From electrophysiological exploration to management of heart arrhythmias: Economic analysis of practices in a high-volume French hospital over two different time periods.

BACKGROUND: Medical devices (MD) used to treat arrhythmias range from electrophysiological exploration catheters to intracardiac ablation catheters, and they are continuously undergoing optimization. The inclusion of innovative MD in Diagnosis Related Groups (DRG) of the French healthcare economic system can lead to financial imbalance for health institutions. The objective of this study was to compare cost-revenue analyses for interventional heart rhythm management in a high-volume French hospital between two time periods. METHODS: For 3 months in 2014 and 3 months in 2017, all of the patients admitted to the interventional rhythmic unit with arrhythmia were included retrospectively in this monocenter study. All arrhythmias were considered. The primary clinical endpoint was the difference between the expenses and incomes, calculated for each patient. The secondary endpoint was the breakdown of costs. RESULTS: 217 patients were included. In 2014 period, the analysis revealed a deficit of 409±1717 euros per patient and an overall deficit for the hospital of 44,635 euros. In 2017 period, the same evaluation indicated a deficit of 446±1316 euros per patient and an overall deficit for the hospital of 48,210 euros. The cost of MD accounts for a significant share of total expenses. CONCLUSION: The profitability for the cardiac rhythm activity at our facility was optimized between 2014 and 2017. The reliance on ambulatory care increased. However, the reduction in the expenses incurred did not increase the profitability for the facility. It was offset by a decrease in DRG tariffs. A flowchart-type structure based on these practices analyses for rhythmic disorder treatments was developed.

Intramyocardial transplantation of mesenchymal stromal cells for chronic myocardial ischemia and impaired left ventricular function: Results of the MESAMI 1 pilot trial.

BACKGROUND: The MESAMI 1 trial was a bicentric pilot study designed to test the feasibility and safety of intramyocardially injected autologous bone marrow-derived mesenchymal stromal cells (MSCs) for the treatment of ischemic cardiomyopathy. METHODS AND RESULTS: The study included 10 patients with chronic myocardial ischemia, left ventricular (LV) ejection fractions (EFs) of ≤35%, and reversible perfusion defects who were on stable optimal medical therapy and were not candidates for revascularization. MSCs (mean: 61.5×10(6) cells per patient) were injected into 10-16 viable sites at the border of the LV scar via a NOGA-guided catheter. Both primary endpoints, feasibility (successful harvest, expansion, and injection of autologous MSCs) and safety (absence of severe adverse events [SAEs]) were met in all 10 patients at the 1-month follow-up time point, and none of the SAEs reported during the full 2-year follow-up period were attributable to the study intervention. The results of secondary efficacy endpoint analyses identified significant improvements from baseline to Month 12 in LVEF (29.4±2.0% versus 35.7±2.5%; p=0.003), LV end-systolic volume (167.8±18.8mL versus 156.1±28.6mL; p=0.04), 6-min walk test and NYHA functional class. CONCLUSIONS: Our results suggest that autologous MSCs can be safely administered to the hearts of patients with severe, chronic, reversible myocardial ischemia and impaired cardiac function and may be associated with improvements in cardiac performance, LV remodeling, and patient functional status. A randomized, double blind, multicenter, placebo-controlled clinical trial (MESAMI 2) will evaluate the efficacy of this treatment approach in a larger patient population. CLINICAL TRIAL REGISTRATION: Unique identifier: NCT01076920.

Sodium channel blocker tests allow a clear distinction of electrophysiological characteristics and prognosis in patients with a type 2 or 3 Brugada electrocardiogram pattern.

