2,441 results on '"Shivkumar, Kalyanam"'
Search Results
2. Insights Into Interaction Between Clip Device and the Mitral Valve Apparatus in the Human Heart.
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Mori, Shumpei, Sato, Takanori, Moussa, Issam, Hanna, Peter, and Shivkumar, Kalyanam
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MitraClip ,anatomy ,chordae tendineae ,mitral regurgitation ,transcatheter edge-to-edge repair - Abstract
Precise appreciation of the 3-dimensional relationship between the edge-to-edge clips and mitral valve apparatus remains clinically challenging. We demonstrate the images of clips observed in situ 4 years after implantation. Detailed observation from this case helps improve our understanding of 3-dimensional clinical cardiac anatomy related to transcatheter edge-to-edge mitral valve repair. (Level of Difficulty: Intermediate.).
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- 2023
3. Photogrammetry of Perfusion-Fixed Heart: Innovative Approach to Study 3-Dimensional Cardiac Anatomy.
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Sato, Takanori, Hanna, Peter, Ajijola, Olujimi, Mori, Shumpei, and Shivkumar, Kalyanam
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anatomy ,imaging ,photogrammetry - Abstract
Photogrammetry generates a 3-dimensional high-resolution model from multiple 2-dimensional photographs. Herein, we demonstrate a photogrammetry of a perfusion-fixed cardiac sample around the left ventricular summit. The single photogrammetric model can be observed from almost all directions and illustrates important anatomical features for the general cardiologist. (Level of Difficulty: Advanced.).
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- 2023
4. Vagal Nerve Stimulation Reduces Ventricular Arrhythmias and Mitigates Adverse Neural Cardiac Remodeling Post-Myocardial Infarction.
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Hadaya, Joseph, Dajani, Al-Hassan, Cha, Steven, Hanna, Peter, Challita, Ronald, Hoover, Donald, Ajijola, Olujimi, Shivkumar, Kalyanam, and Ardell, Jeffrey
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myocardial infarction ,neurocardiology ,sympathetic nervous system ,vagal nerve stimulation ,ventricular tachycardia/ventricular fibrillation - Abstract
This study sought to evaluate the impact of chronic vagal nerve stimulation (cVNS) on cardiac and extracardiac neural structure/function after myocardial infarction (MI). Groups were control, MI, and MI + cVNS; cVNS was started 2 days post-MI. Terminal experiments were performed 6 weeks post-MI. MI impaired left ventricular mechanical function, evoked anisotropic electrical conduction, increased susceptibility to ventricular tachycardia and fibrillation, and altered neuronal and glial phenotypes in the stellate and dorsal root ganglia, including glial activation. cVNS improved cardiac mechanical function and reduced ventricular tachycardia/ventricular fibrillation post-MI, partly by stabilizing activation/repolarization in the border zone. MI-associated extracardiac neural remodeling, particularly glial activation, was mitigated with cVNS.
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- 2023
5. Design and characteristics of the prophylactic intra-operative ventricular arrhythmia ablation in high-risk LVAD candidates (PIVATAL) trial.
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Huang, David, Gosev, Igor, Wood, Katherine, Vidula, Hima, Stevenson, William, Marchlinski, Frank, Supple, Gregory, Zalawadiya, Sandip, Weiss, J, Tung, Roderick, Tzou, Wendy, Moss, Joshua, Kancharla, Krishna, Chaudhry, Sunit-Preet, Patel, Parin, Khan, Arfaat, Schuger, Claudio, Rozen, Guy, Kiernan, Michael, Couper, Gregory, Leacche, Marzia, Molina, Ezequiel, Shah, Anand, Lloyd, Michael, Sroubek, Jakub, Soltesz, Edward, Shivkumar, Kalyanam, White, Casey, Tankut, Sinan, Johnson, Brent, McNitt, Scott, Kutyifa, Valentina, Zareba, Wojciech, and Goldenberg, Ilan
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ablation ,left ventricular assist device ,ventricular tachycardia ,Humans ,Heart-Assist Devices ,Prospective Studies ,Quality of Life ,Risk Factors ,Electrocardiography ,Arrhythmias ,Cardiac ,Tachycardia ,Ventricular ,Heart Failure ,Defibrillators ,Implantable ,Treatment Outcome - Abstract
BACKGROUND: The use of a Left Ventricular Assist Device (LVAD) in patients with advanced heart failure refractory to optimal medical management has progressed steadily over the past two decades. Data have demonstrated reduced LVAD efficacy, worse clinical outcome, and higher mortality for patients who experience significant ventricular tachyarrhythmia (VTA). We hypothesize that a novel prophylactic intra-operative VTA ablation protocol at the time of LVAD implantation may reduce the recurrent VTA and adverse events postimplant. METHODS: We designed a prospective, multicenter, open-label, randomized-controlled clinical trial enrolling 100 patients who are LVAD candidates with a history of VTA in the previous 5 years. Enrolled patients will be randomized in a 1:1 fashion to intra-operative VTA ablation (n = 50) versus conventional medical management (n = 50) with LVAD implant. Arrhythmia outcomes data will be captured by an implantable cardioverter defibrillator (ICD) to monitor VTA events, with a uniform ICD programming protocol. Patients will be followed prospectively over a mean of 18 months (with a minimum of 9 months) after LVAD implantation to evaluate recurrent VTA, adverse events, and procedural outcomes. Secondary endpoints include right heart function/hemodynamics, healthcare utilization, and quality of life. CONCLUSION: The primary aim of this first-ever randomized trial is to assess the efficacy of intra-operative ablation during LVAD surgery in reducing VTA recurrence and improving clinical outcomes for patients with a history of VTA.
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- 2023
6. Ischemia-Induced Ventricular Proarrhythmia and Cardiovascular Autonomic Dysreflexia After Cardioneuroablation
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Chung, Wei-Hsin, Masuyama, Kiyoshi, Challita, Ronald, Hayase, Justin, Mori, Shumpei, Cha, Steven, Bradfield, Jason S, Ardell, Jeffery L, Shivkumar, Kalyanam, and Ajijola, Olujimi
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Cardiovascular ,Heart Disease ,Neurosciences ,cardioneuroablation ,dysautonomia ,ganglionated plexi ablation ,intrinsic cardiac network ,neuromodulation ,ventricular arrhythmias ,Biomedical Engineering ,Cardiorespiratory Medicine and Haematology ,Cardiovascular System & Hematology - Abstract
BackgroundCardioneuroablation (CNA) is an attractive treatment for vasovagal syncope. Its long-term efficacy and safety remain unknown. ObjectiveTo develop a chronic porcine model of CNA to examine ventricular tachyarrhythmia (VT/VF) susceptibility and cardiac autonomic function after CNA.MethodsA percutaneous CNA model was developed by ablation of left- and right-sided ganglionated plexi (GP)(n=5), confirmed by histology. Reproducible bilateral vagal denervation was confirmed following CNA by extracardiac vagal nerve stimulation (ECVNS) and histology. Chronic studies included 16 pigs randomized to CNA (n=8) and sham ablation (n=8). After 6 weeks, animals underwent hemodynamic studies, assessment of cardiac sympathetic and parasympathetic function using sympathetic chain stimulation (SCS) and direct VNS respectively, and proarrhythmic potential following left anterior descending coronary artery (LAD) ligation.ResultsAfter CNA, ECVNS responses remained abolished for 6 weeks despite ganglia remaining in ablated GPs. In the CNA group, direct VNS resulted in paradoxical increases in blood pressure, but not in sham animals (CNA group vs. sham: 8.36±7.0% vs. -4.83±8.7%, respectively, p=0.009). Left SCS (8Hz) induced significant QTc prolongation in the CNA group vs. sham (11.23±4.0% vs. 1.49±4.0%, respectively, p
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- 2023
7. Osteopontin stabilization and collagen containment slows amorphous calcium phosphate transformation during human aortic valve leaflet calcification
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Sivaguru, Mayandi, Mori, Shumpei, Fouke, Kyle W., Ajijola, Olujimi A., Shivkumar, Kalyanam, Samuel, Ashok Z., Bhargava, Rohit, and Fouke, Bruce W.
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- 2024
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8. Cardioneuroablation for the management of patients with recurrent vasovagal syncope and symptomatic bradyarrhythmias: the CNA-FWRD Registry
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Aksu, Tolga, Tung, Roderick, De Potter, Tom, Markman, Timothy M., Santangeli, Pasquale, du Fay de Lavallaz, Jeanne, Winterfield, Jeffrey R., Baykaner, Tina, Alyesh, Daniel, Joza, Jacqueline E., Gopinathannair, Rakesh, Badertscher, Patrick, Do, Duc H., Hussein, Ayman, Osorio, Jose, Dewland, Thomas, Perino, Alexander, Rodgers, Albert J., DeSimone, Christopher, Alfie, Alberto, Atwater, Brett D., Singh, David, Kumar, Kapil, Salcedo, Jonathan, Bradfield, Jason S., Upadhyay, Gaurav, Sood, Nitesh, Sharma, Parikshit S., Gautam, Sandeep, Kumar, Vineet, Forno, Alexander Romeno Janner Dal, Woods, Christopher E., Rav-Acha, Moshe, Valeriano, Chiara, Kapur, Sunil, Enriquez, Andres, Sundaram, Sri, Glikson, Michael, Gerstenfeld, Edward, Piccini, Jonathan, Tzou, Wendy S., Sauer, William, d’Avila, Andre, Shivkumar, Kalyanam, and Huang, Henry D.
