Biomedical subjects
Publications and source records attributed to J M Davy.
A 29-year-old patient presented with Takayasu's arteritis which was revealed by heart failure, epilepsy, right hemiparesis and fever. Transient abnormalities of MRI and CSF (raised protein and cell content) were initially observed. The hypothesis of a hypertensive encephalopathy is suggested.
The mechanisms of action of antiarrhythmic drugs at atrial level are multiple. Antiarrhythmics may act at three levels in the prevention of paroxysmal atrial fibrillation: on the arrhythmogenic atrial substrate, the initiating extrasystoles including those of the pulmonary veins, and in the modulation of the autonomic nervous system. However, there are many modes of initiation which are not well understood so that the preventive role of the antiarrhythmic drugs remains imprecise. Cardioversion of persistent atrial fibrillation has been better analysed in healthy hearts: Class I antiarrhythmics in particular, despite their depressive effects on the conduction which are potentially arrhythmogenic, are beneficial by decreasing the number of reentry circuits, prolonging the atrial refractory period on short cycles and, paradoxically, by increasing the period of excitability in AF. All have a preferential action on anisotropic conduction, especially at the pivotal point of reentry. On the other hand, their role in electrophysiological remodelling in the prevention of immediate recurrences and in pathological atria, remains poorly understood. As for atrial flutter, despite many clinical and experimental studies with antiarrhythmics, the current predominant role of radiofrequency ablation greatly limits the value of these pharmacological studies.
Monophasic action potentials are currents recorded in vivo in the extracellular milieu which can reproduce the repolarisation signal of intracellular action potentials. For a long time unstable and complex to record, they now require simply a firm myocardial contact with a bipolar electrophysiological catheter and modification with recording filters, without a high-pass filter (DC). They have been widely used in recent years to study in vivo modifications of the action potential durations with frequency, epi-, endo-, or intramyocardial cellular topography, endocavity pressure modifications, or antiarrhythmic medication. They allow a unique means of continuous analysis in animals or in patients of the action potentials during polymorphic arrhythmias such as atrial fibrillation, ventricular fibrillation and torsades de pointes, although in these cases the refractory periods can not be measured precisely and continuously, beat after beat. In contrast, their clinical or experimental use in the study of arrhythmias dependent on premature post-depolarisations has without doubt been excessive and disputable, because it appears improbable that authentic premature post-depolarisations could ever be obtained on a monophasic action potential, which always represents the summation of the action potentials of dozens of cells.
The PEPS study had the objective of documenting the acceptability and efficacy of propafenone in 1366 treated patients, after correction of chronic or paroxysmal AF, and followed up over one year. All the cases were validated by quality controls performed by the 196 participating cardiologists. All the events during follow up were validated by a committee of independent experts. The patients, aged 67 +/- 11 years, were in sinus rhythm on inclusion. Propafenone was prescribed at the initial dose of 600 mg/day in 65% of patients. The proportion of patients without relapse of AF was 64 +/- 1% at 12 months. After adjustment, the significant predictors of AF relapse were male sex, previous history of chronic AF and prescription of associated drugs. Neither patient age nor propafenone dose significantly influenced AF relapse. Seven deaths (0.5%) occurred during the study of which 3 were of unknown cause. A pro-arrhythmic effect was observed in 8 patients (0.59%) of which 6 had underlying heart disease. The overall frequency of pro-arrhythmic effects, including the 3 deaths of unknown cause, was therefore 0.81%. Tolerance of treatment with propafenone after correction of AF is therefore satisfactory and the frequency of pro-arrhythmic effects is less than 1%. The efficacy of the treatment for the maintenance of sinus rhythm is in accordance with previously published results.
We report a case of continuous supraventricular tachycardia in a patient affected by Steinert's myotonic dystrophy. The investigation of this tachycardia showed that there was a "slow-fast" common nodal re-entry, rendered continuous by the existence of significant conduction defects in the fast pathway and the slow anterograde pathway. Implantation of a double chamber cardiac stimulator, necessary for conduction defects present in the basal state in this patient allowed, with the evolution of the conduction defects, the complete eradication of reciprocal rhythm entry, without resorting to ablation.
