiation Factor 15 (GDF 15) was 2530 (IQR: 1492-3929) with extremes ranging from 400 to 25632 pg/ml, and 87% of patients had a GDF 15 level > 1200 pg/ml.

At one year follow up, rate of rehospitalization for heart failure and mortality were 5.9% and 13.7% respectively. Nearly half of deaths (45%) were from non-cardiovascular causes. The independent prognostic factors associated with one year outcome (composite endpoint of rehospitalization for HF, death from any cause or stroke) were: signs of peripheral venous congestion, anemia, and pulmonary artery systolic pressure at admission (all p<0.05). GDF 15 and NT-proBNP were associated with outcome in univariable but not in multivariable analysis.

Conclusion: The patients included in our cohort are mainly elderly and hypertensive women, and more than half were diabetic. Majority of patients had impaired longitudinal strain  with increased LV mass, impaired diastolic function, and high levels of GDF 15. The independent prognostic factors associated with one year outcome were: signs of peripheral venous congestion, anemia and PASP.

Keywords: Heart failure with preserved ejection fraction; Echocardiography; comorbidities, outcome.




ACE:                Angiotensin conversion Enzym

AF:                   Atrial fibrillation

ARB:                Angiotensin Receptors Blockers

ARNI:             Angiotensin Receptors Neprilysin Inhibitors

BMI:               Body Mass Index

BNP:               Brain Natriuretic Peptide

CI:                    Confidence intervall

CR:                  Chronic renal insufficiency

COPD:             Chronic obstructive pulmonary disease

Cor:                 Pearson's product-moment correlation

EF:                   Ejection fraction

ESC:                 European Society of cardiology

GDF:                Growth Differentiation Factor

GLS:                Global longitudinal strain

HF:                   Heart failure

HFpEF:            Heart failure with a preserved ejection fraction

HFrEF:             Heart failure with a reduced ejection fraction

LA:                   Left atrium

LAV:                Left atrial volume

LV:                   Left ventricle

LVEF:              Left ventricular ejection fraction

LVH:                Left ventricular hypertrophy

LVM:               Left ventricular mass

MACE:            Major acute cardiovascular events

6M-WT:          6 Minutes’ Walk Test

NT-proBNP:    N terminal pro Brain Natriuretic Peptide

Pg:                    Picograms

Rho:                Spearman's rank correlation

SD:                   Standard deviation

Baseline Characteristics and Outcome of Patients with Heart Failure and Preserved Ejection Fraction Included in an Algerian Cohort


Heart failure (HF) is a global public health issue because of its high prevalence, morbidity and socio-economic impact on the health system. Due to the sudden rise in prevalence and hospitalizations between the 1970s and 1990s, it is commonly referred to as an "epidemic". [1,2]

HF with preserved ejection fraction (HFpEF) accounts for 40 -70% of heart failure cases. [3,4] It is one of the leading causes of morbidity and mortality with a significant impact on quality of life, comparable to that of heart failure with reduced ejection fraction (HFrEF). [5] The prevalence of HFpEF increases with population aging, with a simultaneous increasing prevalence of co-morbidities including hypertension, obesity and diabetes. Labeled as an “orphan disease”, many uncertainties remain about it. The perception of the HFpEF as a heterogeneous and complex entity, depending on the dominant etiology and the various comorbidities, could largely explain the failures of the clinical trials. [6,7] In this report, we describe the clinical aspects, echocardiographic characteristics and the outcome of an Algerian cohort of patients with HFpEF. The description is based on the definitions and threshold values published by the European Society of Cardiology in 2016 on the HFpEF.



This is  a single-center prospective observational study conducted between April 2018 and April 2020, which consecutively included adults patients (≥ 18 years) referred to the echocardiography laboratory of the cardiology department A2 of Mustapha Bacha University Hospital (Algiers, Algeria), in whom the diagnosis of HFpEF was retained according to the criteria of European society of cardiogy (ESC) 2016. Namely, the presence of signs and/or symptoms of heart failure , a rate of N-terminal (NT)-pro B-type natriuretic peptide (NT- proBNP) > 125 pg/ml or BNP > 35 pg/ml with at least one ultrasound criterion of structural heart disease (left ventricle mass ≥ 115 g/m² in men and ≥95 g/m² in women, indexed left atrial volume > 34 ml/m²) or functional abnormality (E/é ≥ 13 and e’ septal and lateral mean < 9 cm/s). Patients were excluded from the study if they had more than moderate valvulopathy, World Health Organization (WHO) class 1, 3, 4, or 5 Pulmonary arterial hypertension, right ventricular arrhythmogenic dysplasia, congenital heart disease, right ventricular infarction, pericardial disease: Tamponnade, constrictive pericarditis or specific cardiomyopathy: viral, inflammatory (Sarcoidosis), genetic (Hypertrophic Cardiomyopathy), restrictive cardiomyopathy. Comprehensive Doppler echocardiography was performed at admission (GE vivid 7) and blood samples were drawn. Patients were followed up to 1 year. The primary endpoint of the study was a composite of death, rehospitalization for heart failure or stroke at 1 year.


