Cardiac Conduction Disturbances Research Articles

Usefulness of Gabapentin as an Alternative/Adjunct Therapy for Delirium: A Retrospective Observational Study.

Antipsychotics are commonly used to treat delirium but can adversely affect the extrapyramidal and cardiac conduction systems. Antipsychotic use has also been reported to be associated with increased mortality in older adults. Therefore, alternative and adjunct medications for delirium are necessary. We retrospectively assessed the efficacy and safety of gabapentin (GBP) as an alternative and adjunct medication for delirium. We retrospectively investigated the records of patients with delirium treated with GBP (71 patients; median age, 81 years; interquartile range, 76-87.5 years; 54.9% males) at a general hospital. We examined duration to delirium improvement, as assessed by the Intensive Care Delirium Screening Checklist (ICDSC) and DSM-5 criteria, as well as adverse events. The median (interquartile range) GBP dose was 200 mg (150-350 mg) /day. A total of 71.8% and 85.9% of the patients failed to meet the diagnostic criteria for delirium at 2 days and 5 days after initial administration, respectively (p<0.05). In subgroup analysis, patients with a history of epilepsy or cerebrovascular disease responded better to GBP than did those without such histories, suggesting that patients with abnormal/borderline neuronal activity respond to GBP even though they do not exhibit seizures. GBP did not induce extrapyramidal symptoms, cardiac conduction disturbances, hyperglycemia, or epilepsy but caused sleepiness and myoclonus. GBP may improve delirium with fewer adverse effects and may be a safe alternative or adjunct treatment for delirium. Dosage adjustment may be necessary to prevent sleepiness.

Depth of implantation in relation to membranous septum as a predictor of conduction disturbances after transcatheter aortic valve implantation

BackgroundConduction disturbances remain one of the most common complications occurring post TAVI. We aim to determine the predictors of cardiac conduction disturbances after Transcatheter Aortic Valve Implantation (TAVI) and propose a relevant predictive model.We included 70 consecutive patients with severe symptomatic AS who underwent TAVI using the self-expanding valve Evolut R or the balloon expandable Sapien XT valve. All patients were subjected to electrocardiographic evaluation pre- and post-TAVI and at 30 days. Clinical, echocardiographic, CT-derived, and procedural parameters were collected and analyzed. ResultsConduction disturbances affected 28 patients (40%): 16 patients (22.9 %) developed Left Bundle Branch Block (LBBB), 7 patients (10%) experienced transient Complete Heart Block (CHB), and 5 patients (7.1%) experienced permanent CHB requiring Permanent Pacemaker Implantation (PPI). We classified predictors into preprocedural and procedural predictors. Multivariate logistic regression analysis of pre-procedural predictors showed that the presence of basal septal calcification is the most powerful independent predictor (OR: 28.63, 95% CI: 4.59–178.68, p < 0.001). Multivariate logistic regression analysis for pre and post procedural predictors showed that the relationship between depth of implantation at the septum and membranous septum expressed in percentage (sDIMS) with cut-off >70.42% is the most powerful independent procedural predictor (OR: 1.11, 95% CI: 1.03–1.2, p 0.006). ConclusionConduction disturbances remain a common complication of TAVI. Presence of basal septal calcification is a non-modifiable risk factor that increase patient propensity of development such complication after TAVI. A depth of implantation exceeding 70% of the membranous septal length has been found to strongly predict conduction disturbances post TAVI. sDIMS can be used in planning the depth of implantation to reduce incidence of conduction disturbances post TAVI.

Prevention and treatment of neonatal lupus – a literature review

Introduction: Neonatal lupus is a syndrome diagnosed in newborns whose mothers suffer from systemic connective tissue diseases with the presence of antibodies to Ro(SS-A) and La(SS-B) antigens. It most often manifests with skin lesions and cardiac conduction disturbances. The aim of the study was to analyse the risk factors for neonatal lupus based on a literature review. In addition, a number of recommendations were formulated for prevention and further management of affected mothers and their children. Materials and methods: We reviewed PubMed, ResearchGate and Google Scholar databases. A combination of keywords: lupus, pregnant, infant, heart block (according to Medical Subject Headings, MeSH) was used to identify relevant publications. Results: Given the lack of protocols for the diagnosis and treatment of neonatal lupus, ensuring that women can monitor foetal heart rate and quickly access obstetric care in the event of abnormal readings is an important aspect in the early diagnosis of the disease. The question of prevention and treatment remains open, but given the results of recent studies, recommendations on prevention and treatment of this syndrome have been designed. Conclusions: 1. Prophylactic maternal intake of hydroxychloroquine. 2. Weekly doppler ultrasound of the umbilical artery and echocardiography. 3. Planning delivery in specialised health care units. 4. Follow-up of the infant until 6–7 months of age.

