Severe cardiac conduction disease associated with titin gene mutation.

Heart block is rare in pediatrics with many possible causes. An association between complete heart block (CHB) and pathogenic titin (TTN) mutations have not been previously described. We report a 9-year-old female with history of leukodystrophy and family history of atrial fibrillation who presented with syncope and conduction abnormalities, including CHB. She underwent pacemaker implantation and genetic testing demonstrated a pathogenic TTN mutation likely responsible for her cardiac findings. Our case suggests an association between TTN mutations and conduction disease and emphasizes broadening gene testing in assessing these patients, especially when a family history is present.

Validation of an automated artificial intelligence system for 12­lead ECG interpretation.

BACKGROUND: The electrocardiogram (ECG) is one of the most accessible and comprehensive diagnostic tools used to assess cardiac patients at the first point of contact. Despite advances in computerized interpretation of the electrocardiogram (CIE), its accuracy remains inferior to physicians. This study evaluated the diagnostic performance of an artificial intelligence (AI)-powered ECG system and compared its performance to current state-of-the-art CIE. METHODS: An AI-powered system consisting of 6 deep neural networks (DNN) was trained on standard 12­lead ECGs to detect 20 essential diagnostic patterns (grouped into 6 categories: rhythm, acute coronary syndrome (ACS), conduction abnormalities, ectopy, chamber enlargement and axis). An independent test set of ECGs with diagnostic consensus of two expert cardiologists was used as a reference standard. AI system performance was compared to current state-of-the-art CIE. The key metrics used to compare performances were sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and F1 score. RESULTS: A total of 932,711 standard 12­lead ECGs from 173,949 patients were used for AI system development. The independent test set pooled 11,932 annotated ECG labels. In all 6 diagnostic categories, the DNNs achieved high F1 scores: Rhythm 0.957, ACS 0.925, Conduction abnormalities 0.893, Ectopy 0.966, Chamber enlargement 0.972, and Axis 0.897. The diagnostic performance of DNNs surpassed state-of-the-art CIE for the 13 out of 20 essential diagnostic patterns and was non-inferior for the remaining individual diagnoses. CONCLUSIONS: Our results demonstrate the AI-powered ECG model's ability to accurately identify electrocardiographic abnormalities from the 12­lead ECG, highlighting its potential as a clinical tool for healthcare professionals.

Post-transcatheter aortic valve implantation isolated PR prolongation: incidence and clinical significance.

AIMS: Conduction abnormalities post-transcatheter aortic valve implantation (TAVI) are common. Post-TAVI PR prolongation was mainly studied as an adjunct to new-onset bundle branch block. The net effect of isolated PR prolongation (IPRP) without post-TAVI QRS changes is not well known. The aim of this study was to define the incidence and clinical significance of post-TAVI IPRP. METHODS AND RESULTS: A total of 1108 consecutive TAVI patients were reviewed. Patients with IPRP were compared with patients without post-TAVI electrocardiogram (ECG) changes. Clinical outcomes included permanent pacemaker implantation (PPI) and overall mortality. A total of 146 patients with IPRP were compared with 290 patients without post-TAVI ECG changes. At 1 year follow-up, 4 (2.7%) and 7 (2.4%) patients underwent PPI (P = 0.838) and 10 (6.8%) and 25 (8.6%) died (P = 0.521), from the study and control groups, respectively. No patient with IPRP and narrow QRS underwent PPI during 1 year post-TAVI, and all death events were non-cardiac except one unknown cause. Permanent pacemaker implantation rates among patients with IPRP and wide QRS were higher (n = 4, 12.1%), compared with patients with wide QRS without post-TAVI ECG change (n = 3, 4%) however not reaching statistical significance (P = 0.126). Multivariate Cox proportional hazards model demonstrated that in patients with narrow QRS, neither PR prolongation nor baseline or maximal PR intervals was associated with the combined endpoint of PPI and mortality. However, in patients with wide QRS, baseline PR intervals and QRS width, but not PR prolongation were associated with the combined outcome. CONCLUSION: Post-TAVI IPRP in patients with narrow QRS is not associated with adverse outcome. This finding may translate clinically into a more permissive approach to these patients.

