Cardiac Conduction Abnormalities Research Articles

NKX2.5 coding exons sequencing reveals novel non-synonymous mutations in patients with sporadic congenital heart diseases among the Tanzanian population

BackgroundThe evolutionally conserved homeobox transcription factor NKX2-5 has been at the forefront in the field of cardiac biology, providing molecular insights into the mechanisms of cardiac development and disease. This homodomain transcription factor is a central regulator of cardiac development and is expressed in both the first and second heart fields (FHF and SHF). Mutations in the NKX2-5 gene have been linked to sporadic cases of congenital heart disease (CHD), making it a significant target for research and study. While several studies have been conducted on Caucasian populations, there is a dearth of knowledge on the effects of NKX2-5 gene mutations in other settings, underscoring the need for further investigation. Due to differences in geographical and ancestral origin, we hypothesize that mutations may vary across different populations. Understanding the genetic factors that cause CHD is essential for providing effective genetic counseling and developing strategies for risk reduction. Additionally, identification of NKX2-5 mutations in individuals with CHDs is crucial because patients with CHDs are at a higher risk of progressive conduction disease and sudden cardiac death, and genetic information is taken into consideration while making decisions regarding pacemakers and implantable cardiac defibrillators. To determine the risk of congenital heart disease among infants, we conducted a study where we sequenced the exon 1 and exon 2 of NKX 2.5 in patients with sporadic CHDs, with the aim of identifying mutations in the NKX2.5 gene.ResultsIn this study, a novel frame-shift disease-causing mutation was discovered in patients with atrial-ventricular septal defect. The mutation, identified as c95_95 del A; cDNA.369–369 delA; g 369–369 delA, resulted in the substitution of phenylalanine to leucine (F295L), which in turn caused a truncated NKX2.5 protein. In addition, a non-synonymous mutation, g 316C > T; cDNA 316C > T leucine to arginine (L37R) substitution, was found in a patient with the tetralogy of Fallot, affecting protein function. Furthermore, a novel non-synonymous mutation identified as g 2295–2298; cDNA 755–758 delins AGGG, was predicted by mutation taster to be disease-causing in a ventricular septal defect. It is worth noting that none of these mutations were found among the control subjects, highlighting their potential significance in the pathogenesis of these cardiac defects.ConclusionMutations in the NKX2.5 gene are associated with congenital heart diseases and provide molecular insight into the pathogenesis of congenital heart diseases. We recommend that patients with NKX2.5 mutations have periodic screening for cardiac conduction abnormalities and be evaluated for potential implanted cardiac defibrillators and pacemakers.

Disturbance of the human gut microbiota in patients with Myotonic Dystrophy type 1

Myotonic dystrophy type 1 (DM1) is a rare autosomal dominant genetic disorder. Although DM1 is primarily characterized by progressive muscular weakness, it exhibits many multisystemic manifestations, such as cognitive deficits, cardiac conduction abnormalities, and cataracts, as well as endocrine and reproductive issues. Additionally, the gastrointestinal (GI) tract is frequently affected, encompassing the entire digestive tract. However, the underlying causes of these GI symptoms remain uncertain, whether it is biomechanical problems of the intestine, involvement of bacterial communities, or both. The primary objective of this study is to investigate the structural changes in the gut microbiome of DM1 patients. To achieve this purpose, 35 patients with DM1 were recruited from the DM-Scope registry of the neuromuscular clinic in the Saguenay–Lac-St-Jean region of the province of Québec, Canada. Stool samples from these 35 patients, including 15 paired samples with family members living with them as controls, were collected. Subsequently, these samples were sequenced by 16S MiSeq and were analyzed with DADA2 to generate taxonomic signatures. Our analysis revealed that the DM1 status correlated with changes in gut bacterial community. Notably, there were differences in the relative abundance of Bacteroidota, Euryarchaeota, Fusobacteriota, and Cyanobacteria Phyla compared to healthy controls. However, no significant shift in gut microbiome community structure was observed between DM1 phenotypes. These findings provide valuable insights into how the gut bacterial community, in conjunction with biomechanical factors, could potentially influence the gastrointestinal tract of DM1 patients.

Hydroxychloroquine and Chloroquine-Induced Cardiac Arrhythmias and Sudden Cardiac Death in Patients with Systemic Autoimmune Rheumatic Diseases: A Systematic Review and Meta-Analysis.

