Electrocardiographic Screening for Prolonged QT Interval to Reduce Sudden Cardiac Death in Psychiatric Patients: A Cost-Effectiveness Analysis.

IMPORTANCE: Sudden cardiac death is a leading cause of mortality in psychiatric patients. Long QT (LQT) is common in this population and predisposes to Torsades-de-Pointes (TdP) and subsequent mortality. OBJECTIVE: To estimate the cost-effectiveness of electrocardiographic screening to detect LQT in psychiatric inpatients. DESIGN, SETTING, AND PARTICIPANTS: We built a decision analytic model based on a decision tree to evaluate the cost-effectiveness and utility of LQT screening from a health care perspective. LQT proportion parameters were derived from an in-hospital cross-sectional study. We performed experts' elicitation to estimate the risk of TdP, given extent of QT prolongation. A TdP reduction of 65% after LQT detection was based on positive drug dechallenge rate and through adequate treatment and electrolyte adjustments. The base-case model uncertainty was assessed with one-way and probabilistic sensitivity analyses. Finally, the TdP related mortality and TdP avoidance parameters were varied in a two-way sensitivity analysis to assess their effect on the Incremental Cost-Effectiveness Ratio (ICER). MAIN OUTCOMES AND MEASURES: Costs, Quality Ajusted Life Year (QALY), ICER, and probability of cost effectiveness thresholds ($ 10,000, $25,000, and $50,000 per QALY). RESULTS: In the base-case scenario, the numbers of patients needed to screen were 1128 and 2817 to avoid one TdP and one death, respectively. The ICER of systematic ECG screening was $8644 (95%CI, 3144-82 498) per QALY. The probability of cost-effectiveness was 96% at a willingness-to-pay of $50,000 for one QALY. In sensitivity analyses, results were sensitive to the case-fatality of TdP episodes and to the TdP reduction following the diagnosis of LQT. CONCLUSION AND RELEVANCE: In psychiatric hospitals, performing systematic ECG screening at admission help reduce the number of sudden cardiac deaths in a cost-effective fashion.

QTc prolongation induced by targeted biotherapies used in clinical practice and under investigation: a comprehensive review.

In anticancer drug development, there has been increasing consideration for the potential of a compound to cause adverse electrocardiographic changes, especially QT interval prolongation, which can be associated with risk of torsades de pointes and sudden death. Irrespective of overt clinical toxicities, QTc assessment can influence decision making during the conduct of clinical studies, including eligibility for protocol therapy, dose delivery or discontinuation, and analyses of optimal dose for subsequent development. Efforts are needed to refine strategies for risk management, avoiding unintended consequences that negatively affect patient access and clinical development of promising new cancer treatments. In this comprehensive review, we will analyze potential effects on QTc prolongations of targeted agents approved by regulatory agencies and under investigation. A thoughtful risk management plan was generated by an organized collaboration between oncologists, cardiologists, and regulatory agencies to support a development program essential for oncology agents with cardiac safety concerns.

[Assessment of clinical-instrumental, morphological data and expression of coxsackie adenovirus receptor in patients with inflammatory cardiac pathology].

In 22 patients with heart failure and/or ventricular arrhythmias presumably of inflammatory etiology the results of clinical and instrumental investigation were analyzed and compared to the endomyocardial biopsy data. In the subgroup of patients with left bundle branch block (LBBB) we revealed features indicative of lesser contribution of inflammatory destruction in pathogenesis of cardiomyopathy. The only virus, detected in biopsy samples, was parvovirus B19. Its persistence in myocardium was not related to activity of inflammation and severity of clinical course. Increased expression of Coxsackie adenovirus receptor (CAR) was found in 20 patients. It was not related to inflammatory cells infiltration and virus persistence in myocardium. Patients with most prominent CAR expression were characteried by right heart dilatation, more severe heart failure and absence of LBBB. Enhancement of CAR expression could reflect the attempt of organism to repair intercellular communications between cardiomyocites and to protect cells from the products of necrotic lysis during long standing inflammation.