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- 2024
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9. Transcatheter Aortic Valve Replacement Guided by Preprocedural Simulation of Fluoroscopic Location of the Membranous Septum.
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Mori, Shumpei, Aksoy, Olcay, Do, Duc H, Dave, Ravi H, and Shivkumar, Kalyanam
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atrioventricular conduction axis ,computed tomography ,membranous septum ,transcatheter aortic valve replacement ,virtual basal ring ,Cardiovascular ,Heart Disease ,Good Health and Well Being - Abstract
We show the virtual simulation of the fluoroscopic location of the membranous septum using preprocedural cardiac computed tomographic data sets. Recognizing the risk distance before the procedure can help individualize implantation strategy to reduce the risk of atrioventricular conduction axis damage during transcatheter aortic valve replacement. (Level of Difficulty: Advanced.).
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- 2023
10. Catecholaminergic axon innervation and morphology in flat-mounts of atria and ventricles of mice.
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Bizanti, Ariege, Zhang, Yuanyuan, Harden, Scott, Chen, Jin, Hoover, Donald, Gozal, David, Cheng, Zixi, and Shivkumar, Kalyanam
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atria ,cardiac ganglia ,heart ,intrinsic cardiac nervous system ,sympathetic efferent ,tyrosine hydroxylase ,ventricles ,Mice ,Animals ,Heart Ventricles ,Immunohistochemistry ,Heart ,Axons ,Myocardium ,Tyrosine 3-Monooxygenase - Abstract
Sympathetic efferent axons regulate cardiac functions. However, the topographical distribution and morphology of cardiac sympathetic efferent axons remain insufficiently characterized due to the technical challenges involved in immunohistochemical labeling of the thick walls of the whole heart. In this study, flat-mounts of the left and right atria and ventricles of FVB mice were immunolabeled for tyrosine hydroxylase (TH), a marker of sympathetic nerves. Atrial and ventricular flat-mounts were scanned using a confocal microscope to construct montages. We found (1) In the atria: A few large TH-immunoreactive (IR) axon bundles entered both atria, branched into small bundles and then single axons that eventually formed very dense terminal networks in the epicardium, myocardium and inlet regions of great vessels to the atria. Varicose TH-IR axons formed close contact with cardiomyocytes, vessels, and adipocytes. Multiple intrinsic cardiac ganglia (ICG) were identified in the epicardium of both atria, and a subpopulation of the neurons in the ICG were TH-IR. Most TH-IR axons in bundles traveled through ICG before forming dense varicose terminal networks in cardiomyocytes. We did not observe varicose TH-IR terminals encircling ICG neurons. (2) In the left and right ventricles and interventricular septum: TH-IR axons formed dense terminal networks in the epicardium, myocardium, and vasculature. Collectively, TH labeling is achievable in flat-mounts of thick cardiac walls, enabling detailed mapping of catecholaminergic axons and terminal structures in the whole heart at single-cell/axon/varicosity scale. This approach provides a foundation for future quantification of the topographical organization of the cardiac sympathetic innervation in different pathological conditions.
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- 2023
11. Topographical mapping of catecholaminergic axon innervation in the flat-mounts of the mouse atria: a quantitative analysis.
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Zhang, Yuanyuan, Bizanti, Ariege, Harden, Scott W, Chen, Jin, Bendowski, Kohlton, Hoover, Donald B, Gozal, David, Shivkumar, Kalyanam, Heal, Maci, Tappan, Susan, and Cheng, Zixi Jack
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Vena Cava ,Superior ,Heart Atria ,Neurons ,Axons ,Animals ,Mice ,Tyrosine 3-Monooxygenase ,Immunohistochemistry ,Heart Disease ,Cardiovascular ,Neurosciences ,Aetiology ,1.1 Normal biological development and functioning ,2.1 Biological and endogenous factors ,Underpinning research - Abstract
The sympathetic nervous system is crucial for controlling multiple cardiac functions. However, a comprehensive, detailed neuroanatomical map of the sympathetic innervation of the heart is unavailable. Here, we used a combination of state-of-the-art techniques, including flat-mount tissue processing, immunohistochemistry for tyrosine hydroxylase (TH, a sympathetic marker), confocal microscopy and Neurolucida 360 software to trace, digitize, and quantitatively map the topographical distribution of the sympathetic postganglionic innervation in whole atria of C57Bl/6 J mice. We found that (1) 4-5 major extrinsic TH-IR nerve bundles entered the atria at the superior vena cava, right atrium (RA), left precaval vein and the root of the pulmonary veins (PVs) in the left atrium (LA). Although these bundles projected to different areas of the atria, their projection fields partially overlapped. (2) TH-IR axon and terminal density varied considerably between different sites of the atria with the greatest density of innervation near the sinoatrial node region (P
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- 2023
12. Sympathetic innervation of the supraclavicular brown adipose tissue: A detailed anatomical study.
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Beyer, Ryan, Bernardes de Souza, Breno, Sorg, Julie, Hoover, Donald, Sacks, Harold, Fishbein, Michael, Chang, Grace, Peacock, Warwick, St John, Maie, Law, James, Symonds, Micheal, Ajijola, Olujimi, Shivkumar, Kalyanam, Srikanthan, Preethi, and Mori, Shumpei
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Humans ,Adipose Tissue ,Brown ,Obesity ,Adiposity ,Thermogenesis ,Cadaver ,Glucose - Abstract
BACKGROUND: The supraclavicular fossa is the dominant location for human brown adipose tissue (BAT). Activation of BAT promotes non-shivering thermogenesis by utilization of glucose and free fatty acids and has been the focus of pharmacological and non-pharmacological approaches for modulation in order to improve body weight and glucose homeostasis. Sympathetic neural control of supraclavicular BAT has received much attention, but its innervation has not been extensively investigated in humans. METHODS: Dissection of the cervical region in human cadavers was performed to find the distribution of sympathetic nerve branches to supraclavicular fat pad. Furthermore, proximal segments of the 4th cervical nerve were evaluated histologically to assess its sympathetic components. RESULTS: Nerve branches terminating in supraclavicular fat pad were identified in all dissections, including those from the 3rd and 4th cervical nerves and from the cervical sympathetic plexus. Histology of the proximal segments of the 4th cervical nerves confirmed tyrosine hydroxylase positive thin nerve fibers in all fascicles with either a scattered or clustered distribution pattern. The scattered pattern was more predominant than the clustered pattern (80% vs. 20%) across cadavers. These sympathetic nerve fibers occupied only 2.48% of the nerve cross sectional area on average. CONCLUSIONS: Human sympathetic nerves use multiple pathways to innervate the supraclavicular fat pad. The present finding serves as a framework for future clinical approaches to activate human BAT in the supraclavicular region.
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- 2023
13. CLSTN3β enforces adipocyte multilocularity to facilitate lipid utilization.
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Qian, Kevin, Tol, Marcus J, Wu, Jin, Uchiyama, Lauren F, Xiao, Xu, Cui, Liujuan, Bedard, Alexander H, Weston, Thomas A, Rajendran, Pradeep S, Vergnes, Laurent, Shimanaka, Yuta, Yin, Yesheng, Jami-Alahmadi, Yasaman, Cohn, Whitaker, Bajar, Bryce T, Lin, Chia-Ho, Jin, Benita, DeNardo, Laura A, Black, Douglas L, Whitelegge, Julian P, Wohlschlegel, James A, Reue, Karen, Shivkumar, Kalyanam, Chen, Feng-Jung, Young, Stephen G, Li, Peng, and Tontonoz, Peter
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Endoplasmic Reticulum ,Adipocytes ,Placenta ,Animals ,Humans ,Mice ,Hypothermia ,Fatty Acids ,Triglycerides ,Calcium-Binding Proteins ,Membrane Proteins ,Thermogenesis ,Female ,Lipid Metabolism ,Adipose Tissue ,Brown ,Lipid Droplets ,Diabetes ,2.1 Biological and endogenous factors ,Aetiology ,1.1 Normal biological development and functioning ,Underpinning research ,General Science & Technology - Abstract
Multilocular adipocytes are a hallmark of thermogenic adipose tissue1,2, but the factors that enforce this cellular phenotype are largely unknown. Here, we show that an adipocyte-selective product of the Clstn3 locus (CLSTN3β) present in only placental mammals facilitates the efficient use of stored triglyceride by limiting lipid droplet (LD) expansion. CLSTN3β is an integral endoplasmic reticulum (ER) membrane protein that localizes to ER-LD contact sites through a conserved hairpin-like domain. Mice lacking CLSTN3β have abnormal LD morphology and altered substrate use in brown adipose tissue, and are more susceptible to cold-induced hypothermia despite having no defect in adrenergic signalling. Conversely, forced expression of CLSTN3β is sufficient to enforce a multilocular LD phenotype in cultured cells and adipose tissue. CLSTN3β associates with cell death-inducing DFFA-like effector proteins and impairs their ability to transfer lipid between LDs, thereby restricting LD fusion and expansion. Functionally, increased LD surface area in CLSTN3β-expressing adipocytes promotes engagement of the lipolytic machinery and facilitates fatty acid oxidation. In human fat, CLSTN3B is a selective marker of multilocular adipocytes. These findings define a molecular mechanism that regulates LD form and function to facilitate lipid utilization in thermogenic adipocytes.
