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Biomedical subjects

A Lazarus

Publications and source records attributed to A Lazarus.

At least 19 recordsLinked to original sources

Relationships among electrophysiological findings and clinical status, heart function, and extent of DNA mutation in myotonic dystrophy.

BACKGROUND: Impulse-conduction abnormalities and arrhythmias are common in myotonic dystrophy (MD). This study was performed to determine whether a correlation exists between electrophysiological (EP) testing data and clinical status, heart function, or size of the DNA abnormality (cytosine-thymine-guanine sequence repeat). METHODS AND RESULTS: Eighty-three MD patients underwent invasive EP studies prompted primarily by the presence of asymptomatic conduction abnormalities. AV conduction disturbances were common and mainly distal (HV interval, 66.2+/-14 ms). AV conduction observed from the surface ECG was generally concordant with endocardial measurements. However, 11 of 20 patients with normal surface ECGs had abnormal subhisian conduction. Atrial arrhythmias were inducible in 41% of cases and correlated with prolongation of the AH interval (P=0.02) and a shorter atrial refractory period (P=0.04). Induction of ventricular arrhythmias (18%) correlated strongly with age (P=0. 0003). After adjustment for age, the extent of DNA mutation correlated with the Walton score (P=0.0018) but not with conduction abnormalities or induction of arrhythmias. CONCLUSIONS: Prolongation of the HV interval is the most common conduction abnormality in MD and can be reliably recognized only by invasive EP testing. It raises the issue of prophylactic pacing to limit the incidence of sudden death in MD. Atrial and ventricular arrhythmias are often inducible, although their predictive value remains to be determined. Young age emerged as the most powerful predictor of inducible ventricular tachyarrhythmias. Conversely, we found no relationship between ECG or EP abnormalities recorded during invasive testing and the DNA mutation size or severity of peripheral muscle involvement.

Adult

Acute hemodynamic effects of biventricular DDD pacing in patients with end-stage heart failure.

OBJECTIVES: The aim of this study was to assess the potential acute benefit of multisite cardiac pacing with optimized atrioventricular synchrony and simultaneous biventricular pacing in patients with drug-refractory congestive heart failure (CHF). BACKGROUND: Prognosis and quality of life in severe CHF are poor. Various nonpharmacological therapies have been evaluated but are restricted in their effectiveness and applications. In the early 1990s, dual chamber pacing (DDD) pacing was proposed as primary treatment of refractory CHF but results were controversial. Recently, tests to evaluate the effect of simultaneous pacing of both ventricles have elicited a significant improvement of cardiac performance. METHODS: Acute hemodynamic study was conducted in 18 patients with severe CHF (New York Heart Association class III and IV) and major intraventricular conduction block (IVCB) (QRS duration = 170+/-37 ms). Using a Swan-Ganz catheter, pulmonary artery pressure, pulmonary capillary wedge pressure (PCWP) and cardiac index (CI) were measured in different pacing configurations: atrial pacing (AAI) mode, used as reference, single-site right ventricular DDD pacing and biventricular pacing with the right ventricular lead placed either at the apex or at the outflow tract. RESULTS: The CI was significantly increased by biventricular pacing in comparison with AAI or right ventricular (RV). DDD pacing (2.7+/-0.7 vs. 2+/-0.5 and 2.4+/-0.6 l/min/m2, p < 0.001). The PCWP also decreased significantly during biventricular pacing, compared with AAI (22+/-8 vs. 27+/-9 mm Hg; p < 0.001). CONCLUSIONS: This acute hemodynamic study demonstrated that biventricular DDD pacing may significantly improve cardiac performance in patients with IVCB and with severe heart failure, in comparison with intrinsic conduction and single-site RV DDD pacing.

Aged

Reliability of an automatic sensing test with beat-to-beat display of the signal amplitude.

In contrast to testing of the capture threshold, the reliability of sensing tests has been little studied. This study was performed to test the automatic sensing algorithm included in the Biotronik pacing systems. The automatic measurements made by the devices were compared with the direct manual measurements made of 271 atrial (72%) or ventricular (28%) electrograms recorded in ten patients. A high correlation (r = 0.995, P < 0.0001) was found between the two types of measurements. The use of this function should facilitate the verification of accurate sensing during the long-term follow-up of pacemaker patients, and offers a tool to analyze the variations in amplitude of intracardiac signals.