CHARACTERISTICS OF COGNITIVE FUNCTIONS DURING THE RECOVERY PERIOD AFTER ISCHEMIC STROKES IN PATIENTS WITH IMPAIRED CARDIAC RHYTHM AND CONDUCTION

Introduction. Disturbances of cardiac rhythm and conduction are risk factors for cognitive impairments.&#x0D; Aim: to determine peculiarities of the cognitive status in patients with impaired heart rhythm and conduction during the recovery period after ischemic non-lacunar strokes.&#x0D; Material and methods. This study included 52 patients with atrial fibrillation, 18 patients with atrioventricular block 2-3 degrees, and 24 patients with sinus rhythm who had an ischemic non-lacunar stroke during the last 6 months. Cognitive status was measured using the MMSE, MoCA, ADAS-cog scales, the Clock Drawing Test, the “5 Words” test, and the frontal assessment battery.&#x0D; Results. According to the MoCA scale, patients with atrial fibrillation and atrioventricular block were significantly more often diagnosed with post-stroke cognitive impairments (71.2% and 77.8%, respectively) compared with patients having sinus rhythm (37.5%). Among patients with cognitive impairments by the MoCA scale, the presence of atrial fibrillation was associated with a significant decrease in MoCA scale scores, compared with sinus rhythm (18.0 (17.0-22.0) versus 22.0 (18.0-23.0)). In patients with sinus rhythm, the clock-drawing test had higher scores (8.0 (7.0-9.0)) compared to cases with atrial fibrillation (7.0 (5.8-8.0)). Patients with sinus rhythm had higher values of the frontal assessment battery (15.0 (14.0-15.0)) compared to atrial fibrillation (13.0 (12.0-14.0)) and atrioventricular blocks (14.0 (13.0- 15.0)).&#x0D; Conclusions. During the first 6 months after schemic non-lacunar strokes, patients with impaired heart rhythm and conduction demonstrated a significant prevalence of cognitive impairments by the MoCA scale and significantly worse scores of cognitive tests for executive functions.

Impact of GLA Variant Classification on the Estimated Prevalence of Fabry Disease: A Systematic Review and Meta-Analysis of Screening Studies.

The diagnosis of Fabry disease (FD) has relevant implications related to the management. Thus, a clear assignment of GLA variant pathogenicity is crucial. This systematic review and meta-analysis aimed to investigate the prevalence of FD in high-risk populations and newborns and evaluate the impact of different GLA variant classifications on the estimated prevalence of FD. We searched the EMBASE and PubMed databases on February 21, 2023. Observational studies evaluating the prevalence of FD and reporting the identified GLA variants were included. GLA variants were re-evaluated for their pathogenicity significance using the American College of Medical Genetics and Genomics criteria and the ClinVar database. The pooled prevalence of FD among different settings was calculated. The study was registered on PROSPERO (CRD42023401663) and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Of the 3941 studies identified, 110 met the inclusion criteria. The pooled prevalence of FD was significantly different according to the clinical setting and criteria used for the pathogenicity assessment. Using the American College of Medical Genetics and Genomics criteria, the pooled prevalence was 1.2% in patients with left ventricular hypertrophy/hypertrophic cardiomyopathy (26 studies; 10 080 patients screened), 0.3% in end-stage renal disease/chronic kidney disease (38 studies; 62 050 patients screened), 0.7% in stroke (25 studies; 15 295 patients screened), 0.7% in cardiac conduction disturbance requiring pacemaker (3 studies; 1033 patients screened), 1.0% in small-fiber neuropathy (3 studies; 904 patients screened), and 0.01% in newborns (15 studies; 11 108 793 newborns screened). The pooled prevalence was different if the GLA variants were assessed using the ClinVar database, and most patients with a discrepancy in the pathogenicity assignment carried 1 of the following variants: p.A143T, p.D313Y, and p.E66Q. This systematic review and meta-analysis describe the prevalence of FD among newborns and high-risk populations, highlighting the need for a periodic reassessment of the GLA variants in the context of recent clinical, biochemical, and histological data. URL: https://crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42023401663.

