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1.  Changing treatment patterns for coronary artery revascularization in Canada: the projected impact of drug eluting stents 
Background
To evaluate current treatment patterns for coronary artery revascularization in Canada and explore the potential impact of drug eluting stents (DES) on these treatment patterns.
Methods
Eleven cardiologists at multiple Canadian academic centers completed a questionnaire on coronary artery revascularization rates and treatment patterns.
Results
Participating physicians indicated slightly higher rates of PTCA, CABG, and stent implantation than reported in CCN publications. Participants estimated that 24% of all patients currently receiving bare metal stents (BMS) would receive DES in the first year following DES approval in Canada, although there was a large range of estimates around this value (5% to 65%). By the fifth year following DES approval, it was estimated that 85% of BMS patients would instead receive DES. Among diabetic patients, estimates ranged from 43% in the first year following approval to 91% in the fifth year. For all patients currently receiving CABG, mean use of DES instead was estimated at 12% in the first year to 42% at five years; rates among diabetic patients currently undergoing CABG were 17% in the first year to 49% in the fifth year.
Conclusions
These results suggest a continued increase in revascularization procedures in Canada. Based on the panel's responses, it is likely that a trend away from CABG towards PTCA will continue in Canada, and will be augmented by the availability of DES as a treatment option. The availability of DES as a treatment option in Canada may change the threshold at which revascularization procedures are considered.
doi:10.1186/1471-2261-4-23
PMCID: PMC544858  PMID: 15596004
2.  Survival of patients treated with intra-aortic balloon counterpulsation at a tertiary care center in Pakistan – patient characteristics and predictors of in-hospital mortality 
Background
Intra-aortic balloon counterpulsation (IABC) has an established role in the treatment of patients presenting with critical cardiac illnesses, including cardiogenic shock, refractory ischemia and for prophylaxis and treatment of complications of percutaneous coronary interventions (PCI). Patients requiring IABC represent a high-risk subset with an expected high mortality. There are virtually no data on usage patterns as well as outcomes of patients in the Indo-Pakistan subcontinent who require IABC. This is the first report on a sizeable experience with IABC from Pakistan.
Methods
Hospital charts of 95 patients (mean age 58.8 (± 10.4) years; 78.9% male) undergoing IABC between 2000–2002 were reviewed. Logistic regression was used to determine univariate and multivariate predictors of in-hospital mortality.
Results
The most frequent indications for IABC were cardiogenic shock (48.4%) and refractory ischemia (24.2%). Revascularization (surgical or PCI) was performed in 74 patients (77.9%). The overall in-hospital mortality rate was 34.7%. Univariate predictors of in-hospital mortality included (odds ratio [95% CI]) age (OR 1.06 [1.01–1.11] for every year increase in age); diabetes (OR 3.68 [1.51–8.92]) and cardiogenic shock at presentation (OR 4.85 [1.92–12.2]). Furthermore, prior CABG (OR 0.12 [0.04–0.34]), and in-hospital revascularization (OR 0.05 [0.01–0.189]) was protective against mortality. In the multivariate analysis, independent predictors of in-hospital mortality were age (OR 1.13 [1.05–1.22] for every year increase in age); diabetes (OR 6.35 [1.61–24.97]) and cardiogenic shock at presentation (OR 10.0 [2.33–42.95]). Again, revascularization during hospitalization (OR 0.02 [0.003–0.12]) conferred a protective effect. The overall complication rate was low (8.5%).
Conclusions
Patients requiring IABC represent a high-risk group with substantial in-hospital mortality. Despite this high mortality, over two-thirds of patients do leave the hospital alive, suggesting that IABC is a feasible therapeutic device, even in a developing country.
doi:10.1186/1471-2261-4-22
PMCID: PMC535904  PMID: 15574201
3.  Progression of coronary calcification in healthy postmenopausal women 
Background
Coronary artery calcium score incrementally improves coronary risk prediction beyond that provided by conventional risk factors. Limited information is available regarding rates of progression of coronary calcification in women, particularly those with baseline scores above zero. Further, determinants of progression of coronary artery calcification in women are not well understood. This study prospectively evaluated rates and determinants of progression of coronary artery calcium score in a group of healthy postmenopausal women.
Methods
We determined coronary calcium score by computed tomography and recorded demographic, lifestyle and health characteristics of 914 postmenopausal women, a subset of those enrolled in the Women's Health Initiative Observational Study. The 305 women with calcium score ≥10 Agatston units at baseline were invited for repeat scan. This analysis includes the 94 women who underwent second scans.
