Ectopic activity in the rat pulmonary vein can arise from simultaneous activation of alpha1- and beta1-adrenoceptors.

BACKGROUND AND PURPOSE: Atrial fibrillation (AF) is the most common electrical cardiac disorder in clinical practice. The major trigger for AF is focal ectopic activity of unknown origin in sleeves of cardiac muscle that extend into the pulmonary veins. We examined the role of noradrenaline in the genesis of ectopic activity in the pulmonary vein. EXPERIMENTAL APPROACH: Mechanical activity of strips of pulmonary vein isolated from male Wistar rats was recorded via an isometric tension meter. Twitch contractions of cardiac myocytes were evoked by electrical field stimulation in a tissue bath through which flowed Krebs-Heinseleit solution warmed to 36-37 degrees C and gassed with 95% O(2) 5% CO(2). KEY RESULTS: The superfusion of noradrenaline induced ectopic contractions in 71 of 76 different isolated pulmonary veins. Ectopic contractions in the pulmonary vein were not associated with electrically evoked twitch contractions. The effect of noradrenaline on the pulmonary vein could be replicated by the simultaneous, but not separate, application of the alpha adrenoceptor agonist phenylephrine and the beta adrenoceptor agonist isoprenaline. The use of selective agonists and antagonists for adrenoceptor subtypes showed that ectopic activity in the pulmonary vein arose from the simultaneous stimulation of alpha(1) and beta(1) adrenoceptors. The application of noradrenaline to isolated strips of left atrium did not induce ectopic contractions (n=10). conclusions: These findings suggest an origin for ectopic activity in the pulmonary vein that requires activation of both alpha and beta adrenoceptors. They also open new perspectives towards our understanding of the triggering of AF.

[Evaluation of the cost of complications of automatic implantable defibrillators]. / Evaluation du coût des complications des défibrillateurs cardiaques automatiques implantables.

The automatic implantable defibrillator (AID) has been shown to prevent sudden death but it frequently gives rise to complications. These complications seem to be costly but they do not figure in the economic assessments of AID. From 1989 to 2003, 202 patients (173 men, age 58 +/- 14 years) received consecutively 264 AID in the same centre of implantation. The authors studied the complications of these implantations. The medical indication was secondary (documented spontaneous ventricular tachycardia or fibrillation) in 145 patients (71.8%) and prophylactic in the remaining 57 patients (28.2%). During the 36 month (+/- 35) follow-up, 40.6% patients had an appropriate treatment: 50.3% in the secondary prevention group versus 15.8% in the prophylactic implantation group. The one year, 5 and 15 year survival rates were 99, 88 and 85% respectively. Eighty seven complications were observed resulting in a long term complication in 36.7% of patients. These complications were: inappropriate electric shock, n=24 (27.6%), fractured catheters, n=12 (13.6%), haematomas, n=12 (13.6%), loss of function of the AID, n=10 (11.4%), infection, n=6 (6.8%), pneumothorax, n=7 (8.0%), and others n=16 (18.4%). The cost of these complications was assessed in terms of hospital stay in intensive care (1010.40 euros per day) or in the general cardiology wards (546.70 euros per day). The complications resulted in 502 days of additional hospital stay (5.77 days per complication) with a total cost of 285 655.20 euros (3283.40 euros per complication). The most expensive complications in terms of hospital stay were: infections (24.5 days), fractured catheter (5.75 days), and postoperative haematoma (5.5 days). These results indicate a significant cost of complications which should be indicated in the economic evaluation of AID.

[Clinical evolution of patients following investigation of atrial vulnerability after a first cerebral ischaemic accident]. / Evolution clinique des patients ayant eu une recherche de vulnérabilité atriale après un premier accident ischémique cérébral.

