In the present study, we sought to investigate the agreement between late gadolinium enhancement (LGE) in cardiovascular magnetic resonance (CMR) and electro-anatomical maps (EAM) of patients with non-ischemic dilated cardiomyopathy (NIDCM) and how it relates with the procedural outcome after catheter ablation of ventricular arrhythmias (VA). We identified 50 patients with NIDCM who underwent CMR and ablation for VA. LGE was detected in 16 patients (32%), mostly in those presenting with sustained VT (15 patients). Low-voltage areas (<1.5 mV) were observed in 23 patients (46%), in 7 patients (14%) without evidence of LGE. Using a threshold of 1.5 mV, a good and partially good agreement between the bipolar EAM and LGE-CMR was observed in only 4 (8%) and 9 (18%) patients, respectively. With further adjustments of EAM to match the LGE, we defined new cut-off limits of median 1.5 mV and 5 mV for bipolar and unipolar maps, respectively. Most VT exits were found in areas with LGE (12 out of 16 patients). VT exits were found in segments without LGE in 2 patients with unsuccessful ablation as well as in 2 patients with successful ablation, P=0.77. In patients with VT recurrence, the LGE volume was significantly larger than in those without recurrence: 12.2 ± 5.8% vs. 6.9 ± 3.4%; P=0.049. Myocardial heterogeneity provides the electrophysiological substrate of ventricular arrhythmias in patients with myocardial infarction. Fibrosis and reduction in the number of gap junctions of surviving myocytes allow the occurrence of re-entry (23). However, the relationship between fibrosis and VA is complex and involves not only fixed anatomical barriers but also functional blocks caused by differences in the fiber orientation, myocardial thickness mismatch or connexin downregulation (24-26). Studies involving EAM in patients with scar-related VT demonstrated that homogenization of the low-voltage areas with elimination of the signals showing abnormal amplitude and fractionation was associated with improved acute and long-term success rates (27). On the other hand, animal studies showed that CMR can be useful to characterize LV fibrosis. Moreover, the amount of LGE has been associated with inducibility of VT and is considered a powerful and independent predictor of adverse prognosis, especially in myocardial infarction patients (28-29). In contrast to ischemic cardiomyopathy, LGE is infrequently found in patients with NIDCM. A previous study of 399 patients with NIDCM demonstrated that LGE was detected in approximately one-fourth of the patients and was associated with a 9-fold increase of risk for SCD (30). In accordance with these data, we observed LGE in approximately one third of the patients, and most of them had a history of spontaneous sustained VT. In contrast to the VT patients who have frequently LGE, all patients with ventricular premature beats but without any sustained VT did not show any evidence of LGE in CMR. These observations support the general understanding that the presence of LGE identifies more advanced cardiomyopathy as well as a higher risk for more malignant ventricular arrhythmias. Although myocardial fibrosis is associated with a higher likelihood for VT occurrence, the absence of LGE in CMR does not completely eliminate the risk for VT. Some patients had sustained ventricular arrhythmias even without detectable scar in CMR, which suggests a poorer negative predictive value for the LGE. Although CMR imaging is currently considered the reference standard for the detection of LV scar, it has a limited spatial resolution in vivo. Therefore, minute scars as well as diffuse fibrosis that can still trigger VA may remain undetected. The alternative approach to detect myocardial scar is to characterize the electrical properties of the myocardium by using bipolar EAM in order to find low-voltage areas and late potentials that are markers of abnormal tissue. However, abnormal fragmentation and amplitudes below 1,5 mV are less frequently found in NIDCM in comparison to post-myocardial infarction patients. These findings illustrate the downsides of the EAM in NIDCM. Moreover, numerous animal and clinical studies underlined other technical drawbacks of the EAM that can influence the size and the characteristics of the low-voltage areas such as mapping electrode size and spacing, the angle of contact with the underlying tissue, wave-front direction (31-33). Recently, Betensky and al. analyzed the agreement between CMR and EAM in patients with NIDCM and found a significant discordance between both approaches in 36% of the patients. Using lower signal intensity threshold of 2 standard deviations they increased the CMR-EAM agreement up to almost 90% (34). In contrast to Betensky, who used a simplified approach analyzing only the septal to lateral disagreement, we choose to perform more precise analysis using the 17 segments AHA model of the LV. We