Results
Mean age of study participants was 65 ± 9 years (mean ± SD), body mass index was 26.1 ± 6.1 kg/m2, and baseline calcium score was 162 ± 220 Agatston units. Mean interval between scans was 3.3 ± 0.7 years. A wide range of changes in coronary calcium score was observed, from -53 to +452 Agatston units/year. Women with lower scores at baseline had smaller annual increases in absolute calcium score. Coronary calcium scores increased 11, 31 and 79 Agatston units/year among women with baseline calcium score in the lowest, middle and highest tertiles. In multivariate analysis, age was not an independent predictor of absolute change in coronary calcium score. Hydroxymethylglutaryl coenzyme A reductase inhibitor (statin) use at baseline was a negative predictor (p = 0.015), whereas baseline calcium score was a strong, positive predictor (p < 0.0001) of progression of coronary calcification.
Conclusion
Among postmenopausal women with coronary calcium score ≥ 10 Agatston units, rates of change of coronary calcium score varied widely. In multivariate analysis, statin use was a negative independent determinant, whereas baseline calcium score was a strong positive predictor of annual change in coronary calcium score.
doi:10.1186/1471-2261-4-21
PMCID: PMC535923  PMID: 15574196
4.  A common genetic factor underlies hypertension and other cardiovascular disorders 
Background
Certain conditions characterised by blood vessel occlusion or vascular spasm have been found to cluster together in epidemiological studies. However the biological causes for these associations remain controversial. This study used a classical twin design to examine whether these conditions are linked through shared environmental exposures or by a common underlying genetic propensity to vasospasm.
Methods
We investigated the association between hypertension, migraine, Raynaud's phenomenon and coronary artery disease in twins from a national register. Phenotype status was determined using a questionnaire and the genetic and environmental association between phenotypes was estimated through variance components analysis.
Results
Responses were obtained from 2,204 individuals comprising 525 monozygotic and 577 dizygotic pairs. There was a significant genetic contribution to all four traits with heritabilities ranging from 0.34 to 0.64. Multivariate model-fitting demonstrated that a single common genetic factor underlies the four conditions.
Conclusions
We have confirmed an association between hypertension, migraine, Raynaud's phenomenon and coronary artery disease, and shown that a single genetic factor underlies them. The demonstration of a shared genetic factor explains the association between them and adds weight to the theory of an inherited predisposition to vasospasm.
doi:10.1186/1471-2261-4-20
PMCID: PMC529445  PMID: 15518590
5.  Hospitalization for heart disease, stroke, and diabetes mellitus among Indian-born persons: a small area analysis 
Background
We set out to describe the risk of hospitalization from heart disease, stroke, and diabetes among persons born in India, all foreign-born persons, and U.S.-born persons residing in New York City.
Methods
We examined billing records of 1,083,817 persons hospitalized in New York City during the year 2000. The zip code of each patient's residence was linked to corresponding data from the 2000 U.S. Census to obtain covariates not present in the billing records. Using logistic models, we evaluated the risk of hospitalization for heart disease, stroke and diabetes by country of origin.
Results
After controlling for covariates, Indian-born persons are at similar risk of hospitalization for heart disease (RR = 1.02, 95% confidence interval 1.02, 1.03), stroke (RR = 1.00, 95% confidence interval, 0.99, 1.01), and diabetes mellitus (RR = 0.96 95% confidence interval 0.94, 0.97) as native-born persons. However, Indian-born persons are more likely to be hospitalized for these diseases than other foreign-born persons. For instance, the risk of hospitalization for heart disease among foreign-born persons is 0.70 (95% confidence interval 0.67, 0.72) and the risk of hospitalization for diabetes is 0.39 (95% confidence interval 0.37, 0.42) relative to native-born persons.
Conclusions
South Asians have considerably lower rates of hospitalization in New York than reported in countries with national health systems. Access may play a role. Clinicians working in immigrant settings should nonetheless maintain a higher vigilance for these conditions among Indian-born persons than among other foreign-born populations.
doi:10.1186/1471-2261-4-19
PMCID: PMC529471  PMID: 15509299
6.  The use of warfarin in veterans with atrial fibrillation 
Background
Warfarin therapy is effective for the prevention of stroke in patients with atrial fibrillation. However, warfarin therapy is underutilized even among ideal anticoagulation candidates. The purpose of this study was to examine the use of warfarin in both inpatients and outpatients with atrial fibrillation within a Veterans Affairs (VA) hospital system.
Methods
This retrospective medical record review included outpatients and inpatients with atrial fibrillation. The outpatient cohort included all patients seen in the outpatient clinics of the VA Connecticut Healthcare System during June 2000 with a diagnosis of atrial fibrillation. The inpatient cohort included all patients discharged from the VA Connecticut Healthcare System West Haven Medical Center with a diagnosis of atrial fibrillation during October 1999 – March 2000. The outcome measure was the rate of warfarin prescription in patients with atrial fibrillation.
Results
A total of 538 outpatients had a diagnosis of atrial fibrillation and 73 of these had a documented contraindication to anticoagulation. Among the 465 eligible outpatients, 455 (98%) were prescribed warfarin. For the inpatients, a total of 212 individual patients were discharged with a diagnosis of atrial fibrillation and 97 were not eligible for warfarin therapy. Among the 115 eligible inpatients, 106 (92%) were discharged on warfarin.
