No incremental clinical information of NT Pro BNP at peak exercise over resting levels in patients with impaired left ventricular function.

There is an increasing tension to use NT Pro BNP blood levels at peak exercise testing. Their possible superiority over resting levels in congestive heart failure or factors associated with their increase have not been adequately studied. We studied 65 patients, 51 males and 14 females with impaired left ventricular function. Mean left ventricular ejection fraction (LVEF) was 35+/-9%. Our findings suggest that in patients with heart failure NT Pro BNP plasma levels at peak exercise do not provide incremental clinical information over resting levels. Baseline NT Pro BNP alone can provide sufficient clinical information.

Heterozygote men with familial hypercholesterolaemia may have an abnormal triglyceride response post-prandially. Evidence for another predictor of vascular risk in familial hypercholesterolaemia.

Familial hypercholesterolaemia (FH) is associated with premature coronary heart disease (CHD). Post-prandial hypertriglyceridaemia has also been associated with cardiovascular disease. Thus, an abnormal post-prandial triglyceride (TG) clearance may contribute to the heterogeneity in the risk of CHD in heterozygous (h) FH. Therefore, we investigated the response of TG levels to a fatty meal in men with hFH. We studied 26 Greek men divided into two groups: the hFH group of 14 men, mean age 39 (SD = 11) years and the control group of 12 healthy men, mean age 43 (50:5) years. An increased TG response to the fatty meal was defined as a post-prandial TG concentration (at 4, 6 or 8 h) greater than the highest TG concentration in any hour in any control individual. All hFH patients had normal baseline fasting TG levels. However, seven hFH men showed an abnormal TG response after the fatty meal; these patients had higher baseline fasting TG levels than others [1.5 (0.2) vs. 1.0 (0.4) mmol/l, p = 0.005]. The hFH men constituted a heterogeneous group regarding their TG response to the fatty meal compared with healthy men because 50% with higher, but nevertheless 'normal' basal TG levels, had an abnormal post-prandial TG response. The reduced activity of low-density lipoprotein receptors in hFH together with other defects in TG handling may explain the abnormal rise of TG levels post-prandially.

Symptoms of hypertrophic cardiomyopathy, with special emphasis on syncope and postprandial exacerbation of symptoms.

We undertook a prospective study of the symptoms of hypertrophic cardiomyopathy with the aim of profiling symptomatic morbidity in detail, determining the prevalence of anxiety and depression, and describing the prevalence and associations of syncope and postprandial symptom exacerbation. A questionnaire was administered to consecutive outpatients; 70 with hypertrophic cardiomyopathy, 43 with coronary artery disease, 32 with idiopathic dilated cardiomyopathy, and to 40 normal subjects. Hypertrophic cardiomyopathy patients underwent exercise testing, echocardiography, and Holter monitoring. Hypertrophic cardiomyopathy patients had a high frequency of cardiac symptoms and, on average, had a level of symptomatic morbidity equivalent to that of chronic stable angina and dilated cardiomyopathy. There was no evidence for an excess of anxiety (14%) or depression (6%) in patients with hypertrophic cardiomyopathy. Syncope and presyncope, especially provoked by exertion or posture change, were characteristic and common symptoms in hypertrophic cardiomyopathy. A history of syncope was associated with an abnormal blood pressure response to exercise in over 50% of cases that may be the mechanism of syncope in some. Postprandial exacerbation of symptoms occurred in over one-third of hypertrophic cardiomyopathy patients, half of coronary disease patients, and infrequently in dilated cardiomyopathy. Hypertrophic cardiomyopathy patients with postprandial symptoms had a greater frequency of angina, were more symptomatic, and had a reduced exercise capacity, suggesting that postprandial symptoms are a marker for more severe disease.

QT interval in cardiac amyloidosis.

