Elevated myocardial extracellular volume fraction is associated with the development of conduction pathway defects following transcatheter aortic valve replacement.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has become an established method of aortic stenosis treatment but suffers from the risk of heart block and pacemaker requirement. Risk stratification for patients who may develop heart block remains imperfect. Simultaneously, myocardial fibrosis as measured by cardiac magnetic resonance imaging (CMR) has been demonstrated as a prognostic indicator of ventricular recovery and mortality following TAVR. However, the association of CMR-based measures of myocardial fibrosis with post-TAVR conduction disturbances has not yet been explored. AIMS: We evaluated whether myocardial fibrosis, as measured by late gadolinium enhancement and extracellular volume (ECV) from CMR would be associated with new conduction abnormalities following TAVR. METHODS: One hundred seventy patients who underwent CMR within 2 months before TAVR were retrospectively reviewed. Septal late gadolinium enhancement (LGE) and ECV measurements were made as surrogates for replacement and interstitial fibrosis respectively. New conduction abnormalities were defined by the presence of transient or permanent atrioventricular block, new bundle branch blocks, and need for permanent pacemaker. Association of myocardial fibrosis and new conduction derangements were tested using receiver operator curve (ROC) and regression analysis in patients with and without pre-existing conduction issues. RESULTS: Forty-six (27.1%) patients developed post-TAVR conduction deficits. ECV was significantly higher among patients who experienced new conduction defects (26.2 ± 3.45% vs. 24.7% ± 4.15%, p value: 0.020). A greater fraction of patients that had new conduction defects had an elevated ECV of ≥26% (54.3% vs. 36.3%, p value: 0.026). ECV ≥ 26% was independently associated with the development of new conduction defects (odds ratio [OR]: 2.364, p value: 0.030). ROC analysis revealed a significant association of ECV with new conduction defects with an area under the receiver operating characteristic curve (AUC) of 0.632 (95% confidence interval: 0.555-0.705, p value: 0.005). The combination of prior right bundle branch block (RBBB) and ECV revealed a greater AUC of 0.779 (0.709-0.839, p value: <0.001) than RBBB alone (Delong p value: 0.049). No association of LGE/ECV with new conduction defects was observed among patients with pre-existing conduction disease. Among patients without baseline conduction disease, ECV was independently associated with the development of new conduction deficits (OR: 3.685, p value: 0.008). CONCLUSION: The present study explored the association of myocardial fibrosis, as measured by LGE and ECV with conduction deficits post-TAVR. Our results demonstrate an association of ECV, and thereby interstitial myocardial fibrosis, with new conduction derangement post-TAVR and introduce ECV as a potentially new risk stratification tool to identify patients at higher risk for needing post-TAVR surveillance and/or permanent pacemaker.

Electrophysiological basis of cardiac arrhythmia in a mouse model of myotonic dystrophy type 1.

Introduction: Myotonic dystrophy type 1 (DM1) is a multisystemic genetic disorder caused by the increased number of CTG repeats in 3' UTR of Dystrophia Myotonia Protein Kinase (DMPK) gene. DM1 patients experience conduction abnormalities as well as atrial and ventricular arrhythmias with increased susceptibility to sudden cardiac death. The ionic basis of these electrical abnormalities is poorly understood. Methods: We evaluated the surface electrocardiogram (ECG) and key ion currents underlying the action potential (AP) in a mouse model of DM1, DMSXL, which express over 1000 CTG repeats. Sodium current (INa), L-type calcium current (ICaL), transient outward potassium current (Ito), and APs were recorded using the patch-clamp technique. Results: Arrhythmic events on the ECG including sinus bradycardia, conduction defects, and premature ventricular and atrial arrhythmias were observed in DMSXL homozygous mice but not in WT mice. PR interval shortening was observed in homozygous mice while ECG parameters such as QRS duration, and QTc did not change. Further, flecainide prolonged PR, QRS, and QTc visually in DMSXL homozygous mice. At the single ventricular myocyte level, we observed a reduced current density for Ito and ICaL with a positive shift in steady state activation of L-type calcium channels carrying ICaL in DMSXL homozygous mice compared with WT mice. INa densities and action potential duration did not change between DMSXL and WT mice. Conclusion: The reduced current densities of Ito, and ICaL and alterations in gating properties in L-type calcium channels may contribute to the ECG abnormalities in the DMSXL mouse model of DM1. These findings open new avenues for novel targeted therapeutics.

