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Objectives The aim of this study was to investigate the effect of renin-angiotensin system blockade on outcomes in patients with aortic regurgitation (AR). Background Angiotensin-converting enzyme (ACE) inhibitors have the potential to reduce afterload, blunt left ventricular wall stress, and limit left ventricular dilation and hypertrophy. However, long-term studies have yielded inconsistent results, and very few have assessed clinical outcomes. Methods The Health Informatics Centre dispensed prescription and morbidity and mortality database for the population of Tayside, Scotland, was linked through a unique patient identifier to the Tayside echocardiography database. Patients diagnosed with at least moderate AR from 1993 to 2008 were identified. Cox regression analysis was used to assess differences in all-cause mortality and cardiovascular (CV) and AR events (heart failure hospitalizations, heart failure deaths, or aortic valve replacement) between those treated with and without ACE inhibitors or angiotensin receptor blockers (ARBs). Results A total of 2,266 subjects with AR (median age 74 years; interquartile range: 64 to 81 years) were studied, with a mean follow-up period of 4.4 ± 3.7 years. Seven hundred and five patients (31%) received ACE inhibitor or ARB therapy. There were 582 all-cause deaths (25.7%). Patients treated with ACE inhibitors or ARBs had significantly lower all-cause mortality and fewer CV and AR events, with adjusted hazard ratios of 0.56 (95% confidence interval [CI]: 0.64 to 0.89; p Conclusions This large retrospective study shows that the prescription of ACE inhibitors or ARBs in patients with moderate to severe AR was associated with significantly reduced all-cause mortality and CV and AR events. These data need to be confirmed by a prospective randomized controlled outcome trial.

The Losartan Intervention For Endpoint Reduction (LIFE) study demonstrated a clear mortality benefit in treating hypertensive patients with electrocardiogram (ECG) evidence of left ventricular hypertrophy (LVH) with losartan rather than atenolol. Previous studies have also shown that identifying and treating echo LVH is associated with prognostic benefits in hypertensive subjects, and is independent of the presence of ECG LVH. We sought to determine how many cases of echo LVH would be missed by applying the ECG criteria for LVH used in the LIFE study.A prospective study of 219 patients with type 2 diabetes recruited from the hospital diabetic clinic.Fifteen ECG criteria were assessed on each subject and compared with the presence or absence of LVH on echocardiography.All the proposed ECG criteria are poor at identifying echo LVH in people with diabetes.Using ECG LVH to select patients for angiotensin receptor blockade would lead to many diabetics with echo LVH missing out on the benefits of treatment. This assumes that the benefits seen in the LIFE study would also occur if the LIFE strategy were extended to echo LVH patients as well as to ECG LVH patients.

The Sphygmocor system purports to be able to assess ascending aortic blood pressure using a transfer function. It has been shown to be accurate when data obtained invasively are used, but has not been tested prospectively using data obtained non-invasively.To investigate the accuracy of this equipment when measurements are obtained non-invasively, as would normally be the case in the clinic setting.The study was observational. Ascending aortic pressure measurements were taken simultaneously with radial artery pressure wave recordings for estimation of ascending aortic blood pressure, in 28 patients undergoing diagnostic cardiac catheterization.The transfer function in the Sphygmocor system significantly underestimated invasively measured systolic blood pressure [mean -7.23 +/- 10.07 mmHg; 95% confidence interval (CI) -3.3 to -11.14 mmHg, P = 0.001] and significantly overestimated invasively measured diastolic blood pressure (mean 12.20 +/- 7.14 mmHg; 95% CI 9.43 to 14.97 mmHg, P0.001). Oscillometrically measured brachial systolic blood pressure was not significantly different from that measured invasively in the ascending aorta (mean 3.36 +/- 10.47 mmHg; 95% CI -0.69 to 7.43 mmHg, P = 0.1), but oscillometric measurement of brachial diastolic blood pressure gave a significant overestimation of that measured invasively (mean 11.70 +/- 7.18 mmHg; 95% CI 8.91 to 14.49 mmHg, P0.001). CONCLUSIONS The transfer function in the Sphygmocor system is no better at estimating ascending aortic blood pressure than are standard peripheral blood pressure measurements. It may be necessary to derive a new transfer system that is based on data that are acquired entirely non-invasively.

OBJECTIVES The study was designed to comprehensively evaluate the circadian effects of aldosterone blockade on autonomic tone and QT dispersion in chronic heart failure (CHF). BACKGROUND Spironolactone therapy given in addition to angiotensin-converting enzyme inhibitors improved survival in CHF, but the mechanism of its benefit is uncertain. Experimental evidence suggests that aldosterone may have detrimental effects on the autonomic nervous system, especially during the morning hours. METHODS Twenty-eight patients with New York Heart Association class II to IV CHF received spironolactone 50 mg daily and placebo for four weeks each in a double-blind crossover fashion. After each treatment phase, a full circadian assessment was undertaken of spironolactone's autonomic effects. The assessment included monitoring heart rate, QT dispersion, continuous Holter recordings, heart rate variability (HRV) and norepinephrine kinetics. RESULTS Spironolactone significantly reduced all indices of QT dispersion. The reductions in QTcmax, QTd and QTcd were greatest at 6 AM. In addition, spironolactone had favorable autonomic effects, which were limited to the morning (6-10 AM), including heart rate reduction and an improvement in HRV. CONCLUSIONS Spironolactone reduced heart rate and improved HRV and QT dispersion in CHF. Its effects were particularly prominent during the morning hours.