Atrial vulnerability reflects the ability of the atrium to fibrillate. ISAV (Ischemic stroke and atrial vulnerability) is a French epidemiological registry whose main goal is to assess the evolution modalities of patients in whom an electrophysiological study of the atrium has been performed. A group of 269 patients with a history of non elucidated ischemic stroke and an electrophysiological study of the atrium performed in a mean delay of 3 months after the stroke has been included. Their mean age at the time of the stroke was 55 +/- 15.8 years. The electrophysiological study has measured the effective refractory period of the atrium, the locoregional right intra-atrial conduction time, the index of latent atrial vulnerability and assessed the inductibility. The mean delay between the date of the stroke and the date of the last news was 4.4 +/- 2.8 years. We observed 12 deaths and 11 patients presented during the follow up a spontaneous atrial arrhythmia and 17 a recurrence of stroke. If we consider the occurrence of the 28 combined events (atrial arrhythmia and/or stroke), it is not correlated with the presence of an atrial septal defect nor with the existence of an atrial vulnerability. On the contrary this occurrence is correlated with tobacco consumption and/or arterial hypertension; 82% of patients have these risk factors versus 54% of patients without events (p = 0.004). This association is not significant in patients younger than 55 years.

[Chronic pulmonary thromboembolism revealing beta-thalassemia intermedia after splenectomy]. / Coeur pulmonaire chronique postembolique révélant une bêtathalassémie intermédiaire après splénectomie.

INTRODUCTION: The clinical expression of beta-thalassemia intermedia is variable and complications are more frequent than in the minor form. Thromboembolism risk increase after splenectomy. Few cases of the type of complications are reported. CASE RECORD: A man was admitted for beta-thalassemia intermedia with moderate chronic hemolysis anemia, complicated by chronic pulmonary thromboembolism and liver iron overload. Post-traumatic splenectomy probably increase the risk of this two complications. The patient's respiratory status improved following bosentan therapy without worsening his hepatopathy. CONCLUSION: The present study also notes that thromboembolism complications can be an indicator of beta thalassemia and interrogate about the risk and the benefit of splenectomy in the treatment of beta-thalassemia intermedia.

[Risk stratification in atrial and ventricular arrhythmias]. / Stratification du risque dans les troubles du rythme auriculaire et ventriculaire.

Atrial fibrillation, the most frequent arrhythmia, has a growing incidence with increasing age and the most important complication of the disease is thromboembolic events that may be prevented by antivitamin K. They are the most efficient therapeutic class for the prevention of these events but they are associated with an increased haemorrhagic risk leading to a reduced prescription in general practice. Optimisation of the management should be based on an individual evaluation of the thromboembolic and haemorrhagic risks, taking into account age, the presence of an associated heart disease, hypertension, diabetes, history of cerebrovascular event, history of previous haemorrhagic event and the ability to achieve a stable target INR. The challenge in ventricular arrhythmias lies in identifying a high risk of sudden death, mainly related to ventricular fibrillation. In patients with structural heart disease, left ventricular dysfunction is the strongest predictor of sudden death. Non invasive markers such as non sustained ventricular tachycardia, late ventricular potentials, decreased heart rate variability and baroreflex sensitivity, and repolarization altemans are further elements to assess risk. However, most of these markers have a poor positive predictive value and a low specificity. In patients with normal hearts, genetic predisposition may in the future identify high risk patients. The electrophysiologic study with programmed ventricular stimulation remains a costly and invasive method and only has a strong positive predictive value in ischemic cardiomyopathy. More precise algorithms for risk stratification are thus needed that may help the strategy of therapy with prophylactic implantable cardioverter defibrillator in the future.

Prognostic value of heart rate variability for sudden death and major arrhythmic events in patients with idiopathic dilated cardiomyopathy.

OBJECTIVE: This study was designed to evaluate the prognostic value of heart rate variability for sudden death, resuscitated ventricular fibrillation or sustained ventricular tachycardia in patients with idiopathic dilated cardiomyopathy. BACKGROUND: Previous studies have shown that heart rate variability could predict arrhythmic events and sudden death in postinfarction patients, but the prognostic value of heart rate variability for arrhythmic events or sudden death in patients with idiopathic dilated cardiomyopathy has not been established. METHODS: Time and frequency domain analysis of heart rate variability on 24-h electrocardiographic (ECG) recording was assessed in 116 patients with idiopathic dilated cardiomyopathy (91 men, aged 51+/-12 years, left ventricular ejection fraction 34+/-12%). RESULTS: Mean follow-up (+/-SD) was 53+/-39 months. Sixteen patients reached one of the defined study end-points (sudden death, resuscitated ventricular fibrillation or sustained ventricular tachycardia) during follow-up. Using multivariate analysis, only reduced standard deviation of all normal-to-normal intervals (SDNN) (p = 0.02) and ventricular tachycardia during 24-h ECG recording (p = 0.02) predicted sudden death and/or arrhythmic events. For SDNN, a cutoff level of 100 ms seemed the best for the risk stratification. CONCLUSIONS: Decrease in heart rate variability is an independent predictor of arrhythmic events and sudden death in idiopathic dilated cardiomyopathy, whether the mechanism of sudden death is ventricular tachyarrhythmia or not.