Mobitz II Atrioventricular Block Following Intracardiac Radiation to the Right Ventricular Outflow Tract.

Cardiac complications from mediastinal radiotherapy are much more prevalent than in years past and are becoming a significant cause of morbidity and mortality in these patients following treatment. We describe a patient with metastatic lung adenosquamous carcinoma extending to the right ventricular outflow tract who would develop a Mobitz type II atrioventricular block following intracardiac radiation therapy requiring permanent pacemaker placement.

Ventricular arrhythmias in Kearns-Sayre syndrome: A cohort study using the National Inpatient Sample database 2016-2019.

BACKGROUND: Degeneration of the cardiac conduction system resulting in complete heart block (CHB), ventricular arrhythmias (VA), and sudden cardiac death (SCD) is recognized in patients with Kearns-Sayre syndrome (KSS) and is potentially preventable with permanent pacemaker (PPM) implantation. However, other mechanisms for SCD have been proposed, and the efficacy of implanting a defibrillator instead of PPM remains to be investigated. METHODS: We utilized the National Inpatient Sample (NIS) database 2016-2019 to investigate the risk of VA or dysrhythmic cardiac arrest (dCA) in KSS patients. We compared the outcomes of KSS to myotonic dystrophy (MD), a more common genetic disorder with similar clinical cardiac features and course. RESULTS: We identified 640 admissions for KSS. VA or dCA were lower in admissions for KSS than MD patients (2.3% vs. 4.5%, p = .009). Device implantation differed between study groups. Approximately, 70% of cases with KSS and conduction abnormalities had pacemaker (± defibrillator) on hospital discharge, compared to 35% in MD. Conduction abnormalities were associated with higher rates of VA or dCA in both study groups. None of the admissions for KSS patients who developed VA or dCA had a pacemaker, and all of them had conduction abnormalities. One-third of admissions for MD patients who developed VA or dCA had a device already implanted prior to the event. CONCLUSION: Despite its effectiveness in preventing VA, PPM remains underutilized in patients with KSS or MD who have conduction abnormalities. PPM alone do not fully prevent VA in MD patients; therefore, addition of defibrillator capacity might be necessary.

Electrocardiographic Abnormalities predicting mortality in COVID-19 pneumonia patients.

Background: Cardiovascular involvement is a significant cause of death in COVID pneumonia. Early electrocardiographic changes may predict cardiovascular involvement and predict mortality in COVID pneumonia patients. Methods: A total of 250 consecutive patients with COVID-19 pneumonia admitted to the emergency were studied for electrocardiographic abnormalities and their relation to mortality. Results: Most patients required supplemental oxygen to maintain optimal saturation. A total of 72% showed ECG abnormalities, and the overall cohort had a mortality of 50%. New-onset atrial fibrillation, left bundle branch block or right bundle branch pattern, and ventricular premature complexes were associated with high mortality. Sinus tachycardia and atrial fibrillation were the most common arrhythmia and were significantly associated with mortality. Conclusions: New-onset atrial fibrillation, intraventricular conduction defects, and sinus tachycardia are associated with increased mortality in COVID pneumonia patients.

Stx4 is required to regulate cardiomyocyte Ca2+ handling during vertebrate cardiac development.

Requirements for vesicle fusion within the heart remain poorly understood, despite the multitude of processes that necessitate proper intracellular trafficking within cardiomyocytes. Here, we show that Syntaxin 4 (STX4), a target-Soluble N-ethylmaleimide sensitive factor attachment receptor (t-SNARE) protein, is required for normal vertebrate cardiac conduction and vesicular transport. Two patients were identified with damaging variants in STX4. A patient with a homozygous R240W missense variant displayed biventricular dilated cardiomyopathy, ectopy, and runs of non-sustained ventricular tachycardia, sensorineural hearing loss, global developmental delay, and hypotonia, while a second patient displayed severe pleiotropic abnormalities and perinatal lethality. CRISPR/Cas9-generated stx4 mutant zebrafish exhibited defects reminiscent of these patients' clinical presentations, including linearized hearts, bradycardia, otic vesicle dysgenesis, neuronal atrophy, and touch insensitivity by 3 days post fertilization. Imaging of Vamp2+ vesicles within stx4 mutant zebrafish hearts showed reduced docking to the cardiomyocyte sarcolemma. Optical mapping of the embryonic hearts coupled with pharmacological modulation of Ca2+ handling together support that zebrafish stx4 mutants have a reduction in L-type Ca2+ channel modulation. Transgenic overexpression of zebrafish Stx4R241W, analogous to the first patient's STX4R240W variant, indicated that the variant is hypomorphic. Thus, these data show an in vivo requirement for SNAREs in regulating normal embryonic cardiac function and that variants in STX4 are associated with pleiotropic human disease, including cardiomyopathy.

