Clinical characteristics and prognostic factors of atrial fibrillation at a tertiary center of Pakistan - From a South-Asian perspective - A cross-sectional study.

BACKGROUND: There is lack of large data from South-Asian region on atrial fibrillation and it is imperative that clinical presentation, prognostic factors, management pursued, and outcomes are known for this part of the world. Once collective evidence for the region is known, region-specific guidelines can be laid forward. OBJECTIVES: To evaluate clinical characteristics and prognostic factors of atrial fibrillation at a tertiary care center of Pakistan. METHODS: This was a retrospective study conducted at a tertiary care center of Pakistan. Period of study ranged from July-December 2018. All hospitalized patients who were admitted with atrial fibrillation as a primary or associated diagnosis were enrolled. RESULTS: A total of 636 patients were enrolled. The mean age was 68.5 ± 12 years and 49.5% (315) were male. 90.6% of the patients were admitted via emergency room. Majority (59.9%) had previously known AF and 40% developed new-onset AF during the hospital stay. Hypertension was the most common co-morbid condition (85.4%) followed by Diabetes Mellitus (40.1%). At least 9% had rheumatic heart disease. The median CHA2DS2VASc and HASBLED scores were 4 and 2 respectively. More than one-third of patients had sepsis as a primary diagnosis (36.8%). The in-hospital mortality of patients with atrial fibrillation was 6.7%. Patients with new-onset AF had higher mortality. Sepsis and stroke were independently associated with a higher mortality. There was no significant difference in median CHA2DS2VASc and HASBLED scores for patients with new-onset and previously known AF. On discharge, 83% of the eligible patients received oral anticoagulation. CONCLUSION: There was higher prevalence of chronic co-morbid conditions in the studied population leading to a higher CHA2DS2VASC Score. Sepsis and stroke were independently associated with higher in-hospital mortality.

Interesting presentation of a broad complex tachycardia during the head up tilt table test.

Broad complex tachycardia (BCT) during head up tilt test (HUTT) is infrequent. Electrophysiology Study (EPS) plays an important part in further differentiation of BCT. We present a case of BCT during HUTT in a patient presenting with presyncope which later on EPS with 3D mapping was diagnosed as ventricular tachycardia. This case highlights the unusual occurrence of BCT during HUTT, the differential diagnosis of BCT and the utility of EPS to reliably identify the type and origin of BCT.

Comparing sensitivity and specificity of pacemaker ID application and cardiac rhythm management device-finder application in identifying cardiac implantable electronic device manufacturer using chest radiograph - An observational study.

BACKGROUND: Smartphone-based applications to identify cardiac implantable electronic devices (CIED) are extremely useful in circumstances, where urgent device interrogation is needed, and a device identification card is not available. Few studies have provided insights regarding the utility of these applications. We have studied two widely available applications i.e., Pacemaker ID app (PMIDa) or Cardiac Rhythm Management Device-Finder (CRMD-f) to identify device manufacturers in CIEDs. METHODS: 547 patients who underwent CIED implantation from the year 2016-2020 in our institute were enrolled. There were 438 Medtronic and 109 St. Jude's devices. All chest radiographs were de-identified and resized into 225*225 pixels focusing on the CIED. PMIDa and CRMD-f applications were used to identify the CIED. Accuracy, sensitivity, specificity, negative predictive value, and positive predictive value for both applications were calculated and compared. RESULTS: Overall, CRMD-f application has higher specificity (93.58 vs. 82.5%) but lower sensitivity (53.6 vs. 55%) than PMIDa. The accuracy of both applications was comparable (61.6% vs. 60.5%). Accuracy varied with CIED model and type tested, and radiograph projection used. Accuracy is greatest with Cardiac-Resynchronization-Therapy (CRT) devices for both applications, followed by a single lead pacemaker. CONCLUSION: CRMD-f has higher accuracy and specificity for CIED manufacturer identification. Both PMIDa and CRMD-f are specific tools to identify CIED but have low sensitivity.

