Showing papers in "Heart in 2012"

Risk prediction models: II. External validation, model updating, and impact assessment

Abstract: Clinical prediction models are increasingly used to complement clinical reasoning and decision-making in modern medicine, in general, and in the cardiovascular domain, in particular. To these ends, developed models first and foremost need to provide accurate and (internally and externally) validated estimates of probabilities of specific health conditions or outcomes in the targeted individuals. Subsequently, the adoption of such models by professionals must guide their decision-making, and improve patient outcomes and the cost-effectiveness of care. In the first paper of this series of two companion papers, issues relating to prediction model development, their internal validation, and estimating the added value of a new (bio)marker to existing predictors were discussed. In this second paper, an overview is provided of the consecutive steps for the assessment of the model's predictive performance in new individuals (external validation studies), how to adjust or update existing models to local circumstances or with new predictors, and how to investigate the impact of the uptake of prediction models on clinical decision-making and patient outcomes (impact studies). Each step is illustrated with empirical examples from the cardiovascular field.

Risk prediction models: I. Development, internal validation, and assessing the incremental value of a new (bio)marker

Abstract: Prediction models are increasingly used to complement clinical reasoning and decision making in modern medicine in general, and in the cardiovascular domain in particular. Developed models first and foremost need to provide accurate and (internally and externally) validated estimates of probabilities of specific health conditions or outcomes in targeted patients. The adoption of such models must guide physician's decision making and an individual's behaviour, and consequently improve individual outcomes and the cost-effectiveness of care. In a series of two articles we review the consecutive steps generally advocated for risk prediction model research. This first article focuses on the different aspects of model development studies, from design to reporting, how to estimate a model's predictive performance and the potential optimism in these estimates using internal validation techniques, and how to quantify the added or incremental value of new predictors or biomarkers (of whatever type) to existing predictors. Each step is illustrated with empirical examples from the cardiovascular field.

Relative ‘apical sparing’ of longitudinal strain using two-dimensional speckle-tracking echocardiography is both sensitive and specific for the diagnosis of cardiac amyloidosis

Abstract: Background The diagnosis of cardiac amyloidosis (CA) is challenging owing to vague symptomatology and non-specific echocardiographic findings. Objective To describe regional patterns in longitudinal strain (LS) using two-dimensional speckle-tracking echocardiography in CA and to test the hypothesis that regional differences would help differentiate CA from other causes of increased left ventricular (LV) wall thickness. Methods and results 55 consecutive patients with CA were compared with 30 control patients with LV hypertrophy (n=15 with hypertrophic cardiomyopathy, n=15 with aortic stenosis). A relative apical LS of 1.0, defined using the equation (average apical LS/(average basal LS + mid-LS)), was sensitive (93%) and specific (82%) in differentiating CA from controls (area under the curve 0.94). In a logistic regression multivariate analysis, relative apical LS was the only parameter predictive of CA (p=0.004). Conclusions CA is characterised by regional variations in LS from base to apex. A relative ‘apical sparing’ pattern of LS is an easily recognisable, accurate and reproducible method of differentiating CA from other causes of LV hypertrophy.

Improvements in risk stratification for the occurrence of cardiovascular disease by imaging subclinical atherosclerosis: a systematic review

Abstract: Context Imaging for subclinical atherosclerosis on top of conventional risk factor assessment may improve risk prediction for the occurrence of cardiovascular disease events in asymptomatic individuals. Objective To systematically review the available evidence on this issue. Data Sources PubMed MEDLINE was systematically searched on 7 September 2011. Study selection Studies were included that evaluated the added value of flow mediated dilation (FMD), carotid intima-media thickness (CIMT), carotid plaques and/or coronary artery calcification (CAC) scoring in the prediction of risk for developing fatal or non-fatal cardiovascular events. Data extraction Data on general study characteristics and the added predictive performance of imaging markers in terms of discrimination, calibration and (re)classification were extracted. Results 25 studies were selected that provided information on added predictive value of FMD (n=2), CIMT (n=12), carotid plaques (n=6) and/or CAC (n=9). Heterogeneity existed across studies in the conventional risk models that were used and in the measurements of the imaging marker. The added predictive value, quantified by the difference in c-index, of FMD, CIMT, carotid plaques or CAC ranged from 0.00 to 0.01 for FMD, from 0.00 to 0.03 for CIMT, from 0.01 to 0.05 for carotid plaque and from 0.05 to 0.13 for CAC. The reported net reclassification improvement (NRI) by the imaging markers ranged from −1.4% to 12% for CIMT, 8% to 11% for carotid plaques, 14% to 25% for CAC and 29% for FMD). Although the definition of intermediate cardiovascular risk varied across studies, the NRI was the highest in those at intermediate cardiovascular risk. Conclusions Published evidence on the added value of atherosclerosis imaging varies across the different markers, with limited evidence for FMD and considerable evidence for CIMT, carotid plaque and CAC. The added predictive value of additional screening may be primarily found in asymptomatic individuals at intermediate cardiovascular risk. Additional research in asymptomatic individuals is needed to quantify the cost effectiveness and impact of imaging for subclinical atherosclerosis on cardiovascular risk factor management and patient outcomes.