Objective: To determine whether low serum cortisol concentrations are associated with adverse prognosis in patients with acute myocardial infarction. Low serum cortisol concentrations have been associated with adverse prognosis in critical illness of diverse etiology. Design: Nested case-control study. Setting: Prospective cohort study of consecutive patients admitted with acute myocardial infarction to nine Scottish hospitals. Patients: A total of 100 patients who survived 30 days (controls) and 100 patients who died within 30 days (cases). Measurements and Main Results: Admission cortisol concentrations were lower in patients who died than those who survived (median, 1189 nmol/L vs. 1355 nmol/L; p < .001). A cortisol concentration in the bottom quartile (

Aims Resting plasma levels of atrial natriuretic peptide and B-type natriuretic peptide rise with left ventricular dysfunction, but little is known about effects of cardiac ischaemia on atrial natriuretic peptide and B-type natriuretic peptide levels during exercise. We investigated exercise levels of atrial natriuretic peptide and B-type natriuretic peptide in patients with suspected angina to determine whether these measurements could improve non-invasive assessment of coronary disease severity. Methods and results One hundred patients performed an exercise test (Bruce protocol) within 2 weeks of coronary angiography. Plasma levels of atrial natriuretic peptide and B-type natriuretic peptide were measured at rest and at peak exercise. Multivariate regression analysis was used to assess effects of age, sex, coronary anatomy, exercise time and ventricular function on atrial natriuretic peptide and B-type natriuretic peptide levels. Increasing age and female sex were significantly associated with higher resting atrial natriuretic peptide levels; age alone was associated with higher exercise atrial natriuretic peptide levels. As expected, left ventricular end-diastolic pressure and disease of left anterior descending and circumflex coronary arteries were associated with increased resting B-type natriuretic peptide levels. However, the usual rise in B-type natriuretic peptide levels during exercise was independently reduced by disease of the right coronary artery. Conclusion This paradoxical effect of right coronary artery disease limits the value of natriuretic peptide measurements as predictors of coronary disease severity. Impaired release of B-type natriuretic peptide may reduce exercise tolerance in patients with right coronary artery disease.

Background Experimental models suggest that brain natriuretic peptide (BNP) can modify left ventricular diastolic performance. The aim of this study was to evaluate the effects of BNP on resting and exercise hemodynamics and neurohormones in patients with isolated diastolic heart failure. Methods and Results Six patients with isolated diastolic heart failure were studied. After baseline hemodynamic measurements were obtained with use of thermistor-tipped pulmonary artery catheters, patients were randomized to receive infusion of BNP or placebo in a single-blind, crossover study. Hemodynamic and neurohormonal parameters were measured at rest after 30 minutes of infusion and during incremental supine bicycle exercise. BNP did not significantly affect resting hemodynamics but attenuated the rise in both pulmonary capillary wedge pressure (placebo, 23±2 mm Hg; BNP, 16±2 mm Hg; P P P Conclusions BNP infusion causes beneficial hemodynamic and neurohormonal effects during exercise in patients with isolated diastolic heart failure.

Aims The presence of pulmonary hypertension (PH) in left ventricular systolic dysfunction (LVSD) and symptomatic heart failure is an ominous sign. There are insufficient data regarding the risk conferred by increasing severity of PH in patients with heart failure. Methods and results We performed a record linkage study in Tayside, Scotland (population ∼400 000) utilizing the Tayside echocardiogram database (>50 000 echocardiograms) maintained by the Health Informatics Centre (HIC). Data sets from the HIC include mortality data, cardiovascular medications, and other healthcare activities linked anonymously by the community health index (CHI) number. Patients were included in the analysis if they had LVSD, had a valid right ventricular systolic pressure (RVSP) measurement, and had a loop diuretic prescription (provided not more than 1 year prior to echocardiogram). A Cox proportional hazard model was used to examine the effects of RVSP on all-cause mortality. A total of 1612 patients [mean age, 75.2 ± 10.9 (SD) years; 57.4% male] met the entry criteria. Mean RVSP for the cohort was 44.9 ± 13.1 mmHg and mean follow-up was 2.8 ± 2.5 years. For each 5 mmHg stepwise increase in RVSP, after adjustment for confounding factors including the degree of LVSD and the presence of chronic obstructive pulmonary disease, the hazard ratio (HR) for all-cause mortality was 1.06 (1.03–1.08, P < 0.001). Conclusions Pulmonary hypertension predicted all-cause mortality in a heterogeneous group of patients with heart failure. Each 5 mmHg rise in RVSP was associated with a 6% increased risk of death.

Background Right ventricular apical pacing can cause dyssynchronous activation of the ventricles, increase sympathetic activation, cause abnormalities in myocardial perfusion, worsen cardiac output and endothelial function, and may be associated with adverse cardiovascular effects. The use of rennin–angiotensin system blockers (RASBs) may be beneficial in counteracting these potentially harmful effects of right ventricular pacing. Objective To explore the impact of RASB use on the outcome in patients with right ventricular pacemakers implanted for complete atrioventricular (AV) block. Methods Patients implanted with right ventricular pacemakers for complete AV block between 1994 and 2009 were identified from the Tayside Pacing Registry. Cox proportional hazards model was used to assess differences in all-cause mortality and congestive heart failure hospitalizations for those receiving RASB during follow-up, adjusted for confounding variables. We also performed 2 sensitivity analyses—a propensity score–matched analysis and time-dependent analyses—to minimize bias. Results Eight hundred twenty patients (57% men; median age 73 years; range 22–103 years) received pacemakers for complete AV block between 1994 and 2008 (54% dual-chamber pacemaker and 46% ventricular demand pacemaker). Two hundred seventy-eight (34%) patients had received RASBs. Mean follow-up was 4.9 ± 4.6 years, with 540 (65%) deaths. RASB use was independently associated with significantly reduced mortality (adjusted hazard ratio 0.67; 95% confidence interval 0.47–0.94; P = .017) and reduced heart failure hospitalization (adjusted hazard ratio 0.42; 95% confidence interval 0.17–0.92; P Conclusions This study suggests that RASBs may confer outcome benefits in patients with right ventricular pacemakers implanted for complete AV block.

