Showing papers in "Heart in 2003"

Drug induced QT prolongation and torsades de pointes

Abstract: In 1966, Francois Dessertenne described a specific electrocardiographic form of polymorphic ventricular tachycardia, which he termed “torsades de pointes” (TdP).w1 w2 The word “torsades” refers to an ornamental motif imitating twisted hairs or threads as seen on classical architectural columns, and “pointes” referred to points or peaks.w1 w2 In the seminal article, Dessertenne made no attempt to suggest the mechanism of TdP and, until recently, there has been considerable conjecture as to the pathophysiology of this arrhythmia. Since the original work by Dessertenne, it has been well recognised that many conditions may cause prolonged or abnormal repolarisation (that is, QT interval prolongation and/or abnormal T or T/U wave morphology), which is associated with TdP. If TdP is rapid or prolonged, it can lead to ventricular fibrillation and sudden cardiac death (fig 1). Essentially, TdP may be caused by either congenital or acquired long QT syndrome (LQTS). In recent years, there has been considerable renewed interest in the assessment and understanding of ventricular repolarisation and TdP. There are several reasons for this. Firstly, the cloning of cardiac ion channels has improved the understanding of the role of ionic channels in mediating cardiac repolarisation, the pathophysiological mechanism of LQTS (congenital and acquired forms), and the pathogenesis of TdP. Secondly, modern molecular techniques have unravelled the mutations in genes encoding cardiac ion channels that cause long QT syndrome, although the genetic defects in about 50% of patients are still unknown. Thirdly, there has been considerable enthusiasm for the development and use of class III antiarrhythmic drugs, which prolong repolarisation and cardiac refractoriness. Unfortunately, drugs that alter repolarisation have now been recognised to increase the propensity for TdP. Finally, an increasing number of drugs, especially non-cardiac drugs, have been recognised to delay cardiac repolarisation and to share the ability with class III …

Biocorrosion of magnesium alloys: a new principle in cardiovascular implant technology?

Abstract: Objectives: To develop and test a new concept of the degradation kinetics of newly developed coronary stents consisting of magnesium alloys. Methods: Design of a coronary stent prototype consisting of the non-commercial magnesium based alloy AE21 (containing 2% aluminium and 1% rare earths) with an expected 50% loss of mass within six months. Eleven domestic pigs underwent coronary implantation of 20 stents (overstretch injury). Results: No stent caused major problems during implantation or showed signs of initial breakage in the histological evaluation. There were no thromboembolic events. Quantitative angiography at follow up showed a significant (p < 0.01) 40% loss of perfused lumen diameter between days 10 and 35, corresponding to neointima formation seen on histological analysis, and a 25% re-enlargement (p < 0.05) between days 35 and 56 caused by vascular remodelling (based on intravascular ultrasound) resulting from the loss of mechanical integrity of the stent. Inflammation (p < 0.001) and neointimal plaque area (p < 0.05) depended significantly on injury score. Planimetric degradation correlated with time (r = 0.67, p < 0.01). Conclusion: Vascular implants consisting of magnesium alloy degradable by biocorrosion seem to be a realistic alternative to permanent implants.

High prevalence of left ventricular systolic and diastolic asynchrony in patients with congestive heart failure and normal QRS duration

Abstract: Objective: To study the possible occurrence of left ventricular (LV) systolic and diastolic asynchrony in patients with systolic heart failure (HF) and narrow QRS complexes. Design: Prospective study. Setting: University teaching hospital. Patients: 200 subjects were studied by echocardiography. 67 patients had HF and narrow QRS complexes (≤ 120 ms), 45 patients had HF and wide QRS complexes (> 120 ms), and 88 served as normal controls. Interventions: Echocardiography with tissue Doppler imaging was performed using a six basal, six mid-segmental model. Main outcome measures: Severity and prevalence of systolic and diastolic asynchrony, as assessed by the maximal difference in time to peak myocardial systolic contraction (T S ) and early diastolic relaxation (T E ), and the standard deviation of T S (T S -SD) and of T E (T E -SD) of the 12 LV segments. Results: The mean (SD) maximal difference in T S (controls 53 (23) ms v narrow QRS 107 (54) ms v wide QRS 130 (51) ms, both p v controls) and in T S -SD (controls 17.0 (7.8) ms v narrow QRS 33.8 (16.9) ms v wide QRS 42.0 (16.5) ms, both p v controls) was prolonged in the narrow QRS group compared with normal controls. Similarly, the maximal difference in T E (controls 59 (19) ms v narrow QRS 104 (71) ms v wide QRS 148 (87) ms, both p v controls) and in T E -SD (controls 18.5 (5.8) ms v narrow QRS 33.3 (27.7) ms v wide QRS 48.6 (30.2) ms, both p v controls) was prolonged in the narrow QRS group. The prevalence of systolic and diastolic asynchrony was 51% and 46%, respectively, in the narrow QRS group, and 73% and 69%, respectively, in the wide QRS group. Stepwise multiple regression analysis showed that a low mean myocardial systolic velocity from the six basal LV segments and a large LV end systolic diameter were independent predictors of systolic asynchrony, while a low mean myocardial early diastolic velocity and QRS complex duration were independent predictors of diastolic asynchrony. Conclusions: LV systolic and diastolic mechanical asynchrony is common in patients with HF with narrow QRS complexes. As QRS complex duration is not a determinant of systolic asynchrony, it implies that assessment of intraventricular synchronicity is probably more important than QRS duration in considering cardiac resynchronisation treatment.

