Dimitri Arangalage

Ultrasound-based teaching of cardiac anatomy and physiology to undergraduate medical students.

BACKGROUND Ultrasonography is a non-invasive imaging modality that offers the opportunity to teach living cardiac anatomy and physiology. AIMS The objectives of this study were to assess the feasibility of integrating an ultrasound-based course into the conventional undergraduate medical teaching programme and to analyse student and teacher feedback. METHODS An ultrasound-based teaching course was implemented and proposed to all second-year medical students (n=348) at the end of the academic year, after all the conventional modules at our faculty. After a brief theoretical and practical demonstration, students were allowed to take the probe and use the ultrasound machine. Students and teachers were asked to complete a survey and were given the opportunity to provide open feedback. RESULTS Two months were required to implement the entire module; 330 (95%) students (divided into 39 groups) and 37 teachers participated in the course. Student feedback was very positive: 98% of students agreed that the course was useful; 85% and 74% considered that their understanding of cardiac anatomy and physiology, respectively, was improved. The majority of the teachers (97%) felt that the students were interested, 81% agreed that the course was appropriate for second-year medical students and 84% were willing to participate to future sessions. CONCLUSIONS Cardiac anatomy and physiology teaching using ultrasound is feasible for undergraduate medical students and enhances their motivation to improve their knowledge. Student and teacher feedback on the course was very positive.

Agreement between the new EuroSCORE II, the Logistic EuroSCORE and the Society of Thoracic Surgeons score: Implications for transcatheter aortic valve implantation

BACKGROUND The Logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) and the Society of Thoracic Surgeons (STS) score are routinely used to identify patients at high surgical risk as potential candidates for transcatheter aortic valve implantation (TAVI). AIMS To compare the new EuroSCORE II with the Logistic EuroSCORE and the STS score. METHODS From October 2006 to June 2011, patients with severe symptomatic aortic stenosis who underwent a TAVI were enrolled prospectively. RESULTS Among 272 patients, the EuroSCORE II was significantly lower and moderately correlated with the Logistic EuroSCORE (9±8% vs. 23±14%, P<0.01; r=0.61, P<0.001), but similar to and poorly correlated with the STS (10±9%, P=0.10; r=0.25, P<0.001). Based on recommended high-risk thresholds (Logistic EuroSCORE≥20%; STS≥10%), a EuroSCORE II≥7% provided the best diagnostic value. However, using the EuroSCORE II, Logistic EuroSCORE or STS score, only 51%, 58% and 37% of patients, respectively, reached these thresholds. Contingency analyses showed that agreements between the EuroSCORE II and the Logistic EuroSCORE or the STS score were modest or poor, respectively, with a risk assessment different in 28% and 36% of patients, respectively. CONCLUSIONS A EuroSCORE II≥7% corresponded to a Logistic EuroSCORE≥20% or STS score≥10%, but correlations and agreements were at best modest and only approximately half of the patients reached these thresholds. Our results highlight the limits of current scoring systems and reinforce the European guidelines stressing the importance of clinical judgment in addition to risk scores.

Relationship between Cognitive Impairment and Echocardiographic Parameters: A Review

With >24 million people affected worldwide, dementia is one of the main public health challenges modern medicine has to face. The path leading to dementia is often long, with a wide spectrum of clinical presentations, and preceded by a long preclinical phase. Previous studies have demonstrated that clinical strokes and covert vascular lesions of the brain contribute to the risk for developing dementia. Although it is not yet known whether preventing such lesions reduces the risk for dementia, it is likely that starting preventive measures early in the course of the disease may be beneficial. Echocardiography is a widely available, relatively inexpensive, noninvasive imaging modality whereby morphologically or hemodynamically derived parameters may be integrated easily into a risk assessment model for dementia. The aim of this review is to analyze the information that has accumulated over the past two decades on the prognostic value of echocardiographic factors in cognitive impairment. The associations between cognitive impairment and echocardiographic parameters, including left ventricular systolic and diastolic indices, left atrial morphologic parameters, cardiac output, left ventricular mass, and aortic root diameter, have previously been reported. In the light of these studies, it appears that echocardiography may help further improve currently used risk assessment models by allowing detection of subclinical cardiac abnormalities associated with future cognitive impairment. However, many limitations, including methodologic heterogeneity and the observational designs of these studies, restrict the scope of these results. Further prospective studies are required before integrating echocardiography into a preventive strategy.

Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) induced by immune checkpoint inhibitors

We read with great interest the articles by Kostine et al 1 (and subsequent correspondence by Arnaud et al 2) and by Belkhir et al. 3 The prognosis of various cancer types has dramatically improved since the advent of immune checkpoint inhibitors (ICIs). Yet, ICI therapy is associated with frequent and potentially organ or life-threatening immune-related adverse events (irAEs), generally mimicking autoimmune or inflammatory conditions.4 Rheumatic disorders have been reported in this setting, mainly rheumatoid arthritis, polymyalgia rheumatica and systemic lupus erythematosus.1–3 Vasculitis seems to occur more seldom, with predominantly medium-vessel to large-vessel involvement.5 Here, we report on a patient with eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss syndrome) following treatment with ICI for a stage IV melanoma. A 34-year-old non-smoking female patient with stage IV melanoma was treated with ipilimumab (a monoclonal antibody targeting the cytotoxic T–lymphocyte associated antigen …

Survival After Fulminant Myocarditis Induced by Immune-Checkpoint Inhibitors

Survival After Fulminant Myocarditis Induced by Immune-Checkpoint Inhibitors Background: Some patients with metastatic melanoma live longer when they are treated with combinations of immune-checkpoint inhibitors (1, 2). However, up to 55% of these patients experience high-grade, immune-related adverse events (3–5). In phase 3 trials of these drugs, immunerelated adverse events involving the heart affected only 0.19% of patients; fulminant myocarditis was the most serious of these (5). Objective: To report what we believe to be the first patient to survive fulminant myocarditis induced by immunecheckpoint inhibitors. Case Report: We admitted a 35-year-old woman with unresectable stage IIIc melanoma of the neck who developed progressive dyspnea 15 days after the first infusion of ipilimumab, 3 mg/kg of body weight, and nivolumab, 1 mg/kg. Physical examination was unremarkable. Electrocardiography revealed sinus tachycardia with a right bundle branch block and ST-segment elevation in the anteroseptal and inferolateral leads. Troponin I levels were 210 μg/L (normal, < 0.045 μg/L), and total creatine kinase levels were 187.6 μkat/L (normal, 0.4 to 3.2 μkat/L). Transthoracic echocardiography revealed a left ventricular ejection fraction of 50%. We discontinued the immunotherapy and began treatment with intravenous methylprednisolone, 1 g/d, and intravenous immunoglobulin therapy (Figure 1). Cardiac magnetic resonance imaging performed the next day showed severely impaired left and right ventricular ejection fractions and diffuse subepicardial late gadolinium enhancement, which confirmed the diagnosis of myocarditis (Figure 2). Four days after admission, the patient developed refractory ventricular tachycardia that led to emergency circulatory support using extracorporeal membrane oxygenation. Left ventricular ejection fraction measured by echocardiography decreased to 10%. We discontinued immunoglobulin therapy and performed plasma exchanges for 3 days. The patient developed hyperthyroidism with an undetectable thyroid-stimulating hormone level, and we diagnosed immune-related hyperthyroidism. This condition progressed to hypothyroidism within 3 days and required levothyroxine therapy. After 8 days of circulatory support, we began tacrolimus therapy with a target whole blood level of 10 to 15 ng/mL. The patient began to improve 2 days later and left the intensive care unit with a left ventricular ejection fraction of 35% on day 18 of admission. At 3-month follow-up, the patient had completely recovered with a left ventricular ejection fraction of 60%. Discussion: To reduce the likelihood of autoimmune disease, 2 cell pathways help keep T-cell immune function in check: cytotoxic T-lymphocyte–associated antigen 4 and programmed death 1. They are known as immune checkpoints, and inhibiting them increases immune system activity. This patient received 1 drug that inhibited the former pathway (ipilimumab) and another drug that inhibited the latter (nivolumab). Recent reports suggest that blocking both pathways may increase the incidence of fulminant myocarditis, and to our knowledge, all published cases of this condition induced by immune-checkpoint inhibitors have been fatal (3, 4). This case report shows that this adverse effect may be reversed, which may justify more aggressive attempts to save future patients. Moreover, 64% of patients who receive drugs that block both pathways survive at least 2 years even when treatment must be discontinued prematurely (1). The magnetic resonance imaging finding of extensive subepicardial late gadolinium enhancement of both ventricles has not been reported previously in patients with fulminant myocarditis induced by immune-checkpoint inhibitors. We advise clinicians to look for it when considering the possibility of this condition. Most immune-related adverse events from checkpoint inhibitors are manageable with corticosteroids and immunoFigure 1. Timeline of LVEF and treatment of fulminant myocarditis during hospitalization in the intensive care unit.

Immune checkpoint inhibitor rechallenge in patients with immune-related myositis

Therapeutic management of many cancers has been revolutionised by the development of immune checkpoint inhibitors (ICI) targeting antiprogrammed death 1 (PD-1)/ligand 1 (PDL1) and anticytotoxic T-lymphocyte antigen 4 leading to durable responses.1 ICIs however can induce several immune-related adverse events (irAE) including musculoskeletal irAEs.2 Among them, ICI-related myositis can be severe and sometimes life threatening.3 4 The current management includes permanent discontinuation of ICIs and steroid treatment. To date, very little is known about the risk of irAE recurrence in case of ICI rechallenge,5 6 especially in myositis for which no case of rechallenge has yet been reported. Through two cases, we report the safety of resuming anti-PD-1/PDL1 in patients …

Usefulness of Late Iodine Enhancement on Spectral CT in Acute Myocarditis

Clinical presentation of acute myocarditis is heterogeneous and often leads to coronary angiography to rule out acute coronary syndrome (ACS). Noninvasive evaluation relies on cardiac magnetic resonance (CMR), with late gadolinium enhancement (LGE) being one of the main parameters [(1)][1]. However