To evaluate the relationship between sudden cardiac death, ventricular arrhythmias and left ventricular hypertrophy in patients with hypertension.Epidemiological studies assessing the importance of left ventricular hypertrophy as a risk factor for sudden cardiac death, studies assessing the prevalence of arrhythmias in left ventricular hypertrophy and studies assessing whether there is an electrophysiological substrate in the hypertrophied myocardium for ventricular dysrhythmias.Current evidence indicates that left ventricular hypertrophy is a risk factor for sudden cardiac death and that ventricular arrhythmias are more prevalent in hypertensive patients with than in those without left ventricular hypertrophy. However, there is a lack of evidence that these dysrhythmias are important as an underlying mechanism for sudden cardiac death, and there is no clear evidence that the hypertrophied myocardium is, itself, an arrhythmogenic substrate for malignant ventricular dysrhythmias. One possible mechanism for sudden cardiac death is myocardial ischaemia, either as a consequence of associated coronary disease or due to left ventricular hypertrophy, but this remains unproved.There is currently no evidence that the ventricular ectopic activity seen in patients with hypertensive left ventricular hypertrophy is a marker for sudden cardiac death. Clarification of the mechanisms involved in sudden cardiac death will help in selecting appropriate preventive and therapeutic strategies for these patients.

ObjectivesThe purpose of this study was to investigate the impact of renin-angiotensin system blockade therapy on outcomes in aortic stenosis (AS).BackgroundAngiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are perceived to be relatively contraindicated in AS. However, inhibitors of the renin-angiotensin system may be beneficial in AS through their cardioprotective and beneficial effects on left ventricular remodeling.MethodsThe Health Informatics dispensed prescribing, morbidity, and mortality database for the population of Tayside, Scotland, was linked through a unique patient identifier to the Tayside echocardiography database (>110,000 scans). Patients with a diagnosis of AS from 1993 to 2008 were identified. Cox regression model (adjusted for confounding variables) and propensity score analysis were used to assess the impact of ACEIs or ARBs on all-cause mortality and cardiovascular (CV) events (CV death or hospitalizations).ResultsA total of 2,117 patients with AS (mean age 73 ± 12 years, 46% men) were identified and 699 (33%) were on ACEI or ARB therapy. Over a mean follow-up of 4.2 years, there were 1,087 (51%) all-cause deaths and 1,018 (48%) CV events. Those treated with ACEIs or ARBs had a significantly lower all-cause mortality with an adjusted hazard ratio of 0.76 (95% confidence interval: 0.62 to 0.92, p < 0.0001) and fewer CV events with an adjusted hazard ratio of 0.77 (95% confidence interval: 0.65 to 0.92, p < 0.0001). The outcome benefits of ACEIs/ARBs were further supported by propensity score analysis.ConclusionsThis large observational study suggests that ACEI/ARB therapy is associated with an improved survival and a lower risk of CV events in patients with AS.

OBJECTIVE--To assess the prevalence of symptomatic and silent myocardial ischaemia in patients with hypertensive left ventricular hypertrophy. DESIGN--Cross sectional study. SETTING--University department of medical cardiology. PATIENTS--90 patients (68 men and 22 women; mean age 57 (range 25 to 79)) with left ventricular hypertrophy due to essential hypertension. INTERVENTIONS--48 hour ambulatory ST segment monitoring (all patients), exercise electrocardiography (n = 79), stress thallium scintigraphy (n = 80), coronary arteriography (n = 35). RESULTS--43 patients had at least one episode of ST segment depression on ambulatory electrocardiographic monitoring. The median number of episodes was 16 (range 1 to 84) with a median duration of 8.6 (range 2 to 17) min. Over 90% of these episodes were clinically silent. 26 patients had positive exercise electrocardiography and 48 patients had reversible thallium perfusion defects despite chest pain during exercise in only five patients. 18 of the 35 patients who had coronary arteriography had important coronary artery disease. Seven of these patients gave no history of chest pain. CONCLUSIONS--Symptomatic and silent myocardial ischaemia are common in hypertensive patients with left ventricular hypertrophy, even in the absence of epicardial coronary artery disease.

Hypertensive patients with the electrocardiographic (ECG) pattern of left ventricular (LV) hypertrophy and strain are at increased risk of sudden death. It has been suggested that ventricular arrhythmias may be responsible. The prevalence and significance of ventricular arrhythmias was therefore studied in 90 hypertensive patients with LV hypertrophy and strain by undertaking 48-hour ambulatory ECG monitoring, ECG signal-averaging and programmed ventricular stimulation. Complex ventricular ectopic activity (Lown grade greater than or equal to 3) was detected in 59 patients (66%). Eleven patients (12%) had episodes of nonsustained ventricular tachycardia. There were no sustained arrhythmias either on ambulatory ECG monitoring or induced by programmed ventricular stimulation. Only 1 patient had ventricular late potentials recorded by the signal-averaged electrocardiogram. Therefore, there was little to suggest an underlying arrhythmogenic substrate in these patients. In conclusion, whereas ventricular arrhythmias occur often in patients with LV hypertrophy associated with systemic hypertension, their significance, if any, remains to be established.