A computational framework for post-TAVR cardiac conduction abnormality (CCA) risk assessment in patient-specific anatomy.

BACKGROUND: Cardiac conduction abnormality (CCA)- one of the major persistent complications associated with transcatheter aortic valve replacement (TAVR) may lead to permanent pacemaker implantation. Localized stresses exerted by the device frame on the membranous septum (MS) which lies between the aortic annulus and the bundle of His, may disturb the cardiac conduction and cause the resultant CCA. We hypothesize that the area-weighted average maximum principal logarithmic strain (AMPLS) in the MS region can predict the risk of CCA following TAVR. METHODS: Rigorous finite element-based analysis was conducted in two patients (Balloon expandable TAVR recipients) to assess post-TAVR CCA risk. Following the procedure one of the patients required permanent pacemaker (PPM) implantation while the other did not (control case). Patient-specific aortic root was modeled, MS was identified from the CT image, and the TAVR deployment was simulated. Mechanical factors in the MS region such as logarithmic strain, contact force, contact pressure, contact pressure index (CPI) and their time history during the TAVR deployment; and anatomical factors such as MS length, implantation depth, were analyzed. RESULTS: Maximum AMPLS (0.47 and 0.37, respectively), contact force (0.92 N and 0.72 N, respectively), and CPI (3.99 and 2.86, respectively) in the MS region were significantly elevated in the PPM patient as compared to control patient. CONCLUSION: Elevated stresses generated by TAVR devices during deployment appear to correlate with CCA risk, with AMPLS in the MS region emerging as a strong predictor that could be used for preprocedural planning in order to minimize CCA risk.

Isolated left bundle branch block in the young: case reports and review of literature.

Isolated left bundle branch block (LBBB) aberrancy is exceedingly rare in the young and its clinical and genetic determinants remain poorly characterized. Furthermore, there is conflicting data on its natural history in the pediatric age group patients. We report the rare phenotype of isolated typical LBBB aberrancy in two healthy children, one of whom carried a likely pathogenic mutation in the coding exon 1 of NKX2-5 (p.Q22R, c.65A > G, rs201442000). Our findings suggest that isolated LBBB aberrancy could be non-progressive in some children, at least in the short term. However, given the paucity of data on this entity, we recommend continued long-term surveillance.

A case of reversible third-degree AV block due to Lyme carditis.

The most common manifestation of Lyme carditis is a varying degree of atrioventricular (AV) conduction block. This case describes a 45-year-old male with third-degree AV block due to Lyme carditis. Treatment with intravenous antibiotics resulted in complete normalization of AV conduction, thereby averting permanent pacemaker implantation.

Electrocardiographic predictors of mortality and sudden cardiac death in patients with end stage renal disease on hemodialysis.

Patients with end stage renal disease (ESRD) on hemodialysis experience a high incidence of cardiovascular mortality, and sudden cardiac death (SCD) accounts for approximately 25% of all deaths in this patient population. Despite this high risk of SCD, many non-invasive SCD risk stratification tools that are frequently applied to other patient populations (such as those with prior myocardial infarction and reduced left ventricular systolic function) may be less useful markers of increased SCD risk in ESRD. Improved SCD risk stratification tools for use specifically in patients on hemodialysis are therefore necessary to optimally target use of primary prevention interventions aimed at decreasing SCD incidence. Electrocardiography is an effective, non-invasive SCD risk stratification tool in hemodialysis patients. This article reviews data supporting the association between various ECG parameters (QT interval, spatial QRS-T angle, signal averaged ECG, heart rate variability, and T-wave alternans) and mortality/SCD in the dialysis population. Despite the association between abnormal ECG parameters and SCD, it remains unclear if these abnormal parameters (such as prolonged QT interval) are mechanistically related to SCD and/or ventricular arrhythmias, or if they are simply markers for more severe cardiac disease, such as left ventricular hypertrophy, that may independently predispose to SCD. Current obstacles that impair widespread implementation of ECG risk stratification in the hemodialysis population are also discussed.

