Genetic testing in the management of inherited cardiac disorders: two cases of Filamin-C arrhythmogenic left ventricular cardiomyopathy.

Background: Arrhythmogenic left ventricular cardiomyopathy (ALVC) is a left ventricle-dominant arrhythmogenic cardiomyopathy (ACM) subtype often associated with malignant ventricular arrhythmias, left ventricular (LV) scar and sudden cardiac death. Awareness about LV involvement is now on the rise. The diagnosis relies on structural abnormalities on cardiac magnetic resonance (CMR) imaging and known ACM-causing genetic mutations. Case summary: A 28-year-old lady (Case 1) was referred for cardiac screening after her father passed away suddenly. Her paternal uncle (Case 2) had been diagnosed with supposed dilated cardiomyopathy prior to referral. Both cases were worked up extensively with an electrocardiogram (ECG), 24-h ambulatory ECG monitor, exercise testing, and CMR imaging. Investigations of Case 1 showed T-wave inversion in the infero-lateral leads and a ventricular ectopic burden of 3% on ambulatory monitoring. Cardiac magnetic resonance imaging revealed moderately reduced LV systolic function (ejection fraction of 40%) with circumferential macroscopic fibrosis. Her uncle (Case 2) also had an impaired and dilated ventricle with extensive scar on CMR. Following the recent introduction of a cardiogenetic service in our unit, both were heterozygous for a pathogenic Filamin-C variant (c.7384+1G>A). Based on CMR findings and genetic results, the diagnosis of both patients was deemed to be ALVC. After years of surveillance, Patient 1 now has an implantable cardioverter defibrillator (ICD) indication. Discussion: The importance of diagnosing patients with ACM lies in the predisposition to sudden cardiac death. Gene-specific treatment algorithms in ACM may alter management strategies, including ICD implantation as primary prevention. An in-depth multidisciplinary discussion and respecting patient autonomy are key factors in any decision pertaining to ICD implantation.

Acute lymphocytic myocarditis presenting as complete heart block in an adult: a case report.

BACKGROUND: Complete heart block (CHB) as a first presentation of acute viral myocarditis is a rare occurrence associated with increased morbidity and mortality. In such cases, an endomyocardial biopsy is recommended to make a clear histological diagnosis aiding to differentiate from other possible conditions such as sarcoiditic myocarditis, giant cell myocarditis, and eosinophilic myocarditis. Insertion of a permanent pacemaker may be considered on a case-to-case basis. CASE PRESENTATION: A previously healthy 21-year-old female presented to the emergency department after having suffered two episodes of syncope on a background of a few days' history of myalgias, chills, and rigors. Electrocardiogram showed high-grade Mobitz II block with intermittent periods of CHB. A bedside echocardiogram upon admission demonstrated normal biventricular systolic function. Given the patient's unstable haemodynamic status and lack of obvious reversible causes for the CHB, a permanent dual-chamber pacemaker was inserted urgently. Initial blood investigations indicated an ongoing inflammatory process highlighting the possibility of myocarditis as a cause of the CHB. Therefore, a troponin level was taken and was noted to be elevated confirming the suspicion of myocarditis. The left ventricular ejection fraction (LVEF) decreased over the following days to approximately 20%, clinically resulting in pulmonary oedema and acute shortness of breath. The patient required aggressive intravenous diuresis and anti-heart failure medication. An endomyocardial biopsy (EMB) confirmed the diagnosis of lymphocytic myocarditis. The patient's condition improved secondary to an improvement in LVEF and resolution of the heart block. A cardiac magnetic resonance (CMR) imaging performed 6 weeks from admission reported an improved LVEF of 51% with no late gadolinium enhancement (LGE). Based on the reassuring CMR findings and the resolution of CHB on follow-up pacemaker checks, it was deemed safe to explant the pacemaker. CONCLUSIONS: Acute myocarditis may be complicated with high-degree AV block and cardiogenic shock necessitating close observation in a critical care unit. A permanent pacemaker may provide atrio-ventricular synchrony which helps stabilise the patient's condition and protect from a prolonged period of heart block. Early myocardial fibrosis on EMB and degree of LGE on CMR are indicators of persistent atrioventricular block. Guideline-directed treatment of heart failure is essential.

