The aim of the present study was to evaluate the acute effects of resistance exercise (RE) leading to failure and RE that was not to failure on 24 h blood pressure (BP) and heart rate variability (HRV) in sedentary normotensive adult women.
Ten women (33.2 ± 5.8 years; 159.3 ± 9.4 cm; 58.0 ±6.4 kg; body fat 28.4 ± 2.8%) randomly underwent three experimental sessions: control (40 minutes of seated rest), RE leading to failure with 3 sets of 10 repetitions maximum (10-RM), and RE not to failure at 60% of 10-RM with 3 sets of 10 repetitions. Immediately post session BP and HRV were measured for 24 h.
Ratings of perceived exertion and heart rate were higher during the 10-RM session when compared with 60% of 10-RM (6.4 ± 0.5 vs 3.5 ± 0.8 and 123.7 ± 13.9 vs 104.5 ± 7.3 bpm, respectively). The systolic, diastolic and mean BP decreased at 07:00 a.m. after the 10-RM session when compared with the control session (−9.0 ± 7.8 mmHg, -16.0 ± 12.9 mmHg and −14.3 ± 11.2 mmHg, respectively). The root mean square of the squared differences between R-R intervals decreased after both the 60% of 10-RM and 10-RM sessions compared with the control session.
An acute RE session leading to failure induced a higher drop of BP upon awakening, while both RE sessions reduced cardiac parasympathetic modulation. RE may be an interesting training strategy to acutely decrease BP in adult women.
Resistance training; Blood pressure; Hypotension
High resting heart rate (HR) is associated with increased cardiovascular risk in general populations, possibly due to elevated blood pressure (BP) or sympathetic over-activity. We studied the association of resting HR with cardiovascular function, and examined whether the hemodynamics remained similar during passive head-up tilt.
Hemodynamics were recorded using whole-body impedance cardiography and continuous radial pulse wave analysis in 522 subjects (age 20–72 years, 261 males) without medication influencing HR or BP, or diagnosed diabetes, coronary artery, renal, peripheral arterial, or cerebrovascular disease. Correlations were calculated, and results analysed according to resting HR tertiles.
Higher resting HR was associated with elevated systolic and diastolic BP, lower stroke volume but higher cardiac output and work, and lower systemic vascular resistance, both supine and upright (p < 0.05 for all). Subjects with higher HR also showed lower supine and upright aortic pulse pressure and augmentation index, and increased resting pulse wave velocity (p < 0.001). Upright stroke volume decreased less in subjects with highest resting HR (p < 0.05), and cardiac output decreased less in subjects with lowest resting HR (p < 0.009), but clear hemodynamic differences between the tertiles persisted both supine and upright.
Supine and upright hemodynamic profile associated with higher resting HR is characterized by higher cardiac output and lower systemic vascular resistance. Higher resting HR was associated with reduced central wave reflection, in spite of elevated BP and arterial stiffness. The increased cardiac workload, higher BP and arterial stiffness, may explain why higher HR is associated with less favourable prognosis in populations.
Arterial stiffness; Cardiac output; Heart rate; Head-up tilt; Systemic vascular resistance
To evaluate the relevance of stress-induced decrease in left ventricular ejection fraction (LVEF) in patients with type-2 diabetes.
A total of 684 diabetic patients with available rest and post-stress gated myocardial perfusion single-photon emission computed tomography (MPS) data were enrolled. An automated algorithm was used to determine the perfusion scores using a 17-segment model. LVEF drop was considered significant if the post-stress LVEF was ≥5% below the rest value. Follow-up data were available in 587 patients that were followed for the occurrence of cardiac death, nonfatal myocardial infarction, or unstable angina requiring revascularization.
A post-stress LVEF drop ≥5% was observed in 167 (24%) patients. Patients with LVEF drop had higher summed stress score (p < 0.05), summed difference score (p < 0.001), and rest LVEF (p < 0.001) compared to patients without. Conversely, summed rest score, a measure of infarct size, was comparable between the two groups. At multivariable analysis, summed difference score and rest LVEF were independent predictors (both p < 0.001) of post-stress LVEF drop. Myocardial perfusion was abnormal in 106 (63%) patients with post-stress LVEF drop and in 296 (57%) of those without (p = 0.16). The overall event-free survival was lower in patients with post-stress LVEF drop than in those without (log rank χ2 7.7, p < 0.005). After adjusting for clinical data and MPS variables, the hazard ratio for cardiac events for post-stress LVEF drop was 1.52 (p < 0.01).
In diabetic patients stress-induced ischemia is an independent predictor of post-stress LVEF drop; however, a reduction in LVEF is detectable also in patients with normal perfusion. Finally, post-stress LVEF drop increases the risk of subsequent cardiac events in diabetic patients.
Diabetes mellitus; Gated myocardial perfusion imaging; Left ventricular ejection fraction; Myocardial stunning
Persons with a systolic blood pressure (BP) of 120 to < 140 or diastolic BP of 80 to < 90 mm hg are classified as having pre-hypertension. Pre-hypertension is associated with cardiovascular disease (CVD) risk factors, incident CVD and CVD mortality. Understanding determinants of pre-hypertension especially in low income countries is a pre-requisite for improved prevention and control.