Hydroxychloroquine (HCQ) and chloroquine (CQ) are foundational treatments for several systemic autoimmune rheumatic diseases, including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Concerns regarding the risk of cardiac arrhythmia and death have been raised, yet the burden of HCQ and CQ-related cardiac toxicities remains unclear. A systematic literature search was conducted in the MEDLINE and Embase databases for articles published between the earliest date and April 2023 reporting cardiac conduction abnormalities in patients with systemic autoimmune rheumatic diseases taking HCQ or CQ. Meta-analysis was performed to calculate the difference in mean QTc and odds ratio of prolonged QTc in those taking HCQ or CQ versus not. Of 2673 unique records, 34 met the inclusion criteria, including 70,609 subjects. Thirty-three studies reported outcomes in HCQ and 9 in CQ. Five studies reported outcomes in RA, 11 in SLE, and 18 in populations with mixed rheumatic diseases. Eleven studies reported mean QTc and OR for prolonged QTc for meta-analysis, all reporting outcomes in HCQ. There was a significant increase in mean QTc among HCQ users in patients with RA (10.29 ms, p = 0.458). There was no difference in mean QTc between HCQ and non-HCQ users in other systemic autoimmune rheumatic diseases. When rheumatic diseases were pooled, HCQ users were more likely to have prolonged QTc (odds ratio 1.57, 95%CI: 1.19, 2.08). QTc prolongation was more likely in patients with systemic autoimmune rheumatic diseases. Clinicians should be aware of potential adverse cardiac events of HCQ and consider QTc monitoring.

Early or late phase cardiac remodelling in metabolic syndrome heart characterized with SQT or LQT

Cardiac conduction abnormalities are the main disorders in metabolic syndrome (MetS), however, their mechanisms are not known yet. Although ventricular arrhythmia pathogenesis reflects the time course of cardiomyocyte action potentials (APs) associated with QT-interval duration, recent studies emphasize the role of intercellular crosstalk between cardiomyocytes and nonmyocytes via passive (electrotonic)-conduction. Therefore, considering the possible intercellular interactions between cardiomyocytes and nonmyocytes as electrophysiological contributors to cardiac-conduction, we hypothesized an early-cardiac-remodeling which is characterized by short QT-interval (SQT) via contributions and modulations of changes in the expressions and localizations of nonmyocytes to the ventricular APs in an early-stage MetS hearts. Significant increases in MetS (14-16 weeks) heart rates and SQT, shortened AP duration with a strong response to β-adrenergic stimulation in the contractile activity of the papillary muscles were determined. The patch-clamp analysis of ventricular cardiomyocytes showed that voltage-dependent Na+-channel currents were increased with decreased L-type Ca2+-channel (LTCC) currents and unchanged K+-channel currents. A hemichannel protein of connexin 43 (Cx43) was highly localized into intercalated discs while phospho-Cx43 was densely localized laterally on the sarcolemma and cytosol with increased total expression levels. A marked high-level positively-stained α-SMA and CD68 cells in interfibrillar spaces of the heart were prominently localized and distributed, implying the possible contributions of myofibroblasts and macrophages to both shortened APs and abnormal electrical conduction in an early-stage MetS heart.Our data propose a previously unrecognized pathway for induction of SQT in the heart: This pathway may include not only the contribution of short ventricular-APs via ionic-mechanisms but also increasing contributions of the electrotonic-cardiomyocyte depolarization, spontaneous electrical activity-associated fast heterogeneous impulse conduction in the heart via non-myocytes. Overall, SQT in early cardiac remodeling may arise with increased interactions between cardiomyocytes and non-myocytes, through increasing contributions of passive-conduction by non-myocytes. TUBITAK SBAG-119S661 & 222S502. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Pattern of Arrhythmia among Hypertensive Patients in South-South, Nigeria: A 24-H Ambulatory ECG (Holter ECG) Study

