Endothelial dysfunction and microvascular abnormalities have been reported in patients with cardiac syndrome X (CSX), but the underlying mechanisms are unclear. Recent insights suggest that the injured endothelial monolayer is regenerated by circulating bone marrow‐derived endothelial progenitor cells (EPCs).
To test the hypothesis that the biology of altered EPCs might contribute to the pathophysiology of CSX.
34 subjects (mean (SD) age: 62 (7) years) were enrolled in the study, including 12 patients with CSX, 12 stable subjects with coronary artery disease (CAD) and 10 healthy controls. The number and adhesive function of EPCs were measured in peripheral‐blood samples from these study participants.
The baseline characteristics in patients with CSX and CAD were enhanced Framingham risk scores, more hypertension and lower high‐density lipoproteins than the controls. Patients with CSX and CAD had significantly decreased endothelium‐dependent flow‐mediated vasodilation (FMD) compared with normal controls (normal controls vs CSX vs CAD: 10.6% (3.5%) vs 6.1% (1.8%) vs 4.1% (1.9%), p<0.001), but the difference was not found in endothelium‐independent nitroglycerine‐mediated vasodilation (p = 0.159). Reduced numbers of colony‐forming units (CFU) of EPCs were noted in patients with CSX and CAD (normal vs CSX vs CAD: 41 (9) vs 30 (7) vs 14 (7) CFU/well, p<0.001). Levels of EPCs were shown to be associated with FMD (r = 0.557, p = 0.001) and high‐density lipoprotein (r = 0.339, p = 0.049). Also, attenuated fibronectin adhesion function of EPCs was found in patients with CSX and CAD compared with normal subjects (104 (12) vs 80 (20) vs 65 (13)/well, p<0.001).
This study clearly showed for the first time that compared with normal subjects, patients with CSX have decreased levels and adhesive function of circulating EPCs. These findings may explain the underlying mechanisms which contribute to the endothelial dysfunction and microvascular abnormalities observed in patients with CSX.
To identify the determinants of appropriate and inappropriate implantable cardioverter‐defibrillator (ICD) discharges in patients with hypertrophic cardiomyopathy (HCM).
Retrospective cohort study.
ICD clinic at an academic hospital.
61 patients with HCM who received ICDs for the primary or secondary prevention of sudden cardiac death (SCD).
(a) Analysis of appropriate and inappropriate ICD discharges; (b) predictors of ICD discharges.
Mean (SD) age at ICD insertion was 46 (18) years (range 10–79). Follow‐up time was 40 (27) months (range 7–151). Eight patients experienced an appropriate discharge, occurring 24.5 (13.6) months after ICD insertion. Appropriate ICD intervention was more common in the secondary (36%) than the primary (8%) prevention group (p = 0.02). Inappropriate ICD discharges occurred in 20 (33%) patients. Multivariate Cox regression analysis identified two significant predictors of inappropriate ICD discharges: (a) age <30 years at the time of ICD insertion (hazard ratio (HR) = 3.0 (95% CI 1.1 to 8.0; p = 0.03) and (b) history of atrial fibrillation (HR = 3.1 (95% CI 1.2 to 8.1; p = 0.02).
ICDs are effective in the prevention of SCD in HCM. However, there is a high incidence of inappropriate ICD discharges.
hypertrophic cardiomyopathy; implantable cardioverter‐defibrillator; sudden cardiac death; atrial fibrillation; survival
MDCT; acute myocardial infarction; minimal stenosis
Cigarette smoking (CS) promotes endothelial dysfunction and atherosclerosis in the vascular bed. The impact of smoking on atrial myocardium is not defined in humans.
To determine the effect of CS on the development of interstitial fibrosis in atrial myocardium.
95 patients (46 smokers and 49 non‐smokers) undergoing coronary artery bypass grafting (CABG).
Main outcome measures
Amount of atrial fibrosis, collagen I, III and IV expression pattern, and quantitative reverse transcriptase‐PCR. Occurrence of postoperative atrial fibrillation (AF).
In the study population, patient age correlated significantly with the amount of atrial fibrosis (r = 0.18; p<0.05). Nicotine misuse (pack years) was identified as the only factor related to atrial fibrosis in smokers (r = 0.311; p<0.05). The amount of fibrosis was higher in patients with postoperative AF (22.9% (6.2%) vs. 27.0% (8.2%); p<0.05). To show a causal relationship between CS and atrial fibrosis, atrial tissue slices from non‐smokers (n = 8) were cultured in the presence of nicotine base (185 and 740 nmol/l). Nicotine base induced mRNA expression of collagen III (up to 10‐fold) in a concentration‐dependent manner resembling the immunohistological collagen expression pattern observed in CS.
