Wing-Hung Leung

Beneficial effect of cholesterol-lowering therapy on coronary endothelium-dependent relaxation in hypercholesterolaemic patients.

Since hypercholesterolaemia is associated with impaired endothelium-dependent vasodilation, a study was conducted to find out whether cholesterol reduction will improve endothelial function in patients with hypercholesterolaemia and normal coronary arteries. 25 men (mean age 51 [SD 8] years) with total serum cholesterol > 6.2 mmol/L) and angiographically normal coronary arteries had their coronary vasomotor responses to intracoronary acetylcholine and nitroglycerin assessed by computer-assisted quantitative angiography at baseline and after 6 months of cholesterol-reducing diet and cholestyramine. Between baseline and follow-up mean total serum cholesterol level fell by 28.7 (SD 5.6)% (p < 0.001); mean low-density lipoprotein (LDL) cholesterol level by 35.6 (8.7)% (p < 0.001); and mean total cholesterol to high-density lipoprotein (HDL) cholesterol ratio by 29.4 (10.6)% (p < 0.001). Acetylcholine significantly reduced the mean segment diameter at baseline, by 21.7 (14.0)% (p < 0.01), but it increased the diameter at follow-up, by 6.16 (13.3)% (p < 0.01), the difference between the two occasions being significant (p < 0.001). Nitroglycerin significantly increased the mean segment diameter, both at baseline, by 18.7 (11.5)% (p < 0.01), and at follow-up, by 19.3 (12.1)% (p < 0.01), the difference between the two responses being not significant. At baseline total cholesterol and LDL cholesterol did not correlate with acetylcholine response, but they did at follow-up (total cholesterol, r = 0.67, p < 0.01; LDL cholesterol, r = 0.64, p < 0.01). Impairment of endothelium-dependent (acetylcholine-induced) dilation of the epicardial coronary arteries in hypercholesterolaemic patients with angiographically normal coronary arteries is thus reversible by reducing serum cholesterol. In addition, the degree of impairment of acetylcholine-induced vasomotor response is related to the cholesterol concentrations after therapy.

Doppler echocardiographic evaluation of left ventricular diastolic function in patients with systemic lupus erythematosus.

Subclinical myocardial involvement frequently occurs in patients with systemic lupus erythematosus (SLE). In this study, left ventricular diastolic function was assessed in 58 patients (54 female and 4 male; mean age 32 +/- 11 years) and in 40 sex-matched and age-matched healthy control subjects (37 female and 3 male; mean age 33 +/- 9 years) by means of pulsed Doppler echocardiography. All subjects had no clinical evidence of overt myocardial disease or abnormal left ventricular systolic function. Compared with the control group, patients with SLE had significantly prolonged isovolumic relaxation time (62 +/- 12 vs 80 +/- 14 msec; p less than 0.01), reduced peak early diastolic flow velocity (peak E) (82 +/- 18 vs 76 +/- 16 cm/sec; p less than 0.05), increased peak late diastolic flow velocity (peak A) (45 +/- 7 vs 53 +/- 8 cm/sec; p less than 0.01), reduced E/A ratio (1.81 +/- 0.32 vs 1.46 +/- 0.29; p less than 0.001), and lower deceleration rate of early diastolic flow velocity (EF slope) (489 +/- 151 vs 361 +/- 185 cm/sec2; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac abnormalities in systemic lupus erythematosus: a prospective M-mode, cross-sectional and Doppler echocardiographic study

