Janet M. McComb

Significance of silent ischemia and microalbuminuria in predicting Coronary events in asymptomatic patients with type 2 diabetes

OBJECTIVES The aim of this study was to investigate the relationships between future coronary heart disease (CHD) events and baseline silent myocardial ischemia (SMI) and microalbuminuria (MA) in subjects with type 2 diabetes (T2D) free from known CHD. BACKGROUND Coronary heart disease is often asymptomatic in subjects with diabetes. There is limited information on the prognostic value of SMI and MA in this group. METHODS Eighty-six patients with T2D and no history of CHD were studied (43 with MA individually matched with 43 normoalbuminuric patients; mean [SD] age 62 [+/-7] years, 62 men). Metabolic assessment, three timed overnight urine collections for albumin excretion rate, a treadmill exercise test and ankle brachial index (ABI) were performed at baseline. Patients were followed for 2.8 years. RESULTS Forty-five (52%) patients had SMI during treadmill testing. At review, there had been 23 coronary (CHD) events in 15 patients. Univariate Cox regression analysis showed that CHD events were significantly related to baseline ABI (p = 0.014), SMI (p = 0.020), MA (p = 0.046), 10-year Framingham CHD risk >30% (p = 0.035) and fibrinogen (p = 0.026). In multivariate analysis, SMI was the strongest independent predictor of CHD events (p = 0.008); risk ratio (95% confidence interval) for SMI: 21 (2 to 204). In the prediction of CHD events, SMI showed higher sensitivity and positive predictive value than MA or Framingham calculated CHD risk. CONCLUSIONS The presence of baseline SMI and MA are associated with future CHD events in asymptomatic patients with T2D and may be of practical use in risk stratification.

Management of recurrent ventricular tachyarrhythmias associated with Q-T prolongation

Eleven patients with acquired prolongation of the Q-Tc interval and recurrent ventricular tachyarrhythmias were studied. Five patients required 5 to 44 direct current shocks to correct prolonged ventricular tachyarrhythmias, and five were given at least two antiarrhythmic agents in an attempt to control the arrhythmias. In 4 of the 11 patients, when thioridazine, diuretic drugs and antiarrhythmic agents were withdrawn and hypokalemia or hypocalcemia corrected, ventricular tachyarrhythmias did not recur. The Q-Tc interval normalized in 2 to 3 days. Ventricular tachyarrhythmias were recurrent in the remaining seven patients, despite withdrawal of the drugs that caused the Q-Tc prolongation, attempted correction of hypokalemia when present and the administration of antiarrhythmic agents to four of the seven. All antiarrhythmic agents were then withdrawn in this group. Immediately on the establishment of overdrive ventricular or atrioventricular sequential pacing in these patients, ventricular tachyarrhythmias were abolished. No breakthrough ventricular tachyarrhythmias occurred during temporary pacing. Temporary pacing was required for an average of 10 days and the Q-Tc interval normalized an average of 5 days from the onset of pacing. Three patients required a permanent pacemaker, one because of chronic complete heart block, one because of the sick sinus syndrome, and one because of frequent ventricular ectopic complexes complicating ischemic heart disease. All 11 patients survived their period of hospitalization.

Arrhythmias after cardiac transplantation.