Conclusions
Ideal anticoagulation candidates with atrial fibrillation are being prescribed warfarin at very high rates within one VA system, in both the inpatient and outpatient settings; we found warfarin use within our VA was much higher than that observed for Medicare beneficiaries in our state.
doi:10.1186/1471-2261-4-18
PMCID: PMC526776  PMID: 15498102
Atrial fibrillation; warfarin; anticoagulation; preventive medicine; guideline adherence
7.  Effect of the G-308A polymorphism of the tumor necrosis factor (TNF)-α gene promoter site on plasma levels of TNF-α and C-reactive protein in smokers: a cross-sectional study 
Background
Plasma levels of tumor necrosis factor (TNF)-α and of C-reactive protein (CRP) are elevated in smokers. Previous studies failed to show an association between the G-308A polymorphism in the promoter region of the TNF-α gene and coronary artery disease (CAD). We investigated whether smoking would interact with the TNF-α G-308A polymorphism in determining plasma levels of TNF-α and CRP.
Methods
Study participants with a complete data set in terms of smoking and the TNF-α G-308A polymorphism were 300 middle-aged male and female industrial employees. After excluding 24 irregular smokers, analyses were performed on 198 "non-smokers" (life-long non-smokers or subjects who quit smoking >6 months ago) as compared to 78 "regular smokers" (subjects currently smoking >3 cigarettes/day). All subjects had a fasting morning blood draw to measure plasma levels of TNF-α and CRP by high-sensitive enzyme-linked immunosorbent assays.
Results
The cardiovascular risk factor adjusted analysis regressing log-transformed CRP levels against smoking status, genotype, and smoking-status-genotype interaction revealed a significant main effect for smoking status (F1,250 = 5.67, p = .018) but not for genotype (F1,250 = 0.33, p = .57). The interaction-term between genotype and smoking status was not significant (F1,250 = 0.09, p = .76). The fully adjusted model with plasma TNF-α failed to show significant main effects for smoking and genotype, as well as for the smoking-status-genotype interaction.
Conclusions
The findings suggest that the TNF-α G-308A polymorphism does not mediate the effect of smoking on plasma CRP levels. It remains to be seen whether other genetic polymorphisms along the inflammatory pathway may modulate vascular risk in smokers.
doi:10.1186/1471-2261-4-17
PMCID: PMC526204  PMID: 15485576
8.  Single nucleotide polymorphisms in the apolipoprotein B and low density lipoprotein receptor genes affect response to antihypertensive treatment 
Background
Dyslipidemia has been associated with hypertension. The present study explored if polymorphisms in genes encoding proteins in lipid metabolism could be used as predictors for the individual response to antihypertensive treatment.
Methods
Ten single nucleotide polymorphisms (SNP) in genes related to lipid metabolism were analysed by a microarray based minisequencing system in DNA samples from ninety-seven hypertensive subjects randomised to treatment with either 150 mg of the angiotensin II type 1 receptor blocker irbesartan or 50 mg of the β1-adrenergic receptor blocker atenolol for twelve weeks.
Results
The reduction in blood pressure was similar in both treatment groups. The SNP C711T in the apolipoprotein B gene was associated with the blood pressure response to irbesartan with an average reduction of 19 mmHg in the individuals carrying the C-allele, but not to atenolol. The C16730T polymorphism in the low density lipoprotein receptor gene predicted the change in systolic blood pressure in the atenolol group with an average reduction of 14 mmHg in the individuals carrying the C-allele.
Conclusions
Polymorphisms in genes encoding proteins in the lipid metabolism are associated with the response to antihypertensive treatment in a drug specific pattern. These results highlight the potential use of pharmacogenetics as a guide for individualised antihypertensive treatment, and also the role of lipids in blood pressure control.
doi:10.1186/1471-2261-4-16
PMCID: PMC524175  PMID: 15453913
Antihypertensive treatment; pharmacogenetics; lipids; minisequencing; genotyping
9.  Disparities in lipid management for African Americans and Caucasians with coronary artery disease: A national cross-sectional study 
Background
Individuals with coronary artery disease are at high risk for adverse health outcomes. This risk can be diminished by aggressive lipid management, but adherence to lipid management guidelines is far from ideal and substantial racial disparities in care have been reported. Lipid treatment and goal attainment information is not readily available for large patient populations seen in the fee-for-service setting. As a result, national programs to improve lipid management in this setting may focus on lipid testing as an indicator of lipid management. We describe the detection, treatment, and control of dyslipdemia for African Americans and Caucasians with coronary artery disease to evaluate whether public health programs focusing on lipid testing can eliminate racial disparities in lipid management.
Methods
Physicians and medical practices with high numbers of prescriptions for coronary artery disease medications were invited to participate in the Quality Assurance Program. Medical records were reviewed from a random sample of patients with coronary artery disease seen from 1995 through 1998. Data related to the detection, treatment, and control of dyslipidemia were abstracted from the medical record and evaluated in cross-sectional stratified and logistic regression analyses using generalized estimation equations.