The aim of the study was to investigate whether cardiac amyloidosis is associated with QT interval abnormalities and ventricular arrhythmias. A controlled study of 30 patients was undertaken at a university cardiology department in a large referral hospital. Thirty patients (18 men, 12 women, mean age 56 +/- 12 years) with systemic amyloidosis verified by biopsy and strong indications of cardiac amyloidosis comprised the study group, with 30 healthy age- and sex-matched individuals serving as controls. Complete M-mode and two-dimensional echocardiographic study was undertaken and QT interval and QTc were calculated. All patients and controls underwent 24-h Holter monitoring for arrhythmias. Left ventricular (LV) wall thickening was found in all patients with cardiac amyloidosis. The LV mass in the patients with cardiac amyloidosis was significantly greater than that of the control group, as was the ratio LV mass/body surface area (p < 0.001). There was no significant difference in the max QT interval or in QTc dispersion between the two groups, although the max QTc was greater in the patients with cardiac amyloidosis. Patients with cardiac amyloidosis did not have a higher incidence of arrhythmias than the controls. Although patients with thickened cardiac walls due to cardiac amyloidosis have a prolonged QTc in comparison with controls, they do not show an increase in interlead QTc dispersion which might suggest the possibility of regional disturbances of the uniformity of repolarization. Patients with cardiac amyloidosis do not have a higher incidence of arrhythmias than controls.

Beat-to-beat variability in stroke volume during VVI pacing as predictor of hemodynamic benefit from DDD pacing.

To determine whether the magnitude of Beat-to-Beat variability in stroke volume (SV) during VVI pacing can predict hemodynamic benefit from DDD pacing, we undertook Doppler recordings of systolic and diastolic LV flow during VVI and DDD pacing in 20 patients (age 54 +/- 9 years) with DDD pacemakers implanted due to AV block. SV increased by 19% +/- 10% from VVI to DDD (P < 0.01). This increase was greater (29% +/- 9%) in patients with a ratio of early (E)/late (A) filling < 1 compared to those with E/A > 1 (10% +/- 9%) (P < 0.001). Beat-to-Beat variability in SV was greater in VVI (13% +/- 8%) compared to DDD (4% +/- 1%) (P < 0.001). Patients with E/A < 1 showed greater Beat-to-Beat variability in SV during VVI pacing (19 +/- 6%) compared to those with E/A > 1 (8% +/- 4%) (P < 0.001). Beat-to-Beat variability in SV during VVI pacing correlated with both percent change in SV from VVI to DDD (r = 0.89, P < 0.001) and E/A (r = -0.71, P < 0.001). In conclusion, patients with E/A < 1 derive greater hemodynamic benefit at rest from DDD pacing compared with E/A > 1. In addition, patients with complete AV block who show large variations in SV during VVI pacing may obtain greater hemodynamic benefit at rest from DDD pacing than patients with small variations.

Effects of lisinopril on cardiorespiratory, neuroendocrine, and renal function in patients with asymptomatic left ventricular dysfunction.

OBJECTIVE: To determine the cardiac, renal, and neuroendocrine effects of lisinopril in men with untreated, symptom free left ventricular systolic dysfunction. DESIGN: A randomised, double blind cross over trial with six week treatment periods to compare lisinopril (10 mg/day) and matching placebo. SETTING: Hospital outpatient department. PATIENTS: Patients with pronounced systolic dysfunction on cross sectional echocardiography due to myocardial infarction at least six months previously, without angina and with no or minimal breathlessness. Eighteen men were identified of whom 15 completed the study. INTERVENTIONS: Lisinopril (10 mg) or placebo given once daily by mouth. MAIN OUTCOME MEASURES: Primary: oxygen consumption at peak exercise. Secondary: resting cardiac function as measured by radionuclide ventriculography and echocardiography, renal function estimated radioisotopically, and plasma indices of neuroendocrine activity. RESULTS: Compared with placebo, lisinopril increased (mean (SD)) peak oxygen consumption during exercise (19.8(3.1) ml/kg/min v 21.4(3.2) ml/kg/min; p < 0.003). Lisinopril did not improve indices of cardiac function at rest. It reduced plasma concentrations of angiotensin II (median values 7 pg/ml to 5 pg/ml; p < 0.02), aldosterone (median values 113 pg/ml to 66 pg/ml; p < 0.05) and atrial natriuretic peptide (median values 69 pg/ml to 40 pg/ml; p < 0.04), but noradrenaline and antidiuretic hormone concentrations did not change. Renal blood flow increased and glomerular filtration rate declined. CONCLUSIONS: Even before the onset of heart failure lisinopril improves the cardiopulmonary response to exercise in patients with systolic ventricular dysfunction.

