Activation of Sonic hedgehog signaling in ventricular cardiomyocytes exerts cardioprotection against ischemia reperfusion injuries

International audience

Ventricular Standstill Following Intravenous Erythromycin and Borderline Hypokalemia

Ventricular standstill (VS) is a potentially fatal arrhythmia that is usually associated with syncope, if prolonged and is rarely asymptomatic[1]. Its mechanism involves either a lack of supraventricular impulse or an interruption in the transmission of these signals from the atria to the ventricles, resulting in a sudden loss of cardiac output[2]. Although rare, ventricular arrhythmias have been associated with intravenous (IV) erythromycin. However, to our knowledge, VS has not been reported following the administration of IV erythromycin. The Authors describe a rare case of asymptomatic VS and subsequent third-degree atrioventricular block, following the administration of IV erythromycin in a 49-year-old woman with borderline hypokalemia. Through this case, the Authors highlight the importance of cardiac monitoring and electrolyte replacement when administering IV erythromycin, as well as discuss several other mechanisms that contribute to ventricular arrhythmias.

Enhanced engraftment and repairing ability of human adipose-derived stem cells, conveyed by pharmacologically active microcarriers continuously releasing HGF and IGF-1, in healing myocardial infarction in rats

International audience

Left Ventricle Non-Compaction Myocardium and Thrombophilia in a Pregnant Woman

Non-compaction of the ventricular myocardium (NCM) is a genetic cardiomyopathy usually due to mutationof the G4.5 gene located in the Xq28 chromosomal region. This congenital disorder is characterized by pronounced trabeculations and intertrabecular recesses resulting from abnormal embryogenesis between the fifth and eighth fetal weeks. The reported prevalence in the general population is between 0.014% and 1.3%. The classic triad of complications includes heart failure, ventricular arrhythmias and systemic embolic events, although some patients have an asymptomatic form. NCM is commonly diagnosed by echocardiography, but contrast ventriculography, CT and MRI can also be used. Here we present a case of left ventricle NCM, manifested after respiratory infection, in a pregnant patient with congenital thrombophilia and a history of myocardial infarction.

Internship in arrhythmology

The arrhythmology focuses on the diagnosis and treatment of heart rhythm disorders and their complications, and has undergone a dramatic evolution over the past two decades. The widespread use of catheter ablation, the introduction of implantable cardioverter defibrillators for the prevention of sudden cardiac death and, finally, the development of cardiac resynchronization therapy led to a gradual loss of the impact of antiarrhythmic drugs as a therapeutic approach. This report was performed as a result of an internship performed in Cardiac Physiology with the duration of 400 hours. The main goal of the internship was to strengthen theoretical knowledge and acquire practical experience in the varied fields of arrhythmology, especially in the areas of Cardiac Pacing and Electrophysiology. During the internship were performed 41 electrophysiologic studies, where Atrioventricular Node Reentrant Tachycardia and Atrial Fibrillation were the most observed arrhythmias. New technologies such as three-dimensional mapping for electrophysiology studies are developing quickly and being use on a daily basis, as they prove to have safe and higher success rates. The proof is that in approximately half of the studies, one of the two mapping systems available, Carto or NavX, was used. In addition, were interrogated 283 pacemakers during the pacing clinics, being the dual chamber with DDD pacing mode the most encountered device. A large number of devices with Cardiac Resynchronization Therapy and/or Implantable Cardioverter Defibrillators were also observed. This report is divided into three chapters. Chapter I is constituted by a revision of the literature and includes concepts such as definition and mechanisms of cardiac arrhythmias; a brief description of the varied diagnostic tools and its recommendations; and a presentation of the different therapeutic approaches available and its indications. The second chapter is a descriptive drawing of the activity performed in the modules of Electrophysiology and Pacing. Lastly, the chapter III presents two clinical cases in Electrophysiology considered interesting from a clinical point of view.

