Four year follow up of aortic valve replacement for isolated aortic stenosis: a link between reduction in pressure overload, regression of left ventricular hypertrophy, and diastolic function

OBJECTIVE—To evaluate changes in left ventricular function and the impact of ventricular hypertrophy and pressure gradient early and late after aortic valve replacement in patients with isolated aortic stenosis.
DESIGN—41 patients with isolated aortic stenosis and normal systolic function underwent cross sectional and Doppler echocardiography two months before and two weeks and four years after aortic valve replacement.
RESULTS—Early after the operation, left ventricular mass index (mean (SD)) decreased from 187 (44) g/m² to 179 (46) g/m², because of a reduction in end diastolic diameter (p < 0.05). Aortic pressure gradients were reduced, as expected. Isovolumic relaxation time was reduced from 93 (20) ms to 78 (12) ms, and deceleration time from 241 (102) ms to 205 (77) ms (p < 0.05). At four years, left ventricular mass index was further reduced to 135 (30) g/m² (p < 0.01) as a result of wall thickness reduction in the interventricular septum (from 14 (1.6) mm to 12 (1.4) mm, p < 0.01) and the posterior wall (from 14 (1.6) mm to 12 (1.3) mm, p < 0.01). Diastolic function, expressed by a reduction in isovolumic relaxation time from 93 (20) ms to 81 (15) ms (p < 0.01) and deceleration time from 241 (102) ms to 226 (96) ms (p < 0.05), remained improved. Prolonged isovolumic relaxation time was associated with significant septal and posterior wall hypertrophy (wall thickness > 13 mm) (p < 0.05), whereas prolonged deceleration time was related to high residual gradient (peak gradient > 30 mm Hg ) (p < 0.01).
CONCLUSIONS—Left ventricular diastolic function improves early after surgery for aortic stenosis in parallel with the reduction in the aortic gradient. However, prolongation of Doppler indices of myocardial relaxation and ventricular filling is observed in patients with significant left ventricular hypertrophy and a residual pressure gradient early after surgery. At four years postoperatively, diastolic function remains improved.


Keywords: diastolic function; hypertrophy regression; aortic valve replacement; aortic stenosis     

Left ventricular function in adults with mild pulmonary insufficiency late after Fallot repair

OBJECTIVE—To assess left ventricular function in adult Fallot patients with residual pulmonary regurgitation.
SETTING—The radiology department of a tertiary referral centre.
PATIENTS—14 patients with chronic pulmonary regurgitation and right ventricular volume overload after repair of tetralogy of Fallot and 10 healthy subjects were studied using magnetic resonance imaging.
MAIN OUTCOME MEASURES—Biventricular volumes, global biventricular function, and regional left ventricular function were assessed in all subjects.
RESULTS—The amount of pulmonary regurgitation in patients (mean (SD)) was 25 (18)% of forward flow and correlated significantly with right ventricular enlargement (p < 0.05). Left ventricular end diastolic volume was decreased in patients (78 (11) v 88 (10) ml/m²; p < 0.05), ejection fraction was not significantly altered (59 (5)% v 55 (7)%; NS). No significant correlation was found between pulmonary regurgitation and left ventricular function. Overall left ventricular end diastolic wall thickness was significantly lower in patients (5.06 (0.72) v 6.06 (1.06) mm; p < 0.05), predominantly in the free wall. At the apical level, left ventricular systolic wall thickening was 20% higher in Fallot patients (p < 0.05). Left ventricular shape was normal.
CONCLUSIONS—Adult Fallot patients with mild chronic pulmonary regurgitation and subsequent right ventricular enlargement showed a normal left ventricular shape and global function. Although the left ventricular free wall had reduced wall thickness, compensatory hypercontractility of the apex may contribute to preserved global function.


Keywords: left ventricular function; pulmonary insufficiency; tetralogy of Fallot; magnetic resonance imaging     

Assessment of ventricular diastolic function in AIDS patients from Congo: a Doppler echocardiographic study

Objective—To investigate the prevalence of left ventricular dysfunction in African patients infected with the human immunodeficiency virus (HIV). The hypothesis was that HIV infected patients with left ventricular dysfunction are asymptomatic.
Methods—M mode, cross sectional, and Doppler echocardiography were performed in 49 consecutive patients (30 HIV positive (HIV+) carriers and 19 AIDS patients). None of the patients or 58 controls had a medical history of cardiovascular abnormalities.
Results—Cardiac abnormalities were not suspected on physical, electrocardiographic, and radiological examination. Forty two of the HIV infected patients had left ventricular diastolic dysfunction; this was more pronounced in AIDS patients than in HIV+ carriers. Systolic function was normal in both stages of HIV infection. Left ventricular isovolumic relaxation time (mean (SD)) increased from 87.2 (12.4) ms in the carrier state to 103.9 (19.3) ms in AIDS (p < 0.05, Bonferoni correction), peak early filling velocity declined from 0.54 (0.1) to 0.44 (0.1) m/s (p < 0.05), and late velocity increased from 0.64 (0.1) to 0.69 (0.2) m/s. A restrictive filling pattern was explained by concentric hypertrophy in 23 HIV infected patients, and by systemic amyloidosis with left ventricular dilatation in 12 of 49 HIV infected patients.
Conclusions—Echocardiography is a useful technique for detecting left ventricular diastolic dysfunction in HIV infected patients with clinically unsuspected cardiac lesions. Systolic function was normal despite the presence of such cardiac abnormalities.