found 23 out of 50 patients with low-voltage areas and 15 (71.4%) of them had sustained VT. Moreover only 16 (32%) patients with low-voltage had also LGE in the CMR. In our study the basal inferolateral, inferior and infero-septal segments were most frequently affected by LGE in contrast to the basal anterior and anteroseptal segments affected in the EAM. However, in the LGE positive patients, the best pace-mapping sites of the clinical VT coincided with areas of LGE. One possible explanation for the low correlation between EAM and LGE-CMR is the non-transmurality of the fibrosis in patients with NIDCM. A previous study in post-infarct patients demonstrated that median bipolar voltage <1.5 mV was only found in segments demonstrating ≥75% infarct transmurality (35). In a recently published article, Zeppenfeld et al. found that EAM voltages showed a linear relationship with the LV wall thickness and the amount of fibrosis in patients with non-ischemic DCM. However, no cutoff value for the voltage could be found to reliably delineate fibrotic areas in NIDCM (36). Regarding the quantification of the arrhythmogenic substrate, we could not find any correlation between the amount of LGE and the size of the low-voltage areas (endo- or epicardial), which can be explained by the impact of LGE transmurality as well as the sparse distribution of the LV fibrosis. In this regard, an advantage of the LGE-CMR is that it can visualize the presence of intramyocardial and epicardial scar which are not visible by endocardial EAM. The reason is that the bipolar EAM has narrower field of view and proved insensitive to delineate scar that lies deeper within the myocardium (37). Previously, Hutchinson et al. reported that by using a unipolar 8.27 mV threshold endocardial it was possible to identify epicardial bipolar low-voltage areas consistent with macroscopic scarring in patients with NIDCM and normal endocardial bipolar voltage (38). However, we found that the agreement between LGE and unipolar maps using this cutoff of 8.27 mV was poor. After adjusting the unipolar and bipolar threshold on the basis of CMR, the resulting median thresholds for the bipolar and unipolar low-voltage maps were 1.5 mV and 5 mV respectively, which are close to those observed in a previous study (37). 4.1 Conclusions LGE was observed in approximately one-third of the patients with dilated cardiomyopathy of non-ischemic origin and ventricular arrhythmias. LGE was seen mainly in patients with sustained VT. The agreement between the distribution or the extent of LGE and bipolar low-voltage areas was fairly poor. No particular cutoff values for bipolar and unipolar electro-anatomical maps could be found. On the other hand, most VT exits in patient with sustained VT were found in areas of LGE. The procedural success after VA ablation were related to LGE volume only.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20269号 / 医博第4228号 / 新制||医||1021(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 横出 正之, 教授 湊谷 謙司, 教授 瀬原 淳子 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Abstract Approximately 1-2 percent of the world population lives with various heart rhythm disorders of supraventricular nature. These arrhythmias can alter the patient's lifestyle and negatively affect the balance between the demands of daily life and functional abilities. To diagnose paroxysmal supraventricular tachycardia (PSVT) can be difficult due to spontaneity of the episodes and the transience nature of the symptoms. Finding the right treatment can also pose a challenge because some of the medicines used are associated with increased toxic risks and requires close monitoring of the patient through regular blood tests. Some patients experience recurrence of symptoms despite optimal treatment measures and adherence to treatment and self-care recommendations.  Studies have shown that patients’ prior knowledge regarding these diagnoses is low. The nurse has a crucial role of informing and making sure that patients receive education in among other things self-care as well as information regarding disease and drugs related complications etc. There is a mutual interaction between daily life and functional health status where daily life makes demands on functional abilities at the same time as these affect how an individual lives their daily lives. In order to experience quality of life and health, the balance between these two must be maintained. The nurse has a pivot role in assisting the patient maintain the balance.  The study’s aim was to highlight the effects of living with supraventricular tachycardia (SVT) on the patient's daily life. The method chosen was literature review. Original articles were obtained from established databases such as PubMed and CINAHL, and the results from 17 articles were analyzed using content analysis. This means that the text was read several times in order to familiarize with the content. Different units were identified and the categories as well as sub-categories were coded. These formed the basis of the headings and subheading used to present the results. Four categories and ten sub-categories were identified from the studies.  