Design and Rationale of the National Tunisian Registry of Heart Failure (NATURE-HF): Protocol for a Multicenter Registry Study.

BACKGROUND: The frequency of heart failure (HF) in Tunisia is on the rise and has now become a public health concern. This is mainly due to an aging Tunisian population (Tunisia has one of the oldest populations in Africa as well as the highest life expectancy in the continent) and an increase in coronary artery disease and hypertension. However, no extensive data are available on demographic characteristics, prognosis, and quality of care of patients with HF in Tunisia (nor in North Africa). OBJECTIVE: The aim of this study was to analyze, follow, and evaluate patients with HF in a large nation-wide multicenter trial. METHODS: A total of 1700 patients with HF diagnosed by the investigator will be included in the National Tunisian Registry of Heart Failure study (NATURE-HF). Patients must visit the cardiology clinic 1, 3, and 12 months after study inclusion. This follow-up is provided by the investigator. All data are collected via the DACIMA Clinical Suite web interface. RESULTS: At the end of the study, we will note the occurrence of cardiovascular death (sudden death, coronary artery disease, refractory HF, stroke), death from any cause (cardiovascular and noncardiovascular), and the occurrence of a rehospitalization episode for an HF relapse during the follow-up period. Based on these data, we will evaluate the demographic characteristics of the study patients, the characteristics of pathological antecedents, and symptomatic and clinical features of HF. In addition, we will report the paraclinical examination findings such as the laboratory standard parameters and brain natriuretic peptides, electrocardiogram or 24-hour Holter monitoring, echocardiography, and coronarography. We will also provide a description of the therapeutic environment and therapeutic changes that occur during the 1-year follow-up of patients, adverse events following medical treatment and intervention during the 3- and 12-month follow-up, the evaluation of left ventricular ejection fraction during the 3- and 12-month follow-up, the overall rate of rehospitalization over the 1-year follow-up for an HF relapse, and the rate of rehospitalization during the first 3 months after inclusion into the study. CONCLUSIONS: The NATURE-HF study will fill a significant gap in the dynamic landscape of HF care and research. It will provide unique and necessary data on the management and outcomes of patients with HF. This study will yield the largest contemporary longitudinal cohort of patients with HF in Tunisia. TRIAL REGISTRATION: ClinicalTrials.gov NCT03262675; https://clinicaltrials.gov/ct2/show/NCT03262675. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/12262.

Epidemiology of heart failure and long-term follow-up outcomes in a north-African population: Results from the NAtional TUnisian REgistry of Heart Failure (NATURE-HF).

The NATURE-HF registry was aimed to describe clinical epidemiology and 1-year outcomes of outpatients and inpatients with heart failure (HF). This is a prospective, multicenter, observational survey conducted in Tunisian Cardiology centers. A total of 2040 patients were included in the study. Of these, 1632 (80%) were outpatients with chronic HF (CHF). The mean hospital stay was 8.7 ± 8.2 days. The mortality rate during the initial hospitalization event for AHF was 7.4%. The all-cause 1-year mortality rate was 22.8% among AHF patients and 10.6% among CHF patients. Among CHF patients, the older age, diabetes, anemia, reduced EF, ischemic etiology, residual congestion and the absence of ACEI/ ARBs treatment were independent predictors of 1-year cumulative rates of rehospitalization and mortality. The female sex and the functional status were independent predictors of 1-year all-cause mortality and rehospitalization in AHF patients. This study confirmed that acute HF is still associated with a poor prognosis, while the mid-term outcomes in patients with chronic HF seems to be improved. Some differences across countries may be due to different clinical characteristics and differences in healthcare systems.

Neonatalogist-performed echography in neonatology: a Tunisian experience.