The etiology and clinical significance of sustained arrhythmias, and atrial and ventricular premature complexes (APCs and VPCs, respectively) after heart transplantation are controversial. Fifty adult recipients surviving > 2 weeks were studied by continuous telemetry while in the hospital and by ambulatory electrocardiographic monitoring at 2, 4, 6, 12 and 24 weeks after transplantation. The median APC frequency was greater among subjects who experienced allograft rejection in the early postoperative period (0.7/hour, range 0 to 23) than among those who did not (0.2/hour, range 0 to 10.4) (p = 0.04). The APC frequency in all subjects decreased from 0.25/hour (range 0 to 23) early to 0/hour (0 to 14) later (p = 0.04). Atrial flutter was the most frequent sustained arrhythmia; it was recorded in 5 of 21 rejectors and in 1 of 29 nonrejectors (p = 0.04), and 11 of 16 episodes (69%) were related to acute rejection temporally. VPCs were recorded in all patients early after transplantation, but the median frequency subsequently decreased from 4.6/hour (range 0.5 to 470) early to 1.25/hour (range 0 to 225) later (p < 0.001). VPC frequency was unrelated to rejection. Sustained ventricular tachycardia was recorded once and was caused by the proarrhythmic effect of flecainide. Thus, APCs and VPCs occur frequently after transplantation. Frequent APCs are associated with rejection, whereas the main determinant of VPC frequency is time after transplantation. Atrial flutter is closely associated with rejection and should be regarded as an indication for endomyocardial biopsy. Ventricular tachycardia occurs seldom, and in this study was due to proarrhythmic drug effects.

Silent myocardial ischemia and microalbuminuria in asymptomatic subjects with non-insulin-dependent diabetes mellitus.

Microalbuminuria is an increase in urinary albumin not detected by conventional dipstick testing and is present in 20% of patients with non-insulin-dependent diabetes mellitus (NIDDM). Mortality in NIDDM patients with microalbuminuria is 60% at 8 years and is mainly due to cardiovascular disease. Because many deaths occur without warning symptoms, we have compared the prevalence and severity of silent myocardial ischemia in asymptomatic NIDDM patients with and without microalbuminuria. We have performed a cross-sectional, case-control study of asymptomatic NIDDM patients attending hospital diabetes clinics. Forty-three patients with microalbuminuria were matched for age, gender, diabetes duration, and smoking status with 43 normoalbuminuric patients. A symptom-limited exercise stress test was performed and reported blind to patient status. The degree of electrocardiographic ST-segment depression, exercise time, work performed, and maximum heart rate with exercise were recorded. Patients with microalbuminuria had a higher prevalence of ischemic response (>1 mm ST depression) (65% vs 40%, p = 0.016), reduced total exercise time (5 vs 7 minutes, p <0.001), reduced work (6 vs 8 METs, p <0.001), and reduced age-predicted maximum heart rate (94% vs 101%, p = 0.004). In multiple logistic regression, albumin excretion rate was shown to be the strongest independent predictor of ischemic response (p = 0.03). Silent myocardial ischemia is common in asymptomatic NIDDM patients but is more common in those with microalbuminuria. In these subjects, the higher prevalence of ischemic response at low workloads suggests a higher probability of future coronary events, and possibly a higher probability of potentially treatable coronary artery disease.

Recurrent ventricular tachycardia associated with QT prolongation after mitral valve replacement and its association with intravenous administration of erythromycin

A 65-year-old woman had severe mitral stenosis and trivial mitral regurgitation. There was no obstructive coronary disease. The mitral valve was replaced with a CarpentierEdwards xenograft. When transferred to the recovery ward she was in sinus rhythm and was receiving intravenous dopamine, the dose of which was gradually reduced. The infusion also contained 20 mEq/liter of potassium chloride. The patients subsequent course is summarized in Figure 1. Erythromycin lactobionate, I g, and cloxacillin sodium, 500 rag, were given by intravenous injection. Within minutes of the injection VT developed, which reverted to sinus rhythm after the intravenous injection of calcium chloride, 5 ml of 10% solution, isoproterenol, 5 #g, and epinephrine, 2.5 ml of a I in 15,000 solution. During the next 24 hours, there were frequent ventricular premature contractions (VPCs ) with episodes of bigeminy and consecutive VPCs despite varying doses of lidocaine and mexiletine. There was sustained VT with hypotension on 3 further occasions, 2 of which immediately followed the administration of intravenous erythromycin and cloxacillin. The serum potassium level was measured several times during this period and was within the normal range on each measurement, the minimum value being 3. 7 mEq/liter. The serum magnesium concentration was 3.19 mg/lO0 ml and serum calcium 9.68 mg/lO0 ml; both values are above the lower limits for our laboratory. Twenty-four hours after the operation, a 12-lead electrocardiogram was recorded (Fig. 2). Compared with the preoperative ECG (Fig. 2a), sinus rhythm was present, the mean QRS axis had moved to the left and a new Q wave was present in lead A VL (Fig. 2b ). Anterior forces were less prominent than before. There was marked prolongation of the QT interval and there was widespread T-wave inversion. VPCs continued to occur frequently (Fig. 2c). Lidocaine and mexiletine treatment were discontinued. Potassium and calcium were given by intravenous injection and isoproterenol was infused in a dose sufficient to maintain the ventricular rate at 90 beats/rain. No further arrhythmias occurred for 6 hours, until the next injection of antibiotics was given. VT recurred and was successfully terminated by direct-current shock. Erythromycin treatment was then

