Prolonged PR Research Articles

Dynamic optimization of CRT pacing using a novel algorithm improves survival in a real-world cohort of patients

Abstract Background The AdaptivCRT (aCRT) algorithm continuously adjusts cardiac resynchronization therapy (CRT) according to intrinsic atrioventricular (AV) conduction status, providing synchronized left-ventricular pacing in patients (pts) with a normal PR interval and adaptive biventricular (BiV) pacing in pts with a prolonged PR interval. Prior secondary analyses of prospective trials demonstrated a reduction in mortality and atrial fibrillation incidence with aCRT. Objective To compare mortality in a large real-world population of pts with and without aCRT using electronic health record (EHR) data. Methods An Optum® de-identified EHR dataset and Medtronic CareLink device data were linked to identify pts (age>18 years) with a CRT implanted between 2014–2018 who survived ≥35 days post implant and with a documented baseline left ventricular ejection fraction (LVEF). Pts were grouped with aCRT set to either Adaptive BiV+LV (aCRT group) or standard CRT (control group). Two pt subgroups were identified: (i) pts with left bundle branch block (LBBB) and no AV block, (ii) pts with either no LBBB or with AV block. Kaplan-Meier curves and log-rank were used to estimate and compare survival between treatment and control groups in both the full cohort and subgroups. Multivariate Cox regression was used to estimate the aCRT treatment effect while controlling for baseline characteristics. Results Among 8624 patients implanted with a CRT device with EHR data available for a median of 23.5 months post implant [IQR: 12.6, 37.3], 3994 patients had the aCRT feature activated. Pts in the aCRT group were younger (median 69 [IQR:60, 76] vs 73 [IQR: 65, 79] years), more frequently female (35% vs 26%), and more frequently had LBBB (72% vs 51%); p's<0.001. Median QRS duration was 150ms (IQR: 133, 164) for the aCRT group and 152ms (IQR: 134, 172) for the control group (p<0.001). Median LVEF was 22% (IQR: 18, 30) for the aCRT group and 25% (IQR: 20, 30) for the control group (p<0.001). Through 60 months post implant, the overall mortality rate was 23.6% (95% CI: 20.7%-26.3%) for the aCRT group and 37.6% for the control group (95% CI: 34.9%-40.1%), p<0.001. Subgroup analysis demonstrated a significant reduction in mortality with aCRT in both pts with LBBB without AV block (Figure, left panel) and pts without LBBB and with AV block (Figure, right panel). After accounting for baseline differences, the reduction in mortality remained significant in the LBBB/no AV block group (HR: 0.54, 95% CI: 0.39–0.76, p<0.001) and trended toward significance in the no LBBB/with AV block group (HR: 0.89, 95% CI: 0.79–1.01; p=0.08). Conclusion In a large, real-world population of pts implanted with CRT devices, the AdaptivCRT algorithm was associated with significantly reduced mortality, with a greater reduction observed among pts with LBBB and without AV block. These results are being tested prospectively in the ongoing AdaptResponse multi-national, randomized clinical trial. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Medtronic, Inc. Cumulative probability of death by group

LIPID EMULSION THERAPY FOR LIFE-THREATENING FLECAINIDE TOXICITY

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: We present a case of flecainide (FLC) toxicity secondary to renal failure treated with intravenous lipid emulsion (ILE) therapy. CASE PRESENTATION: The patient is a 63 year old female with a history of stage IVB uterine carcinosarcoma, chronic kidney disease and supraventricular tachycardia (SVT) on FLC. She was admitted with intra-abdominal hemorrhagic metastases. A rapid response was called due to hypotension, and she was noted to be oliguric for the previous 24 hours with a serum creatinine 2.5 mg/dL (baseline 1.3 mg/dL) and hyponatremic (126 mmol/L). EKG showed a new wide complex rhythm, at 78bpm, QRS widening to 280ms, and prolonged QTc of 631. She subsequently suffered a wide complex tachyarrhythmic cardiac arrest (CA), refractory to two shocks, with return of spontaneous circulation after treatment with sodium bicarbonate (NaHCO3). FLC was discontinued and the patient was started on a hypertonic NaHCO3 drip, but frequent NaHCO3 pushes were required to correct widening of the QRS complex. The hypotension progressed requiring high dose infusions of epinephrine (15 mcg/min) and norepinephrine (90 mcg/min). ILE infusion was started, 20% lipid 1.5 mL/kg administered over 5 minutes, followed by an infusion of 0.25 mL/kg/minute over two hours. A serum FLC level was drawn during ILE infusion and came back elevated at 1.35 mcg/mL (therapeutic level 0.20-1.0 mcg/mL). In the 48 hours following ILE, there was resolution of the wide complex arrhythmias, and vasopressor requirements were reduced by more than 50% DISCUSSION: FLC is a class 1C antiarrhythmic that inhibits Na+ channels and is used for prevention of SVT. It has a narrow therapeutic range and about 30% is renally excreted making acute kidney injury a risk for toxicity. Other risk factors for toxicity are hyponatremia and hypokalemia. Characteristic signs of toxicity include hypotension, lethargy and EKG changes such as QRS widening and PR prolongation. These changes can progress to wide complex brady or tachyarrhythmic CA as seen in our patient. Standard of care is administration of hypertonic NaHCO3 which acts both as a Na+ load to compete with FLC for binding at Na+ channels and as an alkalinizing agent which decreases the ionized receptor-binding form of FLC. However, when NaHCO3 treatment fails, there are few other well studied options. One is VA-ECMO for which our patient was not a candidate. The other is lipid emulsion therapy, which is hypothesized to work by creating a lipid sink to sequester the drug and also has some positive ionotropy. CONCLUSIONS: In our patient, administration of ILE resulted in significant clinical improvement. Unfortunately, the clinical improvement did not sustain after several days and due to overall poor prognosis, the patient was eventually transitioned to comfort measures. REFERENCE #1: Subedi R, Dean R, Chaudhary A. Flecainide toxicity in renal failure. Proc (Bayl Univ Med Cent). 2018 May 9;3(3):328-330. REFERENCE #2: Ghataoura R, Patil S. Flecainide toxicity: a presentation to the emergency department with literature review. BMJ Case Rep. 2020 Feb 28;13(2):e232691. doi: 10.1136/bcr-2019-232691. PMID: 32114494; PMCID: PMC7050315. REFERENCE #3: Valentino MA, Panakos A, Ragupathi L, Williams J, Pavri BB. Flecainide Toxicity: A Case Report and Systematic Review of its Electrocardiographic Patterns and Management. Cardiovasc Toxicol. 2017 Jul;17(3):260-266. doi: 10.1007/s12012-016-9380-0. PMID: 27435408. DISCLOSURES: No relevant relationships by Rebecca Fieles, source=Web Response No relevant relationships by David Gerber, source=Web Response No relevant relationships by Brian Park, source=Web Response No relevant relationships by Harry Rockower, source=Web Response No relevant relationships by Diana Solomon, source=Web Response No relevant relationships by Yanika Wolfe, source=Web Response