Data were analyzed for 4142 persons aged 18 years and older with BP measured in a community cross sectional survey in Uganda. The prevalence of pre-hypertension was estimated and a number of risk factors e.g. smoking, use of alcohol, overweight, obesity, physical activity, sex, age, marital status, place of residence, and consumption of vegetables and fruits were compared among different groups (normotension, pre-hypertension, and hypertension) using bivariate and multivariable logistic regression.
The age standardized prevalence of normal blood pressure was 37.6%, pre-hypertension 33.9%, hypertension 28.5% and raised blood pressure 62%. There was no difference between the prevalence of hypertension among women compared to men (28.9% versus 27.9%). However, the prevalence of pre-hypertension was higher among men (41.6%) compared to women (29.4%). Compared to people with normal blood pressure, the risk of pre-hypertension was increased by being 40 years and above, smoking, consumption of alcohol, not being married, being male and being overweight or obese. Compared to pre-hypertension, hypertension was more likely if one was more than 40 years, had infrequent or no physical activity, resided in an urban area, and was obese or overweight.
More than one in three of adults in this population had pre-hypertension. Preventive and public health interventions that reduce the prevalence of raised blood pressure need to be implemented.
Cardiovascular diseases; Non communicable diseases; Low income countries; Risk factors; Prevalence
The role of β-adrenergic stimulation on viral myocarditis has been investigated in animal models of viral myocarditis. Excess stimulation of β-adrenergic receptors by catecholamines causes phosphorylation/activation of cAMP response element binding protein (CREB) by the cAMP signaling pathway. CREB as an important regulator of gene expression mediates the cardiovascular remodeling process and promotes anti-inflammatory immune responses. However, the CREB expression and phosphorylation have not been studied, and the effects of carvedilol (a nonselective β-adrenoceptor antagonist) on the CREB has not been investigated in the setting of acute viral myocarditis.
This study was therefore designed to examine the effects of carvedilol on the transcriptional factor CREB in a murine model of acute viral myocarditis. In a coxsackievirus B3 murine myocarditis model (Balb/c), effects of carvedilol on plasma noradrenaline, heart rate and blood pressure, myocardial histopathological changes and fibrosis, cardiomyocyte apoptosis, cardiac CREB and phosphorylated CREB, cytokine levels, and viral RNA were studied.
The expression and phosphorylation of CREB were decreased with concomitant increase of IL-6 and TNF-α in murine coxsackievirus-induced acute viral myocarditis. The levels of IL-6 and TNF-α were correlated with the expression of CREB or phosphorylated CREB. Carvedilol increased the cardiac CREB expression and phosphorylation and decreased the plasma catecholamine levels and the production of IL-6 and TNF-α with amelioration of acute viral myocarditis.
These results show that CREB may be involved in the pathophysiology of viral myocarditis and carvedilol exerts some of its beneficial effects by increasing the CREB expression and phosphorylation.
Viral myocarditis; cAMP response element binding protein; Carvedilol
Central obesity in relation to insulin resistance is strongly linked to the development of type 2 diabetes. However, data regarding the association between pericardial and peri-aortic adiposity, a potential estimate of visceral adipose tissue burden, and pre-diabetes status remains unclear.
The aim of this study was to examine whether the degree of pericardial and thoracic peri-aortic adipose tissue, when quantified by multi-detector computed tomography (MDCT), differs significantly in a normal, pre-diabetic, and overtly diabetic population.
We studied 562 consecutive subjects including 357 healthy, 155 pre-diabetic, and 50 diabetic patients selected from participants who underwent annual health surveys in Taiwan. Pre-diabetes status was defined by impaired fasting glucose or impaired glucose intolerance according to American Diabetes Association guidelines. Pericardial (PCF) and thoracic peri-aortic (TAT) adipose tissue burden was assessed using a non-contrast 16-slice multi-detector computed tomography (MDCT) dataset with off-line measurement (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA). Body fat composition, serum high-sensitivity C-reactive protein (hs-CRP) level and insulin resistance (HOMA-IR) were also assessed.
Patients with diabetes and pre-diabetes had greater volume of PCF (89 ± 24.6, 85.3 ± 28.7 & 67.6 ± 26.7 ml, p < 0.001) as well as larger TAT (9.6 ± 3.1 ml vs 8.8 ± 4.2 & 6.6 ± 3.5 ml, respectively, p < 0.001) when compared to the normal group, although there were no significant differences in adiposity between the diabetic and pre-diabetic groups. For those without established diabetes in our study, increasing TAT burden, but not PCF, appear to correlate with insulin resistance (HOMA-IR) and hs-CRP in the multivariable models.
Pre-diabetic and diabetic subjects, compared to normoglycemia, were associated with significantly higher pericardial and peri-aortic adipose tissue burden. In addition, visceral fat accumulation adjacent to the thoracic aorta seemed to exert a significant impact on insulin resistance and systemic inflammation.
Pre-diabetes; Diabetes mellitus; MDCT; Pericardial adipose tissue; Peri-aortic adipose tissue; Insulin resistance
Autoantibodies specific to the angiotensin II type I receptor (anti-AT1-AR) have been implicated in the pathology of congestive heart failure (CHF). Anti-AT1-AR may be associated with left ventricular function in CHF patients treated with perindopril.
Synthetic angiotensin II type 1 receptor (AT1-R) peptides served as the target antigen. ELISA was used to screen the sera of 156 CHF patients, which were divided into positive and negative groups based on their anti-AT1-AR reactivity. Echocardiography and a 6-minute walk test were performed at baseline and after one year of perindopril therapy. The end-point events were compared over a 5-year follow-up.