Effects of two teaching interventions on nursing students’ acquisition of competence in ECG interpretation

Purpose: Nurse ability to recognise patient arrhythmias could contribute to preventing in-hospital cardiac arrest. Research suggests that nurses and nursing students lack competence in electrocardiogram (ECG) interpretation. The aim of this study was to compare the effects of two training strategies on nursing students’ acquisition of competence in ECG interpretation. Materials and methods: A controlled randomised trial with 98 nursing students. Divided in groups of 12–16, participants were randomly allocated to one of the following 3-h teaching intervention groups: 1) traditional instructor-led (TILG), and 2) flipped classroom (FCG). Participants’ competence in ECG interpretation was measured in terms of knowledge (%), skills (%) and self-efficacy (%) using a specifically designed and previously validated toolkit at pre-test and post-test. Two-way MANOVA explored the interaction effect between ‘teaching group’ and ‘time of assessment’ and its impact on participants’ competence. Within-group differences at pre-test and post-test were explored by carrying out paired t-tests. Between-group differences at pre- and post-test were examined by performing independent t-test analysis. Results: There was a statistically significant interaction effect between ‘teaching group’ and ‘time of assessment’ on participants’ competence in ECG interpretation (F(3,190) = 86.541, p = 0.001; Wilks’ Λ = 0.423). At pre-test, differences in knowledge (TILG = 35.12 ± 12.07; FCG = 35.66 ± 10.66), skills (TILG = 14.05 ± 10.37; FCG = 14.82 ± 14.14), self-efficacy (TILG = 46.22 ± 23.78; FCG = 40.01 ± 21.77) and all other variables were non-significant (p > 0.05). At post-test, knowledge (TILG = 55.12 ± 14.16; FCG = 94.2 ± 7.31), skills (TILG = 36.90 ± 16.45; FCG = 86.43 ± 14.32) and self-efficacy (TILG = 70.78 ± 14.55; FCG = 79.98 ± 10.35) had significantly improved, regardless of the training received (p < 0.05). Nonetheless, participants in the FCG scored significantly higher than participants in the TILG in knowledge, skills and self-efficacy (p < 0.05). Conclusion: Flipping the classroom for teaching ECG interpretation to nursing students may be more effective than using a traditional instructor-led approach in terms of immediate acquisition of competence in terms of knowledge, skills and self-efficacy. Further research on the effects of both teaching strategies on the retention of the competence will be undertaken.

Equine exercise electrocardiogram : standardized lungeing test

Dissertação de Mestrado Integrado em Medicina Veterinária

Implantation of mouse embryonic stem cell-derived cardiac progenitor cells preserves function of infarcted murine hearts.

Stem cell transplantation holds great promise for the treatment of myocardial infarction injury. We recently described the embryonic stem cell-derived cardiac progenitor cells (CPCs) capable of differentiating into cardiomyocytes, vascular endothelium, and smooth muscle. In this study, we hypothesized that transplanted CPCs will preserve function of the infarcted heart by participating in both muscle replacement and neovascularization. Differentiated CPCs formed functional electromechanical junctions with cardiomyocytes in vitro and conducted action potentials over cm-scale distances. When transplanted into infarcted mouse hearts, CPCs engrafted long-term in the infarct zone and surrounding myocardium without causing teratomas or arrhythmias. The grafted cells differentiated into cross-striated cardiomyocytes forming gap junctions with the host cells, while also contributing to neovascularization. Serial echocardiography and pressure-volume catheterization demonstrated attenuated ventricular dilatation and preserved left ventricular fractional shortening, systolic and diastolic function. Our results demonstrate that CPCs can engraft, differentiate, and preserve the functional output of the infarcted heart.

Long-term benefit of early pre-reperfusion metoprolol administration in patients with acute myocardial infarction: Results from the Metocard-CNIC trial (Effect of Metoprolol in Cardioprotection during an Acute Myocardial Infarction)