BACKGROUND: Patients with a type 2 or 3 Brugada syndrome (BS) pattern and a negative sodium channel blocker challenge (SCBC) are not considered as affected. Their arrhythmic prognosis is generally considered good, but it has never been specifically evaluated. OBJECTIVE: The purpose of this study was to evaluate the arrhythmic prognosis in patients with a type 2 or 3 electrocardiogram (ECG) not converted to type 1 ECG during an SCBC. METHODS: Clinical data, 12-lead ECG, results of the SCBC and electrophysiological study (EPS), and follow-up were collected. RESULTS: Among the 500 patients who underwent an SCBC in our institution, 158 displayed a type 2 or 3 ECG. After the SCBC, 93 (59%) had a type 1 ECG (positive group [PG]), whereas 65 (41%) remained negative (negative group [NG]). An EPS was performed in 31 (33%) PG patients and 15 (23%) NG patients. Ventricular fibrillation was induced in 21 PG patients (67%), whereas no patient in the NG was inducible (P <.001). During a follow-up of 37 +/- 17 months, no sudden death occurred. Three syncopes were observed in the NG versus one syncope, two ventricular tachycardias, and one appropriate shock in the PG. CONCLUSION: This study demonstrates that the presence or absence of coved type ST-segment elevation during the SCBC denotes a profound electrophysiological difference as demonstrated by the absence of inducibility during EPS in the NG that may be responsible for the good prognosis of patients with a type 2 or 3 ECG pattern not converted to type 1.

Paramyotonia congenita with an SCN4A mutation affecting cardiac repolarization.

Paramyotonia congenita (PC) is linked to mutations of the skeletal muscle voltage-gated sodium channel alpha-subunit gene SCN4A. The authors report a family where the proband and three of her four children have PC (mutation R1448C) and present repolarization abnormalities at electrocardiogram. They demonstrate that the SCN4A alpha-subunit gene is expressed in normal human heart. Cardiac consequences of mutations of the SCN4A gene may be insignificant in standard conditions, but critical if patients with PC are treated with drugs inducing QT prolongation.

[Registration of parasuicide at hospitals and emergency units]. / Registrering av parasuicid ved sykehus og legevakt.

BACKGROUND: Suicide attempts (or parasuicides) is an important health problem. A better system for follow-up and surveillance of this group of patients is needed for better prioritization of preventive measures. MATERIAL AND METHODS: All self-inflicted injuries registered at the hospital and emergency ward in Stavanger, Norway, in 1992 were retrieved from the Norwegian National Injury Sample Registry (n = 403). The form for each patient was filled out on the basis of their hospital record; a judgment of whether the case was a parasuicide or not was made. Patients with a parasuicide in 1992 were followed for a period of on average 5.5 years with respect to new parasuicides. RESULTS: Medication was used in 85% of the cases. About 15% of the parasuiciders went through a new episode within one year of the first registered parasuicide. INTERPRETATION: The results from this study are consistent with findings in other epidemiological studies, and the registration used in this study can be carried out in hospitals and emergency wards without much effort. The registration form should be further developed and tested prospectively.

Transgenic mice overexpressing human KvLQT1 dominant-negative isoform. Part I: Phenotypic characterisation.

OBJECTIVES: The KCNQ1 gene encodes the KvLQT1 potassium channel, which generates in the human heart the slow component of the cardiac delayed rectifier current, I(Ks). Mutations in KCNQ1 are the most frequent cause of the congenital long QT syndrome. We have previously cloned a cardiac KCNQ1 human isoform, which exerts a strong dominant-negative effect on KvLQT1 channels. We took advantage of this dominant-negative isoform to engineer an in vivo model of KvLQT1 disruption, obtained by overexpressing the dominant-negative subunit under the control of the alpha-myosin heavy chain promoter. RESULTS: Three different transgenic lines demonstrated a phenotype with increasing severity. Functional suppression of KvLQT1 in transgenic mice led to a markedly prolonged QT interval associated with sinus node dysfunction. Transgenic mice also demonstrated atrio-ventricular block leading to occasional Wenckebach phenomenon. The atrio-ventricular block was associated with prolonged AH but normal HV interval in His recordings. Prolonged QT interval correlated with prolonged action potential duration and with reduced K(+) current density in patch-clamp experiments. RNase protection assay revealed remodeling of K(+) channel expression in transgenic mice. CONCLUSIONS: Our transgenic mouse model suggests a role for KvLQT1 channels not only in the mouse cardiac repolarisation but also in the sinus node automaticity and in the propagation of the impulse through the AV node.

Transgenic mice overexpressing human KvLQT1 dominant-negative isoform. Part II: Pharmacological profile.