Final analysis covered 138 patients, including 82 positive and 56 negative. The frequency and geometric mean titre of anti-AT1-AR were significantly lower in the positive group after one year of treatment (all P < 0.01, from 100% to 73.2% and from 1:125.3 ± 1.0 to 1:69.2 ± 1.1). Of these, 22 patients showed no antibodies. Both groups showed improvement in left ventricular end-diastole, end-systolic dimensions, ejection fraction, and a 6-minute walk test by perindopril in combination with standard treatment regime for one year (all P < 0.01). However, the 82 patients positive for anti-AT1-AR showed more pronounced improvement than the 56 negative patients (all P < 0.05). However, after 5 years of follow-up, the rate of all causes and cardiovascular mortality attributable to any cause and the re-hospitalisation rate showed no significant differences between the two groups (all P > 0.05).
Perindopril treatment significantly decreased the frequency and geometric mean titre in patients positive for anti-AT1-AR, even to complete ablation. These patients showed greater improvement in left ventricular remodeling and heart function than negative that in patients after one year of perindopril treatment in combination with standard treatment, but no significant differences in endpoint events were observed in the following 5 years. Anti-AT1-AR might be a useful biomarker of over-activation of the renin-angiotensin-aldosterone system for clinical medication.
Anti-AT1-AR; Renin-angiotensin-aldosterone system; Biomarker
Seasonal associations of cardiovascular mortality have been noted in most populations of European origin years ago, but are not well evaluated in Asian populations recently.
Utilizing the electronic Hospitalization Summary Reports (HSRs) from 32 top-ranked hospitals in Beijing, China, we evaluated the association between winter season and the risk of cardiovascular death among hospitalized individuals. General additive models and logistic regression models were adjusted for confounding factors.
Older patients who were admitted to the hospital in the winter months (January, February, November and December) had a death risk that was increased by approximately 30% to 50% (P < 0.01) over those who were admitted in May. However, younger patients did not seem to experience the same seasonal variations in death risk. The excess winter deaths among older patients were associated with ischemic heart disease (RR = 1.22; 95% CI 1.13 to 1.31), pulmonary heart disease (RR = 1.42; 95% CI 1.10 to 1.83), cardiac arrhythmias (RR = 1.67; 95% CI 1.36 to 2.05), heart failure (RR = 1.30; 95% CI 1.09 to 1.54), ischemic stroke (RR = 1.30; 95% CI 1.17 to 1.43), and other cerebrovascular diseases (RR = 1.78; 95% CI 1.40 to 2.25). The risks of mortality were higher in winter months than in the month of May, regardless of the presence or absence of respiratory disease.
Winter season was associated with a substantially increased risk of cardiovascular death among older Chinese cardiovascular inpatients.
Cardiovascular disease; Winter; Seasonality; Older adults; Mortality; Asian population
Mild to moderate cognitive impairment is common amongst long-term survivors of cardiac arrest. In the Target Temperature Management trial (TTM-trial) comatose survivors were randomized to 33°C or 36°C temperature control for 24 hours after cardiac arrest and the effects on survival and neurological outcome assessed. This protocol describes a sub-study of the TTM-trial investigating cognitive dysfunction and its consequences for patients’ and relatives’ daily life.
Sub-study sites in five European countries included surviving TTM patients 180 days after cardiac arrest. In addition to the instruments for neurological function used in the main trial, sub-study patients were specifically tested for difficulties with memory (Rivermead Behavioural Memory Test), attention (Symbol Digit Modalities Test) and executive function (Frontal Assessment Battery). Cognitive impairments will be related to the patients’ degree of participation in society (Mayo-Portland Adaptability Inventory-4), health related quality of life (Short Form Questionnaire–36v2©), and the caregivers’ situation (Zarit Burden Interview©). The two intervention groups (33°C and 36°C) will be compared with a group of myocardial infarction controls.
This large international sub-study of a randomized controlled trial will focus on mild to moderate cognitive impairment and its consequences for cardiac arrest survivors and their caregivers. By using an additional battery of tests we may be able to detect more subtle differences in cognitive function between the two intervention groups than identified in the main study. The results of the study could be used to develop a relevant screening model for cognitive dysfunction after cardiac arrest.
Out-of-hospital cardiac arrest; Hypothermia, induced; Resuscitation; Cardiovascular diseases; Brain injuries; Cognition; Memory; Quality of life; Social participation; Caregivers
Chronic obstructive pulmonary disease (COPD) reduces exercise capacity, but lung function parameters do not fully explain functional class and lung-heart interaction could be the explanation. We evaluated echocardiographic predictors of mortality and six minutes walking distance (6MWD), a marker for quality of life and mortality in COPD.
Ninety COPD patients (GOLD criteria) were evaluated by body plethysmography, 6MWD and advanced echocardiography parameters (pulsed wave tissue Doppler and speckle tracking).