Heart rate variability in idiopathic dilated cardiomyopathy: characteristics and prognostic value.

OBJECTIVES: This study was designed to evaluate heart rate variability (HRV) in patients with idiopathic dilated cardiomyopathy (IDC), to determine its correlation with hemodynamic variables and ventricular arrhythmias and to evaluate its prognostic value in IDC. BACKGROUND: Previous studies have shown that HRV could predict arrhythmic events in patients after infarction, but the characteristics of HRV in IDC have not been fully established. METHODS: Time domain analysis of HRV on 24-h electrocardiographic (ECG) recording was performed in 93 patients with IDC, and results were compared with those in 63 control subjects. RESULTS: Patients with IDC, even those without congestive heart failure, had significantly lower values for HRV than those of control subjects. HRV was related to left ventricular shortening fraction (R = 0.5, p = 0.0001) and to peak oxygen uptake (R = 0.53, p = 0.01). HRV was not different in patients with runs of ventricular tachycardia or in patients with late potentials on the signal-averaged ECG. During a mean follow-up period (+/-SD) of 49.5 +/- 35.6 months, patients with reduced HRV had an increased risk of cardiac death or heart transplantation (p = 0.006). On multivariate analysis, cardiac events were predicted by increased left ventricular end-diastolic diameter (p = 0.0001), reduced standard deviation of all normal to normal RR intervals (p = 0.02) and increased pulmonary capillary wedge pressure (p = 0.04). CONCLUSIONS: Decreased HRV in patients with IDC is related to left ventricular dysfunction and not to ventricular arrhythmias. Analysis of HRV can identify patients with IDC who have an increased risk of cardiac death or heart transplantation.

[Evaluation after 20 years of a case of Takayasu's disease that presented with aortic regurgitation]. / Evolution après 20 ans d'une maladie de Takayasu Révélée par une insuffisance aortique.

Takayasu's disease is a segmental multifocal affection of medium and large arteries. The diagnosis is based on the association of stenotic and aneurismal lesions of the aorta and its branches secondary to an inflammatory infiltration of the media and adventitia. Cases of aortic regurgitation associated with aneurismal dilatation of the ascending aorta as the presenting features of Takayasu's disease, as in this case, are rare. Histological examination of the aortic wall may help establish the diagnosis by showing signs of aortitis. The other usual arterial lesions are sometimes missing at the initial phase of the disease. A late histological diagnosis may be difficult as the inflammatory lesions tend to be progressively replaced by fibrotic lesions or a banal atheroma.

[Indications for automatic implantable defibrillators in patients with the Brugada syndrome]. / Indications du défibrillateur cardiaque automatique implantable dans le syndrome de Brugada.

Brugada syndrome is a primary electrical cardiac disease characterized by an ST segment elevation in V1-V2 leads on surface ECG and an increased risk of polymorphic ventricular tachyarrhythmia (ventricular tachycardia and/or ventricular fibrillation). The objective of the treatment is to prevent sudden death and it therefore includes in some cases the implantation of an automatic implantable cardiac defibrillator (AICD). In secondary prevention (i.e. after a first episode of resuscitated ventricular fibrillation), the implantation of AICD is mandatory (indication of class 1 level A). In primary prevention (i.e. in patients without documented ventricular fibrillation), the guidelines are not definitively established. We may consider two different clinical situations. First, the patient complains from syncope and this justifies the implantation of an AICD. Second, the patient is asymptomatic and the physician has to discuss the implantation of an AICD. Two parameters should be analysed: the pattern of ECG and the result of right programmed ventricular stimulation. An evident ST segment elevation (>2 mm) is associated with a high risk of sudden death. Likewise, the inducibility of a ventricular tachycardia or fibrillation is considered at the present time as a factor linked to sudden death and justifies the implantation of an AICD. On the other hand, a normal resting ECG only associated with a provoked ST segment elevation by class I antiarrhythmic drug (flecainide) defines a group of patients with a low risk of sudden death, and these patients do not require the implantation of an AICD.