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.

Structural features of the heart in children with arrhythmic syndrome due to nonspecific connective tissue disorder

Introduction. Connective tissue is highly organized system, its disorders are characterized by a pronounced polymorphism of morphological and clinical manifestations. The cardiovascular pathology in patients with nonspecific connective tissue disorder attracts attention due to the high risk of complications: rhythm and conduction disorders, infective endocarditis, vascular thromboembolism and sudden cardiac death. Therefore, it’s very important to use up-to-date equipment and methods of early diagnosis of a high risk of fatal events in young.Aim. To investigate the structural features of the heart and their relationship with the process of myocardial remodeling in children with arrhythmic syndrome and nonspecific connective tissue disorder.Materials and methods. Sixty-five children were examined, 40 of them had arrhythmic syndrome in combination with nonspecific connective tissue disorder, and 25 had only minimal manifestations of nonspecific connective tissue disorder without arrhythmic syndrome. Such up-to-date methods as assessment of myocardial remodeling and longitudinal strain, natriuretic peptide assessment were included in the diagnostic algorithm.Results and discussion. The study showed a variety of phenotypic and visceral markers of nonspecific connective tissue disorder in children with arrhythmic syndrome. Arrhythmic syndrome was manifested by monotopic and heterotopic heart rhythm disorders, and structural changes of the heart: mitral valve prolapse and myocardial wall thinning were correlated with a more frequent increase in natriuretic peptide. Speckle-tracking echocardiography showed a significant decrease in longitudinal myocardial strain with predominance of myocardial strain in the anterior basal segment in children with arrhythmic syndrome.Conclusion. Our study showed a variety of phenotypic and visceral markers of undifferentiated connective tissue dysplasia in children with arrhythmic syndrome. The data obtained require further mathematical analysis and the establishment of a possible relationship between the external manifestations of the disease and cardiac rhythm and conduction disturbances.

Guidelines for pharmacotherapy in Alzheimer's disease - A primer on FDA-approved drugs.

The growing prevalence of dementia makes it important for us to better understand its pathophysiology and treatment modalities, to improve the quality of life of patients and caregivers. Alzheimer's disease (AD), a neurodegenerative disease, is the most common form of amnestic dementia in the geriatric population. Pathophysiology of AD is widely attributed to aggregation of amyloid-beta (Aβ) plaques and hyperphosphorylation of tau proteins. Initial treatment modalities aimed to increase brain perfusion in a non-specific manner. Subsequent therapy focused on rectifying neurotransmitter imbalance in the brain. Newer drugs modify the progression of the disease by acting against aggregated Aβ plaques. However, not all drugs used in therapy of AD have been granted approval by the United States Food and Drug Administration (FDA). This review categorizes and summarizes the FDA-approved drugs in the treatment of AD in a manner that would make it a convenient reference for researchers and practicing physicians alike. Drugs that mitigate symptoms of dementia may be categorized into mitigators of Behavioral and Psychological Symptoms of Dementia (BPSD), and mitigators of cognitive decline. BPSD mitigators include brexpiprazole, an atypical antipsychotic with a once-daily dosage suited to treat agitation in dementia patients, and suvorexant, an orexin receptor antagonist used to treat sleep disturbances. Cognitive decline mitigators include cholinesterase inhibitors such as donepezil, rivastigmine, and galantamine and glutamate inhibitors such as memantine. Donepezil is the most commonly prescribed drug. It is cheap, well-tolerated, and may be prescribed orally once daily, or as a transdermal patch once weekly. It increases ACh levels, enhances oligodendrocyte differentiation and also protects against Aβ toxicity. However, regular cardiac monitoring is required due to reports of cardiac conduction side effects. Rivastigmine requires a twice-daily oral dosage or once-daily replacement of transdermal patch. It has fewer cardiac side effects than donepezil, but local application-site reactions have been noted. Galantamine, in addition to improving cognitive symptoms in a short span of time, also delays the development of BPSDs and has minimal drug-drug interactions by virtue of having multiple metabolic pathways. However, cardiac conduction disturbances must be closely monitored for. Memantine, a glutamate regulator, acts as an anti-Parkinsonian agent and an antidepressant, in addition to improving cognition and neuroprotection, and requires a once-daily dosage in the form of immediate-release or sustained-release oral tablets. Disease-modifying drugs such as aducanumab and lecanemab reduce the Aβ burden. Both act by binding with fibrillary conformations of Aβ plaques in the brain. These drugs have a risk of causing amyloid-related imaging abnormalities, especially in persons with ApoE4 gene. Aducanumab is administered once every 4 weeks and lecanemab once every 2 weeks. The decision on the choice of the drug must be made after considering the availability of drug, compliance of patient (once-daily vs. multiple doses daily), cost, specific comorbidities, and the risk-benefit ratio for the particular patient. Other non-pharmacological treatment modalities must also be adopted to have a holistic approach toward the treatment of AD.