Studies show that SVT has negative effects on the patients’ daily life. Symptoms cause anxieties and uncertainties that lead to mental and emotional stress. Some patients withdraw from participating in the social activities for fear of provoking the attacks whereas others are forced to give up participation due to among other things fatigue that results from symptoms attacks. Family life is sometimes disrupted since the symptoms can lead to fatigue that negatively affects family life in that patients do not have the energy to participate in activities in their home or to live up to other requirements of their daily lives.  The diagnosis can even affect economy since patients are forced to cut down on working hours or go into early retirement. Other patients lost their employment due to frequent hos-pital visits or inability to fulfill their duties. Physical activities as well as well-being are negatively affected too in that some patients show signs of impaired physical activities. Patients use different coping strategies such as planning their daily lives around the symp-tomatic periods. In conclusion it is suffice to state that SVT has negative effects on the patients’ daily life. The Patients would benefit from a well-structured and person centered patient education.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a stress-induced arrhythmia, caused by genetic defects in sarcoplasmic reticulum (SR) Ca-release channel RyR2, or its accessory proteins. Our previous studies demonstrated that CPVT mitochondria can absorb RyR2-mediated aberrant Ca release (ACR) and behave as an efficient Ca buffer which is critical in mitigating harmful consequences of ACR. In this study, we test the hypothesis that modulating mitochondrial phosphate (Pi) transport or the tethering between SR-mitochondria, known as Mitochondria-associated-membrane (MAMs), impacts arrhythmogenesis in CPVT. We found that inhibiting mitochondrial Pi carrier (PiC) exacerbated cellular arrhythmias whereas overexpressing PiC in CPVT alleviated both cellular and in vivo arrhythmias. In parallel, disrupting MAMs exacerbated arrhythmogenesis in CPVT, but promoting MAMs by overexpressing mitofusin2 tethering protein reduced cellular arrhythmias. Our study provided both pharmacological and genetic evidence that directing more Ca to mitochondria by enhancing mitochondrial Pi transport or targeting MAMs could be promising therapeutic strategies to reduce CPVT arrhythmia.

No description available.

Although several investigations have shown a relationship between increased epicardial adipose tissue (EAT) and atrial fibrillation (AF), the association between EAT and ventricular tachycardia (VT) has not been evaluated. We investigated the association between EAT and post-ablation VT recurrence. In this study, sixty-one consecutive patients (mean age=62.0±13.9) undergoing VT ablation with pre-procedural cardiac magnetic resonance imaging (MRI) were recruited. EAT thickness was measured using cardiac MRI in the right and left atrioventricular grooves (AVGs), RV free wall, anterior, inferior, and superior interventricular grooves (IVGs). During a mean follow-up period of 392.9±180.2 days, post-ablation VT recurrence occurred in 15 (24.6%) patients. EAT thickness was significantly higher in the VT recurrence group than that in the non-recurrent VT at the right (18.7±5.7 vs. 14.1±4.4 mm; p=0.012) and left (13.3±3.9 vs. 10.4±4.1; p=0.020) AVGs. The best cut-off points for predicting VT recurrence were calculated as 15.5 mm for the right AVG (area under ROC curve=0.74) and 11.5 mm for the left AVG (area under ROC curve=0.72). Multivariate Cox regression analysis showed that pre procedural right AVG-EAT (HR: 1.2; 95% CI: [1.06-1.39], p=0.004) was the only independent predictor of VT recurrence after adjustment for covariates. Kaplan–Meier analysis showed a difference for post-ablation VT recurrence between the two groups with right AVG-EAT thickness cut-off value of <15.5 mm versus ≥15.5 mm (log-rank, p=0.003). Based on the finding of this study, we suggested a new possible imaging marker for risk stratification of post-ablation VT recurrence. A higher EAT may be associated with VT recurrence after catheter ablation of VTs.:Epicardial Adipose Tissue Anatomy Embryology Physiology and Pathophysiology Measurement of EAT EAT and heart disorders Future direction VT Catheter Ablation History of VT ablation Catheter ablation for VT in structural and non-structural heart Outcome of VT catheter ablation Predictors of VT recurrence after catheter ablation Objectives of the thesis Publication Summary References

No description available.