Apical ballooning of the left ventricle: first series in white patients

Abstract: Background: A cardiac syndrome of “apical ballooning” was recently described, consisting of an acute onset of transient extensive akinesia of the apical and mid portions of the left ventricle, without significant stenosis on the coronary angiogram, accompanied by chest symptoms, ECG changes, and a limited release of cardiac markers disproportionate to the extent of akinesia. Until now, this syndrome has been reported only in Japanese patients. Objective: To describe 13 white patients who presented with this syndrome over the previous four years. Results: All but one of the patients were women with a mean age of 62 years. Eight of them presented with chest pain, of whom six had cardiogenic shock. In nine patients a triggering factor was identified: emotional stress in three, trauma in one, pneumonia in one, asthma crisis in one, exercise in two, and cerebrovascular accident in one. In all patients left ventriculography showed very extensive apical akinesia (“apical ballooning”) in the absence of a significant coronary artery stenosis, not corresponding with the perfusion territory of a single epicardial coronary artery. Mean maximal creatine kinase MB and troponin rise were 27.4 μg/l (range 5.2–115.7 μg/l, median 16.6 μg/l) and 18.7 μg/l (range 2.0–97.6 μg/l, median 14.5 μg/l), respectively. Six patients were treated with intra-aortic balloon counterpulsation. One patient died of multiple organ failure. On necropsy, no myocardial infarction was found. In the 12 survivors, left ventricular systolic function recovered completely within three weeks. Conclusions: This is the first series of “apical ballooning” to be reported in white patients. Despite dramatic initial presentation, left ventricle function recovered completely within three weeks in the survivors.

Erectile dysfunction and the cardiovascular patient: endothelial dysfunction is the common denominator

Abstract: Erectile dysfunction (ED) is a common condition and studies predict that it will become even more common in the future. There is increasing evidence to suggest that it is predominantly a vascular disease and may even be a marker for occult cardiovascular disease. The common pathological process is at the level of the endothelium, and cardiovascular risk factor control may be the key to preventing ED. Many men with established cardiovascular disease have ED. Specific guidelines for the management of ED in these patients have been produced by an expert panel. Cardiovascular risk stratification is an important initial step in managing such patients. In cardiac patients considered to have low cardiovascular risk, the management of ED can be safe and effective.

Evaluation of intracoronary stenting by intravascular optical coherence tomography

Abstract: Background: Conventional contrast cineangiography and intravascular ultrasound (IVUS) provide a limited definition of vessel microstructure and are unable to evaluate dissection, tissue prolapse, and stent apposition on a size scale less than 100 μm. Objective: To evaluate the use of intravascular optical coherence tomography (OCT) to assess the coronary arteries in patients undergoing coronary stenting. Methods: OCT was employed in patients having percutaneous coronary interventions. Images were obtained before initial balloon dilatation and following stent deployment, and were evaluated for vessel dissection, tissue prolapse, stent apposition, and stent asymmetry. IVUS images were obtained before OCT, using an automatic pull back device. Results: 42 stents were imaged in 39 patients without complications. Dissection, prolapse, and incomplete stent apposition were observed more often with OCT than with IVUS. Vessel dissection was identified in eight stents by OCT and two by IVUS. Tissue prolapse was identified in 29 stents by OCT and 12 by IVUS; the extent of the prolapse (mean (SD)) was 242 (156) μm by OCT and 400 (100) μm by IVUS. Incomplete stent apposition was observed in seven stents by OCT and three by IVUS. Irregular strut separation was identified in 18 stents by both OCT and IVUS. Conclusions: Intracoronary OCT for monitoring stent deployment is feasible and provides superior contrast and resolution of arterial pathology than IVUS.

Heart failure and the aging population: an increasing burden in the 21st century?

Abstract: Background: Despite an overall decline in age adjusted mortality from coronary heart disease in developed countries, the number of patients with heart failure may be increasing. Objective: To project the future burden of heart failure in Scotland from contemporary epidemiological data. Methods: Scotland, like many industrialised countries, has an aging though numerically stable population (5.1 million). Current estimates of prevalence, general practice (GP) consultation rates, and hospital admission rates related to heart failure were applied to the whole Scottish population. These estimates were then projected over the period 2000 to 2020, on an age and sex specific basis, using expected changes in the age structure of the Scottish population. Results: There are currently estimated to be 40 000 men and 45 000 women aged ≥ 45 years with heart failure in Scotland. On the basis of population changes alone, these figures will rise in men and women by 2300 (6%) and 1500 (3%) by year 2005, and by 12 300 (31%) and 7800 (17%) in the longer term (2020), respectively. On the same basis, the annual number of male and female GP visits is likely to rise by 6400 (6%) and 2500 (2%) by year 2005, and by 35 200 (40%) and 17 300 (16%) in the longer term (124 000 and 126 000 visits), respectively. In the year 2000 about 3500 men and 4300 women in Scotland had an incident hospital admission for heart failure. By the year 2020 these figures are likely to increase by 52% (1800 more) and 16% (717 more) in men and women, respectively. If recent trends in short term case fatality rates continue to improve, the number of men who survive this event will increase by 59% (1700 more). Overall, by 2020 the annual number of male and female hospital admissions associated with a principal diagnosis of heart failure is expected to increase by 34% (from 5500 to 7500) and by 12% (from 7800 to 8500), respectively. Conclusions: Unless rapid and major changes occur in the incidence of heart failure, the burden of this disorder will continue to increase in both primary and secondary care over the next two decades. The greatest increase is likely to occur in men. Future health service planning must take this into account.

The influence of age, sex and other variables on the plasma level of N-terminal pro brain natriuretic peptide in a large sample of the general population

Abstract: Objective: To identify potentially confounding variables for the interpretation of plasma N-terminal pro brain natriuretic peptide (NT-proBNP). Design: Randomly selected subjects filled in a heart failure questionnaire and underwent pulse and blood pressure measurements, ECG, echocardiography, and blood sampling. Setting: Subjects were recruited from four Copenhagen general practices located in the same urban area and were examined in a Copenhagen University Hospital. Patients: 382 women and 290 men in four age groups: 50–59 years (n = 174); 60–69 years (n = 204); 70–79 years (n = 174); and > 80 years (n = 120). Main outcome measures: Associations between the plasma concentration of NT-proBNP and a range of clinical variables. Results: In the undivided study sample, female sex (p 10 [plasma creatinine] (p = 0.0009), low log 10 [plasma glycosylated haemoglobin A1c] (p = 0.0004), and high log 10 [urine albumin] (p 10 [plasma NT-proBNP] by multiple linear regression analysis. Conclusions: A single reference interval for the normal value of NT-proBNP is unlikely to suffice. There are several confounders for the interpretation of a given NT-proBNP concentration and at the very least adjustment should be made for the independent effects of age and sex.

