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Patrick SK Liu-Shiu-Cheong,1,2 Brian J Lipworth,3 Jonathan R Weir-McCall,1,4 J Graeme Houston,5 Allan D Struthers1 1Division of Molecular and Clinical Medicine, University of Dundee, Dundee DD1 9SY, UK; 2Department of Respiratory Medicine, Victoria Hospital, NHS Fife, Kirkcaldy KY2 5AH, UK; 3Scottish Centre for Respiratory Research, Medical Research Institute, University of Dundee, Dundee DD1 9SY, UK; 4Department of Radiology, University of Cambridge, Cambridge CB2 0QQ, UK; 5Imaging Science and Technology, University of Dundee, Dundee DD1 9SY, UKCorrespondence: Brian J LipworthScottish Centre for Respiratory Research, Medical Research Institute, University of Dundee, Ninewells Hospital, Dundee DD1 9SY, United KingdomTel +44 1382 383188Email b.j.lipworth@dundee.ac.ukBackground: Oxidative stress (OS) has been implicated in the development of pulmonary hypertension (PH) and ventricular hypertrophy. Xanthine oxidase is a well-recognised source of reactive oxygen species, which lead to OS. The aim of this proof of concept study was to assess whether allopurinol (xanthine oxidase inhibitor) would reduce right ventricular mass (RVM) in patients with PH-associated chronic lung disease (PH-CLD).Methods: We conducted a randomised, double-blind, parallel-group, placebo-controlled trial in patients with PH-CLD (93% COPD, 7% IPF) who were randomly assigned to receive allopurinol or placebo for 12 months. The primary outcome was the mean change in RVM, as assessed by cardiac magnetic resonance imaging (CMRI). Secondary outcomes included quality of life (QOL), spirometry and six-minute walk test (6MWT).Results: Seventy-one patients were recruited: mean age 71 years, mean pulmonary arterial pressure 30 mm Hg, FEV1 60% and resting SpO2 96%. After 12 months, there was no significant difference in the change in RVM from baseline (allopurinol 1.85g vs placebo 0.97g with mean difference 0.88g, CI − 4.77 to 3.01, p =0.7). There were also no significant changes in other cardiac parameters measured on MRI, in QOL, spirometry and 6MWT. Subgroup analysis showed that allopurinol significantly reduced RVM compared to placebo with -6.16g vs 0.75g and mean difference 6.92g (CI 1.14 to 12.69, p = 0.02) in COPD patients with more severe airflow limitation.Conclusion: Allopurinol had no overall impact on patients with PH-CLD but had potential benefit in COPD patients with more severe airflow limitation.Keywords: pulmonary hypertension, right ventricle, allopurinol, chronic lung disease

Jonathan R Weir-McCall,1 Patrick SK Liu-Shiu-Cheong,2 Allan D Struthers,1 Brian J Lipworth,2 J Graeme Houston1 1Division of Molecular and Clinical Medicine, Medical Research Institute, University of Dundee, Dundee, UK; 2Scottish Centre for Respiratory Research, Medical Research Institute, University of Dundee, Dundee, UK Background: Both pulmonary arterial stiffening and systemic arterial stiffening have been described in COPD. The aim of the current study was to assess pulse wave velocity (PWV) within these two arterial beds to determine whether they are separate or linked processes. Materials and methods: In total, 58 participants with COPD and 21 healthy volunteers (HVs) underwent cardiac magnetic resonance imaging (MRI) and were tested with a panel of relevant biomarkers. Cardiac MRI was used to quantify ventricular mass, volumes, and pulmonary (pulse wave velocity [pPWV] and systemic pulse wave velocity [sPWV]). Results: Those with COPD had higher pPWV (COPD: 2.62 vs HV: 1.78 ms-1, p=0.006), higher right ventricular mass/volume ratio (RVMVR; COPD: 0.29 vs HV: 0.25 g/mL, p=0.012), higher left ventricular mass/volume ratio (LVMVR; COPD: 0.78 vs HV: 0.70 g/mL, p=0.009), and a trend toward a higher sPWV (COPD: 8.7 vs HV: 7.4 ms-1, p=0.06). Multiple biomarkers were elevated: interleukin-6 (COPD: 1.38 vs HV: 0.58 pg/mL, p=0.02), high-sensitivity C-reactive protein (COPD: 6.42 vs HV: 2.49 mg/L, p=0.002), surfactant protein D (COPD: 16.9 vs HV: 9.13 ng/mL, p=0.001), N-terminal pro-brain natriuretic peptide (COPD: 603 vs HV: 198 pg/mL, p=0.001), and high-sensitivity troponin I (COPD: 2.27 vs HV: 0.92 pg/mL, p