Mean 6MWD was 403 (± 113) meters. All 90 subjects had preserved left ventricular (LV) ejection fraction 64.3% ± 8.6%. Stroke volume decreased while heart rate increased with COPD severity and hyperinflation. In 66% of patients, some degree of diastolic dysfunction was present. Mitral tissue Doppler data in COPD could be interpreted as a sign of low LV preload and not necessarily an intrinsic impairment in LV relaxation/compliance. Tricuspid regurgitation (TR) increased with COPD severity and hyperinflation. Age (p < 0.001), BMI (p < 0.001), DLCO SB (p < 0.001) and TR (p 0.005) were independent predictors of 6MWD and a multivariable model incorporating heart function parameters (adjusted r2 = .511) compared well to a model with lung function parameters alone (adjusted r2 = .475). LV global longitudinal strain (p = 0.034) was the only independent predictor of mortality among all baseline, body plethysmographic and echocardiographic variables.
Among subjects with moderate to severe COPD and normal LVEF, GLS independently predicted all-cause mortality. Exercise tolerance correlated with standard lung function parameters only in univariate models; in subsequent models including echocardiographic parameters, longer 6MWD correlated independently with milder TR, better DLCO SB, younger age and lower BMI. We extended the evidence on COPD affecting cardiac chamber volumes, LV preload, heart rate, as well as systolic and diastolic function. Our results highlight lung-heart interaction and the necessity of cardiac evaluation in COPD.
COPD; 6MWD; Exercise capacity; Pulmonary artery pressure; Systolic dysfunction; Diastolic dysfunction; Tissue doppler; Global longitudinal strain
The aim of this cross-sectional study was to determine the association between lowered endothelial function measured by peripheral arterial tonometry (PAT) and cardio-metabolic risk factors. The study population consisted of Finnish municipal workers who were at risk of diabetes or cardiovascular disease and who had expressed a need to change their health behaviour.
A total of 312 middle-aged municipal workers underwent a physical medical examination and anthropometry measurements. Levels of total cholesterol, HDL cholesterol, triglycerides, fasting glucose, glycated haemoglobin, and high sensitivity C-reactive protein were taken from the blood samples. PAT measured the increase in digital pulse volume amplitude during reactive hyperemia, and the index of endothelial function, F-RHI, was defined as the ratio of post-deflation amplitude to baseline amplitude.
In the linear regression model, male sex was associated with lower F-RHI. In sex-adjusted linear regression models, each of the variables; waist circumference, fasting glucose, glycated hemoglobin, triglycerides, body fat percentage, body mass index, current smoking, and impaired fasting glucose or diabetes were separately associated with lower F-RHI, and HDL cholesterol and resting heart rate were associated with higher F-RHI.
HDL cholesterol, sex, body mass index, and current smoking entered a stepwise multivariable regression model, in which HDL cholesterol was associated with higher F-RHI, and smoking, male sex and body mass index were associated with lower F-RHI. This model explains 28.3% of the variability in F-RHI.
F-RHI is associated with several cardio-metabolic risk factors; low level of HDL cholesterol, male sex, overweight and smoking being the most important predictors of a lowered endothelial function. A large part of variation in F-RHI remains accounted for by unknown factors.
Cardiovascular risk; Endothelial dysfunction; Peripheral arterial tonometry; Occupational health care
Ankle-brachial-Index (ABI) measured by manual Dopplersonography is an easily assessable marker of global cardiovascular risk. The aim of this study was to establish novel photo-plethysmography (PPG)-based ABI assessments in an epidemiologic context and to compare its results with those of Doppler.
Two devices for PPG-based ABI assessments (Vicorder, Vascular Explorer) were tested and compared against Doppler in 56 putatively healthy subjects. We determined acceptance, time requirements, agreement of repeat measurements, agreement with Doppler and intra- and inter-observer concordances for both devices and compared the results. Differences between cuff inflation- and deflation-based methods were also studied for Vascular Explorer.
Acceptance was similar for both devices but Vascular Explorer was more time consuming. Agreement of multiple measurements was moderate for both methods highlighting the importance of measurement replicates. Both automated devices showed significantly higher ABI compared to Doppler which can be traced back to higher brachial pressures (Vicorder) or higher ankle pressures (Vascular Explorer). This effect is more pronounced for Vascular Explorer but can be ameliorated using the deflation method of measurement. Intra-observer concordances were similar. Inter-observer concordance was non-significantly better for Vicorder.
Both devices proved to be feasible in epidemiologic studies, but compared to Doppler, do not constitute an advantage regarding time requirement and accuracy of ABI assessment. Since PPG-based ABI values are inflated compared to Doppler, it will be necessary to adjust Doppler-based cut-offs for risk stratification.
Ankle-brachial index; Feasibility; Vascular explorer; Vicorder
Physical training has beneficial effects on exercise capacity, quality of life and mortality in patients after a cardiac event or intervention and is therefore a core component of cardiac rehabilitation. However, cardiac rehabilitation uptake is low and effects tend to decrease after the initial rehabilitation period. Home-based training has the potential to increase cardiac rehabilitation uptake, and was shown to be safe and effective in improving short-term exercise capacity. Long-term effects on physical fitness and activity, however, are disappointing. Therefore, we propose a novel strategy using telemonitoring guidance based on objective training data acquired during exercise at home. In this way, we aim to improve self-management skills like self-efficacy and action planning for independent exercise and, consequently, improve long-term effectiveness with respect to physical fitness and physical activity. In addition, we aim to compare costs of this strategy with centre-based cardiac rehabilitation.
