Effect of acute changes in oxygen tension on flow-mediated dilation. Relation to cardiovascular risk

Objective. Oxygen-dependent changes in vascular diameters may be detrimental when the endothelium is dysfunctional. Design. Endothelial responsiveness was evaluated by brachial ultrasound and flow-mediated/nitroglycerin-mediated dilation (FMD/NMD). FMD/NMD was investigated in males with increased risk of cardiovascular disease (mean age 44±2 years, n =10) and matched controls without risk factors (44±2 years, n =10). FMD/NMD was assessed during normoxia (21% O₂, 79% N₂), while inhaling hypoxic gas (12.5% O₂, FMD_Hyp/NMD), and 100% O₂ supplementation (FMD_O2/NMD). In a second study we addressed the effect of lipid lowering. Twenty persons with cardiovascular risk (mean age 50±2 years) were treated with atorvastatin (80 mg/day) and FMD/NMD was measured during normoxia, hypoxia and oxygen supplementation before, after 1 day and 3 months. Results. Oxygen supplementation evoked vasoconstriction, while FMD_Hyp/NMD was reduced compared to FMD/NMD. Atorvastatin significantly lowered total cholesterol, LDL cholesterol, and ADMA after 1 day of treatment, while triglycerides, ApoB and hsCRP were lowered after 3 months. Atorvastatin did not change FMD/NMD irrespective of oxygen tension. Conclusion. Irrespective of risk factors or atorvastatin, hypoxia reduced endothelial vasodilation while oxygen supplementation evoked vasoconstriction.     

Thoracic aortic aneurysm repair. Direct hospital cost and Diagnosis Related Group reimbursement

Objective. The main objective of this study was to analyze direct hospital cost and to compare cost with existing DRG reimbursement for open repair of thoracic and thoraco-abdominal aortic disease. Study sample and methodology. Between January 2003 and September 2003, the cost of treatment for 24 surgical procedures on ascending aorta and arch, descending or thoraco-abdominal aortic disease were examined prospectively. Seven patients had urgent or emergency surgeries. Ten had sternotomies for disease of the ascending aorta and aortic arch; two had left thoracotomies and three thoraco-laparotomy incisions with procedures performed on x-corporeal circulation. Nine other patients had more distal thoraco-abdominal aortic operations with a clamp-and-sew technique. Micro-cost analysis was performed on each hospital stay, in addition overhead hospital costs were allocated to each procedure. Results. The patients were grouped by discharge diagnosis (ICD-10) and surgical procedure performed (NCSP) into Norwegian DRG code. Patient with surgery on ascending aorta & aortic arch were allocated to DRG 108 (n =9) or 483 (tracheostomy, n =1) while patient with surgery on descending or thoraco-abdominal aorta were allocated to DRG 108 (n =3), 110 (n =4), 111 (n =4) or 483 (tracheostomy, n =3). The mean EuroSCORE for patients with proximal aortic disease was 11 , and the length of stay was 5 days (range 3–8 days), spending 2 days (range 1–7 days) in thoracic intensive care unit. For patients with distal aortic disease the mean Euroscore was 7 , and the mean length of stay 10 days (range 4–23 days) with a mean 4 days (range 1–13 days) in intensive care unit. Eight patients developed medical problems requiring new surgical procedures or prolonged ICU stay. The average direct hospital cost for proximal aortic surgery was USD 15 877 (USD 1 =NOK 7.5) while the respective 100% DRG reimbursement including one patient needing a tracheostomy, was 19 803 USD. For patients with distal aortic disease, average direct hospital cost was 23 005 USD and DRG reimbursement including patients needing a tracheostomy was 31543 USD. Conclusion. Our results underscore previous findings that these patients are resource intensive. This study shows that Norwegian 100% DRG reimbursement did over-compensate observed total hospital costs in this cohort. Detailed analysis showed that this was due to the higher DRG reimbursement for patients needing prolonged ventilatory support. Thus the actual DRG reimbursement seems to be relevant to the tertiary hospital actual costs when these complicated patients are considered as a group. It remains however unclear whether this reimbursement is sufficient to support the scientific infrastructure for new knowledge and skills needed for the further refinement of treatment.     

