Remotely monitored inactivity due to COVID-19 lockdowns. Potential hazard for heart failure patients.

OBJECTIVES: To study the impact of curfews during the COVID-19 pandemic, on the physical activity in patients of heart failure implanted withcardiac implantable electronic devices (CIEDs). METHODS: This was a retrospective single-center study of heart failure patients inserted with remote monitoring (RM)-capable CIED. We analyzed the transmitted data of physical activity and fluid volume status of all patients, before, and during the lockdown periods between February and April 2020. The clinical status of the patients was also evaluated.  Results: Device data from 429 patients implanted with CIED capable of RM were initially evaluated. Patients with an implantable loop recorder, Brugada or Long QT syndromes, and patients with incomplete transmissions were excluded. Eighty-two patients with heart failure were included. The median age was 65 years (58-72), and 53 (64.6%) subjects were men. There was a 27.1% decline in physical activity, and the median physical activity of patients significantly declined from 2.4 to 1.8 hours/day (p=0.000010).  Conclusion: Data obtained by remotely monitored CIED in heart failure patients suggests a significant decline in physical activity during the country lockdown due to the pandemic. Awareness of the future potential hazards in this group of patients is warranted.

Assessment of the quality of anticoagulation management with warfarin in a tertiary care center.

OBJECTIVES: To evaluate the quality of an anticoagulation clinic in a tertiary hospital and identified factors affecting the time in the therapeutic range (TTR) and its relation to different complications. Methods: This single-center retrospective study conducted between March 2015 and June 2016 included 1914 patients receiving warfarin therapy. They were divided into 4 warfarin indication groups: non-valvular atrial fibrillation (AF) (n=403), valvular AF (n=227), prosthetic valves (n=700), and venous or pulmonary embolism (n=584). RESULTS: The median age was 56 (25th, 75th percentiles: [45, 67]) years, and 53.2% were female. The median TTR was 0.52 (0.28, 0.76). Low hemoglobin (0.007) and high alkaline phosphatase (0.020) levels negatively affected the TTR. Venous thromboembolism (VTE) was associated with low TTRs. Minor bleeding occurred in 64 (3.35%), gastrointestinal bleeding in 14 (0.7%), and stroke in 41 (2.2%) patients, with no inter-group differences. The TTR was not associated with minor bleeding (odds ratio [OR]=0.49; p=0.09), gastrointestinal bleeding (OR=0.29; p=0.18), or stroke (OR=1.15; p=0.79). CONCLUSION: Reflecting the real-life experience of anticoagulation control, our patients spend less than half the TTR within the INR. The low target TTR mandates the need to improve service quality and control factors affecting the TTR, including hemoglobin levels and regular visits for patients with VTE.

A de novo splicing variant supports the candidacy of TLL1 in ASD pathogenesis.

Congenital heart disease (CHD) is the most common type of birth defects with family- and population-based studies supporting a strong hereditary component. Multifactorial inheritance is the rule although a growing number of Mendelian forms have been described including candidates that have yet to be confirmed independently. TLL1 is one such candidate that was proposed in the etiology of atrial septal defect (ASD). We describe a girl with congenitally corrected transposition of the great arteries (ccTGA) and ASD secundum whose whole-exome sequencing (WES) revealed a de novo splicing (c.1379-2A>G) variant in TLL1 as well as an inherited truncating variant in NODAL. The identification of this dual molecular diagnosis both supports the candidacy of TLL1 in ASD pathogenesis and highlights the power of WES in revealing multilocus cardiac phenotypes.

Autosomal recessive long QT syndrome, type 1 in eight families from Saudi Arabia.

BACKGROUND: One of the most common primary cardiac arrhythmia syndromes is autosomal dominant long QT syndrome, type 1 (LQT1), chiefly caused by mono-allelic mutations in the KCNQ1 gene. Bi-allelic mutations in the KCNQ1 gene are causal to Jervell and Lange-Nielsen syndrome (JLNS), characterized by severe and early-onset arrhythmias with prolonged QTc interval on surface ECG and sensorineural deafness. Occasionally, bi-allelic mutations in KCNQ1 are also found in patients without any deafness, referred to as autosomal recessive long QT syndrome, type 1 (AR LQT1). METHODS: We used Sanger sequencing to detect the pathogenic mutations in KCNQ1 gene in eight families from Saudi Arabia with autosomal recessive LQT1. RESULTS: We have detected pathogenic mutations in all eight families, two of the mutations are founder mutations, which are c.387-5T>A and p.Val172Met/p.Arg293Cys (in cis). QTc and cardiac phenotype was found to be pronounced in all the probands comparable to the cardiac phenotype in JLNS patients. Heterozygous carriers for these mutations did not exhibit any clinical phenotype, but a significant number of them have sinus bradycardia. CONCLUSION: To the best of our knowledge, this is the first description of a large series of patients with familial autosomal recessive LQT, type 1. These mutations could be used for targeted screening in cardiac arrhythmia patients in Saudi Arabia and in people of Arabic ancestry.