Cardiovascular magnetic resonance measurement of myocardial extracellular volume in health and disease

Abstract: Objective To measure and assess the significance of myocardial extracellular volume (ECV), determined non-invasively by equilibrium contrast cardiovascular magnetic resonance, as a clinical biomarker in health and a number of cardiac diseases of varying pathophysiology. Design Prospective study. Setting Tertiary referral cardiology centre in London, UK. Patients 192 patients were mainly recruited from specialist clinics. We studied patients with Anderson–Fabry disease (AFD, n=17), dilated cardiomyopathy (DCM, n=31), hypertrophic cardiomyopathy (HCM, n=31), severe aortic stenosis (AS, n=66), cardiac AL amyloidosis (n=27) and myocardial infarction (MI, n=20). The results were compared with those for 81 normal subjects. Results In normal subjects, ECV (mean (95% CI), measured in the septum) was slightly higher in women than men (0.273 (0.264 to 0.282 vs 0.233 (0.225 to 0.244), p Conclusions Myocardial ECV, assessed non-invasively in the septum with equilibrium contrast cardiovascular magnetic resonance, shows gender differences in normal individuals and disease-specific variability. Therefore, ECV shows early potential to be a useful biomarker in health and disease.

Bariatric surgery and cardiovascular outcomes: a systematic review

Abstract: Purpose To quantify the impact of bariatric surgery on cardiovascular (CV) risk factors, and on cardiac structure and function. Data sources Three major databases (PubMed, Medline and Cochrane) were searched for original studies written in English. Study selection Original articles reporting CV risk factors or non-invasive imaging parameters for patients undergoing bariatric surgery, from January 1950 to June 2012. Data extraction Data extraction from selected studies was based on protocol-defined criteria that included study design, methods, patient characteristics, surgical procedures, weight loss, changes in CV risk factors, cardiac structure and cardiac function postoperatively. Data synthesis 73 CV risk factor studies involving 19 543 subjects were included (mean age 42 years, 76% female). Baseline prevalence of hypertension, diabetes and hyperlipidaemia were 44%, 24%, and 44%, respectively. Mean follow-up was 57.8 months (range 3–176) and average excess weight loss was 54% (range 16–87%). Postoperative resolution/improvement of hypertension occurred in 63% of subjects, of diabetes in 73% and of hyperlipidaemia in 65%. Echocardiographic data from 713 subjects demonstrated statistically significant improvements in left ventricular mass, E/A ratio, and isovolumic relaxation time postoperatively. Limitations Diagnostic criteria, CV risk factor reporting, and imaging parameters were not uniform across all studies. Study groups were heterogeneous in their demographics, operative technique and follow-up period. Conclusions This systematic review highlights the benefits of bariatric surgery in reducing risk factors for CV disease. There is also evidence for left ventricular hypertrophy regression and improved diastolic function. These observations provide further evidence that bariatric surgery enhances future CV health for obese individuals.

Associations of dietary calcium intake and calcium supplementation with myocardial infarction and stroke risk and overall cardiovascular mortality in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition study (EPIC-Heidelberg)

Abstract: Background It has been suggested that a higher calcium intake might favourably modify cardiovascular risk factors. However, findings of an ultimately decreased risk of cardiovascular disease (CVD) are limited. Instead, recent evidence warns that taking calcium supplements might increase myocardial infarction (MI) risk. Objective To prospectively evaluate the associations of dietary calcium intake and calcium supplementation with MI and stroke risk and overall CVD mortality. Methods Data from 23980 Heidelberg cohort participants of the European Prospective Investigation into Cancer and Nutrition study, aged 35e64 years and free of major CVD events at recruitment, were analysed. Multivariate Cox regression models were used to estimate HRs and 95% CIs. Results After an average follow-up time of 11 years, 354 MI and 260 stroke cases and 267 CVD deaths were documented. Compared with the lowest quartile, the third quartile of total dietary and dairy calcium intake had a significantly reduced MI risk, with a HR of 0.69 (95% CI 0.50 to 0.94) and 0.68 (95% CI 0.50 to 0.93), respectively. Associations for stroke risk and CVD mortality were overall null. In comparison with non-users of any supplements, users of calcium supplements had a statistically significantly increased MI risk (HR¼1.86; 95% CI 1.17 to 2.96), which was more pronounced for calcium supplement only users (HR¼2.39; 95% CI 1.12 to 5.12). Conclusions Increasing calcium intake from diet might not confer significant cardiovascular benefits, while calcium supplements, which might raise MI risk, should be taken with caution.

Left ventricular thrombus formation after acute myocardial infarction

Abstract: Cardiovascular disease remains the leading cause of death in western society. Mortality from acute myocardial infarction (AMI) has decreased since the introduction of primary percutaneous coronary intervention (PCI), which has proved to be superior to thrombolytic therapy by demonstrating lower mortality rates and reduced clinical adverse events. Nevertheless, postinfarct complications still lead to morbidity and mortality in a large number of patients. One of the most feared complications is the occurrence of thromboembolic events (mostly cerebrovascular accidents) due to left ventricular (LV) thrombus formation. The risk of LV thrombus formation is highest during the first 3 months following acute myocardial infarction, but the potential for cerebral emboli persists in the large population of patients with chronic LV dysfunction. Since these thromboembolic events are usually unheralded by warning signs of transient cerebral ischaemia, the only truly satisfactory medical approach is adequate management of these high risk groups. This article discusses the incidence, diagnosis and management of LV thrombus formation after an AMI. The combination of blood stasis, endothelial injury and hypercoagulability, often referred to as Virchow's triad, is a prerequisite for in vivo thrombus formation. In the presence of LV thrombus formation after AMI, the three components of this triad can also be recognised (figure 1). LV regional wall akinesia and dyskinesia result in blood stasis, often recognised on two dimensional echocardiography by the occurrence of spontaneous LV contrast. Prolonged ischaemia leads to subendocardial tissue injury with inflammatory changes. Finally, patients with an acute coronary syndrome display a hypercoagulable state with, for example, increased concentrations of prothrombin, fibrinopeptide A, and von Willebrand factor, and decreased concentrations of the enzyme responsible for cleaving von Willebrand factor (ADAMTS13).w1 w2 This triad can result in the formation of LV thrombus composed …