Cardiovascular fellow-in-training feedback on virtual and simulator-based learning experience during Covid-19 pandemic in a low to middle income country - A cross-sectional study.

BACKGROUND: COVID-19 pandemic has introduced us to a greater need of virtual learning platforms and has resulted in less clinical exposure for fellows-in-training. Virtual and simulator-based learning is not widely available in LMIC. It is imperative to analyze feedback of CV fellow-in-training regarding this mode of learning before large scale implementation. METHODOLOGY: This was an observational study conducted between July-August 2020. A multicentered survey was conducted. Survey questionnaire was disseminated to FIT (fellow-in-training) via Google Forms. The questionnaire contained a total of 24 questions about virtual and simulator-based learning during the pandemic. RESULTS: A total of 68 FIT responded to the survey. The mean age was 29.9 years. There were 37% females and 63% males. Majority (75%) agreed that it was easier for them to reach for online sessions than physical sessions. 60% FIT were confident in asking questions or giving comments during the online sessions. 57.4% FIT felt it easier to go through cardiovascular imaging/illustrations via online platforms. 50% (34) were confident that if online sessions had to continue, they would have enough academic learning before they graduated from the program and 54.4% (37) wanted online sessions to continue even beyond the pandemic days. 37.5% (18 out of 48) agreed that the simulator-based teaching was helping them practice skills in times of less clinical exposure. CONCLUSION: COVID-19 pandemic has significantly impacted cardiovascular FIT learning curve because of less hands-on and lack of physical teaching sessions. LMIC have lack of robust e-learning platforms. Virtual learning is convenient for academic learning with growing acceptance amongst fellows. FIT from LMIC are less acquaint to simulator-based teaching and there is a need to invest in simulator-based cardiovascular teaching in LMIC.

Loperamide-induced cardiotoxicity: a case overlooked?

A young man presented to the emergency department with seizures and recurrent episodes of polymorphic ventricular tachycardia (PMVT)/torsades de pointes (TdP) requiring cardioversion and administration of intravenous magnesium. A battery of tests performed to identify a cause for his arrhythmias and seizures were all normal. A revisit of history with family revealed he had consumed over 100 tablets/day of loperamide for the past 1 year. A prolonged QT interval on his ECG raised concerns for long QT syndrome (LQTS) (congenital or acquired). Our patient was suspected to have loperamide-induced cardiotoxicity. TdP is a specific PMVT that occurs with a prolonged QT interval and is usually drug-induced. Less frequently, congenital LQTS may be implicated. With supportive care, including mechanical ventilation, vasopressors and temporary transvenous overdrive pacing, our patient recovered completely. We describe the importance of a systematic and time-sensitive approach to diagnosing critical illness. Loperamide overdose may cause QT prolongation, life-threatening arrhythmias/cardiogenic shock, or cardiac arrest. Seizures/epilepsy may also be a manifestation in young patients. There is a substantial need to revisit the safety of over-the-counter medications and increasing awareness of manifestations of drug overdose.

Structural and Functional Properties of Subsidiary Atrial Pacemakers in a Goat Model of Sinus Node Disease.

