Premature coronary artery disease and early stage chronic kidney disease.

A 30 year old asymptomatic male with stage 3 chronic kidney disease (CKD) secondary to Focal Segmental Glomerulosclerosis was found to have features of CKD associated cardiomyopathy including left ventricular hypertrophy (LVH) and focal sub-endocardial scarring on cardiac magnetic resonance imaging. There was also a significantly raised CT coronary calcium score and evidence of non-flow limiting coronary artery disease (CAD) on a CT coronary angiogram. Early stage CKD is a major risk factor for cardiovascular risk causing myocardial hypertrophy and fibrosis and coronary artery atheroma. Cardiovascular risk begins to increase from an eGFR of around 75ml/min/1.73m2. The pathophysiology of cardiovascular disease in CKD is under investigation but to date, treatment options are limited. Blood pressure control and statins have the strongest supportive evidence.

Effect of Valvular Surgery in Carcinoid Heart Disease: An Observational Cohort Study.

CONTEXT: Carcinoid heart disease (NET-CHD) is associated with the development of symptom-limited exercise capacity and high rates of morbidity and mortality. OBJECTIVE: This study sought to determine the survival, cardiac function, and functional class following surgery. DESIGN AND SETTING, AND PATIENTS: This was a retrospective observational cohort study between 2005 and 2015 at a European Centre of Excellence for Neuroendocrine Tumours, Queen Elizabeth Hospital Birmingham. England consisting of 62 consecutive patients referred to the NET-Cardiology Service. INTERVENTIONS: Subjects were assessed at referral using transthoracic echocardiography (with saline contrast) and transesophageal echocardiography, and 77% with confirmed NET-CHD underwent cardiovascular magnetic resonance imaging. Symptomatic patients with concomitant severe valvular dysfunction were referred for surgery with stable NET disease. MAIN OUTCOME MEASURE: Survival of patients with proven NET-CHD following medical and surgical treatments was measure. RESULTS: In total, 47/62 patients were diagnosed with NET-CHD. Thirty-two patients (68%) underwent surgery with bioprosthetic valve replacements in all subjects; tricuspid, n = 31; pulmonary, n = 30; mitral, n = 3; and aortic, n = 3. Four patients underwent concomitant coronary artery bypass grafting. There were 4 (13%) early post-operative deaths. One- and 2-y survival rates after surgery were 75 and 69% compared with 45 and 15% in un-operated patients. Post-operatively, functional class was improved (pre-New York Heart Association Classification [NYHA], 2.6 [0.5] vs post-NYHA, 1.7 [1.1]), P < .05, right-ventricular (RV) size was reduced (136 ml/m(2) [25] vs 71 ml/m(2) [7]; P < .01) with preserved RV ejection fraction (61% ± 9 vs 55% ± 10; P = .26). CONCLUSION: Valve surgery improved functional class and resulted in RV reverse remodelling with improved survival rates at 2 y compared with those not proceeding to operation. These data highlight the importance of close collaboration between NET clinicians, cardiology, and cardiothoracic surgery teams. Early referral can improve functional capacity but more research is needed to define the selection of appropriate candidates and randomized data are needed to define the effect of surgery on prognosis.

Variability in cardiac MR measurement of left ventricular ejection fraction, volumes and mass in healthy adults: defining a significant change at 1 year.

OBJECTIVE: Variability in the measurement of left ventricular (LV) parameters in cardiovascular imaging has typically been assessed over a short time interval, but clinicians most commonly compare results from studies performed a year apart. To account for variation in technical, procedural and biological factors over this time frame, we quantified the within-subject changes in LV volumes, LV mass (LVM) and LV ejection fraction (EF) in a well-defined cohort of healthy adults at 12 months. METHODS: Cardiac MR (CMR) was performed in 42 healthy control subjects at baseline and at 1 year (1.5 T Magnetom® Avanto; Siemens Healthcare, Erlangen, Germany). Analysis of steady-state free precession images was performed manually offline (Argus software; Siemens Healthcare) for assessment of LV volumes, LVM and EF by a single blinded observer. A random subset of 10 participants also underwent repeat imaging within 7 days to determine short-term interstudy reproducibility. RESULTS: There were no significant changes in any LV parameter on repeat CMR at 12 months. The short-term interstudy biases were not significantly different from the long-term changes observed at 1 year. The smallest detectable change (SDC) for LVEF, end-diastolic volume, end-systolic volume and LVM that could be recognized with 95% confidence were 6%, 13 ml, 7 ml and 6 g, respectively. CONCLUSION: The variability in CMR-derived LV measures arising from technical, procedural and biological factors remains minimal at 12 months. Thus, for patients undergoing repeat annual assessment by CMR, even small differences in LV function, size and LVM (which are greater than the SDC) may be attributed to disease-related factors. ADVANCES IN KNOWLEDGE: The reproducibility and reliability of CMR data at 12 months is excellent allowing clinicians to be confident that even small changes in LV structure and function over this time frame are real.