Physiological cardiac remodelling in response to endurance exercise training: cellular and molecular mechanisms

Abstract: Exercise training fosters the health and performance of the cardiovascular system, and represents nowadays a powerful tool for cardiovascular therapy. Exercise exerts its beneficial effects through reducing cardiovascular risk factors, and directly affecting the cellular and molecular remodelling of the heart. Traditionally, moderate endurance exercise training has been viewed to determine a balanced and revertible physiological growth, through cardiomyocyte hypertrophy accompanied by appropriate neoangiogenesis (the Athlete's Heart). These cellular adaptations are due to the activation of signalling pathways and in particular, the IGF-1/IGF-1R/Akt axis appears to have a major role. Recently, it has been shown that physical exercise determines cardiac growth also through new cardiomyocyte formation. Accordingly, burgeoning evidence indicates that exercise training activates circulating, as well as resident tissue-specific cardiac, stem/progenitor cells. Dissecting the mechanisms for stem/progenitor cell activation with exercise will be instrumental to devise new effective therapies, encompassing myocardial regeneration for a large spectrum of cardiovascular diseases.

Right ventriculo-arterial coupling in pulmonary hypertension: a magnetic resonance study

Abstract: Objective To quantify right ventriculo-arterial coupling in pulmonary hypertension by combining standard right heart catheterisation (RHC) and cardiac magnetic resonance (CMR) and to estimate it non-invasively with CMR alone. Design Cross-sectional analysis in a retrospective cohort of consecutive patients. Setting Tertiary care centre. Patients 139 adults referred for pulmonary hypertension evaluation. Interventions CMR and RHC within 2 days (n=151 test pairs). Main outcome measures Right ventriculo-arterial coupling was quantified as the ratio of pulmonary artery (PA) effective elastance (E a , index of arterial load) to right ventricular maximal end-systolic elastance (E max , index of contractility). Right ventricular end-systolic volume (ESV) and stroke volume (SV) were obtained from CMR and adjusted to body surface area. RHC provided mean PA pressure (mPAP) as a surrogate of right ventricular end-systolic pressure, pulmonary capillary wedge pressure (PCWP) and pulmonary vascular resistance index (PVRI). E a was calculated as (mPAP − PCWP)/SV and E max as mPAP/ESV. Results E a increased linearly with advancing severity as defined by PVRI quartiles (0.19, 0.50, 0.93 and 1.63 mm Hg/ml/m 2 , respectively; p max increased initially and subsequently tended to decrease (0.52, 0.67, 0.54 and 0.56 mm Hg/ml/m 2 ; p=0.7). E a /E max was maintained early but increased markedly with severe hypertension (0.35, 0.72, 1.76 and 2.85; p a /E max approximated non-invasively with CMR as ESV/SV was 0.75, 1.17, 2.28 and 3.51, respectively (p Conclusions Right ventriculo-arterial coupling in pulmonary hypertension can be studied with standard RHC and CMR. Arterial load increases with disease severity whereas contractility cannot progress in parallel, leading to severe uncoupling.

Pulmonary hypertension: prevalence and mortality in the Armadale echocardiography cohort

Abstract: Background Pulmonary hypertension (PHT) lacks community prevalence and outcome data. Objective To characterise minimum ‘indicative’ prevalences and mortality data for all forms of PHT in a selected population with an elevated estimated pulmonary artery systolic pressure (ePASP) on echocardiography. Design Observational cohort study. Setting Residents of Armadale and the surrounding region in Western Australia (population 165450) referred to our unit for transthoracic echocardiography between January 2003 and December 2009. Results Overall, 10314 individuals (6.2% of the surrounding population) had 15633 echo studies performed. Of these, 3320 patients (32%) had insufficient TR to ePASP and 936 individuals (9.1%, 95% CI 8.6% to 9.7%) had PHT, defined as, ePASP>40 mm Hg. The minimum ‘indicative’ prevalence for all forms of PHT is 326 cases/100000 inhabitants of the local population, with left heart disease-associated PHT being the commonest cause (250 cases/100000). 15 cases of pulmonary arterial hypertension/100000 inhabitants were identified and an additional 144 individuals (15%) with no identified cause for their PHT. The mean time to death for those with ePASP >40 mm Hg, calculated from the first recorded ePASP, was 4.1 years (95% CI 3.9 to 4.3). PHT increased mortality whatever the underlying cause, but patients with PHT from left heart disease had the worst prognosis and those with idiopathic pulmonary arterial hypertension receiving disease-specific treatment the best prognosis. Risk of death increased with PHT severity: severe pulmonary hypertension shortened the lifespan by an average of 1.1 years compared with mild pulmonary hypertension. Conclusions In this cohort, PHT was common and deadly. Left heart disease was the most common cause and had the worst prognosis and treated pulmonary arterial hypertension had the best prognosis.

Rehabilitation after myocardial infarction trial (RAMIT): multi-centre randomised controlled trial of comprehensive cardiac rehabilitation in patients following acute myocardial infarction