Statistical Analysis

Data were expressed as mean ± standard deviation (SD) or n (%) unless otherwise specified. Dichotomous variables were analyzed using chi-square test and continuous variables using Kruskal-Wallis rank sum test. Cox proportional hazard analysis was used to determine the independent prognostic power of each variable to predict the outcome. For all tests, a p-value ≤ 0.05 was considered statistically significant. All statistical analyzes were carried out using R 4.0 software.



One hundred fifty-three consecutive patients were enrolled with a follow-up of one year. The mean age of the study population was 73 ±11 years (ranging from 42 to 91 years) and the majority of patients were female (67%). Baseline characteristics of the study population are presented in Table 1.


Co-morbidities,  risk factors and clinical presentation

Patients were predominantly hypertensive (86%) and diabetic (65%) with a history of atrial fibrillation in 46% of them. 36% of patients were obese, 39% had chronic renal insufficiency (CRI), defined by glomerular filtration rate <60ml/min/1.73m², 26% had coronary artery disease (CAD), and 20% had chronic obstructive pulmonary disease (COPD) . Anemia (HB< 13 g/dL in men and < 12g/dL in women according to the World Health Organization (WHO) definition, was present in 42% of the population .

The majority of our patients had signs of isolated left heart failure (71%), ranging from dyspnea on exertion to orthopnea.  Signs of peripheral venous congestion were noted in 29% of patients. 19% of patients were hospitalized for primary acute heart failure or worsening signs of congestive HF despite a therapeutic adjustment in the ambulatory setting, and the remaining (81%) were managed in the outpatient setting.

When comparing these factors and comorbidities according to gender (Table 2), we noted a statistically significant difference by gender in terms of smoking, Coronary artery disease, and the presence of CRI with a clear male predominance. On the other hand, the comparison of these comorbidities according to age (Table 3) showed a significant increase in COPD with age.

Doppler Echocardiographic measurements

Left ventricular ejection fraction (LVEF) varied from 50 to 77% with an average of 59% ±7%. The average indexed LV mass was 121± 38 g/m² with extremes ranging from 55 to 331 g/m². The prevalence of left ventricular hypertrophy (LVH) was 74% with eccentric type in 51% of patients. Isolated left ventricular remodeling with normal left ventricular mass was noted in 11% of cases, while normal left ventricular geometry was present in 15% of cases.

The average indexed left atrium volume(LAVI) was 48± 19 ml/m² with extremes ranging from 18 to 150 ml/m². 81% of patients had left atrial (LA) dilatation defined by a LAVI > 34ml/m².

The value of the average mitral E/e' ratio (Sepal and lateral) varied from 6 to 37 with an average of 15.8 ± 5.  61% of patients had an E/e' ratio > 14 while 94% of patients had an E/e' ratio > 9.

The peak velocity of tricuspid regurgitation (TR) ranged from 1.94 to 4.18 m/s with an average of 2.86 ± 0.43 m/s. 53% of patients had a TR peak velocity > 2.8 m/s.

The mean  pulmonary artery systolic pressure (PASP) was 43mmHg with extremes ranging from 20 to 84 mmHg. 68% of patients had SPAP > 35mmHg.

The mean value of the global longitudinal strain (GLS) was 14.3% ±4.6) ranging from 3.2 to 24%.  63% of patients had an impaired longitudinal strain defined by a GLS ≤ 16%.

Comparaison according to gender showed a significantly higher E/e' ratio in women while the LV mass was significantly higher in men. That’s expected since the two genders have different cut-offs. Note that there is no significant difference in prevalence of left ventricular hypertrophy.


Blood biomarkers

Regarding blood biomarkers, the mean value of the NT- pro BNP was 2995 ± 5148 pg/ml with extremes ranging from 133 to 35000 pg/ml. Plasmatic concentration of Growth Differentiation Factor 15 (GDF 15) was available in 111 (73%) patients only. The mean GDF 15 value was 4102±4274 pg/ml with a range of 400 to 25632 pg/ml. 70% of patients had values > 1800 pg/ml and 13% had values between 1200 and 1800 pg/ml, while only 13% had values < 1200 pg/ml.  High levels of GDF 15 were significatively associated with age (P=0.004, cor= 0.27) , diabetes (p=0.01, rho=0.24), CRI (P=0.0034, rho=0.44), anemia (P=0.003, rho=0.27), left atrial volume (P=0.002, cor=0.29), atrial fibrillation (P=0.001, rho=0.30), PASP(P=0.032, cor=0.37), NT-ProBNP ( P= 0.001, cor=0.49), and 6 minutes walking distance (P=0.0006, cor=-0.47)

GDF-15 was also sigificatively associated with the use of ACE inhibitors (P=0.02, rho= -0.21) , ARBs (P=0.20, rho= 0.210), and treatment with insulin (P-0.20, rho-0.21).

The 6-minute walking test: The 6-minute walking distance was performed in only 43% of our patients. The average walk distance was 265 ± 146 m, ranging from 100 to 512 m, with a walking distance < 300 meters in 53% of patients. Walking distance decreased inversely with age, especially in women.


With regard to the medical treatment, nearly 90% of patients were under angiotensin receptor antagonists or Angiotensin converting enzyme inhibitors, and 81% were under diuretics. 63% were on beta-blockers, 46% were on statins, 38% were on anti-platelet agents, 31% were on calcium channel blockers, 25% were on Spironolactone, and 6% were on digoxin.