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- 2023
14. Cardiac Resynchronization Therapy for Adult Patients With a Failing Systemic Right Ventricle: A Multicenter Study.
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Kharbanda, Rohit K, Moore, Jeremy P, Lloyd, Michael S, Galotti, Robert, Bogers, Ad JJC, Taverne, Yannick JHJ, Madhavan, Malini, McLeod, Christopher J, Dubin, Anne M, Mah, Douglas Y, Chang, Philip M, Kamp, Anna N, Nielsen, Jens C, Aydin, Alper, Tanel, Ronn E, Shah, Maully J, Pilcher, Thomas, Evertz, Reinder, Khairy, Paul, Tan, Reina B, Czosek, Richard J, Shivkumar, Kalyanam, and de Groot, Natasja MS
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Heart Ventricles ,Humans ,Transposition of Great Vessels ,Treatment Outcome ,Retrospective Studies ,Adult ,Middle Aged ,Female ,Male ,Heart Failure ,Cardiac Resynchronization Therapy ,cardiac resynchronization therapy ,congenital heart disease ,heart failure ,pacing ,systemic right ventricle ,Cardiovascular ,Heart Disease ,Cardiorespiratory Medicine and Haematology - Abstract
Background The objective of this international multicenter study was to investigate both early and late outcomes of cardiac resynchronization therapy (CRT) in patients with a systemic right ventricle (SRV) and to identify predictors for congestive heart failure readmissions and mortality. Methods and Results This retrospective international multicenter study included 13 centers. The study population comprised 80 adult patients with SRV (48.9% women) with a mean age of 45±14 (range, 18-77) years at initiation of CRT. Median follow-up time was 4.1 (25th-75th percentile, 1.3-8.3) years. Underlying congenital heart disease consisted of congenitally corrected transposition of the great arteries and dextro-transposition of the great arteries in 63 (78.8%) and 17 (21.3%) patients, respectively. CRT resulted in significant improvement in functional class (before CRT: III, 25th-75th percentile, II-III; after CRT: II, 25th-75th percentile, II-III; P=0.005) and QRS duration (before CRT: 176±27; after CRT: 150±24 milliseconds; P=0.003) in patients with pre-CRT ventricular pacing who underwent an upgrade to a CRT device (n=49). These improvements persisted during long-term follow-up with a marginal but significant increase in SRV function (before CRT; 30%, 25th-75th percentile, 25-35; after CRT: 31%, 25th-75th percentile, 21-38; P=0.049). In contrast, no beneficial change in the above-mentioned variables was observed in patients who underwent de novo CRT (n=31). A quarter of all patients were readmitted for heart failure during follow-up, and mortality at latest follow-up was 21.3%. Conclusions This international experience with CRT in patients with an SRV demonstrated that CRT in selected patients with SRV dysfunction and pacing-induced dyssynchrony yielded consistent improvement in QRS duration and New York Heart Association functional status, with a marginal increase in SRV function.
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- 2022
15. Single-Cell RNA-Seq Identifies Dynamic Cardiac Transition Program from ADCs Induced by Leukemia Inhibitory Factor.
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Yao, Jiayi, Ma, Feiyang, Zhang, Li, Zhu, Ching, Jumabay, Medet, Yao, Zehao, Wang, Lumin, Zhang, Daoqin, Qiao, Xiaojing, Pellegrini, Matteo, Yao, Yucheng, Wu, Xiuju, Boström, Kristina, Shivkumar, Kalyanam, and Cai, Xinjiang
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ADC ,adipose ,cardiac transition ,cell sequencing ,derived cells ,leukemia inhibitory factor (LIF) ,single ,Leukemia Inhibitory Factor ,NF-E2-Related Factor 2 ,RNA-Seq ,Myocytes ,Cardiac ,Cell Differentiation - Abstract
Adipose-derived cells (ADCs) from white adipose tissue are promising stem cell candidates because of their large regenerative reserves and the potential for cardiac regeneration. However, given the heterogeneity of ADC and its unsolved mechanisms of cardiac acquisition, ADC-cardiac transition efficiency remains low. In this study, we explored the heterogeneity of ADCs and the cellular kinetics of 39,432 single-cell transcriptomes along the leukemia inhibitory factor (LIF)-induced ADC-cardiac transition. We identified distinct ADC subpopulations that reacted differentially to LIF when entering the cardiomyogenic program, further demonstrating that ADC-myogenesis is time-dependent and initiates from transient changes in nuclear factor erythroid 2-related factor 2 (Nrf2) signaling. At later stages, pseudotime analysis of ADCs navigated a trajectory with 2 branches corresponding to activated myofibroblast or cardiomyocyte-like cells. Our findings offer a high-resolution dissection of ADC heterogeneity and cell fate during ADC-cardiac transition, thus providing new insights into potential cardiac stem cells.
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- 2022
16. Sinus Tachycardia: a Multidisciplinary Expert Focused Review.
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Mayuga, Kenneth, Fedorowski, Artur, Ricci, Fabrizio, Gopinathannair, Rakesh, Dukes, Jonathan, Gibbons, Christopher, Hanna, Peter, Sorajja, Dan, Chung, Mina, Benditt, David, Sheldon, Robert, Ayache, Mirna, AbouAssi, Hiba, Grubb, Blair, Hamdan, Mohamed, Stavrakis, Stavros, Singh, Tamanna, Goldberger, Jeffrey, Muldowney, James, Belham, Mark, Kem, David, Akin, Cem, Bruce, Barbara, Zahka, Nicole, Fu, Qi, Van Iterson, Erik, Raj, Satish, Fouad-Tarazi, Fetnat, Goldstein, David, Stewart, Julian, Olshansky, Brian, and Shivkumar, Kalyanam
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autonomic dysfunction ,hyperthyroidism ,inappropriate sinus tachycardia ,post-COVID syndrome ,postural orthostatic tachycardia syndrome ,sinus tachycardia ,COVID-19 ,Humans ,Postural Orthostatic Tachycardia Syndrome ,Tachycardia ,Sinus - Abstract
Sinus tachycardia (ST) is ubiquitous, but its presence outside of normal physiological triggers in otherwise healthy individuals remains a commonly encountered phenomenon in medical practice. In many cases, ST can be readily explained by a current medical condition that precipitates an increase in the sinus rate, but ST at rest without physiological triggers may also represent a spectrum of normal. In other cases, ST may not have an easily explainable cause but may represent serious underlying pathology and can be associated with intolerable symptoms. The classification of ST, consideration of possible etiologies, as well as the decisions of when and how to intervene can be difficult. ST can be classified as secondary to a specific, usually treatable, medical condition (eg, pulmonary embolism, anemia, infection, or hyperthyroidism) or be related to several incompletely defined conditions (eg, inappropriate ST, postural tachycardia syndrome, mast cell disorder, or post-COVID syndrome). While cardiologists and cardiac electrophysiologists often evaluate patients with symptoms associated with persistent or paroxysmal ST, an optimal approach remains uncertain. Due to the many possible conditions associated with ST, and an overlap in medical specialists who see these patients, the inclusion of experts in different fields is essential for a more comprehensive understanding. This article is unique in that it was composed by international experts in Neurology, Psychology, Autonomic Medicine, Allergy and Immunology, Exercise Physiology, Pulmonology and Critical Care Medicine, Endocrinology, Cardiology, and Cardiac Electrophysiology in the hope that it will facilitate a more complete understanding and thereby result in the better care of patients with ST.
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- 2022
17. Sympathetic nervous system hyperactivity results in potent cerebral hypoperfusion in swine.
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Kim, Wi Jin, Dacey, Michael, Samarage, Hashitha Milan, Zarrin, David, Goel, Keshav, Chan, Christopher, Qi, Xin, Wang, Anthony C, Shivkumar, Kalyanam, Ardell, Jeffrey, and Colby, Geoffrey P
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Superior Cervical Ganglion ,Sympathetic Nervous System ,Animals ,Swine ,Vasospasm ,Intracranial ,Cerebrovascular Circulation ,Cerebral hypoperfusion ,Cerebral vasospasm ,SCG ,Superior cervical ganglia ,Sympathetic cerebral vasoconstriction ,Vasospasm ,Neurosciences ,Clinical Sciences ,Pharmacology and Pharmaceutical Sciences ,Neurology & Neurosurgery - Abstract
IntroductionCerebral vasospasm is a complex disease resulting in reversible narrowing of blood vessels, stroke, and poor patient outcomes. Sympathetic perivascular nerve fibers originate from the superior cervical ganglion (SCG) to innervate the cerebral vasculature, with activation resulting in vasoconstriction. Sympathetic pathways are thought to be a significant contributor to cerebral vasospasm.ObjectiveWe sought to demonstrate that stimulation of SCG in swine can cause ipsilateral cerebral perfusion deficit similar to that of significant human cerebral vasospasm. Furthermore, we aimed to show that inhibition of SCG can block the effects of sympathetic-mediated cerebral hypoperfusion.MethodsSCG were surgically identified in 15 swine and were electrically stimulated to achieve sympathetic activation. CT perfusion scans were performed to assess for changes in cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT) and time-to-maximum (TMax). Syngo.via software was used to determine regions of interest and quantify perfusion measures.ResultsSCG stimulation resulted in 20-30% reduction in mean ipsilateral CBF compared to its contralateral unaffected side (p 0.05).ConclusionIn swine, SCG stimulation resulted in significant cerebral perfusion deficit, and this was inhibited by prior local anesthetic injection into the SCG. Inhibiting sympathetic activation by targeting the SCG may be an effective treatment for sympathetic mediated cerebral hypoperfusion.