INTRODUCTION: Echocardiography is an important tool for diagnosis of cardiac abnormalities that can impact the management and outcome of the sick newborn in the intensive care unit. A preliminary echocardiogram performed by the neonatologist under the supervision of a paediatric cardiologist for interpretation and review is an alternate when there is not a cardiologist on site. The aim of this study was to evaluate frequency of use, neonatal characteristics, and indications of neonatologist-performed echocardiography in a Tertiary Neonatal Care Centre in Tunisia. METHODS: Prospective observational study in a tertiary Neonatal Intensive Care Unit (NICU) in Monastir (Tunisia) from April 2015 to February 2017.An echocardiography was indicated in these situations: cyanosis, signs of circulatory shock, clinical signs of heart failure, presence of a murmur, arrhythmia, and abnormal pulses in upper and/or lower extremities, suspected persistent pulmonary hypertension in neonates, clinically suspected patent ductus arteriosus, maternal diabetes mellitus and polymalformative syndrome. The findings of echocardiography were confirmed by pediatric cardiologist in case of structural or functional cardiac abnormalities. RESULTS: 675 echocardiography were performed among them 535 were normal and 25 revealed a persistent arterial duct treated with E2 postaglandins (Prostine®) or paracetamol according to a pre-established protocol. 80 Congenital heart diseases were retained, which represented an incidence of 7 ‰ live births. The second time of our work consisted to study the 55 cases of cardiac diseases confirmed after exclusion of atrial communication. The antenatal diagnosis was made in 11% of cases. The main signs indicating the echocardiogram were the heart murmur (22 cases) followed by cyanosis (6 cases). A malformation association and / or a chromosomal aberration have been noted in 36% of cases. For half of the patients, the cardiac ultrasound was performed before the first 24 hours of life. This examination was completed by a thoracic angioscan in 9 patients. 31% of newborns had an infusion of Prostaglandins for an average duration of 11 days [2-60 days]. One-third of newborns (35 cases) required respiratory assistance. A palliative surgery was made in 7 cases and curative one in 4 cases. The average age at the time of the intervention was 20 days. The neonatal mortality rate was 40%. CONCLUSION: Echocardiography is being utilized progressively on the neonatal unit, and has been indicated to have a high return for both structural and functional cardiac abnormalities. It is important to encourage collaboration with pediatric cardiologists to establish standards for training and to develop guidelines for clinical practice in order to improve neonatal care.

Prevalence and prognostic significance of anemia in patients presenting for ST-elevation myocardial infarction in a Tunisian center.

BACKGROUND: Anemia on admission is a powerful predictor of major cardiovascular events in patients presenting for acute coronary syndromes. We sought to determine the prevalence and prognostic impact of anemia in patients presenting for ST-elevation myocardial infarction (STEMI). METHODS: We analyzed data from a Tunisian retrospective single center STEMI registry. Patients were enrolled between January 1998 and October 2014. Anemic and nonanemic patients were compared for clinical and prognostic features and according to four prespecified hemoglobin level subgroups. In patients with severe anemia, factors associated with in-hospital death were studied. RESULTS: A total of 1498 patients were enrolled. Mean age was 60.47 ± 12.7 years and prevalence of anemia was 36.6%. Anemic patients were more likely to be elderly, hypertensive, and diabetic in comparison to nonanemic patients. In-hospital mortality was significantly higher in anemic patients (14.9% vs. 5%, p < 0.001). Lower hemoglobin levels were significantly associated with a higher prevalence of heart failure on admission, cardiogenic shock, and in-hospital mortality (p < 0.001 for all). In univariate analysis, factors associated with in-hospital death in patients with severe anemia were hypertension (p = 0.044), heart failure on admission (p < 0.001), renal failure on admission (p < 0.001), and primary percutaneous coronary intervention (pPCI) use (p = 0.016). The absence of pPCI use was independently associated with in-hospital death in multivariate analysis (odds ratio = 2.22, 95% confidence interval: 1.07-4.76, p = 0.033). CONCLUSION: According to this study, anemic patients presenting for STEMI have a higher in-hospital mortality rate. The absence of pPCI use was independently associated with in-hospital death.

Risk profile and in-hospital prognosis in elderly patients presenting for acute ST-elevation myocardial infarction in the Tunisian context.