UNPLEASANT SURPRISE: A CASE OF SPONTANEOUS TUMOR LYSIS SYNDROME FROM EXTRANODAL DIFFUSE LARGE B-CELL LYMPHOMA

TOPIC: Pulmonary Manifestations of Systemic Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Approximately a third of the patients with diffuse large B-cell lymphoma present with extranodal involvement.[1] Pleural effusion in diffuse large B-cell lymphoma (DLBCL) foreshadows a poor prognosis.[2] We present a rare case of spontaneous tumor lysis in extranodal DLBCL with unknown primary source, presenting with pleural effusion. CASE PRESENTATION: A 76-year-old man with history of hypertension, diabetes, chronic kidney disease, peripheral vascular disease with bilateral below-knee amputation and stroke, presented with 2 weeks of worsening weakness, decreased appetite, right-sided facial droop, difficulty speaking & trouble urinating; denied hematuria, dysuria, cough, chest pain, abdominal symptoms or history of HIV. On admission, he was hypothermic. Vital signs were stable otherwise. He was a&ox1 and somnolent. Labs remarkable for Na 131mmol/L, bicarbonate 15mmol/L, BUN 84.3mg/dl, creatinine(Cr) 3.72mg/dl, pro-BNP 21699pg/ml, hemoglobin 7.3g/dl, procalcitonin 1.34ng/ml. CT head showed no acute intracranial pathologies. Chest X-ray showed moderate right pleural effusion with partial loculation and right base patchy airspace opacity. Chest CT showed moderate-sized loculated right pleural effusion and small left pleural effusion. He was admitted for community-acquired pneumonia and was started on IV ceftriaxone and azithromycin. On day 2, thoracentesis was done and pleural fluid sent for analysis. On day 5, he was more somnolent and hyperkalemic to 6.8 with anion gap 24, BUN 84mg/dl, Cr 4mg/dl & bicarb 9mmol/L. EKG noted prolonged PR interval. He was started on aggressive IV fluids and sodium bicarbonate drip. Potassium remained elevated despite treatments with calcium gluconate, insulin, dextrose and potassium binders. Uric acid was 31mg/dl, phosphorus 15mg/dl and lactate dehydrogenase 882U/L. Given the lab abnormalities suspicious for tumor lysis syndrome, oncology was consulted. CT abdomen showed nonspecific thickening of the terminal ileum and bladder wall but no lymphadenopathy nor splenic enlargement. Urine cytology negative for malignant cells. Final pathology of pleural fluid showed diffuse large B cell lymphoma with Ki-67 of 80-90%. Rasburicase was given urgently for tumor lysis syndrome. Uric acid became undetectable the next day but Cr was 5.4. After discussion with family, the patient was placed under comfort-care measures as chemotherapy wouldn't be well-tolerated. He passed on day 13. DISCUSSION: Spontaneous tumor lysis syndrome is a rare oncological emergency with multiorgan failure, characterized by an elevation of uric acid, hyperphosphatemia, hypocalcemia, hyperkalemia with no active chemotherapy[3]. Our patient presented with unilateral pleural effusion without detectable lymphadenopathy or hepatosplenomegaly: an extremely rare presentation. CONCLUSIONS: If Cairo-Bishop definition is met, there should be high suspicion for spontaneous tumor lysis syndrome as early treatment can be life-saving. REFERENCE #1: Castillo JJ, Winer ES, Olszewski AJ. Sites of extranodal involvement are prognostic in patients with diffuse large B-cell lymphoma in the rituximab era: an analysis of the Surveillance, Epidemiology and End Results database. Am J Hematol. 2014 Mar;89(3):310-4. doi: 10.1002/ajh.23638. Epub 2014 Feb 19. PMID: 24273125. REFERENCE #2: Porcel, J.M., Cuadrat, I., García-Cerecedo, T. et al. Pleural Effusions in Diffuse Large B-Cell Lymphoma: Clinical and Prognostic Significance. Lung 197, 47–51 (2019). REFERENCE #3: Hsu HH, Chan YL, Huang CC. Acute spontaneous tumor lysis presenting with hyperuricemic acute renal failure: clinical features and therapeutic approach. J Nephrol. 2004 Jan-Feb;17(1):50-6. PMID: 15151259. DISCLOSURES: No relevant relationships by Ahmed Al-Ghrairi, source=Web Response No relevant relationships by Jini Hyun, source=Web Response No relevant relationships by Phyu Thin Naing, source=Web Response No relevant relationships by Rohan Paramesh, source=Web Response

