AL-Radhy A, Al Sagheer N, Shujaa A, Al-Zaazaai A, Al Bakri A, et al. Demographics, Clinical and Therapeutic Characteristics of Hospitalized Heart Failure Patients with Mildly-Reduced Ejection Fraction in Yemen: Data from the Gulf Acute Heart Failure Registry (Gulf CARE)

Adnan AL-Radhy; Nora Al Sagheer; Abdulkafy Shujaa; Ali Al-Zaazaai; Aref Al Bakri; Khaled Al Khamesy; Saleh Bahaj

Research Article

Austin J Endocrinol Diabetes. 2024; 11(1): 1106.

Demographics, Clinical and Therapeutic Characteristics of Hospitalized Heart Failure Patients with Mildly-Reduced Ejection Fraction in Yemen: Data from the Gulf Acute Heart Failure Registry (Gulf CARE)

Adnan AL-Radhy¹; Nora Al Sagheer¹; Abdulkafy Shujaa¹; Ali Al-Zaazaai²; Aref Al Bakri³; Khaled Al Khamesy⁴; Saleh Bahaj⁵

¹Department of Cardiology, Faculty of Medicine and Health Sciences, Sana’a University-Yemen

²St-Marien hospital Bonn Venusberg, department of internal medicine, Bonn, Germany

³Department of physiology, Faculty of Medicine and Health Sciences, Sana’a University-Yemen

⁴MS.C Clinical Pharmacy, Faculty of Medicine and Health Sciences, Wenzhou Medical University-China

⁵Department of microbiology, Faculty of Medicine and Health Sciences, Sana’a University-Yemen

*Corresponding author: Nora Alsagheer, Faculty of Medicine & Health Sciences, Sana’a University, Yemen. Email: nalsageer@gmail.com

Received: July 12, 2024 Accepted: August 02, 2024 Published: August 09, 2024

Abstract

Background: Heart Failure (HF) with mildly reduced ejection fraction (HFmrEF) was recently recognised as a distinct clinical entity with different epidemiological, clinical and echocardiographic characteristics from HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). However, most of the available data about HRmrEF is limited to western countries. Other world regions, including Yemen, lack real-world HFmrEF data, which could help guide diagnosis and prognosis, and treatment.

Objectives: This study describes the demographic, clinical, echocardiographic, and therapeutic characteristics of Acute Heart Failure (AHF) patients in Yemen who satisfied the current clinical definition of HFmrEF.

Methods: We retrospectively analysed Yemeni patients with AHF enrolled in the Gulf aCute heArt failuRe rEgistry (CARE). We stratified patients into three EF groups based on the 2016 European HF guidelines: reduced EF (HFrEF< 40%), mid-range EF, now redefined as mildly reduced HF (HFmrEF, EF 40%-49%), and preserved EF (HFpEF, EF=50%), then compared admission characteristics, in-hospital treatment and on-discharge medications. Results: The study included 1,408 (91.7%) AHF Yemeni patients with echocardiographic data from the Gulf CARE Registry. HFmrEF patients accounted for a quarter (n = 361; 25.6%) of the cohort. The majority had HFrEF (n = 748, 53.1%), and HFpEF had the least proportion (n = 299, 21.2%). Compared to HFrEF and HFpEF, HFmrEF patients were older, had male preponderance and more risk factors. They also had a higher prevalence of CoronaryArtery Disease (CAD), Diabetes Mellitus (DM), and Hypertension (HTN) but lower cases of Valvular Heart Disease (VHD) and Atrial Fibrillation (AF). They had a distinctive clinical profile, de novo HF, lower symptomatic burden and more clinically stable, but higher Left Ventricular Hypertrophy [LVH] and lower prevalence of Pulmonary Hypertension (PHTN).

Conclusion: Hospitalized Yemeni AHF patients stratified by ejection fraction represent heterogeneous groups in terms of demography, clinical presentation, and medications. HFmrEF patients accounted for a large proportion representing a demographically and clinically diverse group with many intermediate features compared to HFrEF and HFpEF patients.