Algorithms

Permanent left ventricular pacing with transvenous leads inserted into the coronary veins.

This paper describes a preliminary experiment-conducted jointly by 2 centers-of permanent left ventricular pacing using leads inserted by the transvenous route and through the coronary sinus into the cardiac veins of the left ventricle free wall. The aim was to obtain permanent biventricular pacing in a totally endocavitary configuration in patients with severe LV dysfunction and drug-refractory heart failure. Two types of leads were used: nonspecific unipolar leads at the beginning of the experiment, followed by leads specifically designed to be used in the coronary sinus in a second step. The electrode could be fitted in an adequate location in 35 of the 47 patients (75.4%), with a 1.15 +/- 0.7 V acute pacing threshold and 11.8 +/- 5.7 mV R wave amplitude. The success rate was significantly higher with the specific electrodes (81.8% vs 53.3%, p < 0.001). The pacing and sensing thresholds upon implantation were not influenced by the type of lead or by the localization of the cardiac vein that was catheterized (great cardiac vein, lateral vein, postero-lateral or posterior vein, mid cardiac vein). In contrast, the pacing threshold was significantly lower (0.8 +/- 0.2 vs 1.8 +/- 0.8 V; p = 0.002) and the R wave amplitude tended to be greater (13.1 +/- 4.5 mV vs 9.3 +/- 6.5 mV; p = 0.07) when the tip electrode could be inserted distally into the vein, by comparison with a proximal site near the ostium. At the end of follow-up (10.2 +/- 8.7 months), 34 out of the 35 leads were still fully functional, with a chronic pacing threshold of 1.8 +/- 0.7 V and a R wave amplitude of 10.7 +/- 6 mV. To conclude, permanent LV pacing via the transvenous route is possible in most patients, with excellent safety and long-term results.

Aged

Reduction in energy pacing thresholds by overlapping biphasic stimulation versus conventional bipolar pacing.

UNLABELLED: Overlapping biphasic (OLBI) stimulation is a new pacing waveform consisting of two simultaneous monophasic pulses of opposite polarities applied to a bipolar electrode. The goal of this prospective study was to compare, using conventional pacing leads, the acute energy pacing thresholds, measured at 0.5-ms pulse duration, associated with bipolar versus OLBI (mode 7 and mode 8) pulse delivery. RESULTS: Thirty one leads were tested in 20 patients. Of these leads, 7 (23%) were implanted chronically, 12 (39%) were in atrial positions, and 19 (61%) in ventricular positions. Energy pacing thresholds were significantly lower (-25.6 +/- 25.6%, P = 0.005) in OLBI mode 8 (1.30 +/- 3.96 microJ) compared to bipolar (1.55 +/- 4.37 microJ) pacing, regardless of the pacing site or length of service of the leads. In contrast, OLBI mode 7, which has an anodal component, at the tip electrode was associated with higher energy pacing thresholds (3.65 +/- 6.48 microJ; +358.3 +/- 219.4%, P = 0.002). CONCLUSIONS: Mode 8 OLBI pacing is associated with lower acute energy pacing thresholds when used with bipolar leads in contact with the myocardium. OLBI pacing may increase pacemaker longevity by reducing long-term energy consumption.

Arrhythmias, Cardiac

Effects of a selective A1-adenosine receptor agonist on heart rate and heart rate variability during permanent atrial fibrillation.