The goal of this trial was to study the long-term effects of intravenous (IV) metoprolol administration before reperfusion on left ventricular (LV) function and clinical events. Early IV metoprolol during ST-segment elevation myocardial infarction (STEMI) has been shown to reduce infarct size when used in conjunction with primary percutaneous coronary intervention (pPCI). The METOCARD-CNIC (Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction) trial recruited 270 patients with Killip class ≤II anterior STEMI presenting early after symptom onset (<6 h) and randomized them to pre-reperfusion IV metoprolol or control group. Long-term magnetic resonance imaging (MRI) was performed on 202 patients (101 per group) 6 months after STEMI. Patients had a minimal 12-month clinical follow-up. Left ventricular ejection fraction (LVEF) at the 6 months MRI was higher after IV metoprolol (48.7 ± 9.9% vs. 45.0 ± 11.7% in control subjects; adjusted treatment effect 3.49%; 95% confidence interval [CI]: 0.44% to 6.55%; p = 0.025). The occurrence of severely depressed LVEF (≤35%) at 6 months was significantly lower in patients treated with IV metoprolol (11% vs. 27%, p = 0.006). The proportion of patients fulfilling Class I indications for an implantable cardioverter-defibrillator (ICD) was significantly lower in the IV metoprolol group (7% vs. 20%, p = 0.012). At a median follow-up of 2 years, occurrence of the pre-specified composite of death, heart failure admission, reinfarction, and malignant arrhythmias was 10.8% in the IV metoprolol group versus 18.3% in the control group, adjusted hazard ratio (HR): 0.55; 95% CI: 0.26 to 1.04; p = 0.065. Heart failure admission was significantly lower in the IV metoprolol group (HR: 0.32; 95% CI: 0.015 to 0.95; p = 0.046). In patients with anterior Killip class ≤II STEMI undergoing pPCI, early IV metoprolol before reperfusion resulted in higher long-term LVEF, reduced incidence of severe LV systolic dysfunction and ICD indications, and fewer heart failure admissions.

Early intravenous beta-blockers in patients with ST-segment elevation myocardial infarction before primary percutaneous coronary intervention

The impact of intravenous (IV) beta-blockers before primary percutaneous coronary intervention (PPCI) on infarct size and clinical outcomes is not well established. This study sought to conduct the first double-blind, placebo-controlled international multicenter study testing the effect of early IV beta-blockers before PPCI in a general ST-segment elevation myocardial infarction (STEMI) population. STEMI patients presenting <12 h from symptom onset in Killip class I to II without atrioventricular block were randomized 1:1 to IV metoprolol (2 × 5-mg bolus) or matched placebo before PPCI. Primary endpoint was myocardial infarct size as assessed by cardiac magnetic resonance imaging (CMR) at 30 days. Secondary endpoints were enzymatic infarct size and incidence of ventricular arrhythmias. Safety endpoints included symptomatic bradycardia, symptomatic hypotension, and cardiogenic shock. A total of 683 patients (mean age 62 ± 12 years; 75% male) were randomized to metoprolol (n = 336) or placebo (n = 346). CMR was performed in 342 patients (54.8%). Infarct size (percent of left ventricle [LV]) by CMR did not differ between the metoprolol (15.3 ± 11.0%) and placebo groups (14.9 ± 11.5%; p = 0.616). Peak and area under the creatine kinase curve did not differ between both groups. LV ejection fraction by CMR was 51.0 ± 10.9% in the metoprolol group and 51.6 ± 10.8% in the placebo group (p = 0.68). The incidence of malignant arrhythmias was 3.6% in the metoprolol group versus 6.9% in placebo (p = 0.050). The incidence of adverse events was not different between groups. In a nonrestricted STEMI population, early intravenous metoprolol before PPCI was not associated with a reduction in infarct size. Metoprolol reduced the incidence of malignant arrhythmias in the acute phase and was not associated with an increase in adverse events.