Keywords: Heart Failure; HFmrEF; Yemen

Introduction

Background

Heart Failure (HF) affects more than 64 million people globally, and the prevalence is expected to continue to increase due to improved post-diagnosis survival and longer life expectancy in the general population. Yet despite significant advancements in treatment, HF morbidity and mortality remain unacceptably high. The heavy burden on health expenditures is also concerning [1-4]. However, current efforts to classify HF subtypes into distinct disease entities recognize differences in pathophysiology and therapeutic approaches that have improved the safety and efficacy of clinical management [1]. Left Ventricular (LV) Ejection Fraction (LVEF) has been the mainstay of HF classification. Up to 2013, the two HF subtypes were preserved EF (HFpEF), described as LVEF = 50%, and HF with reduced EF (HFrEF), defined as LVEF < 40% [3]. The classification omitted patients with LVEF 40-49%, which the American College of Cardiology and American Heart Association (ACC/AHA) HF guidelines were recognized in 2013 [5]. However, changes in terminology for patients with LVEF 40-49% and LVEF definition have undermined comparative studies. Initially, the ACC/AHA labelled them as HF with borderline LVEF and, in 2014, renamed them to HF with Mid-Range EF [6]. Later, the European Society of Cardiology (ESC) HF guidelines in May 2016 recognized mid-range HF as a distinct clinical entity. [7] Recently in 2021, the writing committee of the 2021 ESC/HFA HF guidelines renamed mid-range to mildly-reduced EF (HFmrEF) and revised the LVEF definition from 40-49% to 41-49% [8,9]. Despite concerted efforts to recognize HFmrEF as a distinct clinical entity and inspire epidemiological and review studies, consensus on its clinical characteristics still needs to be reached [10-17]. Specifically, gaps exist in the safety and efficacy of the current evidence-based therapy for HFrEF and HFpEF to HFmrEF patients [18-20]. Since most evidence-based research on the epidemiology of HFmrEF are from western countries with differences in genetics, environment, lifestyles and healthcare delivery to the Middle East and the Arabian Gulf [21-23]. Thus, this study aims to fill the gap by analysing and describing demographics, clinical, echocardiographic, and therapeutic characteristics of HFmrEF patients in Yemen.

Rationale and Aim of the Study

Classification of HF subtypes into distinct clinical entities based on LVEF cut-off points with different morbidity, mortality, pathophysiology and therapeutic outcomes has substantially contributed to improvement in clinical management. However, a firm understanding of the distinguishing demographic and clinical features is necessary to improve the diagnosis, prognosis and treatment of HFmrEF. Yet, in Yemen, such population-based data is lacking. Two studies examined hospitalized Acute Heart Failure (AHF) patients and provided a general description without delineating them into HF subtypes [24,25]. Hence. the present study seeks to describe the demographic, clinical echocardiography and treatment of HFmrEF patients. The findings hope to improve the diagnosis accuracy of HFmrEF patients and determine whether current HF therapies are effective for this recently described HF subtype.

Ethics Approval

This study re-used existing data from the Gulf CARE registry. The Institutional Review Board (IRB) recognises that a study analysing de-identified publicly available data does not constitute human research subjects as defined at 45 CFR 46.102. Thus, the present study did not require IRB review or approval.

Materials and Methods

Study Design

This retrospective cohort study analysed AHF Yemeni patients from the Gulf CARE registry, whose design, methodology and characteristics have been described in detail elsewhere [26,27]. In brief, the Gulf CARE registry is the first prospective, a multinational, multicentre observational survey of patients = 8 years admitted with a diagnosis of AHF to 47 hospitals in seven Middle Eastern countries: Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, United Arab Emirates, and Yemen. The inclusion criteria were all AHF patients >18 years of age admitted to participating hospitals between 14 February 2012 and 14 November 2012, irrespective of aetiology. However, we excluded patients whose final diagnosis was not HF. The Gulf CARE study adopted the 2008 ESC guidelines definition of AHF as a rapid onset or change in the signs and symptoms of HF, resulting in the need for urgent therapy. HF is a clinical syndrome presenting with a combination of symptoms, signs and objective evidence of structural or functional abnormality. The symptoms are dyspnoea at rest or on exercise, fatigue, tiredness, and ankle swelling. The signs are tachycardia, tachypnoea, elevated jugular venous pressure, pulmonary rales, pleural effusion, hepatomegaly, and peripheral oedema. Objective evidence of structural or functional cardiac abnormalities is a third heart sound, murmurs, cardiomegaly, abnormal echocardiogram, and raised natriuretic peptide concentration. AHF was further classified as Acute Decompensated Chronic HF (ADCHF), defined as the worsening of HF in patients with a previous diagnosis or hospitalisation for HF or de novo AHF. Definitions of data variables in the CRF were based on the 2008 ESC guidelines and the 2005 ACC clinical data standards [29]. Exposure to khat is chewing khat plants or leaves within one month after index admission [30].

Data Variables

In the definition of comorbidities, CAD diagnosis was the presence of any of the following conditions. At least one major epicardial coronary artery determined by coronary angiography to have >70% obstruction, history of Myocardial Infarction (MI) associated with wall motion abnormality on echocardiography or gated blood pool imaging, and/or stress testing (with or without imaging). Hypertension was defined as a history of hypertension diagnosed and treated with a hypertensive medication or BP >140 mm Hg systolic or 90 mm Hg diastolic on at least two occasions or BP >130 mm Hg systolic or 80 mm Hg diastolic on at least two occasions for patients with diabetes or Chronic Kidney Disease (CKD). Baseline and admission-based variables captured demographics, comorbidities, risk factors, clinical presentation, laboratory data including troponin and BNP, medication regimens, in-hospital outcome, aetiology, and precipitating factors for AHF. The Gulf CARE registry collected echocardiography and coronary angiogram data along with cardiac procedures such as PCI, coronary artery bypass surgery (CABG), device therapy, or any cardiac surgery data during admission and on follow-up. Follow-up of patients at three months and one year was performed. Follow-up was done by telephone at three months, via phone, or a clinic visit at one year. Data was entered online using a custom-designed electronic Case Record fFrm (CRF) at the Gulf CARE website (www.gulfcare.org). Institutional or national ethical committee or review board approval was obtained in the seven participating countries. The study is registered at clinicaltrials.gov (NCT01467973).