[ES] Las enfermedades cardiovasculares constituyen la principal causa de morbilidad y mortalidad a nivel mundial, causando en torno a 18 millones de muertes cada año. De entre ellas, la más común es la enfermedad isquémica cardíaca, habitualmente denominada como infarto de miocardio (IM). Tras superar un IM, un considerable número de pacientes desarrollan taquicardias ventriculares (TV) potencialmente mortales durante la fase crónica del IM, es decir, semanas, meses o incluso años después la fase aguda inicial. Este tipo concreto de TV normalmente se origina por una reentrada a través de canales de conducción (CC), filamentos de miocardio superviviente que atraviesan la cicatriz del infarto fibrosa y no conductora. Cuando los fármacos anti-arrítmicos resultan incapaces de evitar episodios recurrentes de TV, la ablación por radiofrecuencia (ARF), un procedimiento mínimamente invasivo realizado mediante cateterismo en el laboratorio de electrofisiología (EF), se usa habitualmente para interrumpir de manera permanente la propagación eléctrica a través de los CCs responsables de la TV. Sin embargo, además de ser invasivo, arriesgado y requerir mucho tiempo, en casos de TVs relacionadas con IM crónico, hasta un 50% de los pacientes continúa padeciendo episodios recurrentes de TV tras el procedimiento de ARF. Por tanto, existe la necesidad de desarrollar nuevas estrategias pre-procedimiento para mejorar la planificación de la ARF y, de ese modo, aumentar esta tasa de éxito relativamente baja. En primer lugar, realizamos una revisión exhaustiva de la literatura referente a los modelos cardiacos 3D existentes, con el fin de obtener un profundo conocimiento de sus principales características y los métodos usados en su construcción, con especial atención sobre los modelos orientados a simulación de EF cardíaca. Luego, usando datos clínicos de un paciente con historial de TV relacionada con infarto, diseñamos e implementamos una serie de estrategias y metodologías para (1) generar modelos computacionales 3D específicos de paciente de ventrículos infartados que puedan usarse para realizar simulaciones de EF cardíaca a nivel de órgano, incluyendo la cicatriz del infarto y la región circundante conocida como zona de borde (ZB); (2) construir modelos 3D de torso que permitan la obtención del ECG simulado; y (3) llevar a cabo estudios in-silico de EF personalizados y pre-procedimiento, tratando de replicar los verdaderos estudios de EF realizados en el laboratorio de EF antes de la ablación. La finalidad de estas metodologías es la de localizar los CCs en el modelo ventricular 3D para ayudar a definir los objetivos de ablación óptimos para el procedimiento de ARF. Por último, realizamos el estudio retrospectivo por simulación de un caso, en el que logramos inducir la TV reentrante relacionada con el infarto usando diferentes configuraciones de modelado para la ZB. Validamos nuestros resultados mediante la reproducción, con una precisión razonable, del ECG del paciente en TV, así como en ritmo sinusal a partir de los mapas de activación endocárdica obtenidos invasivamente mediante sistemas de mapeado electroanatómico en este último caso. Esto permitió encontrar la ubicación y analizar las características del CC responsable de la TV clínica. Cabe destacar que dicho estudio in-silico de EF podría haberse efectuado antes del procedimiento de ARF, puesto que nuestro planteamiento está completamente basado en datos clínicos no invasivos adquiridos antes de la intervención real. Estos resultados confirman la viabilidad de la realización de estudios in-silico de EF personalizados y pre-procedimiento de utilidad, así como el potencial del abordaje propuesto para llegar a ser en un futuro una herramienta de apoyo para la planificación de la ARF en casos de TVs reentrantes relacionadas con infarto. No obstante, la metodología propuesta requiere de notables mejoras y validación por medio de es / [CA] Les malalties cardiovasculars constitueixen la principal causa de morbiditat i mortalitat a nivell mundial, causant entorn a 18 milions de morts cada any. De elles, la més comuna és la malaltia isquèmica cardíaca, habitualment denominada infart de miocardi (IM). Després de superar un IM, un considerable nombre de pacients desenvolupen taquicàrdies ventriculars (TV) potencialment mortals durant la fase crònica de l'IM, és a dir, setmanes, mesos i