Predictors of in-hospital mortality among cardiogenic shock patients. Prognostic and therapeutic implications

Cardiogenic shock (CS) has a poor prognosis. The heterogeneity in the mortality through different subgroups suggests that some factors can be useful to perform risk stratification and guide management. We aimed to find predictors of in-hospital mortality in these patients. We analyzed all cases of cardiogenic shock due to medical conditions admitted in our intensive acute cardiovascular care unity from November 2010 till November 2015. Clinical, biochemical and hemodynamic variables were registered, as was the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile at 24 h of CS diagnosis. From a total of 281 patients, 28 died within the first 24 h and were not included in the analysis. A total of 253 patients survived the first 24 h, mean age was 68.8 ± 14.4 years, and 174 (68.8%) were men. Etiologies: acute coronary syndrome 146 (57.7%), acute heart failure 60 (23.7%), arrhythmias 35 (13.8%), and others 12 (4.8%). A total of 91 patients (36.0%) died during hospitalization. We found the following independent predictors of in-hospital mortality: age (odds ratio [OR] 1.032, 95% confidence interval [CI] 1.003–1.062), blood glucose (OR 1.004, 95% CI 1.001–1.008), heart rate (OR 1.014, 95% CI 1.001–1.028), and INTERMACS profile (OR 0.168, 95% CI 0.107–0.266). In patients with CS the INTERMACS profile at 24 h of diagnosis was associated with higher in-hospital mortality. This and other prognostic variables (age, blood glucose, and heart rate) may be useful for risk stratification and to select appropriate medical or invasive interventions.

Arritmias ventriculares en superrespondedores a la terapia de resincronización cardiaca

La terapia de resincronización cardiaca se asocia a mejora de la calidad de vida y reducción de la morbimortalidad de los pacientes con disfunción ventricular grave y QRS ancho. Sobre su papel en la reducción de arritmias ventriculares, hay más discusión. Se comparó la incidencia de arritmias ventriculares en pacientes portadores de desfibrilador automático implantable con función de resincronización cardiaca, según el grado de respuesta ecocardiográfica a la resincronización. Se clasificó a los pacientes en tres subgrupos: superrespondedores, respondedores y no respondedores. Se incluyó a 196 pacientes seguidos durante una mediana de 30,1 [intervalo intercuartílico, 18,0-55,1] meses. Se documentó presencia de arritmias ventriculares en 37 pacientes (18,8%); 3 pacientes (5,9%) del grupo de superrespondedores presentaron arritmias ventriculares, en comparación con 14 (22,2%) del grupo de respondedores y 20 (24,4%) del grupo de no respondedores (p = 0,025). En el análisis multivariable, el implante del dispositivo en prevención secundaria (odds ratio = 4,04; intervalo de confianza del 95%, 1,52-10,75; p = 0,005), la ausencia de superrespuesta ecocardiográfica (odds ratio = 3,81; intervalo de confianza del 95%, 1,04-13,93; p = 0,043), un QRS > 160 ms (odds ratio = 2,39; intervalo de confianza del 95%, 1,00-1,35; p = 0,049) y el tratamiento con amiodarona (odds ratio = 2,47; intervalo de confianza del 95%, 1,03-5,91; p = 0,041) fueron los únicos predictores independientes de aparición de arritmias ventriculares. Los pacientes superrespondedores a la terapia de resincronización cardiaca presentan una disminución significativa en la incidencia de arritmias ventriculares respecto a los demás pacientes. Pese a ello, los episodios arrítmicos no llegan a desaparecer por completo en este subgrupo.

Efficacy and safety of out-of-hospital intravenous metoprolol administration in anterior ST-segment elevation acute myocardial infarction: insights from the METOCARD-CNIC trial

We seek to examine the efficacy and safety of prereperfusion emergency medical services (EMS)–administered intravenous metoprolol in anterior ST-segment elevation myocardial infarction patients undergoing eventual primary angioplasty. This is a prespecified subgroup analysis of the Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction trial population, who all eventually received oral metoprolol within 12 to 24 hours. We studied patients receiving intravenous metoprolol by EMS and compared them with others treated by EMS but not receiving intravenous metoprolol. Outcomes included infarct size and left ventricular ejection fraction on cardiac magnetic resonance imaging at 1 week, and safety by measuring the incidence of the predefined combined endpoint (composite of death, malignant ventricular arrhythmias, advanced atrioventricular block, cardiogenic shock, or reinfarction) within the first 24 hours. From the total population of the trial (N=270), 147 patients (54%) were recruited during out-of-hospital assistance and transferred to the primary angioplasty center (74 intravenous metoprolol and 73 controls). Infarct size was smaller in patients receiving intravenous metoprolol compared with controls (23.4 [SD 15.0] versus 34.0 [SD 23.7] g; adjusted difference –11.4; 95% confidence interval [CI] –18.6 to –4.3). Left ventricular ejection fraction was higher in the intravenous metoprolol group (48.1% [SD 8.4%] versus 43.1% [SD 10.2%]; adjusted difference 5.0; 95% CI 1.6 to 8.4). Metoprolol administration did not increase the incidence of the prespecified safety combined endpoint: 6.8% versus 17.8% in controls (risk difference –11.1; 95% CI –21.5 to –0.6). Out-of-hospital administration of intravenous metoprolol by EMS within 4.5 hours of symptom onset in our subjects reduced infarct size and improved left ventricular ejection fraction with no excess of adverse events during the first 24 hours.