Background: Regular 12-lead electrocardiogram (ECG) often fail to detect cardiac conduction abnormalities. Among hypertensive patients, conduction irregularities such as atrial fibrillation and ventricular tachycardia are recognized occurrences and these can be intermittent or asymptomatic. This study aims to evaluate the conduction abnormalities identified among hypertensives by Holter ECG in a private medical facility in South-South, Nigeria. Methods: This is a retrospective study of five hundred and thirteen patients consisting of 255 males and 258 females Holter ECG who presented at a private medical facility from January 2015- December 2016. Holter ECG data was acquired using Schiller type (MT-101) Holter ECG Machine. Results: Out of the 370 hypertensive patients reviewed, with a mean age of 55.18 ±.14.78, 205(55.41%) had tachycardia, 180(48.65%) had bradycardia, 184(49.73%) had ventricular ectopics while 169(45.68%) had supraventricular ectopics. The most common clinical indication was palpitation 150 (40.54%). The most prevalent age group was 41-60 years; 230 (44.83%) as compared to other age groups in the study. Tachycardia was the most common type of arrhythmia among the subjects. There was a higher incidence of arrhythmias in the female subjects than in the male. Conclusion: Tachycardia and ventricular ectopics were the most common conduction abnormalities observed. Beta blockers and anti-arrhythmics would be helpful for optimization of cardiovascular care. Holter ECG is beneficial in describing and characterizing arrhythmias in hypertensive patients in this population therefore, further studies on larger populations and diverse disease conditions are advocated.

Advanced Cardiac Conduction Abnormalities in Patients on Ibrutinib Therapy

Advanced Cardiac Conduction Abnormalities in Patients on Ibrutinib Therapy

Azathioprine and hydroxychloroquine overdose in Sjögren’s syndrome patient with hypocalcemia: a case report

IntroductionHydroxychloroquine and azathioprine have been routinely used to control and treat primary and secondary Sjögren’s syndrome, which potentially triggered some overdoses by these drugs. Toxicity from hydroxychloroquine and azathioprine manifests in the form of cardiac conduction abnormalities, nausea, vomiting, and muscle weakness. Recognizing these unique drug overdoses and management of these toxicities is important. This case report aims to expand our current understanding of these drug overdoses and their management and also underscores the importance of anticipating and identifying fewer common complications, such as hypocalcemia.Case reportA 34-year-old Persian woman with a history of Sjögren’s syndrome presented to the emergency department 3.5–4 hours after an intentional overdose of hydroxychloroquine and azathioprine and severe hypotension and loss of consciousness. Although the patient was regularly taking other medications, such as fluoxetine, naproxen, and prednisolone, she explicitly clarified that these were not the substances involved in her overdose. Early investigations showed hypokalemia (2.4 mEq/L), hypocalcemia (7.5 mg/dL), and hypoglycemia (65 mg/dL). She was also diagnosed with metabolic acidosis and respiratory alkalosis. The electrocardiogram showed changes in favor of hypokalemia; other lab tests were run on the patient. Supportive treatments were applied, including rapid intravenous fluid dextrose 5%, normal saline, potassium chloride 30 mEq, and calcium gluconate 100 mg. The patient was managed and monitored overnight in the emergency room and recovered without residual side effects.ConclusionHydroxychloroquine and azathioprine toxicity are considered rare, but it is likely to increase in frequency given the prevalence and increase in autoimmune diseases and the increasing usage of these drugs in treating such diseases. We found hypocalcemia as the presentation to this patient, which needs further investigation into the probable mechanism. Clinicians need to consider the unique effects of hydroxychloroquine and azathioprine poisoning and initiate appropriate emergency interventions to improve the outcomes in similar patients.

A Mutational Hotspot in The LAMP2 Gene: Unravelling Intrafamilial Phenotypic Variation and Global Distribution of The c.877C>T Variant: A Descriptive Study.