The juvenile ECG pattern in adolescent athletes and non-athletes in a national cardiac screening program (BEAT-IT).

BACKGROUND: Anterior T wave inversion (TWI) is frequent in healthy adolescent individuals (juvenile ECG pattern), normalising after puberty. Its clinical implications are uncertain. AIM: This study assessed a) national prevalence of anterior TWI, b) ST segment morphology, c) proportion of individuals with a juvenile ECG pattern whose ECG normalises and d) factors predicting TWI persistence >16 years. METHODS: Adolescents (mean 15y) in Malta were systematically invited to enrol in a cardiac screening program. Subjects completed a health questionnaire and an ECG at their school. Participants with TWI were labelled as TWI in V1-V2 or extended TWI (V1-V3/4). The latter were followed at 1 year with a repeat ECG. Those with persistent extended anterior TWI were offered evaluation and surveillance. RESULTS: The prevalence of isolated anterior TWI was 5.0%, commoner in females (6.3%) independent of athletic ability. Extended TWI was commoner in female athletes (4.2%, non-athletes 2.1%). Females often had shallow TWI without overt ST segment abnormalities. Deep TWI and ST segment changes were more frequent in males. Only 0.2% of cases persisted ≥16 years of age. ST segment characteristics were not able to predict T wave normalisation. No events took place during follow up (40 ± 9 months). CONCLUSION: Anterior TWI is a frequent phenomenon in adolescents, especially in females. Female athletes are also more likely to have extended anterior TWI. Only 0.2% of cases have persistent anterior TWI at 16 years of age. Chest wall anatomy may explain this phenomenon in females. It is uncommon in males, hence why surveillance is more prudent.

Six Months After the Patients Stayed Home: A Nationwide Study of Cardiac Mortality and Readmissions Following the First Wave of the COVID-19 Pandemic in Malta.

Background The first COVID-19 wave resulted in a significant decline in acute cardiac admissions (ACAs) and delays to hospital presentation in Malta, as well as an excess of out-of-hospital cardiac arrests. The aim was to investigate the impact of the observed delays in presentation in 2020 on mortality and cardiac readmissions at six months. Methods All ACAs between 28th February and 30th April 2020 (first wave of COVID-19 in Malta) were included, and the corresponding 2019 period was used as a control. ACA was defined as an unplanned admission of an adult (aged ≥16 years) under the care of a cardiologist. Outcomes over the six months following the index ACA included death, cardiac readmission, and planned cardiac intervention at discharge. The term 'death' referred to all-cause mortality. Cardiac readmissions referred to unplanned admissions for acute cardiac pathology following the index ACA. During sub-analyses, ACAs were divided into acute coronary syndrome (ACS) and non-ACS. A first analysis compared the frequency of deaths, cardiac readmissions, and planned interventions between the 2019 and 2020 cohorts. A second analysis investigated differences in six-month survival and freedom from readmission between the two cohorts. Both analyses were followed by a sub-analysis. Results There were 330 ACAs among the 2019 cohort and 220 in 2020. There were no significant differences between the 2019 and 2020 cohorts in all-cause mortality (2019, 8.8% vs 2020, 8.2%, p=0.466) and Kaplan-Meier survival estimates at a six-month follow-up (2019, 169.06 days (95% CI 164.95-173.17) vs 2020, 168.27 days (95% CI 162.82-173.72), p=0.836), including subgroup analysis for non-ACS (2019, 168.52 days (95% CI 163.08-173.96) vs 168.11 days (95% CI 160.93-175.30), p=0.952) and ACS patients (169.81 days (95% CI 163.54-176.09) in 2019 vs 168.45 days (95% CI 160.17-176.73) in 2020, p=0.739). A significantly higher number of patients from the 2019 cohort (75/319, 23.5%) required readmission compared to 2020 (32/212; 15.1%) (p=0.02). Similarly, there was shorter freedom from cardiac readmission among 2019 patients (mean 150.98 days (95% CI 144.63-157.33)) compared to 2020 patients (mean 158.66 days (95% CI 151.58-165.74, p=0.024). During sub-analysis, the difference in freedom from readmission was significant only for non-ACS patients (mean of 145.45 days (95% CI 136.58-154.32) in 2019 vs 158.92 days (95% CI 149.19-168.64) in 2020, p=0.018). Analysis of cardiac interventions during the six months post-index ACA discharge showed significantly more planned cardiac interventions in 2019 (52/319; 16.3%) compared to 2020 (20/212; 9.4%) (p=0.027). Conclusions A delay in presentation of ACAs during COVID-19 in Malta resulted in lower readmission rates and increased freedom from readmissions, with no excess in all-cause mortality at a six-month follow-up. The reasons for the optimistic outcomes of patients admitted during the first wave of COVID-19 may be multifactorial. Reasons may include ongoing fear of hospital presentation, a more holistic approach to patients' in-hospital care during 2020 aimed at reducing further hospital contact post-discharge, and a selection bias secondary to an excess of out-of-hospital cardiac arrests during the initial wave of COVID-19. Further studies will be required to truly assess the collateral impact of non-COVID-19-related illness. Public education on cardiovascular health is vital and must be emphasized during the pandemic.