Central pulse pressure in patients with chronic kidney disease and in renal transplant recipients.

Patients with chronic kidney disease (CKD) and renal transplant recipients (RTR) have increased cardiovascular risk. The value of measuring central pulse pressure (cPP) over brachial pulse pressure (pPP) is not known. Central PP was measured in 597 patients (364 CKD:233 RTR). In multivariate analysis, age and female gender positively correlated with cPP; heart rate and estimated glomerular filtration rate negatively correlated with cPP. Associations for age, heart rate and gender persisted after additional adjustment for pPP and aortic wave reflection. This model accounted for 91% of the variability in cPP, with pPP alone accounting for 74%. Results were similar when both patient groups were analysed separately. A subset of patients with CKD had aortic pulse wave velocity (PWV) and left ventricular mass index (LVMI) measured. There were no differences in the univariate correlations between PWV (r=0.368 vs 0.315; P=0.4) or LVMI (r=0.125 vs 0.163; P=0.7); nor in the multivariate models created for PWV (P=0.1) or LVMI (P=0.1) when either cPP or pPP were used. This study demonstrates that in these patients most of the variability in cPP can be explained by pPP. Additionally, cPP does not appear to provide additional information beyond pPP in determining PWV and LVMI.

Analysis of F9 point mutations and their correlation to severity of haemophilia B disease.

Haemophilia B is an X-linked recessive disorder caused by deficiency of functional coagulation factor IX, which results almost exclusively from mutations in the F9 gene. We sought to determine features, which could distinguish between mutations that cause severe disease symptoms from those that cause non-severe disease symptoms. Towards this objective, we have performed a statistical analysis of reported point mutations in F9. These include: potential local changes in mRNA free energy, codon usage, charge and type of mutated amino acid, location of the mutation with regard to protein secondary structure and functional domain and amino acids' evolutionary conservation scores. Wilcoxon signed-rank tests showed highly significant differences between severe and non-severe disease causing mutations in their effect on free energy of small mRNA fragments and evolutionarily conserved amino acids. Our results suggest that information at the mRNA level as well as conservation of the amino acid correlate well with disease severity. This study demonstrates that computational tools may be used to characterize the severity of haemophilia B associated with point mutations and suggests their utility in predicting the outcome of sequence changes in recombinant proteins.

Understanding the effects of chronic kidney disease on cardiovascular risk: are there lessons to be learnt from healthy kidney donors?

Chronic kidney disease (CKD) is now a recognized global public health problem. It is highly prevalent and strongly associated with hypertension and cardiovascular disease (CVD); far more patients with a glomerular filtration rate below 60 ml min(-1) per 1.73 m(2) will die from cardiovascular causes than progress to end-stage renal disease. A better understanding of the complex mechanisms underlying the development of CVD among CKD patients is required if we are to begin devising therapy to prevent or reverse this process. Observational studies of CVD in CKD are difficult to interpret because renal impairment is almost always accompanied by confounding factors. These include the underlying disease process itself (for example, diabetes mellitus and systemic vasculitis) and the complications of CKD, such as hypertension, anaemia and inflammation. Kidney donors provide an ideal opportunity to study healthy subjects without manifest vascular disease who experience an acute change from having normal to modestly impaired renal function at the time of uninephrectomy. Prospectively examining the cardiovascular consequences of uninephrectomy using donors as a model of CKD may provide useful insight into the pathophysiology of CVD in CKD and, therefore, into how the CVD risk associated with renal impairment might eventually be reduced.

Comparative hospital economics and patient presentation: vertebroplasty and kyphoplasty for the treatment of vertebral compression fracture.