[Postmarketing surveillance in patients with cardiac pace-makers or automatic implantable defibrillators]. / Aspects généraux et réglementaires de la matériovigilance des stimulateurs et des défibrillateurs cardiaques.

This article includes an overview of the actual French control and regulation system of the safety alerts involving pacemakers and implantable cardioverter-defibrillator and an evaluation of the general information and trends about the characteristics of the reported incidents obtained in the last years in that field. The national security agencies have the mission to collect the data on safety and efficacy of medical devices but manufacturers, physicians and patients also have a role to play. The technical appreciation of the necessity of a notification is not easy in some cases but the lack of notification of a severe incident may lead to heavy penal consequences. If doubtful cases, one should keep in mind the spirit of these safety systems: a collective insurance against the risks related to the use of medical devices. In the 10 last years, the annual advisory rate was increased. The pacemakers were recalled more frequently than implantable cardioverter-defibrillators in absolute value but less frequently in relative value (advisories per 100 person-years). This increase may be related to the growing number of device implants and expanding indications for device therapy, to the increasing sophistication of the devices and to the modifications in the regulation aspects of these problems with a closer attention of users and physicians to the several types of malfunctions.

Effect of verapamil on QT interval dynamicity.

Using measurements of QT/RR slopes with a computerized Holter system, QT interval dynamicity was evaluated in 19 patients with normal structural heart before and 2 months after oral treatment with verapamil prescribed for paroxysmal atrioventricular nodal reentrant tachycardia. Verapamil significantly shortened QT at low heart rates, mainly in the diurnal period, and this characteristic may explain, in part, the previously reported protective effect of verapamil against torsades de pointes.

Effect of verapamil on heart rate variability in subjects with normal hearts.

Heart rate variability on 24-hour electrocardiographic recording was assessed in 23 patients without structural heart disease before and after 2 months of oral treatment with verapamil prescribed for paroxysmal atrioventricular nodal reentrant tachycardia. Verapamil had no significant effect on overall heart rate variability in the frequency domain, but it increased ultra low frequency power and decreased the low-frequency/high-frequency ratio, deemed to be a marker of sympathetic activity.

Long-term prognostic value of time domain analysis of signal-averaged electrocardiography in idiopathic dilated cardiomyopathy.

The aim of this study was to evaluate the long-term prognostic value of signal-averaged electrocardiography (SAECG) in idiopathic dilated cardiomyopathy (IDC). Time domain analysis of SAECG was assessed in 131 patients with angiographically confirmed IDC (age 52+/-12 years; 108 men; left ventricular ejection fraction 33+/-12%) using specific criteria in 44 patients with bundle branch block. Late potentials (LP) on SAECG were present in 27% of the patients. Patients with LP had a similar left ventricular ejection fraction and a similar left ventricular end-diastolic diameter than patients with a normal SAECG. With a follow-up of 54+/-41 months, 24 patients suffered cardiac death and 19 had major arrhythmic events (sudden death, resuscitated ventricular fibrillation, or sustained ventricular tachycardia). Patients with LP had an increased risk of all-cause cardiac death (RR 3.3, 95% confidence interval 1.5 to 7.5, p = 0.004) and of arrhythmic events (RR 7.2, 95% confidence interval 2.6 to 19.4, p = 0.0001). Using multivariate analysis, only LP on SAECG (p = 0.001), reduced SD of all normal-to-normal intervals (SDNN) (p = 0.002), increased pulmonary capillary wedge pressure (p = 0.005), and history of sustained ventricular tachyarrhythmia (p = 0.02) predicted cardiac death. A history of previous sustained ventricular tachyarrhythmia (p = 0.0001), reduced SDNN (p = 0.003), and LP on SAECG (p = 0.006) were the only independent predictors of major arrhythmic events. Results were not altered when considering separately patients with or without bundle branch block, or after exclusion of patients with a history of sustained ventricular tachyarrhythmia. This study is one of the first to suggest that LP on SAECG is an independent predictor of all-cause cardiac death and is of high interest for arrhythmia risk stratification in IDC.

