Sudden Death without a Clear Cause after Comprehensive Investigation: An Example of Forensic Approach to Atypical/Uncertain Findings

Sudden death (SD) is defined as the unexpected natural death occurred within an hour after the onset of symptoms or from the last moment the subject has been seen in a healthy condition. Brugada syndrome (BrS) is one of the most remarkable cardiac causes of SD among young people. We report the case of a 20-year-old man who suddenly died after reportedly having smoked cannabis. Autopsy, toxicology, and genetic testing were performed. Autopsy found a long and thick myocardial bridging (MB) at 2 cm from the beginning of the left anterior descending coronary artery. Furthermore, at the histopathological examination, fibrosis and disarray in myocardial area above the MB, fatty tissue in the right ventricle and fibrosis of the sino-atrial node area were found. Toxicology testing was inconclusive, while genetic testing found a rare missense variant of the TTN gene, classified as likely benign, and a variant of unknown significance in the SLMAP gene (a gene that can be associated with BrS). Hence, despite several atypical features were found, no inference on the cause of the death could be made under current evidence.

Visualizing myocardial injury from elective cardioversion with CMR

Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Association of Cardiothoracic Anaesthesiologists Research Grant Background Despite everyday use of electrical interventions in cardiovascular care, the extent and type of concomitant myocardial injury is not fully understood. Current literature disagrees about the question whether and how cardioversion or defibrillation damage the myocardium, especially when serologic markers are used. Such markers are not always cardiac-specific, nor diagnostic for type and region of myocardial injury. These limitations may be overcome by parametric T1 and T2 mapping. We aimed to investigate whether the acute and long-term impact of electrical cardioversion on myocardial structure and function is detectable using CMR imaging. Methods Patients scheduled for elective cardioversion were enrolled to undergo three CMR exams (3 Tesla): on the morning prior to cardioversion to assess pre-existing injury; two to five hours after cardioversion to assess the acute response; and six to ten weeks later to investigate chronic injury. The CMR exam studied left ventricular (LV) function, T2 mapping to measure edema, and extracellular volume (ECV) from T1 maps to measure diffuse fibrosis. Both the degree of injury and proportion (%) of myocardial area affected were analysed. Results Eight patients completed the study, requiring 1-2 shocks (totalling 120-300 J biphasic energy) to achieve sinus rhythm. LV ejection fraction increased after cardioversion from 47 ± 13% to 55 ± 15% (p = 0.020), and was 52 ± 16% at the third exam (p = 0.199). Even prior to intervention, some patients showed edema (baseline T2 > 40ms) afflicting 49 ± 23% of their LV myocardium. Area affected by edema expanded to 72 ± 18% after cardioversion (p = 0.002) and returned to 54 ± 24% by the third exam. T2 rose from baseline (40.4 ± 1.8ms) after cardioversion acutely to 44.1 ± 5.2ms (p = 0.028) and normalized until the late exam (40.8 ± 3.1ms). Myocardial area affected by diffuse fibrosis (ECV > 30%) was 28.3 ± 9.4% at baseline and 38.8 ± 18.9% late after cardioversion (p = 0.018). Pathologic T2 increases (indicative of edema) were not observed in all patients, but individuals with higher baseline ECV also experienced greater T2 increase after cardioversion (r = 0.840, p = 0.036). Conclusion Elective cardioversion improves LV systolic function, but also aggravates myocardial edema and possibly adds to diffuse fibrosis during several weeks thereafter. Such sequelae of cardioversion were observed mainly in patients with a greater burden of pre-existing myocardial injury. More data is needed to corroborate these preliminary findings and to study whether this type of myocardial injury predicts worse outcome. Moreover, changes in CMR markers caused by electrical interventions including defibrillation, may have the potential to confound diagnostic assessments of the underlying cardiac injury. Abstract Figure

The imortance of hyperemic contrast velocity assessment on image-based fractional flow reserve calculation