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- 2022
18. Clinical predictors and implications of cardiac inflammation detected on positron emission tomography (PET) in patients referred for premature ventricular complex (PVC) ablation
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Chung, Wei-Hsin, Hayase, Justin, Do, Duc H., Dixit, Neal, Ajijola, Olujimi, Buch, Eric, Boyle, Noel, Shivkumar, Kalyanam, and Bradfield, Jason S.
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- 2023
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19. Superior cervical ganglion stimulation results in potent cerebral vasoconstriction in swine.
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Kim, Wi Jin, Samarage, Hasitha Milan, Zarrin, David, Goel, Keshav, Chan, Christopher, Qi, Xin, Wang, Anthony, Shivkumar, Kalyanam, Ardell, Jeffrey, and Colby, Geoffrey P
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Brain Disorders ,Neurosciences - Abstract
IntroductionSympathetic activity from the superior cervical ganglion (SCG) has been shown to cause cerebral hypoperfusion in swine, similar to that seen with clinical cerebral vasospasm. Although the mechanism of such perfusion deficit has been speculated to be from pathologic cerebral vasoconstriction, the extent of sympathetic contribution to vasoconstriction has not been wellestablished.ObjectiveWe aimed to demonstrate that SCG stimulation in swine leads to significant cerebral vasoconstriction on digital subtraction angiography (DSA). Additionally, we aimed to show that inhibition of SCG can mitigate the effects of sympathetic-mediated cerebral vasoconstriction.MethodsFive SCGs were surgically identified in Yorkshire swine and were electrically stimulated to achieve sympathetic activation. DSA was performed to measure and compare changes in cerebral vessel diameter. Syngo iFlow was also used to quantify changes in contrast flow through the cerebral and neck vessels.ResultsSCG stimulation resulted in 35-45% narrowing of the ipsilateral ascending pharyngeal, anterior middle cerebral and anterior cerebral arteries. SCG stimulation also decreased contrast flow through ipsilateral ascending pharyngeal, internal carotid and anterior cerebral arteries as seen on iFLow. These effects were prevented with prior SCG blockade. Minimal vessel caliber changes were seen in the posterior cerebral, posterior middle cerebral and internal carotid arteries with SCG stimulation.ConclusionSCG stimulation results in significant luminal narrowing and reduction in flow through various intracranial arteries in swine. The results of sympathetic hyperactivity from the SCG closely models cerebral vasoconstriction seen in human cerebral vasospasm. SCG inhibition is a potential promising therapeutic approach to treating cerebral vasospasm.
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- 2022
20. Rate of Change of Initial Intrinsicoid Deflection Predicts Endocardial Versus Epicardial Ventricular Tachycardia
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Prisco, Anthony R., Hayase, Justin, Olson, Matthew, Brigham, Renee C., Ramirez, David A., Iaizzo, Paul A., Shivkumar, Kalyanam, Bradfield, Jason, and Tholakanahalli, Venkat N.
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- 2024
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21. Multidetector Computed Tomography Assessment of Anatomical Ventricular Tachycardia Isthmuses in Repaired Tetralogy of Fallot
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Moore, Jeremy P., Su, Jonathan, Shannon, Kevin M., Perens, Gregory S., Newlon, Claire, Bradfield, Jason S., and Shivkumar, Kalyanam
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- 2024
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22. Electrophysiology and Arrhythmogenesis in the Human Right Ventricular Outflow Tract
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Aras, Kedar, Gams, Anna, Faye, Ndeye Rokhaya, Brennan, Jaclyn, Goldrick, Katherine, Li, Jinghua, Zhong, Yishan, Chiang, Chia-Han, Smith, Elizabeth H, Poston, Megan D, Chivers, Jacqueline, Hanna, Peter, Mori, Shumpei, Ajijola, Olujimi A, Shivkumar, Kalyanam, Hoover, Donald B, Viventi, Jonathan, Rogers, John A, Bernus, Olivier, and Efimov, Igor R
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Medical Physiology ,Biomedical and Clinical Sciences ,Cardiovascular ,Heart Disease ,Neurosciences ,Acetylcholine ,Adrenergic Agents ,Cardiac Electrophysiology ,Cholinergic Agents ,Electrocardiography ,Female ,Heart Ventricles ,Human Rights ,Humans ,Isoproterenol ,Male ,Pericardium ,Tachycardia ,Ventricular ,Ventricular Premature Complexes ,acetylcholine ,arrhythmias ,cardiac ,heart ventricles ,isoproterenol ,ventricular premature complexes ,arrhythmias ,cardiac ,Cardiorespiratory Medicine and Haematology ,Clinical Sciences ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology ,Clinical sciences ,Medical physiology - Abstract
BackgroundRight ventricular outflow tract (RVOT) is a common source of ventricular tachycardia, which often requires ablation. However, the mechanisms underlying the RVOT's unique arrhythmia susceptibility remain poorly understood due to lack of detailed electrophysiological and molecular studies of the human RVOT.MethodsWe conducted optical mapping studies in 16 nondiseased donor human RVOT preparations subjected to pharmacologically induced adrenergic and cholinergic stimulation to evaluate susceptibility to arrhythmias and characterize arrhythmia dynamics.ResultsWe found that under control conditions, RVOT has shorter action potential duration at 80% repolarization relative to the right ventricular apical region. Treatment with isoproterenol (100 nM) shortened action potential duration at 80% repolarization and increased incidence of premature ventricular contractions (P=0.003), whereas acetylcholine (100 μM) stimulation alone had no effect on action potential duration at 80% repolarization or premature ventricular contractions. However, acetylcholine treatment after isoproterenol stimulation reduced the incidence of premature ventricular contractions (P=0.034) and partially reversed action potential duration at 80% repolarization shortening (P=0.029). Immunolabeling of RVOT (n=4) confirmed the presence of cholinergic marker VAChT (vesicular acetylcholine transporter) in the region. Rapid pacing revealed RVOT susceptibility to both concordant and discordant alternans. Investigation into transmural arrhythmia dynamics showed that arrhythmia wave fronts and phase singularities (rotors) were relatively more organized in the endocardium than in the epicardium (P=0.006). Moreover, there was a weak but positive spatiotemporal autocorrelation between epicardial and endocardial arrhythmic wave fronts and rotors. Transcriptome analysis (n=10 hearts) suggests a trend that MAPK (mitogen-activated protein kinase) signaling, calcium signaling, and cGMP-PKG (protein kinase G) signaling are among the pathways that may be enriched in the male RVOT, whereas pathways of neurodegeneration may be enriched in the female RVOT.ConclusionsHuman RVOT electrophysiology is characterized by shorter action potential duration relative to the right ventricular apical region. Cholinergic right ventricular stimulation attenuates the arrhythmogenic effects of adrenergic stimulation, including increase in frequency of premature ventricular contractions and shortening of wavelength. Right ventricular arrhythmia is characterized by positive spatial-temporal autocorrelation between epicardial-endocardial arrhythmic wave fronts and rotors that are relatively more organized in the endocardium.
