Baseline functional capacity in patients with heart failure risk factors: association with heart failure symptoms and events at 1 year follow-up

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Abstract

.. Conclusion: Adherence to guideline recommended ther.. .. apy was high (>60%) with beta-blockers, statins, and .. Audit of adherence to guidelines for heart .. antiplatelet therapy, but less so with ACE-I, MRAs, ARBs .. failure in a private cardiology clinic in .. and SNIs. There was a very low incidence of contra-indicated .. Greater Newcastle Region, Australia .. therapy. There was a fair proportion of patients with no clear .. reason for non-adherence, highlighting the need to refer to ∗ .. A. Worthington , T. McCallum Pardy .. guidelines when prescribing for every patient. .. Newcastle Cardiology, Australia .. .. .. http://dx.doi.org/10.1016/j.hlc.2015.06.205 We audited a cardiology clinic (n= 1933) run by a sole ... . cardiologist and nurse practitioner, in Greater Newcastle ... 205 Region, Australia, (n ∼546,000.) Patients with heart failure ... . Baseline functional capacity in patients were assessed for adherence to National Heart Foundation ... with heart failure risk factors: association guideline recommended therapy. 110 patients (5.5% of clinic ... .. with heart failure symptoms and events at 1 population) NYHA Class I – II 81%; Class III- IV 19%; .. year follow-up Females 31%; Males 69%; average age 73 years; Male BMI ... .. 31.9, female BMI 31.5. Rhythm - sinus 60%; AF 31%; paced .. H. Yang ∗ , K. Negishi, M. Nolan, Y. Wang, 9%. BP and HR: females 136/71 mmHg, HR 72 bpm; males ... M. Saito, T. Marwick . 133/72 mmHg, HR 68 bpm; Systolic dysfunction 44.5%, pre- ... Menzies Institute for Medical Research, Australia . served systolic function 55.5%; Average EF 43% (range 15% .. .. - 79%), Cause of CCF: CAD 44.5%, DCM 14%, HT 12%, .. . Background: Early treatment may alter progression to tachyarrhythmia 19.1%, valve disease 7.23, viral CM 3%; ... overt heart failure (HF) in those with stage B heart failure . chemotherapy 0.1%. Common comorbidities (>25% preva- .. .. (SBHF). The identification of patients with SBHF usually lence): Dyslipidaemia 67%, HT 62%, AF 51%, CAD 50%; CKD .. 42%, diabetes 32%, PVD 25%, asthma/COPD 25%. Interven- ... relies on echo. We asked whether functional capacity at base. tions: CABG 26%, PCI 16%, AICD 10%; PPM 10%; transplant ... line was associated with new HF symptoms in patients with .. HF risks at follow-up. 1%. .. Methods: Asymptomatic patients ≥65 years, with ≥1 HF Adherence to therapy: Beta Blocker 86%; Statins 67%; anti- ... . risk (hypertension, type 2 diabetes, obesity, family history of . platelets 65.5%; ACE-I 57%; MRA 53.6%; Loop diuretic 50.9%; . . OAC 49%; ARBs 24.5%; Antidiabetic 31%; Antidepressants ... HF, previous chemotherapy or previous cardiac history) were . 27%; nitrates 20%; digoxin 19%; Thiazide Diuretics 17%; DHP .. recruited from local community. Subjects underwent a com. CCB 17%; Ivabradine 10%; Amiodarone 9%; hydralazine ... prehensive echocardiogram. Exercise capacity was measured .. using 6-minute walk test (6MW). The composite outcome 0.9%; contra-indicated drugs 2%. .. Reason for non-adherence: Beta Blockers: n= 15, unknown ... was major adverse cardiac endpoint (MACE) (death, CV . 100%; ACE-I : n = 46, renal dysfunction 32.6%; cough 37%; ... admission and new atrial fibrillation [AF]) and new HF sympunknown 30.4%; MRA n = 50, unknown 46%; renal dysfunc- ... toms. . Results: Among 314 patients (71±5 years; 49% men) with a tion 34%; government restriction 10%; hyperkalaemia 6%; ... other 4%; Ivabradine: n =98, AF 37.7%; government restric- ... mean follow-up of 1 year (6-16 months), 38 developed new HF . tion 33.6%; pacemaker dependent 8.1%; unknown 18.6%: not ... symptoms and 11 developed MACE. Using receiver operating .. characteristic (ROC) curve, 6MW is the best marker for pretolerated 2.3%. .. .. dicting composite CV (Table1a). 6MW distance <450 metres .. was independently associated with outcome with odds ratio .. .. 3.83 (p<0.001) (Table 1b). .. .. .. .. .. Table 1a Receiver Operating Characteristic Table 1b Multivariable logistic model .. .. .. AUC (95%CI) p value OR (95%CI) p value . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 6MW distance 0.68 (0.60, 0.75) <0.001 3.83 (2.08, 7.05) <0.001 .. .. .. Abnormal GLS (-16%) 0.53 (0.44, 0.62) 0.479 1.11 (0.56, 2.17) 0.77 .. .. Abnormal E/e’ (15) 0.54 (0.45, 0.64) 0.345 1.08 (0.43, 2.68) 0.88 .. .. .. Dilated LA (34 m;/m2) 0.51 (0.42, 0.60) 0.785 1.54 (0.80, 2.94) 0.19 .. .. LVH (g/m2) 0.58 (0.49, 0.67) 0.087 1.76 (0.95, 3.26) 0.07 .. .. .. .. .. .. Conclusion: Patients with reduced 6MW distance showed .. .. predictive value of composite CV outcome and early HF .. . 204