Effect of Vitamin D Replacement on Atrial Electromechanical Delay in Subjects with Vitamin D Deficiency.

OBJECTIVES: Limited data are available regarding cardiac arrhythmias in vitamin D (VitD) deficiency. Therefore, we aimed to assess whether atrial electromechanical delay (AEMD) measured by tissue Doppler imaging (TDI), which is an indicator for atrial fibrillation (AF) development, is prolonged in patients with VitD deficiency as compared to the control group. The effect of vitD replacement on AEMD was also evaluated. METHODS: In this prospective study a total of 28 VitD-deficient and 56 age-, gender-, and BMI-matched VitD-sufficient healthy participants were enrolled. P-wave dispersion (PWd) was calculated on the 12-lead electrocardiogram. Both intra- and inter-AEMD were calculated by TDI. Measurements were performed at baseline in both groups and were repeated after 6-month replacement therapy in subjects with vitD deficiency. RESULTS: PWd and inter- and left intra-AEMD were significantly prolonged in patients with VitD deficiency compared to the control group (P < 0.001). While serum 25(OH)D levels were significantly and negatively correlated with left intra-AEMD (r = -0.657, P < 0.001), there was a positive correlation between serum 25(OH)D level and PWd (r = 0.523, P < 0.001). The serum 25(OH)D level was found as the independent predictor of the both left intra- and inter-AEMD in the multivariate linear regression analysis (ß:-0.552, P < 0.001 and ß:-0.555, P < 0.001, respectively). The serum 25(OH)D level was significantly increased after replacement therapy. While inter-AEMD was significantly decreased (P = 0.013), there was no change in PWD and left and right intra-AEMD (P > 0.05) following replacement therapy. CONCLUSION: PWd and left intra- and inter-AEMD are increased in patients with VitD deficiency. The serum 25(OH)D level was found as an independent predictor for AEMD in patients with VitD deficiency. Also a significant decrement was observed in inter-AEMD following vitD replacement therapy. Studies with longer follow-up are needed to investigate whether vitD-deficient patients with prolonged AEMD develop clinical arrhythmia and vitD replacement reduces the risk of atrial arrhythmias.

A Patient With Athlete's Heart Syndrome: When the Abnormal Is Normal.

Long-term athletic training can result in structural and conduction changes within the heart, leading to Athlete's heart syndrome (AHS). This syndrome is characterized by increased left ventricle (LV) dimensions, thickness, and mass. Dynamic exercise significantly contributes to these alterations, with sinus bradycardia being a common conduction abnormality, often accompanied by first-degree atrioventricular (AV) block. However, higher degrees of AV conduction abnormalities, such as second- and third-degree blocks, though rare, might occur due to parasympathetic hypertonia. Prompt evaluation is necessary to rule out underlying structural or infiltrative heart diseases. We present the case of a 66-year-old lifelong long-distance runner with marked sinus bradycardia, AV dissociation, and junctional escape rhythm, alongside left ventricular hypertrophy (LVH) and T-wave repolarization abnormalities. Subsequent studies ruled out possible pathologies, and the patient was diagnosed with AHS, characterized by cardiac remodeling and bradycardia due to prolonged cardiac loading. This case underscores the importance of clinical assessment, cardiac imaging, and exclusion of pathologic causes to distinguish normal physiological adaptations from potentially concerning conditions.

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 (0.018 MPa) compared to nominal condition (0.29 MPa) and ventricular deployment (0.52 MPa). Notably, the preexisting RBBB demonstrated a higher cumulative contact pressure (0.34 MPa) compared to the nominal condition and preexisting LBBB (0.25 MPa). 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.

Risk stratification for the occurrence of ventricular fibrillation in patients with early repolarization syndrome.