Study Population and Data Analysis (Categorization of LVEF)

The present study included Yemeni patients enrolled in the Gulf CARE Registry with a clinical diagnosis of HF with LVEF information. Yemen data came from eight major hospitals across the country. The Gulf CARE study obtained institutional ethical approval in each participating hospital, and all patients provided informed consent. In total, 1,536 Yemeni patients enrolled Gulf CARE registry from February 14, 2012, to November 13, 2012. However, this study included only 1,408 (91.7%) AHF Yemeni patients with echocardiographic data. We adopted the 2016 European HF guidelines definition of HFmrEF (LVEF: 40-49%), HFrEF (LVEF<40%), and HFpEF (LVEF =50%). We stratified HF patients into the three LVEF groups and compared them based on admission characteristics, in-hospital treatment, and on-discharge medications.

Statistical Analysis

We employed descriptive statistics to summarise the data into HFrEF, HFmrEF and HFpEF subtypes. We reported frequencies and percentages for categorical variables, and differences between the three HF subtypes were analysed using Pearson’s 2 test or Fisher’s exact test. For continuous variables, we used measures of central tendency (mean and standard deviation) to summarise the data and analysed using a t-test to compare the difference in means. The level of significance was set at p-value < 0.05. Statistical analysis was conducted using IBM SPSS Statistics version 26.

Results

Initially we analysed the distribution of the three HF subtypes from the 1,408 AHF Yemeni patients included in the study. Most patients had HFrEF (n = 748; 53.1%), followed by HFmrEF (n = 361; 25.6%) and HFpEF (n =299; 21.2%). The findings suggest that in Yemen, about a quarter of patients diagnosed with AHF fall within the HFmrEF LVEF clinical cut-off.

Demographic Characteristics

Demographic characteristics stratified by the three HF subtypes are summarized in Table 1. Overall, the 1,408 AHF patients were old (mean age = 53.5±15.4 years), more males (64.1%), smoked tobacco (34%) and chewed Katt (58%). The mean age of HFmrEF patients was older than HFrEF and HFpEF (57±12.9 vs. 53±14.6 vs. 50±18.9), more males (71.7% vs 70.6% vs 43.1%) and higher rate of smoking (39% vs. 36% vs. 24%) and chewing Katt (68% vs. 61% vs 38%). However, the mean BMI among entire cohort 25.8+4.4 kg/m2 with no significant difference between groups (p= 0.077).

Table 1: Demographic and Baseline Characteristics of AHF patients.




  
    Characteristics 
    EF (< 40%) 
    EF (40�49%) 
    EF (= 50%) 
    All 
    p- 
  
  
    
    (N = 748) 
    (N = 361) 
    (N = 299) 
    (N = 1408) 
    value 
  
  
    Age, mean± SD 
    53.3 ± 14.6 
    57.0 ±12.9 
    51.1 ±18.9 
    53.5 ± 15.4 
    
  
  
    Male 
    528 (70.6%) 
    259 (71.7%) 
    129 (43.1%) 
    916 (65.1%) 
    0 
  
  
    Smoking 
    266 (35.6%) 
    140(38.8%) 
    72 (24.1%) 
    478 (33.9%) 
    0.001 
  
  
    Chowing Katt 
    454 (60.7%) 
    245 (67.9%) 
    114 (38.1%) 
    813 (57.7%) 
    0 
  
  
    Admission for Heart Failure 
    369 (49.3%) 
    94 (26.0%) 
    121 (40.5%) 
    584 (41.5%) 
    0 
  
  
    Known Systolic LV    dysfunction 
    348 (46.5%) 
    77 (21.3%) 
    16 (5.4%) 
    441 (31.3%) 
    
  
  
    Cardiologist 
    551 (73.7%) 
    226(62.6%) 
    238 (79.6%) 
    1015 (72.1%) 
    0 
  
  
    Underlying Heart Disease    & Co-Morbidities 
    
    
    
    
    
  
  
    Known CAD 
    288 (38.5%) 
    189 (52.4%) 
    40 (13.4%) 
    517 (36.7%) 
    0 
  
