Browsing by Subject "Arrhythmia"
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Item Arrhythmia Mechanism and Dynamics in a Humanized Mouse Model of Inherited Cardiomyopathy Caused by Phospholamban R14del Mutation(American Heart Association, 2021) Raad, Nour; Bittihn, Philip; Cacheux, Marine; Jeong, Dongtak; Ilkan, Zeki; Ceholski, Delaine; Kohlbrenner, Erik; Zhang, Lu; Cai, Chen-Leng; Kranias, Evangelia G.; Hajjar, Roger J.; Stillitano, Francesca; Akar, Fadi G.; Pediatrics, School of MedicineBackground: Arginine (Arg) 14 deletion (R14del) in the calcium regulatory protein phospholamban (hPLNR14del) has been identified as a disease-causing mutation in patients with an inherited cardiomyopathy. Mechanisms underlying the early arrhythmogenic phenotype that predisposes carriers of this mutation to sudden death with no apparent structural remodeling remain unclear. Methods: To address this, we performed high spatiotemporal resolution optical mapping of intact hearts from adult knock-in mice harboring the human PLNWT (wildtype [WT], n=12) or the heterozygous human PLNR14del mutation (R14del, n=12) before and after ex vivo challenge with isoproterenol and rapid pacing. Results: Adverse electrophysiological remodeling was evident in the absence of significant structural or hemodynamic changes. R14del hearts exhibited increased arrhythmia susceptibility compared with wildtype. Underlying this susceptibility was preferential right ventricular action potential prolongation that was unresponsive to β-adrenergic stimulation. A steep repolarization gradient at the left ventricular/right ventricular interface provided the substrate for interventricular activation delays and ultimately local conduction block during rapid pacing. This was followed by the initiation of macroreentrant circuits supporting the onset of ventricular tachycardia. Once sustained, these circuits evolved into high-frequency rotors, which in their majority were pinned to the right ventricle. These rotors exhibited unique spatiotemporal dynamics that promoted their increased stability in R14del compared with wildtype hearts. Conclusions: Our findings highlight the crucial role of primary electric remodeling caused by the hPLNR14del mutation. These inherently arrhythmogenic features form the substrate for adrenergic-mediated VT at early stages of PLNR14del induced cardiomyopathy.Item Arrhythmia-related Hospitalization and Comorbid Cannabis Use Disorder: Trend Analysis in US Hospitals (2010-2014)(Cureus, 2019-09-09) Jaladi, Paul Rahul; Patel, Viralkumar; Kuduva Rajan, Shanthini; Rashid, Wahida; Madireddy, Sowmya; Ajibawo, Temitope; Imran, Sundus; Patel, Rikinkumar S.; Neurology, School of MedicineObjective To study the trends of arrhythmia hospitalizations with cannabis use disorders (CUDs) in terms of demographic characteristics and inpatient outcomes. Methods We used the nationwide inpatient sample (NIS) data during the post-legalization period (2010-2014) and included 570,556 arrhythmia inpatients (age, 15-54 years), and 14,426 inpatients had comorbid CUD (2.53%). We used the linear-by-linear association test and independent-sample T-test for assessing the change in hospital outcomes in inpatients with CUD. Results Arrhythmia hospitalizations with CUD increased by 31% (2010-2014). This increasing trend was seen in adults (45-54 years, P < 0.001) and was predominant in males (77.6%). Hypertension (40.6%), hyperlipidemia (17.6%), and obesity (15%) were prevalent medical comorbidities with variable trends over the five years. Among substance use disorders, tobacco (50.9%), and alcohol (31.4%) were major comorbidities with a variable trend (P = 0.003 for each). There was a 71.4% increase in the inpatient mortality rate between 2010 (0.7%) and 2014 (1.2%). The mean length of stay was three days, and the total hospitalization charges have been increasing (P < 0.001), averaging $35,812 per hospital admission. Conclusion Chronic cannabis use or abuse worsens hospitalization outcomes in arrhythmic patients, and more clinical studies are needed to study the causal association between these conditions due to the rising mortality risk.Item Chemotherapy-Related Tumour Lysis Syndrome(Association of Kenya Physicians, 2007) Busakhala, N. W.; Association of Kenya Physicians Scientific Conference (11th : Mar. 2007 : Eldoret, Kenya)Two types of tumour lysis syndrome (TLS) ; 1. Laboratory TLS: 25% increase in potassium, phosphate and uric acid, or decline in calcium from baseline. Occur within 4 days of initiating chemotherapy. Patients on standard of care. Minimum of two out of four criteria. 