Aims Image-based fractional flow reserve (FFR) calculations reported good agreement with FFR measured invasively. The purpose of this study was to perform a retrospective analysis of the cases of a previous study on less invasive FFR calculation (simple FFR: FFRsim) as a simple calculation from hyperemic contrast flow data and three-dimensional coronary parameters. Methods and results We aimed to analyze the relations between the pressure wire-based FFR (FFRmeas) and fixed FFRsim: calculated from the fixed hyperemic velocity, rest FFRsim: calculated using the non-hyperemic frame count data to extrapolate the hyperemic velocity (based on the database used in the FAVOR1 study) hyp FFRsim: the hyperemic velocity derived from the frame count assessment during vasodilation.To calculate the frame count reserve (CFRFC) the resting frame count was divided by the hyperemic frame count; this value was then used to determine the CFRFC/FFRmeas ratio as an indicator of microvascular function in the corresponding myocardial area of the measured coronary vessel. A total of 50 lesions with intermediate stenosis were investigated. Correlation between rest FFRsim (from the resting frame count extrapolated to the hyperemic velocity) and FFRmeas was lower than the correlation between hyp FFRsim and FFRmeas (r=0.761 vs. 0.824). Based on ROC curve analysis for predicting the abnormal FFR of ≤0.80 the AUC were significantly higher for the hyperemia-based parameter than those calculated from resting frame counts. Significantly higher AUC were detected by the hyp FFRsim than by the rest FFRsim: 0.936 (95% CI: 0.828 to 0.985) vs. 0.862 (CI: 0.734 to 0.943); p=0.011. Linear regression analyses between the FFRsim (either by fixed FFRsim or by rest FFRsim or by hyp FFRsim methods) and the FFRmeas showed higher intercepts and less steep of the slopes in the subgroups with presence of microvascular disease defined as CFRFC/FFRmeas <2 than in those without microvascular disease (CFRFC/FFRmeas >2); the difference reached significant level (p=0.019) when calculated by rest FFRsim. Conclusions Hyperemic challenge either by adenosine or regadenoson is required for exact image-based FFR calculation especially in cases of suspicion for microvascular coronary disease. Funding Acknowledgement Type of funding source: None

Role of reciprocal changes in predicting short term prognosis of patients of acute STEMI

Background: Recent studies indicate that STEMI with reciprocal changes is associated with more myocardial area at risk, larger infarct size and less ejection fraction as compared to STEMI without reciprocal changes. We undertook this study for correlating clinical outcome and complications in patients with and without reciprocal changes in ECG in acute STEMI.Methods: Eighty patients were divided into two groups of forty each. One having reciprocal changes in ECG and one without reciprocal changes. The KILLIP class of each patient at time of admission was noted. Patients were monitored for development of any complication, Left ventricular ejection fraction (LVEF) and mortality. BNP levels, Trop I levels, Hba1c levels were obtained at time of admission. Echocardiography was done on the second day of the admission.Results: The patients with reciprocal changes were found to be having a higher KILLIP class on admission. The LVEF of patients with reciprocal changes and who subsequently went on to develop complications was lower than those without reciprocal changes. The number of patients having unsuccessful thrombolysis was significantly higher in the group with reciprocal changes.Conclusions: There was significant association of reciprocal changes in ECG with higher Hba1c, higher KILLIP class and higher incidence of unsuccessful thrombolysis. Moreover, the sensitivity of other markers of poor clinical outcomes, such as BNP and LVEF increases in patients having reciprocal changes in their ECG. The monitoring in such patients should thus be more intensive.