BACKGROUND: The sinoatrial/sinus node (SAN) is the primary pacemaker of the heart. In humans, SAN is surrounded by the paranodal area (PNA). Although the PNA function remains debated, it is thought to act as a subsidiary atrial pacemaker (SAP) tissue and become the dominant pacemaker in the setting of sinus node disease (SND). Large animal models of SND allow characterization of SAP, which might be a target for novel treatment strategies for SAN diseases. METHODS: A goat model of SND was developed (n = 10) by epicardially ablating the SAN and validated by mapping of emergent SAP locations through an ablation catheter and surface electrocardiogram (ECG). Structural characterization of the goat SAN and SAP was assessed by histology and immunofluorescence techniques. RESULTS: When the SAN was ablated, SAPs featured a shortened atrioventricular conduction, consistent with the location in proximity of atrioventricular junction. SAP recovery time showed significant prolongation compared to the SAN recovery time, followed by a decrease over a follow-up of 4 weeks. Like the SAN tissue, the SAP expressed the main isoform of pacemaker hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) and Na+/Ca2+ exchanger 1 (NCX1) and no high conductance connexin 43 (Cx43). Structural characterization of the right atrium (RA) revealed that the SAN was located at the earliest activation [i.e., at the junction of the superior vena cava (SVC) with the RA] and was surrounded by the paranodal-like tissue, extending down to the inferior vena cava (IVC). Emerged SAPs were localized close to the IVC and within the thick band of the atrial muscle known as the crista terminalis (CT). CONCLUSIONS: SAN ablation resulted in the generation of chronic SAP activity in 60% of treated animals. SAP displayed development over time and was located within the previously discovered PNA in humans, suggesting its role as dominant pacemaker in SND. Therefore, SAP in goat constitutes a promising stable target for electrophysiological modification to construct a fully functioning pacemaker.

Atrial Tachycardia Associated With a Tachycardia-Induced Cardiomyopathy in a Patient With Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease that involves multiple organ systems. Cardiovascular involvement in SLE is well described in the literature. Cardiac arrhythmias associated with SLE include sinus tachycardia, atrial fibrillation, and atrial ectopy or atrial tachycardia. In this report, we present the case of a patient with SLE who was found to have focal atrial tachycardia that mimicked sinus tachycardia on a 12-lead electrocardiogram (ECG). She was inappropriately treated as a case of sinus tachycardia initially. But she did not respond to the treatment and developed tachycardia-induced cardiomyopathy despite being on antiarrhythmic medications. She subsequently underwent successful radiofrequency catheter ablation and her left ventricular ejection fraction (LVEF) recovered within three months after the ablation.

Lateral tunnel Fontan atrial tachycardia ablation trans-baffle access is not mandatory as the initial strategy.

BACKGROUND: Mapping and ablation of atrial tachycardia (AT) is commonly performed in lateral tunnel Fontan (LTF) patients, yet there is little information on the need of baffle puncture to access the pulmonary venous atrium (PVA). This study aimed to evaluate the most common chamber location of critical sites for majority of AT in LTF patients. METHODS: Consecutive LTF patients underwent catheter-based high-density mapping and ablation of AT from Nov. 2015 to Mar. 2019. Critical sites were identified by a combination of activation and entrainment mapping. Acute procedural success was defined as AT termination with ablation and non-inducibility of any AT. Predictors for ablation failure were evaluated in retrospect. RESULTS: Fifteen catheter ablation procedures were performed in 9 patients. A total of 15 clinical ATs (mean TCL 369 ± 91 ms) were mapped. The mechanism was macro re-entry in 11 (73%) and micro re-entry in 2. In 11 ATs (73%), 94 ± 5% of tachycardia cycle length (TCL) were mapped inside the tunnel. The commonest site of successful ablation in the tunnel was on the lateral wall (60%). Trans-baffle access was obtained during 5 of 15 procedures (33%). Overall, procedural success was achieved in 9 of 15 procedures (60%). There were no complications. Recurrence of AT was 42% over a follow-up period of 4.3 ± 3.2 years. Faster TCL of 200-300 ms showed a trend towards ablation failure, (OR 17, 95% CI 0.7 to 423, p = 0.08). CONCLUSIONS: Catheter ablation can be performed effectively for ATs in LTF patients usually from inside the tunnel. ATs with critical sites in the PVA are uncommon. This information will help plan ablation in LTF patients without resorting to initial trans-baffle access.

Information theory to tachycardia therapy: electrogram entropy predicts diastolic microstructure of reentrant ventricular tachycardia.