Significance of late ventricular potentials in myotonic dystrophy.

In 39 patients with myotonic dystrophy, we found a high percentage of infrahissian cardiac conduction abnormalities (51%) and late potentials (46%), whereas spontaneous and inducible ventricular arrhythmias were rare. These results suggest that the prolongation of QRSD and the duration of the low-amplitude signal on the signal-averaged electrocardiogram were related to delayed activation of the His and Purkinje tissue rather than true late potentials.

Diagnosis of arrhythmogenic right ventricular cardiomyopathy by fourier analysis of gated blood pool single-photon emission tomography.

To evaluate the diagnostic performance of Fourier phase analysis of gated blood pool single-photon emission computed tomography (GBP SPECT) in arrhythmogenic right ventricular (RV) cardiomyopathy, 18 patients with confirmed arrhythmogenic RV cardiomyopathy underwent GBP SPECT and x-ray cineangiography. Results were compared with data obtained with GBP SPECT in 10 control subjects. This 3-dimensional method demonstrated good correlation with cineangiography for measurements of RV enlargement and extent of the disease; RV and left ventricular segments were analyzed with the same accuracy. Tomographic abnormalities were significant decreased RV ejection fraction, RV dilatation, nonsynchronized contraction of the ventricles, increased RV contraction dispersion, presence of segmental RV wall motion disorders and/or phase delays, and occasionally regional left ventricular abnormalities. RV-delayed phase areas were always present in our population. A scoring system with RV criteria was proposed to diagnose RV disease. Because Fourier analysis of GBP SPECT provides ventricular morphologic information for the right ventricle with the same accuracy as for the left ventricle, it may replace planar radionuclide studies. Therefore, this method is helpful in patients with a strong clinical suspicion of arrhythmogenic RV cardiomyopathy, and should be used as a screening method before right ventriculography.

Detection of acute cardiac allograft rejection with high resolution electrocardiography: experimental study in rats.

BACKGROUND AND METHODS: To diagnose early acute cardiac rejection, we evaluated high-resolution electrocardiography in rats. Heterotopic heart transplantations were performed in allogeneic animals, either treated with cyclosporine or untreated, and in syngeneic animals. High-amplification electrocardiograms were recorded daily, under anesthesia, with two intra-abdominal leads. After amplification (x 5000 to 20,000), the electrocardiographic signal was acquired and analyzed with P-Clamp software. We measured the amplitude (millivolts) and duration (milliseconds) of the auriculogram (P wave) and the ventriculogram (QRS wave), the duration of auriculoventricular conduction (milliseconds; PQ interval) and the heart rate. Twenty-five grafted hearts were fully studied in recipients not treated with cyclosporine (allogeneic n = 16, syngeneic n = 9). RESULTS: In the allogeneic group, acute cardiac rejection was always accompanied by an early and progressive increase in P wave duration and PQ interval, whereas an increase in QRS duration was subsequently recorded. No significant change in P wave, PQ interval, or QRS wave duration was recorded in the syngeneic group, which showed no histologic rejection lesions. A decrease in P wave and QRS wave amplitude was recorded in both groups of animals. In the allogeneic group treated with cyclosporine (n = 21), grafted hearts were removed early (4.5 +/- 0.5 days): 10 cardiac grafts were rejected and 11 were not. An increase in P wave duration > or = 20% was associated with mild rejection in most cases. The sensitivity and specificity of this electrocardiographic sign were excellent (100%). The auricular (right and left atria) and the ventricular (right and left ventricles) tissues were evaluated histologically. In the allogeneic groups (n = 26), the histologic lesions during acute rejection were greater in the auricular myocardium than in the ventricular myocardium. Rejection in the atrial and ventricular myocardium was most often differentiated by one degree according to the Billingham classification. CONCLUSIONS: We concluded that acute cardiac rejection in rats is associated with early conduction disturbances in the atrial myocardium which can be shown by high-resolution electrocardiography.