Non-alcoholic fatty liver disease-related risk of cardiovascular disease and other cardiac complications.

BACKGROUND/AIM: Non-alcoholic fatty liver disease (NAFLD) affects approximately 25% of the global adult population. The aim of this narrative review is to describe the associations between NAFLD and cardiovascular disease (CVD), arrhythmias, cardiac conduction defects, myocardial remodelling and heart failure. We also discuss the potential mechanisms that mediate or attenuate the strength of these associations, and briefly summarize the effect of treatments that both ameliorate NAFLD and decrease risk of CVD. METHODS: Searches of PubMed were performed by the two authors using the terms listed in Appendix. We limited the timeframe to the last decade due to the vast amount of research in the field (up to April 2021) for meta-analyses, reviews and original papers. Only articles published in English were considered. RESULTS: NAFLD is associated with an increased risk of fatal/non-fatal CVD events and other cardiac and arrhythmic complications (left ventricular hypertrophy, aortic-valve sclerosis and certain arrhythmias), independently of common CVD risk factors. There are probably several underlying mechanisms, including hepatic/systemic insulin resistance, atherogenic dyslipidaemia, hypertension and pro-atherogenic, pro-coagulant and pro-inflammatory mediators released from the steatotic/inflamed liver that may be involved. Some genetic polymorphisms, such as PNPLA3 (rs738409 C>G) and TM6SF2 (rs58542926 C>T), may worsen the liver disease, but also attenuate the strength of the association between NAFLD and CVD, possibly via their effects on lipoprotein metabolism. Of the currently tested drugs for treating NAFLD that also benefit the vasculature, pioglitazone and GLP-1 receptor agonists are the most promising. CONCLUSIONS: The complex interplay between the liver and cardiometabolic risk factors contributes to CVD, arrhythmias and cardiac disease in NAFLD. There is an urgent need for a multidisciplinary approach to manage both liver disease and cardiometabolic risk, and to test the cardiovascular and cardiac effects of new drugs for NAFLD.

Drosophila Heart as a Model for Cardiac Development and Diseases.

The Drosophila heart, also referred to as the dorsal vessel, pumps the insect blood, the hemolymph. The bilateral heart primordia develop from the most dorsally located mesodermal cells, migrate coordinately, and fuse to form the cardiac tube. Though much simpler, the fruit fly heart displays several developmental and functional similarities to the vertebrate heart and, as we discuss here, represents an attractive model system for dissecting mechanisms of cardiac aging and heart failure and identifying genes causing congenital heart diseases. Fast imaging technologies allow for the characterization of heartbeat parameters in the adult fly and there is growing evidence that cardiac dysfunction in human diseases could be reproduced and analyzed in Drosophila, as discussed here for heart defects associated with the myotonic dystrophy type 1. Overall, the power of genetics and unsuspected conservation of genes and pathways puts Drosophila at the heart of fundamental and applied cardiac research.

Childhood Bradycardia Associates With Atrioventricular Conduction Defects in Older Age: A Longitudinal Birth Cohort Study.

