Waleed AlHabeeb

Clinical features, management, and short- and long-term outcomes of patients with acute decompensated heart failure: phase I results of the HEARTS database.

The HEart function Assessment Registry Trial in Saudi Arabia (HEARTS) is a national multicentre project, studying clinical features, management, short‐ and long‐term outcomes, and mortality predictors in patients admitted with acute decompensated heart failure (ADHF).

Control of histone H3 phosphorylation by CaMKIIδ in response to haemodynamic cardiac stress

Heart failure is associated with the reactivation of a fetal cardiac gene programme that has become a hallmark of cardiac hypertrophy and maladaptive ventricular remodelling, yet the mechanisms that regulate this transcriptional reprogramming are not fully understood. Using mice with genetic ablation of calcium/calmodulin‐dependent protein kinase II δ (CaMKIIδ), which are resistant to pathological cardiac stress, we show that CaMKIIδ regulates the phosphorylation of histone H3 at serine‐10 during pressure overload hypertrophy. H3 S10 phosphorylation is strongly increased in the adult mouse heart in the early phase of cardiac hypertrophy and remains detectable during cardiac decompensation. This response correlates with up‐regulation of CaMKIIδ and increased expression of transcriptional drivers of pathological cardiac hypertrophy and of fetal cardiac genes. Similar changes are detected in patients with end‐stage heart failure, where CaMKIIδ specifically interacts with phospho‐H3. Robust H3 phosphorylation is detected in both adult ventricular myocytes and in non‐cardiac cells in the stressed myocardium, and these signals are abolished in CaMKIIδ‐deficient mice after pressure overload. Mechanistically, fetal cardiac genes are activated by increased recruitment of CaMKIIδ and enhanced H3 phosphorylation at hypertrophic promoter regions, both in mice and in human failing hearts, and this response is blunted in CaMKIIδ‐deficient mice under stress. We also document that the chaperone protein 14–3–3 binds phosphorylated H3 in response to stress, allowing proper elongation of fetal cardiac genes by RNA polymerase II (RNAPII), as well as elongation of transcription factors regulating cardiac hypertrophy. These processes are impaired in CaMKIIδ‐KO mice after pathological stress. The findings reveal a novel in vivo function of CaMKIIδ in regulating H3 phosphorylation and suggest a novel epigenetic mechanism by which CaMKIIδ controls cardiac hypertrophy.

FBXO32 , encoding a member of the SCF complex, is mutated in dilated cardiomyopathy

BackgroundDilated cardiomyopathy (DCM) is a common form of cardiomyopathy causing systolic dysfunction and heart failure. Rare variants in more than 30 genes, mostly encoding sarcomeric proteins and proteins of the cytoskeleton, have been implicated in familial DCM to date. Yet, the majority of variants causing DCM remain to be identified. The goal of the study is to identify novel mutations causing familial dilated cardiomyopathy.ResultsWe identify FBXO32 (ATROGIN 1), a member of the F-Box protein family, as a novel DCM-causing locus. The missense mutation affects a highly conserved amino acid and is predicted to severely impair binding to SCF proteins. This is validated by co-immunoprecipitation experiments from cells expressing the mutant protein and from human heart tissue from two of the affected patients. We also demonstrate that the hearts of the patients with the FBXO32 mutation show accumulation of selected proteins regulating autophagy.ConclusionOur results indicate that abnormal SCF activity with subsequent impairment of the autophagic flux due to a novel FBXO32 mutation is implicated in the pathogenesis of DCM.

Deletion of low molecular weight protein tyrosine phosphatase (Acp1) protects against stress-induced cardiomyopathy.

The low molecular weight protein tyrosine phosphatase (LMPTP), encoded by the ACP1 gene, is a ubiquitously expressed phosphatase whose in vivo function in the heart and in cardiac diseases remains unknown. To investigate the in vivo role of LMPTP in cardiac function, we generated mice with genetic inactivation of the Acp1 locus and studied their response to long‐term pressure overload. Acp1−/− mice develop normally and ageing mice do not show pathology in major tissues under basal conditions. However, Acp1−/− mice are strikingly resistant to pressure overload hypertrophy and heart failure. Lmptp expression is high in the embryonic mouse heart, decreased in the postnatal stage, and increased in the adult mouse failing heart. We also show that LMPTP expression increases in end‐stage heart failure in humans. Consistent with their protected phenotype, Acp1−/− mice subjected to pressure overload hypertrophy have attenuated fibrosis and decreased expression of fibrotic genes. Transcriptional profiling and analysis of molecular signalling show that the resistance of Acp1−/− mice to pathological cardiac stress correlates with marginal re‐expression of fetal cardiac genes, increased insulin receptor beta phosphorylation, as well as PKA and ephrin receptor expression, and inactivation of the CaMKIIδ pathway. Our data show that ablation of Lmptp inhibits pathological cardiac remodelling and suggest that inhibition of LMPTP may be of therapeutic relevance for the treatment of human heart failure.

Attitude of the Saudi community towards heart donation, transplantation, and artificial hearts.

Objectives: To understand the attitudes of the Saudi population towards heart donation and transplantation. Methods: A survey using a questionnaire addressing attitudes towards organ transplantation and donation was conducted across 18 cities in Saudi Arabia between September 2015 and March 2016. Results: A total of 1250 respondents participated in the survey. Of these, approximately 91% agree with the concept of organ transplantation but approximately 17% do not agree with the concept of heart transplantation; 42.4% of whom reject heart transplants for religious reasons. Only 43.6% of respondents expressed a willingness to donate their heart and approximately 58% would consent to the donation of a relative’s organ after death. A total of 59.7% of respondents believe that organ donation is regulated and 31.8% fear that the doctors will not try hard enough to save their lives if they consent to organ donation. Approximately 77% believe the heart is removed while the donor is alive; although, the same proportion of respondents thought they knew what brain death meant. Conclusion: In general, the Saudi population seem to accept the concept of transplantation and are willing to donate, but still hold some reservations towards heart donation.