Assessment of atrial conduction time in patients with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is closely related to increased cardiovascular risk in women of reproductive age. Atrial conduction abnormalities in these patients have not been investigated in terms of atrial electromechanical delay measured by tissue Doppler imaging (TDI) as an early predictor of atrial fibrillation development. The aim of this study was to evaluate whether TDI-derived atrial conduction time is prolonged in PCOS. METHODS: The study included 51 patients with PCOS and 48 age-matched healthy controls. P-wave dispersion (PWD) was calculated on the 12-lead surface electrocardiogram. Systolic and diastolic left ventricular (LV) functions, atrial electromechanical coupling, intraatrial and interatrial electromechanical delays were measured with conventional echocardiography and TDI. RESULTS: PWD was higher in PCOS women (50.45 ± 3.7 vs 34.73 ± 6.7 ms, p = 0.008). Interatrial and intraatrial electromechanical delay were found longer in patients with PCOS compared to controls (41.9 ± 9.0 vs 22.2 ± 6.6 ms, p < 0.001; 22.6 ± 5.8 vs 5.9 ± 4.7 ms, p < 0.001, respectively). Left atrial (LA) volume index and LV diastolic parameters were significantly different between the groups. PWD was correlated with interatrial electromechanical delay (r = 0.54, p < 0.01). Interatrial electromechanical delay was strongly correlated with homeostatic model assessment insulin resistance index and high-sensitivity C-reactive protein levels (r = 0.68, p < 0.001; r = 0.53, p < 0.001, respectively). Interatrial electromechanical delay was positively correlated with LA volume index and deceleration time (r = 0.31, p = 0.04; r = 0.37, p = 0.021, respectively) and negatively correlated with flow propagation velocity (r = -0.38, p = 0.014). CONCLUSION: This study shows that atrial electromechanical delay is prolonged in PCOS patients. Atrial electromechanical delay prolongation is related to low-grade inflammation, insulin resistance, and LV diastolic dysfunction in PCOS.

Assessment of atrial electromechanical delay in patients with migraine.

Evidence suggests that symptoms of migraine are related to the involvement of the autonomic nervous system. Data on atrial conduction system are limited in migraineurs. We aimed to assess atrial electromechanical delay using tissue Doppler imaging (TDI) in patients with migraine. Forty-five migraine patients and age- and sex-matched 26 control subjects were enrolled in the study. All the patients and controls underwent resting surface electrocardiogram (ECG) and TDI. The maximum P-wave duration (Pmax), minimum P-wave duration (Pmin) and P-wave dispersion (Pd) were measured from the 12-lead ECG. Atrial conduction time was determined from the lateral mitral annulus (PA lateral), septal mitral annulus (PA septal), and lateral tricuspid annulus (PA tricuspid) by TDI. Interatrial (PA lateral-PA tricuspid) and intraatrial (PA septal-PA tricuspid) electromechanical delays were calculated. Pd was significantly higher in migraine patients than in controls (p < 0.05), whereas Pmax and Pmin were not different between both groups (p > 0.05). PA lateral and PA septal durations were significantly higher in migraine patients than in controls (p < 0.001 and p < 0.05, respectively). However, PA tricuspid duration was similar between the groups (p > 0.05). Both interatrial and intraatrial conduction times were delayed in migraineurs as compared to the controls (p < 0.001). Interatrial delay and intraatrial delay variables were found as an independent risk factors separately on predicting atrial conduction abnormalities in migraineurs. An interatrial delay of 18 ms and an intraatrial delay of 5 ms were found to be cutoff values in ROC analysis (p < 0.001). This is the first report to provide a hypothetical suggestion that there is an atrial electromechanical delay in patients with migraine.

Assessment of atrial electromechanical delay in children with acute rheumatic fever.

