[Arrhythmogenic right ventricular dysplasia].
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Biomedical subjects
Publications and source records attributed to G Fontaine.
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Arrhythmogenic right ventricular dysplasia is a polymorphous clinical entity. Its diagnosis is difficult in incomplete forms or at the onset of the disease. The diagnosis is based on the association of clinical, electrocardiographic and electrophysiologic signs which are the result of a specific pathological structure, consisting of fibromuscular bundles isolated from each other by fatty tissue resulting from apoptosis and/or the basic dysplastic phenomenon. These fibers are oriented in a parallel direction and connected at their extremities with normal myocardium. These fibromyocyte bundles seem to constitute a tissue with preferential conduction, which could explain reentry phenomena, and therefore the basis for the pathogenesis of ventricular arrhythmias. The various clinical aspects of ARVD have similar morphological patterns, but a completely different prognosis and outcome.
OBJECTIVES: The aim of the present investigation was to redefine the clinicopathologic profile of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC), with special reference to disease progression and left ventricular (LV) involvement. BACKGROUND: Long-term follow-up data from clinical studies indicate that ARVC is a progressive heart muscle disease that with time may lead to more diffuse right ventricular (RV) involvement and LV abnormalities and culminate in heart failure. METHODS: Forty-two patients (27 male, 15 female; 9 to 65 years old, mean [+/-SD] age 29.6 +/- 18) from six collaborative medical centers, with a pathologic diagnosis of ARVC at autopsy or heart transplantation, and with the whole heart available, were studied according to a specific clinicomorphologic protocol. RESULTS: Thirty-four patients died suddenly (16 during effort); 4 underwent heart transplantation; 2 died as a result of advanced heart failure; and 2 died of other causes. Sudden death was the first sign of disease in 12 patients; the other 30 had palpitations, with syncope in 11, heart failure in 8 and stroke in 3. Twenty-seven patients experienced ventricular arrhythmias (ventricular tachycardia in 17), and 5 received a pacemaker. Ten patients had isolated RV involvement (group A); the remaining 32 (76%) also had fibrofatty LV involvement that was observed histologically only in 15 (group B) and histologically and macroscopically in 17 (group C). Patients in group C were significantly older than those in groups A and B (39 +/- 15 years vs. 20 +/- 8.8 and 25 +/- 9.7 years, respectively), had significantly longer clinical follow-up (9.3 +/- 7.3 years vs. 1.2 +/- 2.1 and 3.4 +/- 2.2 years, respectively) and developed heart failure significantly more often (47% vs. 0 and 0, respectively). Patients in groups B and C had warning symptoms (80% and 87%, respectively, vs. 30%) and clinical ventricular arrhythmias (73% and 82%, respectively, vs. 20%) significantly more often than patients in group A. Hearts from patients in group C weighed significantly more than those from patients in groups A and B (500 +/- 150 g vs. 328 +/- 40 and 380 +/- 95 g, respectively), whereas hearts from both group B and C patients had severe RV thinning (87% and 71%, respectively, vs. 20%) and inflammatory infiltrates (73% and 88%, respectively, vs. 30%) significantly more often than those from group A patients. CONCLUSIONS: LV involvement was found in 76% of hearts with ARVC, was age dependent and was associated with clinical arrhythmic events, more severe cardiomegaly, inflammatory infiltrates and heart failure. ARVC can no longer be regarded as an isolated disease of the right ventricle.
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BACKGROUND: Head-up tilt testing is a useful test for investigating vasovagal syncope. The determination of early, accurate, predictive criteria for a negative result would permit a reduction in the duration of the tilt test. METHODS AND RESULTS: Patients with no drug use and no illnesses other than recurrent unexplained syncope were recruited. In an initial study (110 consecutive patients), we aimed to determine a predictive criterion based on heart rate variations during the first minutes of upright tilting that could distinguish between patients with positive and negative tilt tests (patients with an early continual decrease in heart rate or blood pressure were excluded). Then we tested the predictive value of the established criterion in a second independent sample of patients with unexplained syncope (109 consecutive patients). An early sustained increase in heart rate < or = 18 bpm during the first 6 minutes of upright tilting at a 60 degree angle allowed us to predict negative tilt tests with 100% specificity, 100% positive predictive value, and 88.6% sensitivity. This criterion was validated in the second, prospective arm of the study (96.4% specificity, 98.4% positive predictive value, and 87.3% sensitivity), even with subsequent use of isoproterenol in low doses. CONCLUSIONS: In patients with no drug use and no illnesses other than recurrent unexplained syncope, a simple clinical criterion identifies patients who will not develop syncope during a prolonged upright tilt.