Keywords: HIV infection; AIDS; diastolic dysfunction; black Africans; echocardiography     

Mechanical properties of the common carotid artery in Williams syndrome

OBJECTIVE—To determine whether arterial wall hypertrophy in elastic arteries was associated with alteration in their mechanical properties in young patients with Williams syndrome.
METHODS—Arterial pressure and intima-media thickness, cross sectional compliance, distensibility, circumferential wall stress, and incremental elastic modulus of the common carotid artery were measured non-invasively in 21 Williams patients (mean (SD) age 8.5 (4) years) and 21 children of similar age.
RESULTS—Systolic and diastolic blood pressures were higher in Williams patients (125/66 v 113/60 mm Hg, p < 0.05). The mean (SD) intima-media thickness was increased in Williams patients, at 0.6 (0.07) v 0.5 (0.03) mm (p < 0.001). Normotensive Williams patients had a lower circumferential wall stress (2.1 (0.5) v 3.0 (0.7) mm Hg, p < 0.01), a higher distensibility (1.1 (0.3) v 0.8 (0.3) mm Hg⁻¹.10⁻², p < 0.01), similar cross sectional compliance (0.14 (0.04) v 0.15 (0.05) mm².mm Hg⁻¹, p > 0.05), and lower incremental elastic modulus (7.4 (2.0) v 14.0 (5.0) mm Hg.10²; p < 0.001).
CONCLUSIONS—The compliance of the large elastic arteries is not modified in Williams syndrome, even though increased intima-media thickness and lower arterial stiffness are consistent features. Therefore systemic hypertension cannot be attributed to impaired compliance of the arterial tree in this condition.


Keywords: elastin; Williams syndrome; hypertension; compliance     

Different effects of abnormal activation and myocardial disease on left ventricular ejection and filling times

BACKGROUND—Ventricular activation is often abnormal in patients with dilated cardiomyopathy, but its specific effects on timing remain undetermined.
OBJECTIVE—To investigate the use of the ratio of the sum of left ventricular ejection and filling times to the total RR interval (Z ratio) to dissociate the effects of abnormal activation from those of cavity dilatation.
METHODS—Subjects were 20 normal individuals, 11 patients with isolated left bundle branch block (LBBB, QRS duration > 120 ms), 17 with dilated cardiomyopathy and normal activation, and 23 with dilated cardiomyopathy and LBBB. An additional 30 patients (nine with normal ventricular systolic function and 21 with dilated cardiomyopathy) were studied before and after right ventricular pacing. Left ventricular ejection and filling times were measured by pulsed wave Doppler and cavity size by M mode echocardiography.
RESULTS—Z ratio was independent of RR interval in all groups. Mean (SD) Z ratio was 82 (10)% for normal subjects, 66 (10)% for isolated LBBB (p < 0.01 v normal), 77 (7)% for dilated cardiomyopathy without LBBB (NS v normal), and 61 (7)% for dilated cardiomyopathy with LBBB (p < 0.01 v normal). In the nine patients with normal left ventricular size and QRS duration, Z ratio fell from 88 (6)% in sinus rhythm to 77 (10)% with right ventricular pacing (p = 0.26). In the 21 patients with dilated cardiomyopathy and LBBB, Z ratio rose from 59 (10)% in sinus rhythm to 74 (9)% with right ventricular DDD pacing (p < 0.001).
CONCLUSIONS—Z ratio dissociates the effects of abnormal ventricular activation and systolic disease. It also clearly differentiates right ventricular pacing from LBBB. It may thus be useful in comparing the haemodynamic effects of different pacing modes in patients with or without left ventricular disease.


Keywords: dilated cardiomyopathy; pacemaker; left bundle branch block; echocardiography.     

Patients with acute coronary syndromes express enhanced CD40 ligand/CD154 on platelets