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- 2022
23. Research Opportunities in Autonomic Neural Mechanisms of Cardiopulmonary Regulation A Report From the National Heart, Lung, and Blood Institute and the National Institutes of Health Office of the Director Workshop
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Mehra, Reena, Tjurmina, Olga A, Ajijola, Olujimi A, Arora, Rishi, Bolser, Donald C, Chapleau, Mark W, Chen, Peng-Sheng, Clancy, Colleen E, Delisle, Brian P, Gold, Michael R, Goldberger, Jeffrey J, Goldstein, David S, Habecker, Beth A, Handoko, M Louis, Harvey, Robert, Hummel, James P, Hund, Thomas, Meyer, Christian, Redline, Susan, Ripplinger, Crystal M, Simon, Marc A, Somers, Virend K, Stavrakis, Stavros, Taylor-Clark, Thomas, Undem, Bradley Joel, Verrier, Richard L, Zucker, Irving H, Sopko, George, and Shivkumar, Kalyanam
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Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Neurosciences ,Sleep Research ,Heart Disease ,Cardiovascular ,Lung ,  ,asthma ,atrial fibrillation ,autonomic nervous system ,cardiopulmonary ,chronic obstructive pulmonary disease ,circadian ,heart failure ,pulmonary arterial hypertension ,sleep apnea ,ventricular arrhythmia ,ACE ,angiotensin-converting enzyme ,AD ,autonomic dysregulation ,AF ,atrial fibrillation ,ANS ,autonomic nervous system ,Ach ,acetylcholine ,CNS ,central nervous system ,COPD ,chronic obstructive pulmonary disease ,CSA ,central sleep apnea ,CVD ,cardiovascular disease ,ECG ,electrocardiogram ,EV ,extracellular vesicle ,GP ,ganglionated plexi ,HF ,heart failure ,HFpEF ,heart failure with preserved ejection fraction ,HFrEF ,heart failure with reduced ejection fraction ,HRV ,heart rate variability ,LQT ,long QT ,MI ,myocardial infarction ,NE ,norepinephrine ,NHLBI ,National Heart ,Lung ,and Blood Institute ,NPY ,neuropeptide Y ,NREM ,non-rapid eye movement ,OSA ,obstructive sleep apnea ,PAH ,pulmonary arterial hypertension ,PV ,pulmonary vein ,REM ,rapid eye movement ,RV ,right ventricular ,SCD ,sudden cardiac death ,SDB ,sleep disordered breathing ,SNA ,sympathetic nerve activity ,SNSA ,sympathetic nervous system activity ,TLD ,targeted lung denervation ,Cardiorespiratory Medicine and Haematology ,Clinical Sciences ,Cardiovascular medicine and haematology - Abstract
This virtual workshop was convened by the National Heart, Lung, and Blood Institute, in partnership with the Office of Strategic Coordination of the Office of the National Institutes of Health Director, and held September 2 to 3, 2020. The intent was to assemble a multidisciplinary group of experts in basic, translational, and clinical research in neuroscience and cardiopulmonary disorders to identify knowledge gaps, guide future research efforts, and foster multidisciplinary collaborations pertaining to autonomic neural mechanisms of cardiopulmonary regulation. The group critically evaluated the current state of knowledge of the roles that the autonomic nervous system plays in regulation of cardiopulmonary function in health and in pathophysiology of arrhythmias, heart failure, sleep and circadian dysfunction, and breathing disorders. Opportunities to leverage the Common Fund's SPARC (Stimulating Peripheral Activity to Relieve Conditions) program were characterized as related to nonpharmacologic neuromodulation and device-based therapies. Common themes discussed include knowledge gaps, research priorities, and approaches to develop novel predictive markers of autonomic dysfunction. Approaches to precisely target neural pathophysiological mechanisms to herald new therapies for arrhythmias, heart failure, sleep and circadian rhythm physiology, and breathing disorders were also detailed.
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- 2022
24. High-resolution structure-function mapping of intact hearts reveals altered sympathetic control of infarct border zones
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Zhu, Ching, Rajendran, Pradeep S, Hanna, Peter, Efimov, Igor R, Salama, Guy, Fowlkes, Charless C, and Shivkumar, Kalyanam
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Medical Physiology ,Biomedical and Clinical Sciences ,Heart Disease ,Neurosciences ,Cardiovascular ,Heart Disease - Coronary Heart Disease ,2.1 Biological and endogenous factors ,Aetiology ,Action Potentials ,Animals ,Body Surface Potential Mapping ,Disease Models ,Animal ,Male ,Mice ,Mice ,Inbred C57BL ,Myocardial Infarction ,Myocardium ,Sympathetic Nervous System ,Arrhythmias ,Cardiology ,Innervation ,Mouse models ,Biomedical and clinical sciences ,Health sciences - Abstract
Remodeling of injured sympathetic nerves on the heart after myocardial infarction (MI) contributes to adverse outcomes such as sudden arrhythmic death, yet the underlying structural mechanisms are poorly understood. We sought to examine microstructural changes on the heart after MI and to directly link these changes with electrical dysfunction. We developed a high-resolution pipeline for anatomically precise alignment of electrical maps with structural myofiber and nerve-fiber maps created by customized computer vision algorithms. Using this integrative approach in a mouse model, we identified distinct structure-function correlates to objectively delineate the infarct border zone, a known source of arrhythmias after MI. During tyramine-induced sympathetic nerve activation, we demonstrated regional patterns of altered electrical conduction aligned directly with altered neuroeffector junction distribution, pointing to potential neural substrates for cardiac arrhythmia. This study establishes a synergistic framework for examining structure-function relationships after MI with microscopic precision that has potential to advance understanding of arrhythmogenic mechanisms.
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- 2022
25. The vagus nerve in cardiovascular physiology and pathophysiology: From evolutionary insights to clinical medicine
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Rajendran, Pradeep S., Hadaya, Joseph, Khalsa, Sahib S., Yu, Chuyue, Chang, Rui, and Shivkumar, Kalyanam
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- 2024
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26. Distribution and morphology of calcitonin gene-related peptide (CGRP) innervation in flat mounts of whole rat atria and ventricles
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Chen, Jin, Bendowski, Kohlton T., Bizanti, Ariege, Zhang, Yuanyuan, Ma, Jichao, Hoover, Donald B., Gozal, David, Shivkumar, Kalyanam, and Cheng, Zixi Jack
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- 2024
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27. Vagally-mediated heart block after myocardial infarction associated with plasticity of epicardial neurons controlling the atrioventricular node
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Tompkins, John D, Buckley, Una, Salavatian, Siamak, Shivkumar, Kalyanam, and Ardell, Jeffrey L
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Biomedical and Clinical Sciences ,Neurosciences ,Clinical Sciences ,Heart Disease - Coronary Heart Disease ,Heart Disease ,Cardiovascular ,Neurological ,intrinsic cardiac neurons ,vagus nerve ,electrophysiology ,atrioventricular block ,autonomic ganglion ,Yorkshire pig ,Biochemistry and Cell Biology - Abstract
Imbalances in the opposing actions of sympathetic and parasympathetic nerves controlling the heart enhance risk for arrhythmia and sudden cardiac death after myocardial infarction (MI). Plasticity in peripheral neuron function may underlie the observed changes in cardiomotor nerve activity. We studied vagal control of the heart in pigs after chronic infarction of the left ventricle. Stimulation of the cervical vagus nerve produced greater bradycardic responses 8-weeks after MI. Recordings of epicardial electrocardiograms demonstrate increased severity and duration of atrioventricular (AV) block in MI-pigs during 20 Hz vagal stimulation. Intracellular voltage recordings from isolated neurons of the inferior vena cava-inferior left atrium (IVC-ILA) ganglionated plexus, a cluster of epicardial neurons receiving innervation from the vagus known to regulate the AV node, were used to assess plasticity of membrane and synaptic physiology of intrinsic cardiac neurons (ICNs) after MI. Changes to both passive and active membrane properties were observed, including more negative resting membrane potentials and greater input resistances in MI-pig ICNs, concomitant with a depression of neuronal excitability. Immunoreactivity to pituitary adenylate cyclase-activating polypeptide (PACAP), a cardiotropic peptide known to modulate cardiac neuron excitability, was localized to perineuronal varicosities surrounding pig IVC-ILA neurons. Exogenous application of PACAP increased excitability of control but not MI-ICNs. Stimulation (20 Hz) of interganglionic nerves in the ex vivo whole-mount preparations elicited slow excitatory postsynaptic potentials (sEPSPs) which persisted in hexamethonium (500 μM), but were blocked by atropine (1 μM), indicating muscarinic receptor-mediated inhibition of M-current. Extracellular application of 1 mM BaCl2 to inhibit M-current increased neuronal excitability. The muscarine-sensitive sEPSPs were observed more frequently and were of larger amplitude in IVC-ILA neurons from MI animals. In conclusion, we suggest the increased probability of muscarinic sEPSPs play a role in the potentiation of the vagus nerve mediated-slowing of AV nodal conduction following chronic MI. We identify both a novel role of a muscarinic sensitive current in the regulation of synaptic strength at ICNs projecting to the AV node, and demonstrate changes to both intrinsic plasticity and synaptic plasticity of IVC-ILA neurons which may contribute to greater risk for heart block and sudden cardiac death after MI.
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- 2022
28. Non-invasive Stereotactic Body Radiation Therapy for Refractory Ventricular Arrhythmias: Venturing into the Unknown
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Hayase, Justin, Chin, Robert, Cao, Minsong, Hu, Peng, Shivkumar, Kalyanam, and Bradfield, Jason S
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Biomedical and Clinical Sciences ,Clinical Sciences ,Cardiovascular ,Clinical Trials and Supportive Activities ,Clinical Research ,Heart Disease ,Catheter ablation ,stereotactic body radiation therapy ,ventricular arrhythmias - Abstract
Stereotactic body radiation therapy (SBRT) is a promising new method for non-invasive management of life-threatening ventricular arrhythmias. Numerous case reports and case series have provided encouraging short-term results suggesting good efficacy and safety, but randomized data and long-term outcomes are not yet available. The primary hypothesis as to the mechanism of action for SBRT relates to the development of cardiac fibrosis in arrhythmogenic myocardial substrate; however, limited animal model data offer conflicting insights into this theory. The use of SBRT for patients with refractory ventricular arrhythmias is rapidly increasing, but ongoing translational science work and randomized clinical trials will be critical to address many outstanding questions regarding this novel therapy.