One year outcome

A total of 58 major adverse cardiac events (MACE) including death from any cause, hospitalization for heart failure or stroke were recorded during one year of follow-up, representing a rate of 38%. One year mortality was 13.73%, with nearly hal of cases (45%) from non cardiovascular cause. The rehospitalization rate for heart failure was 5.9%.

In univariable analysis, factors that were associated with the occurance of MACE at one year were: signs of peripheral venous congestion, chronic renal failure, anemia, obesity, atrial fibrillation (All P<0.05), indexed left atrial volume (P= 0.031), systolic arteriel pulmonary pressure (P= 0.0003), the levels of NT-ProBNP (P=0.033), GDF 15 (P= 0.006), as well as the 6 minutes walk-distance (p<0.05). After multivariate adjustment, the independent prognostic factors associated with one year outcome were: signs of peripheral venous congestion (P=0.003, Odds ratio [OR]=8.49), anemia (P=0.026, OR=2.53), and PASP(P=0.024, OR=1.04 per 1 mmHg increase).


Our study prospectively included a population of patients with HFpEF as strictly defined by the criteria of the European Society of Cardiology of 2016. We discuss here in the findings of present study in the light of previous studies dealing with patients with HFpEF (Table 4).

Clinical, echocardiographic and blood biomarkers characteristics

The risk factors and co-morbidities of the patients included in our study were as described above, including patients with HFpEF with predominantly female, and a high prevalence of hypertension, diabetes, and atrial fibrillation. [9,10]

Despite a disparate distribution of co-morbidities with variations by study type (Registry, Randomized Controlled Trial, or community-based study), study population, and geographic region, the most common co-morbidities are hypertension, atrial fibrillation, chronic kidney disease, and diabetes with significant variability between studies.[8].  On the other hand, I PREFER study which included a population of patients with HFpEF from Latin America, the Middle East, and North Africa including Algeria, showed that the population of patients with HFpEF was older, with a predominance of women, obesity, hypertension, and atrial fibrillation compared to patients with reduced LVEF (HFrEF).[9] Our results highlight the high prevalence of hypertension among other risk factors [11,12, 13, 14, 15 ].

The prevalence of diabetes among patients with HFpEF varies widely, with extremes ranging from 5 to 60% depending on the series. [16 ,17] In our series, 66% of patients were diabetic, slightly exceeding the high prevalence series of diabetes. Its prevalence in other Algerian series varies from 45% in patients hospitalized for acute HF regardless of LVEF [18] to 49% in hypertensive patients with normal LVEF. [19] Regional variations in co-morbidities, lifestyle, nutritional patterns, activity, and genetic predisposition can explain these variations worldwide. Despite this high prevalence, diabetes does not appear to be a predictor of new cases of HFpEF, according to Ho and colleagues [20].

The prevalence of anemia in our series was 42%, in line with the results of some published reports indicating that anemia is also very common in this population of patients, with a prevalence varying according to studies and definition of anemia, ranging from 42% to 70%. [21].

The prevalence of chronic renal insufficiency (CRI) was 31%, 49% and 35% in the I-PRESERVE, DIG-PEF, and CHARM-preserved trials, respectively. Our results are in line with these data, since 39% of our patients had CRI.

Obesity was common in our series with a prevalence of 36%, which is consistent with data from previous studies [8, 9]. Obesity (BMI>30 kg/m2) is one of the most common co-morbidities in patients with heart failure and is one of the risk factors for the development of HFpEF. [22] It is common in both types of heart failure, but most studies show that it is more common in HFpEF than in HFrEF with a prevalence of 39% in HFpEF patients versus 27% in HFrEF patients [8]. Its prevalence also shows regional variability with a rate of 40-45% in the Middle East and North Africa, and 31% in Latin America.  [9]

The prevalence of atrial fibrillation (AF) in our series was 46% at the time of diagnosis of HFpEF, similar to previous studies [23, 24, 25] which reported that atrial fibrillation is common in HFpEF with variability depending on study design and diagnostic methods (clinical diagnosis vs. Holter screening). In a meta-analysis of 66,357 patients, the prevalence of permanent AF appears to be slightly higher in patients with HFpEF compared to those with HFrEF (48 vs 44%). [ 26] The prevalence of Coronary artery disease (CAD) in patients with HFpEF is variable according to registries, definitions, and validation methods, ranging from 20% to 76% with an average of 41% [27]. A history of coronary artery disease (history of an acute coronary syndrome, revascularization, or significant coronary artery stenosis) was found in 26% of our patients.

Compared with men, women had lower prevalence rates of coronary artery disease and chronic kidney disease which is consistent with previous studies: PURSUIT?HFpEF [Prospective Multicenter Observational Study of Patients with Heart Failure with Preserved Ejection Fraction] [28], and APOLLON study [29].