Influence of left ventricular hypertrophy and function on the occurrence of ventricular tachycardia in hypertrophic cardiomyopathy.

Sixty-nine patients with hypertrophic cardiomyopathy were studied by 2-dimensional and Doppler echocardiography and 72-hour Holter monitoring to examine the relation between the degree of left ventricular (LV) hypertrophy and dysfunction and the occurrence of ventricular tachycardia (VT). Episodes of nonsustained VT were detected in 20 patients (29%). Maximal wall thickness was not different between patients with (22 +/- 5 mm) and without (21 +/- 5 mm) VT. Total hypertrophy score, calculated as the sum of 10 segmental wall thicknesses, was also similar in both groups (157 +/- 22 and 153 +/- 32 mm, respectively; p = not significant). Furthermore, no significant differences were found between the 2 groups in LV end-diastolic dimension (41 +/- 7 vs 40 +/- 6 mm), fractional shortening (33 +/- 7 vs 34 +/- 10%) and left atrial size (40 +/- 10 vs 41 +/- 11 mm). An LV outflow tract gradient was detected in 25% of patients with and 35% without VT (p = not significant). One or more Doppler indexes of diastolic function were abnormal in 70% of patients, but no difference in any of these indexes was found between those with and without VT. In summary, the occurrence of VT in hypertrophic cardiomyopathy is not related to the degree of LV hypertrophy, outflow tract gradient or dysfunction. This finding suggests a dissociation between the arrhythmogenic substrate and echocardiographic features of the disease.

QT-interval abnormalities in hypertrophic cardiomyopathy.

To examine whether QTc and QTc dispersion across the leads of a surface electrocardiogram (ECG) are different in patients with hypertrophic cardiomyopathy (HCM) compared with normal subjects, we measured QT and calculated QTc in all 12 leads of a surface ECG in 24 patients with HCM and in 20 age- and sex-matched normal control subjects. Maximal QTc was prolonged in HCM patients (465 +/- 24 ms) compared with controls (410 +/- 20 ms) (p < 0.001). QTc dispersion defined as the difference of maximum-minimum QTc was also greater in HCM patients (71 +/- 21 ms) compared with normals (35 +/- 11 ms) (p < 0.001). A correlation was found between the degree of left ventricular hypertrophy expressed by the maximal wall thickness and maximal QTc (r = 0.48, p < 0.02). However, QTc dispersion did not correlate with maximal wall thickness. Thus, patients with HCM show a prolonged QTc (> 440 ms) and increased QTc dispersion compared with normal subjects. In addition, the degree of left ventricular hypertrophy correlates with maximal QTc. The presence of a prolonged QT with increased regional dispersion may be associated with the occurrence of serious ventricular arrhythmia and sudden death in HCM.

Amiodarone reduces QT dispersion in patients with hypertrophic cardiomyopathy.

To compare QT interlead variability (dispersion) in patients who receive a class III antiarrhythmic with those not on antiarrhythmic therapy, we measured QT in all 12 leads of a standard ECG in 24 patients with hypertrophic cardiomyopathy, 12 (50%) of whom were on amiodarone monotherapy and 12 (50%) who were not on amiodarone or other cardioactive medication which could affect QT. Age, functional class, chamber dimension or the degree of left ventricular hypertrophy expressed by maximal wall thickness (21 +/- 5 vs 20 +/- 4 mm; p = NS) was not different between the amiodarone and the non-amiodarone group. Maximal corrected QT (QTc) was greater in patients receiving (488 +/- 25 ms) compared to those not receiving amiodarone (451 +/- 23 ms) (p less than 0.001). However, QTc dispersion defined as the difference of maximum minus minimum QTc was decreased in the amiodarone (48 +/- 10 ms) compared to the non-amiodarone group (78 +/- 17 ms) (p less than 0.001). We conclude that in patients with hypertrophic cardiomyopathy, amiodarone prolongs QTc but reduces QTc dispersion. These results agree with expected changes in ventricular recovery time in patients who receive Class III antiarrhythmic agents and provide further support to the theory that QTc dispersion reflects regional differences in ventricular recovery time.

"Subclinical" pacemaker syndrome: a randomised study of symptom free patients with ventricular demand (VVI) pacemakers upgraded to dual chamber devices.