BACKGROUND: Several signs of malignant early repolarizations have been proposed in patients with early repolarization syndrome (ERS). However, reports have challenged the efficacy of these signs in predicting future ventricular fibrillation (VF) in patients with ERS. OBJECTIVE: This study aimed to assess the predictive value of various electrocardiogram (ECG) markers for future VF events in patients with ERS. METHODS: We retrospectively evaluated the clinical characteristics of 44 patients with ERS to identify risk factors for VF during follow-up. RESULTS: After the initial event, 16 patients experienced VF (VF group), whereas 28 did not (non-VF group). The VF group had a longer QRS interval, more fragmented QRS (fQRS), and a higher T/R voltage ratio than the non-VF group. Wide J waves were more prevalent in the VF group; however, other J-wave markers did not differ between the groups. Positive late potentials recorded on signal-averaged ECGs were more frequent in the VF group. Whereas none of the patients showed spontaneous Brugada syndrome on ECG, the VF group frequently exhibited pilsicainide-induced ST-segment elevation. These ECG markers were significantly associated with the occurrence of VF during follow-up. Patients with multiple ECG factors, including QRS abnormalities (wide QRS or fQRS), wide J waves, and a high T/R ratio, had a worse prognosis than patients without multiple factors, effectively stratifying patient risk. CONCLUSION: The occurrence of VF in patients with ERS may be associated with conduction abnormalities such as QRS widening, fQRS, high T/R ratio, positive late potentials, and pilsicainide test results. Therefore, ECG factors could be useful in identifying high-risk patients.

Predictors and Trends of New Permanent Pacemaker Implantation: A Subanalysis of the International Navitor IDE Study.

Background: The Navitor Investigational Device Exemption (IDE) study is a prospective, multicenter, global study assessing the safety and effectiveness of the Navitor valve in a population with severe, symptomatic aortic stenosis who are at high and extreme surgical risk. The impact of pre-existing conduction abnormalities and implantation technique on new permanent pacemaker implantation (PPI) for the Navitor platform is not fully understood. Therefore, the goal of this analysis was to investigate the associations between patient and procedural factors and the 30-day new PPI rate. Methods: A total of 260 patients who underwent implantation of a Navitor valve in the Navitor IDE study were reviewed. Patients with preprocedural permanent pacemakers (n = 28) were excluded. Baseline risk factors were assessed for statistical significance. Multivariable logistic regression analyses were performed to identify independent predictors of new PPI. Results: Mean age of the pacemaker-naïve population was 83.3 ± 5.2 years, 58.6% were female, average Society of Thoracic Surgeons score was 3.8% ± 1.9%, median frailty score was 1 (interquartile range 1, 2), and 17.7% were deemed at extreme surgical risk. Pre-existing first-degree atrioventricular block and right bundle branch block significantly increased the risk of new PPI postimplantation, whereas left bundle branch block did not. Membranous septum length in relation to noncoronary cusp implant depth was a significant predictor of new PPI, with higher rates of new PPI observed when noncoronary cusp implant depth exceeded membranous septum length. Analysis of implant depth alone revealed deeper implants were associated with a higher rate of new PPI, regardless of patient baseline conduction abnormality. Conclusions: The 30-day rate of new PPI in the Navitor IDE study is associated with patient pre-existing baseline conduction disturbances and implantation depth.

Transthyretin Cardiac Amyloidosis in an Elderly Male With Heart Failure Intolerant to Guideline-Directed Medical Therapy.

Cardiac amyloidosis arises when there is a deposition of abnormal proteins, called amyloids, in the myocardium. It can manifest as overt heart failure, conduction abnormalities, atrial and ventricular arrhythmia, cardiomyopathy, and aortic stenosis. Two main types of proteins identified in cardiac amyloidosis are light-chain amyloid and transthyretin amyloid. Cardiac amyloidosis, although common, is an underdiagnosed cause of heart failure in many cases. A high index of suspicion is needed to make a diagnosis, given that symptoms are not specific. Early diagnosis and treatment of cardiac amyloidosis are associated with reduced morbidity and improved survival. We present a case of a 73-year-old African American male with decompensated heart failure with reduced ejection fraction intolerant to guideline-directed medical therapy who was later found to have cardiac amyloidosis.