CS contributes to the development of atrial fibrosis via nicotine. Atrial fibrosis by itself has been shown to provide an arrhythmogenic substrate, which may increase the likelihood of the occurrence of atrial arrhythmias, including postoperative AF.
selection bias; consent; observational research
Methadone is prescribed to heroin addicts to decrease illicit opioid use. Prolongation of the QT interval in the ECG of patients with torsade de pointes (TdP) has been reported in methadone users. As heroin addicts sometimes faint while using illicit drugs, doctors might attribute too many episodes of syncope to illicit drug use and thereby underestimate the incidence of TdP in this special population, and the high mortality in this population may, in part, be caused by the proarrhythmic effect of methadone.
In this cross‐sectional study interview, ECGs and blood samples were collected in a population of adult heroin addicts treated with methadone or buprenorphine on a daily basis. Of the patients at the Drug Addiction Service in the municipal of Copenhagen, 450 (∼52%) were included. The QT interval was estimated from 12 lead ECGs. All participants were interviewed about any experience of syncope. The association between opioid dose and QT, and methadone dose and reporting of syncope was assessed using multivariate linear regression and logistic regression, respectively.
Methadone dose was associated with longer QT interval of 0.140 ms/mg (p = 0.002). No association between buprenorphine and QTc was found. Among the subjects treated with methadone, 28% men and 32% women had prolonged QTc interval. None of the subjects treated with buprenorphine had QTc interval >0.440s½. A 50 mg higher methadone dose was associated with a 1.2 (95% CI 1.1 to 1.4) times higher odds for syncope.
Methadone is associated with QT prolongation and higher reporting of syncope in a population of heroin addicts.
“Logic dictates that angiotensin converting enzyme inhibitors should remain the preferred drug across the entire spectrum of cardiometabolic disease”
angiotensin; antagonist; infarction; myocardial; receptor
Circulating endothelial progenitor cells (EPCs) are increased in conditions associated with ischaemia and can potentially support angiogenesis and vasculogenesis. EPC levels were also shown to predict outcome in patients with atherosclerotic vascular disease. We tested the hypothesis that circulating EPC can predict outcome in patients with congestive heart failure (CHF).
EPC–colony‐forming units were measured in the peripheral blood of 107 consecutive patients with CHF with New York Heart Association (NYHA) functional class II–IV. Serum levels of vascular endothelial growth factor (VEGF), N‐terminal pro‐B‐type natriuretic peptide (NT‐pro‐BNP) and high‐sensitivity C‐reactive protein (hsCRP) were also measured. End points were defined as CHF‐related hospital admissions and all‐cause mortality.
Age (p = 0.01), diabetes mellitus (p = 0.002) and EPC levels (p = 0.02) were found to be independent predictors of all‐cause mortality. EPC levels did not predict CHF‐related hospitalisations. EPC levels correlated positively with NYHA (p = 0.05, r = 0.19), but did not correlate with VEGF, NT‐pro‐BNP or hsCRP. EPC levels did not differ by the aetiology of CHF.
EPC levels are independent predictors of all‐cause mortality among patients with CHF.
Renin maintains blood pressure through vasoconstriction when there is inadequate salt to maintain volume. In populations where blood pressure is more often high than low, and vascular death more common than haemorrhage or dehydration, therapeutic reductions in renin secretion or response are valuable. Whether long‐term benefits are due entirely to blood pressure reduction remains unproved. The pathway can be blocked at its rate‐limiting step (β blockade or direct renin inhibition), the synthesis of the active product, angiotensin II, or at the receptor for angiotensin. Because renin and sodium are the two main factors in blood pressure control, and renin levels vary inversely with sodium load, blood pressure control requires a combination of natriuresis and blocking the consequential increase in renin activity. Being a large and stable molecule, renin is among the easiest and cheapest of hormone measurements. Understanding the simple biochemistry and physiology of renin permits optimal use of the drugs acting to raise or suppress this hormone.
electronic beam computed tomography; myocardial bridge
To determine the effect of new, persistent or reverted ischaemic ECG abnormalities at ages 50 and 70 years on the risk of subsequent cardiovascular disease.
Design, setting and participants
A prospective community‐based observational cohort of 50‐year‐old men in Sweden, followed for 32 years. 2322 men of age 50 years participated in 1970–3, and 1221 subjects were re‐examined at the age of 70 years.
Main outcome measures
Myocardial infarction (MI), cardiovascular mortality and overall mortality.