The aim of this preliminary study was to evaluate the accuracy of left and right ventricular output computed from a semi-automatic processing of tomographic radionuclide ventriculography data (TRVG) in comparison with the conventional thermodilution method. Twenty patients with various heart diseases were prospectively included in the study. Thermodilution and TRVG acquisitions were carried out on the same day for all patients. Analysis of gated blood pool slices was performed using a watershed-based segmentation algorithm. Right and left ventricular output measured by TRVG correlated well with the measurements obtained with thermodilution (r = 0.94 and 0.91 with SEE = 0.38 and 0.46 l/min, respectively, P < 0.001). The limits of agreement for TRVG and thermodilution measurements were -0.78-1.20 l/min for the left ventricle and -0.34-1.16 l/min for the right ventricle. No significant difference was found between the results of TRVG and thermodilution with respect to left ventricular output (P = 0.09). A small but significant difference was found between right ventricular output measured by TRVG and both left ventricular output measured by TRVG (mean difference = 0.17 l/min, P = 0.04) and thermodilution-derived cardiac output (mean difference = 0.41 l/min, P = 0.0001). It is concluded that the watershed-based semi-automatic segmentation of TRVG slices provides non-invasive measurements of right and left ventricular output and stroke volumes at equilibrium, in routine clinical settings. Further studies are necessary to check whether the accuracy of these measurements is good enough to permit correct assessment of intracardiac shunts.
We documented chronic ventricular arrhythmias in a first group of 58 rats after myocardial infarction (MI), then assessed the effects of spironolactone and fosinopril on morphological indexes and arrhythmias in a second group (n = 33). Rats underwent Holter monitoring at 2 months after MI. Treatment was randomly given from 1 until 4 months after MI: placebo in 12 rats (P), fosinopril in 9 (F) and spironolactone + fosinopril in 12 (SF). The score of ventricular premature beats (VPBs) was related to the MI size and the delay from MI (p < 0.01). VPB's reduction/increase required to demonstrate anti/pro-arrhythmic effects were 55 and 59%. Mass indexes were lower in F and SF (p = 0.01). VPB's difference (4 months vs. 1) was positive in P, significantly lower in F and negative in SF (p = 0.04). In this relevant model of spontaneous and chronic ventricular arrhythmias, SF association did not increase mortality but lowered the arrhythmic score.
A simple ECG curiosity or a precursor of serious arrhythmia, associated with pericardial effusion or a sign of inotropic alteration, the phenomenon of electrical alternans has intrigued clinicians and research workers in its multiple facets, mechanical and electrical, consequences on PR interval, QRS complex or ventricular repolarisation. As a consequence, the causal mechanisms are very different, but these last few years, a predominant role of calcium flux, especially intracellular, has been demonstrated. Recently, clinical interest in this phenomenon has been revived with the demonstration of micro-alternans of repolarisation, apparently a new marker for the risk of sudden death.
OBJECTIVES: The objective of this study was to determine whether a small-size valve prosthesis contributes to exercise intolerance, as assessed by VO2 measurement during an exhaustive cycle ergometer exercise. BACKGROUND: The determinants of exercise capacity after mechanical aortic replacement are not well known. The selection of small valve sizes has, however, been described as an independent predictor of exercise intolerance as assessed by exercise duration. Maximal oxygen uptake (VO2max) is a good index of exercise tolerance. METHODS: Fourteen patients were eligible, with a mean age of 62 +/- 6 years. Before surgery, the mean left ventricular ejection fraction (LVEF) was 73 +/- 8%. Two valve types with small diameter (19 to 21 mm) were used: Medtronic Hall and St Jude Medical. A healthy sedentary control group (n = 14) paired for age, weight and size was constituted. After one year of follow-up, cardiorespiratory tests were performed. In addition, the gradients through the prostheses were determined by continuous pulse Doppler at rest and immediately after the cardiorespiratory test. RESULTS The exercise tolerance was not significantly different between the control group and patient group: VO2 peak (21.7 vs. 20.4 ml/kg/min; p = 0.42), workloads (115 vs. 93 W; p = 0.13) and ventilatory parameters were similar. The mean and peak gradients at rest and during exercise were not correlated with VO2max. CONCLUSIONS: Valve replacement by small aortic prosthesis does not seem to be a factor of exercise intolerance as assessed by VO2max in patients without LVEF dysfunction before surgery.
