Valor pronóstico del incremento de la tensión arterial sistólica con el ejercicio en pacientes hipertensos con enfermedad coronaria conocida o sospechada.

La asociación entre un incremento exagerado de la presión arterial sistólica con el ejercicio (IEPASE) y la probabilidad de eventos cardiovasculares es controvertida. Nuestro propósito fue determinar la posible asociación de un IEPASE con la supervivencia y con el riesgo de eventos cardíacos graves en pacientes hipertensos con enfermedad coronaria conocida o sospechada. Se trata de un estudio retrospectivo y observacional sobre una muestra de 5.226 pacientes con historia de hipertensión arterial y enfermedad coronaria conocida o sospechada referidos a ecocardiografía de ejercicio. El IEPASE se definió como un incremento de la presión arterial sistólica con el ejercicio igual o superior al percentil 95 de esta población (80 mmHg). Los objetivos fueron mortalidad total, mortalidad de origen cardíaco e infarto de miocardio (IM). En un seguimiento medio de 4,7 años, se registraron 978 muertes (371 de origen cardíaco) y 798 IM. Las tasas anuales de mortalidad, mortalidad de origen cardíaco e IM fueron del 2,73; 0,83 y 2,63% en pacientes con IEPASE y de 4,4; 1,58 y 3,98%, respectivamente en aquellos sin IEPASE (p < 0,001; p = 0,012 y p = 0,014, respectivamente). Tras un ajuste multivariado, el IEPASE resultó predictor de mortalidad por cualquier causa (HR: 0,70; IC 95%: 0,52-0,95; p = 0,023) e IM (HR: 0,69; IC 95%: 0,50-0,95; p = 0,022), pero la asociación con mortalidad cardiaca no alcanzó significación estadística (HR: 0,72; IC 95%: 0,43-1,20; p = 0,2). El IEPASE se asoció con mayor probabilidad de supervivencia y menor riesgo de IM en pacientes hipertensos con enfermedad coronaria conocida o sospechada.

Longer-term assessment of trastuzumab-related cardiac adverse events in the Herceptin Adjuvant (HERA) trial

We investigated the incidence of cardiac adverse events in patients with early breast cancer in the Herceptin Adjuvant (HERA) trial who were treated with 1 year of trastuzumab after completion of (neo)adjuvant chemotherapy.

CMR imaging predicts death and other adverse events in suspected cardiac sarcoidosis

OBJECTIVES This study aimed to demonstrate that the presence of late gadolinium enhancement (LGE) is a predictor of death and other adverse events in patients with suspected cardiac sarcoidosis. BACKGROUND Cardiac sarcoidosis is the most important cause of patient mortality in systemic sarcoidosis, yielding a 5-year mortality rate between 25% and 66% despite immunosuppressive treatment. Other groups have shown that LGE may hold promise in predicting future adverse events in this patient group. METHODS We included 155 consecutive patients with systemic sarcoidosis who underwent cardiac magnetic resonance (CMR) for workup of suspected cardiac sarcoid involvement. The median follow-up time was 2.6 years. Primary endpoints were death, aborted sudden cardiac death, and appropriate implantable cardioverter-defibrillator (ICD) discharge. Secondary endpoints were ventricular tachycardia (VT) and nonsustained VT. RESULTS LGE was present in 39 patients (25.5%). The presence of LGE yields a Cox hazard ratio (HR) of 31.6 for death, aborted sudden cardiac death, or appropriate ICD discharge, and of 33.9 for any event. This is superior to functional or clinical parameters such as left ventricular (LV) ejection fraction (EF), LV end-diastolic volume, or presentation as heart failure, yielding HRs between 0.99 (per % increase LVEF) and 1.004 (presentation as heart failure), and between 0.94 and 1.2 for potentially lethal or other adverse events, respectively. Except for 1 patient dying from pulmonary infection, no patient without LGE died or experienced any event during follow-up, even if the LV was enlarged and the LVEF severely impaired. CONCLUSIONS Among our population of sarcoid patients with nonspecific symptoms, the presence of myocardial scar indicated by LGE was the best independent predictor of potentially lethal events, as well as other adverse events, yielding a Cox HR of 31.6 and of 33.9, respectively. These data support the necessity for future large, longitudinal follow-up studies to definitely establish LGE as an independent predictor of cardiac death in sarcoidosis, as well as to evaluate the incremental prognostic value of additional parameters.