Regarding baseline blood biomarkers, levels of GDF-15 were elevated (> 1200 pg/ml) in 87% of our patients and were found to be associated with 1-year outcome in univariable but not in multivariable analysis. Previous studies including larger number of patients have shown that higher GDF 15 levels were associated with worse outcome (all-cause mortality) in patients with HfpEF. [ 30] Thus GDF15, may provide complementary pathophysiological information supporting an independent role of inflammatory cytokine release (GDF15) in the pathophysiology of HFpEF, whereas NT-proBNP, reflects haemodynamic wall tension or stress.  [31] Another finding in our study is the association of baseline levels of GDF-15 and the use of angiotensin-converting enzyme (ACE) inhibitors, which can support the hypothesis that GDF 15 may be an interesting biomarker for treatment  responsiveness, by reduction of cardiac stress due to treatment leading to down-regulation of GDF15 levels. [32]


In the absence of pharmacological treatment that have been shown to be really effective in patients with HFpEF, treatment is based primarily on agressive control of risk factors and co-morbidities and the treatment of signs of congestion by diuretics. According to the medication prescribed to patients included in our study, beta-blockers, diuretics, aldosterone antagonists, and other blockers of the renin-angiotensin system were prescribed in similar proportions to that of previous reports. [33, 34] The majority of our patients received diuretics (82%) and renin-angiotensin-aldosterone system inhibitors (89%). However, our series is distinguished by higher use of angiotensin receptor blockers (ARBs) over ACE inhibitors (67% vs 22%) and may reflect the potential benefit of this therapeutic class as suggested by the results of CHARM-Preserved and I-Preserved trials in patients with HFpEF.

Echocardiographic caracteristics

Left ventricular hypertrophy (LVH): Our cohort is characterized by a high prevalence of LVH, which was present in 74% of patients similar to other trials and registries such as the European PEP-CHF (Europe) [35] study and the American ARIC registry. [36]

Very few studies have distinguished LVH from ventricular remodeling. [8,37].  Fourty-seven percent of our patients had a relative wall thickness ≥0.42, similar to the data from the North African cohort of I-PREFER study which reported a prevalence of relative wall thickness > 0.44 of 40% [9], and those from the TOPCAT study [Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function], which reported concentric remodeling in 34% of cases, while the Latin American and Middle Eastern cohorts of the I-PREFERE study reported a higher prevalence of 66% and 61% respectively. [9]

 Left atrial dilatation: Our series is characterized by a higher prevalence of left atrial (LA) dilatation (81%) compared to TOPCAT (53%) [38] and I-PRESERVE (66%) studies [39]. The CHARM-Preserve ultrasound substudy reported a left atrial indexed volume > 32 ml/m² in 71% of patients [40]. This high prevalence could be explained by the fact that left atrial hypertrophy increases with age, especially in patients with co-morbidities such as hypertension, diabetes, obesity, and atrial fibrillation,[41] which were common in our series.

Although the relationship between LA dilatation and LVH is not yet clear, it is possible that this high prevalence of LA dilatation is also related to the high prevalence of LVH. Indeed, Gavin et al, in their analysis of the TOPCAT sub-study, found that patients with high LV mass had a significantly higher LA volume than patients with low LV mass and low LVH prevalence.[42]

Diastolic dysfunction: In our study, approximately 60% of patients had an average E/e' ratio > 14 at rest, 69% had an E/e' ratio > 13. Our data align with those of the TOPCAT trial [34] and the echocardiographic substudy of CHARME-Preserved [36] and I-PRESERVE [35], which report a prevalence of diastolic dysfunction of 66%, 67%, and 69% respectively.

Similar to data from the echocardiographic substudies of the HFpEF randomized controlled trials (TOPCAT, I-PRESERVEand CHARM Preserved) one-third of our patients had a normal diastolic function at rest at the time of echochardiography. [34, 35, 36]

As expected, echocardiographic findings demonstrated differences in diastolic function status at rest between male and female. Women had higher LV filling pressure as evaluated by E/e’ ratio, and lower left ventricular mass than men, which is consistent with the findings of previous studies [31,43,44].  The PARAMOUNT trial (Prospective comparison of angiotensin receptor neprilysin inhibitor (ARNi) with angiotensin receptor blockers (ARBs) on the management of heart failure with preserved ejection fraction) was the first investigation that provided a detailed sex-specific analysis of LV structure, function, and mechanics in HFpEF [45], and showed that indexed LV mass was significantly lower in women with HFpEF, with a significantly higher E/e’ ratio.

Studies that have examined the correlation of this parameter to left ventricular filling pressures have shown that its use in routine clinical practice is subject to limitations, with a sensitivity of the algorithmic approach that vary very widely between 34% and 87% [45,46,47,48,49] according to the studies, which makes its use as the only echographic criteria for measuring the filling pressures of the LV not recommended.

Despite a preserved ejection fraction, 62% of our patients had an impaired global longitudinal strain (GLS < 16%) as previously described in a recent meta-analysis of 10 studies including 1810 patients with HFpEF and 462 asymptomatic controls [50].  The prevalence of longitudinal systolic dysfunction was significantly higher in patients with HFpEF with an average of 65% ranging from 37% to 95%, compared to only 13% (0% to 30%) in asymptomatic subjects. [48] We didn’t find any difference in LV longitudinal strain between women and men with HFpEF as described in the PARAMOUNT trial.