BACKGROUND: Mean heart rate and irregularity of the rate, i.e., heart rate variability (HRV), are two aspects of heart rate during atrial fibrillation (AF). An important goal of AF therapy is to control mean heart rate during exercise; the determinants of HRV during AF remain poorly known although its prognostic value has been established. OBJECTIVES: To investigate the effects of a stable, long-acting, selective A1-adenosine receptor agonist, SDZ WAG994, on heart rate during exercise and on HRV. METHODS: In a multicenter, double-blind, randomized, placebo-controlled, parallel group study, patients with permanent AF performed a symptom-limited exercise test and underwent 24-hour ECG monitoring on day 1 during treatment with placebo, and on day 2 during treatment with either placebo or 2 mg SDZWAG994 orally. Changes in mean heart rate during exercise and changes in HRV indices between day 1 and day 2 were compared between the two groups. RESULTS: Thirty-two patients (64 +/- 8 years; 81% male; 25% in NYHA Class II; 38% with no structural heart disease) were included in the study. During active treatments, heart rate remained unchanged at rest and increased significantly during exercise. A significant daytime increase in short-term HRV indices (DpNN50 = 4.5% P = 0.01; DrMSSD = 6% P = 0.03; DSDNN Index = 6% P = 0.02) occurred during active treatment. CONCLUSIONS: Selective A1-adenosine receptor agonism with SDZ/WAG994 limits the increase in mean heart rate during exercise in patients with AF. In addition, this agonist selectively increases short-term HRV indices, suggesting that pNN50, rMSSD, and SDNN reflect vagal influences during AF.

Adenosine

[Arrhythmogenic effects of extracorporal lithotripsy in desynchronized mode with a later generation lithotriptor].

Extracorporal lithotripsy has transformed the treatment of renal stones. However, the shock waves can generate arrhythmias which may be severe. To prevent them, the shocks were synchronised to the absolute refractory period of the cardiac cycle with a corollary, an increase in the procedure time. The latest generation of lithotriptors have a number of technical improvements allowing desynchronisation but with a high theoretic risk of arrhythmias. The aim of this study was to assess the arrhythmogenic effects of desynchronised shocks by Holter ECG monitoring during the procedure. This was a prospective randomised study: 25 patients with no previous cardiovascular history were included: 15 men and 10 women with a mean age of 45 years. The originality of this study was the delivery of shock waves in two phases (synchronised versus desynchronised) in a random fashion, the order being unknown to the cardiologist interpreting the recordings. In the synchronised mode, none of the patients developed an arrhythmia. On the other hand, in the desynchronised mode, hyperexcitability was observed in 7 patients, supraventricular in 6 cases (atrial extrasystoles and atrial doublets) and ventricular in 4 cases (VES, ventricular doublets and 1 unsustained ventricular tachycardia). These arrhythmias were asymptomatic and regressed spontaneously. The authors conclude that although they are arrhythmogenic, desynchronised procedures with the latest lithotriptors are acceptable, provided that the patients undergo a cardiological examination beforehand to identify high risk patients and that there is adequate monitoring during the procedure in the presence of an anaesthetist.

Adult

Breaking the glass ceiling.

The glass ceiling is a form of organizational bias and discrimination that prevents qualified professionals from achieving positions of top governance and leadership. This article examines glass ceiling barriers that keep physicians from the upper reaches of management. While these factors apply mainly to women and minority physicians in academia, and are attributable to sexual harassment and discrimination, physicians as a class are frequently denied executive management positions. Such denial results from inadequate preparation for a career in health care administration. Important issues in the professional development of physician executives include mentoring, training and education, administrative experience, and cultural and personality factors. All of those must be considered when making the transition from medicine to management.

Career Mobility

Enhanced expression of IL-12 associated with Th1 cytokine profiles in active pulmonary sarcoidosis.

Sarcoidosis is a multisystem granulomatous disease of unknown etiology characterized by the expansion of activated oligoclonal CD4+ T cells and macrophages at sites of disease. To investigate the immunopathogenesis of sarcoidosis, we analyzed patterns of cytokine expression in bronchoalveolar lavage cells and fluid from patients with pulmonary sarcoidosis and idiopathic pulmonary fibrosis and from normal volunteers. We found dominant type 1 cytokine expression, with elevated mRNA and protein levels of IFN-gamma, but not IL-4, in sarcoid lung cells and fluid compared with those in normal samples. To define immunoregulatory mechanisms important to this type 1 response, we analyzed the expression of IL-12 and IL-10 in lung cells and fluid. Using semiquantitative PCR, we found significantly higher mRNA expression of the regulated IL-12 p40 subunit, but not IL-10, in sarcoid compared with normal lung cells. Consistent with these observations, strikingly elevated levels of p40 protein were found in sarcoid compared with normal bronchoalveolar lavage fluid. Unstimulated and Staphylococcus aureus-stimulated sarcoid alveolar macrophages produced greater amounts of IL-12 than normal alveolar macrophages when cultured in vitro. We hypothesize that sarcoidosis is a Th1-mediated disease driven by chronic, dysregulated production of IL-12 at sites of disease.