Results
Data from the medical records of 1,046 African Americans and 22,077 Caucasians seen in outpatient medical practices in 23 states were analyzed. African-American patients were younger, more likely to be women and to have diabetes, heart failure, and hypertension. The low density lipoprotein cholesterol (LDL-C) testing rate for Caucasian men was over 1.4 times higher than that for African-American women and about 1.3 times higher than that for African-American men. Almost 60% of tested Caucasian men and less than half of tested African Americans were prescribed lipid-lowering drugs. Tested and treated Caucasian men had the highest LDL-C goal attainment (35%) and African-American men the lowest (21%).
Conclusions
Although increased lipid testing is clearly needed for African Americans, improvements in treatment and control are also necessary to eliminate racial disparities in lipid management. Disparities in treatment and goal attainment must be better understood and reflected in policy to improve the health of underserved populations.
doi:10.1186/1471-2261-4-15
PMCID: PMC516441  PMID: 15317654
10.  Outcome after acute myocardial infarction: a comparison of patients seen by cardiologists and general physicians 
Background
The management of acute myocardial infarction (AMI) has improved over the last 50 years with the more frequent use of effective medicines and procedures. The clinical benefit of the speciality of the attending physician is less clear. The United Kingdom National Service Framework for coronary heart disease (CHD) suggested that patients with CHD are likely to benefit from cardiological supervision. We set out to assess the effect of access to cardiologists on survival among AMI patients admitted in two UK hospitals.
Methods
The study was conducted in a university hospital and a district general hospital in England. Information was obtained on age, sex, ethnicity, Carstairs socioeconomic deprivation category derived from postcode of residence, comorbidity, distance from hospital and medication from all patients admitted with acute myocardial infarction in two acute trusts between July 1999 and June 2000. Record linkage to subsequent Hospital Episode Statistics and Registrar General's death records provided follow up information on procedures and mortality up to eighteen months after admission. Cox proportional hazard models were used to investigate the main hypothesis controlling for confounding. The main outcome measure was 18-month survival after myocardial infarction.
Results
Access to a cardiologist was univariately associated with improved survival (hazard ratio 0.16, 95% CI 0.10 to 0.25). This effect remained after controlling for the effect of patient characteristics (hazard ratio 0.22, 95% CI 0.14 to 0.25). The effect disappeared after controlling for access to effective medication (hazard ratio 0.70, 95% CI 0.33 to 1.46).
Conclusions
Access to a cardiologist is associated with better survival compared to no access to a cardiologist among a cohort of patients already admitted with AMI. This effect is mainly due to the more frequent use of effective medicines by the group referred to cardiologists. Hospitals may improve survival by improving access to effective medicines and by coordinating care between cardiologists and general physicians.
doi:10.1186/1471-2261-4-14
PMCID: PMC512285  PMID: 15298699
11.  Arrhythmia-provoking factors and symptoms at the onset of paroxysmal atrial fibrillation: A study based on interviews with 100 patients seeking hospital assistance 
Background
Surprisingly little information on symptoms of paroxysmal atrial fibrillation is available in scientific literature. Using questionnaires, we have analyzed the symptoms associated with arrhythmia attacks.
Methods
One hundred randomly-selected patients with idiopathic paroxysmal atrial fibrillation filled in a structured questionnaire.
Results
Psychic stress was the most common factor triggering arrhythmia (54%), followed by physical exertion (42%), tiredness (41%) coffee (25%) and infections (22%). Thirty-four patients cited alcohol, 26 in the form of red wine, 16 as white wine and 26 as spirits. Among these 34, red wine and spirits produced significantly more episodes of arrhythmia than white wine (p = 0.01 and 0.005 respectively).
Symptoms during arrhythmia were palpitations while exerting (88%), reduced physical ability (87%), palpitations at rest (86%), shortage of breath during exertion (70%) and anxiety (59%). Significant differences between sexes were noted regarding swollen legs (women 21%, men 6%, p = 0.027), nausea (women 36%, men 13%, p = 0.012) and anxiety (females 79%, males 51%, p = 0.014).
Conclusion
Psychic stress was the commonest triggering factor in hospitalized patients with paroxysmal atrial fibrillation. Red wine and spirits were more proarrhythmic than white wine. Symptoms in women in connection with attacks of arrhythmia vary somewhat from those in men.
doi:10.1186/1471-2261-4-13
PMCID: PMC514544  PMID: 15291967
Paroxysmal atrial arrhythmia; triggering factors; symptoms; alcohol.
12.  A randomised controlled trial and cost effectiveness study of systematic screening (targeted and total population screening) versus routine practice for the detection of atrial fibrillation in the over 65s: (SAFE) [ISRCTN19633732] 
Background
Atrial fibrillation (AF) has been recognised as an important independent risk factor for thromboembolic disease, particularly stroke for which it provides a five-fold increase in risk. This study aimed to determine the baseline prevalence and the incidence of AF based on a variety of screening strategies and in doing so to evaluate the incremental cost-effectiveness of different screening strategies, including targeted or whole population screening, compared with routine clinical practice, for detection of AF in people aged 65 and over. The value of clinical assessment and echocardiography as additional methods of risk stratification for thromboembolic disease in patients with AF were also evaluated.