A Patient with Mitochondrial Disease on Dialysis with Long-term Follow-up of Cardiomyopathy: An Autopsy Case Report.

A 59-year-old man developed diabetes at 24 years old and underwent hemodialysis at 42 years old. At 54 years old, cardiac dysfunction with left ventricular hypertrophy was detected, followed by complete atrioventricular block at 57 years old. The patient was diagnosed with mitochondrial disease based on a myocardial biopsy and the presence of a mitochondrial DNA mutation (3243A>G). He died of septic shock at 59 years old, and an autopsy confirmed mitochondrial cardiomyopathy. If progressive cardiac hypertrophy and conduction disturbances are observed in patients with diabetes mellitus on long-term hemodialysis, mitochondrial disease needs to be considered.

Transthyretin amyloid cardiomyopathy

Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed cause of heart failure and arrhythmia. This differential diagnosis should particularly be considered in older patients with left ventricular hypertrophy (LVH) who are also suffering from heart failure with preserved ejection fraction (HFpEF) or aortic valve stenosis. ATTR-CM is caused either by agenetic variation or by aging processes. The extracellular accumulation of amyloid fibrils in the heart causes arestrictive cardiomyopathy, which leads to typical heart failure symptoms as well as cardiac conduction and repolarization disturbances. Extracardiac problems such as acarpal tunnel syndrome can also be indicative for ATTR-CM. The disease can be diagnosed either by amyocardial biopsy or alternatively by apositive bone scintigraphy with the simultaneous exclusion of monoclonal proteins in blood and urine. Besides asymptomatic treatment, the transthyretin (TTR) stabilizer tafamidis is now available, which can significantly delay the disease progress. In the coming years, the approval of further drugs for the treatment of ATTR-CM is to be expected.

НАРУШЕНИЯ СЕРДЕЧНОГО РИТМА И ПРОВОДИМОСТИ У МУЖЧИН МОЛОЖЕ 50 ЛЕТ С КАРДИОГЕННЫМ ШОКОМ ПРИ ИНФАРКТЕ МИОКАРДА

Relevance. Cardiogenic shock remains one of the most common causes of death in myocardial infarction. Aim. To evaluate the features of cardiac rhythm and conduction disturbances in myocardial infarction complicated by cardiogenic shock, as well as their significance for the development of this complication in males under 50 years old to improve prevention and outcomes. Material and methods. The study included males aged 19-49 years old with type I myocardial infarction. The patients were divided into age- comparable groups. The study group consisted of seven patients with cardiogenic shock, the control group - without cardiogenic shock - 223 patients. A comparative analysis of arrhythmias among the variants of the clinical course, complications, as well as their structure in selected groups were performed. The influence of the studied parameters on the risk of cardiogenic shock development in the examined patients was assessed by the method of risk analysis using the Pearson Chi-square test. Results. In the study group, a higher incidence of arrhythmias in the structure of MI complications (85.7%) was revealed than in the control group (24.2%; p=0.003). They were observed in combination with complications of the group of contractile myocardial insufficiency and its mechanical failure (57.1% and 6.3%, respectively; р˂0.0001) and only contractile insufficiency (28.6% and 11.2%; р˂0,0001). In the structure of arrhythmias in the study group, the frequency of observation of atrial fibrillation and flutter (66.7%) prevailed over the control group (4.9%; р˂0.0001), ventricular fibrillation (50.0 and 2.4%, respectively; р˂ 0.0001), supraventricular tachycardias (33.3% and 1.5%; р˂0.0001), supraventricular (33.3% and 8.3%; р=0.03) and polytopic extrasystoles (33.3% and 3 .9%; p=0.0003), ventricular tachycardias (16.7% and 2.0%; p=0.02), complete atrioventricular blockades (16.7% and 2.0%; p=0.02) and asystole (16.7% and 1.5%; p=0.007). The risk of cardiogenic shock development increased with these arrhythmias. Conclusions. The listed types of arrhythmias should be used in the formation of high-risk groups for the cardiogenic shock development in myocardial infarction for monitoring and timely implementation of the necessary treatment. It is also expedient to take them in the prognostic modeling of this complication.