OBJECTIVE: The acquired long QT syndrome results most often from the action of I(Kr) blocking-drugs on cardiac repolarization. We have evaluated a transgenic (TG) mouse (FVB) overexpressing a dominant-negative KvLQT1 isoform, as an in vivo screening model for I(Kr) blocking drugs. RESULTS: In TG mice, six-lead ECGs demonstrated sinus bradycardia, atrioventricular block, and QTc prolongation. Various drugs were injected intraperitoneally after blockade of the autonomic nervous system and serial ECGs were recorded. The end of the initial rapid phase of the T wave corrected for heart rate using a formula for mouse heart (QTrc), was used as a surrogate for the QT interval. Dofetilide, a specific I(Kr) blocker, did not prolong the QTrc interval either in TG or in wild-type (WT) mice but dose-dependently lengthened the sinus period in TG mice but not in WT mice. Other I(Kr) blockers including E 4031, haloperidol, sultopride, astemizole, cisapride and terikalant behaved similarly to dofetilide. Tedisamil, a blocker of the transient outward current, dose-dependently prolonged the QTrc in WT mice but not in TG mice and also reduced the sinus rhythm in both WT and TG mice. Lidocaine dose-dependently shortened the QTrc interval in TG mice and also lengthened the P wave duration. Nicardipine dose-dependently shortened QTrc and also produced sinus arrest in both WT and TG mice. CONCLUSIONS: We conclude that KvLQT1-invalidated TG mice discriminates in vivo drugs that blocks I(Kr) from drugs that block the transient outward current, the sodium current or the calcium current.

Dynamic analysis of the QT interval in long QT1 syndrome patients with a normal phenotype.

AIMS: In families with the long QT syndrome penetrance may be low: up to 70% of gene carriers may have a normal QTc interval. These patients require therapy, similar to that in those with longer QTc intervals, but identifying them, using molecular analysis, is difficult to apply on a large scale. A large French family affected by the long QT1 syndrome was followed-up over a 25-year period. In adult males but not in females, the QTc interval normalized after puberty. We aimed to find clinical criteria, based on ambulatory ECG recordings so that we could improve diagnosis in affected members with a normal QTc. METHODS AND RESULTS: Linkage analysis and direct sequencing were an indicator of the long QT1 gene in our family. Reverse transcription-polymerase chain reaction analysis demonstrated abnormal transcripts in lymphocytes from silent gene carriers. The functional profile of mutated protein isoforms was investigated using the patch-clamp technique. Dynamic analysis of ventricular depolarization was conducted using Holter recordings in patients, and in sex- and age-matched controls. Circadian variations of the QTc interval and the QT/RR relationship were assessed. Sensitivity, specificity, and predictive values were evaluated for proposed clinical criteria. We found that dynamic analysis of the QT interval permitted individual diagnosis in mutation carriers even when the QTc interval was normal (adult males). CONCLUSION: Dynamic analysis of the QT interval is of diagnostic value in the long QT1 syndrome in patients with a normal phenotype. Clinical implications include improvement in screening and patient management.

Steady-state versus non-steady-state QT-RR relationships in 24-hour Holter recordings.

The aim of the present study was to investigate the QT-RR interval relationship in ambulatory ECG recordings with special emphasis on the physiological circumstances under which the QT-RR intervals follow a linear relation. Continuous ECG recordings make it possible to automatically measure QT duration in individual subjects under various physiological circumstances. However, identification of QT prolongation in Holter recordings is hampered by the rate dependence of QT duration. Comparison of QT duration and QT interval rate dependence between different individuals implies that the nature of the QT-RR relationship is defined in ambulatory ECG. Holter recordings were performed in healthy volunteers at baseline and after administration of dofetilide, a Class III antiarrhythmic drug. After dofetilide, beat-to-beat automated QT measurements on Holter tapes were compared with manually measured QT intervals on standard ECGs matched by time. The QT-RR relationship was analyzed at baseline in individual and group data during three different periods: 24-hour, daytime, and nighttime. Data were collected under steady-state or non-steady-state conditions of cycle length and fitted with various correction formulae. Our study demonstrated an excellent agreement between manually and automated measurements. The classic Bazett correction formula did not fit the QT-RR data points in individual or group data. When heart beats were selected for a steady rhythm during the preceding minute, QT-RR intervals fit a linear relationship during the day and night periods, but not during the 24-hour period in both individual and group data. In contrast, in the absence of beat selection, data fit a more complex curvilinear relationship irrespective of the period. Our study provides the basis for comparison of QT interval durations and QT-RR relationships between individuals and between groups of subjects.