Catecholaminergic polymorphic ventricular tachycardia: electrocardiographic characteristics and optimal therapeutic strategies to prevent sudden death

Abstract: Objective: To investigate the clinical outcome, ECG characteristics, and optimal treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT), a malignant and rare ventricular tachycardia. Patients and methods: Questionnaire responses and ECGs of 29 patients with CPVT were evaluated. Mean (SD) age of onset was 10.3 (6.1) years. Results: The initial CPVT manifestations were syncope (79%), cardiac arrest (7%), and a family history (14%). ECGs showed sinus bradycardia and a normal QTc. Mean heart rate during CPVT was 192 (30) beats/min. Most cases were non-sustained (72%), but 21% were sustained and 7% were associated with ventricular fibrillation. The morphology of CPVT was polymorphic (62%), polymorphic and bidirectional (21%), bidirectional (10%), or polymorphic with ventricular fibrillation (7%). There was 100% inducement of CPVT by exercise, 75% by catecholamine infusion, and none by programmed stimulation. No late potential was recorded. Onset was in the right ventricular outflow tract in more than half the cases. During a follow up of 6.8 (4.9) years, sudden death occurred in 24% of the patients, 7% of whom had anoxic brain damage. Autosomal dominant inheritance was seen in 8% of the patients’ families. β Blockers completely controlled CPVT in only 31% of cases. Calcium antagonists partially suppressed CPVT in autosomal dominant cases. Conclusions: CPVT may arise in certain distinct areas but the prognosis is poor. The onset of CPVT may be an indication for an implanted cardioverter-defibrillator.

Effects of isolated obesity on systolic and diastolic left ventricular function

Abstract: Background: Obesity is associated with increased cardiovascular morbidity and mortality. A direct effect of isolated obesity on cardiac function is not well established. Objective: To determine the direct effect of different grades of isolated obesity on echocardiographic indices of systolic and diastolic left ventricular function. Methods: 48 obese and 25 normal weight women were studied. They had no other pathological conditions. Obesity was classed as slight (n = 17; body mass index (BMI) 25–29.9 kg/m 2 ), moderate (n = 20; BMI 30–34.9 kg/m 2 ), or severe (n = 11; BMI ⩾ 35 kg/m 2 ). Echocardiographic indices of systolic and diastolic function were obtained, and dysfunction was assumed when at least two values differed by ⩾ 2 SD from the normal weight group. Results: Ejection fraction (p Conclusions: Subclinical left ventricular diastolic dysfunction is present in all grades of isolated obesity, correlates with BMI, and is associated with increased systolic function in the early stages of obesity.

Athlete’s heart

Abstract: Cardiac enlargement in athletes was already recognised by the end of the 19th century through percussion of the chest in cross country skiers, and was later confirmed by use of radiography and evidence from necropsy. The advent of echocardiography allowed investigators to gain a better insight into the heart of athletes, and these findings were in general confirmed by other techniques such as magnetic resonance imaging. The present review will focus on the impact of different sports and training on cardiac structure and function, and on electrocardiographic alterations associated with athlete’s heart. ### Left ventricle #### Cross sectional studies Physical exercise is associated with haemodynamic changes and alters the loading conditions of the heart. In dynamic exercise the emphasis is on movement with no or minimal development of force. The main haemodynamic features are increases in heart rate and stroke volume, the two components of cardiac output. Systemic vascular resistance drops but the net result is a slight to moderate rise in blood pressure. The load on the heart is predominantly that of volume. In static exercise force is developed with no or minimal movement. The haemodynamic consequences involve a slight elevation of cardiac output, caused by the increase of heart rate, and a more pronounced rise of blood pressure, resulting in a pressure load on the heart. From a theoretical point of view the haemodynamic alterations and the ventricular loading conditions during exercise could, in the long run, lead to left ventricular hypertrophy (LVH). Volume load would lead to enlargement of the left ventricular internal diameter and a proportional increase of wall thickness; this type of adaptation is termed eccentric LVH. The pressure load would induce thickening of the ventricular wall with unchanged internal dimension, or concentric LVH. It was suggested that these cardiac adaptations serve to normalise wall stress. Individual studies showed that cardiac adaptations …

Drug eluting stents: are human and animal studies comparable?

Abstract: Animal models of stenting probably predict human responses as the stages of healing are remarkably similar What is characteristically different is the temporal response to healing, which is substantially prolonged in humans The prevention of restenosis in recent clinical trials of drug eluting stents may represent a near absent or incomplete phase of intimal healing Continued long term follow up of patients with drug eluting stents for major adverse cardiac events and angiographic restenosis is therefore imperative

Prevalence and clinical significance of incidental paraprosthetic valvar regurgitation: a prospective study using transoesophageal echocardiography.