HRS/ACCF Expert Consensus Statement on Pacemaker Device and Mode Selection: Developed in partnership between the Heart Rhythm Society (HRS) and the American College of Cardiology Foundation (ACCF) and in collaboration with the Society of Thoracic Surgeons

Anne M. Gillis, MD, FHRS, Andrea M. Russo, MD, FHRS, FACC, Kenneth A. Ellenbogen, MD, FHRS, FACC, Charles D. Swerdlow, MD, FHRS, CCDS, FACC, Brian Olshansky, MD, FHRS, CCDS, FACC, Sana M. Al-Khatib, MD, MHS, FHRS, CCDS, FACC, John F. Beshai, MD, FHRS, FACC, Janet M. McComb, MD, FHRS, Jens Cosedis Nielsen, MD, Jonathan M. Philpott, MD, Win-Kuang Shen, MD, FHRS, FACC From University of Calgary, Libin Cardiovascular Institute of Alberta, Alberta, Canada, Cooper Medical School of Rowan University, Cooper University Hospital, New Jersey, USA, Virginia Commonwealth University Medical Center, irginia, USA, David Geffen School of Medicine at UCLA, California, USA, University of Iowa Hospital, Iowa, USA, Duke University Medical Center, North Carolina, USA, University of Chicago Hospitals, Illinois, USA, Freeman ospital, Newcastle-upon-Tyne, United Kingdom, Skejby Hospital, Aarhus, Denmark, Mid-Atlantic Cardiothoracic Surgeons, Virginia, USA, Mayo Clinic College of Medicine, Arizona, USA. Representing the Society of Thoracic Surgeons

Electrophysiologic effects of d-sotalol in humans.

Sotalol is a beta-adrenergic blocking agent that prolongs the duration of the cardiac action potential in humans, without affecting the upstroke velocity of depolarization. The dextrorotatory isomer, d-sotalol, retains these class III effects, but has little beta-blocking activity in vitro. d-Sotalol has not been studied extensively in humans. The electrocardiographic (ECG) and electrophysiologic effects of d- and d,l-sotalol were therefore assessed in a prospective randomized study of 20 patients. Each patient received either d-sotalol (1, 1.5 or 2 mg/kg body weight) or d,l-sotalol (1 mg/kg) by intravenous infusion. The QT and QTc intervals were prolonged and refractoriness increased in the atrium, atrioventricular (AV) node, His-Purkinje system and right ventricle after both d- and d,l-sotalol. After d-sotalol, the increases in both QT and QTc intervals and in atrial and ventricular effective refractory periods were dose dependent. Highly significant linear correlation was demonstrated between the plasma sotalol level and the change in QT (r = 0.86, p = 0.001) and QTc intervals (r = 0.79, p = 0.002), and between the plasma sotalol level and the effective refractory period of the right atrium (r = 0.75, p = 0.005) and ventricle (r = 0.70, p = 0.025). This study confirms that d-sotalol has effects consistent with class III properties. It demonstrates these effects in humans, and suggests that d-sotalol may prove to be a useful antiarrhythmic agent.