This randomized controlled trial compares a 12-week telemonitoring guided home-based training program with a regular, 12-week centre-based training program of equal duration and training intensity in low to moderate risk patients entering cardiac rehabilitation after an acute coronary syndrome or cardiac intervention. The home-based group receives three supervised training sessions before they commence training with a heart rate monitor in their home environment. Participants are instructed to train at 70-85% of their maximal heart rate for 45–60 minutes, twice a week. Patients receive individual coaching by telephone once a week, based on measured heart rate data that are shared through the internet. Primary endpoints are physical fitness and physical activity, assessed at baseline, after 12 weeks and after one year. Physical fitness is expressed as peak oxygen uptake, assessed by symptom limited exercise testing with gas exchange analysis; physical activity is expressed as physical activity energy expenditure, assessed by tri-axial accelerometry and heart rate measurements. Secondary endpoints are training adherence, quality of life, patient satisfaction and cost-effectiveness.
This study will increase insight in long-term effectiveness and costs of home-based cardiac rehabilitation with telemonitoring guidance. This strategy is in line with the trend to shift non-complex healthcare services towards patients’ home environments.
Dutch Trial Register: NTR3780. Clinicaltrials.gov register: NCT01732419
Cardiac rehabilitation; Home-based training; Telemonitoring; Physical fitness; Physical activity
Low body mass index (BMI) is associated with a poor outcome in chronic heart failure (CHF). An inverse association between BMI and adiponectin and N-terminal pro-B-type natriuretic peptide (NT-proBNP) has been reported. The aim of the present study was to investigate whether novel markers of neurohormonal activation, inflammation, and endothelial dysfunction are associated with BMI in CHF.
In a cross-sectional study including 171 patients with CHF and a left ventricular ejection fraction (LVEF) ≤45% the impact of BMI on circulating plasma concentrations of adiponectin, α-defensins, high sensitivity C-reactive protein (hsCRP), copeptin, mid-regional pro-adrenomedullin (MR-proADM), NT-proBNP, and mid-regional pro-A-type natriuretic peptide (MR-proANP) were evaluated.
In multivariable linear regression analysis including age, sex, LVEF, New York Heart Association functional classification (NYHA), estimated glomerular filtration rate (eGFR), and diabetes, only NT-proBNP (β = −0.32) and adiponectin (β = −0.39) remained independently associated with BMI. MR-proANP was associated with BMI but adjusting for age attenuated the relation being no longer significant.
Among biomarkers typically increased in patients with CHF only adiponectin and NT-proBNP demonstrated independent inverse associations with BMI. This indicates a direct effect of these two biomarkers enhancing the wasting process seen in CHF.
Biomarkers; Chronic heart failure; Body mass index
Cardiovascular disease is the leading cause of deaths worldwide and the arterial reconstructive surgery remains the treatment of choice. Although large diameter vascular grafts have been widely used in clinical practices, there is an urgent need to develop a small diameter vascular graft with enhanced blood compatibility. Herein, we fabricated a small diameter vascular graft with submicron longitudinally aligned topography, which mimicked the tunica intima of the native arterial vessels and were tested in Sprague–Dawley (SD) rats.
Vascular grafts with aligned and smooth topography were prepared by electrospinning and were connected to the abdominal aorta of the SD rats to evaluate their blood compatibility. Graft patency and platelet adhesion were evaluated by color Doppler ultrasound and immunofluorescence respectively.
We observed a significant higher patency rate (p = 0.021) and less thrombus formation in vascular graft with aligned topography than vascular graft with smooth topography. However, no significant difference between the adhesion rates on both vascular grafts (smooth/aligned: 0.35‰/0.12‰, p > 0.05) was observed. Moreover, both vascular grafts had few adherent activated platelets on the luminal surface.
Bionic vascular graft showed enhanced blood compatibility due to the effect of surface topography. Therefore, it has considerable potential for using in clinical application.
Vascular grafts; Electrospinning; Aligned topography; Thrombosis; Platelet adhesion
Chest pain remains a diagnostic challenge: physicians do not want to miss an acute coronary syndrome (ACS), but, they also wish to avoid unnecessary additional diagnostic procedures. In approximately 75% of the patients presenting with chest pain at the emergency department (ED) there is no underlying cardiac cause. Therefore, diagnostic strategies focus on identifying patients in whom an ACS can be safely ruled out based on findings from history, physical examination and early cardiac marker measurement. The HEART score, a clinical prediction rule, was developed to provide the clinician with a simple, early and reliable predictor of cardiac risk. We set out to quantify the impact of the use of the HEART score in daily practice on patient outcomes and costs.
We designed a prospective, multi-centre, stepped wedge, cluster randomised trial. Our aim is to include a total of 6600 unselected chest pain patients presenting at the ED in 10 Dutch hospitals during an 11-month period. All clusters (i.e. hospitals) start with a period of ‘usual care’ and are randomised in their timing when to switch to ‘intervention care’. The latter involves the calculation of the HEART score in each patient to guide clinical decision; notably reassurance and discharge of patients with low scores and intensive monitoring and early intervention in patients with high HEART scores. Primary outcome is occurrence of major adverse cardiac events (MACE), including acute myocardial infarction, revascularisation or death within 6 weeks after presentation. Secondary outcomes include occurrence of MACE in low-risk patients, quality of life, use of health care resources and costs.