Inappropriate shocks delivered by implantable cardiac defibrillators during oversensing of activity of diaphagmatic muscle.

Two cases are reported (both men, one 72 and one 54 years old) of inappropriate shocks delivered by an implantable cardiac defibrillator (ICD) device, which oversensed the myopotentials induced by deep breathing and Valsalva manoeuvre. No damage to leads was associated with the oversensing of myopotentials. The mechanism of the inappropriate shocks was determined using real time electrograms. Modification of the duration of ventricular detection and decrease in sensitivity made it possible to avoid the oversensing of myopotentials and to deliver ICD treatment.

Localization of the ventricular preexcitation site in Wolff-Parkinson-White syndrome with Doppler tissue imaging.

PURPOSE: The objective of this study was to evaluate the ability of Doppler tissue imaging (DTI) to localize the ventricular emergence site of accessory atrioventricular pathways (Wolff-Parkinson-White syndrome). METHODS: Thirty-three patients were studied prospectively by Doppler tissue imaging (128XP and Sequoia 256 echocardiographic systems; Acuson, Mountain View, Calif) before investigation of Wolff-Parkinson-White syndrome and after radiofrequency ablation of the accessory pathways. The normal appearance of the ventricular contractions was defined in a group of 10 control subjects. The preexcitation zone was determined as a zone of maximum acceleration in "DTI acceleration mode" or as a coded contraction zone in "DTI velocity mode," at the time of the delta wave or before the onset of the QRS complex. RESULTS: The earliest ventricular activation site was correctly localized for 12 of the 15 left-sided pathways (8 anterior or anterolateral, 2 lateral or posterolateral, 2 inferior). When wall motion abnormalities were detected in the left ventricle by DTI, the left-sided localization was confirmed by electrophysiologic exploration. For the right-sided pathways, the localization was correct in only 4 of 11 cases (3 posteroseptal and 1 anterolateral). After effective ablation in all patients, the abnormalities corresponding to the electrophysiologic data disappeared totally in only 11 of 16 patients. CONCLUSION: In the presence of Wolff-Parkinson-White syndrome, DTI localizes contraction abnormalities associated with early activation of a part of the ventricle. However, the interpretation of the images remains difficult because the normal coding of the contraction of the ventricular walls depends on the incidence for which they are investigated. This noninvasive examination seems to be an effective tool for localizing the left-sided accessory pathways of the left ventricle, in particular in the anterior, anterolateral, or inferior walls.

Comparison of circadian blood pressure variations in hypertensive patients with renal artery stenosis and essential hypertension.

Ambulatory blood pressure measurements in 20 hypertensive patients with uni- or bilateral renal artery stenosis were compared with those in 20 essential hypertensive patients. Analysis of the 24 hour blood pressure curve of the renal artery stenosis group shows a tendency to equalization of blood pressure throughout the day. The nocturnal decrease of systolic or diastolic blood pressure was not significantly different between the two groups (9.2 vs. 15.3 mmHg). The blunted curve seems to be related more to the severity of hypertension than to its aetiology, but further studies are required to elucidate this point.

[The heart and hyperkalemia]. / Coeur et hyperkaliémie.

Hyperkalaemia is a common and serious clinical condition in medical and surgical intensive care units. It is mainly encountered in patients with overt or latent cardiac and/or renal failure, and often aggravated by dietetic and therapeutic mismanagement. Hyperkalaemia depresses cardiac contractility, automaticity, conductivity and excitability, leading to ECG changes which must be recognized before clinical cardiovascular deterioration occurs if treatment is to be given to reverse an irremediably fatal evolution: ST-T changes and widening of the QRS with axial deviation shortly precede sinoatrial, intraatrial and atrioventricular block, the characteristic appearances of atrial standstill and ventricular and junctional hyperexcitability. The ECG changes faithfully follow the rise in serum potassium with few exceptions, such as associated electrolytic and acid-base disturbances (usually acidosis). Treatment must be administered as soon as a rise in potassium is observed. It may be administered intravenously (hypertonic glucose and insulin, calcium gluconate, furosemide, buffer solution and, above all, sodium bicarbonate or hypertonic saline) or orally (cation exchange resin). Renal dialysis may be required secondarily.