  
    HTN 
    254 (34.0%) 
    168(46.5%) 
    92 (30.8%) 
    514 (36.5%) 
    0 
  
  
    VHD 
    66 (8.8%) 
    23 (6.4%) 
    102 (34.1%) 
    191 (13.6%) 
    0 
  
  
    Atrial Fibrillation 
    41 (5.5%) 
    8 (2.2%) 
    30 (10.0%) 
    79 (5.6%) 
    0 
  
  
    Diabetes mellitus 
    132 (17.7) 
    107(29.6%) 
    63 (21.0%) 
    302 (21.4%) 
    
  
  
    Hyperlipidaemia 
    93(12.4%) 
    49 (13.6%) 
    6 (2.0%) 
    148 (10.5%) 
    0 
  
  
    Asthma/ COPD, 
    3 (0.4%) 
    8 (2.2%) 
    50 (16.7%) 
    61 (4.3%) 
    0 
  
  
    CKD / Dialysis 
    10 (1.3%) 
    6 (1.7%) 
    5 (1.7%) 
    21 (1.5%) 
    0.878 
  
  
    PVD 
    11 (1.5%) 
    11 (3.0%) 
    7 (2.3%) 
    29 (2.1%) 
    0.207 
  
  
    Stroke/ TIA 
    38 (5.1%) 
    13 (3.6%) 
    10 (3.3%) 
    61 (4.3%) 
    0.336



Table 1: Demographic and Baseline Characteristics of AHF patients.

Clinical Characteristics

Overall, most of the patients had underlying heart diseases. The most prevalent were CAD (50%), HTN (36.5%), VHD (14%) and AF (8.5%). The most frequently encountered comorbidity was DM (21.4%). However, heart diseases significantly varied across the three HF subtypes. Compared to HFrEF and HFpEF, HFmrEF had higher cases of CAD (52% vs 39% vs 13%), DM (29.6% vs 18% vs 21%), and HTN (46.5% vs 34.0% vs 30.8%) but lower cases of VHD (6.4% vs 8.8% vs 34.1%) and AF (2.2% vs 5.5% vs 10.0%). In addition, HFmrEF shared a similar prevalence of hyperlipidaemia with HFrEF and an intermediate prevalence of asthma/COPD, lower than HFpEF but higher than HFrEF. However, HFpEF Patients compared to HFrEF and HFmrEF were younger (51±18.9 vs 53±14.6 vs 57±12.9) with a higher prevalence of comorbidity – VHD (34% vs 8.8% vs 6.4%, AF (10% vs 5.5% vs 2.2%) Asthma/COPD, (17% vs 0.4% vs 2.2%). Three rare conditions with no significant heterogeneity among the three HF subtypes were Chronic Kidney Disease (CKD)/dialysis, peripheral vascular disease (PVD) and Stroke/Transient Ischaemic Attack (TIA). Table 1 summarises the underlying heart disease and comorbidities of the 1,408 AHF patients.

Clinical Presentation and Physical Examination

The most frequently presenting HF symptoms were dyspnoea in almost all cases, with 75% in NYHA Class III/IV, orthopnoea (82.5%), Paroxysmal nocturnal dyspnoea PND: (77%) and easy fatigability (76%), as summarized in Table 2. A striking difference in the clinical presentation of patients was observed among the different HF types. Compared to others, HFmrEF was the least presented in NYHA Class IV (21% vs 49% vs 26%), orthopnoea (69% vs 88% vs 85%), PND (65% vs 84% vs 73%), lower limb oedema (34%, 73%, 62%) and weight gain (18% vs 55% vs 39%). HFmrEF patients were the most frequent group that reported chest pain (72% vs 53% vs 38%). HFmrEF was also associated with the lowest mean heart rate (93±22 vs 98±24 vs 104 ±18) and highest admission mean Systolic BP (136(±27 vs. 125± 29 vs. 131± 30) (p. < 0.05). HFpEF is associated with the lowest mean systolic BP. Overall basal lung crepitations were the most typical clinical sign reported (95%), with no significant differences among HF types. Other relatively common signs of HF were peripheral oedema (65%), raised (> 6 cm) JVP (62.5%), enlarged tender liver (60%), gallop rhythm (56%) and signs of pleural effusion (31%), with significant heterogeneity among the different HF types. All these signs were generally seen significantly more frequently among HFrEF patients than the other two types, except for the S3 gallop rhythm. HFmrEF was associated with the lowest prevalence compared to other types (p<0.05). Gallop rhythm was observed significantly more frequently with HFrEF patients (69%), with no significant difference between HFpEF and HFmrEF patients (41.6% vs 40.8%).

Table 2: Clinical Presentation, Physical examination & Laboratory Data of AHF Patients N (%).