2. Clinical tumour lysis syndrome: Laboratory TLS plus renal failure, cardiac arrhythmias or sudden death. A new definition has been suggested by Cairo and Bishop to include values above upper limit of normal. Study used Hande and Garrow definition.Item Creation of a novel algorithm to identify patients with Becker and Duchenne muscular dystrophy within an administrative database and application of the algorithm to assess cardiovascular morbidity(Cambridge University Press, 2019-03) Soslow, Jonathan H.; Hall, Matthew; Burnette, W. Bryan; Hor, Kan; Chisolm, Joanne; Spurney, Christopher; Godown, Justin; Xu, Meng; Slaughter, James C.; Markham, Larry W.; Pediatrics, School of MedicineBACKGROUND: Outcome analyses in large administrative databases are ideal for rare diseases such as Becker and Duchenne muscular dystrophy. Unfortunately, Becker and Duchenne do not yet have specific International Classification of Disease-9/-10 codes. We hypothesised that an algorithm could accurately identify these patients within administrative data and improve assessment of cardiovascular morbidity. METHODS: Hospital discharges (n=13,189) for patients with muscular dystrophy classified by International Classification of Disease-9 code: 359.1 were identified from the Pediatric Health Information System database. An identification algorithm was created and then validated at three institutions. Multi-variable generalised linear mixed-effects models were used to estimate the associations of length of stay, hospitalisation cost, and 14-day readmission with age, encounter severity, and respiratory disease accounting for clustering within the hospital. RESULTS: The identification algorithm improved identification of patients with Becker and Duchenne from 55% (code 359.1 alone) to 77%. On bi-variate analysis, left ventricular dysfunction and arrhythmia were associated with increased cost of hospitalisation, length of stay, and mortality (p<0.001). After adjustment, Becker and Duchenne patients with left ventricular dysfunction and arrhythmia had increased length of stay with rate ratio 1.4 and 1.2 (p<0.001 and p=0.004) and increased cost of hospitalization with rate ratio 1.4 and 1.4 (both p<0.001). CONCLUSIONS: Our algorithm accurately identifies patients with Becker and Duchenne and can be used for future analysis of administrative data. Our analysis demonstrates the significant effects of cardiovascular disease on length of stay and hospitalisation cost in patients with Becker and Duchenne. Better recognition of the contribution of cardiovascular disease during hospitalisation with earlier more intensive evaluation and therapy may help improve outcomes in this patient population.Item Effects of carvedilol on cardiac autonomic nerve activities during sinus rhythm and atrial fibrillation in ambulatory dogs(Oxford University Press, 2014-07) Choi, Eue-Keun; Shen, Mark J.; Lin, Shien-Fong; Chen, Peng-Sheng; Oh, Seil; Department of Medicine, IU School of MedicineAIMS: We hypothesized that carvedilol can effectively suppress autonomic nerve activity (ANA) in ambulatory dogs during sinus rhythm and atrial fibrillation (AF), and that carvedilol withdrawal can lead to rebound elevation of ANA. Carvedilol is known to block pre-junctional β2-adrenoceptor responsible for norepinephrine release. METHODS AND RESULTS: We implanted radiotransmitters to record stellate ganglion nerve activity (SGNA), vagal nerve activity (VNA), and superior left ganglionated plexi nerve activity (SLGPNA) in 12 ambulatory dogs. Carvedilol (12.5 mg orally