Cardiac arrhythmias and conduction abnormalities in patients with type 2 diabetes

The association between type 2 diabetes (T2D) and the development of cardiac arrhythmias and conduction disturbances has not been extensively studied. Arrhythmia was defined as atrial fibrillation and flutter (AF/AFl), ventricular tachycardia (VT) and ventricular fibrillation (VF), and conduction abnormality as sinus node disease (SND), atrioventricular (AV) block or pacemaker implantation, and intraventricular conduction blocks (IVCB). Incidence rates and Cox regression were used to compare outcomes, and to assess optimal levels for cardiometabolic risk factors and risk associated with multifactorial risk factor control (i.e., HbA1c, LDL-C, systolic blood pressure (SBP), BMI and eGFR), between patients with versus without T2D. The analyses included data from 617,000 patients with T2D and 2,303,391 matched controls. Patients with diabetes and the general population demonstrated a gradual increase in rates for cardiac conduction abnormalities and virtually all age-groups for AF/AFI showed increased incidence during follow-up. For patients with versus without T2D, risks for cardiac arrhythmias were higher, including for AF/AFl (HR 1.17, 95% CI 1.16–1.18), the composite of SND, AV-block or pacemaker implantation (HR 1.40, 95% CI 1.37–1.43), IVCB (HR 1.23, 95% CI 1.18–1.28) and VT/VF (HR 1.08, 95% CI 1.04–1.13). For patients with T2D who had selected cardiometabolic risk factors within target ranges, compared with controls, risk of arrythmia and conduction abnormalities for T2D vs not were: AF/AFl (HR 1.09, 95% CI 1.05–1.14), the composite of SND, AV-block or pacemaker implantation (HR 1.06, 95% CI 0.94–1.18), IVCB (HR 0.80, 95% CI 0.60–0.98), and for VT/VF (HR 0.97, 95% CI 0.80–1.17). Cox models showed a linear risk increase for SBP and BMI, while eGFR showed a U-shaped association. Individuals with T2D had a higher risk of arrhythmias and conduction abnormalities than controls, but excess risk associated with T2D was virtually not evident among patients with T2D with all risk factors within target range. BMI, SBP and eGFR displayed significant associations with outcomes among patients with T2D.

НАРУШЕНИЯ РИТМА И ПРОВОДИМОСТИ У ПАЦИЕНТОВ С ЭЛЕКТРОКАРДИОГРАФИЧЕСКИМ ФЕНОМЕНОМ РАННЕЙ РЕПОЛЯРИЗАЦИИ ЖЕЛУДОЧКОВ

The frequency and nature of cardiac arrhythmias and conduction disturbances in children and adolescents with electrocardiographic syndrome of early ventricular repolarization were studied. It has been determined that cardiac rhythm and conduction disturbances in patients with early ventricular repolarization syndrome are quite common, with a predominance of arrhythmias caused by a change in the automatism function of the sinus node and the presence of intraventricular blockades. It was revealed that in children with this electrocardiographic phenomenon, in the vast majority of cases, there are manifestations of the syndrome of connective tissue dysplasia - minor anomalies in the development of the heart – 84.1%, (p &lt; 0.001), and additional chords are most often recorded in the cavity of the left ventricle – 85.6% (p &lt; 0.001), both isolated and in combination with other anomalies and congenital heart defects. It was found that cardiac rhythm and conduction disturbances in patients with electrocardiographic syndrome of early ventricular repolarization are quite common (78.6±1.84%), with a predominance of cases of arrhythmias caused by changes in the automatism function of the sinus node (p &lt; 0.001) and the presence of intraventricular blocks. In children and adolescents with early ventricular repolarization, additional chords are most often recorded (85.6%, (p &lt; 0.001)), both isolated and in combination with other heart anomalies. The data obtained indicate the presence of a relationship between the early ventricular repolarization syndrome and connective tissue dysplasia, which makes it possible to attribute this electrocardiographic syndrome to the conditions associated with this syndrome.