  
    Characteristics
    EF (< 40%)
    EF (40–49%)
    EF (= 50%)
    All
    p-
  
  
    
    (N = 748)
    (N = 361)
    (N = 299)
    (N = 1408)
    value
  
  
    ADHF
    432 (57.8%)
    121 (33.5%)
    166 (55.5%)
    719 (51.1%)
    
  
  
    New-Onset HF
    316 (42.2%)
    240 (66.5%)
    133 (44.5%)
    689 (48.9%)
    
  
  
    Clinical Presentation
    
    
    
    
    
  
  
    NYHA III- IV
    616 (82.3%)
    228 (63%)
    211 (70.5%)
    1059 (75.3)
    
  
  
    Orthopnea
    659 (88.1%)
    248 (68.7%)
    255 (85.3%)
    1162 (82.5%)
    0
  
  
    PND
    629 (84.1%)
    236 (65.4%)
    218 (72.9%)
    1083 (76.9%)
    
  
  
    LL Swelling 
    545 (72.90%) 
    125 (34.60%) 
    184 (61.50%) 
    854 (60.70%) 
    0 
  
  
    Weight gain 
    414 (55.3%) 
    65 (18.0%) 
    86 (28.8%) 
    565 (40.1%) 
    
  
  
    Chest pain 
    396 (52.9%) 
    260 (72.0%) 
    114 (38.1%) 
    770 (54.7%) 
    
  
  
    Palpitation 
    373 (49.9%) 
    168 (46.5%) 
    134 (44.8%) 
    675 (47.9%) 
    
  
  
    Easy Fatigability 
    641 (85.7%) 
    226 (62.6%) 
    199 (66.6%) 
    1066 (75.7%) 
    
  
  
    Syncope 
    68 (9.1%) 
    28 (7.8%) 
    32 (10.7%) 
    128 (9.1%) 
    
  
  
    Physical examination 
    
    
    
    
    
  
  
    HR, Mean, ±SD 
    104.2 ± 18.2 
    93.5 ± 22.4 
    98.3 ± 24.6 
    100.2 ± 21.3 
    
  
  
    SBP (mmHg) - 
    131.7 ± 32.2 
    136.3 ± 27.1 
    125.1 ± 29.6 
    131.5 ± 30.6 
    
  
  
    DBP (mmHg) - 
    83.3 ± 19.5 
    84.7 ± 16.3 
    76.6 ± 17.0 
    82.3 ± 18.4 
    
  
  
    RR (/min) 
    27.2 ± 4.7 
    24.6 ± 5.7 
    25.7 ± 6.1 
    26.2 ± 5.4 
    
  
  
    BMI (kg/m2) 
    25.7 ± 4.0 
    26.2 ± 4.4 
    25.5 ± 5.2 
    25.8 ± 4.4 
    0.077 
  
  
    mean± SD 
    
    
    
    
    
  
  
    Raised JVP 
    530 (70.90%) 
    161 (44.60%) 
    189 (63.20%) 
    880 (62.50%) 
    0 
  
  
    LL Oedema 
    565 (75.5%) 
    144 (39.9%) 
    200 (66.9%) 
    909 (64.6%) 
    
  
  
    Enlarged Tender Liver 
    522 (69.8%) 
    132 (36.6%) 
    186 (62.2%) 
    840 (59.7%) 
    
  
  
    Gallop 
    518 (69.30%) 
    150 (41.60%) 
    122 (40.80%) 
    790 (56.10%) 
    0 
  
  
    Basal Crepitations 
    722 (96.50%) 
    343 (95.00%) 
    269 (90.00%) 
    1334 (94.70%) 
    
  
  
    Signs of PE 
    280 (37.40%) 
    73 (20.20%) 
    84 (28.10%) 
    437 (31.00%) 
    0 
  
  
    Raised (> 6 cm) JVP, Syncope in last one-year,    Acute decompensated Chronic HF, Acute New-Onset HF, PE Pleural Effusion FH    Family history, CMP Cardiomyopathy, Haemoglobin)



Table 2: Clinical Presentation, Physical examination & Laboratory Data of AHF Patients N (%).

Workup Data

Compared to other HF types, HFmrEF patients were associated with higher mean haemoglobin and total cholesterol levels and higher frequency of elevated Troponin-I/T levels. No significant differences among HF types regarding mean creatinine level. HFpEF, compared to other HF types, were associated with a higher prevalence of AF/Flutter (p<0.05), higher mean pulmonary artery systolic pressure (PASP) (p = 0.015), and lower prevalence of Left Bundle Branch Block (LBBB). HFrEF, compared to others, was associated with a higher prevalence of prolonged QRS duration, LBBB, and significant valve disease. HFmrEF, compared to other HF types, was associated higher prevalence of left ventricular hypertrophy, ECG evidence of ischemia (as pathological Q) or documented ischemia on coronary angiogram than others. On the other hand, the prevalence of AF/Flutter and moderate-Severe VHD was lowest among HFmrEF. Table 3 summarizes the work-up data on AHF patients.

Table 3: Workup Data of AHF patients.