A prospective M-mode, cross-sectional and Doppler echocardiographic study was performed on 75 patients with systemic lupus erythematosus and 60 sex- and age-matched control subjects. Compared with the control group, patients with lupus had an increased prevalence of echocardiographic abnormalities. These included pericardial effusion and/or thickening (37%), left ventricular hypertrophy (12%), global left ventricular hypokinesis (5%), segmental abnormalities of left ventricular wall motion (4%), right ventricular enlargement (4%), focal verrucous valvar thickening (12%), gross valvar thickening and dysfunction (8%), mitral regurgitation (25%) and aortic regurgitation (8%). Two patients with gross mitral valvar thickening and dysfunction subsequently underwent valvar replacement. Correlation between echocardiographic abnormalities and clinical parameters showed that pericardial effusion was significantly associated with pericardial pain (P less than 0.05) and active disease (P less than 0.001), and left ventricular hypertrophy with systemic hypertension (P less than 0.05). Thus, there was a high prevalence of cardiac abnormalities, especially pericardial and valvar lesions, in patients with systemic lupus erythematosus. Echocardiography is invaluable in identifying these abnormalities and should be used routinely for cardiac evaluation of these patients.

A randomized double-blind crossover study comparing the efficacy and tolerability of flecainide and quinidine in the control of patients with symptomatic paroxysmal atrial fibrillation.

Patients with paroxysmal atrial fibrillation (PAF) are prone to recurrence. We compared the efficacy and tolerability of flecainide acetate in the control of PAF by means of conventional treatment with quinidine in 19 patients without structural heart disease. A randomized, placebo-controlled, crossover protocol consisting of 8 weeks of treatment with either agent was used. The recurrence of PAF was documented in a symptom diary and confirmed by event ECG recording. Complete control of symptoms was achieved in 4 of 19 and 2 of 11 of patients with flecainide and quinidine, respectively. Both agents prolonged the time to the first recurrence and significantly reduced the total duration of PAF recurrence by 40% and 47%, respectively (p less than 0.05 compared with placebo). Compared with quinidine, flecainide significantly reduced the frequency of recurrence and the rate of PAF during a recurrent episode. However, treatment with flecainide was associated with a higher incidence of symptomatic sinus pauses and visual disturbances compared with a higher incidence of gastrointestinal side effects with quinidine. During a follow-up period of 32 months, satisfactory control was achieved in 74% of patients with the use of these two antiarrhythmic agents.

Improvement in exercise performance and hemodynamics by labetalol in patients with idiopathic dilated cardiomyopathy

Labetalol, a combined alpha- and beta-blocking agent, was administered to 12 patients (mean age 55 years) with idiopathic dilated cardiomyopathy to examine its effects on symptomatology and exercise performance. Studies were performed before treatment, after 8 weeks of placebo, and after 8 weeks of labetalol therapy in a randomized, crossover, double-blind design. The mean (+/- SEM) dose of labetalol for the group was 275 +/- 29 mg. Compared to treatment with placebo, the maximum duration of symptom-limited exercise was significantly prolonged with labetalol (580 +/- 72 seconds to 683 +/- 71 seconds; p less than 0.005). Both the resting and peak exercise heart rate and systolic blood pressure were significantly reduced. Ascending aortic blood flow velocity was also measured by continuous-wave Doppler technique during exercise. Compared to placebo, treatment with labetalol conferred no significant change in cardiac output at rest but significantly improved cardiac output at maximum exercise (14 +/- 3%; p less than 0.001). Doppler-derived peak aortic flow velocity, acceleration, and flow velocity integral were also significantly improved at maximum exercise. Systemic vascular resistance, as derived from mean blood pressure/cardiac output, was reduced by 12 +/- 3% and 16 +/- 3% at rest and at maximum exercise, respectively. New York Heart Association functional class was improved (3.2 +/- 0.2 to 2.2 +/- 0.3; p less than 0.005). No major side effects from labetalol were encountered. Thus labetalol improves symptomatology, exercise capacity, and exercise hemodynamics and reduces systemic vascular resistance in patients with idiopathic dilated cardiomyopathy.