fins i tot anys després de la fase aguda inicial. Aquest tipus concret de TV normalment s'origina per una reentrada a través dels canals de conducció (CC), filaments de miocardi supervivent que travessen la cicatriu de l'infart fibrosa i no conductora. Quan els fàrmacs anti-arítmics resulten incapaços d'evitar episodis recurrents de TV, l'ablació per radiofreqüència (ARF), un procediment mínimament invasiu realitzat mitjançant cateterisme en el laboratori de electrofisiologia (EF), s'usa habitualment per a interrompre de manera permanent la propagació elèctrica a través dels CCs responsables de la TV. No obstant això, a més de ser invasiu, arriscat i requerir molt de temps, en casos de TVs relacionades amb IM crònic fins a un 50% dels pacients continua patint episodis recurrents de TV després del procediment d'ARF. Per tant, existeix la necessitat de desenvolupar noves estratègies pre-procediment per a millorar la planificació de l'ARF i, d'aquesta manera, augmentar la taxa d'èxit, que es relativament baixa. En primer lloc, realitzem una revisió exhaustiva de la literatura referent als models cardíacs 3D existents, amb la finalitat d'obtindre un profund coneixement de les seues principals característiques i els mètodes usats en la seua construcció, amb especial atenció sobre els models orientats a simulació de EF cardíaca. Posteriorment, usant dades clíniques d'un pacient amb historial de TV relacionada amb infart, dissenyem i implementem una sèrie d'estratègies i metodologies per a (1) generar models computacionals 3D específics de pacient de ventricles infartats capaços de realitzar simulacions de EF cardíaca a nivell d'òrgan, incloent la cicatriu de l'infart i la regió circumdant coneguda com a zona de vora (ZV); (2) construir models 3D de tors que permeten l'obtenció del ECG simulat; i (3) dur a terme estudis in-silico de EF personalitzats i pre-procediment, tractant de replicar els vertaders estudis de EF realitzats en el laboratori de EF abans de l'ablació. La finalitat d'aquestes metodologies és la de localitzar els CCs en el model ventricular 3D per a ajudar a definir els objectius d'ablació òptims per al procediment d'ARF. Finalment, a manera de prova de concepte, realitzem l'estudi retrospectiu per simulació d'un cas, en el qual aconseguim induir la TV reentrant relacionada amb l'infart usant diferents configuracions de modelatge per a la ZV. Validem els nostres resultats mitjançant la reproducció, amb una precisió raonable, del ECG del pacient en TV, així com en ritme sinusal a partir dels mapes d'activació endocardíac obtinguts invasivament mitjançant sistemes de mapatge electro-anatòmic en aquest últim cas. Això va permetre trobar la ubicació i analitzar les característiques del CC responsable de la TV clínica. Cal destacar que aquest estudi in-silico de EF podria haver-se efectuat abans del procediment d'ARF, ja que el nostre plantejament està completament basat en dades clíniques no invasius adquirits abans de la intervenció real. Aquests resultats confirmen la viabilitat de la realització d'estudis in-silico de EF personalitzats i pre-procediment d'utilitat, així com el potencial de l'abordatge proposat per a arribar a ser en un futur una eina de suport per a la planificació de l'ARF en casos de TVs reentrants relacionades amb infart. No obstant això, la metodologia proposada requereix de notables millores i validació per mitjà d'estudis de simulació amb grans cohorts de pacients. / [EN] Cardiovascular diseases represent the main cause of morbidity and mortality worldwide, causing around 18 million deaths every year. Among these diseases, the most common one is the ischaemic heart disease, usually referred to as myocardial infarction (MI). After surviving to a MI, a considerable number of patients develop life-threatening ventricular tachycardias (VT) during the chronic stage of the MI, that is, weeks, months or even years after the initial acute phase. This particular type of VT is typically sustained by reentry through slow conducting channels (CC), which are filaments of surviving myocardium that cross the non-conducting fibrotic infarct scar. When anti-arrhythmic drugs are unable to prevent recurrent VT episodes, radiofrequency ablation (RFA), a minimally invasive procedure performed by catheterization in the electrophysiology (EP) laboratory, is commonly used to interrupt the electrical conduction