Cardiac Conduction Abnormalities Research Articles

Successful cardiac resynchronization therapy reduces negative septal work in patient-specific models of dyssynchronous heart failure.

In patients with dyssynchronous heart failure (DHF), cardiac conduction abnormalities cause the regional distribution of myocardial work to be non-homogeneous. Cardiac resynchronization therapy (CRT) using an implantable, programmed biventricular pacemaker/defibrillator, can improve the synchrony of contraction between the right and left ventricles in DHF, resulting in reduced morbidity and mortality and increased quality of life. Since regional work depends on wall stress, which cannot be measured in patients, we used computational methods to investigate regional work distributions and their changes after CRT. We used three-dimensional multi-scale patient-specific computational models parameterized by anatomic, functional, hemodynamic, and electrophysiological measurements in eight patients with heart failure and left bundle branch block (LBBB) who received CRT. To increase clinical translatability, we also explored whether streamlined computational methods provide accurate estimates of regional myocardial work. We found that CRT increased global myocardial work efficiency with significant improvements in non-responders. Reverse ventricular remodeling after CRT was greatest in patients with the highest heterogeneity of regional work at baseline, however the efficacy of CRT was not related to the decrease in overall work heterogeneity or to the reduction in late-activated regions of high myocardial work. Rather, decreases in early-activated regions of myocardium performing negative myocardial work following CRT best explained patient variations in reverse remodeling. These findings were also observed when regional myocardial work was estimated using ventricular pressure as a surrogate for myocardial stress and changes in endocardial surface area as a surrogate for strain. These new findings suggest that CRT promotes reverse ventricular remodeling in human dyssynchronous heart failure by increasing regional myocardial work in early-activated regions of the ventricles, where dyssynchrony is specifically associated with hypoperfusion, late systolic stretch, and altered metabolic activity and that measurement of these changes can be performed using streamlined approaches.

Assessing post-TAVR cardiac conduction abnormalities risk using an electromechanically coupled beating heart.

Transcatheter aortic valve replacement (TAVR) has rapidly displaced surgical aortic valve replacement (SAVR). However, certain post-TAVR complications persist, with cardiac conduction abnormalities (CCA) being one of the major ones. The elevated pressure exerted by the TAVR stent onto the conduction fibers situated between the aortic annulus and the His bundle, in proximity to the atrioventricular (AV) node, may disrupt the cardiac conduction leading to the emergence of CCA. In this study, an in silico framework was developed to assess the CCA risk, incorporating the effect of a dynamic beating heart and preprocedural parameters such as implantation depth and preexisting cardiac asynchrony in the new onset of post-TAVR CCA. A self-expandable TAVR device deployment was simulated inside an electromechanically coupled beating heart model in five patient scenarios, including three implantation depths and two preexisting cardiac asynchronies: (i) a right bundle branch block (RBBB) and (ii) a left bundle branch block (LBBB). Subsequently, several biomechanical parameters were analyzed to assess the post-TAVR CCA risk. The results manifested a lower cumulative contact pressure on the conduction fibers following TAVR for aortic deployment (0.018MPa) compared to nominal condition (0.29MPa) and ventricular deployment (0.52MPa). Notably, the preexisting RBBB demonstrated a higher cumulative contact pressure (0.34MPa) compared to the nominal condition and preexisting LBBB (0.25MPa). Deeper implantation and preexisting RBBB cause higher stresses and contact pressure on the conduction fibers leading to an increased risk of post-TAVR CCA. Conversely, implantation above the MS landmark and preexisting LBBB reduces the risk.

Recovery of complete left bundle branch block in dilated cardiomyopathy after optimal heart failure treatment: a case report

Complete left bundle branch block (CLBBB) is a significant cardiac conduction abnormality often associated with dilated cardiomyopathy (DCM). This case report highlights the improvement in CLBBB and symptom relief through reverse cardiac remodeling in a patient diagnosed with DCM following an optimized heart failure treatment regimen consisting of an angiotensin-converting enzyme inhibitor, beta-blocker, and mineralocorticoid receptor antagonist. This case highlights the potential of electrical remodeling and conduction system improvement in patients with DCM receiving optimized medical therapy.