Multiple cardiac metastases from urothelial carcinoma case report.

BACKGROUND: Cardiac metastases are rare and frequently remain undiagnosed due to the absence of clinical signs in the majority of cases. Malignancies found to most commonly metastasise to the heart include lung carcinoma, breast carcinoma and lymphoma, while urothelial carcinoma is a rare cause of cardiac metastasis. The patient presented with pyrexia, a rare presentation of metastatic cardiac involvement. Single metastatic lesions are mainly reported in the literature, while multiple metastatic deposits such as in this case are less common. CASE PRESENTATION: A 74-year-old gentleman presented with frequent febrile spikes, a month after undergoing a nephroureterectomy for poorly differentiated urothelial carcinoma. No febrile source was identified, and a computed tomography identified two cardiac lesions. A transthoracic echocardiogram could not detect the cardiac lesions; therefore, cardiac magnetic resonance (CMR) imaging was performed. Three spherical intramyocardial masses were noted at the basal septum, LV apex and the anteromedial papillary muscle. The lesions demonstrated signal characteristics suggestive of cardiac metastases (high fluid content, absence of fat, presence of a surrounding rim of increased extravascular space, absence of deformation within the masses) from the previously resected urothelial carcinoma. The patient was palliated, and he shortly succumbed to his condition. CONCLUSIONS: Urothelial carcinoma is an exceedingly rare cause of cardiac metastasis. CMR is an important imaging modality for localisation and characterisation of suspicious cardiac lesions, aiding in the diagnosis of cardiac metastasis.

Significant Reduction in Pediatric, Population-Based Hospital Admissions Due To COVID-19 in Malta.