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- 2022
29. Living Anatomy of the Pericardial Space A Guide for Imaging and Interventions
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Mori, Shumpei, Bradfield, Jason S, Peacock, Warwick J, Anderson, Robert H, and Shivkumar, Kalyanam
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Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Clinical Sciences ,Heart Disease ,Cardiovascular ,Humans ,Pericardium ,Thorax ,computed tomography ,pericardial recess ,pericardial sinus ,pericardial space ,cardiac anatomy ,Cardiorespiratory Medicine and Haematology ,Cardiovascular medicine and haematology ,Clinical sciences - Abstract
The pericardium of the human heart has received increased attention in recent times due to interest in the epicardial approach for cardiac interventions to treat cardiac arrhythmias refractory to conventional endocardial approaches. To support further clinical application of this technique, it is fundamental to appreciate the living anatomy of the pericardial space, as well as its relationships to the surrounding structures. The anatomy of the pericardial space, however, is extremely difficult regions to visualize. This is due to its complex 3-dimensionality, and the "potential" nature of the space, which becomes obvious only when there is collection of pericardial fluid. This potential space, which is bounded by the epicardium and pericardium, can now be visualized by special techniques as we now report, permitting appreciation of its living morphology. Current sources of knowledge are limited to the dissection images, surgical images, and/or illustrations, which are not necessarily precise or sufficient to provide relevant comprehensive anatomical knowledge to those undertaking the epicardial approach. The authors demonstrate, for the first time to their knowledge, the 3-dimensional living anatomy of the pericardial space relative to its surrounding structures. They also provide correlative anatomy of the left sternocostal triangle as a common site for subxiphoid access. The authors anticipate their report serving as a tool for education of imaging and interventional specialists.
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- 2021
30. Understanding Circadian Mechanisms of Sudden Cardiac Death: A Report From the National Heart, Lung, and Blood Institute Workshop, Part 1: Basic and Translational Aspects
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Delisle, Brian P, George, Alfred L, Nerbonne, Jeanne M, Bass, Joseph T, Ripplinger, Crystal M, Jain, Mukesh K, Hermanstyne, Tracey O, Young, Martin E, Kannankeril, Prince J, Duffy, Jeanne F, Goldhaber, Joshua I, Hall, Martica H, Somers, Virend K, Smolensky, Michael H, Garnett, Christine E, Anafi, Ron C, Scheer, Frank AJL, Shivkumar, Kalyanam, Shea, Steven A, and Balijepalli, Ravi C
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Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Sleep Research ,Heart Disease - Coronary Heart Disease ,Heart Disease ,Cardiovascular ,Hematology ,Animals ,Circadian Rhythm ,Death ,Sudden ,Cardiac ,Humans ,National Heart ,Lung ,and Blood Institute (U.S.) ,United States ,cardiovascular disease ,circadian clocks ,circadian rhythm ,National Heart ,Lung ,and Blood Institute ,sudden cardiac death ,National Heart ,Lung ,and Blood Institute ,Cardiorespiratory Medicine and Haematology ,Clinical Sciences ,Medical Physiology ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology ,Clinical sciences ,Medical physiology - Abstract
Sudden cardiac death (SCD), the unexpected death due to acquired or genetic cardiovascular disease, follows distinct 24-hour patterns in occurrence. These 24-hour patterns likely reflect daily changes in arrhythmogenic triggers and the myocardial substrate caused by day/night rhythms in behavior, the environment, and endogenous circadian mechanisms. To better address fundamental questions regarding the circadian mechanisms, the National Heart, Lung, and Blood Institute convened a workshop, Understanding Circadian Mechanisms of Sudden Cardiac Death. We present a 2-part report of findings from this workshop. Part 1 summarizes the workshop and serves to identify research gaps and opportunities in the areas of basic and translational research. Among the gaps was the lack of standardization in animal studies for reporting environmental conditions (eg, timing of experiments relative to the light dark cycle or animal housing temperatures) that can impair rigor and reproducibility. Workshop participants also pointed to uncertainty regarding the importance of maintaining normal circadian rhythmic synchrony and the potential pathological impact of desynchrony on SCD risk. One related question raised was whether circadian mechanisms can be targeted to reduce SCD risk. Finally, the experts underscored the need for studies aimed at determining the physiological importance of circadian clocks in the many different cell types important to normal heart function and SCD. Addressing these gaps could lead to new therapeutic approaches/molecular targets that can mitigate the risk of SCD not only at certain times but over the entire 24-hour period.
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- 2021
31. Understanding Circadian Mechanisms of Sudden Cardiac Death: A Report From the National Heart, Lung, and Blood Institute Workshop, Part 2: Population and Clinical Considerations
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Delisle, Brian P, George, Alfred L, Nerbonne, Jeanne M, Bass, Joseph T, Ripplinger, Crystal M, Jain, Mukesh K, Hermanstyne, Tracey O, Young, Martin E, Kannankeril, Prince J, Duffy, Jeanne F, Goldhaber, Joshua I, Hall, Martica H, Somers, Virend K, Smolensky, Michael H, Garnett, Christine E, Anafi, Ron C, Scheer, Frank AJL, Shivkumar, Kalyanam, Shea, Steven A, and Balijepalli, Ravi C
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Biomedical and Clinical Sciences ,Medical Physiology ,Cardiovascular Medicine and Haematology ,Clinical Sciences ,Sleep Research ,Cardiovascular ,Heart Disease ,Prevention ,Heart Disease - Coronary Heart Disease ,2.1 Biological and endogenous factors ,Aetiology ,Respiratory ,Good Health and Well Being ,Circadian Rhythm ,Death ,Sudden ,Cardiac ,Humans ,National Heart ,Lung ,and Blood Institute (U.S.) ,Population Surveillance ,United States ,cardiovascular diseases ,circadian clock ,circadian rhythm ,genetics ,National Heart ,Lung ,and Blood Institute ,population ,sudden cardiac death ,National Heart ,Lung ,and Blood Institute ,Cardiorespiratory Medicine and Haematology ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology ,Clinical sciences ,Medical physiology - Abstract
Sudden cardiac death (SCD) is the sudden, unexpected death due to abrupt loss of heart function secondary to cardiovascular disease. In certain populations living with cardiovascular disease, SCD follows a distinct 24-hour pattern in occurrence, suggesting day/night rhythms in behavior, the environment, and endogenous circadian rhythms result in daily spans of increased vulnerability. The National Heart, Lung, and Blood Institute convened a workshop, Understanding Circadian Mechanisms of Sudden Cardiac Death to identify fundamental questions regarding the role of the circadian rhythms in SCD. Part 2 summarizes research gaps and opportunities in the areas of population and clinical research identified in the workshop. Established research supports a complex interaction between circadian rhythms and physiological responses that increase the risk for SCD. Moreover, these physiological responses themselves are influenced by several biological variables, including the type of cardiovascular disease, sex, age, and genetics, as well as environmental factors. The emergence of new noninvasive biotechnological tools that continuously measure key cardiovascular variables, as well as the identification of biomarkers to assess circadian rhythms, hold promise for generating large-scale human data sets that will delineate which subsets of individuals are most vulnerable to SCD. Additionally, these data will improve our understanding of how people who suffer from circadian disruptions develop cardiovascular diseases that increase the risk for SCD. Emerging strategies to identify new biomarkers that can quantify circadian health (eg, environmental, behavioral, and internal misalignment) may lead to new interventions and therapeutic targets to prevent the progression of cardiovascular diseases that cause SCD.
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- 2021
32. Long-Term Outcomes of Cardiac Resynchronization Therapy in Patients With Repaired Tetralogy of Fallot: A Multicenter Study
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Ramdat Misier, Nawin L., Moore, Jeremy P., Nguyen, Hoang H., Lloyd, Michael S., Dubin, Anne M., Mah, Douglas Y., Czosek, Richard J., Khairy, Paul, Chang, Philip M., Nielsen, Jens C., Aydin, Alper, Pilcher, Thomas A., O’Leary, Edward T., Shivkumar, Kalyanam, and de Groot, Natasja M.S.
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- 2024
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33. Real three‐dimensional cardiac imaging using leading‐edge holographic display
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Mori, Shumpei and Shivkumar, Kalyanam
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Medical Physiology ,Biomedical and Clinical Sciences ,Clinical Sciences ,Cardiovascular ,Heart ,Holography ,Humans ,Imaging ,Three-Dimensional ,anatomy ,cardiology ,hologram ,imaging ,medical education ,three-dimensional imaging ,Anatomy & Morphology ,Clinical sciences ,Medical physiology - Abstract
Understanding three-dimensional cardiac anatomy is fundamental for the practice of clinical cardiology. However, if three-dimensional images are displayed on two-dimensional monitors, they fail to provide depth perception. Currently, novel technologies, including the three-dimensional printing, three-dimensional monitors/projectors, and virtual reality applications can provide real three-dimensionality with depth perception. However, their relatively high cost and limited user-friendliness prevent their wide application. We introduce novel and commercially available holographic display, which allows multiple observers to see the full-color holographic images simultaneously without any specific glasses and headgear. This leading-edge technology is immediately applicable in both educational and clinical settings.