through the CCs responsible for the VT permanently. However, besides being invasive, risky and time-consuming, in the cases of VTs related to chronic MI, up to 50% of patients continue suffering from recurrent VT episodes after the RFA procedure. Therefore, there exists a need to develop novel pre-procedural strategies to improve RFA planning and, thereby, increase this relatively low success rate. First, we conducted an exhaustive review of the literature associated with the existing 3D cardiac models in order to gain a deep knowledge about their main features and the methods used for their construction, with special focus on those models oriented to simulation of cardiac EP. Later, using a clinical dataset of a chronically infarcted patient with a history of infarct-related VT, we designed and implemented a number of strategies and methodologies to (1) build patient-specific 3D computational models of infarcted ventricles that can be used to perform simulations of cardiac EP at the organ level, including the infarct scar and the surrounding region known as border zone (BZ); (2) construct 3D torso models that enable to compute the simulated ECG; and (3) carry out pre-procedural personalized in-silico EP studies, trying to replicate the actual EP studies conducted in the EP laboratory prior to the ablation. The goal of these methodologies is to allow locating the CCs into the 3D ventricular model in order to help in defining the optimal ablation targets for the RFA procedure. Lastly, as a proof-of-concept, we performed a retrospective simulation case study, in which we were able to induce an infarct-related reentrant VT using different modelling configurations for the BZ. We validated our results by reproducing with a reasonable accuracy the patient's ECG during VT, as well as in sinus rhythm from the endocardial activation maps invasively recorded via electroanatomical mapping systems in this latter case. This allowed us to find the location and analyse the features of the CC responsible for the clinical VT. Importantly, such in-silico EP study might have been conducted prior to the RFA procedure, since our approach is completely based on non-invasive clinical data acquired before the real intervention. These results confirm the feasibility of performing useful pre-procedural personalized in-silico EP studies, as well as the potential of the proposed approach to become a helpful tool for RFA planning in cases of infarct-related reentrant VTs in the future. Nevertheless, the developed methodology requires further improvements and validation by means of simulation studies including large cohorts of patients. / During the carrying out of this doctoral thesis, the author Alejandro Daniel López Pérez was financially supported by the Ministerio de Economía, Industria y Competitividad of Spain through the program Ayudas para contratos predoctorales para la formación de doctores, with the grant number BES-2013-064089. / López Pérez, AD. (2019). Computational modelling of the human heart and multiscale simulation of its electrophysiological activity aimed at the treatment of cardiac arrhythmias related to ischaemia and Infarction [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/124973

Moricizine is a novel phenothiazine antiarrhythmic agent that depresses the activity of ectopic foci, has a low incidence of adverse effects relative to other agents, and is useful in treating pediatric atrial ectopic tachycardia. A study was conducted to determine the pharmacokinetics of moricizine in children after oral administration. Moricizine was isolated from frozen serum obtained from four male patients (ages 7, 8, 9, and 18 years) receiving the drug for supraventricular tachycardia and analyzed by high-performance liquid chromatography with ultraviolet detection according to an established protocol. Peak serum levels were between 400 and 2000 ng/mL. Elimination of moricizine did not follow simple single-compartment pharmacokinetics. In three patients we observed an increase or slower decline in blood level occurring after 4 hours. Because of the paroxysmal nature of the tachycardias, decreases in patient heart rate could not be correlated with moricizine blood level. These results suggest that the pediatric pharmacokinetics of moricizine excretion are complex and may differ from those seen in adults.

No description available.