OBJECTIVE: To determine whether symptom free patients with single chamber pacemakers benefit from dual chamber pacing. DESIGN: A randomised double blind crossover comparison of ventricular demand (VVI), dual chamber demand (DDI), and dual chamber universal (DDD) modes after upgrading from a VVI device. SETTING: Cardiology outpatient department. PATIENTS: Sixteen patients aged 41-84 years who were symptom free during VVI mode pacing for three or more years. INTERVENTION: Pacemaker upgrade during routine generator change. MAIN OUTCOME MEASURES: Change in subjective (general health perception, symptoms) and objective (clinical assessment, treadmill exercise, and radiological and echocardiographic indices) results between pacing modes before and after upgrading. RESULTS: 75% preferred DDD, 68% found VVI least acceptable with 12% expressing no preference. Perceived general well-being and exercise capacity (p less than 0.01) and treadmill times (p less than 0.05) were improved in DDD mode but VVI and DDI modes were similar. Clinical, echocardiographic, radiological, and electrophysiological indices confirmed the absence of overt pacemaker syndrome, although mitral and tricuspid regurgitation was greatest in VVI mode (p less than 0.01). CONCLUSIONS: Most patients who were satisfied with long term pacing in VVI mode benefited from upgrading to DDD mode pacing suggesting the existence of "subclinical" pacemaker syndrome in up to 75% of such patients. The DDI mode offered little subjective or objective benefit over VVI mode in this population and should be reserved for patients with paroxysmal atrial arrhythmias. VVI mode pacing should be used only for patients with very intermittent symptomatic bradycardia or atrial fibrillation with a good chronotropic response during exercise.

Haemodynamic effects of propofol: induction with 2.5 mg kg-1.

Serial measurements of haemodynamic variables were performed at 1-min intervals in nine ASA I, unpremedicated patients before and for 5 min after induction of anaesthesia with propofol 2.5 mg kg-1. End-tidal carbon dioxide concentration was maintained within the normal range. Stroke volume and left ventricular function were measured by Doppler and cross-sectional echocardiography at the aortic valve. Systemic arterial pressure was measured by automated oscillotonometry and heart rate by electrocardiograph. Stroke volume, cardiac output, systemic vascular resistance, left ventricular stroke work and rate-pressure product were calculated. There was a decrease at all time points in systolic, mean and diastolic arterial pressure. There was an initial increase in heart rate and cardiac output, with a subsequent decrease to less than baseline. There was an initial decrease in systemic vascular resistance followed by partial recovery, and a delayed decrease in left ventricular function as measured by peak aortic blood flow velocity and acceleration.

Long-term results of coronary angioplasty for single vessel, proximal, left anterior descending disease.

The acute and long-term results of coronary angioplasty in 295 patients with isolated, proximal left anterior descending coronary stenosis are reported. The angiographic success rate was 83.4% overall, but 90.5% for non-occluded arteries treated since 1985. Clinical success at hospital discharge was achieved in 79.7%. The median duration of follow-up was 2.9 years and vital status was established in 99.7% at census. Cumulative 5-year cardiac survival was 96.2% after successful angioplasty and 95.6% for all patients. Five-year freedom from all cardiac events including cardiac death, myocardial infarction and repeat intervention was 73.8% amongst successfully treated patients, and 63.0% for all patients. After angioplasty, patients had less angina, required less anti-anginal medication and were more likely to be in gainful employment. Our data indicate that coronary angioplasty is an effective long-term treatment for selected patients with single vessel disease involving the proximal left anterior descending coronary artery.

A randomized double-blind crossover comparison of four rate-responsive pacing modes.