Stepped wedge designs are increasingly used to evaluate the real-life effectiveness of non-pharmacological interventions because of the following potential advantages: (a) each hospital has both a usual care and an intervention period, therefore, outcomes can be compared within and across hospitals; (b) each hospital will have an intervention period which enhances participation in case of a promising intervention; (c) all hospitals generate data about potential implementation problems. This large impact trial will generate evidence whether the anticipated benefits (in terms of safety and cost-effectiveness) of using the HEART score will indeed be achieved in real-life clinical practice.
HEART score; Chest pain; Clinical prediction rule; Risk score implementation; Impact; Stepped wedge design; Cluster randomised trial
A health technology assessment (HTA) of catheter ablation for atrial fibrillation (CA-AF) was commissioned by the Belgian government and performed by the Belgian Health Care Knowledge Centre (KCE). In this context, a systematic review of the economic literature was performed to assess the procedure’s value for money.
A systematic search for economic literature about the cost-effectiveness of CA-AF was performed by consulting various databases: CRD (Centre for Reviews and Dissemination) HTA and CDSR (Cochrane Database of Systematic Reviews) Technology Assessment, websites of HTA institutes, NHS EED (NHS Economic Evaluation Database), Medline (OVID), EMBASE and EconLit. No time or language restrictions were imposed and pre-defined selection criteria were used. The two-step selection procedure was performed by two persons. References of the selected studies were checked for additional relevant citations.
Out of 697 references, seven relevant studies were selected. Based on current evidence and economic considerations, the rationale to support catheter ablation as first-line treatment was lacking.
The economic evaluations for second-line catheter ablation included several assumptions that make the results rather optimistic or subject to large uncertainty. First, overall AAD (antiarrhythmic drugs) use after ablation was higher in reality than assumed in the economic evaluations, which had its impact on costs and effects. Second, several models focused on the impact of ablation on preventing stroke. This was questionable because there was no direct hard evidence from RCTs to support this assumption. An indirect impact through stroke on mortality should also be regarded with caution. Furthermore, all models included an impact on quality of life (QoL)/utility and assumed a long-term impact. Unfortunately, none of the RCTs measured QoL with a generic utility instrument and information on the long-term impact on both mortality and QoL was lacking.
Catheter ablation is associated with high initial costs and may lead to life-threatening complications. Its cost-effectiveness depends on the belief one places on the impact on utility and/or preventing stroke, and the duration of these effects. Having no hard evidence for these important variables is rather troublesome. Although the technique is widely spread, the scientific evidence is insufficient for drawing conclusions about the intervention’s cost-effectiveness.
Atrial fibrillation; Catheter ablation; Cost-Benefit analysis; Review
Cardiovascular diseases (CVDs) are one of the leading causes of death and disability in the world. Over 80% of CVD deaths take place in low-and middle-income countries. One-third of the population aged above 40 years suffers from Hypertension (HTN) and this is largely unreported as there is no registry for CVDs. No guidelines are available for use in health care facilities, especially private health facilities where practice among GPs varies considerably. We aim to conduct a Cluster Randomized Controlled trial delivering a quality HTN-CVD care package at strengthened private health facilities as compared to current practice at private health facilities.
A pragmatic cluster randomized trial, with qualitative and economic studies, will be conducted in Sargodha district of Punjab, Pakistan, from January 2012 to December 2016. At least 912 hypertensives will be registered in the two arms, six clusters per arm. The proposed cluster randomized controlled trial will evaluate the effects of delivering quality HTN-CVD care, through enabled private health care facilities, to achieve better case registration, adherence and hypertension control also blood glucose and serum cholesterol control. The trial will be conducted through the doctors and paramedics at private health facilities. Main outcomes are mean difference in Systolic blood pressure among the two arms. Secondary outcomes are mean change in total serum cholesterol levels and mean change in glycaemic control achieved in the adult hypertensive patients. Individual and Cluster level analysis will be done according to intention-to-treat.
Due to the high burden of disease where 1 in 3 individuals aged above 45 suffers from hypertension, topped with the fact that there is a dearth of a set of available, standardised guidelines for management, the disease is constantly on a hike in Pakistan. The government has made no effort to issue a set of guidelines adapted specifically for our population and this becomes more of a problem when managing CVD in urban population through private practitioners whose practices vary widely.If our set of context sensitive guidelines show an effectiveness in the proposed intervention districts it will be replicated in other such settings.
Current Controlled Trials ISRCTN34381594
Cardiovascular disease; Public private mix; Urban health
An 81 year old female patient diagnosed with a chronic low grade hypereosinophilic syndrome presented with angina and dyspnoea.
She was managed for a non-ST elevated myocardial infarction since her troponin levels were elevated. On day 5, she suffered an acute clinical deterioration with type I respiratory failure and cardiogenic shock, accompanied by deterioration in left ventricular systolic function demonstrated on echocardiography, and this coincided with a marked rise in eosinophil count. Secondary causes of eosinophilia were excluded permitting a diagnosis of Hypereosinophilic Syndrome (HES) to be made. Coronary angiography revealed unobstructed arteries. Supportive treatment for heart failure included diuretic and inotropes but she dramatically improved both clinically and echocardiographically upon commencement of high dose steroids and hydroxycarbamide. Cardiac magnetic resonance imaging (CMR) demonstrated diffuse, shallow endomyocardial enhancement with late gadolinium, consistent with a diagnosis of eosinophilic myocarditis.