Abstract: Background It is widely believed that cardiac rehabilitation following acute myocardial infarction (MI) reduces mortality by approximately 20%. This belief is based on systematic reviews and meta-analyses of mostly small trials undertaken many years ago. Clinical management has been transformed in the past 30–40 years and the findings of historical trials may have little relevance now. Objectives The principal objective was to determine the effect of cardiac rehabilitation, as currently provided, on mortality, morbidity and health-related quality of life in patients following MI. The secondary objectives included seeking programmes that may be more effective and characteristics of patients who may benefit more. Design, setting, patients, outcome measures A multi-centre randomised controlled trial in representative hospitals in England and Wales compared 1813 patients referred to comprehensive cardiac rehabilitation programmes or discharged to ‘usual care’ (without referral to rehabilitation). The primary outcome measure was all-cause mortality at 2 years. The secondary measures were morbidity, health service use, health-related quality of life, psychological general well-being and lifestyle cardiovascular risk factors at 1 year. Patient entry ran from 1997 to 2000, follow-up of secondary outcomes to 2001 and of vital status to 2006. A parallel study compared 331 patients in matched ‘elective’ rehabilitation and ‘elective’ usual care (without rehabilitation) hospitals. Results There were no significant differences between patients referred to rehabilitation and controls in mortality at 2 years (RR 0.98, 95% CI 0.74 to 1.30) or after 7–9 years (0.99, 95% CI 0.85 to 1.15), cardiac events, seven of eight domains of the health-related quality of life scale (‘Short Form 36’, SF36) or the psychological general well-being scale. Rehabilitation patients reported slightly less physical activity. No differences between groups were reported in perceived overall quality of cardiac aftercare. Data from the ‘elective’ hospitals comparison concurred with these findings. Conclusion In this trial, comprehensive rehabilitation following MI had no important effect on mortality, cardiac or psychological morbidity, risk factors, health-related quality of life or activity. This finding is consistent with systematic reviews of all trials reported since 1983. The value of cardiac rehabilitation as practised in the UK is open to question.

Prevalence, timing of diagnosis and mortality of newborns with congenital heart defects: a population-based study

Abstract: Objective To assess the prevalence, timing of diagnosis and infant mortality of congenital heart defects (CHD) with population-based data and using a classification that allows regrouping of the International Paediatric and Congenital Cardiac Code into a manageable number of categories based on anatomic and clinical criteria (ACC-CHD). Design Population-based cohort study. Setting Greater Paris. Patients All cases (live births, terminations of pregnancy for foetal anomaly (TOPFA), foetal deaths) diagnosed prenatally, or up to 1 year of age in the birth cohorts, May 2005–April 2008, for women in Greater Paris (n=317 538 births). Diagnoses were confirmed in specialised centres and subsequently coded and classified into the categories of ACC-CHD by paediatric cardiologists in the study group. Results The total number of CHD was 2867, including 2348 live births (82%), 466 TOPFA (16.2%) and 53 foetal deaths (1.8%). The total prevalence of CHD was 90 per 10 000. After exclusion of ventricular septal defects (VSD), 40% of ‘isolated’ CHD was diagnosed prenatally with about one half of the remaining diagnosed before 7 days of age. Nevertheless, one in five cases of these major CHD was diagnosed after the fourth week. Infant mortality of ‘isolated’ CHD-VSD excluded was 8.5% with 40% of deaths occurring after the fourth week of life. These outcomes varied substantially across categories of ACC-CHD. Conclusions Timing of diagnosis, TOPFA, risk and timing of infant mortality were highly variable across the categories of CHD in ACC-CHD, suggesting that it may be a useful measure of severity, and hence, predictor of outcomes of CHD.

Prediction models for the risk of cardiovascular disease in patients with type 2 diabetes: a systematic review

Abstract: Context A recent overview of all CVD models applicable to diabetes patients is not available. Objective To review the primary prevention studies that focused on the development, validation and impact assessment of a cardiovascular risk model, scores or rules that can be applied to patients with type 2 diabetes. Design Systematic review. Data sources Medline was searched from 1966 to 1 April 2011. Study selection A study was eligible when it described the development, validation or impact assessment of a model that was constructed to predict the occurrence of cardiovascular disease in people with type 2 diabetes, or when the model was designed for use in the general population but included diabetes as a predictor. Data extraction A standardized form was sued to extract all data of the CVD models. Results 45 prediction models were identified, of which 12 were specifically developed for patients with type 2 diabetes. Only 31% of the risk scores has been externally validated in a diabetes population, with an area under the curve ranging from 0.61 to 0.86 and 0.59 to 0.80 for models developed in a diabetes population and in the general population, respectively. Only one risk score has been studied for its effect on patient management and outcomes. 10% of the risk scores are advocated in national diabetes guidelines. Conclusion Many cardiovascular risk scores are available that can be applied to patients with type 2 diabetes. A minority of these risk scores has been validated and tested for its predictive accuracy, with only a few showing a discriminative value of ≥0.80. The impact of applying these risk scores in clinical practice is almost completely unknown, but their use is recommended in various national guidelines.

French Registry on Acute ST-elevation and non ST-elevation Myocardial Infarction 2010. FAST-MI 2010

Abstract: Aim of FAST-MI 2010 To gather data on characteristics, management and outcomes of patients hospitalised for acute myocardial infarction (AMI) at the end of 2010 in France. Interventions To provide cardiologists and health authorities national and regional data on AMI management every 5 years. Setting Metropolitan France. 213 academic (n=38), community (n=110), army hospitals (n=2), private clinics (n=63), representing 76% of centres treating AMI patients. Inclusion from 1 October 2010. Population Consecutive patients included during 1 month, with a possible extension of recruitment up to one additional month (132 centres); 4169 patients included over the entire recruitment period, 3079 during the first 31 days; 249 additional patients declining participation (5.6%). Startpoints Consecutive adults with ST-elevation and non-ST-elevation AMI with symptom onset ≤48 h. Patients with AMI following cardiovascular procedures excluded. Data capture Web-based collection of 385 items (demographic, medical, biologic, management data) recorded online from source files by external research technicians; case-record forms with automatic quality checks. Centralised biology in voluntary centres to collect DNA samples and serum. Long-term follow-up organised centrally with interrogation of municipal registry offices, patients9 physicians, and direct contact with the patients. Data quality Data management in Toulouse University. Statistical analyses: Universite Paris Descartes, Universite de Toulouse, Universite Pierre et Marie Curie-Paris 06, Paris. Endpoints and linkages to other data In-hospital events; cardiovascular events, hospital admissions and mortality during follow-up. Linkage with Institute for National Statistics. Access to data Available for research to any participating clinician upon request to executive committee (fastmi2010@yahoo.fr).