The aim of this study was to compare, both subjectively and objectively, four modern rate-responsive pacing modes in a double-blind crossover design. Twenty-two patients, aged 18 to 81 years, had an activity-sensing dual chamber universal rate-responsive (DDDR) pacemaker implanted for treatment of high grade atrioventricular block and chronotropic incompetence. They were randomly programmed to VVIR (ventricular demand rate-responsive), DDIR (dual chamber demand rate-responsive), DDD (dual chamber universal) or DDDR (dual chamber universal rate-responsive) mode and assessed after 4 weeks of out-of-hospital activity. Five patients, all with VVIR pacing, requested early reprogramming. The DDDR mode was preferred by 59% of patients; the VVIR mode was the least acceptable mode in 73%. Perceived "general well-being," exercise capacity, functional status and symptoms were significantly worse in the VVIR than in dual rate-responsive modes. Exercise treadmill time was longer in DDDR mode (p less than 0.01), but similar in all other modes. During standardized daily activities, heart rate in VVIR and DDIR modes underresponded to mental stress. All rate-augmented modes overresponded to staircase descent, whereas the DDD mode significantly underresponded to staircase ascent. Echocardiography revealed no difference in chamber dimensions, left ventricular fractional shortening or pulmonary artery pressure in any mode. Cardiac output was greater at rest in the dual modes than in the VVIR mode (p = 0.006) but was similar at 120 beats/min. Beat to beat variability of cardiac output was greatest in VVIR mode (p less than 0.0001), with DDIR showing greater variability than DDD or DDDR modes (p less than 0.05). Mitral regurgitation estimated by Doppler color flow imaging was similar in all modes, but tricuspid regurgitation was significantly greater in VVIR than in dual modes (p less than 0.03). Subjects who preferred the DDDR mode and those who found the VVIR mode least acceptable had significantly greater increases in stroke volume when paced in the DDD mode than in the ventricular-inhibited (VVI) mode at rest (22%) when compared with subjects who preferred other modes (2%, p = 0.03). No other objective variable was predictive of subjective benefit from any rate-responsive pacing mode. Thus, dual sensor rate-responsive pacing (DDDR) is superior objectively and subjectively to single sensor (VVIR, DDIR and DDD) pacing and subjective benefit from dual chamber rate-augmented pacing is predictable echocardiographically.

Is accurate rate response programming necessary?

Exercise capacity and general well-being are improved by appropriately programmed rate responsive pacemakers when compared to fixed rate units. Ten patients had activity sensing DDDR units implanted for combined AV block and sinus node incompetence. Ten patients had Sensolog activity sensing VVIR units implanted for complete heart block. The effects of over and under programming of rate response in both dual and single chamber activity sensor rate adaptive pacemakers has been assessed subjectively by visual analog scales and specific activity questionnaires and objectively by graded treadmill testing and the performance of standardized daily activities. Patients were randomly programmed to absent rate response (VVI in the Sensolog group), hyporesponsive (DDD in the dual chamber group), appropriate response (VVIR, DDDR according to Manufacturer's instructions) and over responsive (VVIR+, DDDR+) in a double-blind crossover design. Thirty percent of patients demanded early crossover from VVI, 30% from DDDR+ and 50% from VVIR+. Perception of Exercise Capability was similar to objective exercise treadmill times which were shorter in VVI than in VVIR or VVIR+ (P less than 0.05) or control subjects (P less than 0.001). There was no difference between any dual chamber mode or control subjects. General well-being was poorest in DDDR+ and VVIR+ modes despite objective improvement in exercise capacity. Symptoms were least in VVIR and DDDR and all but one patient chose appropriate programming as their overall preferred mode. Thus, even inaccurate rate response programming results in similar and improved exercise capacity compared to absent rate response but overprogramming is unacceptable to most patients, confirming that appropriate programming and sensor specificity is critical in rate responsive pacing.

Clinical outcome of coronary angioplasty for single-vessel disease.

The acute and long-term results of coronary angioplasty in 412 patients with single-vessel coronary artery disease are reported. Angiographic success was observed in 85.5% of all lesions and 84.7% of all arteries in which dilatation was attempted. Success rates improved during the study; since 1985, the angiographic success rate for non-occluded arteries has been 91.0%. Early complications occurred in 6.8%; angioplasty achieved clinical success in 80.3% of all patients at discharge from hospital. The median duration of follow-up was 772 days, with clinical status established for 98.8% of patients. 5 years after clinically successful angioplasty, cumulative cardiac survival was 96.6% and freedom from cardiac death and myocardial infarction was 90.4% (95.8% and 85.4%, respectively, on intention-to-treat analysis). Within 5 years of successful angioplasty, 12.4% of survivors underwent coronary bypass surgery and 16.9% had repeat angioplasty. Freedom from all cardiac events at 5 years was 70.2% after clinically successful angioplasty and 60.2% on intention-to-treat analysis. Angina symptoms were improved in over 80% of patients and abolished in 75%.