OBJECTIVE—To investigate whether CD40L/CD154 on platelets and soluble CD40L/CD154 may play a role in the inflammatory process of acute coronary syndromes.
DESIGN AND SETTING—Observational study in a university hospital.
PATIENTS—15 patients with acute myocardial infarction, 25 patients with unstable angina, 15 patients with stable angina, and 12 controls.
MAIN OUTCOME MEASURES—CD40L/CD154 on platelets, P-selectin/CD62P on platelets, soluble CD40L/CD154 serum concentrations.
RESULTS—Mean (SD) CD40L/CD154 expression on platelets was 6.2 (2.8) MFI (mean fluorescence intensity) in the infarct group, 11 (3.3) MFI in the unstable angina group (p < 0.001 v infarction), 3.6 (0.9) MFI in the stable angina group (p < 0.01 v infarction; p < 0.001 v unstable angina), and 3.2 (1.0) MFI in the controls (p < 0.01 v infarction; p < 0.001 v unstable angina; NS v stable angina). Soluble CD40L/CD154 concentration was 5.2 (1.1) ng/ml in the infarct group, 4.2 (0.7) ng/ml in the unstable angina group (p < 0.001 v infarction), 2.9 (1.0) ng/ml in stable angina group (p < 0.001 v infarction and unstable angina), and 3.0 (0.5) ng/ml in the controls (p < 0.001 v infarction and unstable angina; NS v stable angina). At a six months follow up, there was lower expression of CD40L/CD154 on platelets in patients with unstable angina (12.3 (3.6) v 3.8 (1.2) MFI, p < 0.0001) and acute myocardial infarction (6.2 (2.8) v 3.5 (0.8) MFI, p < 0.01) compared with their admission values six months earlier. Patients with unstable angina who needed redo coronary angioplasty (PTCA) or who had recurrence of angina were characterised by increased CD40L/CD154 expression on platelets compared with the remainder of the study group (recurrence of angina: 12.7 (3.2) v 9.7 (1.6) MFI, p < 0.05; re-do PTCA: 14.3 (4.2) v 10.3 (2.1) MFI, p < 0.05).
CONCLUSIONS—Both CD40L/CD154 on platelets and soluble CD40L/CD154 are raised in patients with unstable angina and myocardial infarction. These findings suggest that CD40-CD40L/CD154 interactions may play a pathogenic role in triggering and propagation of acute coronary syndromes.


Keywords: acute coronary syndromes; unstable angina; CD40L/CD154; platelets     

Natural history and surgical outcomes for isolated discrete subaortic stenosis in children

OBJECTIVE—To document the natural history and surgical outcomes for discrete subaortic stenosis in children.
DESIGN—Retrospective review.
SETTING—Tertiary care paediatric cardiology centres.
PATIENTS—92 children diagnosed between 1985 and 1998.
MAIN OUTCOME MEASURES—Echocardiographic left ventricular outflow gradient (echograd), and aortic insufficiency (AI).
RESULTS—The mean (SEM) age at diagnosis was 5.3 (0.4) years; the mean echograd was 30 (2) mm Hg, with AI in 22% (19/87) of patients. The echograd and incidence of AI increased to 35 (3) mm Hg and 53% (36/68) (p < 0.05) 3.6 (0.3) years later. The echograd at diagnosis predicted echograd progression and appearance of AI. 42 patients underwent surgery 2.2 (0.4) years after diagnosis. Preoperatively echograd and AI incidence increased to 58 (6) mm Hg and 76% (19/25) (p < 0.05). The echograd was 26 (4) mm Hg 3.7 (0.4) years postoperatively, with AI in 82% (31/38) of patients. Surgical morbidities included complete heart block, need for prosthetic valves, and iatrogenic ventricular septal defects. Eight patients underwent reoperation for recurrent subaortic stenosis. The age at diagnosis of 44 patients followed medically and 42 patients operated on did not differ (5.5 (0.6) v 5.0 (0.6) years, p < 0.05). However, the echograd at diagnosis in the former was less (21 (2) v 40 (5) mm Hg, p < 0.05) and did not increase (23 (2) mm Hg) despite longer follow up (4.1 (0.4) v 2.2 (0.4) years, p < 0.05). The incidence of AI at diagnosis and at last medical follow up was also less (14% (6/44) v 34% (13/38); 40% (17/43) v 76% (19/25), p < 0.05).
CONCLUSIONS—Many children with mild subaortic stenosis exhibit little progression of obstruction or AI and need not undergo immediate surgery. Others with more severe subaortic stenosis may progress precipitously and will benefit from early resection despite risks of surgical morbidity and recurrence.


Keywords: subaortic stenosis; congenital heart disease; cardiac surgery     

Relation between right ventricular enlargement, QRS duration, and right ventricular function in patients with tetralogy of Fallot and pulmonary regurgitation after surgical repair

OBJECTIVE—In patients with repaired tetralogy of Fallot, to examine (1) a possible relation between right ventricular enlargement and QRS prolongation, and (2) the effect of right ventricular enlargement caused by pulmonary regurgitation on the right ventricular ejection fraction, evaluated by three dimensional echocardiography, and global function, evaluated by the myocardial performance index.
DESIGN AND PATIENTS—40 patients with repaired tetralogy were studied. Right ventricular volumes were derived from three dimensional echocardiographic data after this method had been validated by comparison with magnetic resonance imaging in 21 patients. Ejection fraction was calculated from end diastolic and end systolic volumes. The Doppler derived myocardial performance index was measured in all patients. Measured data were correlated with QRS duration.
SETTING—Tertiary cardiac centre for congenital heart disease.
RESULTS—There was good agreement between three dimensional echocardiographic and magnetic resonance assessment of right ventricular volumes and ejection fraction. The z score of the right ventricular end diastolic volume and ejection fraction of all patients was 1.35 and −4.15, respectively. Patients with severe pulmonary regurgitation had a lower right ventricular ejection fraction (p < 0.01) and an increased myocardial performance index (p < 0.01) compared with patients with mild to moderate pulmonary regurgitation. The correlation between ejection fraction and right ventricular end diastolic volume was r = −0.35 (p < 0.05). The mean (SD) QRS duration was 131.89 (25.69) ms, range 80-180 ms. The correlation between QRS duration and right ventricular end diastolic volume was r = 0.6 (p < 0.01).
CONCLUSIONS—There is a correlation between the right ventricular size obtained by three dimensional echocardiography and QRS duration on the surface ECG, indicating mechanoelectrical interaction. The severity of pulmonary regurgitation has a negative influence on right ventricular ejection fraction and combined systolic and diastolic global function, as assessed by myocardial performance.