P4652Magnetic resonance and electroanatomical guided endomyocardial biopsy as a diagnostic tool in the clinician's box: a 5 year experience

Background Percutaneous endo-myocardial biopsy (EMB) is an invasive diagnostic test used to reach or confirm a diagnosis when structural or substrate anomalies are suspected, such as in cardiomyopathies or myocarditis evaluation. In recent years, cardiac magnetic resonance imaging (MRI) and endo-cavitary electro-anatomical mapping (EAM) have been used to localize the most significant myocardial area to sample, therefore increasing EMB overall effectiveness and reliability. Purpose To describe and characterize safety, feasibility and anatomical findings of a large cohort of patients (pts) undergoing diagnostic EMB and to assess its impact on the treatment decision making algorithm. Methods A cohort of all pts undergoing a percutaneous EMB at our Institution from January 2014 to January 2019 was analyzed. All EMB procedures were guided by a pre-procedural cardiac MRI radiological alteration analysis and an endo-cavitary EAM. Intra-cardiac echography (ICE) was used in all procedures, to directly visualize the sample area and to evaluate in real time post-EBM complications. Demographics, clinical data, MRI data, pathological EMB features, and peri-procedural data were systematically retrieved. Results One-hundred and eleven pts were enrolled (78% male, 47±4 y.o., 33% athletes). EMB indication was abnormal MRI findings in 94 (85%), pathological EMB voltages in 10 (9%) and clinical suspect and patient history in 7 (6%) pts. EMB sample area was determined by both MRI and EAM pathological area analysis in 92 (83%) pts, while by EAM alone in 19 (17%) pts (n=6 pathological unipolar EAM; n=13 bipolar and unipolar pathological EAM). The sample site was the right ventricle in 89 (80%), the left ventricle in 20 (18%), and both in 3 (2%) pts. In 103 (93%) pts a concomitant electrophysiological induction study was performed (40% positive for sustained ventricular arrhythmias) and 35 (32%) pts underwent a trans-catheter ablation (TCA) (n=8 epicardial TCA; n=2 endo-epicardial TCA; n=25 endocardial ATC). Only 2 (2%) peri-procedural adverse events were witnessed, specifically femoral pseudo-aneurysms, requiring surgical repair. EMB analysis allowed to confirm 58 (52%) pre-procedural diagnosis and to reach 32 (29%) new diagnosis, while resulting inconclusive or non-specific in the diagnostic process only in 21 (19%) cases [Figure1]. A total of 33 (30%) intra-cardiac devices (ICDs) were implanted contextually in the cohort, of which 9 (8%) solely upon EMB indication; in 4 (4%) other patients, biopsy represented a strong decisional factor in the multi-modality decision process for abstaining from ICD implant. Dashed lines: diagnosis changed upon EMB Conclusion MRI and EAM guided EMBs allowed to finely define a large cohort of patients by representing a disease defining parameter in over 80% of the enrolled pts while and a decision shifting parameter in ICD implant algorithm in a high % of pts.

Reference range of fetal myocardial area by three-dimensional ultrasonography and its applicability in fetuses of pre-gestational diabetic women

Objective To determine the reference range for the myocardial area in healthy fetuses using three-dimensional (3D) ultrasonography and validate these results in fetuses of pregnant women with pre-gestational diabetes mellitus (DM). Methods This cross-sectional retrospective study included 168 healthy pregnant women between gestational weeks 20 and 33+6 days. The myocardial area was measured using spatio-temporal image correlation (STIC) in the four-chamber view. Polynomial regression models were used, and the goodness of fit of the models were evaluated by the coefficient of determination (R2). Intra- and inter-observer reproducibility was determined using the concordance correlation coefficient (CCC). Validation was performed in 30 pregnant women with pre-gestational DM. Results There was a strong correlation (R2=0.71, P<0.0001) between myocardial area and gestational age. There was good intra- and inter-observer reproducibility, with a CCC of 0.86 and 0.83, respectively. However, there was no significant difference in the mean myocardial area between healthy fetuses and fetuses of women with pre-gestational DM (0.11 cm2, P=0.55). Conclusion The reference range was determined for the myocardial area in fetuses, and there was no significant difference in this variable between healthy fetuses and the fetuses of women with pre-gestational DM.