Transthyretin Gene Variants and Associated Phenotypes in Danish Patients with Amyloid Cardiomyopathy

Genotyping divides transthyretin cardiac amyloidosis (ATTR-CA) in hereditary (ATTRv) and wild type (ATTRwt) forms. This study investigated the prevalence and clinical presentation of ATTRv in a contemporary cohort of consecutive ATTR-CA patients diagnosed at a tertiary Danish amyloidosis center. Age at diagnosis, clinical- and echocardiographic data, and transthyretin (TTR) genotype were recorded. Relatives of ATTRv patients underwent clinical phenotyping and predictive gene testing. Genetic testing in 102 patients identified four TTR variant carriers: p.Pro63Ser, p.Ala65Ser (n = 2) and p.Val142Ile. The mean age of ATTRv index patients was significantly lower compared to ATTRwt patients: 70.2 ± 1.2 versus 80.0 ± 6.2, p-value: 0.005. Evaluation of ATTRv families identified seven TTR variant carriers with a median age of 65 years (range 48–76) and three were diagnosed with ATTR-CA by DPD-scintigraphy. Family members with ATTR-CA were all asymptomatic and had normal levels of cardiac biomarkers. In conclusion, the prevalence of ATTRv in a contemporary Danish ATTR-CA cohort is 4%. ATTRv index patients were significantly younger age at diagnosis than ATTRwt patients. Non-p.Leu131Met TTR variants have reduced penetrance at the age of 65 years in which approximately half of variant carriers have asymptomatic ATTR-CA with normal LV systolic function and cardiac biomarker analyses.

Cardiovascular manifestations and echocardiographic findings in pediatric multisystem inflammatory syndrome associated with COVID-19 (MIS-C): A retrospective study

Background: The multisystem inflammatory syndrome in children (MIS-C) has been described recently during COVID-19 pandemic. It is a delayed post-infectious response with a lag time of 4–6 weeks following the exposure to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), involving multiple systems which is being increasingly reported worldwide. Aim: The study aims to investigate and report the cardiovascular manifestation and echocardiographic findings in pediatric patients diagnosed with MIS-C. Materials and Methods: The present study is a retrospective analysis of clinical data gathered from 40 admitted children diagnosed with MIS-C. The study was conducted for 1 year (from 1st June 2020 to 30th May 2021) at Cheluvamba Hospital, a tertiary care center attached to Mysore Medical College And Research Institute, Mysore, Karnataka. Results: Out of 40 children, 21 (52.5%) had manifestation of cardiovascular system in the form of shock, requiring ionotropic support and care at the Intensive Care Unit. Among them, 90% patients show elevated cardiac biomarker (Troponin T), 33.3% had two-dimensional echocardiographic (2D echo) findings in which 9.5% show coronary artery dilatation and 23.8% show left ventricular hypertrophy. Conclusion: MIS-C is a hyperinflammatory syndrome related to SARS-CoV-2 infection. Cardiac involvement is evidenced by perturbation of cardiac chamber size, function, coronary artery abnormalities, and elevated cardiac biomarker. Though, most of the patients responded to the initial treatment and recovered, there is scarcity of data regarding long-term cardiovascular complication.

Very severe aortic stenosis masquerading as acute coronary syndrome

Severe aortic stenosis (AS) may rarely present like acute coronary syndrome with increased cardiac biomarker despite having normal coronaries. Here we describe a case of very severe AS, who presented with exertional and rest angina and a high level of TnI. Angiography revealed normal coronaries. Echocardiography showed very severe AS with peak velocity of 5.08 m/s and maximum and mean gradient of 103 and 54 mm Hg, respectively. The patient subsequently underwent aortic valve replacement (AVR) successfully. Subendocardial ischaemia may occur in patients with severe AS during haemodynamic stress, even in the setting of normal unobstructed coronaries due to supply-demand mismatch. Subsequent degeneration and death of the cardiac myocytes cause cTnI elevation, which anticipates the start of the clinical downhill course in severe AS. Our case highlights the importance of thorough physical examination and early use of echocardiography in patients with angina to detect the presence of severe AS.

Cardiac evaluation in adults with dengue virus infection by serial echocardiography

Background Dengue virus infection (DVI) is a major health problem in many parts of the world. Its manifestations range from asymptomatic infections to severe disease. Although cardiac involvement has been reported in DVI, its incidence has not yet been well established. Methods From July 2016 to January 2018, patients hospitalized at the Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Thailand, with dengue virus infection confirmed by positive NS1 or positive dengue immunoglobulin M findings, participated in the study. We characterized the incidence and change in cardiac function by serial echocardiography and levels of troponin-T and creatine kinase-myocardial band (CK-MB) on the day of admission, the day of defervescence, the first day of hypotension (if any), and at 2 week follow-up. Results Of the 81 patients evaluated, 6 (7.41%) exhibited elevated biomarker levels. There was no difference in clinical presentation amongst dengue fever, dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS), except for the amount of bleeding. Cardiac involvement was found in 22.2% of patients: 3 (3.70%) had left ventricular systolic dysfunction, 3 (3.70%) had transient diastolic dysfunction, 6 (7.41%) had increased levels of at least one cardiac biomarker (troponin-T or CK-MB), and 6 (7.41%) had small pericardial effusion. Myocarditis was suspected in only two patients (with DHF); thus, myocarditis was uncommon in patients with dengue virus infection. Three patients developed DSS during admission and were transferred to the intensive care unit. Conclusion Cardiac involvement in adults with dengue infection was common, ranging from elevated cardiac biomarker to myocarditis. Abnormalities in cardiac function had resolved spontaneously by the day of follow-up, without specific treatment. We found that DHF was a significant risk factor for cardiac involvement. Echocardiography is the investigation of choice for evaluating the haemodynamic status of patients with DVI, especially in severe dengue.

Cardiovascular magnetic resonance imaging in children after recovery from symptomatic COVID-19 or MIS-C: a prospective study

Background Cardiac evaluations, including cardiovascular magnetic resonance (CMR) imaging and biomarker results, are needed in children during mid-term recovery after infection with SARS-CoV-2. The incidence of CMR abnormalities 1–3 months after recovery is over 50% in older adults and has ranged between 1 and 15% in college athletes. Abnormal cardiac biomarkers are common in adults, even during recovery. Methods We performed CMR imaging in a prospectively-recruited pediatric cohort recovered from COVID-19 and multisystem inflammatory syndrome in children (MIS-C). We obtained CMR data and serum biomarkers. We compared these results to age-matched control patients, imaged prior to the SARS-CoV-2 pandemic. Results CMR was performed in 17 children (13.9 years, all ≤ 18 years) and 29 age-matched control patients without SARS-CoV-2 infection. Cases were recruited with symptomatic COVID-19 (11/17, 65%) or MIS-C (6/17, 35%) and studied an average of 2 months after diagnosis. All COVID-19 patients had been symptomatic with fever (73%), vomiting/diarrhea (64%), or breathing difficulty (55%) during infection. Left ventricular and right ventricular ejection fractions were indistinguishable between cases and controls (p = 0.66 and 0.70, respectively). Mean native global T1, global T2 values and segmental T2 maximum values were also not statistically different from control patients (p ≥ 0.06 for each). NT-proBNP and troponin levels were normal in all children. Conclusions Children prospectively recruited following SARS-CoV-2 infection had normal CMR and cardiac biomarker evaluations during mid-term recovery. Trial Registration Not applicable.