Keywords: tetralogy of Fallot; pulmonary regurgitation; right ventricular enlargement; QRS prolongation     

Resetting of the cardiopulmonary baroreflex 10 years after surgical repair of coarctation of the aorta

OBJECTIVE—To characterise cardiopulmonary baroreflex responses and examine the effects of a 45 minute cycling bout late after successful repair of coarctation of the aorta.
SUBJECTS—10 young adults (mean (SEM) age 18.1 (2.6 years)) operated on for coarctation of the aorta 12.7 (3.5) years earlier, and 10 healthy controls.
DESIGN—Forearm blood flow (venous occlusion plethysmography) and vascular resistance, left ventricular internal diastolic diameter, and central venous pressure estimated from an antecubital vein were measured in the supine position at baseline and during five minute applications of lower body negative pressure (LBNP) at −15 mm Hg (LBNP₋₁₅) and −40 mm Hg (LBNP₋₄₀). Venous samples were obtained at baseline and during LBNP₋₄₀ for noradrenaline (norepinephrine), adrenaline (epinephrine), renin activity, and aldosterone. The tests were repeated after 45 minutes of moderate exercise.
RESULTS—Baseline heart rate (78 (9) v 64 (6) beats/min), echocardiographic cardiac output (6.9 (1.1) v 5.0 (0.2) l/min), shortening fraction (41.7 (1.8)% v 33.3 (1.3)%), and forearm blood flow (3.4 (0.4) v 2.3 (0.3) ml/100 g/min) were higher in the coarctation group than in the controls (p < 0.05). Changes in forearm blood flow and forearm vascular resistance from baseline to LBNP₋₄₀ were similar in both groups, but the relation between forearm vascular resistance and estimated central venous pressure or left ventricular internal diastolic diameter was shifted downward in the coarctation group. Plasma adrenaline was increased in the coarctation group (baseline: 3.2 (0.6) v 2.4 (0.3) pmol/l in controls; LBNP₋₄₀: 687 (151) v 332 (42) pmol/l) (p < 0.05). Both groups showed a similar downward displacement of forearm vascular resistance (p < 0.05) after exercise.
CONCLUSIONS—There appears to be resetting of the cardiopulmonary baroreflex to a lower forearm vascular resistance in young adults operated on for coarctation of the aorta, associated with hyperdynamic left ventricular function. Raised circulating adrenaline could contribute to the lower forearm vascular resistance.


Keywords: coarctation of aorta; cardiopulmonary baroreflex; forearm vascular resistance; circulating catecholamines     

Cognitive impairment in heart failure with Cheyne-Stokes respiration

OBJECTIVES—To document the degree of cognitive impairment in stable heart failure, and to determine its relation to the presence of Cheyne-Stokes respiration during sleep.
SUBJECTS—104 heart failure patients and 21 healthy normal volunteers.
METHODS—Overnight oximetry was used (previously validated as a screening tool for Cheyne-Stokes respiration in heart failure). Cognitive function was assessed using a battery of neuropsychological tests. Left ventricular function was assessed by echocardiography.
RESULTS—Heart failure patients performed worse than the healthy volunteers in tests that measured vigilance. Reaction times were 48% slower (0.89 (0.03) s v 0.60 (0.05) s; p < 0.005) and they hit twice as many obstacles on the Steer Clear simulator (75 (6.4) v 33 (4.6); p < 0.005). Cognitive impairment within the heart failure group was unrelated to either the presence of Cheyne-Stokes respiration, the degree of left ventricular dysfunction, or indices of nocturnal oxygenation.
CONCLUSIONS—Vigilance was impaired in heart failure but this did not appear to be related to the presence of Cheyne-Stokes respiration during sleep. Impaired vigilance as measured on the Steer Clear test has been associated with an increased risk of motor vehicle accidents. The issue of fitness to drive in heart failure requires further attention.