Possible changes in the electroencephalogram and electrocardiogram after the introduction of peripheral muscle relaxants

To evaluate the changes in the electroencephalogram (EEG) parameters in time, coinciding with the changes recorded by the electrocardiogram (ECG) channel in patients after the introduction of peripheral muscle relaxants. Twenty-four patients were examined in intensive care units on artificial lung ventilation (ALV). During the study, myographic artifacts were recorded in all patients in the EEG, the elimination of which was impossible without the use of pharmacological agents leading to relaxation of muscles - muscle relaxants of peripheral action. Complete suppression of myographic artifacts on the EEG was noted in all patients after the introduction of peripheral muscle relaxants. However, in 4 of them, EEG changes were noted in the period 2 to 3 minutes after the introduction of muscle relaxants and the disappearance of myographic artifacts on the EEG. These changes coincided in time with the changes recorded by the ECG channel. The EEG changes in time, coinciding with the changes in ECG indicators, suggest the presence of short-term disturbances of the functional state of the basic brain systems, probably due to changes in hemodynamics due to cardiac rhythm and conduction disturbances. It is advisable to record the EEG with the inclusion of an ECG channel in the wiring diagram for synchronous recording.

Las mutaciones missense en el dominio ROD2 de la filamina C muestran un fenotipo con miocardiopatía restrictiva/hipertrófica y miocardio en dientes de sierra

Introduction and objectivesMissense mutations in the filamin C (FLNC) gene have been reported as cause of inherited cardiomyopathy. Knowledge of the pathogenicity and genotype-phenotype correlation remains scarce. Our aim was to describe a distinctive cardiac phenotype related to rare missense FLNC variants in the ROD2 domain. MethodsWe recruited 21 unrelated families genetically evaluated because of hypertrophic cardiomyopathy (HCM)/restrictive cardiomyopathy (RCM) phenotype carrying rare missense variants in the ROD2 domain of FLNC (FLNC-mRod2). Carriers underwent advanced cardiac imaging and genetic cascade screening. Myocardial tissue from 3 explanted hearts of a missense FLNC carrier was histologically analyzed and compared with an FLNC-truncating variant heart sample and a healthy control. Plasmids independently containing 3 FLNC missense variants were transfected and analyzed using confocal microscopy. ResultsEleven families (52%) with 20 assessed individuals (37 [23.7-52.7]) years showed 15 cases with a cardiac phenotype consisting of an overlap of HCM-RCM and left ventricular hypertrabeculation (saw-tooth appearance). During a median follow-up of 6.49 years, they presented with advanced heart failure: 16 (80%) diastolic dysfunction, 3 heart transplants, 3 heart failure deaths) and absence of cardiac conduction disturbances or skeletal myopathy. A total of 6 families had moderate genotype-phenotype segregation, and the remaining were de novo variants. Differential extracellular matrix remodeling and FLNC distribution among cardiomyocytes were confirmed on histology. HT1080 and H9c2 cells did not reveal cytoplasmic aggregation of mutant FLNC. ConclusionsFLNC-mRod2 variants show a high prevalence of an overlapped phenotype comprising RCM, HCM and deep hypertrabeculation with saw-tooth appearance and distinctive cardiac histopathological remodeling.Full English text available from:www.revespcardiol.org/en

Uremic toxins in chronic kidney disease highlight a fundamental gap in understanding their detrimental effects on cardiac electrophysiology and arrhythmogenesis.