Cardiac ARIA Index: Measuring Accessibility to Cardiovascular Services in Rural and Remote Australia via Applied Geographic Spatial Technology

Cardiovascular disease (CVD) continues to impose a heavy burden in terms of cost, disability and death in Australia. Evidence suggests that increasing remoteness, where cardiac services are scarce, is linked to an increased risk of dying from CVD. Fatal CVD events are reported to be between 20% and 50% higher in rural areas compared to major cities. The Cardiac ARIA project, with its extensive use of geographic Information Systems (GIS), ranks each of Australia’s 20,387 urban, rural and remote population centres by accessibility to essential services or resources for the management of a cardiac event. This unique, innovative and highly collaborative project delivers a powerful tool to highlight and combat the burden imposed by cardiovascular disease (CVD) in Australia. Cardiac ARIA is innovative. It is a model that could be applied internationally and to other acute and chronic conditions such as mental health, midwifery, cancer, respiratory, diabetes and burns services. Cardiac ARIA was designed to: 1. Determine by expert panel, what were the minimal services and resources required for the management of a cardiac event in any urban, rural or remote population locations in Australia using a single patient pathway to access care. 2. Derive a classification using GIS accessibility modelling for each of Australia’s 20,387 urban, rural and remote population locations. 3. Compare the Cardiac ARIA categories and population locations with census derived population characteristics. Key findings are as follows: • In the event of a cardiac emergency, the majority of Australians had very good access to cardiac services. Approximately 71% or 13.9 million people lived within one hour of a category one hospital. • 68% of older Australians lived within one hour of a category one hospital (Principal Referral Hospital with access to Cardiac Catheterisation). • Only 40% of indigenous people lived within one hour of the category one hospital. • 16% (74000) of indigenous people lived more than one hour from a hospital. • 3% (91,000) of people 65 years of age or older lived more than one hour from any hospital or clinic. • Approximately 96%, or 19 million, of people lived within one hour of the four key services to support cardiac rehabilitation and secondary prevention. • 75% of indigenous people lived within one hour of the four cardiac rehabilitation services to support cardiac rehabilitation and secondary prevention. Fourteen percent (64,000 persons) indigenous people had poor access to the four key services to support cardiac rehabilitation and secondary prevention. • 12% (56,000) of indigenous people were more than one hour from a hospital and only had access one the four key services (usually a medical service) to support cardiac rehabilitation and secondary prevention.

CARDIAC-ARIA: Measuring the Accessibility to Cardiovascular Services in Rural and Remote Australia Via Applied Geographical Spatial Technology (GIS)

Background/aims: Cardiovascular disease (CVD) continues to impose a heavy burden in terms of cost, disability and death in Australia. Recent evidence suggests that increasing remoteness, where cardiac services are scarce, is linked to an increased risk of dying from CVD. Fatal CVD events are reported to be between 20% and 50% higher in rural areas compared to major cities. Method: This project, with its extensive use of Geographic Information Systems (GIS) technology, will rank 11,338 rural and remote population centres to identify geographical ‘hotspots’ where there is likely to be a mismatch between the demand for and actual provision of cardiovascular services. It will, therefore, guide more equitable provision of services to rural and remote communities. Outcomes: The CARDIAC-ARIA project is designed to; map the type and location of cardiovascular services currently available in Australia, relative to the distribution of individuals who currently have symptomatic CVD; determine, by expert panel, what are the minimal requirements for comprehensive cardiovascular health support in metropolitan and rural communities and derive a rating classification based on the Accessibility and Remoteness Index of Australia (ARIA) for each of Australia's 11,338 rural and remote population centres. Conclusion: This unique, innovative and highly collaborative project has the potential to deliver a powerful tool to highlight and combat the burden imposed by cardiovascular disease (CVD) in Australia.

Rates of attendance at a smoking cessation clinic within a cardiac rehabilitation service