Keywords: Cheyne-Stokes respiration; cognitive function; heart failure; driving     

Combination treatment with trimetazidine and diltiazem in stable angina pectoris

Objective—To assess antianginal efficacy and possible adverse haemodynamic effects of combination treatment with trimetazidine and diltiazem in patients with stable angina.
Design—Double blind, randomised, placebo controlled trial of four weeks duration.
Setting—Outpatient department of two Indian hospitals.
Subjects—64 male patients with stable angina, uncontrolled on diltiazem alone.
Interventions—Diltiazem 180 mg and trimetazidine 60 mg, or diltiazem 180 mg and placebo daily.
Main outcome measure—Change in exercise time to 1 mm ST segment depression.
Results—33 patients (55%) had no exercise induced angina at 3 mm ST segment depression at inclusion in the study (silent ischaemia). Intention to treat analysis showed that of 32 patients in each treatment group, the number (%) of patients responding to trimetazidine compared to placebo was: for anginal attacks, 28 (87.5) v 15 (46.9), p < 0.001; for exercise time to 1 mm ST segment depression, 21 (65.6) v 9 (28.1), p < 0.003; for exercise time to angina, 12 (37.5) v 5 (15.6), p < 0.05; and for maximum work at peak exercise, 17 (53.1) v 8 (25), p < 0.02. Compared to placebo, there was net improvement with trimetazidine in mean anginal attacks of 4.8/week (95% confidence interval (CI) 7.5 to 2.1; p < 0.002); in mean exercise times at 1 mm ST segment depression of 94.2 seconds (95% CI 182.8 to 5.6; p < 0.05), and at onset of angina of 113.1 seconds (95% CI 181.6 to 44.6; p < 0.02); and in mean maximum work at peak exercise of 1.4 metabolic equivalents (95% CI 2.4 to 0.3; p < 0.05).
Conclusions—Patients with stable angina uncontrolled with diltiazem had a clinically important improvement after combination treatment with trimetazidine, without adverse haemodynamic events or increased side effects.

Keywords: trimetazidine;  diltiazem;  blood pressure;  stable angina;  treatment     

N-terminal proatrial natriuretic peptide correlates with systolic dysfunction and left ventricular filling pattern in patients with idiopathic dilated cardiomyopathy

OBJECTIVE—To investigate the diastolic Doppler filling pattern in patients with idiopathic dilated cardiomyopathy and its relation to N-terminal pro-atrial natriuretic peptide (NT-pro-ANP).
METHODS—32 patients (26 male, six female) with idiopathic dilated cardiomyopathy were investigated. All were in sinus rhythm. Conventional M mode echocardiography and Doppler echocardiography was done in each patient. Pulsed wave Doppler inflow signals were obtained and the following variables were measured: maximum E wave, maximum A wave, E/A ratio, E wave deceleration time, A wave deceleration time. NT-pro-ANP was measured using radioimmunoassay.
RESULTS—Mean (SD) left ventricular ejection fraction was 34 (7)% and mean left ventricular end diastolic diameter on M mode echocardiography was 69 (7) mm. Left ventricular filling indices were as follows: maximum E wave velocity, 0.86 (0.22) m/s; maximum A wave velocity, 0.71 (0.24) m/s; E/A ratio, 1.41 (0.65). Mean E wave deceleration time was 140 (50) ms; mean A wave deceleration time was 100 (20) ms. In a stepwise forward regression model, NT-pro-ANP correlated significantly with left atrial diameter (r = 0.603; p < 0.001), left ventricular ejection fraction (r = −0.758; p < 0.001), and Doppler derived E/A ratio (r = 0.740; p < 0.001).
CONCLUSIONS—In patients with idiopathic dilated cardiomyopathy there is a relation between NT-pro-ANP and both systolic and diastolic variables. In a multivariate model NT-pro-ANP correlated with left atrial diameter, left ventricular ejection fraction, and Doppler derived E/A ratio on transmitral inflow.


Keywords: idiopathic dilated cardiomyopathy; transmitral Doppler filling; N-terminal pro-ANP; atrial natriuretic factor     

Relaxation in hypertrophic cardiomyopathy and hypertensive heart disease: relations between hypertrophy and diastolic function

AIM—To determine the relation between the extent and distribution of left ventricular hypertrophy and the degree of disturbance of regional relaxation and global left ventricular filling.
METHODS—Regional wall thickness (rWT) was measured in eight myocardial regions in 17 patients with hypertrophic cardiomyopathy, 12 patients with hypertensive heart disease, and 10 age matched normal subjects, and an asymmetry index calculated. Regional relaxation was assessed in these eight regions using regional isovolumetric relaxation time (rIVRT) and early to late peak filling velocity ratio (rE/A) derived from Doppler tissue imaging. Asynchrony of rIVRT was calculated. Doppler left ventricular filling indices were assessed using the isovolumetric relaxation time, the deceleration time of early diastolic filling (E-DT), and the E/A ratio.
RESULTS—There was a correlation between rWT and both rIVRT and rE/A in the two types of heart disease (hypertrophic cardiomyopathy: r = 0.47, p < 0.0001 for rIVRT; r = −0.20, p < 0.05 for rE/A; hypertensive heart disease: r = 0.21, p < 0.05 for rIVRT; r = −0.30, p = 0.003 for rE/A). The degree of left ventricular asymmetry was related to prolonged E-DT (r = 0.50, p = 0.001) and increased asynchrony (r = 0.42, p = 0.002) in all patients combined, but not within individual groups. Asynchrony itself was associated with decreased E/A (r = −0.39, p = 0.01) and protracted E-DT (r = 0.69, p < 0.0001) and isovolumetric relaxation time (r = 0.51, p = 0.001) in all patients. These correlations were still significant for E-DT in hypertrophic cardiomyopathy (r = 0.56, p = 0.02) and hypertensive heart disease (r = 0.59, p < 0.05) and for isovolumetric relaxation time in non-obstructive hypertrophic cardiomyopathy (n = 8, r = 0.87, p = 0.005).
CONCLUSIONS—Non-invasive ultrasonographic examination of the left ventricle shows that in both hypertrophic cardiomyopathy and hypertensive heart disease, the local extent of left ventricular hypertrophy is associated with regional left ventricular relaxation abnormalities. Asymmetrical distribution of left ventricular hypertrophy is indirectly related to global left ventricular early filling abnormalities through regional asynchrony of left ventricular relaxation.