Abstract

symptoms. 6MW is a safe and feasible test in the community, potentially useful to select patients for HF prevention. http://dx.doi.org/10.1016/j.hlc.2015.06.206 206 Calcium dysregulation and arrhythmia underlie hypertrophic heart failure with preserved ejection fraction C. Curl ∗ , A. Raaijmakers, C. Chandramouli, T. Harding, J. Bell, S. Harrap, L. Delbridge University of Melbourne, Australia Heart failure with preserved ejection fraction (HFpEF) is characterised by diastolic dysfunction with inadequate ventricular filling at normal pressures. The underlying cellular aetiology of this disease is poorly understood due partly to the lack of appropriate models. The aim of this study was to characterise the in vivo cardiac and isolated cardiomyocyte functional status in the Hypertrophic Heart Rat (HHR), a newly discovered model of HFpEF. Echocardiography was performed in adult (28-30 week) male HHR and NHR (Normal Heart Rat) using a GE Vivid 9 echocardiography system (General Electric, CT, USA). Electrocardiograms were recorded on MacLab data acquisition system. Cardiomyocytes isolated by collagenase digestion were fura 2-AM loaded. Single myocyte contractility and [Ca2+ ]i were measured by edge-detection and microfluorimetry under basal conditions (3Hz, 2.0mM Ca2+ , 37 ◦ C). HHR had significantly greater cardiac weight index (4.56±0.2 vs 3.24±0.1mg/g), cardiomyocyte length (163.1±2.3 vs 132.5±1.0␮m) cardiomyocyte width (35.8±0.7 vs 29.7±0.3␮m) and cardiomyocyte volume (44.34±1.3 vs 29.84±0.4pL) when compared with NHR. Diastolic dysfunction (31.02±3.4 vs 21.71±2.5 E/E’) along with relatively preserved systolic function (72.93±1.89 vs 80.14±0.94 ejection fraction %) indicative of HFpEF phenotype was apparent in the HHR. Significantly higher levels of contractility were exhibited in the HHR when compared with NHR (94% increase) along with higher amplitude Ca2+ (91% increase) and increased arrhythmic activity. This data strongly supports the contention that HFpEF has a different cellular phenotype to failure originating from systolic dysfunction and that interventional strategies targeted to increase cardiomyocyte Ca2+ loading may not be appropriate where failure presents with preserved systolic function. http://dx.doi.org/10.1016/j.hlc.2015.06.207

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207 Cardiomyocyte mineralocorticoid receptor regulates cardiac functional responses to ischaemia; the role of sex and NOS inhibition L. Bienvenu 1,2,∗ , J. Morgan 1 , L. Delbridge 2 , M. Young 1 1 MIMR-PHI

Institute of Medical Research, Clayton, VIC, Australia 2 Department of Physiology, The University of Melbourne, Melbourne, VIC, Australia

Mineralocorticoid receptor (MR) antagonists are protective in patients post-myocardial infarction and are beneficial even when plasma aldosterone levels are normal. Moreover, experimental and clinical evidence suggests that sex differences observed in heart failure may have an MRdependent mechanism. The aim of this study was to characterise the role of cardiomyocyte MR signalling in ischaemia/reperfusion (I/R) injury and recovery in a model of a mineralocorticoid-independent insult, i.e. chronic nitric oxide deficiency. Male and female (8 weeks of age), wild type (WT) and cardiomyocyte MR knockout (myo-MRKO) mice were uninephrectomised and given (i) high salt (VEH: 0.9%NaCl, 0.4%KCl) or (ii) high salt plus the nitric oxide synthase (NOS) inhibitor L-NG -Nitroarginine methyl ester (L-NAME) (L-NAME: 150mg/kg/day, 0.9%NaCl, 0.4%KCl) to drink. At 8 weeks of treatment hearts were Langendorffperfused, subjected to 20 minutes global ischaemia plus 45 minutes reperfusion (n=7-9 per group). Basal left ventricular developed pressure (LVDevP) was increased by L-NAME/salt treatment in female but not male hearts. During ischaemia, peak contracture was increased only in female WT and myo-MRKO hearts by NOS inhibition and time to contracture was shorter in female WT vs. myo-MRKO suggesting worse injury. At the end of reperfusion, recovery of LVDevP was significantly greater in myo-MRKO hearts compared to WT in both sexes (% basal LVDevP (mmHg): female WT;VEH:73±6, L-NAME/salt:56±4, female myo-MRKO;VEH:91±5, L-NAME/salt:85±7, p<0.05). These data indicate that cardiomyocyte MR contribute to cardiac dysfunction post-ischaemia/reperfusion following chronic, aldosterone-independent activation of MR. Further studies are investigating the molecular mechanisms involved in sexand MR-regulation of cardiac function and injury. http://dx.doi.org/10.1016/j.hlc.2015.06.208