There is no known strategy to differentiate which multicomponent electrograms in sinus rhythm maintain reentrant ventricular tachycardia (VT). Low entropy in the voltage breakdown of a multicomponent electrogram can localize conditions suitable for reentry but has not been validated against the classic VT activation mapping. We examined whether low entropy in a late and diversely activated ventricular scar region characterizes and differentiates the diastolic path of VT and represents protected tissue channels devoid of side branches. Intraoperative bipolar electrogram (BiEGM) activation and entropy maps were obtained during sinus rhythm in 17 patients with ischemic cardiomyopathy and compared with diastolic activation paths of VT (total of 39 VTs). Mathematical modeling of a zigzag main channel with side branches was also used to further validate structural representation of low entropy in the ventricular scar. A median of one region per patient (range: 1-2 regions) was identified in sinus rhythm, in which BiEGM with the latest mean activation time and adjacent minimum entropy were assembled together in a high-activation dispersion region. These regions accurately recognized diastolic paths of 34 VTs, often to multiple inducible VTs within a single individual arrhythmogenic region. In mathematical modeling, side branching from the main channel had a strong influence on the BiEGM composition along the main channel. The BiEGM obtained from a long unbranched channel had the lowest entropy compared with those with multiple side branches. In conclusion, among a population of multicomponent sinus electrograms, those that demonstrate low entropy and are delayed colocalize to critical long-protected channels of VT. This information is pertinent for planning VT ablation in sinus rhythm. NEW & NOTEWORTHY Entropy is a measure to quantify breakdown in information. Electrograms from a protected tissue channel can only possess a few states in their voltage and thus less information. In contrast, current-load interactions from side branches in unprotected channels introduce a number of dissimilar voltage deflections and thus high information. We compare here a mapping approach based on entropy against a rigorous reference standard of activation mapping during VT and entropy was assessed in sinus rhythm.

Structural and functional remodeling of the atrioventricular node with aging in rats: The role of hyperpolarization-activated cyclic nucleotide-gated and ryanodine 2 channels.

BACKGROUND: Aging is associated with an increased incidence of atrioventricular nodal (AVN) dysfunction. OBJECTIVE: The aim of this study was to investigate the structural and functional remodeling in the atrioventricular junction (AVJ) with aging. METHODS: Electrophysiology, histology, and immunohistochemistry experiments on male Wistar Hannover rats aged 3 months (n = 24) and 2 years (n = 15) were performed. Atrio-His (AH) interval, Wenkebach cycle length (WBCL), and AVN effective refractory period (AVNERP) were measured. Cesium (2 mM) was used to block hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, while ryanodine (2 µM) was used to block ryanodine 2 (RyR2) channels. Protein expression from different regions of the AVJ was studied using immunofluorescence. The expression of connexins (connexin 43 and connexin 40), ion channels (Hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4), voltage sensitive sodium channel (Nav1.5), and L-Type calcium channel (Cav1.3)), and calcium handling proteins (RyR2 and sarco/endoplasmic reticulum calcium ATPaset type 2a (SERCA2a)) were measured. Morphological characteristics were studied with histology. RESULTS: Without drugs to block HCN and RyR2 channels, there was prolongation of the AH interval, WBCL, and AVNERP (P < .05) with aging. In young rats only, cesium prolonged the AH interval, WBCL, and AVNERP (P < .01). Ryanodine prolonged the AH interval and WBCL (P < .01) in both young and old rats. Immunofluorescence revealed that with aging, connexin 43, HCN4, Nav1.5, and RyR2 downregulate in the regions of the AVJ and connexin 40, SERCA2a, and Cav1.3 upregulate (P < .05). Aging results in cellular hypertrophy, loosely packed cells, a decrease in the number of nuclei, and an increase in collagen content. CONCLUSION: Heterogeneous ion channel expression changes were observed in the AVJ with aging. For the first time, we have shown that HCN and RyR2 play an important role in AVN dysfunction with aging.

Pulmonary Vein Re-Isolation as a Routine Strategy Regardless of Symptoms: The PRESSURE Randomized Controlled Trial.