PURPOSE: There may be an increase in the risk of atrial arrhythmia due to left atrial enlargement and the influence on conduction system in acute rheumatic fever. The aim of this study is to investigate atrial electromechanical delay and P-wave dispersion in patients with acute rheumatic fever. PATIENTS: A total of 48 patients diagnosed with acute rheumatic fever and 40 volunteers of similar age, sex, and body mass index were included in the study. The study groups were compared for M-mode echocardiographic parameters, interatrial electromechanical delay, intra-atrial electromechanical delay, and P-wave dispersion. RESULTS: Maximum P-wave duration, P-wave dispersion, and interatrial electromechanical delay were significantly higher in patients with acute rheumatic fever compared with the control group (p < 0.001). However, there was no difference in terms of intra-atrial electromechanical delay (p > 0.05). For patients with acute rheumatic fever, a positive correlation was identified between the left atrium diameter and the P-wave dispersion and interatrial electromechanical delay (r = 0.524 and p < 0.001, and r = 0.351 and p = 0.014, respectively). Furthermore, an important correlation was also identified between the P-wave dispersion and the interatrial electromechanical delay (r = 0.494 and p < 0.001). CONCLUSION: This study shows the prolongation of P-wave dispersion and interatrial electromechanical delay in acute rheumatic fever. Left atrial enlargement can be one of the underlying reasons for the increase in P-wave dispersion and interatrial electromechanical delay.

[The implantable cardiac defibrillator: indications and complications]. / De implanteerbare defibrillator: indicaties en complicaties van de ICD.

The implantation of an implantable cardiac defibrillator (ICD) is indicated as a secondary prevention measure for sudden cardiac death in patients surviving a life-threatening ventricular arrhythmia that had no reversible or treatable cause. An ICD is indicated as a primary prevention measure for sudden cardiac death in patients with a left-ventricular ejection fraction (LVEF) ≤ 35%. A biventricular ICD is indicated in patients with heart failure class ≥ II according to the New York Heart Association classification, a widened QRS complex and an LVEF ≤ 35%. Guidelines do not differentiate between men and women or according to age, but there is no evidence in the literature for decreased mortality from applying ICD therapy in women and in patients older than 70-75 years. This is relevant in discussions over the cost-effectiveness of the treatment. Sudden cardiac death occurs most frequently in patients with an LVEF ≥ 35%; the effect of ICDs as a primary prevention measure in this patient group has, however, never been investigated. The most important complications following ICD implantation are inappropriate ICD shocks and lead dysfunction. Automated home-monitoring enables early detection of technical defects.

Cardiac electrophysiological assessment in patients with sarcoidosis.

BACKGROUND: Sarcoidosis is a multisystem granulomatous disease of unknown origin that can cause sudden death. OBJECTIVE: Electrophysiological evaluation of patients with suspected sarcoidosis with cardiac involvement. METHODS: We studied 22 patients with mean age of 55.32 ± 13.13 years, diagnosed with sarcoidosis and suspected cardiac involvement. These patients underwent clinical evaluation, laboratory tests, electrocardiogram, echocardiogram, 24-hour Holter, technetium or gallium scintigraphy and electrophysiological study. In selected cases, we performed positron emission tomography or magnetic resonance imaging. Patients were followed up in the outpatient care service with quarterly visits. RESULTS: Cardiac involvement was confirmed in four (18.2%) patients. Ventricular extrasystoles with density > 100/24 h were documented in 24-Holter monitoring in 12 (54.5%) patients. Electrophysiological studies revealed an increased HV interval in seven patients (31.8%) and increased Wenckebach point in four (18.2%) patients. There was induction of atrial fibrillation in seven patients (31.8%) and sustained ventricular tachycardia in one patient (4.5%). Four patients with confirmed cardiac sarcoidosis had documented ventricular extrasystoles with density > 100/24 h. Out of these, two had prolonged HV interval and atrial fibrillation was induced in two of them. Sustained ventricular tachycardia was not induced in any of these patients. After mean follow-up period of 20.9 ± 15.7 months, one patient with cardiac sarcoidosis had sudden death. CONCLUSION: Patients with sarcoidosis and suspected cardiac involvement have a high prevalence of ventricular extrasystoles (VEs) and conduction system disorders.