Younger patients with HFpEF had higher indexed LV mass compared with older patients. Atrial size increased with increasing age. Older age was associated with similar rates of abnormal relative wall thickness and abnormal filling pressures. Our results join data published from patients with left ventricular ejection fraction ≥45% from 3 large HFpEF trials (TOPCAT, I-PRESERVE, and CHARM preserved [51]

Older age was also associated with higher PASP in our study.  These finding correlate with data that demonstrate that pulmonary artery systolic pressure increases with advancing age in normal adults, suggesting that age-associated blood vessel stiffening may contribute to these differences in pulmonary artery systolic pressure.[52]


The mortality and hospitalization of heart failure (HHF) rate vary in HFpEF population according to the design of studies, patient status (hospitalized vs ambulatory) , the threshold used to define a preserved LVEF, and the inclusion end exclusion criteria. [53] Accordingly, mortality was higher in studies that included only hospitalized patients. [54,55].

In-hospital mortality varies from 2,4 % to 4,9 % [50] in observational studies, with slightly higher mortality at 30 days (5 %) and, 60 and 90 days (9,5 %), while the one-year mortality varies from 20 % to 29%. [56]. Our results showed slightly lower one-year mortality as compared to data from other studies, with a rate of 13.7%. indeed, our study included both inpatients and outpatients, but the vast majority were outpatients. There is also a change in the distribution of the causes of death towards non-cardiovascular causes in relation to an increase in non-cardiovascular comorbidities, [57] especially in HFpEF patients [ 58], emphasizing the key role of comorbidities in these patients [59]. In our study, 45% of deaths were from a non-cardiovascular cause.

Overall, 28-30% of hospitalizations in major HFpEF Randomized control trials [60] were related to HF, and patients with HFpEF seem to have an early risk of HF-specific hospitalization of ∼10–30%. In our study, the global rate of Hospitalization of HF was 5.9% only, perhaps because of a large proportion of ambulatory patients included in our study.



The majority of patients in our cohort are elderly and hypertensive women, more than half of whom have diabetes. Patients had a high prevalence of alteration in longitudinal systolic function with an increase in LV mass, an alteration in diastolic function, and high levels of GDF-15. The independent prognostic factors of one year outcome were signs of peripheral venous congestion, anemia and PASP.