Background This study explored the association between childhood bradycardia and later-life cardiac phenotype using longitudinal data from the 1946 National Survey of Health and Development (NSHD) birth cohort. Methods and Results Resting heart rate was recorded at 6 and 7 years of age to provide the bradycardia exposure defined as a childhood resting heart rate <75 bpm. Three outcomes were studied: (1) echocardiographic data at 60 to 64 years of age, consisting of ejection fraction, left ventricular mass index, myocardial contraction fraction index, and E/e'; (2) electrocardiographic evidence of atrioventricular or ventricular conduction defects by 60 to 64 years of age; and (3) all-cause and cardiovascular mortality. Generalized linear models or Cox regression models were used, and adjustment was made for relevant demographic and health-related covariates, and for multiple testing. Mixed generalized linear models and fractional polynomials were used as sensitivity analyses. One in 3 older adults with atrioventricular conduction defects had been bradycardic in childhood, with defects being serious (Mobitz type II second-degree atrioventricular block or higher) in 12%. In fully adjusted models, childhood bradycardia was associated with 2.91 higher odds of atrioventricular conduction defects (95% CI, 1.59-5.31; P=0.0005). Associations persisted in random coefficients mixed generalized linear models (odds ratio, 2.50; 95% CI, 1.01-4.31). Fractional polynomials confirmed a linear association between the log odds of atrioventricular conduction defects at 60 to 64 years of age and resting heart rate at 7 years of age. There was no association between bradycardia in childhood and mortality outcomes or with echocardiographic parameters and ventricular conduction defects in older age. Conclusions Longitudinal birth cohort data indicate that childhood bradycardia trebles the odds of having atrioventricular conduction defects in older age, 88% of which are benign. In addition, it does not influence mortality or heart size and function. Future research should concentrate on identifying children at risk.

New Insights into the Development and Morphogenesis of the Cardiac Purkinje Fiber Network: Linking Architecture and Function.

The rapid propagation of electrical activity through the ventricular conduction system (VCS) controls spatiotemporal contraction of the ventricles. Cardiac conduction defects or arrhythmias in humans are often associated with mutations in key cardiac transcription factors that have been shown to play important roles in VCS morphogenesis in mice. Understanding of the mechanisms of VCS development is thus crucial to decipher the etiology of conduction disturbances in adults. During embryogenesis, the VCS, consisting of the His bundle, bundle branches, and the distal Purkinje network, originates from two independent progenitor populations in the primary ring and the ventricular trabeculae. Differentiation into fast-conducting cardiomyocytes occurs progressively as ventricles develop to form a unique electrical pathway at late fetal stages. The objectives of this review are to highlight the structure-function relationship between VCS morphogenesis and conduction defects and to discuss recent data on the origin and development of the VCS with a focus on the distal Purkinje fiber network.

Identification of a SCN5A founder mutation causing sudden death, Brugada syndrome, and conduction blocks in Southern Italy.

BACKGROUND: The genetic architecture of Brugada syndrome (BrS) is emerging as an increasingly complex area of investigation. The identification of genetically homogeneous populations can provide mechanistic insights and improve genotype-phenotype correlation. OBJECTIVE: To characterize and define the clinical implications of a novel BrS founder mutation. Using a haplotype-based approach we investigated whether 2 SCN5A genetic variants could derive from founder events. METHODS: Single nucleotide polymorphisms were genotyped in 201 subjects, haplotypes reconstructed, and mutational age estimated. Clinical phenotypes and historical records were collected. RESULTS: A SCN5A variant (c.3352C>T; p.Gln1118Ter) was identified in 3 probands with BrS originating from south Italy. The same mutation was identified in a proband from central Italy and in 1 U.S. resident subject with Italian ancestry. The 5 individuals carried a common core haplotype, whose frequency was extremely low in local noncarrier probands and in population controls (0%-6.06%). The clinical presentation included multigenerational dominant transmission of Brugada electrocardiographic pattern, high incidence of sudden cardiac death (SCD), and cardiac conduction defects (CCD). We reconstructed 7-generation pedigrees with common geographic origin. Variant's age estimates suggested that origin of the p.Gln1118Ter dates back 76 generations (95% confidence interval: 28-200). A second SCN5A variant (c.5350G>A; p.Glu1784Lys) identified in the region did not show similar founder signal. CONCLUSION: p.Gln1118Ter is a novel BrS/CCD/SCD founder mutation. We illustrate how these findings provide insights on the inheritance patterns and phenotypes associated with SCN5A mutation.

Permanent Pacemaker Post Cardiac Surgery: where do we Stand?

Abstract Cardiac arrhythmias and requirement for permanent pacemaker (PPM) post open-heart surgery are some of the complications that can contribute to significant morbidities postoperatively and delay in normal recovery if not treated promptly. The reported rate of a PPM following isolated, elective coronary artery bypass grafting is < 1%, while following aortic or mitral valve surgery it is reported to be < 5%. There are several perioperative factors that can contribute to the increased likelihood of PPM requirement including preoperative rhythm, severity and location of cardiac ischaemia, perioperative variables, and the cardiac procedures performed. Optimization of such factors can possibly lead to a lower rate of PPM and, therefore, a lower rate of complications. This literature review focuses on PPM following each procedural type and how to minimize it.