We studied the effects of dronedarone (SR 33589) on the action potentials, membrane ionic currents, and arrhythmic activity in control rats and in rats after myocardial infarction, a model known to develop anomalous electrical activity. Dronedarone increased action potential duration in normal hearts. It had little effect on the action potentials that were already prolonged in the postmyocardial infarcted (PMI) rats. Particularly, dronedarone reduced the late sustained K(+) current, I(K) (or Isus) by 69%. Dronedarone induced only a tonic block of I(K). Similar relative inhibitions of I(K) by dronedarone were obtained in young, sham, and PMI rats, even if I(K) was less in sham than in young and further reduced in PMI rats. The EC(50) values were 0.78 and 0.85 microM in sham and PMI rats. Dronedarone induced a weak increase in the fast transient outward current, I(to). Time-to-peak and inactivation time constant of I(to) were decreased by dronedarone that also induced a marked slowing of I(to) recovery from inactivation. Similar effects were observed on the reduced I(to) recorded in PMI rats. Holter monitoring study in control, unthetered animals showed that dronedarone had no proarrhythmic effect. On rats, which after myocardial infarction exhibited ventricular premature beats, dronedarone significantly decreased beat occurrence during the 7-day treatment; this effect was sustained for two more weeks. Thus, dronedarone exerts antiarrhythmic effects on PMI rat heart. Its effects are attributable for the most part to the inhibition of outward K(+) currents and the increase in effective refractory period.
In 1995, Wijffels and Alessie, using a curious goat model of atrial fibrillation, introduced the concept of atrial remodelling. The classical atrial substrate (anatomopathological-dilatation and hypokinesis-, and electrophysiological-short refractory periods and decreased conduction-), appeared not only to be one of the causes of atrial fibrillation but also the consequence of atrial fibrillation itself, the mechanism being a vicious circle. In addition to ventricular rhythmic cardiomyopathy, responsible for cardiac failure, the concept of atrial rhythmic cardiomyopathy with the same mechanical and electrophysiological consequences, has developed. These changes, characterised mainly by calcium overload associated with cellular hibernation and differentiation, have not been totally elucidated but have already renewed the physiopathology of atrial fibrillation.
UNLABELLED: The aims of the study were to analyze the clinical features, the penetrance and the mode of inheritance of 13 French families with dilated cardiomyopathy using diagnostic criteria recently established by a European collaboration. METHODS: Screening consisted of physical examination, ECG and Echo of all the probands first degree relatives (n = 118). Using major Echo criteria [ejection fraction (EF) < 45% or FS < 25% and left ventricular diameter (LVD) > 117% of the predictive value], or combined minor Echo/ECG criteria, relatives were classified as affected, unknown or healthy. RESULTS: (1) Adult affected relatives (n = 31) were identified with major Echo criteria in 74% of cases, and with combined minor Echo/ECG criteria in 26% of cases. (2) In the unknown relatives (n = 21), the most common abnormality was an isolated left ventricular dilation (67%). (3) Mode of inheritance was autosomal dominant (AD) in 11 families and possibly autosomal recessive in two. (4) In AD families, the penetrance was incomplete in adults (72%), age-related (O.R.: 1.3 per 10 years; 95% CI 1.03-1.56) and sex-related [greater in men (87%) than in women (61%), actuarial survival curve: P<0.002]. (5) Mortality related to end stage heart failure was 2.2 times as high as mortality related to sudden death (11% vs. 5%). CONCLUSIONS: (1) In the absence of a specific phenotype of FDC, the characterization of relatives appears more accurate when minor criteria were added. (2) Since high mortality (16%) and incomplete penetrance frequently give rise to small nuclei of clinically affected and alive relatives per family, the accurate model of penetrance that we proposed might be helpful in the future to enhance the statistical power of linkage analysis in this disease.