Chronic kidney disease (CKD) and cardiovascular disease (CVD) have an estimated 700-800 and 523 million cases worldwide, respectively, with CVD being the leading cause of death in CKD patients. The pathophysiological interplay between the heart and kidneys is defined as the cardiorenal syndrome (CRS), in which worsening of kidney function is represented by increased plasma concentrations of uremic toxins (UTs), culminating in dialysis patients. As there is a high incidence of CVD in CKD patients, accompanied by arrhythmias and sudden cardiac death, knowledge on electrophysiological remodeling would be instrumental for understanding the CRS. While the interplay between both organs is clearly of importance in CRS, the involvement of UTs in pro-arrhythmic remodeling is only poorly investigated, especially regarding the mechanistic background. Currently, the clinical approach against potential arrhythmic events is mainly restricted to symptom treatment, stressing the need for fundamental research on UT in relation to electrophysiology. This review addresses the existing knowledge of UTs and cardiac electrophysiology, and the experimental research gap between fundamental research and clinical research of the CRS. Clinically, mainly absorbents like ibuprofen and AST-120 are studied, which show limited safe and efficient usability. Experimental research shows disturbances in cardiac electrical activation and conduction after inducing CKD or exposure to UTs, but are scarcely present or focus solely on already well-investigated UTs. Based on UTs data derived from CKD patient cohort studies, a clinically relevant overview of physiological and pathological UTs concentrations is created. Using this, future experimental research is stimulated to involve electrophysiologically translatable animals, such as rabbits, or in vitro engineered heart tissues.

Association of anti-Ro seropositivity with cardiac rhythm and conduction disturbances.

Anti-Ro/La autoantibodies are especially prevalent in autoimmune diseases but are also relatively frequent in healthy adults. Their arrhythmogenic effect on the immature cardiac conductive system is well established, with substantial evidence demonstrating an increased risk for congenital atrioventricular block in neonates of seropositive mothers. Despite their wide distribution and their arrhythmogenic potential effect, there are no large population studies conducted in seropositive adults. Thus, this is the first large population-based study to examine the association of anti-Ro/La seropositivity with cardiac rhythm and conduction disturbances. This cross-sectional designed study involved the electronic health records of the largest health maintenance organization in Israel. All subjects that were tested positive for anti-Ro/anti-La antibodies between the years 2002 and 2019 were included and were matched by age, gender, and place of residence, with controls. Rates of different cardiac rhythm and conduction disturbances were compared between groups. Sensitivity analyses were performed using propensity score matching. The study population included 17 231 anti-Ro/La seropositive subjects and 84 368 controls. Anti-Ro seropositive patients had higher rates of conduction disturbances (3.0 vs. 1.7%, P < 0.001) and rhythm disturbances (10.5 vs. 7.0%, P < 0.001). Patients who tested positive for anti-La alone did not demonstrate a significant association with arrhythmias. Multivariate logistic regression analysis, controlling for possible confounders, showed an increased risk for cardiac conduction disturbances [odds ratio (OR) 1.44, 95% confidence interval (CI) 1.25-1.66, P < 0.001], as well as for cardiac rhythm disturbances (OR 1.21, 95% CI 1.11-1.31, P < 0.001) among anti-Ro seropositive patients. However, the association with rhythm disturbances was more robust in certain subgroup analyses. Anti-Ro seropositivity is positively associated with adult cardiac conduction disturbances and, to a lesser extent, cardiac rhythm disturbances, regardless of the presence of concurrent autoimmune disease.

ROD2 domain filamin C missense mutations exhibit a distinctive cardiac phenotype with restrictive/hypertrophic cardiomyopathy and saw-tooth myocardium

Introduction and objectivesMissense mutations in the filamin C (FLNC) gene have been reported as cause of inherited cardiomyopathy. Knowledge of the pathogenicity and genotype-phenotype correlation remains scarce. Our aim was to describe a distinctive cardiac phenotype related to rare missense FLNC variants in the ROD2 domain. MethodsWe recruited 21 unrelated families genetically evaluated because of hypertrophic cardiomyopathy (HCM)/restrictive cardiomyopathy (RCM) phenotype carrying rare missense variants in the ROD2 domain of FLNC (FLNC-mRod2). Carriers underwent advanced cardiac imaging and genetic cascade screening. Myocardial tissue from 3 explanted hearts of a missense FLNC carrier was histologically analyzed and compared with an FLNC-truncating variant heart sample and a healthy control. Plasmids independently containing 3 FLNC missense variants were transfected and analyzed using confocal microscopy. ResultsEleven families (52%) with 20 assessed individuals (37 [23.7-52.7]) years showed 15 cases with a cardiac phenotype consisting of an overlap of HCM-RCM and left ventricular hypertrabeculation (saw-tooth appearance). During a median follow-up of 6.49 years, they presented with advanced heart failure: 16 (80%) diastolic dysfunction, 3 heart transplants, 3 heart failure deaths) and absence of cardiac conduction disturbances or skeletal myopathy. A total of 6 families had moderate genotype-phenotype segregation, and the remaining were de novo variants. Differential extracellular matrix remodeling and FLNC distribution among cardiomyocytes were confirmed on histology. HT1080 and H9c2 cells did not reveal cytoplasmic aggregation of mutant FLNC. ConclusionsFLNC-mRod2 variants show a high prevalence of an overlapped phenotype comprising RCM, HCM and deep hypertrabeculation with saw-tooth appearance and distinctive cardiac histopathological remodeling.