English

BACKGROUND Organophosphate compounds (OPC) are important cause of poisoning in developing countries. They are irreversible cholinesterase inhibitors and produce signs and symptoms pertaining to various organ systems via their muscarinic and nicotinic effects. The cardiac manifestations include hemodynamic instability and various arrhythmias. Here, in this study, we described various electrocardiographic (ECG) changes in patients of OPC poisoning in our population. METHODS This is a descriptive, cross-sectional study conducted at tertiary academic centre. All patients (>14 years and < 75 years) with history of OPC poisoning were included. Diagnosis was made on the basis of history and clinical features. ECG analysis of each patient was done for rate, rhythm, ST segment and T wave changes, PR and QTc interval, conduction defects and atrial and ventricular premature complexes before and after administration of atropine. RESULTS A total of 54 patients with OPC poisoning were included. The mean age was 28 ± 14.5 years. The predominant age group was < 30 years. There was female predominance with male : female ratio of 1 : 1.45. The most common ECG finding was sinus arrhythmia (tachycardia 25.9 % and bradycardia 20.4 %), followed by prolonged QTc (14.8 %), ST - T changes (11.1 %), premature ventricular complexes (PVCs) (7.4 %), prolonged PR interval (3.7 %) and atrial fibrillation (1.9 %). There was no mortality. The mean ICU and Hospital stay was three and six days respectively. CONCLUSIONS Sinus arrhythmia was the most common ECG changes followed by prolonged QTc, ST - T segment changes and PVCs in our setup. Careful observation of these ECG changes and timely intervention can prevent from sudden cardiac death in these patients. KEY WORDS Cardiac, Complications, Electrocardiogram, Organophosphates, Poisoning

Abstract P356: Dual Dysfunction Of Kir2.1 Underlies Conduction And Excitation-contraction Coupling Defects Promoting Arrhythmias In A Mouse Model Of Andersen-tawil Syndrome Type 1

Background: Andersen-Tawil syndrome type 1 (ATS1), caused by trafficking deficient mutations in the gene KCNJ2 coding the inward rectifier K + channel Kir2.1, is associated with life-threatening arrhythmias, which in some patients resemble catecholaminergic polymorphic ventricular tachycardia (CPVT), but the mechanisms are poorly understood. We tested the hypothesis that dysfunction of two different populations of mutant Kir2.1 channels, one at the sarcolemma, and the other at the sarcoplasmic reticulum (SR) membrane, directly alters conduction and intracellular calcium dynamics, respectively, to promote the ATS1 phenotype and arrhythmias that resemble CPVT. Methods: We generated a new mouse model of ATS1 by a single i.v. injection of cardiac specific adeno-associated viral (AAV) transduction with Kir2.1 Δ314-315 . In-vivo and cellular, structural and functional analyses of the model were carried out by electrocardiogram (ECG), magnetic resonance imaging (MRI), intracardiac stimulation, patch-clamping, membrane fractionation, western blot, immunolocalization and live calcium imaging. Results: Our mouse model carrying mutant Kir2.1 Δ314-315 recapitulated the ATS1 phenotype without modifying ventricular function. On ECG, Kir2.1 Δ314-315 mice had prolonged PR, QRS and QT intervals and occasional U waves. They showed significantly slower conduction velocities than wildtype mice in response to flecaidine-induced Na + -channel blockade, additional QT prolongation in response to isoproterenol, and increased vulnerability to cardiac fibrillation. Cardiomyocytes from Kir2.1 Δ314-315 mice had significantly reduced inward rectifier K + and Na + inward currents, depolarized resting membrane potential and prolonged action potential duration. Immunolocalization in wildtype cardiomyocytes and skeletal muscle cells revealed a novel SR microdomain of functional Kir2.1 channels contributing to intracellular Ca 2+ homeostasis. Kir2.1 Δ314-315 cardiomyocytes showed defects in SR Kir2.1 localization and function, which contributed to abnormal spontaneous Ca 2+ release events. Conclusions: Cardiac-specific AAV transduction with Kir2.1 Δ314-315 in mice recapitulates the ATS1 phenotype by disrupting localization and function of Kir2.1 channels at the SR, and the Kir2.1-Na V 1.5 channelosome at the sarcolemma. These results reveal a novel dual mechanism of arrhythmogenesis in ATS1 involving defects in Kir2.1 channel trafficking and function at two different microdomains. They also provide the first demonstration at the molecular level of the mechanism underlying the overlap between ATS1 and CPVT associated with defects in intracellular calcium homeostasis.