Methods
The study design was a multi-centre randomised controlled trial with a study population of patients aged 65 and over from 50 General Practices in the West Midlands. These purposefully selected general practices were randomly allocated to 25 intervention practices and 25 control practices. GPs and practice nurses within the intervention practices received education on the importance of AF detection and ECG interpretation. Patients in the intervention practices were randomly allocated to systematic (n = 5000) or opportunistic screening (n = 5000). Prospective identification of pre-existing risk factors for AF within the screened population enabled comparison between high risk targeted screening and total population screening. AF detection rates in systematically screened and opportunistically screened populations in the intervention practices were compared to AF detection rate in 5,000 patients in the control practices.
doi:10.1186/1471-2261-4-12
PMCID: PMC509245  PMID: 15283871
13.  Treatment of mechanically-induced vasospasm of the carotid artery in a primate using intra-arterial verapamil: a technical case report 
Background
Despite improvements in the safety and efficacy of endovascular procedures, considerable morbidity may still be attributed to vasospasm. Vasospasm has proven amenable to pharmacological intervention such as nitrates, intravenous calcium channel blockers (CCBs), and intra-arterial papaverine, particularly in small vessels. However, few studies have focused on medium to large vessel spasm. Here we report the use of an intra-arterial CCB, verapamil, to treat flow-limiting mechanically-induced spasm of the common carotid artery (CCA) in a primate. We believe this to be the first such report of its kind.
Case presentation
As part of a study assessing the placement feasibility and safety of a catheter capable of delivering intra-arterial cerebroprotective therapy, a female 16 kg baboon prophylaxed with intravenous nitroglycerin underwent transfemoral CCA catheterization with a metallic 6-Fr catheter without signs of acute spasm. The protocol dictated that the catheter remain in the CCA for 12 hours. Upon completion of the protocol, arteriography revealed a marked decrease in CCA size (mean cross-sectional area reduction = 31.6 ± 1.9%) localized along the catheter length. Intra-arterial verapamil (2 mg/2cc) was injected and arteriography was performed 10 minutes later. Image analysis at 6 points along the CCA revealed a 21.0 ± 1.7% mean increase in vessel diameter along the length of the catheter corresponding to a 46.7 ± 4.0% mean increase in cross-sectional area. Mean systemic blood pressure did not deviate more than 10 mm Hg during the procedure.
Conclusions
Intraluminal CCBs like verapamil may constitute an effective endovascular treatment for mechanically-induced vasospasm in medium to large-sized vessels such as the CCA.
doi:10.1186/1471-2261-4-11
PMCID: PMC499548  PMID: 15265235
14.  Resting tachycardia, a warning sign in anorexia nervosa: case report 
Background
Among psychiatric disorders, anorexia nervosa has the highest mortality rate. During an exacerbation of this illness, patients frequently present with nonspecific symptoms. Upon hospitalization, anorexia nervosa patients are often markedly bradycardic, which may be an adaptive response to progressive weight loss and negative energy balance. When anorexia nervosa patients manifest tachycardia, even heart rates in the 80–90 bpm range, a supervening acute illness should be suspected.
Case presentation
A 52-year old woman with longstanding anorexia nervosa was hospitalized due to progressive leg pain, weakness, and fatigue accompanied by marked weight loss. On physical examination she was cachectic but in no apparent distress. She had fine lanugo-type hair over her face and arms with an erythematous rash noted on her palms and left lower extremity. Her blood pressure was 96/50 mm Hg and resting heart rate was 106 bpm though she appeared euvolemic. Laboratory tests revealed anemia, mild leukocytosis, and hypoalbuminemia. She was initially treated with enteral feedings for an exacerbation of anorexia nervosa, but increasing leukocytosis without fever and worsening left leg pain prompted the diagnosis of an indolent left lower extremity cellulitis. With antibiotic therapy her heart rate decreased to 45 bpm despite minimal restoration of body weight.
Conclusions
Bradycardia is a characteristic feature of anorexia nervosa particularly with significant weight loss. When anorexia nervosa patients present with nonspecific symptoms, resting tachycardia should prompt a search for potentially life-threatening conditions.
doi:10.1186/1471-2261-4-10
PMCID: PMC503388  PMID: 15257758
anorexia nervosa; bradycardia; tachycardia; malnutrition
15.  A simulation study of the reaction of human heart to biphasic electrical shocks 
Background
This article presents a study, which examines the effects of biphasic electrical shocks on human ventricular tissue. The effects of this type of shock are not yet fully understood. Animal experiments showed the superiority of biphasic shocks over monophasic ones in defibrillation. A mathematical computer simulation can increase the knowledge of human heart behavior.