BACKGROUND AND PURPOSE: Previous studies evaluating vertebral augmentation procedure costs have not made detailed comparisons between vertebroplasty and kyphoplasty. Our study contrasts hospital costs for vertebroplasty versus kyphoplasty for the treatment of vertebral compression fractures in routine clinical practice in the United States. MATERIALS AND METHODS: This retrospective cohort study analyzed 2007-2008 hospital discharge and billing records from the Premier Perspective data base. The primary outcome variable, differences in total hospital cost between vertebroplasty and kyphoplasty, was assessed by using analysis of covariance. RESULTS: Three thousand six hundred seventeen patients received vertebroplasty (64% inpatient, 36% outpatient), and 8118 received kyphoplasty (54% inpatient, 46% outpatient). Approximately 75% were women, and most were white. Mean total unadjusted inpatient costs were $9837 for vertebroplasty versus $13 187 for kyphoplasty (P < .0001). Outpatient vertebroplasty costs were $3319 versus $8100 for kyphoplasty (P < .0001). Lower vertebroplasty costs were largely due to differences in hospital supply and OR. Mean vertebroplasty OR costs were $73.60 (anesthesia), $112.06 (recovery room), and $990.12 (surgery) versus $172.16 (anesthesia), $257.47 (recovery room), and $1,471.49 (surgery) with kyphoplasty. Adjustments for age, sex, admission status, and disease severity accentuated the differences. Mean adjusted inpatient costs were $11 386 for vertebroplasty versus $16 182 for kyphoplasty (P < .0001), and outpatient costs were $2997 for vertebroplasty versus $7010 for kyphoplasty (P < .0001). After adjustments for the same covariates, length-of-stay differences were no longer evident (P = .4945). CONCLUSIONS: Performing vertebroplasty versus kyphoplasty reduces hospital costs by nearly $5000 for inpatient procedures and by more than $4000 for outpatient procedures.

T2-weighted magnetic resonance imaging to assess myocardial oedema in ischaemic heart disease.

Cardiovascular magnetic resonance imaging (CMR) is an established clinical tool for the identification of irreversible myocardial injury. More recently, experience with stress-perfusion CMR has increased sufficiently so that this now provides an accurate and reliable aid to clinical decision-making in patients with ischaemic heart disease. T2-weighted or "black blood" imaging is a technique used less frequently to examine the myocardium but one that is growing in stature. This article explains the rationale behind the technique and reviews recent data illustrating clinical and research scenarios in which the addition of T2-weighted sequences to standard cardiac scanning protocols might be warranted.

Aortic distensibility and arterial-ventricular coupling in early chronic kidney disease: a pattern resembling heart failure with preserved ejection fraction.

OBJECTIVES: To examine arterial and left ventricular function and their interaction in patients with early-stage chronic kidney disease (CKD). DESIGN AND SETTING: Cross-sectional observational study in a university teaching hospital. PATIENTS: 117 patients with stage 2 (60-89 ml/min/1.73 m(2)) or stage 3 (30-59 ml/min/1.73 m(2)) non-diabetic CKD, without overt cardiovascular disease were compared with 40 controls. INTERVENTIONS: Aortic distensibility and left ventricular mass were assessed using cardiac magnetic resonance imaging. Systolic and diastolic ventricular function and arterial-ventricular elastance (stiffness) were assessed by transthoracic echocardiography. MAIN OUTCOME MEASURES: Arterial stiffness as measured by aortic distensibility and arterial elastance. Left ventricular mass, left ventricular systolic and diastolic function, including end-diastolic and end-systolic elastance and their relationship with arterial elastance. RESULTS: Compared with controls, patients with CKD 2 and CKD 3 had reduced aortic distensibility (4.12 (1.3) vs 2.94 (1.8) vs 2.18 (1.8)x10(-3) mm Hg, p<0.01), increased arterial elastance (1.4 (1.3) vs 1.65 (0.40) vs 1.74 0.48) mm Hg, p<0.05) and increased end-systolic (1.88 (0.48) vs 2.43 (0.83) vs 2.42(0.78) mm Hg/ml, p<0.05) and end diastolic elastances (0.07 (0.04) vs 0.11 (0.04) vs 0.12 (0.04, p<0.01). Aortic distensibility was positively correlated with estimated glomerular filtration rate (r = 0.349, p<0.01) and indices of elastance were inversely correlated (r = 0.284, p<0.05). Systolic function was not impaired in patients with early CKD compared with controls but diastolic filling velocities (Em) were reduced (8.1 (0.9) vs 7.9 (0.6) vs 7.5 (0.7) cm/s, p<0.01) while mean left atrial pressure (E/Em) was increased (5.6 (1.1), vs 7.4 (1.8) vs 8.0 (2.4), p<0.01) and end-diastolic elastance was increased. CONCLUSIONS: Early-stage CKD is characterised by reduced aortic distensibility and increases in arterial, ventricular systolic and diastolic stiffness; arterial-ventricular coupling is preserved. This pattern of pathophysiological abnormalities resembles that seen in heart failure with preserved ejection fraction and may account for the high levels of cardiovascular morbidity and mortality in patients at all stages of CKD. TRIAL REGISTRATION NUMBER: NCT00291720.