A Zebrafish Loss-of-Function Model for Human CFAP53 Mutations Reveals Its Specific Role in Laterality Organ Function.

Establishing correct left-right asymmetry during embryonic development is crucial for proper asymmetric positioning of the organs. Congenital heart defects, such as dextrocardia, transposition of the arteries, and inflow or outflow tract malformations, comprise some of the most common birth defects and may be attributed to incorrect establishment of body laterality. Here, we identify new patients with dextrocardia who have mutations in CFAP53, a coiled-coil domain containing protein. To elucidate the mechanism by which CFAP53 regulates embryonic asymmetry, we used genome editing to generate cfap53 zebrafish mutants. Zebrafish cfap53 mutants have specific defects in organ laterality and randomization of asymmetric gene expression. We show that cfap53 is required for cilia rotation specifically in Kupffer's vesicle, the zebrafish laterality organ, providing a mechanism by which patients with CFAP53 mutations develop dextrocardia and heterotaxy, and confirming previous evidence that left-right asymmetry in humans is regulated through cilia-driven fluid flow in a laterality organ.

A delayed spontaneous expulsion of a three teeth bridge after 6 months period of aspiration in the right lung following cardiac surgery.

Aspiration of loose teeth is a well-known complication of endo-tracheal intubation hence the importance of oral check by anesthetist prior to ventilation. Artificaial teeth crown (single) or bridges (multiple) can be fixed or removable by the patient. The presence of a foreign body in the lung tissue or airways is a clinical situation that needs aggressive management as it can lead to refractory infections and possible death. We report this unique case of aspirarin of a three bridge teeth (10 mm × 30 mm) following cardiac surgery. The case is complicated by pneumonia, chronic cough and severe bouts of cyanosis and finally removed by spontaneous expulsion after 6 months following forceful cough.

Positional mapping of PRKD1, NRP1 and PRDM1 as novel candidate disease genes in truncus arteriosus.

BACKGROUND: Truncus arteriosus (TA) is characterised by failure of septation of the outflow tract into aortic and pulmonary trunks and is associated with high morbidity and mortality. Although ranked among the least common congenital heart defects, TA provides an excellent model for the role of individual genes in cardiac morphogenesis as exemplified by TBX1 deficiency caused by point mutations or, more commonly, hemizygosity as part of the 22q11.2 deletion syndrome. The latter genetic lesion, however, is only observed in a proportion of patients with TA, which suggests the presence of additional disease genes. OBJECTIVE: To identify novel genes that cause Mendelian forms of TA. METHODS AND RESULTS: We exploited the occurrence of monogenic forms of TA in the Saudi population, which is characterised by high consanguinity, a feature conducive to the occurrence of Mendelian phenocopies of complex phenotypes as we and others have shown. Indeed, we demonstrate in two multiplex consanguineous families that we are able to map TA to regions of autozygosity in which whole-exome sequencing revealed homozygous truncating mutations in PRKD1 (encoding a kinase derepressor of MAF2) and NRP1 (encoding a coreceptor of vascular endothelial growth factor (VEGFA)). Previous work has demonstrated that Prkd1(-/-) is embryonic lethal and that its tissue-specific deletion results in abnormal heart remodelling, whereas Nrp1(-/-) develops TA. Surprisingly, molecular karyotyping to exclude 22q11.2 deletion syndrome in the replication cohort of 17 simplex TA cases revealed a de novo hemizygous deletion that encompasses PRDM1, deficiency of which also results in TA phenotype in mouse. CONCLUSIONS: Our results expand the repertoire of molecular lesions in chromatin remodelling and transcription factors that are implicated in the pathogenesis of congenital heart disease in humans and attest to the power of monogenic forms of congenital heart diseases as a complementary approach to dissect the genetics of these complex phenotypes.