Hypereosinophilic Syndrome can masquerade as a myocardial infarction causing decompensated heart failure. Early recognition and treatment with steroids can improve outcome.
Patients with Down’s syndrome and shunt lesions are at high risk of developing pulmonary arterial hypertension (PAH) earlier than patients without Down’s syndrome. However, data on the efficacy of PAH-specific therapy in patients with Down’s syndrome are limited. The aim of this retrospective analysis was to determine the long-term efficacy of the dual endothelin receptor antagonist, bosentan, in Eisenmenger's syndrome (ES) patients with Down’s syndrome.
In this observational study adults with Down’s syndrome with a confirmed diagnosis of ES (World Health Organization functional class III) and receiving bosentan therapy and were followed up long term. Clinical evaluation at baseline and follow-up visits included resting transcutaneous arterial oxygen saturation and laboratory assessments. Exercise capacity was evaluated using a 6-minute walk test where transcutaneous arterial oxygen saturation at peak exercise (SpO2), 6-minute walk distance (6MWD) and Borg dyspnoea index were assessed. A full echocardiographic assessment was conducted at baseline and follow-up visits.
Overall, seven adults (mean age 29.6 ± 11.2 years; 57% male) received bosentan at a starting dose of 62.5 mg twice daily. This was increased to the target dose of 125 mg twice daily 4 weeks later. All patients remained on bosentan until the end of the study. After a mean (± standard deviation) duration of 52.2 ± 3.9 months (range: 46.0–55.5 months), 6MWD had increased from 199.6 ± 69.1 metres to 303.7 ± 99.9 metres (P < 0.05) and SpO2 at the end of the 6-minute walk test had increased from 61.6 ± 7.6% to 74.7 ± 6.2% (P < 0.05). Echocardiography demonstrated a significant change in acceleration time from 62.9 ± 11.6 m/s to 83.0 ± 9.6 m/s (P = 0.0156), and acceleration time/ejection time ratio from the pulmonary flow from 0.24 ± 0.04 at baseline to 0.30 ± 0.02 (P = 0.0156) at final follow-up.
Long-term treatment with bosentan significantly improved exercise capacity and oxygen saturation following exercise in adult ES patients with Down’s syndrome. These data confirm that the presence of Down’s syndrome does not affect the response to oral bosentan therapy.
Bosentan; Eisenmenger’s syndrome; Down’s syndrome; Long-term
Data on the use of circulating microRNAs (miRNAs) as biomarkers of cardiovascular diseases are emerging. Little, however, is known on the expression profile of circulating of microRNAs in congenital heart malformations with a systemic right ventricle that is prone to functional impairment. We aimed to test the hypothesis that circulating miRNA profile is altered in patients late after atrial switch operation for complete transposition of the great arteries (TGA) and further explored possible relationships between alteration of circulating miRNAs and systemic ventricular contractility.
Circulating miRNA expression profiling of serum samples from 5 patients and 5 healthy controls was performed. The results were validated in 26 patients and 20 controls using real-time quantitative reverse-transcription polymerase chain reaction for candidate miRNAs with fold changes >3 by expression profiling. Systemic ventricular myocardial acceleration during isovolumic contraction (IVA) was determined by colour tissue Doppler echocardiography.
Compared with controls, patients had significantly lower systemic ventricular IVA (p = 0.002). Of the 23 upregulated miRNAs identified by profiling, 11 were validated to be increased in patients compared with controls: miR-16, miR-106a, miR-144*, miR-18a, miR-25, miR-451, miR-486-3p, miR-486-5p, miR-505*, let-7e and miR-93. Among the validated 11 miRNAs, miR-18a (r = −0.45, p = 0.002) and miR-486-5p (r = −0.35, p = 0.018) correlated negatively with systemic ventricular IVA for the whole cohort.
A distinct serum miRNA expression signature exists in adults with complete TGA after atrial switch operation, with serum miR-18a and miR-486-5p being associated with systemic ventricular contractility.
MicroRNA; Transposition of the great arteries; Atrial switch; Systemic ventricular function
Micro-albuminuria is a recognized predictor of cardiovascular morbidity and mortality in patients with coronary artery disease. We have previously reported, in diabetic and non-diabetic patients, that an increased urinary excretion of IgM is associated with higher cardiovascular mortality. The purpose of this study was to investigate the pattern of urinary IgM excretion in patients with acute coronary syndrome (ACS) and its correlation to cardiovascular outcome.
Urine albumin, and IgM to creatinine concentration ratios were determined in 178 consecutive patients presenting with chest pain to the Department of Emergency Medicine (ED) at the University Hospital of Lund. Fifty eight (23 female) patients had ACS, 55 (19 female) patients had stable angina (SA), and 65 (35 female) patients were diagnosed as non-specific chest pain (NS).
Urine albumin and IgM excretions were significantly higher in patients with ACS (p = 0.001, and p = 0.029, respectively) compared to patients with NS-chest pain. During the 2 years follow-up time, 40 (19 female) patients suffered a new major cardiovascular event (ACS, acute heart failure, stroke) and 5 (4 male/1 female) patients died of cardiovascular cause. A high degree of albuminuria and IgM-uria significantly predicted cardiovascular mortality and morbidity (HR = 2.89, 95% CI: 1.48 - 5.66, p = 0.002). Microalbuminuric patients (≥3 mg/mmol) with high IgM-uria (≥0.005 mg/mmol) had a 3-fold higher risk for cardiovascular new events compared to patients with low IgM-uria (RR = 3.3, 95% CI: 1.1 - 9.9, p = 0.001).