Abstract P361: Reduced Cardiac Tmem65 In Mouse Hearts Results In Intercalated Disc Defects And Eventual Dilated Cardiomyopathy With Cardiac Fibrosis

The intercalated disc (ICD) is unique membrane structure that is indispensable to normal heart function. However, its structural organization is not well understood. Previously, we showed that the ICD-bound transmembrane protein 65 (Tmem65) was required for connexin 43 (Cx43) localization in cultured mouse neonatal cardiomyocytes. Here, we investigated the role of Tmem65 in ICD organization in vivo . A mouse model was established by injecting CD1 mouse pups (3-7 days after birth) with recombinant adeno-associated virus 9 (rAAV9) harboring Tmem65 (or scrambled) shRNA. Quantitative polymerase chain reaction (qPCR) and immunoblots confirmed greater than 85% reduction in Tmem65 expression (7.1±0.7% remained for Tmem65 proteins; 14.4±2.5% remained for Tmem65 transcripts, n =4) in mouse ventricles compared to control hearts. Tmem65 knockdown (KD) mice exhibited heart failure-like symptoms as early as 3 weeks post viral administration. Specifically, Tmem65 KD mice developed eccentric hypertrophic cardiomyopathy in 3 weeks and dilated cardiomyopathy with severe cardiac fibrosis in 7 weeks, as confirmed by H&E and Masson’s Trichrome staining. Echocardiography and electrocardiography, respectively, showed depressed hemodynamics (19.27±1.46ml/min for cardiac output in control hearts vs. 6.63±0.52ml/min for Tmem65 KD hearts, n =6) and impaired conduction, including prolonged PR (22.7±1.85ms in control hearts vs. 28.89±3.85ms in Tmem65 KD hearts, n≥8), QRS intervals (10.47±0.42ms in control hearts vs. 16.35±0.36ms in Tmem65 KD hearts, n≥8), and slowed heart rate (415±10bpm in control hearts vs. 347±16bpm in Tmem65 KD hearts, n≥8) in Tmem65 KD mouse hearts. Immunoprecipitation and super-resolution microscopy confirmed the physical interaction and localization between Tmem65 and voltage-gated sodium channel β subunit (β1) at the ICD and this interaction was evidently required for the establishment of perinexal nanodomains and voltage-gated sodium channel 1.5 (NaV1.5) localization to the ICD. Disrupting Tmem65 function, thus, impaired perinexal structure, reduced conduction velocity, and ultimately resulted in cardiomyopathy in vivo .

Current evidence for the risk of PR prolongation, QRS widening, QT prolongation, from lopinavir, ritonavir, atazanavir, and saquinavir: A systematic review.

Background:Lopinavir, ritonavir, atazanavir, and saquinavir had been reportedly used or suggested for coronavirus disease 2019 (COVID-19) treatment. They may cause electrocardiography changes. We aim to evaluate risk of PR prolongation, QRS widening, and QT prolongation from lopinavir, ritonavir, atazanavir, and saquinavir.Methods:In accordance with preferred reporting items for systematic reviews and meta-analyses guidelines, our search was conducted in PubMed Central, PubMed, EBSCOhost, and ProQuest from inception to June 25, 2020. Titles and abstracts were reviewed for relevance. Cochrane Risk of Bias Tool 2.0 and Downs and Black criteria was used to evaluate quality of studies.Results:We retrieved 9 articles. Most randomized controlled trials have low risk of biases while all quasi-experimental studies have a positive rating. Four studies reporting PR prolongation however only 2 studies with PR interval >200 ms. One of which, reported its association after treatment with ritonavir-boosted saquinavir treatment while another, during treatment with ritonavir-boosted atazanavir. No study reported QRS widening >120 ms with treatment. Four studies reporting QT prolongation, with only one study reaching QT interval >450 ms after ritonavir-boosted saquinavir treatment on healthy patients. There is only one study on COVID-19 patients reporting QT prolongation in 1 out of 95 patients after ritonavir-boosted lopinavir treatment.Conclusion:Limited evidence suggests that lopinavir, ritonavir, atazanavir, and saquinavir could cause PR prolongation, QRS widening, and QT prolongation. Further trials with closer monitoring and assessment of electrocardiography are needed to ascertain usage safety of antivirals in COVID-19 era.

Phase I study of mirvetuximab soravtansine (MIRV) and rucaparib for recurrent endometrial, platinum-resistant ovarian, fallopian tube or primary peritoneal cancer

Phase I study of mirvetuximab soravtansine (MIRV) and rucaparib for recurrent endometrial, platinum-resistant ovarian, fallopian tube or primary peritoneal cancer

Differential cardiotoxic electrocardiographic response to doxorubicin treatment in conscious versus anesthetized mice.