  1. Braunwald E. Shattuck reading—cardiovascular medicine at the turn of the millennium: triumphs, concerns, and opportunities. N Engl J Med. 1997; 337(19):1360-1369. DOI: 10.1056/NEJM199711063371906
  2. McCullough PA, Philbin EF, Spertus JA, Scott Kaatz, Keisha R Sandberg, and al. Confirmation of a heart failure epidemic: findings from the Resource Utilization Among Congestive Heart Failure (REACH) study. J Am Coll Cardiol. 2002; 39(1):60-69. DOI: 10.1016/s0735-1097(01)01700-4
  3. Owan TE, Redfield MM. Epidemiology of diastolic heart failure.ProgCardiovasc Dis. 2005;47(5):320-332. DOI: 10.1016/j.pcad.2005.02.010.
  4. Owan TE, Hodge DO, Herges RM, Steven J Jacobsen, Veronique L Roger, and al. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N EnglJMed. 2006;355:251-259. DOI: 10.1056/NEJMoa052256
  5. Braunwald E. Heart failure. JACC Heart Fail. 2013;1(1):1-20. DOI: 10.1016/j.jchf.2012.10.002
  6. Sanjiv J. Shah, Daniel H. Katz, Senthil Selvaraj, Michael A Burke, Clyde W Yancy and al. Phenomapping for novel classification of heart failure with preserved ejection fraction. Circulation 2015. January 20(3): 269-279. DOI: 10.1161/CIRCULATIONAHA.114.010637
  7. M. Galinier et al. Preserved Ejection Fraction Heart Failure - Status and Prospects. Cardiology- /journal/article/0029203. November 27, 2019
  8. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. The Task Force for the diagnosis and treatment of acute and chronicheart failure of the European Society of Cardiology. Eur Heart J 2016;37:2129–2200.
  9. M. Vaduganathan, A. Michel, K. Hall, C. Mulligan, S. Nodari  and al. Spectrum of epidemiological and clinical findings in patients with heart failure with preserved ejection fraction stratified by study design: a systematic review. European Journal of Heart Failure (2016) 18, 54–65 doi:10.1002/ejhf.442. DOI: 10.1002/ejhf.442.
  10. José A. Magaña-Serrano, Wael Almahmeed, Efrain Gomez, Mostafa Al-Shamiri, Djamila Adgar, and al. Prevalence of Heart Failure With Preserved Ejection Fraction in Latin American, Middle Eastern, and North African Regions in the I PREFER Study (Identifification of Patients With Heart Failure and PREserved Systolic Function: An Epidemiological Regional Study). Am J Cardiol 2011;108:1289 –1296). DOI: 10.1016/j.amjcard.2011.06.044
  11. S. Benkhedda, A. Chibane, A. Temmar, et al. Prevalence of cardiovascular risk factors associated to hypertension in the Algerian population. Report SAHA, J Hypertens, 23, Suppl. 2, 2005,"
  12. Benkhedda, S; Chibane, A; Temmar, et al. Hypertension in Algeria: an epidemiological overview: P3. 377, Journal of Hypertension, 22, S396, 2004, LWW"
  13. Benkhedda, S; Chibane, A; Atif, et al. Prevalence of cardiovascular risk factors associated with hypertension in the Algerian population. A national survey journal of hypertension, 23,s 188-s189,2005,"lippincott williams & wilkins 530 walnut st, philadelphia, pa 19106-3261 usa
  14. Benkhedda, S; Chibane, A; Temmar, et al. HTA in Algeria: frequency and epidemiological characteristics-survey results SAHA1, Arch Mal Coeur Opinion 97, 51-52, 2004,"
  15. Benkhedda, S; Chibane, A; Temmar, et al. Hypertension: Prevalence, awareness, treatment, and control in Algeria. Result of the national survey journal of hypertension, 23, s295-s295, 2005,""lippincott williams & wilkins 530 walnut st, philadelphia, pa 19106-3261 usa"""
  16. Kelly McHugh , Adam D DeVore , Jingjing Wu, Roland A Matsouaka, Gregg C Fonarow, and al. Heart Failure With Preserved Ejection Fraction and Diabetes: JACC State-of-the-Art Review. J Am Coll Cardiol. 2019 Feb 12;73(5):602-611. DOI: 10.1016/j.jacc.2018.11.033
  17. A P. Ambrosy, G C. Fonarow, J Butler, O Chioncel, S J Greene, and al. The Global Health and Economic Burden of Hospitalizations for Heart Failure Lessons Learned From Hospitalized Heart Failure Registries. Journal of the American College of Cardiology Vol. 63, No. 12, 2014. DOI: 10.1016/j.jacc.2013.11.053
  18. D. Djermane, M. Djouhri, F.Z. Amorouayeche, A. Azzouz, S. Ouabdeslem, and al.. Intra-hospital prognosis of acute heart failure: Preliminary results in an Algerian population, Archives of Cardiovascular Diseases Supplements, 11, 1.40, 2019, Elsevier". Doi : 10.1016/j.acvdsp.2018.10.085
  19. N. Taleb-Bendiab,  S. Benkhedda, L. Henaoui,N. Meziane-Tani. Assessment of the study of longitudinal systolic function by 2D strain in hypertensive patients with preserved LVEF, Archives of Cardiovascular Diseases Supplements, 10,1,109, 2018, Elsevier. Doi : 10.1016/j.acvdsp.2017.11.222
  20. Jennifer E Ho, Asya Lyass, Douglas S Lee, Ramachandran S Vasan, William B Kannel, and al. Predictors of new-onset heart failure: differences in preserved versus reduced ejection fraction. Circ. Heart Fail. 6, 279-286 (2013). DOI: 10.1161/CIRCHEARTFAILURE.112.972828
  21. K. Okuno, Y. Naito, M. Asakura, M. Sugahara, T. Horimatsu, and al. Anemia has an impact on prognosis in heart failure with preserved ejection fraction with mild chronic kidney disease Heart & Vasculature 34 (2021) 100796. DOI: 10.1016/j.ijcha.2021.100796
  22. KA Ammar, MM Redfield, DW Mahoney, M Johnson, S J Jacobsen, and al. Central obesity: association with left ventricular dysfunction and mortality in the community. Am Heart J. 2008 Nov;156(5):975-81.  DOI: 10.1016/j.ahj.2008.06.018