Danon disease is defined by a clinical trio of cardiomyopathy, skeletal myopathy, and cognitive impairment. It results from the lysosomal-associated membrane protein-2 (LAMP2) gene variants. The aim of study is determination of genotype and phenotype of a newly diagnosed Iranian family with a unique phenotype due to a pathogenic variant of the LAMP2 gene along with a phenotypic comparison of all reported patients. In this descriptive study, we evaluated the demographic data, clinical features, management procedures, as well as genetic analysis of both patients in this newly diagnosed family. Whole genome sequencing (WGS) and in silico structural and functional predictions were applied. A comprehensive search of the c.877C>T variant in LAMP2 was conducted using the PubMed, Google Scholar, VarSome, ClinVar, Human Gene Mutation Database (HGMD), and Franklin databases to identify any genotype-phenotype correlations. Nine patients were carriers of the c.877C>T variant. All patients were male, and displayed variable degrees of left ventricular hypertrophy (LVH) that ranged from mild to severe. All patients exhibited typical cardiac conduction abnormalities consistent with Danon disease. Four underwent heart transplants and survived. Skeletal muscle involvement and cognitive impairment were observed in four patients each. The mean age of onset was 14 years. The proband in this study exhibited an earlier onset of cardiac symptoms. Genetic analysis is the preferred diagnosis approach for Danon disease and can assist families in managing affected patients, identify carriers, and assist with future family planning. This study highlights the intrafamilial phenotypic variability of Danon disease. It is possible that variants of this gene may be frequent in Iran.

The rise of counterfeit medication: an emerging threat?

Madam, Heart failure (HF) is a multifaceted clinical syndrome arising from a functional or structural cardiac condition that hampers the adequate filling or expulsion of blood into the systemic circulation. It is estimated that heart failure affects around 26 million people globally and significantly adds to healthcare expenditures on a worldwide scale1. Furthermore, in 2016, approximately 16 percent of deaths in Pakistan were due to heart related disorders. This number grew to 29 percent in 20222. HF can greatly diminish the functional capability of a patient and heighten the risk of mortality. Therefore, it is essential to accurately diagnose and proficiently manage this condition to improve the quality of life of the patient. Spironolactone, the first mineralocorticoid receptor antagonist (MRA) to be developed, is prescribed for the management of hypertension, primary hyperaldosteronism, and peripheral oedema linked to cardiac failure3. When HF occurs and cardiac output decreases, it stimulates the renin-angiotensin-aldosterone system (RAAS) which in turn causes salt and water reabsorption and thus increases venous return to the heart which further contributes to congestive heart failure and heart fails to pump the additional fluid and pooling occurs. Here MRAs are very affective as they inhibit the function of aldosterone and hence fluid retention does not occur. Unfortunately, the beneficial effects of spironolactone do not occur without substantial adverse effects. Firstly, spironolactone is associated with sexual adverse events due to its affinity for androgen and progesterone receptors. There have been reports of male patients experiencing gynecomastia and breast pain. Secondly, spironolactone has been classified as potassium sparing diuretic hence hyperkalemia (defined as serum K+ > 5.5 mEq/L) is a common side effect3. Hyperkalemia can manifest as muscle weakness or paralysis, metabolic acidosis, cardiac conduction abnormalities, and life-threatening cardiac arrhythmias4. These cardiac arrythmias can have serious consequences, including cardiac arrest and stroke. In conclusion heart failure, if not treated immediately, can be fatal. Spironolactone is a drug used for management of heart failure; however, it has some detrimental effects on the cardiovascular system such as development of serious cardiac arrythmias. Hyperkalemia, due to potassium sparing nature of MRAs, is the primary cause of these life-threatening effects thus it is recommended to assess serum potassium levels and renal function of a patient with heart failure before prescribing spironolactone. Moreover, patients who are being treated with spironolactone should be periodically monitored to prevent any casualty.

Kearns–Sayre syndrome with type 1 diabetes mellitus: A case report

Kearns–Sayre syndrome (KSS) is a rare genetic mitochondrial myopathy with a typical onset before 20 years of age. It is a variant of chronic progressive external ophthalmoplegia. It is defined by a characteristic triad of progressive external ophthalmoplegia, pigmentary retinopathy, and cardiac conduction abnormalities. The prevalence rate of KSS is ~1–3 per 100,000 individuals. Here, we report a rare case of an 18 year-old Indian female with KSS and type 1 diabetes mellitus.