  
    Characteristics 
    EF (< 40%) 
    EF (40–49%) 
    EF (= 50%) 
    All 
    p- 
  
  
    
    (N = 748) 
    (N = 361) 
    (N = 299) 
    (N = 1408) 
    value 
  
  
    High Troponin-I/T 
    73 ± 9.8% 
    112 ± 31.0% 
    63 ± 21.1% 
    248 ± 17.6% 
    
  
  
    Hg (g/dL) M±SD 
    12.7 ± 2.4 
    14.0 ± 2.6 
    13.3 ± 2.7 
    13.1 ± 2.6 
    0 
  
  
    Creatinine    mg/dL) 
    1.305 ± .9090 
    1.124 ± .9178 
    1.123 ± 1.1752 
    1.220 ± .9772 
    
  
  
    ECG 
    
    
    
    
    
  
  
    AF/Flutter, 
    59 (7.9%) 
    16 (4.4%) 
    44 (14.7%) 
    119 (8.5%) 
    
  
  
    LV    hypertrophy 
    224 (29.9%) 
    155 (42.9%) 
    96 (32.1%) 
    475 (33.7%) 
    
  
  
    ST-Depression/    T- 
    344 (46.0%) 
    209 (57.9%) 
    86 (28.8%) 
    639 (45.4%) 
    
  
  
    Inversion 
    
    
    
    
    
  
  
    STEMI 
    57 (7.6%) 
    92 (25.5%) 
    29 (9.7%) 
    178 (12.6%) 
    
  
  
    Pathological    Q 
    215 (28.7%) 
    126 (34.9%) 
    23 (7.7%) 
    364 (25.9%) 
    
  
  
    LBBB 
    176 (23.5%) 
    29 (8.0%) 
    4 (1.3%) 
    209 (14.8%) 
    
  
  
    Echo 
    
    
    
    
    
  
  
    Large LA 
    645 (86.2%) 
    231 (64.0%) 
    159 (53.2%) 
    1035 (73.5%) 
    
  
  
    Conc. LVH 
    139 (18.6%) 
    164 (45.4%) 
    101 (33.8%) 
    404 (28.7%) 
    
  
  
    MR, 
    304 (40.6.%) 
    74 (20.5%) 
    28 (9.4%) 
    406 (28.8%) 
    
  
  
    TR, 
    17 (2.3%) 
    9 (2.5%) 
    42 (14.0%) 
    68 ((4.8%)) 
    
  
  
    PASP    (mmHg), 
    55.0 ± 15.4 
    53.1 ± 17.5 
    71.2 ± 25.5 
    58.8 ± 20.4 
    0 
  
  
    Significant    CAD* 
    63 (8.4%) 
    52 (14.4%) 
    -6.70% 
    135 (11.6%) 
    
  
  
    *Significant    CAD on CAG Pulmonary Artery Systolic    Pressure (PASP) (mmHg), mean ± SD, QRS Duration = > 0.12 msec.    Coronary Angiogram within one year of AHF patients, Normal    coronaries/non-significant CAD, Normal /non-significant CAD



Table 3: Workup Data of AHF patients.

Pharmacological Management

Table 4 summarizes the results of in-hospital medications and Guideline-Directed Medical Therapy (GDMT) stratified by three HF subtypes. The most prescribed HF medications on admission were aspirin, diuretics, statin, and digoxin. Specifically, 400 patients (28%) were on Beta-Blockers (BB), 671 (48%) on Angiotensin-Converting Enzyme Inhibitor (ACE-I), 45 (3.2%) on Angiotensin Receptor Antagonist (ARB), and 143 (10.2%) on aldosterone receptor antagonist (MRAs). Compared to HFrEF and HFpEF, fewer HFmrEF patients were on digoxin, diuretics, and oral anticoagulants (p < 0.001) but more on clopidogrel and Statin (p < 0.005). A similar proportion of HFrEF and HFpEF was on diuretics and oral anticoagulants. Fewer HFpEF patients were prescribed oral nitrates ACE-I and ARBs and more on Calcium Channel Blockers (CCB). More HFrEF received Mineralocorticoid Receptor Antagonists (MRAs). On discharge diuretics, BBs and ACE-I were prescribed equally to HFmrEF and HFrEF (p < 0.001), but HFrEF was more frequent on MRAs. Digoxin prescription is similar to HFpEF but less than HFrEF (p < 0.001). Aspirin, clopidogrel, and statin were prescribed more to HFmrEF than others (p < 0.001 except for clopidogrel that was non-significant for HFrEF versus HFpEF.

Table 4: Baseline, In-hospital medications and Use of GDMT stratified by the different HF groups.