The characteristics of neurocardiogenic syncope (NCS) in elderly patients remain unclear. We compared the hemodynamic profiles of young and older patients with consecutive and positive head-up tilt tests (HUT). Continuous, noninvasive, and reliable monitoring of arterial pressure (AP) and heart rate (HR) was done throughout 46 consecutive positive HUTs of symptomatic patients. The population (12-82 years old) was divided into two groups: younger patients, Y (n = 25, < or = 65 years), and older patients, O (n = 21). Changes in AP and HR after the first minute of tilting, during the stable orthostatic phase and during syncope were compared. Except for systolic pressure, baseline hemodynamic parameters were similar in Y and O. No difference appeared in the mean time elapsed before syncope (19+/-9 vs 22+/-2 min). Asymptomatic hypotension was observed, only in O, 1 minute after tilting, followed by a progressive fall in the mean AP before syncope (0+/-0.9 vs -1+/-0.7 mmHg/min) without HR increase (0.7+/-1 vs 0+/-0.6 beats/min). This pressure slope was strongly related to age (r = 0.54, P < 0.001). Hemodynamic recording during HUT identifies a dysautonomic pattern in elderly patients with NCS and the abnormal AP/HR responses to orthostasis may be a feature specific to this population. Although the central mechanism of NCS is common to all ages, the age-related characteristics of the trigger event may indicate the need for specific management at different ages.
OBJECTIVE: To evaluate the combined assessment of reflow and collateral blood flow by myocardial contrast echocardiography after myocardial infarction. DESIGN: Myocardial contrast echocardiography was performed in patients with acute myocardial infarction shortly after successful coronary reperfusion (TIMI 3 patency) by direct angioplasty. Collateral flow was assessed before coronary angioplasty, and contrast reflow was evaluated 15 minutes after reperfusion. The presence of contractile reserve was assessed by low dose dobutamine echocardiography (5 to 15 micrograms/kg/min) at (mean (SD)) 3 (2) days after myocardial infarction. Recovery of segmental function (myocardial viability) was evaluated by resting echocardiography at a two month follow up. The study was prospective. PATIENTS: 35 consecutive patients referred for acute transmural myocardial infarction. RESULTS: Contrast reflow was observed in 20 patients (57%) and collateral flow in 14 (40%). Contrast reflow and collateral contrast flow were both correlated with reversible dysfunction on initial dobutamine echocardiography and at follow up (p < 0.05). The presence of reflow or collateral flow on myocardial contrast echocardiography was a highly sensitive (100%) but weakly specific (60%) indicator of segmental dysfunction recovery. Simultaneous presence of contrast reflow and collateral flow was more specific of reversible dysfunction than reflow alone (90% v 60%). CONCLUSIONS: Combined assessment of reflow and collateral blood flow enhanced the sensitivity of myocardial contrast echocardiography in predicting myocardial viability after acute, reperfused myocardial infarction. The simultaneous presence of reflow and collateral blood flow was highly specific of recovery of segmental dysfunction.
The aim of the study was to determine whether facilitation of reentry by potassium-channel openers is related to dispersion of refractoriness and/or modification of anisotropic properties of ventricular myocardium. The dispersion of ventricular effective refractory period (VERP), longitudinal and transverse ventricular conduction velocities (thetaL and thetaT, respectively), and wavelength [lambda = VERP x theta(L or T)] were studied in Langendorff-perfused left ventricular epicardium in 20 rabbits during infusion of incremental doses of levcromakalim or nicorandil. Dispersion of refractoriness was assessed using standard deviation of VERP mean (SD-VERP), dispersion index (DI; SD-VERP/mean VERP), and maximum dispersion (Dmax = VERPmax - VERPmin). Ventricular conduction velocities and anisotropic ratio were not modified, whatever the dose used. VERP and lambda were significantly shortened at high concentrations of levcromakalim and nicorandil. At these doses, SD-VERP, DI, and Dmax were increased significantly. Analysis of ventricular tachycardia induction, performed using a high-resolution ventricular mapping system, confirmed that heterogeneity and shortening of VERP were factors inducing functional conduction block. Our data suggest that, in rabbit left ventricular epicardium, functional conduction block facilitating the occurrence of reentry could be initiated by shortening and, especially, by dispersion of refractoriness during infusion of potassium-channel openers.