Objectives: Smoking cessation has been shown to be an important intervention for preventing cardiovascular events and improving the health of patients with heart disease. However, unaided quit attempts in these patients often leads to high rates of failure and a return to smoking. Outpatient smoking cessation clinics using face-to-face counseling, ongoing behavioral support, advice on smoking pharmacotherapy and objective monitoring, have been found to be one of the most effective interventions for improving quit smoking rates. An outpatient smoking cessation clinic was trialed within a cardiac rehabilitation service in order to explore its effects on smoking rates for patients with or at risk of heart disease. Attendance rates to the clinic were also monitored. Methods: A descriptive exploratory design was used for this newly developed clinic. Patients who currently smoked tobacco and who had a history of either coronary artery disease, heart failure, atrial fibrillation or those seen under a chest pain assessment service were invited to an outpatient ‘Cardiac Patients Smokers Clinic’. Initially patients were offered up to 10 clinic visits over a 3 month period. Follow-up clinic visits were conducted at 3, 6 and 12 months. A portable carbon monoxide meter was used to objectively measure levels of smoking and validate smoking abstinence. Primary outcomes included rates of attendance. Results: Preliminary findings showed 24 per cent of participants (N = 6) completed all their clinic visits and remained smoke free as measured by their ongoing expired carbon monoxide readings. Clinic attendance rates appeared lowest for those with significant mental health issues such as schizophrenia or substance abuse. However, rates of attendance were improved by having an administration officer make reminder telephone calls prior to clinic visits. Conclusions: Early findings indicate the feasibility of providing a specialist smoking cessation clinic within a cardiac rehabilitation service. Further, that reminder telephone calls prior to appointments improved attendance rates in patients with heart disease to this type of clinic. However, future investigations are warranted.

Protocol for a randomised blocked design study using telephone and text-messaging to support cardiac patients with diabetes : a cross cultural international collaborative project

Background The prevalence of type 2 diabetes is rising internationally. Patients with diabetes have a higher risk of cardiovascular events accounting for substantial premature morbidity and mortality, and health care expenditure. Given healthcare workforce limitations, there is a need to improve interventions that promote positive self-management behaviours that enable patients to manage their chronic conditions effectively, across different cultural contexts. Previous studies have evaluated the feasibility of including telephone and Short Message Service (SMS) follow up in chronic disease self-management programs, but only for single diseases or in one specific population. Therefore, the aim of this study is to evaluate the feasibility and short-term efficacy of incorporating telephone and text messaging to support the care of patients with diabetes and cardiac disease, in Australia and in Taiwan. Methods/design A randomised controlled trial design will be used to evaluate a self-management program for people with diabetes and cardiac disease that incorporates the use of simple remote-access communication technologies. A sample size of 180 participants from Australia and Taiwan will be recruited and randomised in a one-to-one ratio to receive either the intervention in addition to usual care (intervention) or usual care alone (control). The intervention will consist of in-hospital education as well as follow up utilising personal telephone calls and SMS reminders. Primary short term outcomes of interest include self-care behaviours and self-efficacy assessed at baseline and four weeks. Discussion If the results of this investigation substantiate the feasibility and efficacy of the telephone and SMS intervention for promoting self management among patients with diabetes and cardiac disease in Australia and Taiwan, it will support the external validity of the intervention. It is anticipated that empirical data from this investigation will provide valuable information to inform future international collaborations, while providing a platform for further enhancements of the program, which has potential to benefit patients internationally.

Comparative genomic analysis of human Chlamydia pneumoniae isolates from respiratory, brain and cardiac tissues

Chlamydia pneumoniae is an obligate intracellular bacterium implicated in a wide range of human diseases including atherosclerosis and Alzheimer's disease. Efforts to understand the relationships between C. pneumoniae detected in these diseases have been hindered by the availability of sequence data for non-respiratory strains. In this study, we sequenced the whole genomes for C. pneumoniae isolates from atherosclerosis and Alzheimer's disease, and compared these to previously published C. pneumoniae genomes. Phylogenetic analyses of these new C. pneumoniae strains indicate two sub-groups within human C. pneumoniae, and suggest that both recombination and mutation events have driven the evolution of human C. pneumoniae. Further fine-detailed analyses of these new C. pneumoniae sequences show several genetically variable loci. This suggests that similar strains of C. pneumoniae are found in the brain, lungs and cardiovascular system and that only minor genetic differences may contribute to the adaptation of particular strains in human disease.

PW376 A pilot study of a post-discharge nurse-led, educational intervention on cardiac self-efficacy and anxiety in post-PCI patients