Analysis of Cardiac Rhythm and Conduction Abnormalities Associated with Intravenous Lacosamide Administration

Analysis of Cardiac Rhythm and Conduction Abnormalities Associated with Intravenous Lacosamide Administration

Unveiling Alarming Trends: Worsening All Cause Mortality in US Adults over 25 with Amyloid 1999-2020 Analysis

Introduction: Amyloidosis is a collective term for conditions with an abnormal extracellular deposition of amyloid protein. Amyloidosis can be classified based on the location of deposition (localized vs systemic) and by the different subtypes of proteins which are created as a result of a variety of diseases (plasma cell dyscrasias, chronic inflammation, nephrotic syndrome, genetic). Depending on the affected organs, amyloidosis can present with, not limited to, hepatomegaly, renal impairment, nerve conduction impairment, cardiac conduction abnormalities, restrictive cardiomyopathy, and multiorgan failure. In the last century there has been an increase in innovations leading to a better understanding of the pathology, diagnostic tests, staging, and treatment options for amyloidosis. Our study aims to compare all cause mortality trends in adults over 25 years old diagnosed with amyloidosis in the United States. Methods: The national mortality trends from 1999 to 2020 for all subtypes of amyloid were analyzed from the CDC WONDER database. The data was extracted using ICD codes E85 (Amyloidosis) with subgroups E85.0 (Non-neuropathic heredofamilial amyloidosis), E85.3 (Secondary systemic amyloidosis), E85.4 (Organ-limited amyloidosis), E85.8 (Other amyloidosis), and E85.9 (Amyloidosis, unspecified. Data was stratified for age groups above 25 years old. Age-adjusted mortality rates (AAMRs) were calculated per 100,000 people and death certificate data was stratified by reported sex, race/ethnicity, and US census region. Results: Between 1999 and 2020 there were 40,015 deaths from amyloid. Our analysis revealed that all-cause AAMR per 100,000 people with amyloid showed an increasing trend between 1999 to 2020 (Figure 1). Subgroup analysis on race/ethnicity revealed the AAMR for the Black population has been consistently higher to other groups (Table 1). On average, from 1999 to 2020, the Black population had the highest AAMR (1.52 AAMR) followed by the White population (0.78 AAMR), Hispanic (0.55 AAMR), and Asian (0.5 AAMR). Further subgroup analysis revealed men have a higher AAMR (1.9 AAMR, 2020) compared to women (0.8 AAMR, 2020). Overall there are similar census region trends of all mortality in Amyloid: North (1.5 AAMR, 2020), Midwest (1.5 AAMR, 2020), South (1.0, AAMR, 2020) and West (1.3 AAMR, 2020). Conclusion: Due to advancement in technology, amyloid diseases are becoming more widely recognized and increasingly diagnosed. Unfortunately, treatment of amyloidosis remains limited to early diagnosis and treatment of the underlying condition. This includes modalities such as chemotherapy and stem cell transplantation for plasma cell dysplasias and TTR stabilizers for hereditary amyloidosis. These trends in increase in AAMR likely reflect the increased awareness/diagnostics of amyloid disease and complications. The African American population may have higher AAMR due to socioeconomic and environmental factors, health disparities, and research bias. We also suspect men have a higher ATTR than women as it has been reported that ATTR and AL Amyloidosis tends to occur more frequently in men than women and is associated with more severe disease (Kroi et al., 2020, Desport et al., 2012). Further research is necessary to expand on the disparities seen with the ultimate goal of providing targeted therapies to reverse this downward trend.

An increase in intercellular crosstalk and electrotonic coupling between cardiomyocytes and nonmyocytes reshapes the electrical conduction in the metabolic heart characterized by short QT intervals in ECGs.

Cardiac conduction abnormalities are disorders in metabolic syndrome (MetS), however, their mechanisms are unknown. Although ventricular arrhythmia reflects the changes in QT-interval of electrocardiograms associated with the changes in cardiomyocyte action potential durations (APDs), recent studies emphasize role of intercellular crosstalk between cardiomyocytes and nonmyocytes via passive (electrotonic)-conduction. Therefore, considering the possible increase in intercellular interactions of nonmyocytes with cardiomyocytes, we hypothesized an early-cardiac-remodeling characterized by short QT-interval via contributions and modulations of changes by nonmyocytes to the ventricular APs in an early-stage MetS hearts. Following the feeding of 8-week-old rats with a high-sucrose diet (32%; MetS rats) and validation of insulin resistance, there was a significant increase in heart rate and changes in the electrical characteristics of the hearts, especially a shortening in action potential (AP) duration of the papillary muscles. The patch-clamp analysis of ventricular cardiomyocytes showed an increase in the Na+ -channel currents while there were decreases in l-type Ca2+ -channel (LTCC) currents with unchanged K+ -channel currents. There was an increase in the phosphorylated form of connexin 43 (pCx43), mostly with lateral localization on sarcolemma, while its unphosphorylated form (Cx43) exhibited a high degree of localization within intercalated discs. A high-level positively-stained α-SMA and CD68 cells were prominently localized and distributed in interfibrillar spaces of the heart, implying the possible contributions of myofibroblasts and macrophages to both shortened APDs and abnormal electrical conduction in MetS hearts. Our data propose a previously unrecognized pathway for SQT induction in the heart. This pathway includes not only the contribution of short ventricular-APDs via ionic mechanisms but also increasing contributions of the electrotonic-cardiomyocyte depolarization, spontaneous electrical activity-associated fast heterogeneous impulse conduction in the heart via increased interactions and relocations between cardiomyocytes and nonmyocytes, which may be an explanation for the development of an SQT in early-cardiac-remodeling.