The Doppler echocardiographic indexes of the tricuspid and mitral valves were assessed in 74 normal subjects (35 women and 39 men, mean age 45 years). A reproducibility study was also performed to examine the various sources of technical and biological variability. There were significantly higher peak early and late flow velocities across the mitral valve than across the tricuspid valve (0.67 ± 0.13 and 0.47 ± 0.12 vs 0.51 ± 0.08 and 0.35 ± 0.09 m·s−1, respectively; all p < 0.0001). There was no significant difference between the early:late (E:A) velocity ratios of the 2 valves (1.65 ± 0.73 vs 1.75 ± 0.67, p < 0.01). There was a steeper mitral early deceleration slope (−3.59 ± 1.07 vs −2.95 ± 0.91 m·s−2) but no significant difference in pressure half-times across the 2 valves (47 ± 7 vs 51 ± 12 ms, p < 0.1). No influence of gender or body surface area could be demonstrated. There was a weak but significant relation between mitral peak early, peak atrial velocity and E:A ratio and age (r = −0.39, p < 0.001, r = 0.23, p < 0.01, and r = −0.245, p < 0.01, respectively). There was no significant correlation between any of the tricuspid flow parameters and age. Respiration caused pronounced variability in the tricuspid Doppler indexes and all tricuspid flows were sampled and analyzed only during inspiration. The intra- and interobserver variabilities were small for all of the Doppler indexes measured, but the day-to-day variability was quite significant especially for the pressure halftime, deceleration and acceleration slope values. The present study documents in detail the normal Doppler flow characteristics of the tricuspid valve and compares them with the normal mitral flow parameters in the same subject.

To examine whether endogenous aldosterone can cause either arrhythmias (and some of their underlying mechanisms) or endothelial dysfunction in patients with coronary artery disease (CAD) but without heart failure.Aldosterone blockade has been shown to reduce the incidence of sudden death in patients with heart failure. This could be caused by a reduction in arrhythmias or in coronary events. Whether either effect also occurs in other cardiac patients without heart failure is currently unknown.We performed a randomized, placebo-controlled, double-blind crossover study on 98 patients with CAD but without heart failure on standard therapy, comparing 12.5-50 mg/day spironolactone (3 months) with placebo. Endothelial function was assessed by bilateral forearm venous occlusion plethysmography. Ventricular extrasystoles, procollagen III N-terminal peptide (PIIINP) and QT interval length were used to represent arrhythmias and their determinants.Spironolactone produced a highly significant 75% reduction in ventricular extrasystoles (median 192, range 48-744) on placebo compared with spironolactone (median 48, range 19.2-288, P0.003). Spironolactone also decreased the QT interval from a mean of 440 +/- 28 to a mean of 425 +/- 25 (P0.001) and a collagen marker (PIIINP) from a mean of 3.6 +/- 0.9 to a mean of 3.0 +/- 0.8 (P0.001), but did not significantly change endothelial dysfunction or heart rate variability.These results suggest that despite conventional therapy, endogenous aldosterone can be an arrhythmogenic influence in patients with CAD, but without heart failure. The possible mechanisms are that aldosterone promotes myocardial fibrosis and lengthens the QTc interval as well as decreasing potassium in CAD patients without heart failure.

Background: Diagnosing suspected left ventricular systolic dysfunction (LVSD) in the community is a challenge for GPs. We developed and validated a clinical prediction rule (CPR) for LVSD based on history, examination and electrocardiogram (ECG). Methods: Prospective cohort studies of 458 symptomatic patients (derivation cohort) and 535 patients (validation cohort) in 26 general practices in Tayside and Fife, Scotland. All patients underwent a structured clinical examination and ECG and the ‘reference standard’ investigation of echocardiography to establish the presence of LVSD. Results: Four elements from the clinical history and examination were all independently associated with LVSD—male sex [adjusted odds ratio (OR) 2.5; 95% CI 1.1, 5.0], presence of orthopnoea (OR 5.4; 1.9, 13.8) history of myocardial infarction (OR 5.6; 2.3, 13.6) and elevated jugular venous pulsations (OR 15.1; 4.6, 49.3). Addition of ECG (OR 20.6; 2.7, 158.6) provides important diagnostic information in terms of probability of LVSD. A CPR based on the presence or absence of these five elements will generate probabilities ranging from 1% to 97% for LVSD when applied to an individual patient. In the validation cohort, the model under-predicted the probability of LVSD, particularly at lower levels of expected risk, reflecting differences in the risk-factor profiles of the derivation and validation cohorts. Conclusions: The derived CPR provides quantitative estimates of post-test probability for LVSD. This rule requires further validation in other populations and settings because of the difficulties encountered in the validation cohort.

Background In coronary artery disease (CAD), a potentially reversible factor leading to cardiac death is left ventricular hypertrophy (LVH). However, LVH will only have a large impact overall in CAD if it is highly prevalent. Therefore we aimed to assess the prevalence of LVH in patients with stable, treated angina and its relationship with blood pressure (BP). Methods Three hundred twenty-two consecutive patients with angiographically confirmed coronary artery disease were recruited. Echocardiographic LV mass was performed and correlated with both office and 24-h ambulatory BP. Results Of the 267 patients with LV mass measurements, 195 (73%) had LVH. The mean 24-h ambulatory BP reading was systolic 125 ± 12 mm Hg and diastolic 68 ± 8 mm Hg in the LVH group. Of the LVH patients 62% had a nonhypertensive 24-h BP reading. On multivariate logistic regression analysis, factors independently related to LVH were history of hypertension (odds ratio [OR] 1.848, 95% confidence interval [CI] 1.051–3.248), body mass index (OR 1.085, 95% CI 1.011–1.165), and age (OR 1.039, 95% CI 1.004–1.076). Conclusions We conclude that echo LVH is very common in patients with stable, treated angina and the majority of these patients had a nonhypertensive BP at the time of study. Studies are now required to determine whether identifying and vigorously treating LVH in CAD would reduce the risk of premature death in these patients.