IntroductionDoxorubicin (DOX), an anticancer drug used in chemotherapy, causes significant cardiotoxicity. This study aimed to investigate the effects of DOX on mouse cardiac electrophysiology, in conscious versus anesthetized state.MethodsMale and female C57BL/6 mice were injected with saline, 20 or 30 mg/kg DOX. ECGs were recorded 5 days post‐injection in conscious and isoflurane anesthetized states. ECGs were analyzed using a custom MATLAB software to determine P, PR, QRS, QTc, and RR intervals as well as heart rate variability (HRV).ResultsECGs from the same mouse demonstrated P wave and QTc shortening as well as PR and RR interval prolongation in anesthetized versus conscious saline‐treated mice. ECG response to DOX was also modulated by anesthesia. DOX treatment induced significant ECG modulation in female mice alone. While DOX20 treatment caused decrease in P and QRS durations, DOX30 treatment‐induced QTc and RR interval prolongation in anesthetized but not in conscious female mice. These data suggest significant sex differences and anesthesia‐induced differences in ECG response to DOX. HRV measured in time and frequency domains, a metric of arrhythmia susceptibility, was increased in DOX20‐treated mice compared to saline.ConclusionsThis study for the first time identifies that the ECG response to DOX is modulated by anesthesia. Furthermore, this response demonstrated stark sex differences. These findings could have significant implications in clinical diagnosis of DOX cardiotoxicity.

B-PO05-033 PACEMAKER IMPLANTATION AFTER SELECTIVE ALCOHOL SEPTAL ABLATION

Complete heart block (CHB) with permanent pacemaker (PPM) placement is a known risk of alcohol septal ablation (ASA) for hypertrophic cardiomyopathy. Historically, the incidence has been around 10% in all-comer populations. However, rates of 25% are reported in centers that selectively target older, higher risk patients (pts). Understanding predictors of CHB in this evolving cohort is important. Report baseline characteristics, associated factors (AF) of PPM placement, longer-term pacing need following ASA in a high-volume HCM center. 94 consecutive pts underwent ASA from 2/2017 to 12/2020. 25 were excluded due to prior septal reduction or device. Criteria for PPM included persistent post-ASA CHB >24 hours, recurrent pacing due to 2nd degree HB/ transient CHB >24 hours. 69 pts (mean age 65.7 ± 11 years, females 53.6%) were included. 19 (27.5%) required PPM prior to discharge, 6 (31.5%) of whom were prohibitive surgical risk for myectomy (20.3% PPM rate in pts not at prohibitive surgical risk). All had reduction in peak provoked gradient (pre-procedure mean 149.8 mm Hg vs. post-procedure mean 10.5 mmHg, p<0.01) and improved NYHA class. Comparison of baseline clinical, ECG, and procedural characteristics (e.g., peak troponin and gradient reduction) yielded no AF of PPM implantation, with exception of intraprocedural CHB (OR 12.4, 95% CI 3.4 - 45.3, p<0.0001). Post procedure PR prolongation >50 ms (OR 6.1, 95% CI 1.5 - 24.5, p = 0.01), first-degree AV block with RBBB and LAFB (OR 6.1, 95% CI 1.5 - 24.5, p = 0.01) and change in QRS axis >700 (OR 5.3, 95% CI 1.4 - 18.9, p= 0.01) was also associated with PPM. At 1 month, 16 pts (84.2%) required >1% RV pacing (mean 59.2%) suggesting appropriateness of PPM implantation. At 3 months 10 pts (52.6%) required pacing (mean 52.4%) indicating some late recovery. No procedural factors were associated with PPM following ASA with exception of intraprocedural CHB. Daily ECGs identified dynamic abnormalities associated with PPM. Short term follow up suggests PPM criteria are appropriate, with longer term follow up showing some recovery. As higher risk cohorts are targeted for ASA, PPM risk factors of long term pacing will be vital.

B-AB03-01 DOSE-DEPENDENT TRANSIENT AV NODAL CONDUCTION BLOCK USING REVERSIBLE ELECTROPORATION

Membrane pores created with pulsed electrical fields (PF) can be reversible if delivered sub-threshold allowing for purposeful reversible electroporation (RE) of tissue. To evaluate the response of AV node to RE pulses in a preclinical model. Under general anesthesia, percutaneous femoral venous access was obtained in two swine. Abbreviated pulses were delivered to the AV node area using a 9mm lattice-tip catheter with varying PF waveforms using a custom mapping system and PF generator (Sphere-9, Prism-1, HexaPulse; Affera Inc, MA). RE pulses were delivered at either low-dose or high-dose. AV conduction was monitored following delivery. In sinus rhythm, a His potential was successfully recorded. A total of 9 low-dose and 7 high-dose RE pulses were delivered. Immediately following low-dose applications, PR prolongation (median 104 ms, IQR 10, 232ms) was observed in 7 of 9 applications (no change in 2 of 9); there was complete recovery to baseline in 6 of 7 within 4.7±3.7sec (the last 1 of 7 recovered to 10ms of baseline after 64 sec of observation). With high-dose RE, complete AV block occurred in 6 of 7 (PR prolongation in the remaining 1 of 7); there was complete recovery to baseline in 5 of 7 in 152±84 sec (the last 2 of 7 both recovered to within 30ms of baseline after 56 and 710 sec of observation, respectively). Pulsed electrical fields can be employed in a manner as to cause reversible conduction block of AV conduction in a dose-dependent manner. If reproduced clinically in other myocardial tissues, this introduces a potentially novel approach to interrogating arrhythmias.