OBJECTIVES: The goal of this study was to determine whether a strategy of early re-isolation of pulmonary vein (PV) reconnection in all patients, regardless of symptoms, would reduce the recurrence of atrial fibrillation (AF) and improve quality of life. BACKGROUND: Lasting pulmonary vein isolation (PVI) remains elusive. PV reconnection is strongly linked to the recurrence of arrhythmia. METHODS: A total of 80 patients with paroxysmal AF were randomized 1:1 after contact force-guided PVI to receive either standard care or undergo a repeat electrophysiology study after 2 months regardless of symptoms (repeat study). At the initial procedure, PVI was demonstrated by entrance/exit block and adenosine administration after a minimum 20-min wait. At the repeat study, all sites of PV reconnection were re-ablated. Patients recorded electrocardiograms daily and whenever symptomatic for 12 months using a handheld monitor. Recurrence was defined as ≥30 s of atrial tachyarrhythmia (AT) after a 3-month blanking period. The Atrial Fibrillation Effect on Quality-of-Life Questionnaire was completed at baseline and at 6 and 12 months. RESULTS: All 40 patients randomized to repeat study attended for this after 62 ± 6 days, of whom 25 (62.5%) had reconnection of 41 (26%) PVs. There were no complications related to these procedures. Subjects recorded a total of 32,203 electrocardiograms (380 [335 to 447] per patient) during 12.6 (12.2 to 13.2) months of follow-up. AT recurrence was significantly lower for the repeat study group (17.5% vs. 42.5%; p = 0.03), as was AT burden (p = 0.03). Scores on the Atrial Fibrillation Effect on Quality-of-Life Questionnaire were higher in the repeat study group at 6 months (p < 0.001) and 12 months (p = 0.02). CONCLUSIONS: A strategy of routine repeat assessment with re-isolation of PV reconnection improved freedom from AT recurrence, AT burden, and quality of life compared with current standard care. (The Effect of Early Repeat Atrial Fibrillation [AF] on AF Recurrence [PRESSURE]; NCT01942408).

Ablation index, a novel marker of ablation lesion quality: prediction of pulmonary vein reconnection at repeat electrophysiology study and regional differences in target values.

AIMS: Force-Time Integral (FTI) is commonly used as a marker of ablation lesion quality during pulmonary vein isolation (PVI), but does not incorporate power. Ablation Index (AI) is a novel lesion quality marker that utilizes contact force, time, and power in a weighted formula. Furthermore, only a single FTI target value has been suggested despite regional variation in left atrial wall thickness. We aimed to study AI's and FTI's relationships with PV reconnection at repeat electrophysiology study, and regional threshold values that predicted no reconnection. METHODS AND RESULTS: Forty paroxysmal atrial fibrillation patients underwent contact force-guided PVI, and the minimum and mean AI and FTI values for each segment were identified according to a 12-segment model. All patients underwent repeat electrophysiology study at 2 months, regardless of symptoms, to identify sites of PV reconnection. Late PV reconnection was seen in 53 (11%) segments in 25 (62%) patients. Reconnected segments had significantly lower minimum AI [308 (252-336) vs. 373 (323-423), P < 0.0001] and FTI [137 (92-182) vs. 228 (157-334), P < 0.0001] compared with non-reconnected segments. Minimum AI and FTI were both independently predictive, but AI had a smaller P value. Higher minimum AI and FTI values were required to avoid reconnection in anterior/roof segments than for posterior/inferior segments (P < 0.0001). No reconnection was seen where the minimum AI value was ≥370 for posterior/inferior segments and ≥480 for anterior/roof segments. CONCLUSION: The minimum AI value in a PVI segment is independently predictive of reconnection of that segment at repeat electrophysiology study. Higher AI and FTI values are required for anterior/roof segments than for posterior/inferior segments to prevent reconnection.