Keywords: hypertrophic cardiomyopathy; hypertensive heart disease; isovolumetric relaxation; diastolic function     

Isoprenaline and inducibility of atrioventricular nodal re-entrant tachycardia

Objectives—To examine the effect of isoprenaline on slow and fast pathway properties and tachycardia initiation.
Design—Consecutive patients, prospective study.
Setting—Referral centre for cardiology, academic hospital.
Patients—24 patients suffering from common type atrioventricular nodal re-entrant tachycardia (AVNRT).
Interventions—Programmed electrical stimulation and radiofrequency catheter ablation of the slow pathway.
Measurements and main results—AVNRT was induced before and after the administration of isoprenaline in nine patients (group 1), before isoprenaline only in five (group 2), and after isoprenaline only in 10 (group 3). The anterograde effective refractory period of the fast pathway was prolonged significantly during isoprenaline administration in group 1 (405 (31) v 335 (34) ms, p < 0.001) and shortened in group 2 (308 (57) v 324 (52) ms, p = 0.005). There was also significant shortening in group 3 (346 (85) v 395 (76) ms, p < 0.001). Isoprenaline administration did not result in a significant change of the anterograde effective refractory period of the slow pathway in groups 1 and 3, but eliminated slow pathway conduction in group 2. Isoprenaline significantly shortened the minimal and maximal atrial to His bundle conduction interval recording in response to each extrastimulus of the slow pathway (210 (24) v 267 (25) ms, p < 0.001 and 275 (25) v 328 (25) ms, p < 0.001, respectively) in group 1 and significantly prolonged these intervals (331 (34) v 274 (34) ms and 407 (33) v 351 (33) ms, respectively) in group 3. In all groups only minimal changes in the refractory period of the atrium occurred after isoprenaline administration. The effect of isoprenaline was also measured on the ventricular effective refractory period and on the minimal and maximal length of the ventriculoatrial (V₂-A₂) interval during ventricular pacing. Isoprenaline did not result in a significant change of the ventricular effective refractory period in groups 1 and 2 nor of the shortest and longest V₂-A₂ interval. In group 3, however, the ventricular effective refractory period and the shortest and longest V₂-A₂ interval shortened significantly after isoprenaline administration.
Conclusions—In group 1 isoprenaline did not affect inducibility of AVNRT because it prolonged the fast pathway refractory period without affecting slow pathway conduction. In group 2 isoprenaline shortened the fast pathway refractory period and appeared to abolish slow pathway conduction. Consequencely, isoprenaline prevented induction of AVNRT. In group 3 isoprenaline facilitated induction of AVNRT. This effect seemed primarily to be the result of shortening of retrograde refractoriness of the fast pathway with prolongation of slow pathway anterograde conduction and refractory period.

Keywords: atrioventricular re-entrant tachycardia;  isoprenaline     

Atrial fibrillation is associated with a lower exercise capacity in male chronic heart failure patients

Objective—To study the influence of atrial fibrillation on peak oxygen uptake (peak O₂) in chronic heart failure. An unfavourable effect of atrial fibrillation has been shown in several patient populations, but the results have not been consistent in chronic heart failure.
Methods—Data were analysed from male heart transplant candidates who were able to perform graded bicycle ergometry until exhaustion with respiratory gas analysis and measurement of heart rate. Patients in atrial fibrillation (n = 18) were compared with patients in sinus rhythm (n = 93).
Results—Age, weight, height, and aetiology of chronic heart failure did not differ significantly between the two groups. Cardiac catheterisation at supine rest showed that heart rate was comparable, but that stroke volume and cardiac output were lower (p < 0.05) in atrial fibrillation. Systolic and diastolic left ventricular function, assessed by radionuclide angiography at rest, were not significantly different. Peak O₂ (mean (SD): 13.8 (3.6) v 17.1 (5.6) ml/kg/min; p < 0.01) and peak work load (78 (27) v 98 (36) W; p < 0.05) were lower in the patients with atrial fibrillation, though respiratory gas exchange ratio and Borg score were similar in the two groups. Patients with atrial fibrillation had a higher heart rate sitting at rest before exercise (93 (16) v 84 (16) beats/min) and at peak effort (156 (23) v 140 (25) beats/min) (p < 0.05).
Conclusions—Atrial fibrillation is associated with a 20% lower peak O₂ in patients with chronic heart failure, suggesting that preserved atrial contraction or a regular rhythm, or both, are critical to maintain cardiac output and exercise performance.