B-PO03-009 DUAL AV NODE PATHWAYS MASQUERADING AS SYMPTOMATIC ATRIOVENTRICULAR CONDUCTION DISEASE: THE IMPORTANCE OF TREADMILL STRESS TESTING IN ESTABLISHING SYMPTOM-ARRHYTHMIA CORRELATION

Markedly prolonged AV conduction intervals (PR intervals >300ms) may represent slow pathway conduction in patients with previously undiagnosed dual AV node physiology. Treadmill stress testing is a simple and effective way to distinguish between dual AV node physiology and true AV nodal disease in patients with exertional dyspnea. 61 yo female with no significant past medical history referred to EP clinic for dual chamber pacemaker implantation. The patient presented with exercise intolerance secondary to exertional dyspnea and AV nodal conduction block thought to be contributing to her symptoms. Baseline EKG showed normal sinus rhythm and markedly prolonged PR interval at 420 ms. All other studies, including echocardiogram and pertinent bloodwork, were within normal limits. The patient agreed to proceed with exercise treadmill stress testing in an attempt to correlate her symptoms with suspected arrhythmias (AV conduction block). N/A Treadmill stress testing was performed. The patient exercised for 7 min 29 sec in a standard Bruce protocol (9.2 METS). Test was terminated secondary to fatigue and dyspnea. She exhibited a normal chronotropic response (86% MPHR). No ST segment changes consistent with ischemia were observed. Importantly, review of EKGs performed during testing revealed abrupt shortening of the PR interval during exercise. This response to exercise was consistent mechanistically with the existence of dual AV node physiology, as well as preferential fast-pathway conduction and retrograde slow-pathway block during exertion. Identification of dual-AVN physiology excluded the need for pacemaker implantation. While a markedly elevated PR interval can cause exertional dyspnea secondary to dyssynchronous atrial systole or progression to AV conduction block (Mobitz Type I/II). Establishing a symptom-arrhythmia correlation is a crucial diagnostic step. As outlined above, treadmill testing identified dual AVN physiology, and revealed benign preferential slow pathway conduction at rest as the source of the prolonged PR interval. This test excluded AV nodal disease as the source of symptoms, and ensured that the patient did not undergo unnecessary pacemaker implantation.

Predictive Factors for Recurrence of Serious Arrhythmias in Patients with Acute Digoxin Poisoning.

Although digoxin poisoning has declined in the past decades, it still has deleterious outcomes. The hallmark of serious life-threatening arrhythmias remains challenging due to its non-specific initial presentation. Therefore, this study aimed to evaluate the initial predictive factors for recurrent serious arrhythmias and the need for temporary pacing in acute digoxin-poisoned patients. This retrospective cohort study included all patients with acute digoxin poisoning admitted to Tanta University Poison Control Center from 2017 to 2020. Demographic and toxicological data, poisoning severity score (PSS), laboratory investigations, and serial ECG monitoring data were documented. Patients were divided according to their age into a childhood group and adolescence & adulthood group. Each age group was divided into two subgroups according to the presence of recurrent serious arrhythmias. Patient outcomes, including intensive care unit admission, temporary pacing, and in-hospital mortality were recorded. A percentage of 37.34% (n = 31) of the included patients had recurrent serious arrhythmias in both groups. Recurrent serious arrhythmias groups had significantly low heart rate, prolonged PR interval, high PSS, Mobitz II dysrhythmias, elevated serum digoxin, serum potassium and serum creatinine, and increased adverse outcomes compared to other groups. Logistic regression analysis showed that only serum digoxin and potassium levels were significant independent predictors of recurrent serious arrhythmias and temporary pacing. Serum digoxin level had an excellent discriminatory power with the best sensitivity and specificity, followed by serum potassium level in both groups. Thus, monitoring serum digoxin and potassium levels is essential in all patients with acute digoxin poisoning, especially with limited Fab availability.

Cardiac effects of rapid intravenous loading of lacosamide in patients with epilepsy

BackgroundLacosamide (LCM) is a new antiseizure medication, and intravenous (IV) loading of LCM is recently used against status epilepticus. IV loading of LCM is usually well-tolerated; however, there are concerns about LCM-induced serious adverse cardiac events. This study was aimed at investigating whether rapid IV loading of LCM is associated with adverse cardiac or hemodynamic events in cases of epilepsy emergencies in real-world settings. MethodsWe reviewed medical records of consecutive adult epilepsy patients who received a single loading dose (400 mg) of IV LCM between January 2019 and December 2020 and included patients who exhibited status epilepticus or acute repetitive seizures. Electrocardiography findings, blood pressure, and heart rate before and after the IV infusion of LCM were collected. ResultsOf the 85 patients included, 32.9 % (28/85 patients) had experienced at least one cardiac adverse event. The most common adverse events were new-onset first-degree atrioventricular block (19 patients) and hypotension (seven patients). Atrial fibrillation and bradycardia developed in two patients and atrial flutter in one. There were significant increases in the mean PR interval (from 169.3 msec to 184.5 msec, P < 0.01) and decreases in the mean heart rate (from 91.7 to 86.9, P = 0.01) after IV loading of LCM. Older age was significantly associated with a higher magnitude of the PR interval difference between before and after IV loading of LCM. ConclusionsIn cases of epilepsy emergencies, adverse cardiac events commonly developed after IV loading of LCM, although most adverse events were mild in severity or not clinically significant. Elderly patients or patients with underlying cardiac diseases were prone to exhibiting a more prolonged PR interval after IV loading of LCM. Thus, the loading dose of IV LCM should be infused under careful ECG monitoring in these patients.