  
    Pharmacological Class 
    EF (< 40%) 
    EF (40–49%) 
    EF (= 50%) 
    All 
    p-value 
  
  
    
    (N = 748) 
    (N = 361) 
    (N = 299) 
    (N = 1408) 
    
  
  
    Digoxin 
    
    
    
    
    
  
  
    - Before 
    211 (28.2%) 
    23 (6.4%) 
    58 (19.4%) 
    292 (20.7%) 
    0 
  
  
    - On Discharge 
    344 (46.0%) 
    54 (15.0%) 
    48 (16.1%) 
    446 (31.7%) 
    0 
  
  
    Calcium blockers 
    
    
    
    
    
  
  
    - Before 
    10 (1.3%) 
    13 (3.6%) 
    39 (13.0%) 
    62 (4.4%) 
    0 
  
  
    - On Discharge 
    7 (0.9%) 
    18 (5.0%) 
    49 (16.4%) 
    74 (5.3%) 
    0 
  
  
    Aspirin 
    
    
    
    
    
  
  
    - Before 
    429 (57.4%) 
    236 (65.4%) 
    86 (28.8%) 
    751 (53.3%) 
    0 
  
  
    - On Discharge 
    565 (75.5%) 
    324 (89.8%) 
    180 (60.2%) 
    1069 (75.9%) 
    0 
  
  
    Clopidogrel 
    
    
    
    
    
  
  
    – Before 
    69 (9.2%) 
    92 (25.5%) 
    10 (3.3% 
    171 (12.1%) 
    0 
  
  
    - On Discharge 
    181 (24.2%) 
    220 (60.9%) 
    71 (23.7%) 
    472 (33.5%) 
    0 
  
  
    Statin 
    
    
    
    
    
  
  
    - Before 
    195 (26.1%) 
    138 (38.2%) 
    27 (9.0%) 
    360 (25.6%) 
    0 
  
  
    - On Discharge 
    359 (48.0%) 
    267 (74.0%) 
    94 (31.4%) 
    720 (51.1%) 
    0 
  
  
    Diuretics 
    
    
    
    
    
  
  
    - Before 
    369 (49.3%) 
    123 (34.1%) 
    150 (50.2%) 
    642 (45.6%) 
    0 
  
  
    - On Discharge 
    691 (92.4%) 
    324 (89.8%) 
    233 (77.9%) 
    1248 (88.6%) 
    0 
  
  
    Oral Nitrates 
    
    
    
    
    
  
  
    - Before 
    125 (16.7%) 
    58 (16.1%) 
    6 (2.0%) 
    189 (13.4%) 
    0 
  
  
    - On Discharge 
    211 (28.2%) 
    95 (26.3%) 
    22 (7.4%) 
    328 (23.3%) 
    0 
  
  
    Oral Anticoagulants 
    
    
    
    
    
  
  
    - Before 
    86 (11.5%) 
    13 (3.6%) 
    37 (12.4%) 
    136 (9.7%) 
    0 
  
  
    - On Discharge 
    152 (20.3%) 
    38 (10.5%) 
    60 (20.1%) 
    250 (17.8%) 
    0 
  
  
    beta blockers (BBs) 
    
    
    
    
    
  
  
    Before Admission 
    216 (28.9%) 
    146 (40.4%) 
    38 (12.7%) 
    400 (28.4%) 
    0 
  
  
    On Discharge BB 
    569 (76.1%) 
    286 (79.2%) 
    123 (41.1%) 
    978 (69.5%) 
    0 
  
  
    ACEi) 
    
    
    
    
    
  
  
    Before Admission 
    412 (55.1%) 
    188 (52.1%) 
    71 (23.7%) 
    671 (47.7%) 
    0 
  
  
    On Discharge 
    551 (73.7%) 
    275 (76.2%) 
    151 (50.5%) 
    977 (69.4%) 
    0 
  
  
    ARBs) 
    
    
    
    
    
  
  
    Before Admission 
    25 (3.3%) 
    16 (4.4%) 
    4 (1.3%) 
    45 (3.2%) 
    0.075 
  
  
    On Discharge 
    122 (16.3%) 
    38 (10.5%) 
    20 (6.7%) 
    180 (12.8%) 
    0 
  
  
    MRAs 
    
    
    
    
    
  
  
    Before Admission 
    118 (15.8%) 
    13 (3.6%) 
    12 (4.0%) 
    143 (10.2%) 
    0 
  
  
    On Discharge 
    592 (79.1%) 
    132 (36.6%) 
    107 (35.8%) 
    831 (59.0%) 
    0 
  
  
    ACE-I: Angiotensin Converting    Enzyme Inhibitors; ARBs: Angiotensin Receptor Antagonists); MRAs: Aldosterone    Receptor Antagonists; BBs: Beta Blockers



Table 4: Baseline, In-hospital medications and Use of GDMT stratified by the different HF groups.