Recent evidence points to a role for the renin-angiotensin-aldosterone system (RAAS) in the pathogenesis of atherosclerosis and its complications, including acute angina pectoris. Two large trials in heart failure have clearly demonstrated that blocking aldosterone improves mortality1,2 and that this benefit occurs over and above standard therapy with angiotensin-converting enzyme (ACE) inhibitors. The question that naturally arises from these landmark studies is whether aldosterone blockade would produce the same benefits in patients with coronary artery disease (CAD) but no heart failure. There are three reasons to believe this might be the case. Firstly, angiotensin II (Ang II) and aldosterone produce similar biological effects and Ang II withdrawal has been shown to benefit patients with angina; aldosterone blockade may therefore follow in the footsteps of ACE inhibitors, as it did in heart failure, and produce benefits in vascular patients without heart failure. Secondly, one of the main mechanisms which is thought to be responsible for the benefit of aldosterone blockade in the Randomised ALdactone Evaluation Study (RALES) and Eplerenone Post-AMI Heart Failure Survival Study (EPHESUS), is that it improves endothelial/ vascular function3,4 and endothelial/vascular dysfunction is the fundamental abnormality in angina pectoris. Finally, aldosterone blockade has been shown to reduce atherosclerosis in animal studies of atherosclerosis without heart failure, which are analogous to CAD patients.5

To find out whether B-type natriuretic peptide (BNP) detects silent myocardial ischaemia in patients with type 2 diabetes, since many of these patients have silent ischaemia leading to unexpected cardiac deaths.Prospective cross-sectional study with consecutive recruitment of patients.Outpatient, single centre.219 patients with type 2 diabetes. Patients were excluded if they had a history or evidence of cardiac failure.BNP, echocardiography and exercise tolerance test (ETT). BNP was compared with the ETT result in all patients and specifically in those who had no apparent ischaemic heart disease (IHD).121 patients had no history of IHD or cardiac failure and of these patients 85 had a clearly abnormal or normal ETT result. BNP was higher in patients with an abnormal than with a normal ETT (mean 58.2 (SD 46.3) v 24.4 (SD 15.7) pg/ml, p0.001). In univariate analysis BNP was an independent predictor of an abnormal ETT (p0.001). In multivariate analysis BNP remained an independent predictor of the ETT result. BNP concentration over 20 pg/ml predicted an abnormal ETT result with a sensitivity of 87% and specificity of 37%, and BNP over 40 pg/ml had a sensitivity of 63% and a specificity of 81%.BNP is of value in predicting silent ischaemia on exercise testing in asymptomatic patients with type 2 diabetes.

Background: ECG and BNP have been assessed as screening tests for LVSD and heart failure. However, echocardiography also provides information about valvular disease and LVH. We assessed how good these screening tests are in identifying whether the subsequent echocardiogram will have any significant abnormality. Aims: To re-appraise the ECG and BNP as screening tests for echocardiography since there are important practical deficiencies in our current knowledge in this area. Methods: General practitioners referred suspected heart failure patients for clinical assessment, echocardiography, electrocardiography, and BNP measurement. The accuracy of each screening test and combinations of screening tests were calculated for LVSD, heart failure, valvular disease, and LVH. Results: The sensitivities of the ECG for LVSD, heart failure, LVH and valvular disease were 97%, 95%, 76%, and 69%, respectively. The corresponding figures for BNP were 86%, 82%, 59%, and 48%, respectively. When patients with atrial fibrillation and murmurs were excluded, the values for ECG were 94%, 87%, 53%, and 55%, while for BNP they were 83%, 73%, 50%, and 32%. Conclusions: ECG interpretation and BNP are adequate screening tests to detect LVSD or heart failure but fail to screen for other echocardiographic abnormalities, like valvular disease and LVH. This remains the case even if patients with atrial fibrillation or heart murmurs are excluded on the basis that they require echocardiography anyway.

Three studies have clearly shown that a prolonged QT dispersion (QTD) is the best predictor of cardiac death in patients with type 2 diabetes mellitus (DM). This was originally believed to be because QTD identified electrical inhomogeneity, but recent data suggests that this is unlikely. The alternative possibility is that QTD is a convenient identifier of hidden but lethal cardiac abnormalities. We explored whether the latter possibility is true by examining exactly what spectrum of cardiac abnormalities, if any, are over-represented in diabetics with a prolonged QTD. Two hundred nineteen patients with type 2 DM who had been first diagnosed with DM 3 to 6 years previously underwent intensive cardiac examinations. Patients with prolonged QTD had a significantly increased incidence of myocardial ischemia and left ventricular (LV) hypertrophy, and to a lesser extent, autonomic dysfunction. The main independent determinant of a prolonged QTD was ischemia, as seen on both ambulatory ST-segment monitoring (p

Introduction The presence of pulmonary hypertension in left ventricular systolic dysfunction (LVSD) is an ominous sign. It remains unclear the level at which pulmonary hypertension conveys a mortality risk in patients with LVSD. Methods We performed a record-linkage study in Tayside, UK (population approximately 400 000) utilising the Tayside echocardiogram database (>100 000 echo9s) maintained by the Health Informatics Centre (HIC). Datasets from HIC include mortality data and other health care activities linked anonymously by the community health index (CHI) number. Patients were included in the analysis if they had LVSD and had a right ventricular systolic pressure (RVSP) measurement. Cox proportional hazards regression analysis was used to examine the effects of different ranges of RVSP measures on all cause mortality. Results 2910 patients (mean age, 74.5±11.4 years; 43 % male) met entry criteria. Mean RVSP was 43.3 ± 12.7 mm Hg and median follow was 362 days (IQR 129–850 days). There was a significant correlation between RVSP and survival (p Conclusion An RVSP of greater than 42 mm Hg is predictive of increased mortality in heart failure. This is finding is independent of LVSD and COPD.

