Rate-Control or Rhythm-Contol: Where do we stand?

Atrial fibrillation is the most common sustained rhythm disturbance and its prevalence is increasing worldwide due to the progressive aging of the population. Current guidelines clearly depict the gold standard management of acute symptomatic atrial fibrillation but the best-long term approach for first or recurrent atrial fibrillation is still debated with regard to quality of life, risk of new hospitalizations, and possible disabling complications, such as thromboembolic stroke, major bleeds and death. Some authors propose that regaining sinus rhythm in all cases, thus re-establishing a physiologic cardiac function not requiring a prolonged antithrombotic therapy, avoids the threat of intracranial or extracranial haemorrhages due to Vitamin K antagonists or aspirin. On the contrary, advocates of a rate control approach with an accurate antithrombotic prophylaxis propose that such a strategy may avoid the risk of cardiovascular and non cardiovascular side effects related to antiarrhythmic drugs. This review aims to explore the state of our knowledge in order to summarize evidences and issues that need to be furthermore clarified

Myocarditis Presenting with Ventricular Arrhythmias: Role of Electroanatomical Mapping-Guided Endomyocardial Biopsy in Differential Diagnosis

Non

Small-molecule inhibition of MuRF1 attenuates skeletal muscle atrophy and dysfunction in cardiac cachexia

Background; Muscle ring finger 1 (MuRF1) is a muscle‐specific ubiquitin E3 ligase activated during clinical conditions associated with skeletal muscle wasting. Yet, there remains a paucity of therapeutic interventions that directly inhibit MuRF1 function, particularly in vivo. The current study, therefore, developed a novel compound targeting the central coiled coil domain of MuRF1 to inhibit muscle wasting in cardiac cachexia. Methods; We identified small molecules that interfere with the MuRF1–titin interaction from a 130 000 compound screen based on Alpha Technology. A subset of nine prioritized compounds were synthesized and administrated during conditions of muscle wasting, that is, to C2C12 muscle cells treated with dexamethasone and to mice treated with monocrotaline to induce cardiac cachexia. Results; The nine selected compounds inhibited MuRF1–titin complexation with IC50 values <25 μM, of which three were found to also inhibit MuRF1 E3 ligase activity, with one further showing low toxicity on cultured myotubes. This last compound, EMBL chemical core ID#704946, also prevented atrophy in myotubes induced by dexamethasone and attenuated fibre atrophy and contractile dysfunction in mice during cardiac cachexia. Proteomic and western blot analyses showed that stress pathways were attenuated by ID#704946 treatment, including down‐regulation of MuRF1 and normalization of proteins associated with apoptosis (BAX) and protein synthesis (elF2B‐delta). Furthermore, actin ubiquitinylation and proteasome activity was attenuated. Conclusions; We identified a novel compound directed to MuRF1's central myofibrillar protein recognition domain. This compound attenuated in vivo muscle wasting and contractile dysfunction in cardiac cachexia by protecting de novo protein synthesis and by down‐regulating apoptosis and ubiquitin‐proteasome‐dependent proteolysis