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There is a limited experience with catheter ablation for treatment of ventricular tachycardia (VT) in Chagasic cardiomyopathy. A 30-year-old woman experienced episodes of palpitations and syncope due to attacks of VT. A diagnosis of Chagas disease was established on a biological basis. Two-dimensional echo and contrast ventriculography showed an apical aneurysm with thrombus. Surgery was indicated to resect the aneurysm and ablate the VT. Ventricular tachycardia recurred 1 month later despite therapy, including amiodarone. Two clinical frequent and well-tolerated tachycardias were identified. The site of origin was located in the right ventricular apex and in the apical-lateral wall of the left ventricle, respectively. Catheter ablation was performed at two sites with DC shocks (total energy 600 J) after unsuccessful radiofrequency ablation. Holter recordings performed during the post-operative period showed only infrequent extrasystoles. After follow-up of 24 months the patient remains asymptomatic. Drug-refractory VT in Chagasic cardiomyopathy can be ablated by medium-energy DC shocks after failure of radiofrequency ablation.
A young patient with congestive heart failure had pathological findings of myocarditis superimposed on the substrate of a non-arrhythmogenic form of right ventricular dysplasia. The only clinical findings suggestive of right ventricular dysplasia were T-wave inversions on the right precordial leads.
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M cells as well as vortex like reentrant tachycardia could explain the torsade de pointes pattern leading to sudden death at night in a patient with arrhythmogenic right ventricular dysplasia and saddle-back ST segment elevation in lead V2. The mechanism of the torsade is explained by the two-dimensional structure of the right ventricular free wall reconstructed from paraffin blocks. This case may represent a particular form of Brugada's syndrome and cases of sudden death in young males in South East Asia.
BACKGROUND: Arrhythmogenic right ventricular dysplasia, a disorder that may lead to severe ventricular arrhythmias and sudden death, is characterized by the progressive replacement of myocardial cells by fat and fibrous tissue. We examined whether the loss of myocardial cells in this disease could result from cell death by apoptosis (programmed cell death). METHODS: Specimens obtained at autopsy from the right ventricular myocardium of eight patients with arrhythmogenic right ventricular dysplasia and four age-matched normal subjects were analyzed. To identify individual cells undergoing apoptosis, we performed in situ end-labeling of fragmented DNA on paraffin sections using biotinylated deoxyuridine triphosphate and the enzyme terminal deoxynucleotidyl transferase. We also examined the level of expression of CPP-32, a cysteine protease required for apoptotic cell death in mammalian cells, using immunohistochemical techniques. RESULTS: Apoptosis was detected in the right ventricular myocardium of six of the eight patients with arrhythmogenic right ventricular dysplasia and was absent in the controls. High levels of expression of CPP-32 were associated with positive in situ end-labeling of fragmented DNA. CONCLUSIONS: These results indicate that apoptotic myocardial cell death occurs in arrhythmogenic right ventricular dysplasia and may contribute to the loss of myocardial cells in this disorder.
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INTRODUCTION: An RS interval > 100 msec in precordial leads has been recently described for the diagnosis of ventricular tachycardia (VT). The aim of this study was to assess the value of this criterion when applied to patients with right bundle branch block pattern, left-axis deviation (fascicular) VT sensitive to verapamil. METHODS AND RESULTS: Eleven patients (mean age 31 +/- 11 years; range 16 to 51) had a mean heart rate of 164 +/- 37 beats/min (range 107 to 230) during VT. The QRS complex axis was -92 degrees +/- -15 degrees (range -80 to -115). The mean QRS duration was 121 +/- 9 msec (range 105 to 140). The mean RS interval was 67 +/- 9 msec (range 60 to 80). Fusion beats were present in 2 patients (18%), and AV dissociation confirmed by electrophysiologic study was found on ECG in 8 (73%) of 11. During tachycardia, the QRS-H' interval was 19 +/- 10 msec (range 10 to 30) in 6 of 11 patients. In seven patients, a fast, unique (or double) presystolic potential lasting 32 msec (range 12 to 40) occurring before the onset of the QRS complex was found at the site of origin of VT, localized in the inferior apical left ventricular septum. In all cases, VT was successfully treated by catheter ablation. CONCLUSION: A wide QRS complex tachycardia with right bundle branch block and left-axis deviation sensitive to verapamil observed in a young patient without structural heart disease should not be confused with supraventricular tachycardia with aberrancy but rather suggests the presence of fascicular VT. As opposed to VT associated with structural heart disease, the RS interval is < 80 msec in all precordial leads in all cases. Independent of this parameter, AV dissociation detectable on surface ECG has a sensitivity of 73%, which increases to 82% in the presence of fusion beats.