  23. M J Lenzen, W J M Scholte op Reimer, E Boersma, P J M J Vantrimpont, F Follath, and al. Differences between patients with a preserved and a depressed left ventricular function: a report from the EuroHeart Failure Survey. Eur. Heart J. 25, 1214-1220 (2004). DOI: 10.1016/j.ehj.2004.06.006
  24. R S. Bhatia, J V Tu, D S. Lee, P C. Austin, J. Fang, and al. Outcome of heart failure with preserved ejection fraction in a population-based study. Engl. J. Med. 355, 260-269 (2006). DOI: 10.1056/NEJMoa051530
  25. D S. Lee, P Gona, R S Vasan, M G Larson, E J Benjamin, and al. Relation of disease pathogenesis and risk factors to heart failure with preserved or reduced ejection fraction: insights from the framingham heart study of the national heart, lung, and blood institute. Circulation 119, 3070-3077 (2009). DOI: 10.1161/CIRCULATIONAHA.108.815944.
  26. Z J Eapen, M A Greiner, G C Fonarow, Z Yuan, R M Mills, and al. Associations between atrial fibrillation and early outcomes of patients with heart failure and reduced or preserved ejection fraction. Am Heart J 2014; 167: 369-375. e2. DOI: 10.1016/j.ahj.2013.12.001
  27. C S Lam, E. Donal, E Kraigher-Krainer, R S Vasan, and al. Epidemiology and clinical course of heart failure with preserved ejection fraction.Eur. J. Heart Fail. 13, 18-28 (2011). DOI: 10.1093/eurjhf/hfq121
  28. Y. Sotomi, S.Hikoso, D. Nakatani, H. Mizuno, K. Okada, and al. Sex Differences in Heart Failure With Preserved Ejection Fraction. J Am Heart Assoc. 2021;10:e018574.
  29. B Özlek, E Özlek, S Kahraman , M Tekinalp , H Zencirk?ran A?u?,  and al. Gender disparities in HFmrEF and HFpEF. Anatol J Cardiol 2019; 21: 242-52. DOI:10.14744/AnatolJCardiol.2019.71954
  30. A B Mendez Fernandez, A F Gregori, A G Osuna, S M Perez, M J P Buxo, and al. Growth differentiation factor 15 as mortality predictor in heart failure patients with non-reduced ejection fraction. ESC Heart Fail . 2020 Oct;7(5):2223-2229. doi: 10.1002/ehf2.12621
  31. M M.Y. Chan, R.Santhanakrishnan, J P.C. Chong, Z. Chen, B C. Tai, and al. Growth differentiation factor 15 in heart failure with preserved vs. reduced ejection fraction European Journal of Heart Failure (2016) 18, 81–88 doi:10.1002/ejhf.431
  32. M. Wesseling, J.H.C. de Poel and S. C.A. de Jager. Growth differentiation factor15 in adverse cardiacremodelling: from biomarker to causal player. ESC Heart Failure2020;7:1488–1501
  33. E. Donal, LH Lund, E. Oger, C Hage, H. Persson, and al. New echocardiographic predictors of clinical outcome in patients presenting with heart failure and a preserved left ventricular ejection fraction: a subanalysis of the Ka (Karolinska) Ren (Rennes) Study. Eur J Heart Fail 2015; 17: 680–8. DOI: 10.1002/ejhf.291
  34. R T. Campbell, PS  Jhund, D. Castagno, NM Hawkins, MC. Petrie, and al. What have we learned about patients with heart failure and preserved ejection fraction from DIGPEF, CHARM-preserved, and I-PRESERVE? J Am Coll Cardiol 2012;60:2349—56. DOI: 10.1002/ejhf.291
  35. JG. Cleland, M. Tendera, J. Adamus,  N. Freemantle, L. Polonski, and al. The perindopril in elderly people with chronic heart failure (PEP-CHF) study. Eur Heart J 2006; 27(19):2338-2345. DOI: 10.1093/ eurheartj/ehl250
  36. DK Gupta, AM. Shah, D. Castagno,  M Takeuchi, L R Loehr, and al. Heart Failure with Preserved Ejection Fraction in African-Americans - The Atherosclerosis Risk in Communities (ARIC) Study. JACC Heart Fail 2013;1(2):156-163. DOI: 10.1016/j.jchf.2013.01.003
  37. Gomez-Soto FM, Romero SP, Bernal JA, et al. a propensity-adjusted case-control study. Int J Cardiol 2010; 139 (3):276-282.
  38. AM. Shah, S J. Shah, I S. Anand, et al. Cardiac Structure and Function in Heart Failure with Preserved Ejection Fraction: Baseline Findings from the Echocardiographic Study of the Treatment Of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) Trial. Circ Heart Fail. 2014 January ; 7(1): 104–115.
  39. M. R. Zile, J. S. Gottdiener, S. J. Hetzel, et al. Prevalence and Significance of Alterations in Cardiac Structure and Function in Patients With Heart Failure and a Preserved Ejection Fraction Circulation. 2011; 124:2491-2501.
  40. Persson et al. Diastolic Dysfunction in Heart Failure with Preserved Systolic Function: Need for Objective Evidence Results from the CHARM Echocardiographic Substudy-CHARMESJACC Vol. 49, No. 6, 2007. February 13, 2007:687-94
  41. Rossi A, Gheorghiade M, Triposkiadis F, et al. Left atrium in heart failure with preserved ejection fraction: structure, function, and significance. Circ Heart Fail 2014; 7 1042-1049.
  42. Gavin A. Lewis, Erik B. Schelbert, Simon G. Williams et al.  Biological Phenotypes of HFpEF. JACC VOL. 70, NO. 17, 2017:2186 – 200
  43. M. Tadic, C. Cuspidi, S. Plein, E. Belyavskiy, F. Heinzel, and al. Sex and Heart Failure with Preserved Ejection Fraction: From Pathophysiology to Clinical Studies. J. Clin. Med. 2019, 8, 792; doi:10.3390/jcm8060792
  44. M. Gori., C.S. Lam., D.K. Gupta., A.B. Santos., S. Cheng, and al.Sex-specific cardiovascular structure and function in heart failure with preserved ejection fraction. Eur. J. Heart Fail. 2014;16:535–542. doi: 10.1002/ejhf.67. 
  45. Obokata M, Kane GC, Reddy YN, et al. A Simultaneous Invasive-Echocardiographic Study. Circulation. 2017; 135(9): 825-838. 
  46. Lancellotti P, Galderisi M, Edvardsen T, et al. results of the multicentre EACVI Euro-Filling study. Eur Heart J Cardiovasc Imaging. 2017;18(9):961-968.
  47. Balaney B, Medvedofsky D, Mediratta A, et al. Invasive Validation of the Echocardiographic Assessment of Left Ventricular Filling Pressures Using the 2016 Diastolic Guidelines: Head-to-Head Comparison with the 2009 Guidelines. J Am Soc Echocardiogr. 2018; 31(1): 79-88. 