0261 : Prognostic value of the “infarct-like” pattern and cardiovascular magnetic resonance parameters for long-term outcome after an acute myocarditis

Objective To assess the prognostic value of the clinically infarct-like pattern and cardiac magnetic resonance (CMR) parameters on long-term outcome after acute myocarditis. Methods Between 2006 and 2015, 112 consecutive patients with CMRbased diagnosis of acute myocarditis according to the Louise-Lake criteria were identified in our institution. Of them, 88 were available for clinical follow-up and represent our studied population. Patients were divided into Infarct-like, (n=48) (association of acute chest pain, raised Troponin and STElevation) and non-infarct-like, (n=40) with any other presentation. The composite primary endpoint of Major CardioVascular Events included: all-cause mortality, cardiac mortality, recurrence of myocarditis, heart failure or sustained ventricular tachycardia. Results During follow-up, 21 patients (24%) experienced MACE and the infarct-like patients were significantly more at risk for MACE than group B patients (HR 2.4, 95% CI [1.01 – 5.80] p=0.04). Patients of the Group A exhibited in particular a higher risk of sustained ventricular tachycardia and recurrence of myocarditis as compared with group B patients (p=0.03). Infarct-like patients had lower CMR-derived left (p=0.03) and right (p=0.001) ventricular ejection fractions, and exhibited larger areas of late Gadolinium enhancement (LGE) (p=0.001) as compared with group B patients. In multivariate analysis, both initial NYHA functional class>II and LGE mass were independent predictors for long-term MACE occurrence after acute myocarditis (HR 5.8 and 1.07 per g respectively, p=0.007). Moreover, a threshold of LGE mass>17g provided a high discrimination for MACE occurrence (AUC of 0.81). Conclusion The infarct-like pattern of acute myocarditis is associated with MACE, especially sustained ventricular tachycardia and recurrence of myocarditis. The author hereby declares no conflict of interest

0083 : Hyperhemia on the first-pass MRI perfusion for the diagnosis of acute myocarditis

Background MRI is the current way for the diagnosis of acute myocarditis, based on the Lake Louise criteria (presence of at least two of the three following criteria: myocardial edema, hyperaemia and/or a late Gadolinium enhancement). The first-pass perfusion sequence, used for detecting myocardial ischemia, may also be used to highlight a myocardial hyperemia in acute myocarditis. Purpose The aim of our study was to assess subepicardial hyperemia, seen on the first pass perfusion sequence by MRI, as a new method for the diagnosis of acute myocarditis. Method 47 patients (mean age = 42.4±15,6 years; 35 men) with acute myocarditis were included and compared to 16 healthy controls (without heart disease). The first-pass perfusion was evaluated by two blinded observers and compared to myocardial late Gadolinium enhancement, considered the reference method for the diagnosis of acute myocarditis, using both a qualitative (visual analysis) and a semi-quantitative method (ratio of the signals: infarction hyperaemia / healthy myocardium). Results 24 (51.1%) patients with myocarditis exhibited detectable hyperemia. Qualitative analysis showed good inter-observer variability (kappa = 0.75). There was an increase of the signal intensity in the myocardium with hyperhemia as compared to the adjacent normal myocardium (myocarditis vs controls: 1.08±0.03 vs 0.95±0.05, p=0.03; myocarditis with hyperhemia vs myocarditis non hyperhemia: 1.22±0.04 vs 0.94 ±0.04, p Conclusion Hyperhemia on the First-pass perfusion sequence, is a valuable and reproducible tool for the diagnosis of acute myocarditis. The author hereby declares no conflict of interest

0574: Determinants and prognostic value of Galectin-3 in patients with aortic valve stenosis - the COFRASA-GENERAC study

Background Identifying subgroups of asymptomatic patients with aortic stenosis (AS) who may benefit from early intervention is a critical challenge due to the risk of sudden death and irreversible myocardial dysfunction without preceding symptoms. In this study, we analyzed the determinants and prognostic value of Galectin-3 in a large cohort of patients with AS. Methods We included patients with at least mild degenerative AS enrolled in 2 ongoing prospective clinical studies, COFRASA and GENERAC, aiming at assessing the determinants of AS occurrence and progression. Results Between November 2006 and July 2013, 583 patients were prospectively enrolled. Severe AS was diagnosed in 312 (56%) patients among whom 220 (38%) were symptomatic. Age (p No significant association was found between Galectin-3 and echocardio-graphic parameters of AS severity including aortic valve area (p=0.41), mean transvalvular gradient (p=0,27), and AS jet velocity (p=0.52). Galectin-3 did not provide diagnostic evidence of severe AS (area under the curve=0.53). Galectin-3 was not influenced by symptomatic status. Echocardiographic parameters of LV remodeling were not associated with Galectin-3 in multivariate analysis. Event-free survival analysis revealed no prognostic value of Galectin-3. Conclusions The main determinants of Galectin-3 level were age and renal function. There was no association between Galectin-3 and symptomatic status and echocardiographic parameters associated with LV remodeling. Galectin-3 didn’t provide prognostic information on the occurrence of AS related events. These results do not support the use of Galectin-3 in the decision making process of patients with AS.