Permanent left bundle branch area pacing improves mitral regurgitation and cardiac function in patients with right bundle branch block

BackgroundPermanent left bundle branch area pacing (LBBAP) has been established as an effective means to correct left bundle branch block. Right bundle branch block (RBBB), emerge as a distinct form of cardiac conduction abnormality, can be seen in the context of LBBAP procedure. However, the correction potential of LBBAP in patients with RBBB remains largely unexplored.ObjectiveThe objective of this study was to evaluate the efficacy and safety of permanent LBBAP in patients with RBBB.MethodsNinety-two consecutive patients who underwent successful permanent LBBAP were recruited from May. 2019 to Dec. 2022 in Fuwai Central China Cardiovascular Hospital. Among them, 20 patients with RBBB were included in our analysis. These patients were followed up at 1, 3, 6 and 12 months post-LBBAP. The QRS duration (QRSd) on the V1 lead of the 12-lead elctrocardiogram was measured and compared before and after the LBBAP procedure. Additionally, mitral regurgitation, tricuspid regurgitation and cardiac function were assessed using transthoracic echocardiography, specifically focusing on left ventricular ejection fraction (LVEF) and mitral regurgitation severity. The acute pitfills and delayed complications associated with the LBBAP procedure were recorded to evaluate its safety. SPSS 23.0 was used to perform statistical analysis with Student’s t test or one way ANOVA or nonparametric tests (paired Wilcoxon test). A p value less than 0.05 was defined as significant.ResultsThe demographic breakdown of the RBBB cohort revealed a mean age of 66.35 ± 11.55 years, 60% being male. Comorbidities were prevalent, including severe atrioventricular block (AVB) in 75%, sick sinus syndrome (SSS) in 20%, heart failure in 25%, atrial fibrillation in 30%, coronary heart diseases in 45%, hypertension in 35%, and diabetes mellitus in 15%. Regarding the LBBAP procedure, the average operation time was 106.53 ± 2.72 min, with 45% of patients (9 individuals) requiring temporary cardiac pacing during the surgery. Notably, the LBBAP procedure significantly narrow the QRS duration in RBBB patients, from 132.60 ± 31.49ms to 119.55 ± 18.58 ms (P = 0.046). Additionally, at the 12-month follow-up, we observed a marked improvement in LVEF, which increased significantly from 55.15 ± 10.84% to 58.5 ± 10.55% (P = 0.018). Furthermore, mitral regurgitation severity improved, with a median reduction from 4.46 (0.9, 7.3) to 2.29 (0, 3.49) cm2 (P = 0.033). Importantly, no cases of ventricular septum perforation or pericardial effusion were reported during the LBBAP procedure or during the follow-up period.ConclusionLBBAP provides an immediate reduction in QRS duration for patients suffering from RBBB, accompanied by improvements in mitral regurgitation and cardiac function as evident in the 12-month follow-up period.

Risk of mortality associated to chronic kidney disease in patients with complete left bundle branch block