Type 2 diabetes, glucose homeostasis and incident atrial fibrillation: the Atherosclerosis Risk in Communities study

Abstract: Background Type 2 diabetes has been inconsistently associated with the risk of atrial fibrillation (AF) in previous studies that have frequently been beset by methodological challenges. Design Prospective cohort study. Setting The Atherosclerosis Risk in Communities (ARIC) study. Participants Detailed medical histories were obtained from 13 025 participants. Individuals were categorised as having no diabetes, pre-diabetes or diabetes based on the 2010 American Diabetes Association criteria at study baseline (1990–2). Main outcome measures Diagnoses of incident AF were obtained to the end of 2007. Associations between type 2 diabetes and markers of glucose homeostasis and the incidence of AF were estimated using Cox proportional hazards models after adjusting for possible confounders. Results Type 2 diabetes was associated with a significant increase in the risk of AF (HR 1.35, 95% CI 1.14 to 1.60) after adjustment for confounders. There was no indication that individuals with pre-diabetes or those with undiagnosed diabetes were at increased risk of AF compared with those without diabetes. A positive linear association was observed between HbA1c and the risk of AF in those with and without diabetes (HR 1.13, 95% CI 1.07 to 1.20) and HR 1.05, 95% CI 0.96 to 1.15 per 1% point increase, respectively). There was no association between fasting glucose or insulin in those without diabetes, but a significant association with fasting glucose was found in those with the condition. The results were similar in white subjects and African-Americans. Conclusions Diabetes, HbA1c level and poor glycaemic control are independently associated with an increased risk of AF, but the underlying mechanisms governing the relationship are unknown and warrant further investigation.

Left atrial minimum volume and reservoir function as correlates of left ventricular diastolic function: impact of left ventricular systolic function

Abstract: Objective Left atrial (LA) maximum volume (LAV max ) is an indicator of left ventricular (LV) diastolic function. However, LAV max is also influenced by systolic events, whereas the LA minimum volume (LAV min ) is directly exposed to LV pressure. The authors hypothesised that LAV min may be a better correlate of LV diastolic function than LAV max . Design Cross-sectional. Setting University hospital. Patients 357 participants from a community-based cohort study. Methods LA volumes and reservoir function, measured as total LA emptying volume (LAEV) and LA emptying fraction (LAEF), were assessed by real-time three-dimensional echocardiography. LV diastolic function was assessed by trans-mitral early (E) and late (A) Doppler velocities and mitral early diastolic velocity by tissue-Doppler (e9). LV systolic function was assessed by LV ejection fraction (LVEF) and global longitudinal strain (GLS) by speckle-tracking. Results LAV min significantly increased with worsening diastolic dysfunction (p max was less pronounced (p=0.07). LAEV and LAEF decreased with worsening diastolic dysfunction (both p min and LAV max were significant predictors of E/e9, with higher parameter estimates for LAV min . In multivariate models, LAV min resulted strongly associated with E/e9 (β=0.45, p max was not (β=−0.16, p=0.08). LA reservoir function was better associated with GLS than LVEF. In multivariate analyses, GLS was significantly associated with LAV max (β=−0.15, p=0.002), LAEV (β=−0.37, p min . Conclusions LAV min is a better correlate of LV diastolic function than LAV max . The impact of LV longitudinal systolic function on LA reservoir function might explain the weaker relation between LAV max and LV diastolic function.

Diffusion-weighted MRI determined cerebral embolic infarction following transcatheter aortic valve implantation: assessment of predictive risk factors and the relationship to subsequent health status

Abstract: Background ‘Silent’ cerebral infarction and stroke are complications of transcatheter aortic valve implantation (TAVI). Objective To assess the occurrence of cerebral infarction, identify predictive risk factors and examine the impact on patient health-related quality of life (HRQoL). Methods Cerebral diffusion weighted MRI of 31 patients with aortic stenosis undergoing CoreValve TAVI was carried out. HRQoL was assessed at baseline and at 30 days by SF-12v2 and EQ5D questionnaires. Results New cerebral infarcts occurred in 24/31 patients (77%) and stroke in 2 (6%). Stroke was associated with a greater number and volume of cerebral infarcts. Age (r=0.37, p=0.042), severity of atheroma (arch and descending aorta; r=0.91, p Conclusion Multiple small cerebral infarcts occurred in 77% of patients with TAVI. The majority of infarcts were ‘silent’ with clinical stroke being associated with a both higher infarct number and volume. Increased age and the severity of aortic arch atheroma were independent risk factors for the development of new cerebral infarcts. Overall HRQoL improved and there was no association between the number of new cerebral infarcts and altered health status.

Maintenance of sinus rhythm with an ablation strategy in patients with atrial fibrillation is associated with a lower risk of stroke and death

Abstract: Objective To investigate whether catheter ablation of atrial fibrillation (AF) reduces stroke rate or mortality. Methods An international multicentre registry was compiled from seven centres in the UK and Australia for consecutive patients undergoing catheter ablation of AF. Long-term outcomes were compared with (1) a cohort with AF treated medically in the Euro Heart Survey, and (2) a hypothetical cohort without AF, age and gender matched to the general population. Analysis of stroke and death was carried out after the first procedure (including peri-procedural events) regardless of success, on an intention-to-treat basis. Results 1273 patients, aged 58±11 years, 56% paroxysmal AF, CHADS 2 score 0.7±0.9, underwent 1.8±0.9 procedures. Major complications occurred in 5.4% of procedures, including stroke/TIA in 0.7%. Freedom from AF following the last procedure was 85% (76% off antiarrhythmic drugs) for paroxysmal AF, and 72% (60% off antiarrhythmic drugs) for persistent AF. During 3.1 (1.0–9.6) years from the first procedure, freedom from AF predicted stroke-free survival on multivariate analysis (HR=0.30, CI 0.16 to 0.55, p Conclusion Restoration of sinus rhythm by catheter ablation of AF is associated with lower rates of stroke and death compared with patients treated medically.