Progressive involvement of cardiac conduction system in paediatric patients with Kearns-Sayre syndrome: how to predict occurrence of complete heart block and sudden cardiac death?

AIMS: The aims of this study are to evaluate the progressive involvement of the cardiac conduction system in the Kearn-Sayre syndrome (KSS) and to establish criteria for the prevention of episodes of syncope or sudden cardiac death. METHODS AND RESULTS: This is a prospective monocentric study including KSS patients, with diagnosis based on clinical manifestations, muscle biopsy, and genetic tests, before the age of 18. All patients underwent cardiac screening examination with 12-lead electrocardiogram (ECG), 24-h Holter monitoring, and pacemaker (PM) interrogation twice a year. Fifteen patients (nine males, mean age 16.6 ± 3.9 years) with a sporadic KSS were recruited. All subjects manifested at least one of the intraventricular conduction defects (IVDs): 1 right bundle branch block (RBBB), 2 left anterior fascicular block (LAFB), 11 a bi-fascicular block (RBBB + LAFB), and 1 left posterior fascicular block. Most children with bi-fascicular block developed LAFB before the RBBB (P = 0.0049). In six patients, IVD degenerated into atrioventricular block (AVB). Endocavitary PM was implanted in 11 patients (6 with AVB and 5 with a bi-fascicular block), while an implantable cardioverter-defibrillator only in one patient with a non-sustained ventricular tachycardia. Four died at mean age of 14.7 ± 2.6 years, but none of them suddenly. CONCLUSION: Even a 'simple' ECG can predict the arrhythmic risk and the occurrence of catastrophic events in young patients with KSS. Left anterior fascicular block precedes RBBB in determining the bi-fascicular block and this can predict an inexorable progression of the conduction defects even in a short time. Pacemaker implantation may be indicated in these patients since the first bi-fascicular block manifestation.

Clinical characterization of the first Belgian SCN5A founder mutation cohort.

AIMS: We identified the first Belgian SCN5A founder mutation, c.4813 + 3_4813 + 6dupGGGT. To describe the clinical spectrum and disease severity associated with this mutation, clinical data of 101 SCN5A founder mutation carriers and 46 non-mutation carrying family members from 25 Belgian families were collected. METHODS AND RESULTS: The SCN5A founder mutation was confirmed by haplotype analysis. The clinical history and electrocardiographic parameters of the mutation carriers and their family members were gathered and compared. A cardiac electrical abnormality was observed in the majority (82%) of the mutation carriers. Cardiac conduction defects, defined as PR or QRS prolongation on electrocardiogram (ECG), were most frequent, occurring in 65% of the mutation carriers. Brugada syndrome (BrS) was the second most prevalent phenotype identified in 52%, followed by atrial dysrythmia in 11%. Overall, 33% of tested mutation carriers had a normal sodium channel blocker test. Negative tests were more common in family members distantly related to the proband. Overall, 23% of the mutation carriers were symptomatic, with 8% displaying major adverse events. As many as 13% of the patients tested with a sodium blocker developed ventricular arrhythmia. One family member who did not carry the founder mutation was diagnosed with BrS. CONCLUSION: The high prevalence of symptoms and sensitivity to sodium channel blockers in our founder population highlights the adverse effect of the founder mutation on cardiac conduction. The large phenotypical heterogeneity, variable penetrance, and even non-segregation suggest that other genetic (and environmental) factors modify the disease expression, severity, and outcome in these families.

Association of statin induced reduction in serum coenzyme Q10 level and conduction deficits in motor and sensory nerves: An observational cross-sectional study.