Ventricular Parasystole in Cardiomyopathy Patients: A Link Between His-Purkinje System Damage and Ventricular Fibrillation.

BACKGROUND: The clinical relevance and prognostic implications of ventricular parasystole are unknown. OBJECTIVES: This study sought to assess the prevalence of ventricular parasystole in patients with implantable cardioverter-defibrillators (ICDs) and ventricular parasystole's association with ventricular arrhythmias and conduction system abnormalities. METHODS: This study retrospectively evaluated patients who underwent ICD interrogation at a single center between June 1, 2019, and August 31, 2020, and reviewed all available ICD and electrocardiogram data. This study identified patients with ventricular parasystole and compared the prevalence of ventricular fibrillation (VF), ventricular tachycardia (VT), and new conduction system abnormalities in those with ≥5 years of intrinsic QRS-complex electrocardiograms to those without parasystole. RESULTS: This study included 374 patients (age 57 ± 21 years, 72% male, 45% nonischemic, 32% ischemic cardiomyopathy), of which, 104 (28%) had VT only, 39 (10%) VF only, and 10 (3%) both VT/VF. Ventricular parasystole was identified in 33 patients (9%); parasystolic foci were predominantly from the His-Purkinje system. Compared with those without parasystole, patients with parasystole had a significantly higher rate of VF (36% vs 11%; P < 0.01), but not VT (42% vs 29%; P = 0.12). Patients with parasystole, compared with those without parasystole, had a higher prevalence of new conduction abnormalities, particularly progressive intraventricular conduction delay (11 of 18 [61%] vs 12 of 83 [14%]; P < 0.01) and new right bundle branch block (4 of 18 [22%] vs 1 of 83 [1%]; P < 0.01). CONCLUSIONS: Ventricular parasystole was strongly associated with new conduction system abnormalities and VF in patients who have cardiomyopathy with ICDs, suggesting a potential link between VF and His-Purkinje damage in this patient population.

A Rare Case of High-Grade Atrioventricular Block in Granulomatosis With Polyangiitis.

Granulomatosis with polyangiitis (GPA) is an autoimmune disease that affects small and medium-sized vessels. It is classically known to present with renal and respiratory tract symptoms. However, the disease can manifest in other organ systems, especially cardiovascular involvement. Though there are multiple reports of cardiac involvement in GPA, it is not commonly evaluated and is often overlooked in patients with GPA. Heart disease in GPA has a wide range of presentations ranging from subacute and silent to severe abnormalities, which can prove fatal if not identified and treated appropriately. Identifying cardiac involvement early in patients with no apparent signs can help with prevention strategies and follow-up to avoid significant complications. Pericarditis is the most common pathology noted in GPA, followed by cardiomyopathy, coronary artery disease, valvular disease, and conduction abnormality. In our report, we present a case of GPA in a young male with asymptomatic conduction abnormality of the heart. Although it was silent at the presentation, identifying the initial electrocardiogram (ECG) changes prompted us to admit him to the telemetry floor. Continuous telemetry monitoring helped us identify the progression of the conduction abnormality, which otherwise could have been missed. This led us to correlate to his symptoms which he later developed during his admission course. His symptoms subsided after prompt treatment. If not identified early, these cardiac abnormalities can delay management, leading to increased disease burden and morbidity. Hence, essential cardiac work with at least ECG and continuous telemetry monitoring is recommended.

Coved and Saddleback ST-Segment Elevations: Brugada Phenocopy vs Brugada Syndrome.

We report a case of a middle-aged man who presented with near syncope, fever, and dysuria and was incidentally found to have coved ST-segment elevations in leads V1 and V2 confirming Brugada type 1 ECG (electrocardiogram) pattern. This ECG pattern morphed into saddleback ST-segment elevations in precordial leads consistent with type 2 Brugada the following day. Additionally, the patient reported a positive family history of sudden cardiac death. This initial presentation made it impossible to differentiate Brugada phenocopy (BrP) from Brugada syndrome (BrS). Continuous cardiac monitoring was initiated, electrophysiology consulted and fever managed with antipyretics. The patient was diagnosed with prostatitis and bacteremia from E. coli and managed with antibiotics. There were no electrolyte abnormalities nor was the patient on any medications other than tamsulosin for his chronic benign prostate hypertrophy. Once the fever resolved the patient's ECG returned to normal, thus confirming the diagnosis of BrS on day 3 post-admission. Differentiating between BrP and BrS requires ruling out possible underlying causes and determining if resolution in ECG patterns occurs.