Variations of temperature, impedance and power and the relationship between these three factors were studied in 20 patients during 351 applications of radiofrequency energy delivered by a generator with a regulated output power. The applications were divided into 3 groups according to the maximal temperature attained: group I (< 50 degrees C; n = 112), group II (50-60 degrees C; n = 100), and group III (60-70 degrees C; n = 139). Analysis of the total duration of time of applications (average +/- standard deviation) showed: the duration (seconds) was 23.9 +/- 11.9 seconds for group I, 36.1 +/- 18.7 seconds for group II and 45 +/- 23.6 seconds for group III. The time to attain maximal temperature was 6.8 +/- 9.6 seconds in group I, 11.7 +/- 12.7 in group II and 10 +/- 10.4 seconds in group III. The impedance remained under 200 omega in all applications, the target temperature being set at 70 degrees C. Analysis of the first three seconds of application: correlations coefficients between temperature and impedance were -0.08 (p < 0.001) in group I and -0.23 (p < 0.0001) in groups II and III. These coefficients were recalculated with respect to the average power delivered during the applications: < 40 watts (n = 79), r = -0.33; < 30 watts (n = 55), r = -0.41; < 20 watts (n = 33), r = 0.49 and < 10 watts (n = 15), r = -0.7 (p < 0.0001). The authors conclude that radiofrequency generators with thermal regulation allow early interruption of ineffective applications of radiofrequency and avoid increases in impedance. The poor correlations observed between increase in temperature (measured at the tip of the catheter) and the fall in impedance (related to tissue heating) for the first 3 groups, show that temperature alone is not a good indicator of contact. The improvement of the correlations for decreasing output power applications indicates better thermal transfer between the electrode and endocardium. Therefore a low power delivered in the first seconds at > 50 degrees C is to be interpreted as a marker of the quality of contact and a predictive factor of efficacy.
Radiofrequency energy was used for the ablation of chronic recurrent ventricular tachycardia (VT) in 58 patients who were divided into two groups: 44 cases with structural myocardial disease (36 men and 8 women: mean age 55 years; range: 14 to 85 years) with an average left ventricular ejection fraction of 38% (range: 15 to 80%): these patients had myocardial infarction (28 cases), arrhythmogenic right ventricular dysplasia (11 cases), idiopathic dilated cardiomyopathy (2 cases), operated congenital heart disease (2 cases) and operated valvular heart disease (1 case). The clinical success rate after the first session of radiofrequency ablation was 34%. When (according to our modified protocol of fulguration) 160 joule cathodal shocks were delivered to the same catheter previously used for RF ablation during the same session or secondarily (13 cases), the success rate increased to 76%. The average follow-up period of the 37 survivors was 16.7 months. The second group consists of 14 cases without structural myocardial disease (10 men and 4 women, mean age 41 years, range 14 to 69 years) with an average left ventricular ejection fraction of 61%. These patients had idiopathic ventricular tachycardia (10 cases) and verapamil-sensitive ventricular tachycardia (4 cases). The primary success of radiofrequency ablation alone was 43%. When combined with fulguration during the same of radiofrequency ablation alone was 43%. When combined fulguration during the same of at a later session, the success rate increased to 71.3%. The average follow-up period of the 13 survivors was 19 months (range 0.3 to 39 months). No significant difference was observed between the groups with or without structural myocardial disease after radiofrequency or fulguration ablation, not only with respect to global results but also after analysis of subgroups with, for example, post-infarction ventricular tachycardia or arrhythmogenic right ventricular dysplasia. However, clinical success was obtained after a single session of radiofrequency ablation alone in 8 of the 9 cases of incessant ventricular tachycardia in patients with structural myocardial disease.