99m Tc-Sestamibi SPECT is a Useful Technique for Viability Detection. Results of a Comparison with NH 3 /FDG PET

Objective - Assessment of myocardial viability by 99m Tc-Sestamibi Single Photon Emission Computerized Tomography (SPECT) has been suggested as a more readily available and cheaper alternative to Positron Emission Tomography (PET) with 13 N-ammonia (NH 3 ) and 18 F-fluoro-deoxy-glucose (FDG). We hypothesized that a semi-quantitative evaluation by SPECT could delineate myocardial viability with an acceptable concordance to PET. Design - Fifty patients (age 57 &#45 7 years; ejection fraction 28 &#45 8%), with ischemic cardiomyopathy, underwent SPECT and PET imaging in random order. Viability by SPECT was defined as a defect size <50% of the segment area, or a defect representing &#83 50% of the segment but with a mean activity &#83 50% of peak activity. PET viability was defined as a perfusion score >2 and FDG score &#104 2 (five-point scale, 0 = normal, 4 = absent activity). Results - By segmental comparison to PET, SPECT yielded a sensitivity and specificity of 87% and 82% for detection of viable myocardium. The positive and negative predictive values were 96% and 58%, respectively. Conclusion - In patients with severe ischemic cardiomyopathy 99m Tc-Sestamibi SPECT can delineate viable myocardium with an acceptable segmental concordance to NH 3 /FDG PET.     

ECG changes in patients with acute ethanol intoxication

Objectives. To assess how ethanol in potential lethal serum concentrations affects features of the ECG that may be associated with cardiac arrhythmias. Design. We included 84 patients, who were hospitalised with assumed acute ethanol intoxication. In the emergency room resting ECG was recorded and blood was collected for serum osmolality measurement used as a proxy for ethanol level. Thirty-two also had ECG recorded at discharge. Twenty-seven hospitalised patients without known alcohol ingestion served as controls. ECG segment durations were compared with controls and related to intoxication level. Results. In subjects with moderately elevated to high serum osmolality, the P wave and QTc intervals were prolonged compared with sober subjects. P wave, PR, QRS and QTc intervals were longer when the subjects had high blood ethanol levels (at admission) than at discharge (p-values: 0.0001, 0.0002, 0.010 and < 0.0001 for P wave, PR, QRS and QTc intervals. n = 32). Conclusions. Ethanol at high to very high blood concentration causes several changes in the ECG that might be associated with increased risk of arrhythmias.     

The NORwegian study on DIstrict treatment of ST-Elevation Myocardial Infarction (NORDISTEMI)

Objectives. Thrombolysis is the treatment of choice for patients with ST-elevation myocardial infarction (STEMI) living in rural areas with long transfer delays to percutaneous coronary intervention (PCI). This trial compares two different strategies following thrombolysis: to transfer all patients for immediate coronary angiography and intervention, or to manage the patients more conservatively. Design. The NORwegian study on DIstrict treatment of STEMI (NORDISTEMI) is an open, prospective, randomized controlled trial in patients with STEMI of less than 6 hours of duration and more than 90 minutes expected time delay to PCI. A total of 266 patients will receive full-dose thrombolysis, preferably prehospitally, and then be randomized to either strategy. Our primary endpoint is the one year combined incidence of death, reinfarction, stroke or new myocardial ischaemia. The study is registered with ClinicalTrials.gov, number NCT00161005. Results. By April 2006, 109 patients have been randomized. Thrombolysis has been given prehospitally to 52% of patients. The median transport distance from first medical contact to catheterization laboratory was 155 km (range 90–396 km). Results of the study are expected in 2008.

Trial registration: ClinicalTrials.gov identifier: NCT00161005.     

Inverse Association Between Birth Weight,Birth Length and Serum Total Cholesterol in Adulthood

Objectives - To investigate whether impaired fetal growth, measured by low birth weight and short birth length, is linked with raised levels of serum lipids and increased risk and mortality of coronary heart disease. Design - The association between birth length, birth weight, Ponderal Index and total serum cholesterol was examined in 545 Danish men and women aged 31 to 51 years who participated in the Ebeltoft Health Promotion Project in Denmark. Results - No associations were found in women. For men, a negative association was found between birth weight and serum total cholesterol, with a fall in mean serum total cholesterol from 6.03 mmol/l at birth weight below 3300 g to 5.64 mmol/l at birth weight above 4000. A similar association was found between birth length and serum cholesterol, with a mean value of 6.23 mmol/l at birth length below 51 cm and a mean value of 5.56 mmol/l at birth length above 54 cm. No associations were found for Ponderal Index. Between 3% and 8% of the variance in serum total cholesterol could be explained by the statistical models used in this study. Conclusion - Our findings support the hypothesis of a negative association between birth weight, birth length and elevated serum cholesterol in adult life, but only in men.     

Adventitial Myofibroblasts Play no Major Role in Neointima Formation After Angioplasty

Abstract

Objective—Myofibroblasts migrating from adventitia have been suggested to constitute a majority of neointimal cells after angioplasty. We sought to examine this hypothesis by use of smoothelin, which is a marker for the quiescent smooth muscle cell (SMC) phenotype while not expressed by myofibroblasts. Design—Balloon angioplasty was performed in left iliac arteries of 25 rabbits that were killed after 3-56 days. Arterial cross-sections were immunostained for (X-actin (general marker), smoothelin (quiescent SMC phenotype), and Ki-67 (proliferative phenotype).