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- 2021
34. Are device-detected atrial high-rate episodes a risk marker for stroke?
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Hanna, Peter, Buch, Eric, and Shivkumar, Kalyanam
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- 2023
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35. Mechanism of Ventricular Premature Beats Elicited by Left Stellate Ganglion Stimulation During Acute Ischemia of the Anterior Left Ventricle
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Boukens, Bastiaan JD, Dacey, Michael, Meijborg, Veronique MF, Janse, Michiel J, Hadaya, Joseph, Hanna, Peter, Swid, M Amer, Opthof, Tobias, Ardell, Jeffrey, Shivkumar, Kalyanam, and Coronel, Ruben
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Medical Physiology ,Biomedical and Clinical Sciences ,Clinical Research ,Neurosciences ,Cardiovascular ,Heart Disease ,Action Potentials ,Animals ,Disease Models ,Animal ,Electric Stimulation ,Female ,Heart ,Heart Rate ,Myocardial Ischemia ,Stellate Ganglion ,Sus scrofa ,Time Factors ,Ventricular Premature Complexes ,Ischaemia ,Arrhythmias ,Autonomic nervous system ,Repolarization ,Injury current ,Cardiorespiratory Medicine and Haematology ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology - Abstract
AimsEnhanced sympathetic activity during acute ischaemia is arrhythmogenic, but the underlying mechanism is unknown. During ischaemia, a diastolic current flows from the ischaemic to the non-ischaemic myocardium. This 'injury' current can cause ventricular premature beats (VPBs) originating in the non-ischaemic myocardium, especially during a deeply negative T wave in the ischaemic zone. We reasoned that shortening of repolarization in myocardium adjacent to ischaemic myocardium increases the 'injury' current and causes earlier deeply negative T waves in the ischaemic zone, and re-excitation of the normal myocardium. We tested this hypothesis by activation and repolarization mapping during stimulation of the left stellate ganglion (LSG) during left anterior descending coronary artery (LAD) occlusion.Methods and resultsIn nine pigs, five subsequent episodes of acute ischaemia, separated by 20 min of reperfusion, were produced by occlusion of the LAD and 121 epicardial local unipolar electrograms were recorded. During the third occlusion, left stellate ganglion stimulation (LSGS) was initiated after 3 min for a 30-s period, causing a shortening of repolarization in the normal myocardium by about 100 ms. This resulted in more negative T waves in the ischaemic zone and more VPBs than during the second, control, occlusion. Following the decentralization of the LSG (including removal of the right stellate ganglion and bilateral cervical vagotomy), fewer VPBs occurred during ischaemia without LSGS. During LSGS, the number of VPBs was similar to that recorded before decentralization.ConclusionLSGS, by virtue of shortening of repolarization in the non-ischaemic myocardium by about 100 ms, causes deeply negative T waves in the ischaemic tissue and VPBs originating from the normal tissue adjacent to the ischaemic border.
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- 2021
36. A single cell transcriptomics map of paracrine networks in the intrinsic cardiac nervous system.
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Moss, Alison, Robbins, Shaina, Achanta, Sirisha, Kuttippurathu, Lakshmi, Turick, Scott, Nieves, Sean, Hanna, Peter, Smith, Elizabeth H, Hoover, Donald B, Chen, Jin, Cheng, Zixi Jack, Ardell, Jeffrey L, Shivkumar, Kalyanam, Schwaber, James S, and Vadigepalli, Rajanikanth
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Cardiovascular medicine ,Molecular physiology ,Systems neuroscience ,Transcriptomics ,Neurosciences ,Cardiovascular ,Heart Disease - Abstract
We developed a spatially-tracked single neuron transcriptomics map of an intrinsic cardiac ganglion, the right atrial ganglionic plexus (RAGP) that is a critical mediator of sinoatrial node (SAN) activity. This 3D representation of RAGP used neuronal tracing to extensively map the spatial distribution of the subset of neurons that project to the SAN. RNA-seq of laser capture microdissected neurons revealed a distinct composition of RAGP neurons compared to the central nervous system and a surprising finding that cholinergic and catecholaminergic markers are coexpressed, suggesting multipotential phenotypes that can drive neuroplasticity within RAGP. High-throughput qPCR of hundreds of laser capture microdissected single neurons confirmed these findings and revealed a high dimensionality of neuromodulatory factors that contribute to dynamic control of the heart. Neuropeptide-receptor coexpression analysis revealed a combinatorial paracrine neuromodulatory network within RAGP informing follow-on studies on the vagal control of RAGP to regulate cardiac function in health and disease.
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- 2021
37. Neuroscientific therapies for atrial fibrillation
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Hanna, Peter, Buch, Eric, Stavrakis, Stavros, Meyer, Christian, Tompkins, John D, Ardell, Jeffrey L, and Shivkumar, Kalyanam
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Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Cardiovascular ,Neurosciences ,Heart Disease ,2.1 Biological and endogenous factors ,Aetiology ,Action Potentials ,Animals ,Anti-Arrhythmia Agents ,Atrial Fibrillation ,Atrial Remodeling ,Autonomic Denervation ,Autonomic Nervous System ,Electric Stimulation Therapy ,Heart ,Heart Rate ,Humans ,Neurotransmitter Agents ,Spinal Cord Stimulation ,Treatment Outcome ,Vagus Nerve Stimulation ,Atrial fibrillation ,Autonomic nervous system ,Neurocardiology ,Neuromodulation ,Vagus nerve ,Cardiorespiratory Medicine and Haematology ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology - Abstract
The cardiac autonomic nervous system (ANS) plays an integral role in normal cardiac physiology as well as in disease states that cause cardiac arrhythmias. The cardiac ANS, comprised of a complex neural hierarchy in a nested series of interacting feedback loops, regulates atrial electrophysiology and is itself susceptible to remodelling by atrial rhythm. In light of the challenges of treating atrial fibrillation (AF) with conventional pharmacologic and myoablative techniques, increasingly interest has begun to focus on targeting the cardiac neuraxis for AF. Strong evidence from animal models and clinical patients demonstrates that parasympathetic and sympathetic activity within this neuraxis may trigger AF, and the ANS may either induce atrial remodelling or undergo remodelling itself to serve as a substrate for AF. Multiple nexus points within the cardiac neuraxis are therapeutic targets, and neuroablative and neuromodulatory therapies for AF include ganglionated plexus ablation, epicardial botulinum toxin injection, vagal nerve (tragus) stimulation, renal denervation, stellate ganglion block/resection, baroreceptor activation therapy, and spinal cord stimulation. Pre-clinical and clinical studies on these modalities have had promising results and are reviewed here.
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- 2021
38. Cardiac sympathetic denervation and mental health
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Khalsa, Sahib S, Clausen, Ashley N, Shahabi, Leila, Sorg, Julie, Gonzalez, Sarah E, Naliboff, Bruce, Shivkumar, Kalyanam, and Ajijola, Olujimi A
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Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Research ,Heart Disease ,Mental Health ,Post-Traumatic Stress Disorder (PTSD) ,Behavioral and Social Science ,Depression ,Anxiety Disorders ,Cardiovascular ,Mental health ,Good Health and Well Being ,Humans ,Retrospective Studies ,Sympathectomy ,Tachycardia ,Ventricular ,Treatment Outcome ,Cardiac arrhythmia ,Autonomic nervous system ,Anxiety ,PTSD ,Neurosciences ,Pharmacology and Pharmaceutical Sciences ,Neurology & Neurosurgery ,Medical physiology - Abstract
BackgroundBilateral cardiac sympathetic denervation (BCSD) is a surgical treatment for refractory ventricular arrhythmias. Although the procedure has shown efficacy at reducing cardiac arrhythmias, its impact on mental health is unknown. In the current study we examined associations between the BCSD procedure and mental health.Methods10 ventricular arrhythmia patients undergoing BCSD completed assessments of anxiety, depression, and posttraumatic stress symptoms at pre- and post-BCSD time points. Wilcoxon signed rank and Mann-Whitney U tests were used to examine differences in mental health symptoms in the pre- and post-BSCD states. Point biserial correlations were used to explore associations between BCSD response and mental health symptoms.ResultsA significant reduction of anxiety symptoms was observed from pre- to post-BCSD. At the post-BCSD assessment, participants who successfully responded to the BCSD procedure exhibited lower anxiety symptoms compared to non-responders. However, no significant relationships were identified for depressive or PTSD symptoms.ConclusionThe BCSD procedure is associated with reduced anxiety shortly after successful treatment for refractory ventricular arrhythmias in a small sample. Longitudinal surveillance of mental health symptoms after BCSD may be warranted to monitor the impact of this procedure on mental health.
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- 2021
39. Sinus rhythm QRS morphology reflects right ventricular activation and anatomical ventricular tachycardia isthmus conduction in repaired tetralogy of Fallot
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Moore, Jeremy P., Shannon, Kevin M., Khairy, Paul, Waldmann, Victor, Bessière, Francis, Burrows, Austin, Su, Jonathan, and Shivkumar, Kalyanam
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- 2023
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40. Demonstration of feasibility and technique of transesophageal endoscopic epicardial access in a porcine model
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Weitzner, Zachary N., Cha, Steven, Challita, Ronald, Ajijola, Olujimi, Mori, Shumpei, Shivkumar, Kalyanam, Dutson, Erik, and Sedarat, Alireza
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- 2023
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41. Cardiac Conduction System Pacing: A Comprehensive Update
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Vijayaraman, Pugazhendhi, Chelu, Mihal G., Curila, Karol, Dandamudi, Gopi, Herweg, Bengt, Mori, Shumpei, Jastrzebski, Marek, Sharma, Parikshit S., Shivkumar, Kalyanam, Tung, Roderick, Upadhyay, Gaurav, Vernooy, Kevin, Welter-Frost, Allan, Whinnett, Zachary, Zanon, Francesco, and Ellenbogen, Kenneth A.