Keywords: peak oxygen uptake;  exercise capacity;  chronic heart failure;  atrial fibrillation     

Coronary flow reserve is supranormal in endurance athletes: an adenosine transthoracic echocardiographic study

OBJECTIVE—To compare coronary flow reserve in endurance athletes and healthy sedentary controls, using adenosine transthoracic echocardiography.
METHODS—29 male endurance athletes (mean (SD) age 27.3 (6.6) years, body mass index (BMI) 22.1 (1.9) kg/m²) and 23 male controls (age 27.2 (6.1) years, BMI 23.9 (2.6) kg/m²) with no coronary risk factors underwent transthoracic echocardiographic assessment of distal left anterior descending coronary artery (LAD) diameter and flow, both at rest and during intravenous adenosine infusion (140 µg/kg/min).
RESULTS—Distal LAD diameter and flow were adequately assessed in 19 controls (83%) and 26 athletes (90%). Distal LAD diameter in athletes (2.04 (0.25) mm) was not significantly greater than in sedentary controls (1.97 (0.27) mm). Per cent increase in LAD diameter following 400 µg sublingual nitrate was greater in the athletes than in the controls, at 14.1 (7.2)% v 8.8 (5.7)% (p < 0.01). Left ventricular mass index in athletes exceeded that of controls, at 130 (19) v 98 (14) g/m² (p < 0.01). Resting flow among the athletes (10.6 (3.1) ml/min; 4.4 (1.2) ml/min/100 g left ventricular mass) was less than in the controls (14.3 (3.6) ml/min; 8.2 (2.2) ml/min/100 g left ventricular mass) (both p < 0.01). Hyperaemic flow among the athletes (61.9 (17.8) ml/min) exceeded that of the controls (51.1 (14.6) ml/min; p = 0.02), but not when corrected for left ventricular mass (25.9 (5.6) v 28.5 (7.4) ml/min/100 g left ventricular mass; NS). Coronary flow reserve was therefore substantially greater in the athletes than in the controls, at 5.9 (1.0) v 3.7 (0.7) (p < 0.01).
CONCLUSIONS—Coronary flow reserve in endurance athletes is supranormal and endothelium independent vasodilatation is enhanced. Myocardial hypertrophy per se does not necessarily impair coronary flow reserve. Adenosine transthoracic echocardiography is a promising technique for the investigation of coronary flow reserve.


Keywords: coronary flow reserve; athlete; adenosine transthoracic echocardiography     

A comparison of left ventricular abnormalities associated with glucose intolerance in African Caribbeans and Europeans in the UK

OBJECTIVE—To determine whether abnormalities of the left ventricle differ by glucose tolerance status, to explore reasons for differences, and to assess ethnic differences in these relations.
DESIGN—Population based prevalence study.
SETTING—London, UK.
PATIENTS—1152 African Caribbeans and Europeans.
METHODS—Echocardiograms, blood pressure, obesity, fasting and two hour blood glucose, insulin and lipids, and urinary albumin excretion rate were measured.
MAIN OUTCOME MEASURES—Left ventricular mass index, wall thickness, and early (E) to atrial (A) wave ratio.
RESULTS—Left ventricular mass index was greater in diabetic Europeans than in normoglycaemic Europeans (mean (SE), 95.6 (5.0) v 79.7 (0.8) g/m², p = 0.001) and in diabetic African Caribbeans than in normoglycaemic African Caribbeans (88.6 (2.5) v 82.4 (0.9) g/m², p = 0.02). Similar, but weaker associations were observed for the E:A ratio. β Coefficients between left ventricular mass index and fasting glucose in the normoglycaemic range, adjusted for age and sex, were 2.43 in Europeans (p = 0.05) and 3.74 in African Caribbeans (p = 0.02). These were attenuated to 1.19 (p = 0.4) and 3.03 (p = 0.08) in Europeans and African Caribbeans, respectively, when adjusted further for blood pressure and obesity. Adjustments for other risk factors made little difference to the coefficients. There were no ethnic differences in risk factor relations.
CONCLUSIONS—Abnormalities of the left ventricle occur in response to glucose intolerance and are observable into the normoglycaemic range. These disturbances are largely accounted for by associated obesity and hypertension. African Caribbeans have a greater degree of left ventricular structural impairment, emphasising the importance of tight blood pressure control.