Abstract Background To assess the accuracy of findings from the clinical history, symptoms, signs and diagnostic tests (ECG, CXR and natriuretic peptides) in relation to the diagnosis of left ventricular systolic dysfunction (LVSD) in a primary care setting. Methods Diagnostic accuracy systematic review, we searched Medline (1966 to March 2008), EMBASE (1988 to March 2008), Central, Cochrane and ZETOC using a diagnostic accuracy search filter. We included cross-sectional or cohort studies that assess the diagnostic utility of clinical history, symptoms, signs and diagnostic tests, against a reference standard of echocardiography. We calculated pooled positive and negative likelihood ratios and assessed heterogeneity using the I2 index. Results 24 studies incorporating 10,710 patients were included. The median prevalence of LVSD was 29.9% (inter-quartile range 14% to 37%). No item from the clinical history or symptoms provided sufficient diagnostic information to "rule in" or "rule out" LVSD. Displaced apex beat shows a convincing diagnostic effect with a pooled positive likelihood ratio of 16.0 (8.2–30.9) but this finding occurs infrequently in patients. ECG was the most widely studied diagnostic test, the negative likelihood ratio ranging from 0.06 to 0.6. Natriuretic peptide results were strongly heterogeneous, with negative likelihood ratios ranging from 0.02 to 0.80. Conclusion Findings from the clinical history and examination are insufficient to "rule in" or "rule out" a diagnosis of LVSD in primary care settings. BNP and ECG measurement appear to have similar diagnostic utility and are most useful in "ruling out" LVSD with a normal test result when the probability of LVSD is in the intermediate range.

Background: COPD is associated with significant cardiovascular mortality. Left ventricular hypertrophy (LVH) is a pivotal cardiovascular risk factor. The prevalence of LVH in COPD is currently unknown.Methods: We performed a pilot study of 93 normoxemic patients with COPD and 34 control subjects. Patients underwent echocardiography to measure left ventricular (LV) dimensions, ECG, measurement of serum B-type natriuretic peptide (BNP) levels, and 24-h BP recording. Spirometry and oxygen saturations were also recorded.Results: The oxygen saturations of patients with COPD were normal, at 96.5% (95% CI, 96.1%-97.0%), with a mean FEV(1) of 70.0% predicted (95% CI, 65.2%-74.8%). A total of 30.1% of patients with COPD met the echocardiographic criteria for LVH based on LV mass index, with more LVH in female patients than in male patients (43.2% vs 21.4%, P = .02). The LV mass index in patients with COPD was 96.2 g/m(2) (95% CI, 90.1-102.7 g/m(2)) vs 82.9 g/m(2) (95% CI, 75.8-90.6 g/m(2)) in control subjects ( P = .017). The LV mass index remained high in patients with COPD in the absence of a hypertension history (94.5 g/m(2) vs 79.9 g/m(2), P = .015) and with 24-h systolic BP <135 mm Hg (96.7 g/m(2) vs 82.5 g/m(2), P = .024). The LV ejection fraction (mean = 63.4%) and BNP (mean = 28.7 pg/mL) were normal in patients with COPD. The mean 24-h BP was normal in patients with COPD, at 125/72 mm Hg. ECG was less sensitive for detecting LVH than was echocardiography.Conclusion: LVH with normal LV ejection fraction and BNP levels was present in a significant proportion of normotensive, normoxemic patients with COPD, especially female patients. Clinical trials are, therefore, indicated to evaluate treatments to regress LVH in patients with COPD. [ABSTRACT FROM AUTHOR]