Meta-analyses of the association between cytochrome CYP2C19 loss- and gain-of-function polymorphisms and cardiovascular outcomes in patients with coronary artery disease treated with clopidogrel

Abstract: Aims To perform a meta-analysis of the association between CYP2C19 loss- and gain-of-function variants and cardiovascular outcomes and bleeding in patients with coronary artery disease treated with clopidogrel, and to explore the causes of heterogeneity between studies. Methods A comprehensive literature search was conducted. A random-effects model was used to summarise the results. In the presence of between-study heterogeneity, a meta-regression analysis was performed to identify study characteristics explaining this heterogeneity. Results Patients who carried a loss-of-function allele, mainly CYP2C19*2, did not present an increased risk of a cardiovascular event, HR ¼1.23 (95% CI 0.97 to 1.55). Substantial heterogeneity was observed between studies (I 2 ¼35.6), which was partially explained by the study sample size: the pooled HR was higher among studies with a sample size <500 patients (HR ¼3.55; 95% CI 1.66 to 7.56) and lower among studies with a sample size $500 (HR ¼1.06; 95% CI 0.89 to 1.26). CYP2C19*2 was associated with an increased risk of a stent thrombosis (HR ¼2.24; 95% CI 1.52 to 3.30). The gain-of-function allele, mainly CYP2C19*17, was associated with a lower risk of cardiovascular events (HR ¼0.75; 95% CI 0.66 to 0.87) and a higher risk of major bleeding (HR ¼1.26; 95% CI 1.05 to 1.50). Conclusions Not only CYP2C19 loss-of-function but also gain-of-function alleles should be considered to define the pharmacogenetic response to clopidogrel. The results question the relevance of the CYP2C19 loss-of-function alleles in the prediction of major cardiovascular events beyond stent thrombosis in coronary patients treated with clopidogrel. The gain-of-function variant is associated with a lower risk of cardiovascular events but a higher risk of bleeding.

The long-term survival and the risks and benefits of implantable cardioverter defibrillators in patients with hypertrophic cardiomyopathy

Abstract: Objective Implantable cardioverter defibrillators (ICDs) are routinely used to prevent sudden cardiac death (SCD) in selected hypertrophic cardiomyopathy (HCM) patients, but the determinants of device-related complications, therapies and long-term cardiovascular mortality in ICD recipients are not known. Design Retrospective observational cohort study. Setting Single-centre tertiary referral cardiomyopathy clinic. Patients 334 consecutively evaluated HCM patients (median age 40 years, 62% male, 92% primary prevention) at risk of SCD treated with ICD. Thirty-six patients (11%) received concurrent cardiac resynchronisation therapy for heart failure symptoms. Results During the 1286 patient-years of follow-up, cardiovascular mortality (including transplantation) occurred in 22 (7%) patients (1.7%/year) and was associated with New York Heart Association (NYHA) class III/IV (adjusted HR=9.38, 95% CI 3.31 to 26.55, p≤0.001), percentage fractional shortening (HR=0.92, 95% CI 0.87 to 0.96, p=0.001) and implantation for secondary prevention (HR=0.07, 95% CI 0.01 to 0.86, p=0.04). There were no SCD. Twenty-eight (8%) patients received appropriate shocks (2.3%/year), which were predicted by baseline fractional shortening (HR=0.96, 95% CI 0.92 to 0.99, p=0.04). Fifty-five (16%) patients received inappropriate shocks (4.6%/year). Sixty (18%) patients experienced implant-related complications (5.1%/year), including two deaths. Adverse ICD-related events (inappropriate shocks and/or implant complications) were seen in 101 (30%) patients (8.6%/year). Patients with cardiac resynchronisation therapy were more likely to develop implant complications than those with single-chamber ICDs (HR=4.39, 95% CI 1.44 to 13.35, p=0.009) and had a higher 5-year cardiovascular mortality than did the rest of the cohort (21% vs 6%, p Conclusions HCM patients with an ICD have a significant cardiovascular mortality and are exposed to frequent inappropriate shocks and implant complications. These data suggest that new strategies are required to improve patient selection for ICDs and to prevent disease progression in those that receive a device.

An epidemiological appraisal of the association between heart rate variability and particulate air pollution: a meta-analysis

Abstract: Objective Studies on the association between short-term exposure to ambient air pollution and heart rate variability (HRV) suggest that particulate matter (PM) exposure is associated with reductions in measures of HRV, but there is heterogeneity in the nature and magnitude of this association between studies. The authors performed a meta-analysis to determine how consistent this association is. Data source The authors searched the Pubmed citation database and Web of Knowledge to identify studies on HRV and PM. Study selection Of the epidemiologic studies reviewed, 29 provided sufficient details to be considered. The meta-analysis included 18667 subjects recruited from the population in surveys, studies from patient groups, and from occupationally exposed groups. Data extraction Two investigators read all papers and computerised all relevant information. Results The authors computed pooled estimates from a random-effects model. In the combined studies, an increase of 10 μg/m 3 in PM 2.5 was associated with significant reductions in the time-domain measurements, including low frequency (−1.66%, 95% CI −2.58% to −0.74%) and high frequency (−2.44%, 95% CI −3.76% to −1.12%) and in frequency-domain measurements, for SDNN (−0.12%, 95% CI −0.22% to −0.03%) and for rMSSD (−2.18%, 95% CI −3.33% to −1.03%). Funnel plots suggested that no publication bias was present and a sensitivity analysis confirmed the robustness of our combined estimates. Conclusion The meta-analysis supports an inverse relationship between HRV, a marker for a worse cardiovascular prognosis, and particulate air pollution.