Risk factors for the occurrence of typical atrial flutter in patients undergoing pulmonary vein isolation

Highlights. Cavatricuspid isthmus ablation with pulmonary vein isolation is indicated to all patients with documented or intraoperatively induced typical atrial flutter. The preventive cavatricuspid isthmus ablation remains an issue of concern. The article discusses the risk factors for the onset of typical atrial flutter pulmonary vein isolation.Aim. To determine the need for preventive ablation of the cavatricuspid isthmus in patients referred to elective pulmonary vein isolation.Methods. 632 patients (the mean age of 63 years) were enrolled in a single-center retrospective study between 2015 to 2018. The inclusion criteria were as follows: paroxysmal AF, absence of documented AFL. All patients underwent pulmonary vein isolation. The exclusion criteria were as follows: a history of typical or AFL. The endpoints included major cardiovascular events, reoperations, occurrence of AFL. The primary endpoint was the absence of paroxysms of AF and AFL during the blind period. The secondary endpoint was the absence of AF paroxysms documented on the ECG or according to Holter monitoring data. The follow-up period was 12 months.Results. During the blind period, AF paroxysms were recorded in 148 (23.7%) patients. The efficiency of the operation within one year was 78.2% (494 patients). 138 patients (21.8%) had recurrent tachycardia. Of them, 28 patients (4.4%) were diagnosed with atrial fibrillation and others (17.4%) had AFL. Risk factors for AFL included COPD found in 18 patients (64.29%) (OR 25.4; CI 95%; 10.991-58.609), chronic heart failure in 20 patients (71.43%) (OR 7.434; CI 95%; 3.209-17.225), prolonged pr interval in 18 patients (64.29%) (OR 5.77; CI 95%; 2.288-14.5), a history of myocardial infarction in 6 patients (28.57%) (OR 6.591; CI 95%; 2.447-17.751), and smoking in 7 patients (67.86%) (OR 11.034; CI 95%; 4.849-25.112).Conclusion. Chronic obstructive pulmonary disease, chronic heart failure, a history of myocardial infarction, and smoking prolong right atrial conduction time, thereby increasing the risk of AFL in the postoperative period. Preventive cavatricuspid isthmus ablation should be considered in patients with risk factors for developing AFL.

Expert consensus document on automated diagnosis of the electrocardiogram: The task force on automated diagnosis of the electrocardiogram in Japan. Part 1: Nomenclature for diagnosis and abnormal findings.

As these terms should accurately represent the abnormal findings and conditions as much as possible, we propose to unify these terms into terminologies that are not confusing and easy to understand for everyone.

The precordial R' wave: A novel discriminator between cardiac sarcoidosis and arrhythmogenic right ventricular cardiomyopathy in patients presenting with ventricular tachycardia.

Cardiac sarcoidosis (CS) with right ventricular (RV) involvement can mimic arrhythmogenic right ventricular cardiomyopathy (ARVC). Histopathological differences may result in disease-specific RV activation patterns detectable on the 12-lead electrocardiogram. Dominant subepicardial scar in ARVC leads to delayed activation of areas with reduced voltages, translating into terminal activation delay and occasionally (epsilon) waves with a small amplitude. Conversely, patchy transmural RV scar in CS may lead to conduction block and therefore late activated areas with preserved voltages reflected as preserved R' waves. The purpose of this study was to evaluate the distinct terminal activation patterns in precordial leads V1 through V3 as a discriminator between CS and ARVC. Thirteen patients with CS affecting the RV and 23 patients with gene-positive ARVC referred for ventricular tachycardia ablation were retrospectively included in a multicenter approach. A non-ventricular-paced 12-lead surface electrocardiogram was analyzed for the presence and the surface area of the R' wave (any positive deflection from baseline after an S wave) in leads V1 through V3. An R' wave in leads V1 through V3 was present in all patients with CS compared to 11 (48%) patients with ARVC (P=.002). An algorithm including a PR interval of ≥220 ms, the presence of an R' wave, and the surface area of the maximum R' wave in leads V1 through V3 of ≥1.65 mm2 had 85% sensitivity and 96% specificity for diagnosing CS, validated in a second cohort (18 CS and 40 ARVC) with 83% sensitivity and 88% specificity. An easily applicable algorithm including PR prolongation and the surface area of the maximum R' wave in leads V1 through V3 of ≥1.65 mm2 distinguishes CS from ARVC. This QRS terminal activation in precordial leads V1 through V3 may reflect disease-specific scar patterns.

Long‐term Consumption of Artificial Sweeteners Does not Affect Cardiovascular Function but May Cause Cardiac Electrophysiological Abnormalities in Rats