Superior Cardiac Hemodynamics of Atrioventricular Synchrony Over Rate Responsive Pacing at Submaximal Exercise: Observations in Activity Sensing DDDR Pacemakers

LAU, C.‐P., ET AL.: Superior Cardiac Hemodynamics of Atrioventricular Synchrony Over Rate Responsive Pacing at Submaximal Exercise: Observations in Activity Sensing DDDR Pacemakers. The relative hemodynamic profile between dual chamber pacing (DDD) and activity sensing rate responsive pacing (VVIR) was compared in ten patients with dual chamber rate responsive pacemakers (Synergist 11). With a double blind, randomized exercise protocol, DDDR pacemakers were programmed into VVI, VVIR, and DDD (AV interval 150 msec) modes and in seven patients the test in the DDD mode was repeated with the AV interval programmed at 75 msec. A treadmill exercise test of 6‐minutes duration (2 stages, Stage 1 at 2 mph, 0% gradient and Stage II at 2 mph, 15% gradient) was performed at each of the programmed settings, with a rest period of 30 minutes in between tests. Cardiac output was assessed using continuous‐wave Doppler sampling ascending aortic flow and expressed as a percentage of the value achieved during VVI pacing. During exercise, pacing rate between DDD and VVIR pacing was similar but was higher with DDD at the first minute of recovery (91 ± 4vs 81 ± 3 beat/min, respectively). Cardiac output was significantly higher at rest, during low level exercise, and recovery with DDD pacing compared with VVIR pacing (resting: 21 ± 14 vs ‐2 ± 7%; Stage I: 36 ± 6 vs 16 ± 7%; Stage II: 25 ± 15 vs 10 ± 8%; recovery: 26 ± 12 vs 4 ± 9%; p < 0.05 in all cases). Systolic blood pressure was significantly higher during low level of exercise in the DDD mode. Shortening of the AV interval to 75 msec did not significantly affect cardiac output during exercise, but cardiac output after exercise was reduced (2 ± 6 vs 23 ± 6% at an AV interval of 150 msec, p < 0.02). By enhancing the stroke volume, DDD pacing improves cardiac hemodynamics at rest, during low level exercise, and early postexercise recovery.

Long‐Term Stability of P Wave Sensing in Single Lead VDDR Pacing: Clinical Versus Subclinical Atrial Undersensing

Optimal function of a single lead P wave synchronous rate adaptive ventricular pacing system (VDDR) requires reliable P wave sensing over time and during daily activities. The stability of P wave sensing and the incidence of sensitivity reprogramming in a single pass lead with a diagonally arranged bipole was assessed in 30 patients with complete atrioventricular block over a follow‐up period of 12 ± 1 months (range 6 months to 3 years). Atrial sensing was assessed during clinic visits, by physical maneuvers (postural changes, breathing, Valsalva maneuver, walking and isometric exercise), maximum treadmill exercise and Holter recordings. P wave amplitude at implantation was 1.21 ± 0.09 (0.5–3.6) mV, and the atrial sensing threshold remained stable over the entire period of follow‐up. Using an atrial sensitivity based on twice the sensing threshold at 1 month, P wave undersensing was found in 2, 4, 3, and 7 patients during clinic visit, physical maneuvers, exercise, and Holter recordings, respectively. Atrial sensitivity reprogramming was performed in three patients based on the correction of undersensing during physical maneuvers. Although eight patients had atrial undersensing on Holter recordings, the number of undersensed P waves was small (total 101 beats or 0.013%± 0.001% of total ventricular beats) and no patient was symptomatic. One patient had intermittent atrial undersensing at the highest sensitivity, but the VDDR mode was still functional most of the time. No patient had myopotential interference at ihe programmed sensitivity. One patient developed chronic atrial fibrillation and was programmed to the VVIR mode. Thus, single lead VDDR pacing is a stable pacing mode in 97% of patients. Because of the large variability of P wave amplitude, the use of a sensitivity margin at least three times the atrial sensitivity threshold will maximize atrial sensing and minimize the need for atrial sensitivity reprogramming (1/30 patients). Physical maneuvers and exercise tests are effective means for rapid assess ment of the adequacy of P wave sensing.