Results—Adventitial cells became transiently actinpositive (myofibroblasts) but did not express smoothelin at any time point. In media, angioplasty induced transient proliferation and coinciding transient decrease in smoothelin expression. Neointimal cells, present 7 days after angioplasty, were initially proliferating and smoothelin-negative but changed to non-proliferating, smoothelin-positive cells after 56 days where 82 ± 10% of cells stained positive for smoothelin. This phenotypic modulation of medial and intimal cells began in media and moved gradually towards the lumen.

Conclusion—At late follow-up, the majority of intimal cells are smoothelin-positive indicating that adventitial myofibroblasts play no major role for neointima formation.     

Repeated image analyses improves accuracy in assessing arterial flow-mediated dilatation

Objectives. A high degree of variability has been reported regarding the ultrasound-based assessment of flow-mediated dilatation. We wanted to investigate the variability and find out how it might be reduced most efficiently. Design. Brachial artery flow-mediated dilatation was measured by high-resolution ultrasound in 22 healthy adults on two consecutive days. Two observers analysed all images twice. The total variance was split into variance components and estimated hierarchically using the method of restricted maximum likelihood. Results. The relative proportional contributions from intraobserver (residual), interobserver, interpatient and interday variance components, with percentage dilatation as outcome variable, were 0.41, 0.18, 0.25, and 0.15, respectively. Conclusions. The major source of variability when assessing flow-mediated dilatation was found to be intraobserver variability. The simplest way to reduce total variability is for the observer to average results from repeated image analyses. We suggest that three repetitions are sufficient. This will reduce the total variance by 30%.     

Poor maintenance of sinus rhythm after electrical cardioversion of patients with atrial fibrillation or flutter: a 5‐year follow‐up of 268 consecutive patients

Objective—To report long‐term results of direct current (DC)‐cardioversion in unselected patients with atrial fibrillation (AF) or flutter.

Design—The study was a retrospective 5‐year follow‐up of all patients undergoing DC‐cardioversion for AF or flutter at our institution between 1993 and 1997.

Results—Three hundred and eighty‐five DC‐cardioversions were performed in 268 patients. Two hundred and forty‐nine patients underwent cardioversion for the first time. Of these, 183 (74%) were converted to sinus rhythm. During the first month of follow‐up 105 (57%) relapsed into AF. Only 33 patients (13%) of the 249 patients scheduled for cardioversion remained in sinus rhythm after 1 year. In multivariate analysis arrhythmia duration was the only variable that was associated with successful cardioversion. Periprocedural complications occurred in 9.9% of the cardioversions.

Conclusion—In daily routine only a minority of patients will maintain sinus rhythm after DC‐cardioversion for AF or flutter. Also, DC‐cardioversion is not without risk. These observational data suggest a conservative approach to re‐establishment of sinus rhythm in patients with AF.     

Total hip arthroplasty in Denmark

Background The annual number of total hip arthroplasties (THA) has increased in Denmark over the past 15 years. There is, however, limited detailed data available on the incidence of THAs.

Methods We calculated the incidence rates (IR) of primary THA and revision in Denmark between 1996 and 2002 and estimated the demands for primary THA in Denmark until 2020. We used data from the Danish Hip Arthroplasty Registry, a nationwide and popula-tion-based clinical database, to identify patients who had undergone primary THA (n = 37 144) or revision arthroplasties (n = 6 446). Age and sex-specific data on the Danish population were obtained from the StatBank Denmark. All IRs were standardized according to two standards, i.e. the Danish population in 1996 and the European standard population (18 age groups). The future demands for primary THA were estimated using the age and sex-specific incidence of primary THA for 2002 as a reference, and taking into account the expected changes in the age distribution of the population and the trend in IRs seen in Denmark between 1996 and 2002.

Results The annual overall standardized IRs of primary THAs and revisions increased from 101 (95% confidence interval (CI): 97.6–104) to 134 (CI: 131–138) and from 19.2 (CI: 17.9–20.5) to 21.1 (CI: 19.8–22.4) per 100 000 inhabitants from 1996 to 2002, respectively (IRs adjusted to the Danish population in 1996). The IRs of primary THAs and revisions increased by 30% and 10% during this period. The relative increase in IRs of primary THAs was found to be similar in both women and men. The increase was higher among patients aged 50–59 years, however. Furthermore, a decrease in IRs was seen in patients who underwent primary THA due to rheumatoid arthritis. IRs of primary THAs have been estimated to increase by 22% in 2020 compared with 2002, based only on the expected changes in the age distribution of the population. However, assuming that the annual age and sex-independent increase in the IRs seen in the period 1996–2002 will continue, the IR of primary THA is estimated to increase by as much as 210% in 2020.

Interpretation The overall annual standardized IRs of primary THAs and revisions in Denmark increased during the period from 1996 to 2002. Moreover, the demands for THA procedures in the coming decades may exceed the current capacity due to the ageing population and a continued age and sex-independent increase in surgical activity.