OBJECTIVES: Little is known about the risk profile and in-hospital prognosis of elderly patients presenting for ST-elevation myocardial infarction (STEMI) in Tunisia. We sought to determine in-hospital prognosis of elderly patients with STEMI in a Tunisian center. METHODS: The study was carried out on a retrospective registry enrolling 1403 patients presenting with STEMI in a Tunisian center between January 1998 and January 2013. Patients ≥75 years old were considered elderly. Risk factors and in-hospital prognosis were compared between elderly and younger patients, and then predictive factors of in-hospital death were determined in elderly patients. RESULTS: Out of the overall population, 211 (15%) were part of the elderly group. Compared to younger patients, elderly patients were more likely to have arterial hypertension but less likely to be smokers and obese. Thrombolysis was significantly less utilized in the elderly group (22.3% vs. 36.6% in the younger group, p<0.001), whereas the use primary percutaneous coronary intervention was comparable between the two sub-groups (24.2% vs. 28.8%, p=0.17). The incidence of in-hospital complications was higher in the elderly group, and so was the in-hospital mortality rate (14.2% vs. 8.1%, p=0.005). Heart failure on-admission, renal failure on-admission, and inotropic agents use were independently associated to in-hospital death in the elderly group. CONCLUSIONS: In the Tunisian context, elderly patients presenting with STEMI have higher prevalence of risk factors and a worse in-hospital course in comparison to younger patients. Clinical presentation on-admission has a strong impact on in-hospital prognosis.

Effect of the PPARγ C161T gene variant on serum lipids in ischemic stroke patients with and without type 2 diabetes mellitus.

Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-activated transcription factor involved in the regulation of lipid metabolism, diabetes, obesity, atherogenesis and inflammation. PPARγ genetic variation has been associated with metabolic and cardiovascular diseases. The aim of this study was to explore, for the first time, the relationship between PPARγ C161T polymorphism and the risk of ischemic stroke (IS) among patients with type 2 diabetes mellitus (T2DM). A total of 196 patients with IS (117 diabetics and 79 nondiabetics) and 192 controls were recruited to enroll in this study. PPARγ C161T genotyping was performed by PCR-RFLP technique. The 161T allele as compared with C allele was found to be higher in controls than in IS patients (with or without T2DM). After adjusting for multiple risk factors, the T allele carriers had significantly reduced IS risk (OR=0.575, 95% CI 0.348-0.951, p=0.030) compared to the CC homozygotes which increased significantly the risk in IS patients with T2DM (OR=1.85, 95% CI 1.23-2.62). Moreover, the triglycerides (TG) and ApoB levels in CC homozygote carriers were significantly higher than those in T allele carriers. These results indicate that the C161T of PPARγ may reduce the risk of IS by modulation of adipose metabolism especially TG and ApoB in IS patients with T2DM.

Platelet glycoprotein IIIa (platelet antigen 1/platelet antigen 2) polymorphism and 1-year outcome in patients with stable coronary artery disease.

Platelet glycoprotein IIb/IIIa is a membrane receptor which plays a key role in coronary artery disease and thrombotic events. However, there is a considerable controversy regarding the clinical impact of glycoprotein IIIa platelet antigen 1 (PlA1)/platelet antigen 2 (PlA2) polymorphism as a risk factor for myocardial infarction. To evaluate the association between glycoprotein IIIa PlA1/PlA2 polymorphism and 1-year cardiovascular events occurrence in aspirin-treated patients with stable coronary artery disease. We prospectively included 188 postacute coronary syndrome patients (183 men) aged 59 ± 10 years and receiving aspirin (250 mg/day). The clinical outcome at 1 year was the composite end point of nonfatal myocardial infarction, stroke, recurrent unstable angina or cardiac death. Genotyping for PlA1/PlA2 polymorphism was conducted using PCR and restriction fragment length polymorphism analysis. The genotype distribution of glycoprotein IIIa PlA1/PlA2 polymorphism was PlA1/PlA1, 55.3%; PlA1/PlA2, 39.3% and PlA2/PlA2, 4%. Incidence of composite end point in homozygous PlA1/PlA1 carriers was significantly higher than in PlA2/PlA2 and PlA1/PlA2 patients [14.4 vs. 3.6% odds ratio 4.5 (1.2-16.6, 95% confidence interval); P = 0.012]. Multivariate analysis identified three strong predictive factors of cardiac death: age more than 65 years [odds ratio = 6.8, (1.4-34, 95% confidence interval); P = 0.018], ventricular ejection fraction less than 50% [odds ratio = 8.6, (1.7-42.6, 95% confidence interval); P = 0.008] and homozygous PlA1/PlA1 genotype [odds ratio = 8.8, (1.0-78.6, 95% confidence interval); P = 0.014]. Our results demonstrated that glycoprotein IIIa PlA1/PlA1 genotype carriers have a significantly increased risks of acute vascular ischemic events associated with a poor prognosis at 1 year. These postacute coronary syndrome patients might require an optimized secondary antithrombotic prophylaxis strategy.