OBJECTIVE: This population-based, retrospective study aimed to determine whether there was a drop in pediatric admissions during the first year of COVID-19 in Malta, as reported in other centers worldwide, as well as to determine any differences in patient characteristics when compared to the previous year. MATERIALS AND METHODS: All unplanned pediatric medical admissions to Mater Dei Hospital from March 1, 2020 (a few days before the first case of COVID-19 in Malta) till February 28, 2021 (study period) and the corresponding period in 2019/20 (control period) and characteristics of patients admitted during the first 10 weeks (first wave of COVID-19) were analyzed. RESULTS: Pediatric admissions dropped by 57.7% during the first year of COVID-19 (1601 vs. 3789 in 2019). During the first wave of COVID-19, a higher percentage of neonates were admitted in 2020 when compared to all other ages. There was a lower prevalence of respiratory illnesses during the first wave of COVID-19 (31.6% vs. 47.5% in 2019, P < .001), with a higher prevalence of cases related to child abuse or adverse socio-economic circumstances (2020, 9 [3.4%] vs 1 [0.1%] in 2019, P < .001). Following school closures, a drop in communicable disease admissions was recorded (68 [42.2%] vs. 421 [70.3%] in 2019, P < .001). A negative correlation between daily pediatric admissions and active COVID-19 cases in Malta was noted (r (68) = -0.33, P = .005). CONCLUSION: The drop in admissions likely represents fear of contracting COVID-19 in hospital environments, together with a decline in communicable diseases due to school closures. Guardians' concerns must be alleviated as best as possible by effective public health measures.

Progressive encephalomyelitis with rigidity and myoclonus (PERM).

Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a subtype of stiff-person syndrome (formerly stiff-man syndrome). It is rare and disabling, and characterised by brainstem symptoms, muscle stiffness, breathing issues and autonomic dysfunction. We describe a 65-year-old man who presented with odynophagia together with tongue and neck swelling, followed by multiple cranial nerve palsies culminating in bilateral vocal cord paralysis with acute stridor. He subsequently developed progressive generalised hypertonia and painful limb spasms. Serum antiglycine receptor antibody was strongly positive, but antiglutamic acid decarboxylase and other antibodies relating to stiff-person syndrome were negative. We diagnosed PERM and gave intravenous corticosteroids and immunoglobulins without benefit; however, following plasma exchange he has made a sustained improvement.

When the patients stayed home: the impact of the COVID-19 pandemic on acute cardiac admissions and cardiac mortality in Malta.

Aim: This study aimed to investigate the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on all types of acute cardiac admissions (ACAs) and cardiac mortality in Malta. Methods: Number, characteristics and delay to presentation of ACAs to our institution during the study period (28 February-30 April 2020) were compared with the corresponding 2019 period. Non-parametric correlation analyses between daily SARS-CoV-2 cases in Malta, Italy and the UK and daily ACAs were performed. Differences in cardiac death distribution (community vs. in-hospital) during the two periods were analysed. Results: There was a significant decline in daily ACAs in 2020 (median 3 [IQR 3]) vs. 2019 (median 5 [IQR 4]), p < 0.001. Patient characteristics were comparable. Delay to presentation for 2020 ACAs was significantly higher across all categories (ST-elevation myocardial infarction [STEMI] median: 2019 [1 h, IQR 1] vs. 2020 [4 h, IQR 43.8], p = 0.009; non-ST-elevation-acute coronary syndrome [NSTE-ACS] median: 2019 [4 h, IQR 71] vs. 2020 [48 h, IQR 199], p = 0.001; non-ACS median: 2019 [24 h, IQR 95] vs. 2020 [84 h, IQR 499.8], p < 0.001). There was a significant negative correlation between ACAs and daily Malta SARS-CoV-2 infection cases (r s = -0.298, p = 0.018) but not with cases in Italy and the UK when controlling for Malta cases. Significantly more cardiac deaths occurred in the community in 2020 (107, 61.8%) compared to 2019 (87, 46.8%) (p = 0.004). Conclusion: Fear of SARS-CoV-2 infection led to a significant avoidance of acute cardiac care with an accompanying rise in community cardiac deaths, suggesting a need for better public education on recognising and addressing cardiovascular symptoms.

The Impact of COVID-19 on Hospitalised COPD Exacerbations in Malta.