Methods
The research presented in this article was done with different models representing a three-dimensional wedge of ventricular myocardium. The electrophysiology was described with Priebe-Beuckelmann model. The realistic fiber twist, which is specific to human myocardium was included. Planar electrodes were placed at the ends of the longest side of the virtual cardiac wedge, in a bath medium. They were sources of electrical shocks, which varied in magnitude from 0.1 to 5 V. In a second arrangement ring electrodes were placed directly on myocardium for getting a better view on secondary electrical sources. The electrical reaction of the tissue was generated with a bidomain model.
Results
The reaction of the tissue to the electrical shock was specific to the initial imposed characteristics. Depolarization appeared in the first 5 ms in different locations. A further study of the cardiac tissue behavior revealed, which features influence the response of the considered muscle. It was shown that the time needed by the tissue to be totally depolarized is much shorter when a biphasic shock is applied. Each simulation ended only after complete repolarization was achieved. This created the possibility of gathering information from all states corresponding to one cycle of the cardiac rhythm.
Conclusions
The differences between the reaction of the homogeneous tissue and a tissue, which contains cleavage planes, reveals important aspects of superiority of biphasic pulses. ...
doi:10.1186/1471-2261-4-9
PMCID: PMC449708  PMID: 15212691
16.  Non-invasive evaluation of ventricular refractoriness and its dispersion during ventricular fibrillation in patients with implantable cardioverter defibrillator 
Background
Local ventricular refractoriness and its dispersion during ventricular fibrillation (VF) have not been well evaluated, due to methodological difficulties.
Methods
In this study, a non-invasive method was used in evaluation of local ventricular refractoriness and its dispersion during induced VF in 11 patients with VF and/or polymorphic ventricular tachycardia (VT) who have implanted an implantable cardioverter defibrillator (ICD). Bipolar electrograms were simultaneously recorded from the lower oesophagus behind the posterior left ventricle (LV) via an oesophageal electrode and from the right ventricular (RV) apex via telemetry from the implanted ICD. VF intervals were used as an estimate of the ventricular effective refractory period (VERP). In 6 patients, VERP was also measured during sinus rhythm at the RV apex and outflow tract (RVOT) using conventional extra stimulus technique.
Results
Electrograms recorded from the RV apex and the lower esophagus behind the posterior LV manifested distinct differences of the local ventricular activities. The estimated VERPs during induced VF in the RV apex were significantly shorter than that measured during sinus rhythm using extra stimulus technique. The maximal dispersion of the estimated VERPs during induced VF between the RV apex and posterior LV was that of 10 percentile VF interval (40 ± 27 ms), that is markedly greater than the previously reported dispersion of ventricular repolarization without malignant ventricular arrhythmias (30–36 ms).
Conclusions
This study verified the feasibility of recording local ventricular activities via oesophageal electrode and via telemetry from an implanted ICD and the usefulness of VF intervals obtained using this non-invasive technique in evaluation of the dispersion of refractoriness in patients with ICD implantation.
doi:10.1186/1471-2261-4-8
PMCID: PMC425578  PMID: 15186504
17.  The association between air travel and deep vein thrombosis: Systematic review & meta-analysis 
Background
Air travel has been linked with the development of deep vein thrombosis (DVT) since the 1950s with a number of plausible explanations put forward for causation. No systematic review of the literature exploring this association has previously been published.
Methods
A comprehensive search was undertaken (Data bases searched were: MEDLINE, EMBASE, Cochrane Library) for studies that estimated both the incidence and the risk of DVT in air travellers relative to non-air travellers.
Results
In total 254 studies were identified but only six incidence studies and four risk studies met inclusion criteria justifying their use in a systematic review. Incidence of symptomatic DVT ranged from (0%) in one study to (0.28%) which was reported in pilots over ten years. The incidence of asymptomatic DVT ranged from (0%) to (10.34%). Pooled odds ratios for the two case control studies examining the risk of DVT following air travel were 1.11 (95% CI: 0.64–1.94). Pooled odds ratios for all models of travel including two studies of prolonged air travel (more than three hours) were 1.70 (95% CI: 0.89–3.22).
Conclusion
We found no definitive evidence that prolonged (more than 3-hours) travel including air travel, increases the risk of DVT. There is evidence to suggest that flights of eight hours or more increase the risk of DVT if additional risk factors exist.
doi:10.1186/1471-2261-4-7
PMCID: PMC434500  PMID: 15151705
18.  Signaling of angiotensin II-induced vascular protein synthesis in conduit and resistance arteries in vivo 
Background
From in vitro studies, it has become clear that several signaling cascades are involved in angiotensin II-induced cellular hypertrophy. The aim of the present study was to determine some of the signaling pathways mediating angiotensin II (Ang II)-induced protein synthesis in vivo in large and small arteries.