Lo Score-15, uno strumento multifunzionale per la ricerca e la pratica clinica

The aim of this paper is to stimulate thoughts about employing an instrument such as the SCORE-15 as an aid in clinicians’ daily work. Already validated for research in Family and Couple Therapy, this easy to administer instrument makes it possible to obtain an immediate perception of family/couple characteristics, their process of change throughout treatment, and the results of therapeutic interventions. We present a study conducted over a 5-year period during which 69 families and couples received treatment at the same training school in family and relational therapy. Participants completed the SCORE-15 during treatment. We compared participants’ responses from the first and last administration of the questionnaire (n=171) after dividing the sample according to the role of the members within the family/couple and the type of therapeutic setting (family, couple, or parental). Using a specifically designed version of the SCORE, we also compared the therapists’ perception of change with that of the family members. This comparison opens the possibility of using SCORE in clinical practice. Lastly, we present a clinical case to illustrate the utility of SCORE as an instrument of orientation and frequent feedback in therapeutic work.Propòsito de este trabajo es estimular la reflexión sobre el empleo de una hierramenta validada para la evaluación de terapias familiares y de pareja, el SCORE-15: se trata de un cuestionario de facil administración que permite de obtener una fotografia inmediata de las caracteristicas de la familia/pareja, del cambio y del proceso terapéutico en curso. La muestra està costituida por 171 Score en primera y ultima administración, relacionados a 69 familias/parejas, recolectados durante 5 anos en la misma escuela de formaciòn en terapia Familiar Sistemica Relacional. Con el objetivo de monitorear las tendencias en el tiempo y los exitos de las terapias desarroladas, se han confrontado la puntuaciòn obtenida por los SCORE al inicio y a la conclusión de la terapia, dividiendo la muestra también en funciòn del rol de los miembros al interior de la familia/pareja y a los tipos de entornos terapéuticos (familiar, de pareja o parental). La investigaciòn ha incluido también la comparación entre el cambio percibido por el terapeuta, anotado gracias a una especifica versiòn de SCORE, y lo deducido por el modelo de cuestionario compilado por los miembros de la familia/pareja: esta comparación abre la posibilidad de utilizar SCORE como ayuda en la pràctica clìnica de las/los terapeutas. Sigue la descripción de un caso en el cual se ilustra el posible empleo de SCORE como hierramenta de orientación y de colección de feedback en el trabajo clinico en curso y hecho.Scopo di questo lavoro è stimolare una riflessione relativa all’uso di uno strumento validato per la valutazione delle terapie familiari e di coppia, lo SCORE-15. Tale strumento, di facile somministrazione, permette di ottenere una fotografia pressoché immediata delle caratteristiche della famiglia/coppia, del cambiamento e del processo terapeutico in corso. Sono stati presi in considerazione 171 Score in prima e ultima somministrazione, relativi a 69 famiglie/coppie, raccolti nell’arco temporale di 5 anni, presso la stessa scuola di formazione in terapia familiare e relazionale. Al fine di monitorare l’andamento nel tempo e gli esiti delle terapie condotte, sono stati confrontati i punteggi ottenuti dalla somministrazione dello SCORE a inizio e fine terapia, suddividendo il campione anche in base al ruolo dei membri all’interno della famiglia/coppia e alla tipologia di setting terapeutico (familiare, di coppia o genitoriale). L’obiettivo dell’indagine ha incluso anche il confronto tra il cambiamento percepito dal terapeuta, rilevato attraverso la specifica versione dello SCORE, e quello rilevato dal modello di questionario compilato dai membri della famiglia: tale confronto apre la possibilità di impiegare lo SCORE come alleato nella pratica clinica dei terapeuti. Viene infine presentato un caso clinico illustrativo del possibile uso dello Score come strumento orientativo e di feedback rispetto al lavoro terapeutico in svolgimento e svolto

Rate-Control or Rhythm-Control: Where do we stand?

Atrial fibrillation is the most common sustained rhythm disturbance and its prevalence is increasing worldwide due to the progressive aging of the population. Current guidelines clearly depict the gold standard management of acute symptomatic atrial fibrillation but the best-long term approach for first or recurrent atrial fibrillation is still debated with regard to quality of life, risk of new hospitalizations, and possible disabling complications, such as thromboembolic stroke, major bleeds and death. Some authors propose that regaining sinus rhythm in all cases, thus re-establishing a physiologic cardiac function not requiring a prolonged antithrombotic therapy, avoids the threat of intracranial or extracranial haemorrhages due to Vitamin K antagonists or aspirin. On the contrary, advocates of a rate control approach with an accurate antithrombotic prophylaxis propose that such a strategy may avoid the risk of cardiovascular and non cardiovascular side effects related to antiarrhythmic drugs. This review aims to explore the state of our knowledge in order to summarize evidences and issues that need to be furthermore clarified

Cardiac pacemaker battery discharge after external electrical cardioversion for broad QRS Complex Tachycardia

External electrical cardioversion or defibrillation may be necessary in patients with implanted cardiac pacemaker (PM) or implantable cardioverter defibrillator (ICD). Sudden discharge of high electrical energy employed in direct current (DC) transthoracic countershock may damage the PM/ICD system resulting in a series of possible device malfunctions. For this reason, when defibrillation or cardioversion must be attempted in a patient with a PM or ICD, some precautions should be taken, particularly in PM dependent patients, in order to prevent damage to the device. We report the case of a 76-year-old woman with a dual chamber PM implanted in the right subclavicular region, who received two consecutive transthoracic DC shocks to treat haemodynamically unstable broad QRS complex tachycardia after cardiac surgery performed with a standard sternotomic approach. Because of the sternal wound and thoracic drainage tubes together with the severe clinical compromise, the anterior paddle was positioned near the pulse generator. At the following PM test, a complete battery discharge was detected