OBJECTIVE: The reduction of Coenzyme Q10 (CoQ10) levels following statin use has been linked to cause peripheral neuropathy. Hence, this study was planned to explore the effect of statin on the serum HMGCR (3-hydroxy-3-methyl-glutaryl-coenzyme A reductase), serum CoQ10 levels and nerve conduction and their correlation. PATIENTS AND METHODS: In an open labelled, cross-sectional, observational study, estimation of serum HMGCR and CoQ10 levels was performed in 50 atorvastatin/rosuvastatin users and 50 normal healthy volunteers (NHV). Statin users were also subjected to nerve conduction studies (NCS). RESULTS: Mean serum HMGCR level in NHV was higher (73.58 ± 7.64 ng/ml; p = 0.003) than that in statin users (49.11 ± 1.98 ng/ml). Similarly, mean serum CoQ10 levels was also lower (30.54 ± 2.03 ng/ml, p < 0.0001) in statin users than in NHV (49.43 ± 3.23 ng/ml). Amongst the 50 statin users, 29 had impaired NCS in sural, tibial and common peroneal nerve with lower mean serum CoQ10 levels (24.05 ± 1.96 ng/ml; p < 0.0001). Significant negative correlation was observed between onset time of action potential (AP) of the sural nerve and serum CoQ10 (r=-0.32) and HMGCR (r=-0.43) levels. There was significant positive correlation of conduction velocity of sural (r = 0.38) and tibial (r = 0.31) nerves with serum CoQ10 level. While conduction velocity in sural (r = 0.37) and common peroneal (r = 0.34) nerves positively correlated with serum HMGCR levels. The amplitude of the AP of the common peroneal nerve positively correlated with both serum CoQ10 (r = 0.52) and HMGCR (r = 0.46) levels. CONCLUSION: Statin users had lower serum CoQ10 and HMGCR levels associated with nerve conduction deficits suggesting a role of CoQ10 in the occurrence of the neurological adverse effects.

Cardiovigilance in COVID 19.

The COVID19 (Corona Virus Disease: pandemic started in 2019) pandemic has created not only a public health problem, but as a clinical challenge as well. To the cardiologist, COVID 19 presents a wide spectrum of possibilities for clinical decision-making intervention and improvement. Cardiac dysfunction has been identified as a risk factor, a prognostic factor, a diagnostic tool, differential diagnosis, a complication of COVID 19, and a side effect of its treatment. Certain cardiotropic drugs have been implicated in the pathogenesis of COVID 19. The risk of transmission of COVID 19 is an occupational hazard which cannot be ignored by cardiologists. This review discusses the need and scope of cardio vigilance in COVID 19 management.

Straightjacket/α2δ3 deregulation is associated with cardiac conduction defects in myotonic dystrophy type 1.

Cardiac conduction defects decrease life expectancy in myotonic dystrophy type 1 (DM1), a CTG repeat disorder involving misbalance between two RNA binding factors, MBNL1 and CELF1. However, how DM1 condition translates into conduction disorders remains poorly understood. Here we simulated MBNL1 and CELF1 misbalance in the Drosophila heart and performed TU-tagging-based RNAseq of cardiac cells. We detected deregulations of several genes controlling cellular calcium levels, including increased expression of straightjacket/α2δ3, which encodes a regulatory subunit of a voltage-gated calcium channel. Straightjacket overexpression in the fly heart leads to asynchronous heartbeat, a hallmark of abnormal conduction, whereas cardiac straightjacket knockdown improves these symptoms in DM1 fly models. We also show that ventricular α2δ3 expression is low in healthy mice and humans, but significantly elevated in ventricular muscles from DM1 patients with conduction defects. These findings suggest that reducing ventricular straightjacket/α2δ3 levels could offer a strategy to prevent conduction defects in DM1.

Myotonic Dystrophy Type 2 - Data from the Serbian Registry.

BACKGROUND: Myotonic dystrophy type 2 (DM2) is a multisystem disorder, mostly presented with mild but heterogeneous spectrum of symptoms. OBJECTIVE: The aim of this research was to provide detailed sociodemographic, clinical and laboratory data of a large DM2 cohort from the Serbian registry. METHODS: In 2008, we started to prospectively enter data of all DM patients. We also retrospectively collected data of patients hospitalized from 1990 until 2008. RESULTS: At the end of 2017, registry comprised 87 (68%) of 128 genetically confirmed DM2 patients in Serbia, i.e. 1.2 registered cases per 100,000 inhabitants. Female subjects were more prevalent (63%). The diagnostic delay was 11.8±11.3 years. The most common first symptoms in our patients were lower limb weakness, handgrip myotonia and limb pain, although some percentage of patients presented with cataracts or extrapyramidal symptoms and signs. Lens opacities were present in 75% of patients. Severe ECG abnormalities were noted in 8% and pacemaker was implanted in 5% of DM2 subjects. Pulmonary restriction was observed in 10% of DM2 patients. Insulin resistance and diabetes mellitus were frequent in our cohort (21% and 17%, respectively). Male subjects more frequently had snoring, baldness, sterility, polyneuropathy, lower HDL and higher glycaemia, while waddling gait and increased muscle reflexes were more common in females. CONCLUSIONS: This registry offers a spectrum of different features presented in Serbian DM2 population, which could be at service of earlier diagnosis and better treatment.