Electrocardiographic features and need for pacemaker in cardiac amyloidosis: Analysis of 58 cases

AimAmyloidosis is a disease in which amyloid fibrils can be deposited in different cardiac structures, and several electrocardiographic abnormalities can be produced by this phenomenon. The objective of this study was to describe the most common basal electrocardiographic alterations in patients diagnosed with cardiac amyloidosis (CA) and to determine if these abnormalities have an impact on the need of pacemaker. MethodsThis retrospective study included patients who had an established diagnosis of CA [light-chain cardiac amyloidosis (LA-CA) or transthyretin cardiac amyloidosis (TTR-CA)] between January 2013 and March 2021. The baseline heart rate, the percentage of patients with a pseudo-infarct pattern, low-voltage pattern or cardiac conduction disturbances, and the impact of these factors on the need of pacemaker were analysed. ResultsFifty-eight patients with CA (20 with LA-CA and 38 with TTR-CA) were included, and the majority were male (69.0%). Twenty-one patients had atrial fibrillation (AF) at diagnosis. Thirty-five patients had a pseudo-infarct pattern, 35% had a low-voltage pattern, and 22% had criteria for ventricular hypertrophy. Two hirds had a conduction disorder: 18 patients with first degree atrioventricular block, 12 right bundle branch block, 3 left bundle branch block and 25 with a branch hemiblock. There were no differences between LA-CA and TTR-CA. Patients with TTR-CA had a greater need for pacemakers in the follow-up (39 ± 40 meses). Bundle branch block was a predictor of the need for a permanent pacemaker (HR 23.43, 4.09–134.09, IC 95%, p = 0.01). ConclusionsElectrocardiographic abnormalities in patients diagnosed wich CA are heterogeneus. Most frecuent is the presence of conduction disorders, the pseudoinfarction pattern, followed by the low voltage pattern. Patients with any bundle branch block at the baseline electrocardiogram need more frecuent to require a pacemaker during follow-up, especially in TTR-CA.

Study of cardiotoxicity in patients with oncological pathology during chemotherapy

Background. Cardiological complications occur in 20% of all patients receiving chemotherapy for oncological diseases (the most severe are cardiac rhythm and conduction disturbances, myocardial ischemia and the development of heart failure), which complicates further high-quality antitumor therapy. In addition, 44% of all cancer patients have concomitant cardiovascular pathology, more often coronary artery disease and essential hypertension are detected. Carrying out cardiotoxic chemotherapy in this group of patients worsens the prognosis of concomitant disease.Aim. Conduct a retrospective analysis of 237 patients undergoing antitumor therapy at different stages of treatment. The analysis included those patients who received drugs with a mechanism of myocardial damage according to type 1 cardiotoxicity — doxorubicin, cyclophosphamide, Herceptin.Methods. Review of case histories of 237 patients treated in 2021 with doxorubicin (146 patients), cyclophosphamide (86 patients), Herceptin (5 patients).Results. The use of chemotherapy with the drugs listed above causes irreversible myocardial dysfunction due to the death of cardiomyocytes with the development of left ventricular dysfunction and heart failure, and also worsens the course of concomitant cardiovascular pathology in patients. For more detailed data, further research is needed, which is continuously ongoing.Conclusion. To date, the fact of the negative impact of chemotherapy on the cardiovascular system is indisputable, however, detailed studies are required. At Meshalkin National Medical Research Center, it is planned to conduct an electrocardiography, an echocardiography with an assessment of the ejection fraction, a general longitudinal strain of the left ventricle myocardium and left ventricle diastolic dysfunction, laboratory tests (troponin T and I, B-type Natriuretic Peptide (BNP), NT-proBNP) and also a comparison of these data with perfusion tomoscintigraphy of the myocardium of each patient undergoing chemotherapy treatment to identify early criteria for the development of cardiotoxicity after each cycle and at the end of chemotherapy, taking into account the total doses of drugs to obtain more accurate and up-to-date data.