Mortality, Morbidity and the Current Standard of Evidence-based Management Amongst Patients Living in Regional New Zealand with Severe Heart Failure (1997–2011): The Nelson Marlborough Heart Failure Study

Abstract

Background: While it has been shown that induction of atrial fibrillation (AF) depresses left ventricular function, the characterisation of the molecular mechanisms that contribute to left ventricular dysfunction in AF is incomplete. Aim: To investigate the impact of ventricular electromechanical irregularity (varying R–R intervals), generated by AF, oncalciumhandlinggeneandproteinexpression,with anaddedemphasis on thephosphorylationof keyproteins such as phospholamban (PLN). Methods: Cell culture experiments were conducted in rat ventricular myocytes during which electrical field pacing (ave. 2Hz) was applied at either an irregular vs regular drive train. To complement these studies, the effect of acute irregular vs regular pacing was performed in anaesthetised sheep for 30min. Expression of the SR Ca2+ ATPase (SERCA) and PLNwere evaluated by RT-PCR and immunoblotting. Results: There was significant reduction in the relative expression of serine 16 phosphorylation of PLN in the <36% was undertaken, based on transthoracic echocardiograms performed between December 1, 1997 and March 31, 2011. Five-year survival rates, acute admission numbers, medication use, access to implantable cardioverter-defibrillators (ICDs), quality of life based on the EQ-5D health questionnaire and self-reported New York Heart Association (NYHA) class were derived. Results:Mean LVEFwas 25.54± 7.25%. Five-year cumulative survivalwas 36.9%. Themean annual admission rate was 210/100,000; 46.33% were re-admissions in the same year. Acute medical admission was associated with an increased risk ofmortality (χ2 = 6.27, p< 0.02). Prescription rates forACE inhibitors, beta-blockers and spironolactone were 68.3%, 74.2% and 24.9% respectively. Of these, only 17.6%, 19.0% and 16.4%were onmaximum recommended doses. ICDs were inserted in 11.47% of patients aged ≤75 years as of 2006, who had also survived ≥18 months with LVEF persistently ≤30% for ≥3 months. Mean EQ-5D visual analogue score was 72.6± 0.032 and self-reported NYHA class 2.09± 0.11. Strong correlation was observed between NYHA class symptoms and overall quality of life (Pearson’s r=−0.59). Conclusion: Current medical and device therapy amongstheart failurepatients inNelsonandMarlborough is sub-optimal. Superior management to that observed here has been demonstrated through the implementation of dedicated heart failure services. irregularpaced rat ventricularmyocytes (57± 4%,p< 0.05). Thisfindingwas consistentwithourobservation that acute irregular pacing in the sheep resulted in reduced contractility of the ventricle (positive dp/dtmax, pre 1976± 178, post 1030± 114, p< 0.05) and reduced relative phosphorylation of PLN (cont 1.12, paced 0.85ADU). Of interest, PLNphosphorylationwas also lower in the left atrial tissue taken from the irregularly paced hearts (cont 1.01± 0.06, paced 0.59± 0.10 ADU, p< 0.05). Conclusions: The irregular ventricular rhythm induced by atrial fibrillation results in significant expression/phosphorylation changes of PLN, a key protein involved in cardiomyocyte calcium handling.