Lamotrigine use and potential for adverse cardiac effects: A retrospective evaluation in a Veteran population

ObjectiveTo identify the impact of lamotrigine (LTG) on cardiac rhythm and conduction abnormalities for Veterans, an especially vulnerable population. BackgroundIn October 2020 the US Food and Drug Administration (FDA) added a new warning to the label of lamotrigine (Lamictal™) regarding its potential to cause cardiac rhythm and conduction abnormalities [1]. This warning came following in vitro data which suggested Class IB antiarrhythmic effects occurring at clinically achievable concentrations of lamotrigine [2]. However, it is unclear whether the in vitro findings will result in adverse clinical outcomes. Our objective was to assess for evidence for adverse clinical outcomes in a vulnerable population and examine for subtler signs of an association between lamotrigine and cardiac rhythm disturbances. MethodsA retrospective chart review was conducted using records between 10-01-2017 and 07-06-2021, identifying patients at the William S. Middleton Memorial Veterans Hospital who were prescribed lamotrigine. Data collected included: dates of lamotrigine initiation or discontinuation, lamotrigine dosing over the time of the prescription and maximum lamotrigine dose, any cardiac-related ICD-10-CM codes or a history of a cardiology appointment, EKGs with any abnormalities or changes, any concomitantly prescribed medications with known potential to cause cardiac abnormalities, any cardiac deaths. This retrospective chart review was approved by the University of Wisconsin-Madison Institutional Review Board. ResultsTwo hundred and thirty-three (189 male) patients with a lamotrigine prescription and 41.2 % (n = 96) of these patients had an EKG performed while prescribed lamotrigine. The average age of patients was 64.3 ± 13.0 (range 29 to 90) years and mean maximum lamotrigine daily dose was 250.8 ± 148.2 mg (range 25 to 800 mg). Nearly half (47.9 %, 46/96) of the patients were prescribed a concomitant sodium channel blocking medication in addition to lamotrigine. Eighty-four of the patients (87.5 %, 84/96) had a cardiac diagnosis, while 12 (12.5 %, 12/96) did not. A total of 12 deaths occurred within the review period, with two cardiac deaths from congestive heart failure. Four cases did not have information on cause of death. No LTG-associated cardiac adverse effects were noted as part of clinical care, though rash was noted in 5 cases. A total of 7 (7.3 %, 7/96) patients were found to have EKG abnormalities potentially related to lamotrigine, including 7.1 % (6/84) of those with a cardiac diagnosis and 8.3 % (1/12) of those without a cardiac diagnosis. ConclusionsWhile recent FDA warnings have suggested caution regarding cardiac complications associated with lamotrigine based on in vitro studies, the clinical implications are uncertain. Despite selecting a particularly vulnerable population, this retrospective chart review did not identify any deaths due to cardiac rhythm or conduction causes, nor demonstrate unambiguous cardiac complications related to lamotrigine. Even using permissive criteria (including any prolonged PR or QTc) to examine for subtle effects, only a low incidence (<10 %) of potential complications was found. Broader implications of this study are limited by the number of patients included and the retrospective nature of the study. Therefore, further studies are warranted to evaluate a link between cardiac complications and the use of lamotrigine, including the role of concomitant medications such as other sodium channel blocking agents and psychotropic medications.