Association between decreasing estimated glomerular filtration rate and risk of cardiac conduction defects in patients with type 2 diabetes.

AIM: We aimed to assess the association between decreasing estimated glomerular filtration rate (eGFR) or abnormal albuminuria and the risk of certain cardiac conduction defects in patients with type 2 diabetes mellitus (T2DM). METHODS: We examined a hospital-based sample of 923 patients with T2DM discharged from our Division of Endocrinology over the years 2007-2014. Standard electrocardiograms (ECGs) were performed in all patients. eGFR was estimated by using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, whilst albuminuria was measured by an immuno-nephelometric method on morning spot urine samples. RESULTS: A total of 253 (27.4%) patients had some type of cardiac conduction defects on standard ECGs (defined as at least one heart block among first-degree atrioventricular block, second-degree block, third-degree block, left bundle branch block, right bundle branch block, left anterior hemi-block or left posterior hemi-block). Prevalence of patients with eGFRCKD-EPI < 30 mL/min/1.73 m2, eGFRCKD-EPI 59-30 mL/min/1.73 m2 or abnormal albuminuria (i.e. urinary albumin-to-creatinine ratio ≥ 30 mg/g) were 7.0%, 29.4% and 41.3%, respectively. After adjustment for known cardiovascular risk factors, diabetes-related variables and potential confounders, there was a significant, graded association between decreasing eGFR values and risk of any cardiac conduction defects [adjusted-odds ratios of 2.05 (95% CI: 1.2-3.5), 2.85 (95% CI: 1.6-5.1) and 3.62 (95% CI: 1.6-8.1) for eGFRCKD-EPI 89-60, eGFRCKD-EPI 59-30 and eGFRCKD-EPI < 30 mL/min/1.73 m2, respectively]. Conversely, abnormal albuminuria was not independently associated with an increased risk of any conduction defects (adjusted-odds ratio: 1.09, 95% CI: 0.7-1.6). CONCLUSION: Decreasing eGFR is independently associated with an increased risk of cardiac conduction defects in hospitalized patients with T2DM.

Relation of elevated serum uric acid levels to first-degree heart block and other cardiac conduction defects in hospitalized patients with type 2 diabetes.

AIMS: Several studies have reported that moderately elevated serum uric acid levels are associated with an increased risk of tachyarrhythmias (mainly atrial fibrillation) in patients with and without type 2 diabetes mellitus (T2DM). It is currently unknown whether an association also exists between elevated serum uric acid levels and cardiac conduction defects in patients with T2DM. METHODS: We retrospectively analyzed a hospital-based sample of 967 patients with T2DM discharged from our Division of Endocrinology over the years 2007-2014. Standard electrocardiograms were performed on all patients and were interpreted by expert cardiologists. RESULTS: Overall, 267 (27.6%) patients had some type of conduction defects on electrocardiograms (defined as at least one block among first-degree atrio-ventricular block, second-degree block, third-degree block, left bundle branch block, right bundle branch block, left anterior hemi-block or left posterior hemi-block). Patients in the 3rd serum uric acid tertile had a higher prevalence of any cardiac conduction defects than those belonging to 2nd or 1st tertile, respectively (35.8% vs. 25.0% vs. 22.6%; p<0.0001). Elevated serum uric acid levels were associated with a nearly twofold increased risk of cardiac conduction defects after adjustment for age, sex, hemoglobin A1c, diabetes duration, metabolic syndrome, chronic kidney disease, chronic obstructive pulmonary disease, ischemic heart disease, valvular heart disease and medication use (adjusted-odds ratio 1.84, 95% confidence intervals 1.2-2.9; p=0.009). CONCLUSIONS: Moderately elevated serum uric acid levels are associated with an increased prevalence of any cardiac conduction defects in hospitalized patients with T2DM, independent of multiple risk factors and potential confounding variables.