Introduction Hospitalisation for percutaneous coronary intervention (PCI) is often short, with limited nurse-teaching time and poor information absorption. Currently, patients are discharged home only to wait up to 4-8 weeks to commence a secondary prevention program and visit their cardiologist. This wait is an anxious time for patients and confidence or self-efficacy (SE) to self-manage may be low. Objectives To determine the effects of a nurse-led, educational intervention on participant SE and anxiety in the early post-discharge period. Methods A pilot study was undertaken as a randomised controlled clinical trial. Thirty-three participants were recruited, with n=13 randomised to the intervention group. A face-to-face, nurse-led, educational intervention was undertaken within the first 5-7 days post-discharge. Intervention group participants received standard post-discharge education, physical assessment, with a strong focus on the emotional impact of cardiovascular events and PCI. Early reiteration of post-discharge education was offered, along with health professional support with the aim to increase patients’ SE and to effectively manage their post-discharge health and well being, as well as anxieties. Self-efficacy to return to normal activities was measured to gauge participants’ abilities to manage post-PCI after attending the intervention using the cardiac self-efficacy (CSE) scale. State and trait anxiety was also measured using the State-Trait Anxiety Inventory (STAI) to determine if an increase in SE would influence participant anxiety. Results There were some increases in mean CSE scores in the intervention group participants over time. Areas of increase included return to normal social activities and confidence to change diet. Although reductions were observed in mean state and trait anxiety scores in both groups, an overall larger reduction in intervention group participants was observed over time. Conclusion It is essential that patients are given the education, support, and skills to self-manage in the early post-discharge period so that they have greater SE and are less anxious. This study provides some initial evidence that nurse-led support and education during this period, particularly the first week following PCI, is beneficial and could be trialled using alternate modes of communication to support remote and rural PCI patients and extend to other cardiovascular patients.

Cardiac remodeling in Drosophila arises from changes in actin gene expression and from a contribution of lymph gland-like cells to the heart musculature

Understanding the basis of normal heart remodeling can provide insight into the plasticity of the cardiac state, and into the potential for treating diseased tissue. In Drosophila, the adult heart arises during metamorphosis from a series of events, that include the remodeling of an existing cardiac tube, the elaboration of new inflow tracts, and the addition of a layer of longitudinal muscle fibers. We have identified genes active in all these three processes, and studied their expression in order to characterize in greater detail normal cardiac remodeling. Using a Transglutaminase-lacZ transgenic line, that is expressed in the inflow tracts of the larval and adult heart, we confirm the existence of five inflow tracts in the adult structure. In addition, expression of the Actin87E actin gene is initiated in the remodeling cardiac tube, but not in the longitudinal fibers, and we have identified an Act87E promoter fragment that recapitulates this switch in expression. We also establish that the longitudinal fibers are multinucleated, characterizing these cells as specialized skeletal muscles. Furthermore, we have defined the origin of the longitudinal fibers, as a subset of lymph gland cells associated with the larval dorsal vessel. These studies underline the myriad contributors to the formation of the adult Drosophila heart, and provide new molecular insights into the development of this complex organ. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

A functional polymorphism in the 5HTR2C gene associated with stress responses also predicts incident cardiovascular events.

Previously we have shown that a functional nonsynonymous single nucleotide polymorphism (rs6318) of the 5HTR2C gene located on the X-chromosome is associated with hypothalamic-pituitary-adrenal axis response to a stress recall task, and with endophenotypes associated with cardiovascular disease (CVD). These findings suggest that individuals carrying the rs6318 Ser23 C allele will be at higher risk for CVD compared to Cys23 G allele carriers. The present study examined allelic variation in rs6318 as a predictor of coronary artery disease (CAD) severity and a composite endpoint of all-cause mortality or myocardial infarction (MI) among Caucasian participants consecutively recruited through the cardiac catheterization laboratory at Duke University Hospital (Durham, NC) as part of the CATHGEN biorepository. Study population consisted of 6,126 Caucasian participants (4,036 [65.9%] males and 2,090 [34.1%] females). A total of 1,769 events occurred (1,544 deaths and 225 MIs; median follow-up time = 5.3 years, interquartile range = 3.3-8.2). Unadjusted Cox time-to-event regression models showed, compared to Cys23 G carriers, males hemizygous for Ser23 C and females homozygous for Ser23C were at increased risk for the composite endpoint of all-cause death or MI: Hazard Ratio (HR) = 1.47, 95% confidence interval (CI) = 1.17, 1.84, p = .0008. Adjusting for age, rs6318 genotype was not related to body mass index, diabetes, hypertension, dyslipidemia, smoking history, number of diseased coronary arteries, or left ventricular ejection fraction in either males or females. After adjustment for these covariates the estimate for the two Ser23 C groups was modestly attenuated, but remained statistically significant: HR = 1.38, 95% CI = 1.10, 1.73, p = .005. These findings suggest that this functional polymorphism of the 5HTR2C gene is associated with increased risk for CVD mortality and morbidity, but this association is apparently not explained by the association of rs6318 with traditional risk factors or conventional markers of atherosclerotic disease.