At 50 years of age, after adjusting for established conventional risk factors, T wave abnormalities, ST segment depression, major Q/QS pattern and ECG‐left ventricular hypertrophy were all found to be independent risk factors for the main outcome measures during the 32 years of follow‐up. When ECG variables were re‐measured at 70 years of age, they were still found to be independent risk factors for the mortality outcomes, but lost in significance for prediction of MI. Regarding mortality, it was twice as dangerous to have persistent T wave abnormalities (HR 4.63; 95% CI 2.18 to 9.83) or ST segment depression (HR 5.66; 95% CI 1.77 to 18.1), as with new T wave abnormalities (HR 2.20; 95% CI 1.48 to 3.29) or ST segment depression (HR 2.55; 95% CI 1.74 to 3.75), developing between ages 50 and 70 years. The addition of “ECG indicating ischaemia” significantly increased the predictive power of the Framingham score (p<0.001).
It is worthwhile to obtain serial ECGs for proper risk assessment, since persistent ST‐T abnormalities carried twice as high a risk for future mortality compared with new or reverted abnormalities.
chest pain; ECG changes; pericarditis
See articles on pages 1026 and 1081
cost–benefit analysis; hypertension; cardiovascular diseases; ACE inhibitors
coronary artery occlusion; ventricular remodelling
To evaluate the radiation‐dose‐reduction potential of automatic exposure control (AEC) in 16‐slice and 64‐slice multislice computed tomography (MSCT) of the coronary arteries (computed tomography angiography, CTA) in patients. The rapid growth in MSCT CTA emphasises the necessity of adjusting technique factors to reduce radiation dose exposure.
A retrospective data analysis was performed for 154 patients who had undergone MSCT CTA. Group 1 (n = 56) had undergone 16‐slice MSCT without AEC, and group 2 (n = 51), with AEC. In group 1, invasive coronary angiography (ICA) had been performed in addition. Group 3 (n = 47) had been examined using a 64‐slice scanner (with AEC, without ECG‐triggered tube current modulation).
In group 1, the mean (SD) effective dose (ED) for MSCT CTA was 9.76 (1.84) mSv and for ICA it was 2.6 (1.27) mSv. In group 2, the mean ED for MSCT CTA was 5.83 (1.73) mSv, which signifies a 42.8% dose reduction for CTA by the use of AEC. In comparison to ICA, MSCT CTA without AEC shows a 3.8‐fold increase in radiation dose, and the radiation dose of CTA with AEC was increased by a factor of 1.9. In group 3, the mean ED for MSCT CTA was 13.58 (2.80) mSV.
This is the first study to show the significant dose‐reduction potential (42.8%) of AEC in MSCT CTA in patients. This relatively new technique can be used to optimise the radiation dose levels in MSCT CTA.
This NICE technology appraisal guidance on cardiac resynchronisation therapy provides additional treatment options for some of the groups of people covered in the earlier guidance on implantable cardioverter defibrillators.
heart failure; cardiac resynchronisation therapy
The EUropean trial on Reduction Of cardiac events with Perindopril in stable coronary Artery disease (EUROPA) trial has recently reported.
To assess the cost effectiveness of perindopril in stable coronary heart disease in the UK.
Clinical and resource use data were taken from the EUROPA trial. Costs included drugs and hospitalisations. Health‐related quality of life values were taken from published sources. A cost‐effectiveness analysis is presented as a function of the risk of a primary event (non‐fatal myocardial infarction, cardiac arrest or cardiovascular death) in order to identify people for whom treatment offers greatest value for money.
The median incremental cost of perindopril for each quality‐adjusted life year (QALY) gained across the heterogeneous population of EUROPA was estimated as £9700 (interquartile range £6400–£14 200). Overall, 88% of the EUROPA population had an estimated cost per QALY below £20 000 and 97% below £30 000. For a threshold value of cost effectiveness of £30 000 per QALY gained, treatment of people representing the 25th, 50th (median) and 75th centiles of the cost effectiveness distribution for perindopril has a probability of 0.999, 0.99 and 0.93 of being cost effective, respectively. Cost effectiveness was strongly related to higher risk of a primary event under standard care.
Whether the use of perindopril can be considered cost effective depends on the threshold value of cost effectiveness of healthcare systems. For the large majority of patients included in EUROPA, the incremental cost per QALY gained was lower than the apparent threshold used by the National Institute for Health and Clinical Excellence in the UK.
cost–benefit analysis; hypertension; cardiovascular diseases
anatomy; anomaly; coronary artery disease; coronary arteries