Aortic valve disease (AVD) is the most common form of valvular heart disease in the western world. The only proven therapy for severe AVD is open aortic valve replacement, with trans-catheter aortic valve implantation emerging as a promising modality to treat severe aortic stenosis in a selected group of patients. AVD has a long asymptomatic phase with symptoms occurring late in the disease and once symptoms develop, prognosis is poor. There is a growing appreciation that aortic valvular heart disease incorporates a disease process that extends beyond the valve itself leading to an aortic valvular 'heart' disease. The renin-angiotensin system is known to modulate adverse left ventricular remodeling and myocardial fibrosis, which could be caused by increased load caused by the AVD. In this review, the authors explore evidence that suggest that drugs that target the renin-angiotensin system may have a potential therapeutic role in AVD. [ABSTRACT FROM AUTHOR]

Background: Right ventricular apical pacing can cause dyssynchronous activation of the ventricles, increase sympathetic activation, cause abnormalities in myocardial perfusion, worsen cardiac output and endothelial function, and may be associated with adverse cardiovascular effects. The use of rennin-angiotensin system blockers (RASBs) may be beneficial in counteracting these potentially harmful effects of right ventricular pacing. Objective: To explore the impact of RASB use on the outcome in patients with right ventricular pacemakers implanted for complete atrioventricular (AV) block. Methods: Patients implanted with right ventricular pacemakers for complete AV block between 1994 and 2009 were identified from the Tayside Pacing Registry. Cox proportional hazards model was used to assess differences in all-cause mortality and congestive heart failure hospitalizations for those receiving RASB during follow-up, adjusted for confounding variables. We also performed 2 sensitivity analyses--a propensity score-matched analysis and time-dependent analyses--to minimize bias. Results: Eight hundred twenty patients (57% men; median age 73 years; range 22-103 years) received pacemakers for complete AV block between 1994 and 2008 (54% dual-chamber pacemaker and 46% ventricular demand pacemaker). Two hundred seventy-eight (34%) patients had received RASBs. Mean follow-up was 4.9 ± 4.6 years, with 540 (65%) deaths. RASB use was independently associated with significantly reduced mortality (adjusted hazard ratio 0.67; 95% confidence interval 0.47-0.94; P = .017) and reduced heart failure hospitalization (adjusted hazard ratio 0.42; 95% confidence interval 0.17-0.92; P <.001). Conclusions: This study suggests that RASBs may confer outcome benefits in patients with right ventricular pacemakers implanted for complete AV block. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The demand-control (D-C) model of job strain has generated a considerable body of empirical support in predicting psychological health outcomes in the context of work. This study aimed to extend previous work using the D-C model of job strain to predict caregiver burden and satisfaction in the informal caregivers of patients with heart failure. DESIGN AND METHOD: Data were gathered from 60 caregiver/patient dyads in a cross-sectional design. Patients with chronic stable heart failure were recruited from out-patient clinics. The dependent variables were caregiver burden and satisfaction. Demand and control were measured using both patient- and caregiver-derived measures. RESULTS: The D-C model accounted for 15 and 19% of the variance in caregiver burden, after controlling for age, gender and relationship to the patient. Lower control was associated with higher burden. The D-C model did not predict caregiver satisfaction. CONCLUSION: The D-C model was associated with caregiver burden, but not satisfaction in caregivers, with control being the dominant predictor. Research linking the theory and findings from job strain and informal caregiving studies may elucidate both fields of research. Using the demand-control model of job strain to predict caregiver burden and caregiver satisfaction in the informal caregivers of heart failure patients. [ABSTRACT FROM AUTHOR]