Avaliação eletrofisiológica cardíaca em pacientes com sarcoidose / Cardiac electrophysiological assessment in patients with sarcoidosis / Evaluación electrofisiológica cardíaca en pacientes con sarcoidosis

FUNDAMENTO: Sarcoidose é uma doença granulomatosa multissistêmica de origem desconhecida que pode causar morte súbita. OBJETIVO: Avaliação eletrofisiológica de pacientes com sarcoidose com suspeita de comprometimento cardíaco. MÉTODOS: Foram estudados 22 pacientes com média de idade de 55,32 ±13,13 anos, com diagnóstico de sarcoidose e suspeita de comprometimento cardíaco. Foram submetidos à avaliação clínica, exames laboratoriais, eletrocardiograma, ecocardiograma, Holter de 24h, cintilografia com gálio ou tecnécio e estudo eletrofisiológico. Em casos selecionados foi realizada tomografia por emissão de pósitrons ou ressonância magnética. Os pacientes foram seguidos ambulatoriamente com consultas trimestrais. RESULTADOS: Comprometimento cardíaco foi comprovado em quatro (18,2 por cento) pacientes. Extrassístoles ventriculares com densidade > 100/24h foram documentadas no Holter de 24h em 12 (54,5 por cento) pacientes. O estudo eletrofisiológico revelou aumento do intervalo HV em sete (31,8 por cento) e ponto de Wenckebach aumentado em quatro (18,2 por cento) pacientes. Houve indução de fibrilação atrial em sete (31,8 por cento) e de taquicardia ventricular sustentada em um (4,5 por cento). Nos quatro pacientes com sarcoidose cardíaca confirmada, extrassístoles ventriculares, com densidade > 100/24h foram documentadas em todos, dois apresentavam intervalo HV prolongado e fibrilação atrial foi induzida em dois. Taquicardia ventricular sustentada não foi induzida em nenhum desses pacientes. Após período médio de acompanhamento de 20,9 ± 15,7 meses, um paciente com sarcoidose cardíaca apresentou morte súbita. CONCLUSÃO: Pacientes com sarcoidose e suspeita de envolvimento cardíaco apresentam alta prevalência de EVs e distúrbios do sistema de condução.

BACKGROUND: Sarcoidosis is a multisystem granulomatous disease of unknown origin that can cause sudden death. OBJECTIVE: Electrophysiological evaluation of patients with suspected sarcoidosis with cardiac involvement. METHODS: We studied 22 patients with mean age of 55.32 ± 13.13 years, diagnosed with sarcoidosis and suspected cardiac involvement. These patients underwent clinical evaluation, laboratory tests, electrocardiogram, echocardiogram, 24-hour Holter, technetium or gallium scintigraphy and electrophysiological study. In selected cases, we performed positron emission tomography or magnetic resonance imaging. Patients were followed up in the outpatient care service with quarterly visits. RESULTS: Cardiac involvement was confirmed in four (18.2 percent) patients. Ventricular extrasystoles with density > 100/24h were documented in 24-Holter monitoring in 12 (54.5 percent) patients. Electrophysiological studies revealed an increased HV interval in seven patients (31.8 percent) and increased Wenckebach point in four (18.2 percent) patients. There was induction of atrial fibrillation in seven patients (31.8 percent) and sustained ventricular tachycardia in one patient (4.5 percent). Four patients with confirmed cardiac sarcoidosis had documented ventricular extrasystoles with density > 100/24h. Out of these, two had prolonged HV interval and atrial fibrillation was induced in two of them. Sustained ventricular tachycardia was not induced in any of these patients. After mean follow-up period of 20.9 ± 15.7 months, one patient with cardiac sarcoidosis had sudden death. CONCLUSION: Patients with sarcoidosis and suspected cardiac involvement have a high prevalence of ventricular extrasystoles (VEs) and conduction system disorders.