Chronic kidney disease (CKD) is associated with cardiac conduction defects and is a strong risk factor for heart failure. Complete left bundle branch block (cLBBB), a cardiac conduction abnormality, may have an unfavorable effect on ventricular mechanical synchrony and lead to the progression of heart failure. Once heart failure develops, it seems to act together with underlying CKD in a vicious circle. Therefore, this study aimed to explore the influence of CKD in patients with cLBBB by assessing the estimated glomerular filtration rate (eGFR). We examined a hospital-based sample of 416 adult patients with cLBBB from 2010 to 2013. The eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Cox proportional hazard models were used to estimate the hazard ratio for all-cause mortality and cardiovascular mortality. A total of 416 adult patients with a mean age of 71 ± 13 years were enrolled. The median follow-up period was 3.6 years. After adjusting for clinical, electrocardiographic parameters, and medication use, cox regression analysis showed that total mortality was significantly associated with older age (Hazard Ratio (HR) = 1.03, 95% CI = 1.01–1.05, p = 0.002), presence of congestive heart failure (HR = 2.39, 95% CI = 1.63–3.49, p < 0.001), advanced CKD (HR = 2.48, 95% CI = 1.71–3.59, p < 0.001), higher HR (HR = 1.02, 95% CI = 1.01–1.03, p < 0.001) and without use of ACEI/ARB (HR = 0.59, 95% CI = 0.41–0.85, p = 0.005) were independent predictors of the total mortality. Multivariate Cox hazard regression analysis demonstrated that, in comparison to patients lacking cLBBB, the coexistence of CKD (eGFR < 60 mL/min/1.73 m2) among those with LBBB significantly heightened the risks of both total mortality (HR ratio of 5.01 vs. 2.40) and CV death (HR ratio of 61.78 vs. 14.41) even following adjustment for clinical covariates and ECG parameters. In summary, within patients exhibiting cLBBB, the presence of CKD serves as a significant risk factor for all-cause mortality.

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.

Isolated cardiac sarcoidosis: a case report

Introduction. Ventricular arrhythmias are a risk factor for sudden cardiac death. Abnormalities of cardiac rhythm and conduction may be the only subjective manifestation of isolated cardiac sarcoidosis, which occurs in 25% of the total number of patients with this disease.Brief description. We present a case of isolated cardiac sarcoidosis in a young female patient, the main clinical manifestation of which was attacks of palpitations caused by ventricular tachycardia and episodes of cardiogenic shock without a cardiovascular history. Echocardiography and contrast-enhanced cardiac magnetic resonance imaging (MRI) revealed asymmetric left ventricular hypertrophy and focal myocardial masses. Cardiac tumor and sarcoidosis were suspected. The final diagnosis was based on the results of histological and immunohistochemical analysis of endomyocardial biopsies documenting sarcoidosis. No systemic manifestations of sarcoidosis were found.Discussion. The case demonstrates the potential of a comprehensive paraclinical study in the diagnosis of cardiac sarcoidosis and its differential diagnosis with other cardiac pathologies.Conclusion. Cardiac sarcoidosis is difficult to diagnose and requires histological verification in patients with LV hypertrophy and arrhythmias, and physicians should be aware about this rare disease with unfavorable prognosis without specific treatment.

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.

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 &amp; 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

Background: Bruton tyrosine kinase inhibitors, such as ibrutinib, are medications that are actively used for Chronic Lymphocytic Leukemia (CLL) and several lymphomas. They work by inhibiting Bruton’s tyrosine kinase therefore affecting B cell proliferation. Ibrutinib itself is associated with multiple cardiotoxicities including atrial fibrillation, ventricular arrhythmias, heart failure, and bleeding. There are well-established studies that show the incidence of atrial fibrillation with ibrutinib therapy. However, only a few reports show an association between ibrutinib therapy and advanced heart block. Case presentation: We present two unique cases of patients who presented to the emergency room with syncope while being on ibrutinib therapy for CLL. At presentation, the patients were found to have conduction abnormalities seen on their EKG that included complete heart block in one patient and sick sinus syndrome in the other. Ultimately, each patient was treated with a pacemaker, ibrutinib therapy was discontinued, and they were started on alternative therapy for their CLL. Discussion: No clear mechanism has been established for how ibrutinib therapy causes these conduction abnormalities. This case series proposes a possible mechanism of advanced conduction abnormalities that is caused by ibrutinib therapy that is associated with the NOTCH gene. We propose that the downregulation of the NOTCH gene may prevent cardiac myocyte remodeling and therefore can cause conduction abnormalities as seen in our patients along with others that presented with advanced heart block with 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+ &gt; 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.