Abstract: OBJECTIVE: To assess the prevalence, mechanisms, and significance of paraprosthetic regurgitation detected incidentally by transoesophageal echocardiography (TOE) in patients after heart valve replacement. DESIGN: Prospective observational study. SETTING: Tertiary referral centre. PATIENTS: 360 consecutive patients (mean (SD) age 65.8(9.5) years, 193 women) undergoing elective first ever valve replacement. METHODS: Postoperative and follow up TOE, and tests for haemolysis and anaemia. RESULTS: There were 243 aortic, 90 mitral, and 27 double valve replacements, using 316 mechanical and 44 tissue valves, giving 270 aortic and 117 mitral valves. One patient with severe paraprosthetic mitral regurgitation underwent immediate reoperation and was excluded from subsequent analyses. Paraprosthetic jets were detected around 16 (6%) of the aortic and 38 (32%) of the mitral valves (p < 0.05) at the postoperative study. Follow up TOE was available for 151 aortic and 67 mitral valves, 0.9 (0.5) years after operation. Paraprosthetic jets were present in 15 (10%) of the aortic and 10 (15%) of the mitral valves (NS). Two thirds of the aortic and a fifth of the mitral jets were new. Paraprosthetic jets were more common in aortic valves in a supra-annular (12 of 88, 14%) than in an intra-annular position (4 or 182, 2%; p < 0.005) and in mitral valves inserted with continuous (36 of 88, 41%) rather than interrupted sutures (2 of 28, 7%; p < 0.001). Lactate dehydrogenase concentration was higher in patients with paraprosthetic jets than in those without (752 (236) v 654 (208) IU/l, p < 0.001). Haemoglobin and haptoglobin concentrations were not different. CONCLUSIONS: Small paraprosthetic leaks are common, are related to surgical factors, are not associated with increased subclinical haemolysis, and are benign during the first year after heart valve replacement.

Twenty year comparison of a Bjork-Shiley mechanical heart valve with porcine bioprostheses

Abstract: Objective: To compare survival and outcome in patients receiving a mechanical or bioprosthetic heart valve prosthesis. Design: Randomised prospective trial. Setting: Tertiary cardiac centre. Patients: Between 1975 and 1979, patients were randomised to receive either a Bjork-Shiley or a porcine prostheses. The mitral valve was replaced in 261 patients, the aortic in 211, and both valves in 61 patients. Follow up now averages 20 years. Main outcome measures: Death, reoperation, bleeding, embolism, and endocarditis. Results: After 20 years there was no difference in survival (Bjork-Shiley v porcine prosthesis (mean (SEM)): 25.0 (2.7)% v 22.6 (2.7)%, log rank test p = 0.39). Reoperation for valve failure was undertaken in 91 patients with porcine prostheses and in 22 with Bjork-Shiley prostheses. An analysis combining death and reoperation as end points confirmed that Bjork-Shiley patients had improved survival with the original prosthesis intact (23.5 (2.6)% v 6.7 (1.6)%, log rank test p < 0.0001); this difference became apparent after 8–10 years in patients undergoing mitral valve replacement, and after 12–14 years in those undergoing aortic valve replacement. Major bleeding was more common in Bjork-Shiley patients (40.7 (5.4)% v 27.9 (8.4)% after 20 years, p = 0.008), but there was no significant difference in major embolism or endocarditis. Conclusions: Survival with an intact valve is better among patients with the Bjork-Shiley spherical tilting disc prosthesis than with a porcine prosthesis but there is an attendant increased risk of bleeding.

Creatinine clearance and adverse hospital outcomes in patients with acute coronary syndromes: findings from the global registry of acute coronary events (GRACE)

Abstract: Objective: To determine whether creatinine clearance at the time of hospital admission is an independent predictor of hospital mortality and adverse outcomes in patients with acute coronary syndromes (ACS). Design: A prospective multicentre observational study, GRACE (global registry of acute coronary events), of patients with the full spectrum of ACS. Setting: Ninety four hospitals of varying size and capability in 14 countries across four continents. Patients: 11 774 patients hospitalised with ACS, including ST and non-ST segment elevation acute myocardial infarction and unstable angina. Main outcome measures: Demographic and clinical characteristics, medication use, and in-hospital outcomes were compared for patients with creatinine clearance rates of > 60 ml/min (normal and minimally impaired renal function), 30‐60 ml/min (moderate renal dysfunction), and < 30 ml/min (severe renal dysfunction). Results: Patients with moderate or severe renal dysfunction were older, were more likely to be women, and presented to participating hospitals with more comorbidities than those with normal or minimally impaired renal function. In comparison with patients with normal or minimally impaired renal function, patients with moderate renal dysfunction were twice as likely to die (odds ratio 2.09, 95% confidence interval 1.55 to 2.81) and those with severe renal dysfunction almost four times more likely to die (odds ratio 3.71, 95% confidence interval 2.57 to 5.37) after adjustment for other potentially confounding variables. The risk of major bleeding episodes increased as renal function worsened. Conclusion: In patients with ACS, creatinine clearance is an important independent predictor of hospital death and major bleeding. These data reinforce the importance of increased surveillance efforts and use of targeted intervention strategies in patients with acute coronary disease complicated by renal dysfunction.

Experience with transcatheter closure of secundum atrial septal defects using the Amplatzer septal occluder: a single centre study in 236 consecutive patients

Abstract: Aim: To evaluate the safety and efficacy of transcatheter closure of secundum atrial septal defects (ASD) with the Amplatzer septal occluder. Methods: 236 consecutive patients with a significant ASD (age 6 months to 46 years, median 5 years; body weight 6.5–79 kg, median 18 kg) were considered for transcatheter closure with the Amplatzer septal occluder; 18 patients with defects that were too large or with a deficient inferior margin were excluded from attempted transcatheter closure after initial transthoracic (4) or transoesophageal echocardiography (14). Results: At cardiac catheterisation, devices were not implanted in 18 patients because the stretched diameter of the ASD was too large (4), the device was unstable (4), compromised the mitral valve (1), or obstructed the upper right pulmonary vein (1); eight patients with additional systemic or pulmonary vein anomalies (5) or a Qp:Qs less than 1.5 (3) were excluded after angiographic and haemodynamic assessment. Thus ASD closure was done successfully in 200 patients (procedure time 25–210 minutes, median 66 minutes; fluoroscopy time 2.5–60 minutes, median 12 minutes), among whom 22 had multiple ASDs (14) or a septal aneurysm (8). The diameter of the devices ranged between 6–34 mm. Severe procedure related complications (retroperitoneal bleeding, air embolism) occurred in two cases. At follow up (33 days to 4.3 years, median 2.3 years) complete closure was documented in 94%, with a trivial residual shunt in 12 patients. Conclusions: The Amplatzer septal occluder is very efficient and offered interventional ASD closure in 84.7% of our group of consecutive patients, with excellent intermediate results.