FUNDAMENTOS: Sarcoidosis es una enfermedad granulomatosa multisistémica de origen desconocido que puede causar la muerte súbita. OBJETIVOS:Evaluación electrofisiológica de los pacientes con sarcoidosis con sospecha de afectación cardíaca. MÉTODOS:Se estudiaron a 22 pacientes con una media de edad de 55,32 ± 13,13 años, con diagnóstico de sarcoidosis y sospecha de afectación cardíaca.Se sometieron a evaluación clínica, exámenes de laboratorio, electrocardiograma, ecocardiograma, Holter de 24 h, centellografía con galio o tecnecio y estudio electrofisiológico. En los casos seleccionados se realizó tomografía por emisión de positrones o la resonancia magnética.Los pacientes fueron seguidos en ambulatorio, en consultas trimestrales. RESULTADOS:La afectación cardíaca se comprobó en cuatro (18,2 por ciento) pacientes.Extrasístoles ventriculares con densidad > 100/24 h se documentaron en el Holter de 24 h en 12 (54,5 por ciento) pacientes.Los estudios electrofisiológicos revelaron un aumento del intervalo HV en siete (31,8 por ciento) y punto de Wenckebach aumentado en cuatro (18,2 por ciento) pacientes. No hubo inducción de fibrilación auricular en siete (31,8 por ciento) y de taquicardia ventricular sostenida en uno (4,5 por ciento). En los cuatro pacientes con sarcoidosis cardiaca confirmada, extrasístoles ventriculares (EVs), con densidad > 100/24 h se documentaron en todos, dos presentaban prolongación del intervalo HV y fibrilación auricular se indujo en dos. La taquicardia ventricular sostenida no fue inducida en cualquiera de estos pacientes. Después de un periodo medio de seguimiento de 20,9 ± 15,7 meses, un paciente con sarcoidosis cardíaca tuvo muerte súbita. CONCLUSIÓN: Los pacientes con sarcoidosis y sospecha de afectación cardíaca tienen una alta prevalencia de EVs y trastornos del sistema de conducción.

Curative percutaneous catheter ablation using radiofrequency energy for accessory pathways in all locations: results in 100 consecutive patients.

Patients with accessory pathway-mediated supraventricular tachycardia have typically been treated with drugs or surgery. Although catheter ablation using high voltage direct current shocks has been used to treat patients with drug-refractory supraventricular tachycardia, there are associated disadvantages, including damage due to barotrauma as well as the need for general anesthesia. Recently, transcatheter radiofrequency energy has evolved as an alternative to direct current shock or surgery to ablate accessory pathways. Percutaneous catheter ablation of 109 accessory pathways with use of radiofrequency energy was attempted in 100 consecutive patients. Patient age ranged from 3 to 67 years. The patients had been treated for recurrent tachycardia with a mean of 2.7 +/- 0.2 antiarrhythmic agents that either proved ineffective or caused unacceptable side effects. In seven patients previous attempts at accessory pathway ablation with use of direct current shock had been unsuccessful. Forty-five (41%) of the pathways were left free wall, 43 (40%) were septal and 21 (19%) were right free wall. Eighty-nine (89%) of the 100 patients had successful radiofrequency ablation at the time of hospital discharge. In all but 12 patients the ablation was accomplished in a single session. Complications attributable to the procedure, but not to the ablation itself, occurred in four patients (4%). No patient developed atrioventricular block or other cardiac arrhythmias. Over a mean follow-up period of 10 months, nine patients had some return of accessory pathway conduction; a repeat ablation procedure was successful in all five patients in whom it was attempted. It is concluded that a catheter ablation procedure using radiofrequency energy can be performed on accessory pathways in all locations. The procedure is effective and safer, less costly and more convenient than cardiac surgery and can be considered as an alternative to lifelong medical therapy in any patient with symptomatic accessory pathway-mediated tachycardia.