Methods
Newly synthesized proteins were labeled during 4 hours with tritiated leucine in conscious control animals, or animals infused for 24 hours with angiotensin II (400 ng/kg/min). Hemodynamic parameters were measure simultaneously. Pharmacological agents affecting signaling cascades were injected 5 hours before the end of Ang II infusion.
Results
Angiotensin II nearly doubled the protein synthesis rate in the aorta and small mesenteric arteries, without affecting arterial pressure. The AT1 receptor antagonist Irbesartan antagonized the actions of Ang II. The Ang II-induced protein synthesis was associated with increased extracellular signal-regulated kinases (ERK)1/2 phosphorylation in aortic, but not in mesenteric vessels. Systemic administration of PD98059, an inhibitor of the ERK-1/2 pathway, produced a significant reduction of protein synthesis rate in the aorta, and only a modest decrease in mesenteric arteries. Rapamycin, which influences protein synthesis by alternative signaling, had a significant effect in both vessel types. Rapamycin and PD98059 did not alter basal protein synthesis and had minimal effects on arterial pressure.
Conclusion
ERK1/2 and rapamycin-sensitive pathways are involved in pressure-independent angiotensin II-induced vascular protein synthesis in vivo. However, their relative contribution may vary depending on the nature of the artery under investigation.
doi:10.1186/1471-2261-4-6
PMCID: PMC419351  PMID: 15134586
Remodeling; Resistance arteries; Conduit arteries; Rapamycin; ERK-1/2
19.  A randomized trial to assess the impact of an antithrombotic decision aid in patients with nonvalvular atrial fibrillation: the DAAFI trial protocol [ISRCTN14429643] 
Background
Decision aids are often advocated as a means to assist patient and health care provider decision making when faced with complicated treatment or screening decisions. Despite an exponential growth in the availability of decision aids in recent years, their impact on long-term treatment decisions and patient adherence is uncertain due to a paucity of rigorous studies. The choice of antithrombotic therapy for nonvalvular atrial fibrillation (NVAF) is one condition for which a trade-off exists between the potential risks and benefits of competing therapies, and the need to involve patients in decision making has been clearly identified. This study will evaluate whether an evidence-based patient decision aid for patients with NVAF can improve the appropriateness of antithrombotic therapy use by patients and their family physicians.
Design
A multi-center, two-armed cluster randomized trial based in community family practices in which patients with NVAF will be randomized to decision aid or usual care. Patients will receive one of four decision aids depending on their baseline stroke risk. The primary outcome is the provision of "appropriate antithrombotic therapy" at 3 months to study participants (appropriateness defined as per the 2001 American College of Chest Physicians recommendations for NVAF). In addition, the impact of this decision aid on patient knowledge, decisional conflict, well-being, and adherence will be assessed after 3 months, 6 months, and 12 months.
doi:10.1186/1471-2261-4-5
PMCID: PMC419350  PMID: 15128463
20.  The influence of statins on the free intracellular calcium concentration in human umbilical vein endothelial cells 
Background
Statins are cholesterol-lowering drugs that are widely used to reduce the risk of cardiac infarction. Their beneficial clinical effects, however, are not restricted to their influence on cholesterol production. As several studies have shown that they have a potency of relaxing blood vessels.
Methods
We measured the effects of statins on the intracellular free calcium concentration ([Ca2+]i) in human umbilical vein endothelial cells (HUVEC) after acute application and 24-h-preincubation of statins.
Results
Incubation of the cells for 24 h with cerivastatin or fluvastatin significantly increased the resting [Ca2+]i. For cerivastatin this effect manifested at a concentration of 1 μM. Increase of resting [Ca2+]i in the presence of cerivastatin also occurred when the nitric oxide synthase was inhibited. Transient Ca2+ release induced by histamine was not affected.
Conclusions
The increase of resting [Ca2+]i after incubation with cerivastatin or fluvastatin may provide an explanation for the direct effects of statins on the endothelial-dependent vasodilatation and restoration of endothelial activity in vivo.
doi:10.1186/1471-2261-4-4
PMCID: PMC419349  PMID: 15125784
Endothelium; Free Intracelluar Calcium; Nitric Oxide; Hydroxymethylglutaryl CoA Reductase Inhibitors; Arteriosclerosis.
21.  Ross operation in children and young adults: the Alder Hey case series 
Background
The ideal prosthesis for aortic valve replacement in children and young adults has not been found yet. In recent years there has been a renewed interest in the replacement of aortic valve with the pulmonary autograft owing to its advantages of lack of anticoagulation, potential for growth and excellent haemodynamic performance. The purpose of this study was to review our institutional experience at Alder Hey hospital with the Ross procedure in children and young adults.
Methods
From November 1996 to September 2003, 38 patients (mean age, 13.1 ± 5.7 years) underwent the Ross procedure for various aortic valve diseases using the root replacement technique. Clinical and echocardiographic follow-up was performed early (within 30 days), 3 to 6 months, and yearly after surgery. Medical records of all patients were reviewed retrospectively.