Influence of access site selection on PCI-related adverse events in patients with STEMI: meta-analysis of randomised controlled trials

Abstract: Objective A meta-analysis of all randomised controlled studies that compare outcomes of transradial versus the transfemoral route to better define best practice in patients with ST elevation myocardial infarction (STEMI). Design A Medline and Embase search was conducted using the search terms ‘transradial,’ ‘radial’, ‘STEMI’, ‘myocardial’ and ‘infarction’. Setting Randomised controlled studies that compare outcomes of transradial versus the transfemoral route. Patients A total of nine studies were identified that consisted of 2977 patients with STEMI. Interventions Studies that compare outcomes of transradial versus the transfemoral route. Main outcome measures The primary clinical outcomes of interest were (1) mortality; (2) major adverse cardiac events (MACE); (3) major bleeding and (4) access site complications. Results Transradial PCI was associated with a reduction in mortality (OR 0.53, 95% CI 0.33 to 0.84; p=0.008), MACE (OR 0.62, 95% CI 0.43 to 0.90; p=0.012), major bleeding events (OR 0.63, 95% CI 0.35-1.12; p=0.12) and access site complications (OR 0.30, 95% CI 0.19 to 0.48; p Conclusions This meta-analysis demonstrates a significant reduction in mortality, MACE and major access site complications associated with the transradial access site in STEMI. The meta-analysis supports the preferential use of radial access for STEMI PCI.

Cardiac disease and cognitive impairment: a systematic review

Abstract: Cognitive impairment in cardiac patients may interfere with disease management. This review describes studies examining specific cognitive impairments in cardiac patients and studies that investigate the link between echocardiographic and cognitive measures. Executive function impairments were frequently reported in different patient groups. Also, lower cardiac output and worse left ventricular diastolic function are linked to executive function deficits. In cardiac patients, special attention should be paid to these executive function impairments in view of their role in disease management and independent living. Interventions that stimulate executive function should be encouraged and integrated in cardiac treatment protocols.

Calcification of the abdominal aorta as an independent predictor of cardiovascular events: a meta-analysis

Abstract: Context Abdominal aortic calcification (AAC) is a common finding in patients with atherosclerosis. Objective The aim of this study was to demonstrate the incremental value of AAC in predicting long term cardiovascular (CV) outcome by conducting a meta-analysis of observational studies. Data sources MEDLINE and Cochrane databases. Study selection Longitudinal studies with at least 2 years of follow-up, reporting the influence of AAC on CV outcome of general population patients. Data extraction Four separate end points—coronary events, cerebrovascular events, all CV events and CV related death—were tested for their relationship with AAC at baseline, using weighted random effects meta-analysis. Heterogeneity was calculated using Q and I 2 statistic tests. Publication bias was assessed by funnel plot symmetry and trim and fill methods. The importance of calcium quantification was also explored (sensitivity analysis). Results 10 studies were included. An increased relative risk (RR) was found for all end points: for coronary events (five studies, n=11250) 1.81 (95% CI 1.54 to 2.14); for cerebrovascular events (four studies, n=9736) 1.37 (1.22 to 3.54); for all CV events (four studies, n=4960) 1.64 (1.24 to 2.17); and for CV death (three studies, n=4986) 1.72 (1.03 to 2.86). Analysis of studies presenting results in categories (no/minimal, moderate and severe calcification) revealed a stepwise increase in the RR for all end points. Significant heterogeneity was found in the included studies. Sources of heterogeneity were identified in the publication date, duration of follow-up, and mean age and gender differences in the included patient cohorts. Conclusion Existing data suggest that AAC is a strong predictor of CV related events or death in the general population. The predictive impact is greater in more calcified aortas. The generalisability of the meta-analysis is limited by heterogeneity in the coronary events, all CV events and CV death end points.

The athlete's heart

Abstract: Athlete's heart is the term given to the complex of structural, functional, and electrical remodelling that accompanies regular athletic training. It is an important physiological adaption which helps athletes perform better in physical tasks than non-athletes and one of the physiological changes that may make a good athlete great. The fact that the heart of an athlete is different to the non-athlete's was recognised in the late 19th century based on clinical examination, with the recognition of cardiac enlargement and bradycardia among more highly trained athletes. Our understanding of this syndrome has gradually expanded in parallel with the development of new invasive and non-invasive tools for the examination of cardiac structure and function. Initially, the chest x-ray and ECG demonstrated important features of cardiac chamber enlargement in athletes. The next steps incorporated invasive haemodynamic measures at rest and with exercise. An additional source of understanding of the athlete's heart has been examination of cardiac pathology specimens. More recently the use of imaging techniques such as echocardiography and cardiac MRI have played a central role in advancing our understanding of what constitutes an athlete's heart and in applying this information in clinical settings. Study of the athlete's heart has been undertaken and is important for a number of key reasons: first, to understand how cardiac adaptation contributes to improved athletic performance; second, to guide development of training regimens which will optimise cardiac adaptation and thus enhance athletic performance; and third, to allow differentiation of the normal athlete's heart from important disease states which may share similar morphologic features. It is the third of these reasons that has assumed most importance in the cardiology and sports medicine worlds. The aim of this article is for clinicians to learn about the key features of the athlete's heart and to understand concepts used to …