Ethnic differences in cardiovascular disease

Abstract: People of non-European origin form around 7% of the total UK population. Most of these are of South Asian (that is, from the Indian subcontinent) or Black African (that is, from the Caribbean and West Africa) descent. For these migrants, as for virtually all population groups living in the western world, cardiovascular disease (CVD) is the main cause of death. But there are striking ethnic differences in CVD risk. Disease presentation may differ, challenging diagnostic skills, and therapeutic requirements and responses may also not be uniform. The study of ethnic differences in CVD has provided valuable aetiological clues, not just for ethnic minority groups but also for the majority population. Migrants of South Asian descent worldwide have elevated risks of morbid and mortal events because of ischaemic heart disease (IHD).1 In the UK, mortality from IHD in both South Asian men and women is 1.5 times that of the general population (fig 1),2 and South Asians have not benefited to the same extent from the general decline in deaths caused by IHD over the last few decades. These ethnic differences are greatest in the youngest age groups. Figure 1 Standardised mortality ratios (SMR) for heart disease and stroke in South Asians and African Caribbeans compared to Europeans, age 20–69, from 1989–92. Adapted from Wild and McKeigue,2 with permission from the BMJ Publishing Group. These ethnic differences have been extensively studied, and while classical risk factors, such as smoking, blood pressure, obesity, and cholesterol vary substantially between subgroups of South Asians—such that in some cases, levels are equivalent to, or lower than, a comparable European population—levels of glucose intolerance, central obesity (as measured by waist to hip ratio), fasting triglyceride, and insulin are uniformly elevated compared to Europeans (table 1).3 As the elevated risk of IHD is shared by …

A meta-analysis comparing the prognostic accuracy of six diagnostic tests for predicting perioperative cardiac risk in patients undergoing major vascular surgery

Abstract: Objective: To evaluate the discriminatory value and compare the predictive performance of six non-invasive tests used for perioperative cardiac risk stratification in patients undergoing major vascular surgery. Design: Meta-analysis of published reports. Methods: Eight studies on ambulatory electrocardiography, seven on exercise electrocardiography, eight on radionuclide ventriculography, 23 on myocardial perfusion scintigraphy, eight on dobutamine stress echocardiography, and four on dipyridamole stress echocardiography were selected, using a systematic review of published reports on preoperative non-invasive tests from the Medline database (January 1975 and April 2001). Random effects models were used to calculate weighted sensitivity and specificity from the published results. Summary receiver operating characteristic (SROC) curve analysis was used to evaluate and compare the prognostic accuracy of each test. The relative diagnostic odds ratio was used to study the differences in diagnostic performance of the tests. Results: In all, 8119 patients participated in the studies selected. Dobutamine stress echocardiography had the highest weighted sensitivity of 85% (95% confidence interval (CI) 74% to 97%) and a reasonable specificity of 70% (95% CI 62% to 79%) for predicting perioperative cardiac death and non-fatal myocardial infarction. On SROC analysis, there was a trend for dobutamine stress echocardiography to perform better than the other tests, but this only reached significance against myocardial perfusion scintigraphy (relative diagnostic odds ratio 5.5, 95% CI 2.0 to 14.9). Conclusions: On meta-analysis of six non-invasive tests, dobutamine stress echocardiography showed a positive trend towards better diagnostic performance than the other tests, but this was only significant in the comparison with myocardial perfusion scintigraphy. However, dobutamine stress echocardiography may be the favoured test in situations where there is valvar or left ventricular dysfunction.

Cardiac and vascular pathophysiology in hypertension.

Abstract: Hypertension is one the earliest recorded medical conditions (Nei Jin by Huang Ti around 2600BC); it has shaped the course of modern history1 and the consequences of hypertension (myocardial infarction, strokes, and heart failure) will soon be the leading global cause of death. Nevertheless, despite intensive research, the aetiology of hypertension remains obscure; only around 5% of cases have an identifiable cause.2 Indeed, primary or essential hypertension is perhaps better not considered a disease at all,w1 rather (as suggested by Sir Geoffrey Rose) a level of blood pressure above which treatment does more good than harm. An individual’s blood pressure depends on the complex interplay of heart and blood vessels and understanding this relation is the key to understanding the pathophysiology of hypertension. ### Relation between mean pressure and mean flow in the human circulation The role of the circulation is to deliver blood to the tissues and flow occurs because of the pressure difference established by the pumping action of the heart. The relation between the pressure difference and flow can be described by a relation that is analogous to Ohm’s Law for electrical current (box 1) and sometimes termed Darcy’s Law. \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \[{\Delta}P\ =\ Q\ {\times}\ R\] \end{document} (where ΔP = pressure difference. Q = bulk flow, R = resistance) This relation can be restated for the whole circulation in terms of mean arterial pressure, cardiac output, and peripheral resistance (box 2). \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \[MAP\ =\ CO\ {\times}\ PVR\] \end{document} (where MAP = mean arterial pressure, CO = cardiac output (= stroke volume × heart rate), PVR = total peripheral vascular resistance) Although a simplification, this emphasises that an elevation of mean blood pressure can only come about as a result of an increase in cardiac output (CO), an increase in total peripheral vascular resistance (PVR), or a combination of both. CO is a consequence of left ventricular pump function, which in turn depends on a number of factors (fig 1) including …

Normal values of B type natriuretic peptide in infants, children, and adolescents