Large-scale trials of angiotensin converting enzyme (ACE) inhibitors after acute myocardial infarction (AMI) suggest that the benefits are greatest in patients with left ventricular (LV) dysfunction. However, early evaluation of LV function in all patients after AMI by current methods can be difficult due to a lack of resources and skilled personnel. Thus a clinical algorithm that could be used at the bedside to reliably identify patients with a left ventricular ejection fraction (LVEF)or = 40% would be helpful as an occasional alternative to echocardiography. We have devised such an algorithm based on the presence of one of: (i) clinical signs of heart failure; (ii) an index Q-wave anterior myocardial infarction; (iii) lack of thrombolytic therapy when there is a history of two or more previous myocardial infarctions and a CK rise1000 U/l. We tested this new algorithm prospectively in the coronary care units of two hospitals (one UK and one USA). In the UK centre, the sensitivity and specificity of the algorithm at identifying patients with a LVEFor = 40% were 82% and 72%, respectively. In the US centre, the sensitivity of the algorithm was 91% and the specificity 78% at identifying patients with LV dysfunction. We have validated a simple clinical algorithm which can be used at the bedside for identifying patients who would benefit from an ACE inhibitor after AMI.

OBJECTIVE--To evaluate the waveforms of left atrial area changes obtained by automated boundary detection with newly developed acoustic quantification technology. DESIGN--All subjects had measurements of left atrial areas taken in the apical four chamber, parasternal long axis, and parasternal short axis views using both conventional echocardiographic methods and automatic boundary detection on two occasions separated by at least a week. On the second visit measurements were also repeated in healthy volunteers after acute intravenous volume loading with 1 litre of saline over 2-5 minutes. SETTING--A university medical school echocardiographic laboratory. SUBJECTS--12 healthy male volunteers and 8 patients with cardiac disease (5 with congestive heart failure, 1 with mitral stenosis, and 2 with hypertensive left ventricular hypertrophy, and dilated left atria). RESULTS--There was close correlation between conventionally derived left atrial areas and those obtained by automatic boundary detection, particularly in the apical four chamber view (r = 0.98). Both inter and intra observer variabilities (coefficient of variation) for left atrial areas measured by automatic boundary detection were good (4.7-14.2% and 8.1-18.6% respectively). The reproducibility (coefficient of variation) for derived indices of left atrial function, however, was much poorer (10.4-104.8% and 12.5-88% respectively). After acute volume loading significant increases in left atrial area were observed at all stages in the cardiac cycle. CONCLUSIONS--These data demonstrate that although the reproducibility of left atrial functional indices is poor, instantaneous left atrial cavity measurements with automatic boundary detection are reproducible. This suggests that automatic boundary detection may assist in serial non-invasive measurement of left atrial size to assess disease states and treatments.

Background As IT dominates cardiology, the ability of centres to link clinical databases to perform outcome based research has increased significantly. Good quality research relies on the ability to accurately identify and characterise the disease of interest in the population. Heart Failure is one such disease that is often challenging to define from datasets. Uniquely we have the ability to link the Tayside echocardiography dataset to other regional datasets including dispensed prescription and hospitalisation data. Echocardiography reports are commonly comprised of structured, usually numerical values, and a free text component to store overall conclusions or impressions. We therefore sought to develop a computer algorithm to determine LV function from the free text and subsequently to validate the ability to define systolic HF based upon LVSD and loop diuretic therapy. Methods We iteratively the algorithm to process the free text component the reports and determine the degree of impairment. The algorithm was comprised of a lexicon of words and phrases and applied with negation detection. This was repetitively enhanced by recurrent processing of a subset of the data. The final algorithm was subsequently applied to the full dataset and was validated, first, against blinded manual review of a subset of reports and second by blinded review of the stored images. The data were then linked using a unique patient identifier to the dispensed prescribing data to determine loop diuretic use. The specificity of diagnosis of systolic heart failure was examined by blinded case note review. Results The database contained 153 836 reports on 63 309 individuals. The lexicon comprised 488 keywords or phrases. When applied to the data 145 525 reports were classified (94.4%), while 8584 remained unclassified. (5969 (70%) contained no information in the free text fields, and the remainder provided either insufficient data on left ventricular function or severe spelling or typographical errors, preventing matching.) 19 758 were classified as having LVSD (5378 (27%) mild, 818 (4%) mild to moderate, 4646 (24%) moderate, 583 (3%) moderate to severe and 8333 (42%) severe). The validation of 1000 reports reviewed for the presence or absence of LVSD found concurrence with the algorithm in 980 (98%) cases. Blinded review of the stored movies and images revealed a 90% concordance for the presence or absence of LVSD. Record linkage with the dispensed prescription dataset identified 9875 individuals with LVSD who also received loop diuretic therapy. Validation, by case note review, demonstrated a 91% concordance with a clinical diagnosis of systolic HF. Conclusion A computer algorithm can quickly and accurately identify the degree of LVSD from the free text component on an echocardiogram report and the presence of LVSD and combined with loop diuretic use is specific for a diagnosis of systolic heart failure.

Summary In view of the increased risk of cardiac events in systemic hypertension, particularly in patients with left ventricular hypertrophy, it is important to have reliable methods of assessing cardiac structure and function and myocardial perfusion in these patients. While echocardiography is the noninvasive method of choice for measuring the severity of left ventricular hypertrophy there is no alternative at present to invasive coronary angiography to define accurately coronary artery anatomy. Nuclear cardiological investigations are extremely useful in the assessment of systolic and diastolic function at rest and during exercise. Furthermore, myocardial perfusion imaging is of value in identifying myocardial ischaemia and assessing the functional importance of coronary artery lesions. Recent studies have also suggested that nuclear cardiology investigations may be the best way to identify nonfunctioning but viable areas of the myocardium which may benefit from revascularization.