Management of the failing Fontan circulation

Abstract: The ‘Fontan circulation' has evolved to include a variety of surgical procedures designed to overcome the absence of two distinct ventricular chambers.1 w1–w3 Inherent to this circulation is chronic elevation of right atrial and vena caval pressure, and absence of a dedicated power source to serve the pulmonary circulation, making low pulmonary vascular resistance and optimal systemic ventricular function the essential ingredients of a successful Fontan circulation.2 Originally designed for the single left ventricle, modifications to the original atriopulmonary connections extended repairs to complex ventricular anatomy, and are now most commonly performed for single right ventricular anatomy associated with hypoplastic left heart syndrome. Together with improved perioperative management, creation of the Fontan circulation in two stages (superior cavopulmonary anastomosis followed by later Fontan completionw4), and performance of Fontan procedures at a younger age, have led to reduced operative mortality associated with the Fontan procedure of ≤5% (compared with 15–30% in earlier decades); survival at 20 years is presently 85%.3 w5 Over the last two decades, the initial survivors of the atriopulmonary Fontan repairs have reached adulthood, bringing a multiplicity of haemodynamic complications and sequelae of their abnormal circulatory status. The atriopulmonary connection is now obsolete as a surgical option, and the current surviving adults with this circulation do not reflect contemporary Fontan outcomes. Nonetheless, their attendant compendium …

Cost-effectiveness of dabigatran etexilate for the prevention of stroke and systemic embolism in UK patients with atrial fibrillation

Abstract: Objective To assess the cost-effectiveness of dabigatran etexilate, a new oral anticoagulant, versus warfarin and other alternatives for the prevention of stroke and systemic embolism in UK patients with atrial fibrillation (AF). Methods A Markov model estimated the cost-effectiveness of dabigatran etexilate versus warfarin, aspirin or no therapy. Two patient cohorts with AF (starting age of Results Patients treated with dabigatran etexilate experienced fewer ischaemic strokes (3.74 dabigatran etexilate vs 3.97 warfarin) and fewer combined intracranial haemorrhages and haemorrhagic strokes (0.43 dabigatran etexilate vs 0.99 warfarin) per 100 patient-years. Larger differences were observed comparing dabigatran etexilate with aspirin or no therapy. For patients initiating treatment at ages Conclusions This economic evaluation suggests that the use of dabigatran etexilate as a first-line treatment for the prevention of stroke and systemic embolism is likely to be cost-effective in eligible UK patients with AF.

Low-grade inflammation and the phenotypic expression of myocardial fibrosis in hypertrophic cardiomyopathy

Abstract: Objective To investigate the role of inflammation in the phenotypic expression of myocardial fibrosis in hypertrophic cardiomyopathy (HCM). Design Clinical study. Setting Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland. Subjects Twenty-four patients with a single HCM-causing mutation D175N in the α-tropomyosin gene and 17 control subjects. Main outcome measures Endomyocardial biopsy samples taken from the patients with HCM were compared with matched myocardial autopsy specimens. Levels of high-sensitivity C-reactive protein (hsCRP) and proinflammatory cytokines were measured in patients and controls. Myocardial late gadolinium enhancement (LGE) in cardiac MRI (CMRI) was detected. Results Endomyocardial samples in patients with HCM showed variable myocyte hypertrophy and size heterogeneity, myofibre disarray, fibrosis, inflammatory cell infiltration and nuclear factor kappa B (NF-κB) activation. Levels of hsCRP and interleukins (IL-1β, IL-1RA, IL-6, IL-10) were significantly higher in patients with HCM than in control subjects. In patients with HCM, there was a significant association between the degree of myocardial inflammatory cell infiltration, fibrosis in histopathological samples and myocardial LGE in CMRI. Levels of hsCRP were significantly associated with histopathological myocardial fibrosis. hsCRP, tumour necrosis factor α and IL-1RA levels had significant correlations with LGE in CMRI. Conclusions A variable myocardial and systemic inflammatory response was demonstrated in patients with HCM attributable to an identified sarcometric mutation. Inflammatory response was associated with myocardial fibrosis, suggesting that myocardial fibrosis in HCM is an active process modified by an inflammatory response.

Maternal cardiovascular events during childbirth among women with congenital heart disease

Abstract: Objectives To define the epidemiology of adverse cardiovascular events among women with congenital heart disease (CHD) hospitalised for childbirth in the USA. Design and setting The 1998–2007 Nationwide Inpatient Sample, an administrative dataset representative of overall US hospital admissions, was used to identify hospitalisations for delivery. Main outcome measures Logistic regression was used to estimate ORs for cardiovascular outcomes (arrhythmia, heart failure, cerebrovascular accident, embolism, death or a combined outcome) for women with and without CHD. Covariates included age, number of medical comorbidites, pulmonary hypertension, hospital teaching status, insurance status and method of delivery. Results Annual deliveries for women with CHD increased 34.9% from 1998 to 2007 compared with an increase of 21.3% in the general population. Women with CHD were more likely to sustain a cardiovascular event (4042/100 000 vs 278/100 000 deliveries, univariate OR 15.1, 95% CI 13.1 to 17.4, multivariable OR 8.4, 95% CI 7.0 to 10.0). Arrhythmia, the most common cardiovascular event, was more frequent among women with CHD (2637/100 000 vs 210/100 000, univariate OR 12.9, 95% CI 10.9 to 15.3, multivariable OR 8.3, 95% CI 6.7 to 10.1). Death occurred in 150/100 000 patients with CHD compared with 8.2/100 000 patients without CHD (multivariable OR 6.7, 95% CI 2.9 to 15.4). Complex CHD was associated with greater odds of having an adverse cardiovascular event than simple CHD (8158/100 000 vs 3166/100 000, multivariable OR 2.0, 95% CI 1.4 to 3.0). Conclusions Maternal CHD is associated with a markedly increased risk of adverse cardiovascular events and death during admission for delivery.