Abstract: Objective: To determine normal values of plasma B type natriuretic peptide from infancy to adolescence using a commercially available rapid assay. Setting: Tertiary referral centre. Design: The study was cross sectional. Plasma BNP concentration was measured in 195 healthy infants, children, and adolescents from birth to 17.6 years using the triage BNP assay (a fluorescence immunoassay). Results: During the first week of life, the mean (SD) plasma concentration of BNP in newborn infants decreased significantly from 231.6 (197.5) to 48.4 (49.1) pg/ml (p = 0.001). In all subjects older than two weeks plasma BNP concentration was less than 32.7 pg/ml. There was no significant difference in mean plasma BNP measured in boys and girls younger than 10 years (8.3 (6.9) v 8.5 (7.5) pg/ml). In contrast, plasma concentration of BNP in girls aged 10 years or older was significantly higher than in boys of the same age group (12.1 (9.6) v 5.1 (3.5) pg/ml, p Conclusions: Plasma BNP concentrations in newborn infants are relatively high, vary greatly, and decrease rapidly during the first week of life. In children older than 2 weeks, the mean plasma concentration of BNP is lower than in adults. There is a sex related difference in the second decade of life, with higher BNP concentrations in girls. BNP concentrations in girls are related to pubertal stage.

Injection drug use and right sided endocarditis

Abstract: If William Osler were alive today he would no doubt remark on the fundamental change in the nature of the disease that he originally described. Staphylococcal endocarditis in injection drug users is now the dominant form of the disease in many urban communities where there is a high incidence of injection drug use and homelessness. At our institution (a tertiary care, university affiliated hospital in inner Vancouver), 63% of 116 hospitalisations between 1994 and 2000 for infective endocarditis (IE) were in injection drug users. Right sided endocarditis accounts for 10% of all IE in population based surveys1 and a higher proportion of IE in injection drug users. Modern echocardiographic techniques have considerably augmented our ability to diagnose IE and to understand its natural history. Despite this, there are many areas in which our understanding of right sided IE remains incomplete. Right sided IE has a significant morbidity and mortality that adds a notable economic burden to stretched inner city health care facilities. The challenges of caring for this population of patients should not be underestimated and demands a logical and coordinated approach among care providers and physicians from a variety of specialties. This article reviews aspects of the epidemiology, clinical features, diagnosis, and treatment of right sided IE in injection drug users. Although right sided IE may occur in association with congenital heart disease and instrumentation of the right heart, it is overwhelmingly a disease of injection drug users, at least in western populations. Among injection drug users presenting with fever, 13% will have echocardiographic evidence of IE.2 If injection drug users with bacteraemia from an inner city demographic are considered, up to 41% will have evidence of IE.3 The pathogenic mechanisms that explain the increased prevalence of right sided IE in injection drug users are not …

Blood culture negative endocarditis: analysis of 63 cases presenting over 25 years

Abstract: Objective: To analyse cases of blood culture negative endocarditis (BCNE) seen at St Thomas’ Hospital, London, between 1975 and 2000. Methods: Data on all episodes of endocarditis with negative blood cultures seen at St Thomas’ Hospital between 1975 and 2000 were collected prospectively and analysed retrospectively. Results: Sixty three patients with BCNE were seen during the study period: 48 (76%) with native and 15 (24%) prosthetic valve infection. BCNE accounted for 12.2% of the 516 cases of endocarditis seen at St Thomas’ Hospital. The diagnosis of endocarditis was clinically definite by the Duke criteria in only 21% (7 of 34) of cases of pathologically proven native valve endocarditis but in 62% (21 of 34) of cases by the St Thomas’ modifications of the criteria. Comparable figures for the 11 cases of pathologically proven prosthetic valve endocarditis were 45% and 73%. Despite negative blood cultures a causative organism was identified in 31 (49%) of the 63 cases: in 15 by serology (8 Coxiella burnetii , 6 Bartonella species, and 1 Chlamydia psittaci ); in 9 cases by culture of the excised valve; in 3 by microscopy of the excised valve, on which large numbers of Gram positive cocci were seen although the culture was sterile; and in the other 4 by isolation from a site other than the excised valve (2 respiratory specimens, 1 from the pacemaker tip, and 1 from an excised embolus). In addition 5 of the 6 cases of Bartonella infection were confirmed by polymerase chain reaction study of the excised valve. Two thirds of the 32 patients for whom no pathogen was identified had received antibiotics before blood was cultured. Thus truly “negative” endocarditis was very uncommon (6% of the cases). Conclusion: If blood cultures are negative in definite or suspected endocarditis, serum should be analysed for Bartonella , Coxiella , and Chlamydia species antibodies, and the excised valve or (rarely) embolus should be analysed by microscopy, culture, histology, and relevant polymerase chain reaction. Other specimens may be relevant. The Duke criteria performed poorly in BCNE; St Thomas’ additional minor criteria gave more definite diagnoses.

Tissue Doppler, strain, and strain rate echocardiography for the assessment of left and right systolic ventricular function.

Abstract: Tissue Doppler (TDE), strain, and strain rate echocardiography are emerging real time ultrasound techniques that provide a measure of wall motion. They offer an objective means to quantify global and regional left and right ventricular function and to improve the accuracy and reproducibility of conventional echocardiography studies. Radial and longitudinal ventricular function can be assessed by the analysis of myocardial wall velocity and displacement indices, or by the analysis of wall deformation using the rate of deformation of a myocardial segment (strain rate) and its deformation over time (strain). A quick and easy assessment of left ventricular ejection fraction is obtained by mitral annular velocity measurement during a routine study, especially in patients with poor endocardial definition or abnormal septal motion. Strain rate and strain are less affected by passive myocardial motion and tend to be uniform throughout the left ventricle in normal subjects. This paper reviews the underlying principles of TDE, strain, and strain rate echocardiography and discusses currently available quantification tools and clinical applications.