Cardiac Sarcoidosis Diagnostic Challenges and Management: A Case Report and Literature Review.

Sarcoidosis can be presented as cardiac sarcoidosis (CS), which is challenging to diagnose due to its clinical silence. Ventricular arrhythmias and atrioventricular blocks can be fatal and cause sudden death in patients with cardiac sarcoidosis. Five percent of sarcoidosis patients have clinically evident cardiac sarcoidosis. However, autopsy reports and imaging studies have shown a higher prevalence of cardiac involvement. Early recognition is important to prevent such detrimental consequences. Cardiac sarcoidosis is increasingly being diagnosed owing to increased awareness among physicians and new diagnostic tools like MRI and positron emission tomography (PET) scan replacing traditional endomyocardial biopsy. A definitive diagnosis of CS remains challenging due to the non-specific clinical findings that can present similar symptoms of common cardiac disease; therefore, the imaging and biopsies are substantial for diagnosis confirmation. Pharmacological and Implantable devices are two main therapeutic approaches in cardiac sarcoidosis, in which steroids and pacemaker therapy have shown better outcomes. This review summarizes the available data related to the prevalence, prognosis, diagnosis, and management of cardiac sarcoidosis.

Diagnosing Lyme Carditis Presenting With Complete Heart Block.

Diagnosing self-limited conduction abnormality of Lyme carditis in absence of pathognomonic skin rash or history of tick bite is challenging but necessary to avoid placement of pacemaker particularly in young patients. High degree of clinical suspicion, rapidly progressing conduction block and prompt response to antibiotics may help in diagnosis.

Intraventricular Conduction Disturbances After Transcatheter Aortic Valve Implantation.

Despite significant improvements in transcatheter aortic valve implantation (TAVI) outcomes, periprocedural conduction disturbances, such as new-onset left bundle branch block (LBBB) and new pacemaker implantation (PMI), remain relatively frequent concerns. The development of periprocedural conduction disturbances can be explained by the proximity between the aortic valve and the conduction system. Although prior studies reported heterogeneity in PMI rates after TAVI, current evidence supports the potentially deleterious consequence of LBBB and PMI, and several predisposing factors have been reported. Therefore, new strategies to avoid conduction disturbances and to improve their management are required, particularly with the current trend to expand TAVI to a low-risk population.

Massive accumulation of globotriaosylceramide in various tissues from a Fabry patient with a high antibody titer against alpha-galactosidase A after 6 years of enzyme replacement therapy.

Fabry disease is an X-linked metabolic disorder due to a pathogenic mutation of the GLA gene. The accumulation of globotriaosylceramide (Gb3) damages multiple organs, including the heart, kidney and nervous system, especially in classical type Fabry disease. Enzyme replacement therapy (ERT) using recombinant alpha-galactosidase A has been shown to remove Gb3 from organs and to improve the prognosis of Fabry disease. We herein report the case of a 67-year-old classical type Fabry patient who had been treated with ERT for 6 years and who continuously showed a high antibody titer against recombinant alpha-galactosidase A during therapy. A post-mortem examination was performed after sudden death. A histological examination revealed the massive accumulation of Gb3 in various organs, even after long term ERT. In addition to the typical pathological findings as reported in tissue biopsy samples, the serious accumulation of Gb3 in the cardiac conduction system and the endocrine system was detected. Since the start of ERT for this patient might be too late to improve organ damage and prognosis, ERT should be started before the appearance of major organ involvement for the effective elimination of Gb3 and changes in the therapeutic strategy might be considered if the patient shows a high antibody titer against recombinant alpha-galactosidase A.