Aims 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). Methods and results Our prospective registry enrolled 2610 ADHF patients admitted to 18 hospitals in Saudi Arabia between October 2009 and December 2010, and followed mortality rates until January 2013. The patients included 66% men and 85.5% Saudis, with a median age (interquartile range) of 61.4 (15) years; 64% had acute on chronic heart failure (HF), 64.1% diabetes mellitus, 70.6% hypertension, and 55.7% CAD. Exacerbating factors for hospital admission included acute coronary syndromes (37.8%), infections (20.6%), non‐compliance with low‐salt diet (25.2%), and non‐compliance with HF medications (20%). An LVEF <40% was found in 73%. In‐hospital use of evidence‐based medications was high. All‐cause cumulative mortality rates at 30 days, 6 months, 1 year, 2 years, and 3 years were 8.3, 13.7, 19.5, 23.5, and 24.3%, respectively. Important independent predictors of mortality were history of stroke, acute on chronic HF, systolic blood pressure <90 mmHg upon presentation, estimated glomerular filtration rate <60 mL/min, and haemoglobin <10 g/dL. Conclusion Patients with ADHF in Saudi Arabia presented at a younger age and had higher rates of CAD risk factors compared with those in developed countries. Most patients had reduced LV systolic function, mostly due to ischaemic aetiology, and had poor long‐term prognosis. These findings indicate a need for nationwide primary prevention and HF disease management programmes.

For many years, data about heart failure (HF) was only limited to Western countries but in the last few years, well designed heart failure registries have been conducted in many developing countries. The purpose of this review is to summarize the current status regarding the epidemiology and management of heart failure in Middle East Arab countries (MEACs) by analysis of the results of the latest HF registries performed in these countries and to anticipate future perspectives, quality initiatives and areas of research and development. Data has shown that the average age of affected individuals is at least 10 years younger than their Western counterparts. Heart failure with preserved ejection fraction was generally under-represented in these registries to less than 30% of the whole population of heart failure. Coronary artery disease (CAD) constitutes about 55% of causes of heart failure in this region in comparison to about 70% in Western countries. An area that needs development is the investment in establishing specialized heart failure programs to cut the circle of non-compliance and repeated HF admissions to the hospitals. Advances in heart transplantation and mechanical circulatory support will continue to slow down and we are not expecting major changes in the near future but on the other hand, implantation of electronic devices like ICD and CRT is expected to increase significantly in the coming years in these countries.

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. © 2014 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

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