OBJECTIVE: To report two cases of chronic constrictive pericarditis that appear to be related to the intake of bromocriptine for Parkinson's disease. CASE SUMMARY: Two white men (aged 63 and 69 y) were treated with bromocriptine for four (40 mg/d) and two years (30 mg/d), respectively, with a cumulative dose intake of 58.4 and 21.9 g, respectively. The patients experienced dyspnea with bilateral lower-limb edema and pleural effusion, suggesting right cardiac dysfunction. Echocardiography, computed tomography, and cardiac catheterization results were compatible with a diagnosis of constrictive pericarditis, so pericardectomy was performed on both patients. The anatomic pathology examination showed a fibrous pericardium; cultures were sterile. In the first case, pleural effusion recurred seven months after the pericarditis; bromocriptine was suspected and treatment was discontinued. In the second case, just prior to the pericardectomy, an episode of mental confusion occurred and prompted the cessation of bromocriptine therapy. DISCUSSION: To the best of our knowledge, only one case of constrictive pericarditis induced by bromocriptine therapy has previously been described in the literature. CONCLUSIONS: Our cases call attention to a possible association between bromocriptine use in patients who have Parkinson's disease and constrictive pericarditis.
The ECG appearances of His bundle pathology are very variable and endocavitory recordings are often required to confirm the diagnosis which may be suspected by close analysis of the surface ECG. Truncular AVB is a serious condition as the block is infranodal but with a supraventricular and therefore a narrow QRS complex: it may be median with a double His potential or proximal and distal, which are more difficult to diagnose. Hisian extrasystoles are particularly polymorphic, either overtly, suggesting successively atrial and ventricular extrasystoles, or masked with deceptive pseudo-1st or 2nd degree atrioventricular block. More rarely, hisian tachycardias complicating congenital heart disease in children are observed, particularly in the postoperative period.
INTRODUCTION: Clinical treatment with a combination of Class IA and III antiarrhythmic drugs is not recommended, as they both favor bradycardia-dependent proarrhythmic events such as torsades de pointes (TdP). However, this theoretical additive effect on ventricular repolarization has never been demonstrated and could be questioned as other Class I drugs, such as mexiletine, a Class IB drug, limit the number of sotalol-induced TdP in dogs with AV block, suggesting the possibility of an antagonistic action of Class I properties against Class III effects. METHODS AND RESULTS: We compared the electrophysiologic and proarrhythmic effects of sotalol (Class III) alone and combined with quinidine (Class IA) in a canine model of acquired long QT syndrome. Seven hypokalemic (K+: 3 +/- 0.1 mEq/L) dogs with chronic AV block had a demand pacemaker implanted and set at a rate of 25 beats/min. They were submitted to two (sotalol-alone and sotalol-plus-quinidine) experiments 48 hours apart using a randomized cross-over protocol. They were pretreated with quinidine (10 mg/kg + 1.8 mg/kg per hour) or saline infused throughout the experiment, and given sotalol (4.5 mg/kg + 1.5 mg/kg per hour) for 2 hours, 30 minutes after the beginning of the pretreatment infusion during both experiments. Ventricular and atrial cycle lengths were similarly increased by sotalol after quinidine or saline. The sotalol-induced prolongation of the QT interval was significantly shorter in quinidine-pretreated dogs (24 +/- 7 msec after quinidine vs 40 +/- 8 msec after saline). Fewer dogs developed TdP: significantly during the first hour of infusion (1/7 sotalol-plus-quinidine vs 6/7 sotalol-alone dogs, P < 0.05) but nonsignificantly during the second hour (3/7 vs 6/7). CONCLUSION: In this model, the sotalol-plus-quinidine combination is at least no more arrhythmogenic than either of the drugs given alone.