Clinical Presentation, Predictors, and Outcomes Among Mineralocorticoid Receptor Antagonist (MRA)-Eligible Acute Heart Failure Patients in the Heart Function Assessment Registry Trial in Saudi Arabia (HEARTS)

Mineralocorticoid receptor antagonist (MRA) therapy is indicated after myocardial infarction in patients with acute heart failure (AHF) with an ejection fraction ≤40% and lacking contraindications. We analyzed clinical presentations, predictors, and outcomes of MRA-eligible patients within a prospective registry of patients with AHF from 18 hospitals in Saudi Arabia, from 2009 to 2010. For this subgroup, mortality rates were followed until 2013, and the clinical characteristics, management, predictors, and outcomes were compared between MRA-treated and non-MRA-treated patients. Of 2609 patients with AHF, 387 (14.8%) were MRA eligible, of which 146 (37.7%) were prescribed MRAs. Compared with non-MRA-treated patients, those prescribed MRAs more commonly exhibited non-ST-segment elevation myocardial infarction, acute on chronic heart failure, past history of ischemic heart disease, and severe left ventricular systolic dysfunction; were more commonly administered oral furosemide and digoxin; and had higher in-hospital recurrent congestive HF rates. Mortality did not significantly differ (P > .05) between groups. In Saudi Arabia, 37.7% of eligible patients received MRA treatment, which is higher than that in developed countries. The lack of long-term survival benefit raises concerns about systematic problems, for example, proper follow-up and management after hospital discharge, warranting further investigation.

Atrial Fibrillation in Patients Hospitalized With Heart Failure: Patient Characteristics and Outcomes From the HEARTS Registry

Effect of atrial fibrillation (AF) on short- and long-term outcomes in heart failure (HF) is controversial. Accordingly, we examined this relationship in a national multicenter project using data from the Hearts Function Assessment Registry Trial in Saudi Arabia that studied the clinical features and outcomes of patients admitted with de novo and acute on chronic HF. Out of 2593 patients with HF, 449 (17.8%) had AF at presentation. Patients with AF were more likely to be males and older (mean age 65.2 ± 15.0 vs 60.5 ± 14.8 years) to have a history of ventricular tachycardia/ventricular fibrillation (3.1% vs 1.9%) or cerebrovascular accident (15.0% vs 8.5%). However, they were less likely to have diabetes (66.0% vs 55.9%) or coronary artery disease (55.6% vs 42.3%). The 1-, 2-, and 3-year crude mortality rates were significantly higher in patients with AF (23.2% vs 18.3%, 27.4% vs 22.3%, and 27.8% vs 23.2%, respectively). However, there was no significant difference in mortality after adjusting for covariates. Thus, in patients admitted with HF, AF upon presentation was not associated with increased mortality.

Clinical characteristics, management and outcomes of patients with chronic heart failure: Results from the heart function assessment registry trial in Saudi Arabia (HEARTS-chronic)

BACKGROUND Several registries have described patients hospitalized with heart failure (HF), but only few looked at outpatients in the ambulatory setting mostly without long-term follow-up. We sought to determine the clinical characteristics, management, and 1-year outcomes of patients with chronic HF in Saudi Arabia. METHODS Part of a prospective multicenter nationwide registry; HEart function Assessment Registry Trial in Saudi Arabia (HEARTS) and included chronic HF patients referred to four HFCs between September 2009 and December 2011. RESULTS We enrolled 685 patients with mean age 55.66±15.97years, 70.1% were men and 96.1% were Saudis. The main etiologies of HF were CAD (38.8%), dilated cardiomyopathy (36.5%), and hypertension (10.5%). Severe left ventricular dysfunction was present in 70.6% and median NT-proBNP was 2934.37pg/ml. The prescription rates of evidence based therapies (EBTs) before admission to HFC, at discharge from 1st clinic visit, and at 1-year follow up were 90%, 91% and 94% for beta-blockers, 79%, 80%, and 86% for ACEi/ARBs and 44%, 45%, and 42% for aldosterone antagonists; respectively. ICD was inserted in 21.9% and CRT in 6.6% at enrollment and increased to 29.1% and 8.8% after one year respectively. The all-cause mortality rate at 1year was 9% and 93.7% of which was cardiac-related. The all-cause one-year hospitalization rate was 39% and the total emergency room visit rate was 50%. CONCLUSIONS Chronic HF patients in Saudi Arabia are younger, commonly have severe LV systolic dysfunction and have relatively high annual mortality and re-hospitalization rates.

PT058 Clinical Presentation, Predictors, And Outcomes of Aldosterone Therapy-Eligible Acute Heart Failure Patients: A Sub-Study of The Heart Function Assessment Registry Trial In Saudi Arabia (Hearts)

O ST E R A B ST R A C T S Conclusion: This is the first study about time of day impact on AHFS treatment. Vital signs are significant different between daytime and nighttime, which made us think about the treatment options. Therefore, it is clinically important to know about the nighttime is high prevalence of AHFS patients in whom we should consider vasodilator therapy. Disclosure of Interest: None Declared