twice a day) was given for 7 days during sinus rhythm (n = 8). Four of the eight dogs and an additional four dogs were paced into persistent AF. Carvedilol reduced heart rate [from 103 b.p.m. (95% confidence interval (CI), 100-105) to 100 b.p.m. (95% CI, 98-102), P = 0.044], suppressed integrated nerve activities (Int-NAs, SGNA by 17%, VNA by 19%, and SLGPNA by 12%; all P < 0.05 vs. the baseline), and significantly reduced the incidence (from 8 ± 6 to 3 ± 3 episodes/day, P < 0.05) and total duration (from 68 ± 64 to 16 ± 21 s/day, P < 0.05) of paroxysmal atrial tachycardia (PAT). Following the development of persistent AF, carvedilol loading was associated with AF termination in three dogs. In the remaining five dogs, Int-NAs were not significantly suppressed by carvedilol, but SGNA significantly increased by 16% after carvedilol withdrawal (P < 0.001). CONCLUSION: Carvedilol suppresses ANA and PAT in ambulatory dogs during sinus rhythm.Item Effects of renal sympathetic denervation on the stellate ganglion and brain stem in dogs(Elsevier, 2017-02) Tsai, Wei-Chung; Chan, Yi-Hsin; Chinda, Kroekkiat; Chen, Zhenhui; Patel, Jheel; Shen, Changyu; Zhao, Ye; Jiang, Zhaolei; Yuan, Yuan; Ye, Michael; Chen, Lan S.; Riley, Amanda A.; Persohn, Scott A.; Territo, Paul R.; Everett, Thomas H., IV; Lin, Shien-Fong; Vinters, Harry V.; Fishbein, Michael C.; Chen, Peng-Sheng; Medicine, School of MedicineBACKGROUND: Renal sympathetic denervation (RD) is a promising method of neuromodulation for the management of cardiac arrhythmia. OBJECTIVE: We tested the hypothesis that RD is antiarrhythmic in ambulatory dogs because it reduces the stellate ganglion nerve activity (SGNA) by remodeling the stellate ganglion (SG) and brain stem. METHODS: We implanted a radiotransmitter to record SGNA and electrocardiogram in 9 ambulatory dogs for 2 weeks, followed by a second surgery for RD and 2 months SGNA recording. Cell death was probed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. RESULTS: Integrated SGNA at baseline and 1 and 2 months after RD were 14.0 ± 4.0, 9.3 ± 2.8, and 9.6 ± 2.0 μV, respectively (P = .042). The SG from RD but not normal control dogs (n = 5) showed confluent damage. An average of 41% ± 10% and 40% ± 16% of ganglion cells in the left and right SG, respectively, were TUNEL positive in RD dogs compared with 0% in controls dogs (P = .005 for both). The left and right SG from RD dogs had more tyrosine hydroxylase-negative ganglion cells than did the left SG of control dogs (P = .028 and P = .047, respectively). Extensive TUNEL-positive neurons and glial cells were also noted in the medulla, associated with strongly positive glial fibrillary acidic protein staining. The distribution was heterogeneous, with more cell death in the medial than lateral aspects of the medulla. CONCLUSION: Bilateral RD caused significant central and peripheral sympathetic nerve remodeling and reduced SGNA in ambulatory dogs. These findings may in part explain the antiarrhythmic effects of RD.Item Energy drink consumption: a rising public health issue(IMR Press, 2022) Kaur, Amandeep; Yousuf, Hamza; Ramgobin-Marshall, Devyani; Jain, Rahul; Jain, Rohit; Medicine, School of MedicineEnergy drink (ED) consumption has become a growing public health issue over the past few decades. Despite claims of being safe and beneficial, EDs have been linked to particularly fatal outcomes associated with the cardiovascular system which include atrial and ventricular arrhythmias, myocardial infarctions, cardiomyopathies, and sudden cardiac death. Large quantities of caffeine, taurine, sugars, and B-vitamins may be contributing to these outcomes by increasing the heart rate, blood pressure (BP), and contractility of the heart in addition to prolonging the QTc. There is still a substantial amount of unknown information on EDs that warrants more research and a dire need for age regulations, transparency of ingredients, clear labeling of adverse effects, and most importantly, education of consumers.Item Epicardial Fat Distribution Assessed with Cardiac CT invArrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy(RSNA, 2018-12) Aliyari Ghasabeh, Mounes; Te Riele, Anneline S. J. M.; James, Cynthia A.; Chen, H. S. Vincent; Tichnell, Crystal; Murray, Brittney; Eng, John; Kral, Brian G.; Tandri, Harikrishna; Calkins, Hugh; Kamel, Ihab R.; Zimmerman, Stefan L.; Medicine, School of MedicinePurpose To compare epicardial fat in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) with that in healthy subjects. Materials and Methods In this retrospective study, cardiac CT scans in 44 patients with ARVD/C (mean age, 39 years ± 12; 23 men) were compared with those in 45 control group participants between January 2008 and July 2015. Volumes of intrathoracic adipose tissue, mediastinal adipose tissue (MAT), and total epicardial adipose tissue (EAT) were quantified. EAT was subdivided into three regions—right ventricular (RV) EAT, left ventricular (LV) EAT, and peri-atrial EAT (atrial EAT)—and normalized to MAT for all regions. Logistic regression and receiver operating characteristic analysis were performed to evaluate the association between epicardial fat with the diagnosis of ARVD/C. Results Total EAT volume was higher in patients with ARVD/C than in healthy control group participants (median, 98 mL vs 76 mL, respectively; P = .04). Regionally, LV and RV EAT volumes were higher in patients with ARVD/C than in control group participants, most notably when indexed to MAT (median LV EAT index: 0.49 vs 0.15, respectively; median RV EAT index: 0.91 vs 0.52; P ˂ .0005 for both). The optimal cutoff for diagnosis of ARVD/C was an LV EAT index of 0.24, with a sensitivity and specificity of 91% and 71%, respectively. Atrial EAT volume and total intrathoracic adipose tissue volume were not different between groups. RV diameter showed a positive correlation with total EAT index and LV EAT index (r = 0.21, P = .05 and r = 0.33, P = .002, respectively). Conclusion Higher amounts of right ventricular and left ventricular epicardial fat are found in hearts with arrhythmogenic right ventricular dysplasia/cardiomyopathy, particularly adjacent to the left ventricle, which correlates with disease severity and helps differentiate patients from healthy subjects.Item Long-term intermittent high-amplitude subcutaneous nerve stimulation reduces sympathetic tone in ambulatory dogs(Elsevier, 2018-03) Yuan, Yuan; Jiang, Zhaolei; Zhao, Ye; Tsai, Wei-Chung; Patel, Jheel; Chen, Lan S.; Shen, Changyu; Lin, Shien-Fong; Chen, Huei-Sheng Vincent; Everett, Thomas H., IV; Fishbein, Michael C.; Chen, Zhenhui; Chen, Peng-Sheng; Medicine, School of MedicineBACKGROUND: Reducing sympathetic efferent outflow from the stellate ganglia (SG) may be antiarrhythmic. OBJECTIVE: The purpose of this study was to test the hypothesis that chronic thoracic subcutaneous nerve stimulation (ScNS) could reduce SG nerve activity (SGNA) and control paroxysmal atrial tachycardia (PAT). METHODS: Thoracic ScNS was performed in 8 dogs while SGNA, vagal nerve activity (VNA), and subcutaneous nerve activity (ScNA) were monitored. An additional 3 dogs were used for sham stimulation as controls. RESULTS: Xinshu ScNS and left lateral thoracic nerve ScNS reduced heart rate (HR). Xinshu ScNS at 3.5 mA for 2 weeks reduced mean average SGNA from 5.32 μV (95% confidence interval [CI] 3.89-6.75) at baseline to 3.24 μV (95% CI 2.16-4.31; P = .015) and mean HR from 89 bpm (95% CI 80-98) at baseline to 83 bpm (95% CI 76-90; P = .007). Bilateral SG showed regions of decreased tyrosine hydroxylase staining with increased terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive nuclei in 18.47% (95% CI 9.68-46.62) of all ganglion cells, indicating cell death. Spontaneous PAT episodes were reduced from 9.83 per day (95% CI 5.77-13.89) in controls to 3.00 per day (95% CI 0.11-5.89) after ScNS (P = .027). Left lateral thoracic nerve ScNS also led to significant bilateral SG neuronal death and significantly reduced average SGNA and HR in dogs. CONCLUSION: ScNS at 2 different sites in the thorax led to SG cell death, reduced SGNA, and suppressed PAT in ambulatory dogs.