Increased left ventricular mass index and nocturnal systolic blood pressure in patients with Type 2 diabetes mellitus and microalbuminuria

Aims To compare left ventricular mass (LVM) index and function in patients with Type 2 diabetes mellitus with and without microalbuminuria and to investigate the clinical determinants of left ventricular hypertrophy.

Sinus node function after cardiac transplantation.

OBJECTIVES This study aimed to examine changes over time in sinus mode function after cardiac transplantation; to determine the incidence, natural history and etiology of sinus node dysfunction in transplant recipients; and to identify any early predictors of long-term sinus node function. BACKGROUND Bradyarrhythmias caused by sinus node dysfunction are common immediately after cardiac transplantation. Existing electrophysiologic studies have been limited by small numbers and have reported an unexpectedly high incidence of sinus node dysfunction (approximately 50%) compared with the incidence of bradyarrhythmias in other studies. There have been no previous studies reporting serial electrophysiologic data. Thus, the natural history of sinus node dysfunction after transplantation has not been adequately described. METHODS Serial electrophysiologic studies of sinus node function and 24-h ambulatory electrocardiographic recordings were performed at 1, 2, 3 and 6 weeks and 3 and 6 months after transplantation in 40 adult recipients. RESULTS The overall incidence of sinus node dysfunction was 17.5% (7 of 40). Six patients (15%) had sinus node dysfunction from week 1; one developed sinus node dysfunction at 3 months. Sinus node recovery time returned to normal by 6 weeks in all six patients with early sinus node dysfunction, but abnormalities of sinoatrial conduction persisted in two. Two patients who required pacing during ambulatory monitoring at 2 weeks after transplantation (temporary pacemaker 50 beats/min, demand) received a permanent pacemaker. One patient required pacing at 3 weeks and continued to require pacing 6 months after transplantation. CONCLUSIONS The incidence of sinus node dysfunction after cardiac transplantation is lower than has been previously reported in electrophysiologic studies. Sinus node automaticity improves with time, although abnormalities of sinoatrial conduction may persist. The best predictor of permanent pacing requirements is the temporary pacing requirements during 24-h Holter monitoring 2 and 3 weeks after transplantation, with temporary pacing set at 50 beats/min on demand.

News from the Heart Rhythm SocietyHRS/ACCF Expert Consensus Statement on Pacemaker Device and Mode Selection: Developed in partnership between the Heart Rhythm Society (HRS) and the American College of Cardiology Foundation (ACCF) and in collaboration with the Society of Thoracic Surgeons

Anne M. Gillis, MD, FHRS, Andrea M. Russo, MD, FHRS, FACC, Kenneth A. Ellenbogen, MD, FHRS, FACC, Charles D. Swerdlow, MD, FHRS, CCDS, FACC, Brian Olshansky, MD, FHRS, CCDS, FACC, Sana M. Al-Khatib, MD, MHS, FHRS, CCDS, FACC, John F. Beshai, MD, FHRS, FACC, Janet M. McComb, MD, FHRS, Jens Cosedis Nielsen, MD, Jonathan M. Philpott, MD, Win-Kuang Shen, MD, FHRS, FACC From University of Calgary, Libin Cardiovascular Institute of Alberta, Alberta, Canada, Cooper Medical School of Rowan University, Cooper University Hospital, New Jersey, USA, Virginia Commonwealth University Medical Center, irginia, USA, David Geffen School of Medicine at UCLA, California, USA, University of Iowa Hospital, Iowa, USA, Duke University Medical Center, North Carolina, USA, University of Chicago Hospitals, Illinois, USA, Freeman ospital, Newcastle-upon-Tyne, United Kingdom, Skejby Hospital, Aarhus, Denmark, Mid-Atlantic Cardiothoracic Surgeons, Virginia, USA, Mayo Clinic College of Medicine, Arizona, USA. Representing the Society of Thoracic Surgeons