Development of the heart: (1) formation of the cardiac chambers and arterial trunks

Abstract: Through the 20th century, knowledge of the events occurring during cardiac development was clouded by conflicting descriptions, coupled with use of notably different terminologies. Furthermore, not all accounts were based on direct study of embryonic material, instead being constructed on the basis of interpretations of previous reports, supported by inferences made from the structure of the congenitally malformed heart. Such processes, in themselves, are understandable, since it is axiomatic that proper appreciation of the events occurring during formation of the heart will aid in the analysis of the morphogenesis of cardiac malformations, this being a desirable prerequisite in the search for optimal treatment. Over the past decade, this has all changed. There has been an explosion of work, both anatomical and molecular, devoted to cardiac development. Advances in technology, coupled with the use of suitable animal models, now enable us to provide a more accurate account of the steps involved in formation and septation of the cardiac chambers. Not all of this new information is concordant with the “classical” accounts. In these reviews, therefore, we will describe, first, the steps involved in formation of the primary heart tube, and its conversion to the four cardiac chambers and the paired arterial trunks. We will then look in greater detail at the events occurring during the separation of the initial solitary heart tube into discrete systemic and pulmonary circulations. The mesodermal tissues that give rise to the heart first become evident when the embryo is undergoing the process known as gastrulation. In the human, this occurs during the third week of development, while for the mouse, at a comparable stage of development, around seven days will have elapsed from fertilisation, and the embryo will be in the presomitic stage. The embryonic plate in humans, initially possessing two layers, is ovoid, and is …

In-stent stenosis: pathology and implications for the development of drug eluting stents.

Abstract: Over 1.5 million percutaneous coronary revascularisation procedures are performed annually world wide, most being intracoronary stenting. Despite enormous advances in devices, the major limitation is in-stent stenosis (ISS) (reviewed by Bennett and O'Sullivan1). Although ISS rates are 10–20% in selected patients, we now stent total occlusions, saphenous vein bypass grafts, both angioplasty and ISS sites, diabetic patients, and small vessels. Thus, real ISS rates are much higher, up to 59% in some high risk lesions. Until recently, the only effective treatment for ISS was brachytherapy. Brachytherapy reduces target vessel revascularisation rates and binary restenosis rates, and increases minimum luminal diameters (MLDs) compared with control vessels, maintained to three years.1 Although effective, brachytherapy is not universally accepted, due predominantly to late thrombosis and the logistics of administering radioactivity. In contrast, drug eluting stents containing the immunosuppressive agent rapamycin and the antimitotic agent paclitaxel have shown encouraging reductions in ISS in de novo lesions,2,3 and possibly in ISS lesions. This review examines the pathology of ISS and how drugs bound to stents interrupt the normal response to vessel injury. Overdistension of the diseased vessel causes endothelial disruption, internal elastic lamina fracture, and medial dissection. Lumen enlargement is caused by a combination of plaque reduction (compression/embolisation), axial plaque redistribution towards the proximal and distal segments outside the stent, plaque extrusion, and vessel expansion. Many processes then contribute to restenosis (fig 1 and table 1). View this table: Table 1 Pathogenic processes leading to in-stent stenosis Figure 1 Possible outcomes following angioplasty and mechanisms responsible for restenosis. (A) Schematic representation of the diseased vessel before intervention, showing the structure of the vessel wall and a stenotic vessel segment. (B) Following angioplasty there is dissection of both the intima of the plaque and the vessel media, associated with an enlargement of the treated segment. Angioplasty is either successful …

Factors associated with survival to hospital discharge among patients hospitalised alive after out of hospital cardiac arrest: change in outcome over 20 years in the community of Göteborg, Sweden

Abstract: Objective: To describe the change in survival and factors associated with survival during a 20 year period among patients suffering from out of hospital cardiac arrest and being hospitalised alive. Patients: All patients hospitalised alive in the community of Goteborg after out of hospital cardiac arrest between 1 October 1980 and 1 October 2000 were included. Methods: Patient data were prospectively computerised with regard to factors at resuscitation. Data on medical history and hospitalisation were retrospectively recorded. Patients were divided into two groups (the first and second 10 year periods). Setting: Community of Goteborg, Sweden. Results: 5505 patients suffered from cardiac arrest during the time of the survey. Among them 1310 patients (24%) were hospitalised alive. Survival (discharged alive) was 37.5% during the first part and 35.1% during the second part (NS). The following were independent predictors of an increased chance of survival: ventricular fibrillation/tachycardia as the first recorded rhythm (odds ratio (OR) 3.46, 95% confidence interval (CI) 2.36 to 5.07); witnessed arrest (OR 2.50, 95% CI 1.52 to 4.10); bystander initiated cardiopulmonary resuscitation (OR 2.00, 95% CI 1.42 to 2.80); the patient being conscious on admission to hospital (OR 6.43, 95% CI 3.61 to 11.45); sinus rhythm on admission to hospital (OR 1.53, 95% CI 1.12 to 2.10); and treatment with lidocaine in the emergency department (OR 1.64, 95% CI 1.16 to 2.31). The following were independent predictors of a low chance of survival: age > 70 years (median) (OR 0.65, 95% CI 0.47 to 0.88); atropine required in the emergency department (OR 0.35, 95% CI 0.16 to 0.75); and chronic treatment with diuretics before hospital admission (OR 0.59, 95% CI 0.43 to 0.81). Conclusion: There was no improvement in survival over time among initial survivors of out of hospital cardiac arrest during a 20 year period. Major indicators for an increased chance of survival were initial ventricular fibrillation/tachycardia, bystander cardiopulmonary resuscitation, arrest being witnessed, and the patient being conscious on admission. Major indicators for a lower chance were high age, requirement for atropine in the emergency department, and chronic treatment with diuretics before cardiac arrest.