Dynamic analysis of dofetilide-induced changes in ventricular repolarization.

OBJECTIVE: To use dynamic electrocardiographic (ECG) techniques to study the influence of heart rate on dofetilide-induced QT prolongation among healthy volunteers. BACKGROUND: The extent to which heart rate modulates QT prolongation induced by the new class III antiarrhythmic drug dofetilide is a matter of debate. METHODS: Ten healthy volunteers underwent two 24-hour ECG recordings, one in the absence of dofetilide and the other after a single oral dose of 0.5 mg dofetilide. Two 4-hour periods were defined during the second recording: Dh, which corresponded to stable high concentration of the drug, and D1, which corresponded to low concentration of the drug. Corresponding baseline recording periods, Ch and C1, matched by time with Dh and D1 were selected from the control ECG recording in the absence of dofetilide. QT versus R-R relations were compared in the presence and absence of dofetilide. The QT versus R-R relation slope was used as an index of the rate dependence QT prolongation. Rate-independent changes in QT duration were also analyzed. RESULTS: During Dh, dofetilide induced a mean 12% lengthening of ventricular repolarization. Dynamic ECG analysis showed that this prolongation increased as R-R cycles became longer, a phenomenon known as reverse rate dependence. However, QT prolongation persisted at the shortest (600 ms) R-R cycle length that could be analyzed. During D1, dynamic ECG analysis showed a persistent, although small, effect of dofetilide on both QT prolongation (3%) and reverse rate dependence of this effect. CONCLUSIONS: Dofetilide prolongs QT duration, and this class III effect is influenced by heart rate. Although dofetilide-induced QT prolongation decreases when the R-R cycle shortens, this reverse rate dependence is only partial because marked QT prolongation persists at an R-R cycle of 600 ms. The results of our study indicated that dynamic ECG techniques can be useful in detection of subtle, drug-induced changes in the duration of ventricular repolarization.

Amiodarone reduces transmural heterogeneity of repolarization in the human heart.

OBJECTIVES: The present work was designed to test the effects of amiodarone therapy on action potential characteristics of the three cell types observed in human left ventricular preparations. BACKGROUND: The electrophysiologic basis for amiodarone's exceptional antiarrhythmic efficacy and low proarrhythmic profile remains unclear. METHODS: We used standard microelectrode techniques to investigate the effects of chronic amiodarone therapy on transmembrane activity of the three predominant cellular subtypes (epicardial, midmyocardial [M] and endocardial cells) spanning the human left ventricle in hearts explanted from normal, heart failure and amiodarone-treated heart failure patients. RESULTS: Tissues isolated from the ventricles of heart failure patients receiving chronic amiodarone therapy displayed M cell action potential duration (404+/-12 ms) significantly briefer (p < 0.05) than that recorded in tissues isolated from normal hearts (439+/-22 ms) or from heart failure patients not treated with amiodarone (449+/-18 ms). Endocardial cells from amiodarone-treated heart failure patients displayed longer (p < 0.05) action potential duration (363+/-10 ms) than endocardial cells isolated from normal hearts (330+/-6 ms). As a consequence, the heterogeneity of ventricular repolarization in tissues from patients treated with amiodarone was considerably smaller than in the two other groups, especially at long pacing cycle lengths. CONCLUSIONS: These findings may explain, at least in part, the reduction of ventricular repolarization dispersion and the lower incidence of torsade de pointes observed with chronic amiodarone therapy as compared with other class III agents.

Abnormalities of cardiac repolarization in multiple sclerosis: relationship with a model of allergic encephalomyelitis in rat.