Adult

A prospective multicenter study demonstrating clinical benefit with a new accelerometer-based DDDR pacemaker. Dromos Dr Investigators Group.

From November 1994 to October 1995, 63 patients (average age 66 years; 41 men) from 15 centers implanted with the Biotronik Dromos DR and Ergos TC 03 pulse generators were prospectively screened with an exercise test in the DDD mode for the presence of chronotropic incompetence (CI). Both pulse generators incorporate an identical accelerometer-based motion sensor. CI was defined as a maximum heart rate < 60% of age predicted maximum heart rate or 100 beats/min. Twenty-five patients (40%) met the criteria for CI. Two weeks later, CI patients were required to complete paired metabolic exercise testing in the DDD and DDDR modes on consecutive days with a 24-hour rest period. The order of testing was randomized and performed double blinded to minimize potential biases. Three patients who did not reach the anaerobic threshold (AT) and one patient who was unable to perform the metabolic testing were excluded from the analysis. Compared to the DDD mode, there were statistically significant improvements in the DDDR mode for all five endpoints: heart rate (84 +/- 3.6 vs 113 +/- 3.5 beats/min; P < 0.0001); total exercise time (8.23 +/- 0.71 vs 9.15 +/- 0.65 min; P = 0.0005); maximum VO2 (17.76 +/- 1.36 vs 20.43 +/- 1.75 mL/kg per min; P = 0.0001); VO2 at AT (13.1 +/- 0.87 vs 14.59 +/- 0.79 mL/kg per min; P < 0.01); and exercise time to AT (5.65 +/- 0.61 vs 6.33 +/- 0.53 min; P = 0.02). In conclusion, the results of paired metabolic exercise tests with the Dromos DR and Ergos TC 03 pulse generators demonstrate a clear clinical benefit using the accelerometer-based sensor in the CI patient.

Acceleration

Multisite pacing for end-stage heart failure: early experience.

Our objective was to improve hemodynamics by synchronous right and left site ventricular pacing in patients with severe congestive heart failure (CHF). Previous studies reported a benefit of dual chamber pacing with a short AV delay in patients with severe CHF. Other works, however, show contradictory results. Deleterious effects due to a desynchronization of right (RV) and left ventricular (LV) contractions have been suggested. This study included eight subjects with widened QRS and end-stage heart failure despite maximal medical therapy, who refused, or were not eligible to undergo heart transplantation, Each patient underwent a baseline, invasive hemodynamic evaluation with insertion of three temporary leads to allow different pacing configurations, including RV apex and outflow tract pacing, and biventricular pacing between the RV outflow tract and LV and RV apex and LV. According to the results of this baseline study, the configuration of preexistent pacemakers was modified or new systems were implanted to allow biventricular pacing, which, in patients with sinus rhythm, was atrial triggered. Biventricular pacing increased the mean cardiac index (CI) by 25% (from a baseline of 1.83 +/- 0.30 L/min per m2, P < 0.006), decreased the mean V wave by 26% (from a baseline of 36 +/- 12 mmHg, P < 0.004), and decreased pulmonary capillary wedge pressure by 17% (from a baseline of 31 +/- 10 mmHg, P < 0.01). Four patients died (1 preoperatively, 1 intraoperatively, 2 within 3 months, and 1 of a noncardiac cause). The four surviving patients have clinically improved from New York Heart Association Functional Class IV to Class II. In these survivors, CI decreased by 15% (P < 0.007) when multisite pacing was turned off during follow-up. In patients with end-stage heart failure, multisite pacing may be associated with a rapid and sustained hemodynamic improvement.

Aged