Left atrial anatomy relevant to catheter ablation

The rapid development of interventional procedures for the treatment of arrhythmias in humans, especially the use of catheter ablation techniques, has renewed interest in cardiac anatomy. Although the substrates of atrial fibrillation (AF), its initiation and maintenance, remain to be fully elucidated, catheter ablation in the left atrium (LA) has become a common therapeutic option for patients with this arrhythmia. Using ablation catheters, various isolation lines and focal targets are created, the majority of which are based on gross anatomical, electroanatomical, and myoarchitectual patterns of the left atrial wall. Our aim was therefore to review the gross morphological and architectural features of the LA and their relations to extracardiac structures. The latter have also become relevant because extracardiac complications of AF ablation can occur, due to injuries to the phrenic and vagal plexus nerves, adjacent coronary arteries, or the esophageal wall causing devastating consequences.

Le pore oméga, un défaut biophysique commun aux mutations des canaux Nav1.5 causant le développement des arythmies associées à la cardiomyopathie dilatée

Les canaux sodiques dépendants du voltage (Nav) sont des protéines transmembranaires largement exprimées au sein de l’organisme. Ils sont responsables de l’initiation des potentiels d’action au niveau des cellules excitables et régissent ainsi de nombreuses fonctions physiologiques telles que les fonctions cognitives et sensorielles, les fonctions motrices et la fonction cardiaque. Au niveau du coeur, le sous-type Nav1.5 est majoritairement exprimé à la surface des cardiomyocytes. Leurs dysfonctions sont traditionnellement associées à de nombreux troubles électriques cardiaques. Des mutations de ces canaux ont récemment été reliées au développement d’un phénotype clinique complexe associant diverses arythmies et la cardiomyopathie dilatée (DCM), une atteinte morphologique. L’objectif de mon doctorat a donc été l’identification mais aussi la caractérisation d’un potentiel défaut biophysique commun à l’ensemble des mutations Nav1.5 associées au développement de ce phénotype clinique atypique. Premièrement, nous nous sommes intéressés à deux mutations des canaux Nav1.5 retrouvées chez des patients atteints de DCM, et dont les altérations biophysiques ont été décrites comme divergentes. L’étude parallèle de ces deux mutants nous a amenés à identifier une caractéristique commune : la création d’une nouvelle voie de perméation alternative au sein des canaux Nav1.5, le pore oméga. Dans un second temps, nous avons souhaité consolider l’association entre la création du pore oméga et le développement pathologique. Cette seconde étude portant sur deux autres mutants Nav1.5 a permis de confirmer l’apparition d’un pore oméga et ainsi d’accroître la suspicion du caractère délétère de ce pore oméga. Finalement, à l’aide d’une cinquième mutation des canaux Nav1.5, nous avons investigué les conséquences physiopathologiques de la création d’un pore oméga. Cette étude, a clairement démontré les conséquences néfastes d’un tel pore au niveau de l’homéostasie ionique cellulaire. Ces perturbations se répercutent par la suite sur les signaux électriques, les propriétés morphologiques mais aussi fonctionnelles des cardiomyocytes. Les études menées lors de mon doctorat ont ainsi abouti à l’identification du pore oméga comme étant une caractéristique biophysique commune aux mutations des canaux Nav1.5 associées au développement des arythmies et de la dilatation cardiaque.