METHOD: Data was collected retrospectively from electronic hospital records during the periods 1st March until 10th May in 2019 and 2020. RESULTS: There was a marked decrease in AECOPD admissions in 2020, with a 54.2% drop in admissions (n = 119 in 2020 vs. n = 259 in 2019). There was no significant difference in patient demographics or medical comorbidities. In 2020, there was a significantly lower number of patients with AECOPD who received nebulised medications during admission (60.4% in 2020 vs. 84.9% in 2019; p ≤ 0.001). There were also significantly lower numbers of AECOPD patients admitted in 2020 who received controlled oxygen via venturi masks (69.0% in 2020 vs. 84.5% in 2019; p = 0.006). There was a significant increase in inpatient mortality in 2020 (19.3% [n = 23] and 8.4% [n = 22] for 2020 and 2019, respectively, p = 0.003). Year was found to be the best predictor of mortality outcome (p = 0.001). The lack of use of SABA pre-admission treatment (p = 0.002), active malignancy (p = 0.003), and increased length of hospital stay (p = 0.046) were also found to be predictors of mortality for AECOPD patients; however, these parameters were unchanged between 2019 and 2020 and therefore could not account for the increase in mortality. CONCLUSIONS: There was a decrease in the number of admissions with AECOPD in 2020 during the COVID-19 pandemic, when compared to 2019. The year 2020 proved to be a significant predictor for inpatient mortality, with a significant increase in mortality in 2020. The decrease in nebuliser and controlled oxygen treatment noted in the study period did not prove to be a significant predictor of mortality when corrected for other variables. Therefore, the difference in mortality cannot be explained with certainty in this retrospective cohort study.

Congenitally corrected transposition of the great arteries (CCTGA).

A 33-year-old man presented with a 3-week history of breathlessness and cough. He disclosed that he was informed regarding a heart defect as a child in his home country but was unaware of its nature and was never followed up. Examination revealed a pansystolic murmur (loudest at the apex), a hyperdynamic, displaced apex, and pulmonary oedema. An ECG showed atrial fibrillation with a regular broad-complex ventricular rhythm. Following electrical cardioversion, the ECG revealed complete heart block, therefore explaining the regular atrial fibrillation. An urgent transthoracic echocardiography (TTE) confirmed the anatomy of congenitally corrected transposition of the great arteries (CCTGA) with torrential tricuspid regurgitation and impaired systemic right ventricle. Cardiac MRI identified a ventricular septal defect which was not visible on TTE. The patient showed a transient improvement following fluid offloading and ACE inhibition, with a more definitive improvement after cardiac resynchronisation therapy (CRT).

WITHDRAWN: COVID-19 related acute decline in paediatric admissions in Malta, a population-based study.

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Rising Incidence of Glioblastoma Multiforme in a Well-Defined Population.

Background and Objectives The incidence of glioblastoma multiforme (GBM) ranges from 0.59 to 5 per 100,000 persons, and it is on the rise in many countries. The reason for this rise is multifactorial, and possible contributing factors include an aging population, overdiagnosis, ionizing radiation, air pollution and others. The aim of this study is to conduct an epidemiological study of GBM in a well-defined population over a 10-year period and determine its significance, while comparing results with international standards. Materials and Methods All histological diagnoses of GBM in Malta from 2008 to 2017 were identified. Poisson regression was used to determine significance in incidence variation. Log-rank tests were used to compare the survival distributions of each variable. Cox regression for survival analysis with the Breslow method for ties was then performed to consider the overall model. Results A total of 100 patients (61 males; mean age 60.29±10.09 years) were diagnosed with GBM over the period 2008 to 2017. There was a significant increase in incidence from 0.73 to 4.49 per 100,000 over the 10-year period (p≤0.001). The most common presenting complaint was limb paresis (29%). Approximately 65% of patients were treated with maximum safe resection (MSR). Using Cox regression analysis, younger age at presentation and treatment with MSR significantly improved survival (p=0.026 and p≤0.001, respectively). The median survival was 10 months. Conclusions An increasing incidence of GBM is becoming evident, while the median survival remains low. This troubling trend emphasizes the importance of further research into GBM etiology and treatment.