In patients with chest pain, an increased urine IgM excretion, is associated with coronary artery disease and long-term cardiovascular complications. Measuring urine IgM concentration could have a clinical value in risk stratification of patients with ACS.
Urine IgM; Microalbuminuria; Acute coronary syndrome; Chest pain; Cardiovascular mortality
INR (International Normalized Ratio) is the biological reference test for the monitoring of vitamin K antagonist (VKA) therapy. Overdosage of VKAs causes about 17,000 hospitalizations and 5,000 deaths each year in France. To avoid these complications, monitoring and blood sampling conditions must be rigorous. In France, more than half of INRs are carried out at home. The aim was to determine blood-sampling conditions at home, transit time and the quality of the laboratory reagents used.
Questionnaire-based, descriptive epidemiological cross-sectional prevalence study involving home care nurses, family physicians (FPs) and clinical laboratories. Setting: Brittany, France, 2008. Study of the pre-analytical phase of INRs sampled at home and its influence on INR results.
The study included 291 FPs, 249 home care nurses, and 49 laboratories. 32.5% of reported INRs were outside the therapeutic range. Samples were drawn into unsuitable tubes in 5.5% of cases and delivered in a chilled condition in 9% of cases. In urban areas 50% of the tubes took more than 2 hours to reach the laboratory compared with 71% from rural areas. The average International Sensitivity Index (ISI) of the thromboplastin was 1.62. The INRs provided by the laboratories were not analyzable in 64.7% of cases where blood samples had been taken at home.
Blood sample quality, transit time and the reagents used are currently inadequate. The majority of INRs taken at home are not reliable. FPs should consider these drawbacks in comparison with alternative solutions to increase patient safety.
Hypertrophic cardiomyopathy (HCM) is a genetic condition, and relatives of affected persons may be at risk. Cardiac troponin biomarkers have previously been shown to be elevated in HCM. This study examines the new highly-sensitive cardiac troponin I (hsTnI) assay in a HCM screening population.
Nested case–control study of consecutive HCM sufferers and their relatives recruited from May 2010 to September 2011. After informed consent, participants provided venous blood samples and clinical and echocardiographic features were recorded. Associations between the natural log (ln) of the contemporary troponin I (cTnI) and hsTnI assays and markers of cardiac hypertrophy were examined. Multiple regression models were fitted to examine the predictive ability of hsTnI for borderline or definite HCM.
Of 107 patients, 24 had borderline and 19 had definite changes of HCM. Both TnI assays showed significant, positive correlations with measures of cardiac muscle mass. After age and sex adjustment, the area under the receiver operator characteristic (AUROC) curve for the outcome of HCM was 0.78, 95% CI [0.65, 0.90], for ln(hsTnI), and 0.66, 95% CI [0.51, 0.82], for ln(cTnI) (p=0.11). Including the hsTnI assay in a multiple-adjusted “screening” model for HCM resulted in a non-significant improvement in both the AUROC and integrated discrimination index.
Both cTnI and hsTnI show a graded, positive association with measures of cardiac muscle mass in persons at risk of HCM. Further studies will be required to evaluate the utility of these assays in ECG- and symptom-based identification of HCM in at-risk families.
Hypertrophic cardiomyopathy; High-risk screening; Troponin I; Biomarkers; Highly-sensitive assays
In adults, impaired myocardial repolarization and increased risk of arrhythmia are known consequences of open heart surgery. Little is known, however, about post-operative consequences of cardiopulmonary bypass surgery in children. The aim of this study was to assess ventricular repolarization and coronary perfusion after bypass surgery for atrial septal defect (ASD) repair in children.
Twelve patients with ASD were assessed one day before and 5–6 days after ASD repair. Myocardial repolarization (corrected QT interval, QTc, QT dispersion, QTd, and PQ interval) was determined on 12-lead electrocardiograms. Coronary flow in proximal left anterior descending artery (peak flow velocity in diastole, PFVd) was assessed by transthoracic Doppler echocardiography.
Ten of the 12 (83%) children had normal myocardial repolarization before and after surgery. After surgery, QTc increased 1-9% in 5 (42%) patients, decreased 2-11% in 5 (42%) patients and did not change in 2 (16%) patients. Post-op QTc positively correlated with bypass time (R=0.686, p=0.014) and changes in PFVd (R=0.741, p=0.006). After surgery, QTd increased 33-67% in 4 (33%) patients, decreased 25-50% in 6 patients (50%) and did not change in 2 (16%) patients. After surgery, PQ interval increased 5-30% in 4 (33%) patients, decreased 4-29% in 6 (50%) patients and did not change in 1 (8%) patient. Post-op PQ positively correlated with bypass time (R=0.636, p=0.027). As previously reported, PFVd significantly increased after surgery (p<0.001).
Changes in QTc, PQ and PFVd are common in young children undergoing surgery for ASD repair. Post-op QTc significantly correlates with bypass time, suggesting prolonged cardiopulmonary bypass may impair ventricular repolarization. Post-op QTc significantly correlates with PFVd changes, suggesting increased coronary flow may also impair ventricular repolarization. The clinical significance and reversibility of these alternations require further investigations.
ECG; ASD; Repolarization; Heart surgery