Optimal Angiographic View for Implantation of Self-Expanding Transcatheter Aortic Valves

Background. Transcatheter aortic valve implantation is safe and effective alternative to surgical treatment of severe aortic valve stenosis among patients of all risk groups. Optimal implantation depth is key for successful hemodynamic and clinical&#x0D; Results. Despite the improvement of prostheses design and increasing experience of operators cardiac conduction abnormalities and paravalvular leak continue to be a significant complication of this procedure, directly affecting the long-term prognosis. Self-expanding valves require special approaches for optimal angiographic projection to assess the implantation depth of the prosthesis. &#x0D; Aims in this study we compared coplanar view and cusp overlap technique during self-expanding aortic valves implantation. &#x0D; Methods. We performed a retrospective analysis of 81 TAVI performed in Russian Research Center of Surgery. The patients were divided into two groups depending on the implantation projection: coplanar view (CV) and cusp overlap technique (COT). The incidence of cardiac conduction abnormalities (cumulative incidence of third degree AV block and left bundle branch block) depending on the implantation projection was analyzed. The procedural characteristics in the form of contrast agent volume, fluoroscopic time and operator comfort were also evaluated. &#x0D; Results. After TAVI 16 (51.6%) and 13 (26.0%) patients had cardiac conduction disturbances (cumulative incidence of third degree AV block and left bundle branch block) in the CV and COT respectively (p = 0.019). In the CV group, 2 (6.5%) patients, and in the COT group, 3 (6%) patients had third degree AV block (p = 0.935) and 14 (45.2%) и 10 (20%) left bundle branch block (p = 0,016). In the COT group, there was a significant decrease contrast media (181 66.4 mL vs. 158.9 50.8 mL, p = 0.032). Fluoroscopic time also decreased (23.2 7.7 min vs. 21.3 6.8 min), but without a significant difference (p = 0.678). According to the results of the operator survey, the COT projection was more comfortable. &#x0D; Conclusions. Optimal implantation depth is an important condition for achieving hemodynamic efficiency of the prosthesis and reducing the risk of conduction abnormalities. Operator comfort, better assessment of the implantation depth, safety and efficiency of the cusp overlap technique allow its use as the main implantation view for TAVI.

Prevalence of metabolic syndrome and its association with atrial arrhythmias in patients with implanted permanent pacemaker for cardiac conduction abnormality

The objective of the study was to find the prevalence of metabolic syndrome along with identifying the atrial arrhythmias, QTC interval, and coronary artery disease among these patients during follow-ups. Among 171 subjects who were implanted with permanent pacemakers, metabolic syndrome was present in 90 (52.6 %). Prevalence of Arrhythmias was 49 (28.7 %), atrial tachycardia (AT)/atrial fibrillation (AF) was seen in 29 (17 %) patients. Our study showed that there is a strong association between metabolic syndrome and atrial arrhythmias. Metabolic syndrome, age, coronary artery disease and Systolic blood pressure were good independent predictors of atrial arrhythmias among patients with pacemaker implantation.

Clinical characteristics and prognostic impact of immune checkpoint inhibitor-associated myocarditis in advanced non-small cell lung cancer.

Myocarditis is a rare immune-related adverse events (irAEs) with high mortality rates, with few reports on its clinical characteristics and prognostic impact. This study designed to explore the associations between cardiac parameters and outcomes of myocarditis in advanced non-small cell lung cancer (NSCLC) who treated with immune checkpoint inhibitor (ICI). Fourteen patients diagnosed with ICI-associated myocarditis by clinicians were admitted to the study analysis. By Cox univariate and multivariate survival analyses, potential risk factors for the development of severe myocarditis were identified. Survival analysis was also performed to explore the prognosis of patients with myocarditis. Among patients with myocarditis, higher B-type natriuretic peptide (BNP) levels (P= 0.04) and conduction block (P= 0.03) were associated with progression to severe myocarditis. In addition, high lactate dehydrogenase (LHD) levels (P= .04) and myocarditis onset within 2 months (P= 0.02) were prognostic factors of severe myocarditis. The median progression-free survival (PFS) time and median overall survival (OS) time for all patients were 5.9 months and 18.5 months, respectively. However, there were no statistical differences between mild and severe cohorts in terms of PFS and OS (PFS: 4.5 vs. 8.5 months, P= 0.17; OS: 21.3 vs. 18.5months, P= 0.36). And we found that the earlier occurrence of myocarditis, worse PFS prognosis (4.5 months vs. 10.5 months, P= 0.008), while no difference in OS (18.5 months vs. 21.3 months, P= 0.35). Compared to mild myocarditis, severe myocarditis presented with higher BNP levels and cardiac conduction abnormalities. In addition, patients with mild and early myocarditis tended to have better survival rates.