  48. Sato K, Grant ADM, Negishi K, et al. Reliability of updated left ventricular diastolic function recommendations in predicting elevated left ventricular filling pressure and prognosis. Am Heart J. 2017;189:28-
  49. Andersen OS, Smiseth OA, Dokainish H, et al. Estimating Left Ventricular Filling Pressure by Echocardiography. J Am Coll Cardiol. 2017 Apr 18;69(15):1937-1948.
  50. Morris DA, Ma XX, Belyavskiy B, et al. Left ventricular longitudinal systolic function analyzed by 2d speckle-tracking echocardiography in heart failure with preserved ejection fraction: a meta-analysis. Open Heart 2017;4:           e000630.
  51. J Tromp, L Shen, P S. Jhund, I S. Anand, P E Carson, and al.  Age-Related Characteristics and Outcomes of Patients With Heart Failure With Preserved Ejection Fraction. J Am Coll Cardiol 2019;74:601–12
  52. G C Kane, A Sachdev, H R Villarraga, N M Ammash, J K Oh, and al. Impact of age on pulmonary artery systolic pressures at rest and with exercise. Echo Research and Practice.  Vol: 53–61 (2016) DOI: .
  53. Somaratne, J. B. et al. The prognostic significance of heart failure with preserved left ventricular ejection fraction: a literature-based meta-analysis. Eur. J. Heart Fail. 11, 855–862 (2009).
  54. Perez De Isla, L. et al. Diastolic heart failure in the elderly: in-hospital and long-term outcome after the first episode. Int. J. Cardiol. 134, 265–270 (2009).
  55. M. Vaduganathan et al. Spectrum of epidemiological and clinical findings in patients with heart failure with preserved ejection fraction stratified by study design: a systematic review. European Journal of Heart Failure (2016) 18, 54–65 doi:10.1002/ejhf.442.
  56. Fonarow, G. C. et al. Characteristics, treatments, and outcomes of patients with preserved systolic function hospitalized for heart failure: a report from the OPTIMIZE-HF registry. J. Am. Coll. Cardiol. 50,768–777 (2007).
  57. Roger VL. Epidemiology of heart failure. Circ Res. 2013 Aug 30; 113 (6):646-59. Doi: 10.1161/ CIRCRESAHA. 113. 300268.
  58. Roger VL, Weston SA, Redfield MM et al. Trends in heart failure incidence and survival in a community-based population. JAMA. 2004 Jul 21; 292 (3):344-50.
  59. Pardeep S. Jhund and Luigi Tavazzi. Has the ‘epidemic’ of heart failure been replaced by a tsunami of co-morbidities? European Journal of Heart Failure (2016) 18, 500–502 doi:10.1002/ejhf.529.
  60. Massie BM, Carson PE, McMurray JJ, Komajda M, McKelvie R, Zile MR, Anderson S, Donovan M, Iverson E, Staiger C, Ptaszynska A. Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med 2008;359:2456–2467.
  61. Wang J, Khoury DS, Yue Y, et al. Preserved left ventricular twist and circumferential deformation, but depressed longitudinal and radial deformation in patients with diastolic heart failure. Eur Heart J 2008; 29: 1283-9.
  62. Liu YW, Tsai WC, Su CT, et al. Evidence of left ventricular systolic dysfunction detected by automated function imaging in patients with heart failure and preserved left ventricular ejection fraction. J Card Fail 2009; 15: 782-9.
  63. Phan TT, Shivu GN, Abozguia K, et al. Left ventricular torsion and strain patterns in heart failure with normal ejection fraction are similar to age-related changes. Eur J Echocardiogr 2009;10:793-800.
  64. Tan YT, Wenzelburger F, Lee E, et al. The pathophysiology of heart failure with normal ejection fraction: exercise echocardiography reveals complex abnormalities of both systolic and diastolic ventricular function involving torsion, untwist, and longitudinal motion. J Am Coll Cardiol 2009; 54: 36-46.
  65. Kasner M, Gaub R, Sinning D, et al. Global strain rate imaging for the estimation of diastolic function in HFNEF compared with pressure-volume loop analysis Eur J Echocardiogr 2010; 11: 743-51.
  66. Morris DA, Gailani M, Vaz Pérez A, et al. Left atrial systolic and diastolic dysfunction in heart failure with normal left ventricular ejection fraction. J Am Soc Echocardiogr 2011; 24: 651-62.
  67. Yip GW, Zhang Q, Xie JM, et al. insights from speckle-tracking echocardiography. Heart 2011; 97: 287-94.
  68. Abe H, Caracciolo G, Kheradvar A, et al. Contrast echocardiography for assessing left ventricular vortex strength in heart failure: a prospective cohort study. Eur Heart J Cardiovasc Imaging 2013; 14: 1049-60.
  69. Obokata M, Negishi K, Kurosawa K, et al. Incremental diagnostic value of the strain with leg lifts in heart failure with preserved ejection fraction. JACC Cardiovasc Imaging 2013; 6 749-58.
  70. Pellicori P, Kallvikbacka-Bennett A, Khaleva O, et al. Global longitudinal strain in patients with suspected heart failure and a normal ejection fraction: does it improve diagnosis and risk stratification? Int J Cardiovasc Imaging 2014; 30:69–79.
  71. Kraigher-Krainer E, Shah A, Gupta D et al. Impaired systolic function by strain imaging in heart failure with preserved ejection fraction. JACC 2014 ; 5 : 447-456.
  72. Menet A, Graft L, Ennezat PV, et al. Is mechanical dyssynchrony a therapeutic target in heart failure with preserved ejection fraction? Am Heart J 2014; 168: 909-16.
  73. Luo XX, Fang F, Lee AP, et al. What can three-dimensional speckle tracking echocardiography contribute to evaluate global left ventricular systolic performance in patients with heart failure? Int J Cardiol 2014;172: 132-7
  74. Wang J,