Rate Responsive Pacing with a Minute Ventilation Sensing Pacemaker during Pregnancy and Delivery

A minute ventilation sensing rate responsive pacemaker was implanted in a 29‐week pregnant woman with symptomatic complete atrioventricular (AV) block under echocardiographic and electrocardiographic (EGG) guidance. Satisfactory rate responses during a submaximal treadmill exercise test and daily activities were achieved. The course of pregnancy and cesarean section is discussed. During the cesarean section and after the delivery of the baby, changes in the ventilator settings confirmed that the pacing rate was closely correlated with both the tidal volume (r = 0.94, P<0.02) and the respiratory rate (r = 0.93, P < 0.05).

A Comparative Evaluation of a Minute Ventilation Sensing and Activity Sensing Adaptive‐Rate Pacemakers During Daily Activities

Most studies evaluating the rate response of adaptive‐rate pacemakers have been based on treadmill or bicycle exercise. These studies disregard the fact that few pacemaker recipients voluntarily undertake such activities. The rate responses of nine patients (mean age 62 years, range 33 79 years) with implanted minute ventilation sensing (Meta) pacemakers were studied. The indications for pacing were complete heart block (seven patients), six sinus syndrome (one patient), and five nodal disease (one patient). Significant improvement in maximum distance covered during a 12‐minute walking test was observed in the rate adaptive compared to the VVI pacing mode (989 ± 104 vs 921 ± 90 m. P < 0.02). The rate responses of this pacemaker during daily activities were recorded with telemetry during a variety of structured daily activities. The rate responses were also compared to those of an externally attached Activitrax pacemaker in each patient and to a group of ten age and sex matched volunteers. For less strenuous activities such as walking, descending stairs, washing, and bed making, both pacemakers achieved adequate rate responses compared to normal subjects. For more strenuous activities, the Activitrax pacemaker failed to achieve an adequate rate response. For example. the pacing rate achieved on ascending stairs was lower than that achieved on descending stairs (92 ± 3 vs 102 ± 3 bpm, P < 0.02). The direction of rate responses was more appropriate for the Meta pacemaker. Similar to the normal subjects, the maximum rate was reached before the end of an activity with the Activitrax pacemaker. A significant delay was observed with the Meta pacemaker and the rate response was achieved during the recovery period of some activities (e.g., maximum pacing rate was achieved at 45 ± 35 sec after ascending stairs with the Meta pacemaker). In conclusion, the Meta pacemaker improved submaximal exercise capacity. This study suggests the two different rate adaptive pacemakers differed in their proportionality and speed of rate responses.

Usefulness of labetalol in chronic atrial fibrillation

Beta-adrenergic blocking agents are useful in controlling excessive ventricular rate in chronic atrial fibrillation (AF) but often reduce exercise capacity. To investigate the advantage of labetalol--a unique beta blocker with alpha-blocking property--in chronic AF, 10 patients without underlying structural heart disease were studied with treadmill test, 12-minute walk and 24-hour ambulatory electrocardiographic monitoring. Patients were randomized and crossed over to receive 4 phases of treatment (placebo, digoxin, digoxin with half-dose labetalol, and full-dose labetalol). Exercise durations were 14.1 +/- 1.5, 14.2 +/- 1.5, 16.1 +/- 1.1 and 15.6 +/- 1.1 minutes, respectively, indicating that labetalol did not reduce exercise tolerance. Although digoxin had no advantage over placebo in controlling maximal heart rate (177 +/- 2 vs 175 +/- 3 beats/min), labetalol, both as monotherapy or as an adjunct to digoxin, was advantageous (156 +/- 4 vs 177 +/- 2 beats/min, p less than 0.01, and 154 +/- 4 vs 177 +/- 2 beats/min, p less than 0.01, respectively). The rate-pressure product was consistently lowered by labetalol at rest and during exercise. At peak exercise, the addition of labetalol to digoxin reduced the maximal rate-pressure product achieved from 30,900 +/- 1300 to 24,100 +/- 2,000 mm Hg/min (p less than 0.01) and the maximal rate-pressure product was lowest with full-dose labetalol (22,300 +/- 1,600 mm Hg/min). During submaximal exercise on treadmill or during the 12-minute walk, the combination of labetalol and digoxin produced the best heart rate control, whereas labetalol monotherapy was comparable to digoxin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)