Background Volume overload seen in mitral regurgitation (MR) leads to neuro-endocrine activation including heightened sympathetic activity. Experimental data have reported protective effects of beta-blockers (BBs) on myocardial function in MR suggesting that BB therapy may be beneficial in MR. However, the effect of BB therapy on clinical outcomes in MR has not been defined. Hence, in this large observational study we investigated the impact of BB therapy on clinical outcome in patients with moderate to severe MR. Methods The Health Informatics dispensed prescribing, morbidity and mortality database for the population of Tayside, Scotland was linked through a unique patient identifier to the Tayside echocardiography database (>110 000 scans). Patients with a diagnosis of moderate or severe MR from 1993 to 2008 were identified. Cox regression model (adjusted for age, gender, left ventricular dimensions and function, left atrial diameter, cardiovascular (CV) history and concurrent CV medications) was used to assess the impact of BB therapy on all-cause mortality and cardiovascular events (CV death or hospitalisations). Results A total of 4437 patients with moderate to severe MR (mean age 74 ±11 years, 46% males) were identified. MR was categorised as functional in 2523 (57%) and organic in 1894 (43%) while 1324 (30%) were on BBs. Over a mean follow-up of 3.9 years there were 2287 (51%) all-cause deaths and 2333 (52%) CV events. Those treated with BBs had a significantly lower all-cause mortality with an adjusted HR of 0.65 (95% CI 0.56 to 0.75, p Conclusions This large observational study suggests that BB therapy is associated with an improved survival and a lower risk of CV events in patients with moderate to severe MR. These observations needs to be confirmed in prospective studies and support the rationale for undertaking a future randomised clinical trial.

M-mode echocardiograms of 202 cardiac patients were studied with respect to the pattern of left ventricular (LV) geometry. Patients with normal LV mass and volume were separated from those who had LV hypertrophy or enlargement on the basis of LV mass and volume indexed to body surface area. The relative wall thickness that is currently used to classify LV hypertrophy/enlargement was found to be inadequate for differentiating between concentric and eccentric types of LV hypertrophy. A new M-mode echocardiographic classification is therefore proposed that accurately separates the different types of LV enlargement; it also allows identification of patients who have chronically dilated left ventricles at the expense of thin walls and thus have normal LV mass.

BACKGROUND--Classically, the ST-T configuration in the electrocardiogram of patients with left ventricular hypertrophy is said to have a typical pattern of ST depression together with asymmetrical T wave inversion (the so-called left ventricular strain pattern). However, many patients with left ventricular hypertrophy may also have ischaemic heart disease. To revise the electrocardiographic criteria for left ventricular hypertrophy the ST-T configuration in patients with left ventricular hypertrophy documented by echocardiography and with normal coronary arteries was assessed. METHODS--24 patients were selected for this study. All had left ventricular hypertrophy documented by echocardiography, normal coronary arteries by cardiac catheterisation, and ST and/or T wave abnormalities in the lateral leads of their electrocardiogram. There were eight patients with aortic valve disease and 16 with hypertension who had coronary angiography as part of an investigation into the risk factors of sudden cardiac death caused by hypertensive left ventricular hypertrophy. No patient was receiving digitalis preparations or had electrolyte disturbances, and none had a previous myocardial infarction or ventricular conduction defect. RESULTS--Typical electrocardiographic evidence of left ventricular strain was found in approximately two thirds (63%) of patients and 95% of this subgroup had asymmetrical T wave inversion. Flat ST segment depression, with or without T wave inversion or isolated T wave inversion (symmetrical or asymmetrical) in the anterolateral leads, was seen in the remaining 37% of patients. CONCLUSIONS--These findings indicate that left ventricular hypertrophy without coronary artery disease can cause variable types of ST-T abnormalities in the anterolateral leads including the typical left ventricular strain pattern and non-specific ST-T changes. Non-specific abnormalities could not be distinguished from those of coronary artery disease and may adversely affect the accuracy of the electrocardiographic criteria for the diagnosis of left ventricular hypertrophy because they do not accord with the criteria for left ventricular strain.

Left ventricular dimensions were measured on M-mode echocardiograms, both by the Penn Convention and the Recommendations of the American Society of Echocardiographers in a sample cardiac population. The measurements of interventricular septum and the posterior wall of the left ventricle were significantly larger (P less than 0.001) using American Society Recommendations compared to using the Penn Convention. However, the left ventricular internal dimension at end-diastole was significantly larger (P less than 0.001) when measured by the Penn Convention. As a result of the differences in left ventricular dimensions, the left ventricular mass indexed to body surface area was significantly higher (P less than 0.001) using American Society as opposed to Penn measurements. On the other hand, left ventricular volume indexed to body surface area was significantly higher (P less than 0.001) on Penn measurements than on American Society estimates. These differences should be considered in any study where criteria of normality are to be applied. Good positive correlation (r greater than 0.9) between Penn and American Society estimates of indexed left ventricular volume allowed development of a regression equation to convert volumes from one convention to another. As a result, an upper normal limit of 100 ml/m2 for indexed left ventricular volume is suggested for measurements made using the Penn Convention.