Comparison with National and International Data

Table 5 summarizes a comparison of this study's findings of demographic and clinical results from national and international registries and study findings. Data from western countries suggest variable geographical distribution and prevalence of HFmrEF [12]. North American registries indicate HFmrEF prevalence ranges between 13% in the Get with The Guidelines – HF (GWTG-HF) study [31] and 7.5% in the PINNACLE study, the largest descriptive analysis of HFmrEF patients to date [32]. European registries report a relatively higher HFmrEF prevalence, between 21% in the Swedish registry [33] and 24% in the ESC-HF-LT registry [34]. However, clinical trials report a lower prevalence, 17% in CHARM [35], 15% in TOPCAT [36] and DIG [37], and 11% in PARADIGM–PARAGON) [38], and in clinical settings, 13-26% among in-patients and 9-21% among outpatients [1]. Most existing HFmrEF studies enrolled patients with chronic HF, with fewer studies on HFmrEF patients with AHF [39-42, 52]. The relatively higher prevalence of HFmrEF (25.6%) in this Yemeni AHF cohort compared to 21-22.8% reported in the Middle East by sub-analysis of the Gulf CARE Registry [43-45] and 22% of the Gulf DYSPNEA registry [46-49] remains unknown. However, a higher prevalence of HFmrEF (36.4%) than our study has been reported among 633 rural HF patients [42].

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Citation: AL-Radhy A, Al Sagheer N, Shujaa A, Al-Zaazaai A, Al Bakri A, et al. Demographics, Clinical and Therapeutic Characteristics of Hospitalized Heart Failure Patients with Mildly-Reduced Ejection Fraction in Yemen: Data from the Gulf Acute Heart Failure Registry (Gulf CARE). Austin J Endocrinol Diabetes. 2024; 11(1): 1106.

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Editor/Year	Current 2022	(1) Al-Jarallah 2020	(2)� Kaplon-Cie´slicka et al. 2022		(3) Farmakis, D 2017	(4) Shah KS et al. 2017	(5)Rickenbacher 2017
Total & HFmrEF %	1408 (25.6%)	4577 (21%)	5951 (18%)		3257 (25%)	39,982 (8.2%)	622 (17%)
Demographic & Comorbidities
Age	57.0 ±12.9	61 (53-70)	71 [62–79]		-	81	70
Male	-71.70%	-60	60%		-36.20%	52	53.7
Smoking	-38.80%	-23	15%		-26.70%	8	60.2
CAD	-52.40%	-74	52%		28.7%)	55	79.6
HTN	-46.50%	-67	68%		76.5%)	75	82.4
AF	-2.20%	-9.6	56%		-24.60%	37	39.6
DM	-29.60%	-54	38%		-45.70%	42	39.8
COPD	-2.20%	-	19%		-22.40%	26.9	21.3
VHD	-6.40%	-	14%		-15.50%	11
Clinical Manifestations
De-Novo	66.50%	-		27%	37.20%
Orthopnea	68.70%	72			56.90%		63.6
NYHA III- IV	63%	69		78%	(47.0%)/(34.8%)		71.3
LL swelling	34.60%	35		58%	40.20%		45.8
HR, beats/min	93.5	80-107		86	106.6	80	76 (15)
SBP, mean	136.3	143		130	139.8	141	127 (19)
Gallop	41.60%	34			-		13.2
Rales	95%	93		72%	64.40%		45.8
Raised JVP	44.60%	43			3.90%		63.8
Medication
Diuretic	-34.10%	-52		80	-97.40%	60	-89.8
Digitalis	-6.40%			25	-27.90%	15	-13.9
Oral nitrate	-16.10%	-30		26		19	-32.4
Statin	-38.20%	-57				43
Beta-blocker	-40.40%	-47		77	-51.70%	37	-73.1
ACE inhibitor	-52.10%	-45		79	-68.70%	50+ARB	(90.7) +
ARB	-4.40%	-12			-12.00%
MRA	-3.60%	-8.5			-26.90%	7	-33.3
[1] Al-Jarallah 2020, Gulf-Care [42], (2) Kaplon-Cie´slicka et al. 2022, European HF Registry [65], [3] Farmakis, D 2017, ALARM-HF [9] Europe countries [39], [4] Shah KS et al. 2017 Get with The Guidelines-HF USA, [54], [5] Rickenbacher TIME-CHF Total No 622 & HFmrEF [40].

Demographics, Clinical and Therapeutic Characteristics of Hospitalized Heart Failure Patients with Mildly-Reduced Ejection Fraction in Yemen: Data from the Gulf Acute Heart Failure Registry (Gulf CARE)

Abstract

Introduction

Background

Rationale and Aim of the Study

Ethics Approval

Materials and Methods

Study Design

Data Variables

Study Population and Data Analysis (Categorization of LVEF)

Statistical Analysis

Results

Demographic Characteristics

Clinical Characteristics

Clinical Presentation and Physical Examination

Workup Data

Pharmacological Management

Comparison with National and International Data

Discussion

Main Findings

Baseline Clinical Characteristics of AHF Subtypes

Pharmacological Management

Limitations

Conclusion

References