Simultaneous, long-term monitoring of valve and cardiac activity in the blue mussel Mytilus edulis exposed to copper

Valve and cardiac activity were simultaneously measured in the blue mussel (Mytilus edulis) in response to 10 d copper exposure. Valve movements, heart rates and heart-rate variability were obtained non-invasively using a Musselmonitor(R) (valve activity) and a modified version of the Computer-Aided Physiological Monitoring system (CAPMON; cardiac activity). After 2 d exposure of mussels (4 individuals per treatment group) to a range of dissolved copper concentrations (0 to 12.5 mu M as CuCl2) median valve positions (% open) and median heart rates (beats per minute) declined as a function of copper concentration. Heart-rate variability (coefficient of variation for interpulse durations) rose in a concentration-dependent manner. The 48 h EC50 values (concentrations of copper causing 50% change) for valve positions, heart rates and heart-rate variability were 2.1, 0.8, and 0.06 mu M, respectively. Valve activity was weakly correlated with both heart rate (r = 0.48 +/- 0.02) and heart-rate variability (r = 0.32 +/- 0.06) for control individuals (0 mu M Cu2+). This resulted from a number of short enclosure events that did not coincide with a change in cardiac activity. Exposure of mussels to increasing copper concentrations (greater than or equal to 0.8 mu M) progressively reduced the correlation between valve activity and heart rates (r = 0 for individuals dosed with greater than or equal to 6.3 mu M Cu2+), while correlations between valve activity and heart-rate variability were unaffected. The poor correlations resulted from periods of valve flapping that were not mimicked by similar fluctuations in heart rate or heart-rate variability. The data suggest that the copper-induced bradycardia observed in mussels is not a consequence of prolonged valve closure.

High population prevalence of cardiac troponin I measured by a high-sensitivity assay and cardiovascular risk estimation: the MORGAM Biomarker Project Scottish Cohort

Aims
Our aim was to test the prediction and clinical applicability of high-sensitivity assayed troponin I for incident cardiovascular events in a general middle-aged European population.

Methods and results
High-sensitivity assayed troponin I was measured in the Scottish Heart Health Extended Cohort (n = 15 340) with 2171 cardiovascular events (including acute coronary heart disease and probable ischaemic strokes), 714 coronary deaths (25% of all deaths), 1980 myocardial infarctions, and 797 strokes of all kinds during an average of 20 years follow-up. Detection rate above the limit of detection (LoD) was 74.8% in the overall population and 82.6% in men and 67.0% in women. Troponin I assayed by the high-sensitivity method was associated with future cardiovascular risk after full adjustment such as that individuals in the fourth category had 2.5 times the risk compared with those without detectable troponin I (P < 0.0001). These associations remained significant even for those individuals in whom levels of contemporary-sensitivity troponin I measures were not detectable. Addition of troponin I levels to clinical variables led to significant increases in risk prediction with significant improvement of the c-statistic (P < 0.0001) and net reclassification (P < 0.0001). A threshold of 4.7 pg/mL in women and 7.0 pg/mL in men is suggested to detect individuals at high risk for future cardiovascular events.

Conclusion
Troponin I, measured with a high-sensitivity assay, is an independent predictor of cardiovascular events and might support selection of at risk individuals.

Tumor suppressor Ras-association domain family 1 isoform A is a novel regulator of cardiac hypertrophy

BACKGROUND: Ras signaling regulates a number of important processes in the heart, including cell growth and hypertrophy. Although it is known that defective Ras signaling is associated with Noonan, Costello, and other syndromes that are characterized by tumor formation and cardiac hypertrophy, little is known about factors that may control it. Here we investigate the role of Ras effector Ras-association domain family 1 isoform A (RASSF1A) in regulating myocardial hypertrophy.

METHODS AND RESULTS: A significant downregulation of RASSF1A expression was observed in hypertrophic mouse hearts, as well as in failing human hearts. To further investigate the role of RASSF1A in cardiac (patho)physiology, we used RASSF1A knock-out (RASSF1A(-)(/)(-)) mice and neonatal rat cardiomyocytes with adenoviral overexpression of RASSF1A. Ablation of RASSF1A in mice significantly enhanced the hypertrophic response to transverse aortic constriction (64.2% increase in heart weight/body weight ratio in RASSF1A(-)(/)(-) mice compared with 32.4% in wild type). Consistent with the in vivo data, overexpression of RASSF1A in cardiomyocytes markedly reduced the cellular hypertrophic response to phenylephrine stimulation. Analysis of molecular signaling events in isolated cardiomyocytes indicated that RASSF1A inhibited extracellular regulated kinase 1/2 activation, likely by blocking the binding of Raf1 to active Ras.

CONCLUSIONS: Our data establish RASSF1A as a novel inhibitor of cardiac hypertrophy by modulating the extracellular regulated kinase 1/2 pathway.