Results
There was 1 perioperative death. The patients were followed-up for a median interval of 36 months and up to 7 years. One patient died 3 years after surgery secondary to ventricular arrhythmia with overall mortality of 5.3%. Actuarial survival at 7 years was 94 ± 2.5% and there was 100% freedom from reoperation for autograft valve dysfunction or any other cause. Balloon dilatation was required in 2 patients for pulmonary homograft stenosis. The haemodynamics at the latest follow-up were also similar to those at the time of discharge after surgery. There was no progression in the degree of aortic regurgitation for 11 patients with trivial and 3 with mild regurgitation.
Conclusion
Our experience demonstrates that Ross operation is an attractive option for aortic valve replacement in children and young adults. Not only can the operation be accomplished with a low operative risk but the valve function stays normal over a long period of time with minimal alteration in lifestyle and no need for repeated operations to replace the valve as a result of somatic growth of the children.
doi:10.1186/1471-2261-4-3
PMCID: PMC416475  PMID: 15096281
Ross procedure; aortic valve disease; pulmonary autograft; aortic valve replacement; paediatric cardiac surgery
22.  Relationship between blood pressure measurements recorded on patients' charts in family physicians' offices and subsequent 24 hour ambulatory blood pressure monitoring 
Background
In most western countries 20% of adults have hypertension. Reports in the literature suggest that from 31 to 86% of treated patients are not at recommended target levels. However it is important to consider how we are determining whether targets are unmet and the degree to which they are unmet. Our underlying hypothesis is that white coat effect is partially responsible for the reported low rates of control of hypertension by primary care practitioners.
Methods
The study population consists of 1142 patients who are being assessed for enrolment in two community-based randomized controlled trials. Patients must have essential hypertension, be on antihypertensive medication, and must not have met their blood pressure targets. We are reporting on the proportion of patients who have not achieved target, and the degree to which they have not achieved their target. We also report on the mean daytime blood pressures on 24 hour ABPM and compare these to mean blood pressures found on the patients' charts.
Results
We identified 3284 patient charts of patients with hypertension. Of these, 1142 were determined to be "out of control" (did not achieve target) and 436 agreed to undergo 24 hour ABPM for final determination of eligibility. Overwhelmingly (95.8% of the time) it was the systolic blood pressure that was not under control. However, most of the patients who had not achieved target according to our criteria were within 10 mmHg of the recommended targets. Isolated systolic blood pressure was the best predictor of elevated mean daytime blood pressure on 24 hour ABPM.
Conclusions
At least 35% of patients had not achieved target blood pressure levels and this is primarily due to lack of control of systolic blood pressure. The best predictor of continuing hypertension on 24 hour ABPM was the mean systolic blood pressure on the patients chart. However, only 69% of patients who were uncontrolled according blood pressures recorded in the chart were uncontrolled according to 24 hour ABPM criteria. This suggests that the white coat effect makes blood pressure measurements in the doctor's offices, at least as currently done, not sufficiently accurate for determining treatment endpoint.
doi:10.1186/1471-2261-4-2
PMCID: PMC400734  PMID: 15050033
23.  Reversibility of stress-echo induced ST-segment depression by long-term oral n-3 PUFA supplementation in subjects with chest pain syndrome, normal wall motion at stress-echo and normal coronary angiogram 
Background
Normal coronary arteries may coexist with abnormal coronary and systemic endothelial function in patients with chest pain. Recent work by the renowned Pisa echo-group elegantly suggests that isolated ST-segment depression during stress-echo (SE) can be used as a marker of coronary endothelial dysfunction, in the absence of stress-inducible wall motion abnormalities and in the absence of angiographically-significant coronary artery disease (CAD). The long chain n-3 polyunsaturated fatty acids (PUFAs) have been reported to possess several properties that may positively influence vascular function. The present study's hypothesis is that a 4 month-course of oral supplementation with n-3 PUFAs can reverse endothelial dysfunction.
Methods
Subjects were selected on the basis of the following criteria: 1) reported chest pain syndrome, 2) significant ST-segment depression during an otherwise normal SE, 3) absence of angiographically-significant CAD. Subjects underwent a 4-month course of oral supplementation with commercially available n-3 PUFA, 1 g once a day. Normalization of endothelial dysfunction was defined, at the end of the supplementation period, by the absence of significant ST-segment depression during repeat SE. We tested the aforementioned hypothesis in a very small series of consecutive subjects, with the intent to produce a hypothesis-generating study.
Results
Seven out of the total nine subjects enrolled (77.8%) had normal ST-segment during repeat SE performed after the 4 month course of therapy.
Conclusions
A striking rate of reversion of SE-induced ST-segment depression after oral n-3 PUFAs suggests reversion of coronary endothelial dysfunction; nonetheless these data need to be validated in larger, placebo-controlled studies.
doi:10.1186/1471-2261-4-1
PMCID: PMC387825  PMID: 15038833
echocardiography; endothelium; microcirculation; stress; vasodilation; ST segment depression; n-3 PUFA

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