Ca(2+)-Clock-Dependent Pacemaking in the Sinus Node Is Impaired in Mice with a Cardiac Specific Reduction in SERCA2 Abundance.

BACKGROUND: The sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2) pump is an important component of the Ca(2+)-clock pacemaker mechanism that provides robustness and flexibility to sinus node pacemaking. We have developed transgenic mice with reduced cardiac SERCA2 abundance (Serca2 KO) as a model for investigating SERCA2's role in sinus node pacemaking. METHODS AND RESULTS: In Serca2 KO mice, ventricular SERCA2a protein content measured by Western blotting was 75% (P < 0.05) lower than that in control mice (Serca2 FF) tissue. Immunofluorescent labeling of SERCA2a in ventricular, atrial, sinus node periphery and center tissue sections revealed 46, 45, 55, and 34% (all P < 0.05 vs. Serca2 FF) lower labeling, respectively and a mosaic pattern of expression. With telemetric ECG surveillance, we observed no difference in basal heart rate, but the PR-interval was prolonged in Serca2 KO mice: 49 ± 1 vs. 40 ± 1 ms (P < 0.001) in Serca2 FF. During exercise, heart rate in Serca2 KO mice was elevated to 667 ± 22 bpm, considerably less than 780 ± 17 bpm (P < 0.01) in Serca2 FF. In isolated sinus node preparations, 2 mM Cs(+) caused bradycardia that was equally pronounced in Serca2 KO and Serca2 FF (32 ± 4% vs. 29 ± 5%), indicating no change in the pacemaker current, I f. Disabling the Ca(2+)-clock with 2 µM ryanodine induced bradycardia that was less pronounced in Serca2 KO preparations (9 ± 1% vs. 20 ± 3% in Serca2 FF; P < 0.05), suggesting a disrupted Ca(2+)-clock. Mathematical modeling was used to dissect the effects of membrane- and Ca(2+)-clock components on Serca2 KO mouse heart rate and sinus node action potential. Computer modeling predicted a slowing of heart rate with SERCA2 downregulation and the heart rate slowing was pronounced at >70% reduction in SERCA2 activity. CONCLUSIONS: Serca2 KO mice show a disrupted Ca(2+)-clock-dependent pacemaker mechanism contributing to impaired sinus node and atrioventricular node function.

The Year in Cardiology 2012: arrhythmia and pacing.

This is a commissioned review for 'A Year in Cardiology 2012', focusing on recent developments in the field of arrhythmias and pacing.

Validation of a prediction score model to distinguish acute coronary syndromes from other conditions causing raised cardiac troponin T levels.

OBJECTIVE: Serum cardiac troponins can be elevated in acute coronary syndromes (ACS) and other non-ACS conditions. We investigated the usefulness of a prediction score model comprising clinical variables to distinguish patients with ACS from other non-ACS conditions. METHODS: Two independent, non-randomized observational cohorts (groups 1 and 2) were examined, comprising consecutive patients who were admitted to a university teaching hospital and found to have a raised serum troponin T level (>or=0.01 microg/l). The international definition was used to confirm acute myocardial infarction. Multivariate logistic regression identified clinical variables in the first cohort, which were used to construct a score model for distinguishing between ACS and non-ACS, and this score was re-evaluated in the second cohort. RESULTS: Of the 313 patients in group 1, a score model was formulated using logarithm troponin T, ischaemic chest pain, ST depression and atrial fibrillation or flutter. Using a score of more than or equal to 1.5, sensitivity and specificity for predicting non-ACS were 0.81 and 0.84. The area under the curve was 0.900 (95% confidence interval 0.867-0.934). Sensitivity and specificity for predicting non-ACS among the 341 patients in group 2 using the same model and a score of more than or equal to 1.5 were 0.76 and 0.89, respectively, and the area under the curve was 0.918 (confidence interval 0.887-0.945). CONCLUSION: A prediction score model using simple clinical variables has been validated, and this can help clinicians in distinguishing patients with ACS from other non-ACS conditions.