Keywords: echocardiography; glucose tolerance; left ventricular mass index; ethnic differences     

Symptomatic improvement after radiofrequency catheter ablation for typical atrial flutter

OBJECTIVE—To assess the changes in quality of life, arrhythmia symptoms, and hospital resource utilisation following catheter ablation of typical atrial flutter.
DESIGN—Patient questionnaire to compare the time interval following ablation with a similar time interval before ablation.
SETTING—Tertiary referral centre.
PATIENTS—63 consecutive patients were studied. Four patients subsequently underwent an ablate and pace procedure, two died of co-morbid illnesses, and two were lost to follow up. The remaining 55 patients form the basis of the report.
RESULTS—Patients were followed for a mean (SD) of 12 (9.5) months. Atrial flutter ablation resulted in an improvement in quality of life (3.8 v 2.5, p < 0.001) and reductions in symptom frequency score (2.0 v 3.5, p < 0.001) and symptom severity score (2.0 v 3.8, p < 0.001) compared with preablation values. There was a reduction in the number of patients visiting accident and emergency departments (11% v 53%, p < 0.001), requiring cardioversion (7% v 51%, p < 0.001), or being admitted to hospital for a rhythm problem (11% v 56%, p < 0.001). Subgroup analysis confirmed that patients with atrial flutter and concomitant atrial fibrillation before ablation and those with atrial flutter alone both derived significant benefit from atrial flutter ablation. Patients with concomitant atrial fibrillation had an improvement in quality of life (3.5 v 2.5, p < 0.001) and reductions in symptom frequency score (2.3 v 3.5, p < 0.001) and symptom severity score (2.2 v 3.7, p < 0.001) compared with preablation values.
CONCLUSIONS—Ablation of atrial flutter is recommended both in patients with atrial flutter alone and in those with concomitant atrial fibrillation.


Keywords: atrial flutter; radiofrequency ablation; quality of life     

Left ventricular remodelling and brain natriuretic peptide after first myocardial infarction

OBJECTIVE—To investigate the relation between brain natriuretic peptide (BNP) concentrations and left ventricular remodelling characteristics after acute myocardial infarction.
DESIGN—Consecutive sample prospective cohort study.
SETTING—District general hospital coronary care unit in the north of England.
PATIENTS—133 initial survivors of a first myocardial infarction who received thrombolytic treatment.
INTERVENTIONS—Patients had transthoracic echocardiography and BNP concentrations measured at three to seven days (early) and two months (late).
MAIN OUTCOME MEASURES—Wall motion index  1.2, end systolic left ventricular volume index and mortality at one year.
RESULTS—Patients with an early wall motion index of  1.2 had higher early and late BNP concentrations (early BNP mean (SEM) 629 (76.2) pg/ml v 334 (20.8) pg/ml, p = 0.001 and late BNP 584 (79.5) pg/ml v 343 (25.0) pg/ml, p = 0.001). Patients with an increase in end systolic left ventricular volume index of > 10% also had higher early and late BNP concentrations (early BNP p = 0.034 and late BNP p = 0.001). Early BNP was significantly associated with one year mortality (p = 0.003).
CONCLUSIONS—Higher BNP concentrations early after first myocardial infarction are associated with adverse left ventricular remodelling characteristics. This may help explain why BNP is such a strong predictor of outcome after myocardial infarction.


Keywords: brain natriuretic peptide; wall motion index; left ventricular volume index; myocardial infarction     

Effect of levosimendan on myocardial contractility, coronary and peripheral blood flow, and arrhythmias during coronary artery ligation and reperfusion in the in vivo pig model

OBJECTIVE—To determine whether levosimendan, a calcium sensitiser that facilitates the activation of the contractile apparatus by calcium, improves myocardial contractile function during severe ischaemia and reperfusion without exacerbating the incidence of arrhythmias.
DESIGN—Pigs were pretreated orally twice daily for 10 days with 0.08 mg/kg levosimendan or placebo. On day 11 the left main coronary artery was ligated for 30 minutes, followed by 30 minutes of reperfusion. A bolus dose of levosimendan, 11.2 µg/kg intravenously, or placebo was given 30 minutes before coronary ligation, followed by a continuous infusion of 0.2 µg/kg/min levosimendan or placebo for the remainder of the experiment.
RESULTS—During the ischaemic period, cardiac output was higher in the levosimendan group than in the placebo group (mean (SD): 2.6 (0.5) v 2.0 (0.2) l/min, p < 0.05) and systemic vascular resistance was lower (2024 (188) v 2669 (424) dyne.s⁻¹.cm⁻⁵, p < 0.005). During reperfusion, cardiac output and contractility (LV_maxdP/dt (pos), 956 (118) v 784 (130) mm Hg/s, p < 0.05) were increased by levosimendan. The incidence of ischaemic ventricular fibrillation and tachycardia was similar in the two groups but there were more arrhythmic events (ventricular tachycardia and ventricular fibrillation) in the levosimendan treated group (8/12 levosimendan v 1/9 control p = 0.05).
CONCLUSIONS—Levosimendan improved cardiac output and myocardial contractility during coronary artery ligation and reperfusion. However, it increased the number of arrhythmic events during ischaemia in this model of in vivo regional ischaemia.


Keywords: calcium sensitisers; myocardial ischaemia; arrhythmias