Ventricular repolarization was investigated for the first time in 48 multiple sclerosis (MS) patients using measurement of QTc interval on standard electrocardiographic recordings. The repolarization process was prolonged significantly in MS compared to control subjects (P = 0.0001). This result was confirmed with an animal model of MS, i.e., the experimental allergic encephalomyelitis in rat. The contribution of prolonged QT to syncopal attack or sudden cardiac death in MS patients need further investigation.

Military shoplifting.

Shoplifting is a crime generally attributed to women. This article describes a population of mostly male active duty military shoplifters. Several cases are presented and discussed in detail. Shoplifting, and the psychiatric theories explaining the behavior, are placed in perspective with a literature review. The significance of shoplifting in the military is discussed by examining the law, appellate opinions, and the range of punishments. The article concludes by providing suggestions for conducting a medico-legal evaluation.

[Variability of sinus rhythm and cardiac failure]. / Variabilité du rythme sinusal et insuffisance cardiaque.

Under pathological conditions, the autonomic nervous system, which continually regulates cardiac function, may have adverse effects on pump function and electrical activation. The sinus rhythm is an indirect marker of the different components of the autonomic nervous system and changes in the heart rate reflect the permanent variation of vagal and sympathetic tone. Analysis of variability in the temporal or frequential domaines, provides information about the modulation of the different components of the autonomic nervous system. In the post-infarction period, studies have shown that the heart rate variability is an independent predictive factor of cardiovascular mortality. The data available in patients with cardiac failure is limited. There is a decrease in heart rate variability and this decrease seems to be associated with a higher risk.

[Arrhythmogenic effects of sultopride chlorhydrate: clinical and cellular electrophysiological correlation]. / Effets arythmogènes du chlorydrate de sultopride: corrélation clinique et électrophysiologique cellulaire.

This study was designed following the first documented case of torsades de pointes induced by sultopride hydrochloride, a substituted benzamide neuroleptic drug. The patient, a 48 year-old woman with no known cardiovascular disease, had been treated for several years with this drug. She was admitted for severe bronchospasm requiring artificial ventilation. Twenty-one hours after her admission, she developed several episodes of torsades de pointes, which were successfully treated with magnesium sulphate. At that time, the QT interval was 500 ms for a heart rate of 108 b.min-1 (QTc of 668 ms, and theoretical QTc 370 ms). On the fourth day, QTc was 548 ms and theoretical QTc 370 ms. The sultopride was stopped on the fifth day. Two days later, QTc was 397 ms. Six months later, there was no recurrence. Several cases of TdP or sudden death have been reported in patients receiving neuroleptic drugs. The effects of sultopride hydrochloride were therefore tested on isolated ferret Purkinje fibres, using the microelectrode technique. Three concentrations of the drug (D1, D2, D3) were tested, as well as normal Tyrode solution. Maximum diastolic potentials (Vmax) were -88.37 +/- 0.89 mV (control), -89.08 +/- 1.20 mV (D1), -90.00 +/- 1.06 mV (D2), and -90.14 +/- 1.20 mV (D3). Vmax was not affected by sultopride during pacing at 1,000 ms of cycle length. The duration of the action potential increased with the drug concentration. There was no early after-depolarisation (EAD) during control, and 7 out of 9 fibers had EAD and 3 out of 9 triggered activity in D3. The solvent (benzyl alcohol) did not modify the action potential.(ABSTRACT TRUNCATED AT 250 WORDS)

Coenzyme A in dog kidneys during hypothermic perfusion.

In kidneys perfused hypothermically for 48 hr, both major intracellular pools of CoA (present in cytosol and mitochondria) decreased when solutions with intracellular or extracellular electrolyte composition without CoA precursors were used. The presence of substrates such as glucose or caprylic acid in the perfusate did not counteract the depletion of CoA. The addition of the CoA precursors pantethine and adenosine together with respiratory substrates to the perfusion medium counteracted the loss of CoA. The best solution in this respect among 16 different perfusates tested contained palmitic acid and L-carnitine together with CoA precursors and dibutyryl cyclic AMP. With this solution, we obtained good preservation of the cytosolic and the mitochondrial pool of CoA.