Noncoding RNAs and Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes in Cardiac Arrhythmic Brugada Syndrome.

Hundreds of thousands of people die each year as a result of sudden cardiac death, and many are due to heart rhythm disorders. One of the major causes of these arrhythmic events is Brugada syndrome, a cardiac channelopathy that results in abnormal cardiac conduction, severe life-threatening arrhythmias, and, on many occasions, death. This disorder has been associated with mutations and dysfunction of about two dozen genes; however, the majority of the patients do not have a definite cause for the diagnosis of Brugada Syndrome. The protein-coding genes represent only a very small fraction of the mammalian genome, and the majority of the noncoding regions of the genome are actively transcribed. Studies have shown that most of the loci associated with electrophysiological traits are located in noncoding regulatory regions and are expected to affect gene expression dosage and cardiac ion channel function. Noncoding RNAs serve an expanding number of regulatory and other functional roles within the cells, including but not limited to transcriptional, post-transcriptional, and epigenetic regulation. The major noncoding RNAs found in Brugada Syndrome include microRNAs; however, others such as long noncoding RNAs are also identified. They contribute to pathogenesis by interacting with ion channels and/or are detectable as clinical biomarkers. Stem cells have received significant attention in the recent past, and can be differentiated into many different cell types including those in the heart. In addition to contractile and relaxational properties, BrS-relevant electrophysiological phenotypes are also demonstrated in cardiomyocytes differentiated from stem cells induced from adult human cells. In this review, we discuss the current understanding of noncoding regions of the genome and their RNA biology in Brugada Syndrome. We also delve into the role of stem cells, especially human induced pluripotent stem cell-derived cardiac differentiated cells, in the investigation of Brugada syndrome in preclinical and clinical studies.

Transcatheter Aortic Valve Implantation and Cardiac Conduction Abnormalities: Prevalence, Risk Factors and Management.

Over the last decades, transcatheter aortic valve implantation (TAVI) or replacement (TAVR) has become a potential, widely accepted, and effective method of treating aortic stenosis in patients at moderate and high surgical risk and those disqualified from surgery. The method evolved what translates into a noticeable decrease in the incidence of complications and more beneficial clinical outcomes. However, the incidence of conduction abnormalities related to TAVI, including left bundle branch block and complete or second-degree atrioventricular block (AVB), remains high. The occurrence of AVB requiring permanent pacemaker implantation is associated with a worse prognosis in this group of patients. The identification of risk factors for conduction disturbances requiring pacemaker placement and the assessment of their relation to pacing dependence may help to develop methods of optimal care, including preventive measures, for patients undergoing TAVI. This approach is crucial given the emerging evidence of no worse outcomes for intermediate and low-risk patients undergoing TAVI in comparison to surgical aortic valve replacement. This paper comprehensively discusses the mechanisms, risk factors, and consequences of conduction abnormalities and arrhythmias, including AVB, atrial fibrillation, and ventricular arrhythmias associated with aortic stenosis and TAVI, as well as provides insights into optimized patient care, along with the potential of conduction system pacing and cardiac resynchronization therapy, to minimize the risk of unfavorable clinical outcomes.

Clinical Case of Mccune-Albright-Braitsev Syndrome (MAS)

The presented clinical case describes orphan disease known as MAS with manifested symptoms of precocious puberty, recurrent ovarian cysts, fibrous dysplasia, café-au-lait skin pigmentation and abnormal cardiac conduction. The pathogenesis is based on the GNAS gene mutation that cause hyperactivation of glycoprotein hormone receptors and hypersecretion. There are genetic tests that confirm the diagnosis, however, given the high percentage of false negative results, in most cases the disease is diagnosed based on a combination of clinical and laboratory-instrumental data. Given the high clinical variability and absence of management algorithms for patient with this syndrome, the article pinpoints the necessity of thorough examination of patients to select further management tactics. Multidisciplinary approach and collegiate case management will improve diagnosis of the disease and prevent the development of severe complications.