Background: In patients with Covid-19, myocardial injury and increased inflammation are associated with morbidity and mortality. We designed a proof-of-concept randomized controlled trial to evaluate whether treatment with canakinumab prevents progressive respiratory failure and worsening cardiac dysfunction in patients with SARS-CoV2 infection, myocardial injury, and high levels of inflammation. Hypothesis: The primary hypothesis is that canakiumab will shorten time to recovery. Methods: The three C study (canakinumab in Covid-19 Cardiac Injury, NCT04365153) is a double-blind, randomized controlled trial comparing canakinumab 300 mg IV, 600 mg IV, or placebo in a 1:1:1 ratio in hospitalized Covid-19 patients with elevations in troponin and C-reactive protein (CRP). The primary endpoint is defined as the time in days from randomization to either an improvement of two points on a seven category ordinal scale or discharge from the hospital, whichever occurs first up to 14 days postrandomization. The secondary endpoint is mortality at day 28. A total of 45 patients will be enrolled with an anticipated 5 month follow up period. Results: Baseline characteristics for the first 20 randomized patients reveal a predominantly male (75%), elderly population (median 67 years) with a high prevalence of hypertension (80%) and hyperlipidemia (75%). CRPs have been markedly elevated
Introduction: The electrocardiogram (ECG) plays an important role in the diagnosis of heart diseases. However, most patterns of diseases are based on old datasets and stepwise algorithms that provide limited accuracy. Improving diagnostic accuracy of the ECG can be done by applying machine learning algorithms. This requires taking existing scanned or printed ECGs of old cohorts and transforming the ECG signal to the raw digital (time (milliseconds), voltage (millivolts)) form. Objectives: We present a MATLABbased tool and algorithm that converts a printed or scanned format of the ECG into a digitized ECG signal. Methods: 30 ECG scanned curves are utilized in our study. An image processing method is first implemented for detecting the ECG regions of interest and extracting the ECG signals. It is followed by serial steps that digitize and validate the results. Results: The validation demonstrates very high correlation values of several standard ECG parameters: PR interval 0.984 +/− 0.021 (p-value < 0.001), QRS interval 1+/− SD (p-value < 0.001), QT interval 0.981 +/− 0.023 p-value <0.001, and RR interval 1 +/− 0.001 p-value <0.001. Conclusion: Digitized ECG signals from existing paper or scanned ECGs can be obtained with more than 95% of precision. This makes it possible to utilize historic ECG signals in machine learning algorithms to identify patterns of heart diseases and aid in the diagnostic and prognostic evaluation of patients with cardiovascular disease. INDEX TERMS Electrocardiogram, digitization, Matlab tool, image processing.
NKX2-5 mutations are associated with different forms of congenital heart disease. Despite the knowledge gained from molecular and animal studies, genotype-phenotype correlations in humans are limited by the lack of large cohorts and the incomplete assessment of family members. We hypothesized that studying the role of NKX2-5 in inbred populations with homogeneous genetic backgrounds and high consanguinity rates such as Lebanon could help closing this gap. We sequenced NKX2-5 in 188 index CHD cases (25 with ASD). Five variants (three segregated in families) were detected in eleven families including the previously documented p.R25C variant, which was found in seven patients from different families, and in one healthy individual. In 3/5 familial dominant ASD cases, we identified an NKX2-5 mutation. In addition to the heterogeneity of NKX2-5 mutations, a diversity of phenotypes occurred within the families with predominant ASD and AV block. We did in fact identify a large prevalence of Sudden Cardiac Death (SCD) in families with truncating mutations, and two patients with coronary sinus disease. NKX2-5 is thus responsible for dominant familial ASD even in consanguineous populations, and a wide genetic and phenotypic diversity is characteristic of NKX2-5 mutations in the Lebanese population.
Aims In COVID-19, myocardial injury is associated with systemic inflammation and higher mortality. Our aim was to perform a proof of concept trial with canakinumab, a monoclonal antibody to IL-1β, in patients with COVID-19, myocardial injury, and heightened inflammation. Methods and Results This trial required hospitalisation due to COVID-19, elevated troponin, and a C reactive protein concentration more than 50 mg/L. The primary endpoint was time to clinical improvement at day 14, defined as either an improvement of two points on a seven category ordinal scale or discharge from the hospital. The secondary endpoint was mortality at day 28. Forty-five patients were randomly assigned to canakinumab 600 mg (n = 15), canakinumab 300 mg (n = 14), or placebo (n = 16). There was no difference in time to clinical improvement compared to placebo (recovery rate ratio (RRR) for canakinumab 600 mg 1.15, 95% confidence interval (CI) 0.46-2.91; RRR for canakinumab 300 mg 0.61, 95% CI 0.23-1.64). At day 28, 3 (18.8%) of 15 patients had died in the placebo group, compared with 3 (21.4%) of 14 patients with 300 mg canakinumab, and 1 (6.7%) of 15 patients with 600 mg canakinumab. There were no treatment-related deaths, and adverse events were similar between groups. Conclusion There was no difference in time to clinical improvement at day 14 in patients treated with canakinumab, and no safety concerns were identified. Future studies could focus on high dose canakinumab in the treatment arm and assess efficacy outcomes at day 28.
BackgroundPulmonary arterial hypertension (PAH) is a rare disease with an incidence rate of 2–6 cases per million per year. Our knowledge of the disease in the Middle East and North Africa (MENA) region is limited by the small number of clinical studies and the complete absence of genetic studies.MethodsOur aim was to shed light on the clinical and genetic characteristics of PAH in Lebanon and the region by using exome sequencing on PAH patients referred to the American University of Beirut Medical Center (AUBMC). Twenty-one idiopathic, hereditary and Congenital Heart Disease (CHD) PAH patients were prospectively recruited, their clinical data summarized, and sequencing performed.ResultsThe mean age at diagnosis was 33 years with a female preponderance of 70%. The mean pulmonary artery pressure at the time of diagnosis was 55. Genetic testing showed that 5 out of 19 idiopathic and Congenital Heart Disease PAH patients had Bone Morphogenetic Protein Receptor 2 (BMPR2) mutations at 25% prevalence, with 2 of these patients exhibiting a novel mutation. It also showed the presence of 1 BMPR2 mutation with 100% penetrance in a heritable PAH family. In the remaining cases, the lack of a complete genotype/phenotype correlation entailed a multigenic inheritance; suspected interactions involved previously associated genes T-box transcription factor 4 (TBX4), Bone Morphogenic Protein 10 (BMP10) and Growth Differentiation Factor 2 (GDF2).ConclusionsThis is the first study that looks into the genetic causes of PAH, including known and new BMPR2 mutations, in the MENA region. It is also the first study to characterize the clinical features of the disease in Lebanon.Electronic supplementary materialThe online version of this article (10.1186/s12881-018-0608-7) contains supplementary material, which is available to authorized users.
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