Introduction Artificial sweeteners are commonly used as sugar substitutes. Because they have virtually no calories, they are believed to be useful in combatting obesity, metabolic syndrome, and diabetes. However, there is still uncertainty about their potential health problems. Recent population studies have suggested that consumption of artificial sweeteners was associated with adverse cardiovascular events - in particular, increasing coronary artery disease, stroke and all-cause mortality. Nevertheless, those population association studies cannot establish a causal relationship. We hypothesized that long-term consumption of artificial sweeteners could cause cardiovascular dysfunction. Thus, in this study we investigated the effect of long-term (1 year) consumption of artificial sweeteners (Equal and Splenda, 2 commonly used artificial sweeteners) in drinking water on cardiovascular health in rats. Methods Adult Sprague-Dawley rats (both sexes, 4-5 months old) were randomized into the following 3 groups: control group (n=21), artificial sweetener Equal group (n=21) and Splenda group (n=18). In the artificial sweetener groups, Equal or Splenda (at concentration of 2 packs per cup of water) was added to the drinking water, while drinking water alone was used in the control rats. The treatment was administered for 12 months. At the end of the treatment, blood pressure, pulse wave velocity (an index of arterial stiffness), left ventricular pressure and cardiac function were measured using catheter approach and echocardiography. ECG and cardiac electrophysiology was determined using intracardiac catheter approach. Blood glucose and lipids levels were also measured. Results Rats consistently consumed more sweetened water in both Equal and Splenda groups than that in the control group (e.g., 45±6ml in control, 72±5ml in Equal and 74±14ml in Splenda groups at 2 week treatment, P<0.01). The body weight was comparable among the 3 groups. The blood pressure and pulse wave velocity were not altered after 1-year treatment. There were no significant differences in left ventricular wall thicknesses, chamber dimension and cardiac function evaluated with cardiac echocardiography and left ventricular hemodynamic at the end of the experiment. There were no differences in blood lipids and glucose levels. Artificial sweeteners did not affect heart rate and atrial effective refractory period. However, rats in both Equal and Splenda groups had longer PR intervals (63±5ms in Equal, 68±6 ms in Splenda, vs 56±8ms in control, p<0.01) and a tendency of increased atrial fibrillation inducibility (60% in Equal, 70% in Splenda vs 31% in control). The survival (15/21 in Equal, 10/18 in Splenda, and 16/21 in control) was not significantly affected by the 1-year treatment. Conclusions Long-term consumption of artificial sweeteners in drinking water did not affect blood glucose and lipids levels. The artificial sweeteners did not affect blood pressure and cardiovascular function but caused some electrophysiological abnormalities with prolonged PR interval and a tendency of increased atrial fibrillation inducibility in rats. The 1-year survival was not significantly affected in these animals.

Rhythm monitoring strategies for atrial fibrillation detection in patients with cryptogenic stroke: A systematic review and meta-analysis.

ObjectiveTo summarize data on atrial fibrillation (AF) detection rates and predictors across different rhythm monitoring strategies in patients with cryptogenic stroke (CS) or embolic stroke of undetermined source (ESUS).MethodsMEDLINE, Embase, and Web of Science were searched to identify all published studies providing relevant data through July 6, 2020. Random-effects meta-analysis method was used to pool estimates.ResultsWe included 47 studies reporting on a pooled population of 8,215 patients with CS or ESUS. Using implantable cardiac monitor (ICM), the pooled rate of AF was 12.2% (95% CI 9.4–15.0) at 3 months, 16.0% (95% CI 13.2–18.8) at 6 months, 18.7% (95% CI 15.7–21.7) at 12 months, 22.8% (95% CI 19.1–26.5) at 24 months, and 28.5% (95% CI 17.6–39.3) at 36 months. AF rates were significantly higher in patients with ESUS vs CS (22.0% vs 14.2%; p < 0.001) at 6 months, and in studies using Reveal LINQ vs Reveal XT ICM (19.1% vs 13.0%; p = 0.001) at 12 months. Using mobile cardiac outpatient telemetry (MCOT), the pooled rate of AF was 13.7% (95% CI 10.2–17.2) at 1 month. Predictors of AF detection with ICM included older age, CHA2DS2-VASc score, left atrial enlargement, P wave maximal duration and prolonged PR interval.ConclusionThe yield of ICM increases with the duration of monitoring. More than a quarter of patients with CS or ESUS will be diagnosed with AF during follow-up. About one in seven patients had AF detected within a month of MCOT, suggesting that a non-invasive rhythm monitoring strategy should be considered before invasive monitoring.

“A CROSS SECTIONAL, DESCRIPTIVE STUDY ON SYSTEMIC ILLNESSES AND CARDIAC FUNCTION ABNORMALITIES IN CHILDREN”

Background:There are wide number of diseases of almost every system in the body which can affect heart in a number of different ways including increasing demands on the heart ,ventricular dysfunction ,rhythm abnormalities ,valve abnormalities ,pulmonary pressures and lot more.Cardiac involvement in systemic diseases is usually silent or oligosymptomatic and includes different pathophysiological mechanisms such as myocardial inflammation, infarction ,subendocardial vasculitis,valvular disease and different patterns of fibrosis. Objective : To study association between systemic illnesses (hematological, endocrinal , renal) and cardiac function abnormalities as ventricular function,cardiac dimensions ,pulmonary artery pressure and pericardial effusion,for early diagnosis and treatment to decrease morbidity and mortality in patient with systemic illness. Design/Method:It was a cross sectional,descriptive study The present study was conducted in the Department of Pediatrics, LLRM Medical College,Meerut,Uttar Pradesh over a period of 1 year (June 2019-June 2020) Results: Cardiac findings in all three groups show ECG abnormalities and echocardiographic changes compared to general population. ECG abnormalities were prolonged PR interval and sinus tachycardia while echocardiographic changes mainly left ventricular(LV) dilatation and hypertrophy ,increased cardiac output ,ventricular dysfunction and pulmonary arterial hypertension(PAH),were noted in a significant proportion of patients. Conclusion:Systemic illnesses affect cardiac parameters in various ways including prolonged PR interval,cardiac dilatation,chamber hypertrophy ,high cardiac output,high cardiac index ,PAH and ventricular dysfunction.