Response variability to aspirin and one-year prediction of vascular events in patients with stable coronary artery disease.

The aim of this study was to assess the association between "aspirin non responsiveness" in patients with coronary artery diseases (CAD) and the risk of major adverse cardiovascular events (MACE). 204 patients with CAD receiving aspirin (250 mg/d) were included. Both Collagen/Epinephrine Closure Time (CEPI-CT) and urinary Thromboxane B2 (uTxB2) concentration was used to determine the patients aspirin responsiveness. The clinical primary endpoint was the occurrence of MACE including: cardiovascular death, MI, stroke or transient ischemic attack. The secondary endpoint was the occurrence of Recurrent Acute Vascular Event (RAVE: MI, stroke or transient ischemic attack). After 1-year follow-up, no responders diagnosed by CEPI-CT had a trend for higher risk of MACE (13% vs 7.4%; P = 0.22) and significant higher risk of RAVE (OR = 2.1; 95%CI: 1.7-2.4; P = 0.01) when compared to good responders. Multivariate analysis showed that CEPI-CT < 143 s was the only independent predictor of RAVE (OR = 6.3; 95% CI: 1.2-32.2; P = 0.026). Aspirin non-responsiveness, diagnosed by the uTxB2, was not associated with an increased risk of either MACE or RAVE. Our results, reinforce the importance of being able to diagnose laboratory "aspirin non responsiveness", and extend the evidence that aspirin non responsiveness may explain in part the occurrence of RAVE.

Screening for aspirin resistance in stable coronary artery patients by three different tests.

BACKGROUND: Aspirin (ASA) failure to inhibit in vitro platelet function had been termed ASA resistance. The prevalence of this phenomenon as measured with different platelet function tests varies widely among studies. OBJECTIVES: In this study, we propose to determine the prevalence of ASA non-responsiveness in stable coronary artery patients using three different tests. PATIENTS AND METHODS: One hundred ninety-one patients with a stable coronary artery disease and receiving secondary ASA prophylaxis (250 mg/day) were tested. For each patient the ASA-induced platelet inhibition was determined using three different tests: Ivy Bleeding time (BT), collagen/epinephrine closure time (CEPI-CT; PFA-100, Dade-Behring) and urinary 11-dehydrothromboxane B2 (uTxB2) excretion level. The agreement between these tests was evaluated by kappa statistics test. RESULTS: The prevalence of biological ASA resistance was 15.7% (n=30), 20.4% (n=39) and 24.6% (n=47) by BT, PFA-100 and UTxB2, respectively. Only fourteen patients (7.3%) were non-responders for two tests: 6 (3.1%) BT/ PFA-100; 1 (0.5%) BT/UTxB2; 7 (3.7%) PFA-100/UTxB2). A poor agreement was found between these three methods and only 3 patients were resistant with all the tests (1.6%). CONCLUSION: The lack of agreement supposed that different types of aspirin resistance exist. Thus, combination of two tests or more could be a primary solution for a better identification of ASA resistant patients. This hypothesis must be confirmed by a large-scale randomized study with clinically well-defined endpoints.