Cardiovascular malformations in infants of diabetic mothers

Abstract: Objective: To compare the prevalence at live birth and the spectrum of cardiovascular malformations in infants born to diabetic mothers with pre-existing diabetes with that in infants of non-diabetic mothers. Design: Prospective study of all live births in the resident population of one health region, with recording of details of the outcome of all pregnancies of women with pre-existing diabetes and of all live born babies with cardiovascular malformations. Results: In the six years 1995–2000 there were 192 618 live births in the study population. Cardiovascular malformations were confirmed in 22 of 609 (3.6%) babies with diabetic mothers and in 1417 of 192 009 (0.74%) babies with non-diabetic mothers. The odds ratio for a cardiovascular malformation with maternal diabetes was 5.0 (95% confidence interval 3.3 to 7.8). Combination of these results with previous reports and comparison with the spectrum of cardiovascular malformations in infants of non-diabetic mothers shows a greater than threefold excess of transposition of the great arteries, truncus arteriosus, and tricuspid atresia. Conclusions: Pre-existing maternal diabetes is associated with a fivefold increase in risk of cardiovascular malformations. Transposition of the great arteries, truncus arteriosus, and tricuspid atresia are overrepresented to produce a substantial excess of these malformations.

A single serum glucose measurement predicts adverse outcomes across the whole range of acute coronary syndromes.

Abstract: Objectives: To analyse the relation between serum glucose concentration and hospital outcome across the whole spectrum of acute coronary syndromes. Methods: This was a prospective cohort study of 2127 patients presenting with acute coronary syndromes. The patients were stratified into quartile groups (Q1 to Q4) defined by serum glucose concentrations of 5.8, 7.2, and 10.0 mmol/l. The relation between quartile group and major in-hospital complications was analysed. Results: The proportion of patients with acute myocardial infarction increased incrementally across the quartile groups, from 21.4% in Q1 to 47.9% in Q4 (p < 0.0001). The trend for frequency of in-hospital major complications was similar, particularly left ventricular failure (LVF) (Q1 6.4%, Q4 25.2%, p < 0.0001) and cardiac death (Q1 0.7%, Q4 6.1%, p < 0.0001). The relations were linear, each glucose quartile increment being associated with an odds ratio of 1.46 (95% confidence interval (CI) 1.27 to 1.70) for LVF and 1.52 (95% CI 1.17 to 1.97) for cardiac death. Although complication rates were higher for a discharge diagnosis of acute myocardial infarction than for unstable angina, there was no evidence that the effects of serum glucose concentration were different for the two groups, there being no significant interaction with discharge diagnosis in the associations between glucose quartile and LVF (p = 0.69) or cardiac death (p = 0.17). Similarly there was no significant interaction with diabetic status in the associations between glucose quartile and LVF (p = 0.08) or cardiac death (p = 0.09). Conclusion: Admission glycaemia stratified patients with acute coronary syndromes according to their risk of in-hospital LVF and cardiac mortality. There was no detectable glycaemic threshold for these adverse effects. The prognostic correlates of admission glycaemia were unaffected by diabetic status and did not differ significantly between patients with acute myocardial infarction and those with unstable angina.

The variation of plasma concentrations of a novel, adipocyte derived protein, adiponectin, in patients with acute myocardial infarction

Abstract: Adiponectin is a new member of adipocyte derived proteins belonging to the soluble defence collagens.1 Plasma adiponectin concentrations in obese subjects are decreased in spite of an adipose specific expression.1 More interestingly, the patients with chronic coronary artery disease exhibited lower plasma adiponectin concentrations compared to body mass index (BMI) matched control subjects.2 On the other hand, adiponectin accumulates in the vascular subendothelial space when the endothelial barrier is damaged.3 In vitro, adiponectin suppresses the expression of adhesion molecules in the vascular endothelial cells and cytokine production from macrophages.2,4 Therefore, the molecule may be involved in the inflammation and tissue repairing processes. Acute coronary syndrome is often precipitated by acute thrombosis.5 It is commonly accepted that the rupture or the erosion of plaques by the inflammatory process leads to coronary thrombosis and acute myocardial infarction (AMI). The C reactive protein (CRP) concentrations in the acute phase are suggested to reflect pre-existing coronary plaque instability associated with the onset of AMI. The significance of adiponectin in acute coronary syndrome has never been investigated. In the present study, we examined the serial change in plasma adiponectin concentrations and its relation to plasma CRP concentration in …

Development of the heart: (3) formation of the ventricular outflow tracts, arterial valves, and intrapericardial arterial trunks

Abstract: In the first part of our review of cardiac development,1 we explained the changes occurring during the transformation of the solitary primary heart tube into the primordiums of the definitive heart, describing how this involved the processes of looping, and subsequent formation from the primary tube of the components of the atriums and ventricles. In the second part of our review,2 we then accounted for the steps involved in separation of the atrial and ventricular chambers, emphasising that the processes were more complicated than the simple formation of partitions within the respective atrial and ventricular primordiums. The subject of this, our third review, is the transformation of the initially solitary outflow portion of the heart tube into the intrapericardial parts of the aorta and the pulmonary trunk, their arterial valves and sinuses, and the subarterial ventricular outflow tracts. In our first review, we summarised some of the problems that continue to plague the understanding of the development of these outflow structures. Thus, initially the entirety of the primary heart tube contained within the confines of the pericardial cavity possesses a myocardial phenotype. Yet, in the definitive heart, the walls of the intrapericardial arterial trunks, along with the sinuses of the arterial valves, and small parts of the subarterial ventricular outlets, have an arterial or fibrous phenotype. The steps involved in the changes of the walls from the myocardial to the arterial and fibrous phenotypes have yet to be clarified. And then, cushions, or ridges, of endocardial tissue initially fuse to divide the entirety of the solitary outflow segment into the presumptive systemic and pulmonary outlets. With subsequent development, these cushions lose their septal function, as the arterial valves and trunks, along with the subpulmonary muscular infundibulum, develop as free-standing structures with their own discrete walls within the pericardial …