We present a patient with QT interval prolongation and torsades de pointes of multifactorial etiology who was successfully treated over the short term with intravenous amiodarone, despite resultant further QT interval prolongation

Objective: To assess the comparative contribution of clinical assessment, electrocardiography, and chest radiography to the diagnosis of left ventricular systolic dysfunction in patients admitted to a general medical ward with acute dyspnoea. Design: Prospective cross sectional study. Setting: Acute medical admissions ward of a teaching hospital. Subjects: 71 randomly selected patients admitted with acute dyspnoea. Main outcome measures: Sensitivity and specificity of each investigation and logistic regression analysis of each variable in identifying left ventricular systolic dysfunction. Results: Clinical assessment in this cohort of patients with severe dyspnoea was generally sensitive (sensitivity 81%). Patients were divided into three groups on the basis of clinical assessment. In the first group (37 patients) the diagnosis of systolic dysfunction was clear, in the second (22) it was in doubt, and in the third (12) it was unlikely. The sensitivity of clinical assessment in identifying left ventricular systolic dysfunction was 81% and the specificity was 47%. The specificity of diagnosis was improved by electrocardiography (69%) and chest radiography (92%). Logistic regression analysis showed that isolated pulmonary crepitations were a comparatively poor predictor of left ventricular systolic dysfunction (2=10.215, P=0.0014) but that a full clinical examination had reasonable predictive value (2=24.82, P Conclusion: Clinical assessment in patients admitted with acute dyspnoea is comparatively accurate. Patients with abnormal results on chest radiography, electrocardiography, and clinical examination have a high likelihood of having left ventricular systolic dysfunction. Echocardiography contributes little more to the diagnosis in these patients and may be more efficiently directed towards patients in whom the diagnosis is still in doubt after clinical assessment, chest radiography, and electrocardiography. Key messages The availability of echocardiography is limited for patients admitted to hospital with acute dyspnoea The presence of isolated lung crepitations is a poor predictor of left ventricular systolic dysfunction Full clinical assessment is sensitive in detecting left ventricular systolic dysfunction, with specificity being added by either chest radiography or electrocardiography Echocardiography should be reserved for cases with the most diagnostic doubt

To investigate the significance of the electrocardiographic (ECG) pattern of left ventricular hypertrophy and strain, two groups of asymptomatic patients with essential hypertension were compared. The patients were similar in terms of age, smoking habit, serum cholesterol and blood pressure levels, but differed in the presence (Group I, n = 23) or absence (Group II, n = 23) of the ECG pattern of left ventricular hypertrophy and strain. Group I patients had significantly more episodes of exercise-induced ST segment depression (14 versus 4, p less than 0.05) and reversible thallium perfusion abnormalities (11 of 23 versus 3 of 23, p less than 0.05) despite similar exercise capacity and absence of chest pain. Nonsustained ventricular tachycardia was detected on 24 h ambulatory ECG monitoring in two patients in Group I, but no patient in Group II. Coronary arteriography performed in 20 Group I patients demonstrated significant coronary artery disease in 8 patients. This study has shown that there is a subgroup of hypertensive patients with ECG left ventricular hypertrophy and strain who have covert coronary artery disease. This can be detected by thallium perfusion scintigraphy, and may contribute to the increased risk known to be associated with this ECG abnormality.

Considerable attention has properly been focused in recent years on electrocardiographs abnormalities in patients with essential hypertension. It has been well established that both voltage evidence of left ventricular (LV) hypertrophy and LV hypertrophy and strain are ominous risk factors. A better understanding of the strain pattern in patients with LV hypertrophy has arisen from experimental animal studies showing how an increase in cardiac mass can lead to myocardial ischemia and from clinical studies showing that the patient with LV hypertrophy and strain is at risk from myocardial ischemia as a consequence of both associated coronary artery disease and increased LV mass. All the clinical syndromes associated with myocardial ischemia are increased in patients with LV hypertrophy and therefore earlier recognition of both cardiac involvement and myocardial ischemia is likely to improve survival in this particularly high-risk group of patients.

Short-term therapy with angiotensin converting enzyme (ACE) inhibitors for hypertension is effective and well tolerated, and compared with beta blockers, may cause fewer adverse reactions. Furthermore, enalapril has been observed to have a greater effect on systolic blood pressure than beta blockers. We therefore decided to compare the ACE inhibitor enalapril and the beta blocker atenolol as monotherapy in a double-blind study of patients with mild to moderate hypertension.After a four-week placebo run-in period, 162 patients were allocated randomly to receive atenolol (50 to 100 mg daily) or enalapril (20 to 40 mg daily) for 12 weeks. To assess the influence of these drugs on quality of life, a series of psychologic tests was performed, and a subset of patients also underwent treadmill exercise and pulmonary function tests.In 147 patients who completed the study, enalapril reduced supine blood pressure by 19/12 mm Hg, compared with 9/7 mm Hg for atenolol (p less than 0.001/p less than 0.005). The modest blood pressure response to atenolol was not due to poor compliance. A target blood pressure of 140/90 mm Hg or less was achieved by 35 percent of enalapril-treated atenolol (p less than 0.01). The frequency and severity of adverse effects with the two drugs were similar, and few important differences emerged from the quality-of-life assessments.At the doses used, enalapril induced a greater short-term blood pressure response than atenolol; long-term studies of its safety and efficacy are required.

Three thousand seven hundred and eighty-three patients with non-malignant hypertension attending the Glasgow Blood Pressure Clinic between 1968 and 1983 were followed prospectively for an average of 6.5 years. Left ventricular hypertrophy (LVH) was present at the outset in 34.5% of the men, and 12.8% had ST-T changes. The corresponding figures for women were 21.5% and 8.8%. The prevalence of LVH increased with the severity of hypertension and was higher for a given blood pressure level in men than in women. All-cause age-adjusted mortality, expressed as deaths per 1000 patient-years, was 27.6 for men with normal electrocardiographs, 43.2 for men with LVH only (P less than 0.001) and 56.9 for men with LVH and ST-T changes (P less than 0.001). Similar trends were seen in women. The excess risk associated with LVH, with or without ST-T changes, could not be explained by age, increased blood pressure at referral to the clinic, or smoking habit, when these factors were considered either separately or in combination (regression analysis). Thus, our study demonstrates that LVH, with or without ST-T changes is an independent risk factor for mortality in hypertensive patients.