People and money matter: investment lessons from the Ontario Heart Health Program, Canada

Resource allocation is a critical issue for public health decision-makers. Yet little is known about the level and type of resources needed to build capacity to plan and implement comprehensive programs. This paper examines the relationships between investments and changes in organizational capacity and program implementation in the first phase (1998-2003) of the Ontario Heart Health Program (OHHP)--a province-wide, comprehensive public health program that involved 40 community partnerships. The study represents a subset of findings from a provincial evaluation. Investments, organizational capacity of public health units and implementation of heart health activities were measured longitudinally. Investment information was gathered annually from the provincial government, local public health units and community partners using standard reports, and was available from 1998 to 2002. Organizational capacity and program implementation were measured using a written survey, completed by all health units at five measurement times from 1994 to 2002. Combining provincial and local sources, the average total investment by year five was $1.66 per capita. Organizational capacity of public health units and implementation of heart health activities increased both before and during the first 2 years of the OHHP, and then plateaued at a modest level for capacity and a low level for implementation after that. Amount of funding was positively associated with organizational capacity, yet this association was overpowered by the negative influence of turnover of a key staff position. Regression analysis indicated that staff turnover explained 23 per cent of local variability in organizational capacity. Findings reinforce the need for adequate investment and retention of key staff positions in complex partnership programs. Better accounting of public health investments, including monetary and in-kind investments, is needed to inform decisions about the amount and duration of public health investments that will lead to effective program implementation. (AU)

The treatment of coronary artery disease in patients with chronic kidney disease.

Premature cardiovascular disease is the largest cause of mortality, and a major cause of morbidity, in patients with chronic kidney disease (CKD). Patients with end-stage kidney disease (ESKD) are at extreme risk, but cardiovascular event rates are increased even in early CKD. There is little controlled trial evidence on which to base treatment, as most therapeutic trials have excluded CKD patients. Current treatment strategies are therefore based upon small prospective studies or retrospective analyses of controlled trials and registry data. It is thus unclear whether CKD patients benefit from modern secondary preventive treatments in the same manner as patients with normal renal function. There is a need for randomized trials to identify effective drugs to prevent and treat coronary artery disease in CKD. Revascularization by CABG in CKD has been widely reported in registry data to provide better results than medical treatment or angioplasty. Recent angioplasty data in patients with CKD, however, show improving results, and the risks of CABG in CKD remain high. It is not clear which revascularization technique has a better outcome in patients 'equally suitable' on angiographic criteria for either procedure. The high rate of late adverse cardiovascular events after both CABG and angioplasty accentuates the need for effective secondary preventive therapy disease in these high-risk patients.

Routine chest radiography after permanent pacemaker implantation: is it necessary?

BACKGROUND AND AIMS: Chest radiographs (CXRs) are performed routinely after permanent pacemaker implantation to identify pacemaker lead position and exclude pneumothorax. We assessed the clinical value and need for this procedure. DESIGN: Retrospective analysis of pacemaker data and CXRs following permanent pacemaker insertion between December 2002 and February 2004. MATERIALS AND METHODS: Post-procedural CXRs were available in 125/126 consecutive patients after either first endocardial pacemaker implantation or insertion of at least one new lead. Subclavian vein puncture was used for venous access in all cases. CXRs were examined to establish the incidence of pneumothorax and assess pacing lead positions. The clinical records were examined in all patients who had subsequent CXRs or a further pacemaker procedure to identify the indication for these and to establish whether CXR had influenced patient management. RESULTS: In total, 192 post-procedural CXRs were performed, either postero-anterior (PA) and/or lateral views. Ventricular and/or atrial pacing lead contour and electrode position was considered radiographically appropriate in 86% CXRs. Fourteen per cent of post-procedural radiographs were considered to have radiologically sub-optimal pacemaker lead positioning. None of the patients with these "abnormal" radiographs experienced subsequent pacemaker complications or had further radiographs recorded at a later date. Later repeat CXRs were performed in 16 patients (13%) but only 3 patients (2%) had pacing abnormalities as the primary indication. All three had satisfactory pacing lead position on initial post-implantation and later radiographs, but required further procedures for lead re-positioning. Iatrogenic pneumothorax occurred in one patient (incidence 0.8%) in our series. CXR confirmed the clinical diagnosis and allowed an assessment of size to guide treatment. CONCLUSION: Routine CXR after permanent pacemaker insertion is not necessary in uncomplicated cases with adequate pacing characteristics.