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- 2023
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42. Innervation and Neuronal Control of the Mammalian Sinoatrial Node a Comprehensive Atlas
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Hanna, Peter, Dacey, Michael J, Brennan, Jaclyn, Moss, Alison, Robbins, Shaina, Achanta, Sirisha, Biscola, Natalia P, Swid, Mohammed A, Rajendran, Pradeep S, Mori, Shumpei, Hadaya, Joseph E, Smith, Elizabeth H, Peirce, Stanley G, Chen, Jin, Havton, Leif A, Cheng, Zixi Jack, Vadigepalli, Rajanikanth, Schwaber, James, Lux, Robert L, Efimov, Igor, Tompkins, John D, Hoover, Donald B, Ardell, Jeffrey L, and Shivkumar, Kalyanam
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Adrenergic Neurons ,Animals ,Atrioventricular Node ,Autonomic Nervous System ,Biomarkers ,Cholinergic Neurons ,Coronary Vessels ,Female ,Ganglia ,Autonomic ,Heart Atria ,Humans ,Male ,Medical Illustration ,Myocardial Contraction ,Phenotype ,Sinoatrial Node ,Swine ,Swine ,Miniature ,Synapses ,Ventricular Function ,Left ,Vesicular Acetylcholine Transport Proteins ,autonomic nervous system ,electrophysiology ,neuroanatomy ,neurophysiology ,sinoatrial node ,Cardiorespiratory Medicine and Haematology ,Clinical Sciences ,Cardiovascular System & Hematology - Abstract
[Figure: see text].
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- 2021
43. Optical vagus nerve modulation of heart and respiration via heart-injected retrograde AAV.
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Fontaine, Arjun K, Futia, Gregory L, Rajendran, Pradeep S, Littich, Samuel F, Mizoguchi, Naoko, Shivkumar, Kalyanam, Ardell, Jeffrey L, Restrepo, Diego, Caldwell, John H, Gibson, Emily A, and Weir, Richard F Ff
- Abstract
Vagus nerve stimulation has shown many benefits for disease therapies but current approaches involve imprecise electrical stimulation that gives rise to off-target effects, while the functionally relevant pathways remain poorly understood. One method to overcome these limitations is the use of optogenetic techniques, which facilitate targeted neural communication with light-sensitive actuators (opsins) and can be targeted to organs of interest based on the location of viral delivery. Here, we tested whether retrograde adeno-associated virus (rAAV2-retro) injected in the heart can be used to selectively express opsins in vagus nerve fibers controlling cardiac function. Furthermore, we investigated whether perturbations in cardiac function could be achieved with photostimulation at the cervical vagus nerve. Viral injection in the heart resulted in robust, primarily afferent, opsin reporter expression in the vagus nerve, nodose ganglion, and brainstem. Photostimulation using both one-photon stimulation and two-photon holography with a GRIN-lens incorporated nerve cuff, was tested on the pilot-cohort of injected mice. Changes in heart rate, surface electrocardiogram, and respiratory responses were observed in response to both one- and two-photon photostimulation. The results demonstrate feasibility of retrograde labeling for organ targeted optical neuromodulation.
- Published
- 2021
44. Rationale and Design of the Multicenter Catheter Ablation of Ventricular Tachycardia Before Transcatheter Pulmonary Valve Replacement in Repaired Tetralogy of Fallot Study
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Moore, Jeremy P., Aboulhosn, Jamil A., Zeppenfeld, Katja, Waldmann, Victor, Bessière, Francis, Blom, Nico A., Combes, Nicolas, Fish, Frank A., McLeod, Christopher J., Kanter, Ronald J., Tan, Weiyi, Patel, Nimesh, von Alvensleben, Johannes C., Kamp, Anna, Lloyd, Michael S., Anderson, Charles C., Tan, Reina B., Mariucci, Elisabetta, Levi, Daniel S., Salem, Morris, Shivkumar, Kalyanam, and Khairy, Paul
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- 2023
- Full Text
- View/download PDF
45. Massive Air Embolism During Atrial Fibrillation Ablation: Averting Disaster in a Time of Crisis.
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Do, Duc H, Khakpour, Houman, Krokhaleva, Yuliya, Mori, Shumpei, Bradfield, Jason, Boyle, Noel G, and Shivkumar, Kalyanam
- Subjects
AF ,atrial fibrillation ,LAA ,left atrial appendage ,LV ,left ventricle ,RCA ,right coronary artery ,air embolism ,atrial fibrillation ,catheter ablation ,Cardiovascular ,Heart Disease - Abstract
A 62-year-old male with symptomatic persistent atrial fibrillation underwent radiofrequency catheter ablation. During exchange of the saline irrigation bag, the patient developed sudden hypotension and bradycardia and was found to have a massive air embolism. Air was successfully aspirated with catheters, and the patient did not suffer any permanent sequelae. (Level of Difficulty: Intermediate.).
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- 2021
46. Arrhythmic Risk Profile and Outcomes of Patients Undergoing Cardiac Sympathetic Denervation for Recurrent Monomorphic Ventricular Tachycardia After Ablation
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Dusi, Veronica, Gornbein, Jeffrey, H., Duc, Sorg, Julie M, Khakpour, Houman, Krokhaleva, Yuliya, Ajijola, Olujimi A, Macias, Carlos, Bradfield, Jason S, Buch, Eric, Fujimura, Osamu A, Boyle, Noel G, Yanagawa, Jane, Lee, Jay M, Shivkumar, Kalyanam, and Vaseghi, Marmar
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Research ,Cardiovascular ,Heart Disease ,Anti-Arrhythmia Agents ,Catheter Ablation ,Cicatrix ,Comorbidity ,Defibrillators ,Implantable ,Electrophysiologic Techniques ,Cardiac ,Female ,Heart ,Humans ,Male ,Middle Aged ,Retrospective Studies ,Risk Adjustment ,Secondary Prevention ,Sympathectomy ,Tachycardia ,Ventricular ,United States ,ablation ,autonomic ,cardiac sympathetic denervation ,ventricular tachycardia ,Cardiorespiratory Medicine and Haematology ,Cardiovascular medicine and haematology - Abstract
Background Cardiac sympathetic denervation (CSD) has been used as a bailout strategy for refractory ventricular tachycardia (VT). Risk of VT recurrence in patients with scar-related monomorphic VT referred for CSD and the extent to which CSD can modify this risk is unknown. We aimed to quantify arrhythmia recurrence risk and impact of CSD in this population. Methods and Results Adjusted competing risk time to event models were developed to adjust for risk of VT recurrence and sustained VT/implantable cardioverter-defibrillator shocks after VT ablation based on patient comorbidities at the time of VT ablation. Adjusted VT and implantable cardioverter-defibrillator shock recurrence rates were estimated for the subgroup who subsequently required CSD after ablation. The expected adjusted recurrence rates were then compared with the observed rates after CSD. Data from 381 patients with scar-mediated monomorphic VT who underwent VT ablation were analyzed, excluding patients with polymorphic VT. Sixty eight patients underwent CSD for recurrent VT. CSD reduced the expected adjusted VT recurrence rate by 36% (expected rate of 5.61 versus observed rate of 3.58 per 100 person-months, P=0.01) and the sustained VT/implantable cardioverter-defibrillator shock rates by 34% (expected rate of 4.34 versus observed 2.85 per 100 person-months, P=0.03). The median number of sustained VT/implantable cardioverter-defibrillator shocks in the year before versus the year after CSD was reduced by 90% (10 versus 1, P
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- 2021
47. Massive Air Embolism During Atrial Fibrillation Ablation Averting Disaster in a Time of Crisis
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H., Duc, Khakpour, Houman, Krokhaleva, Yuliya, Mori, Shumpei, Bradfield, Jason, Boyle, Noel G, and Shivkumar, Kalyanam
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Cardiovascular ,Heart Disease ,AF ,atrial fibrillation ,LAA ,left atrial appendage ,LV ,left ventricle ,RCA ,right coronary artery ,air embolism ,atrial fibrillation ,catheter ablation - Abstract
A 62-year-old male with symptomatic persistent atrial fibrillation underwent radiofrequency catheter ablation. During exchange of the saline irrigation bag, the patient developed sudden hypotension and bradycardia and was found to have a massive air embolism. Air was successfully aspirated with catheters, and the patient did not suffer any permanent sequelae. (Level of Difficulty: Intermediate.).
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- 2021
48. Genotype Predicts Outcomes in Fetuses and Neonates With Severe Congenital Long QT Syndrome
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Moore, Jeremy P, Gallotti, Roberto G, Shannon, Kevin M, Bos, J Martijn, Sadeghi, Elham, Strasburger, Janette F, Wakai, Ronald T, Horigome, Hitoshi, Clur, Sally-Ann, Hill, Allison C, Shah, Maully J, Behere, Shashank, Sarquella-Brugada, Georgia, Czosek, Richard, Etheridge, Susan P, Fischbach, Peter, Kannankeril, Prince J, Motonaga, Kara, Landstrom, Andrew P, Williams, Matthew, Patel, Akash, Dagradi, Federica, Tan, Reina B, Stephenson, Elizabeth, Krishna, Mani Ram, Miyake, Christina Y, Lee, Michelle E, Sanatani, Shubhayan, Balaji, Seshadri, Young, Ming-Lon, Siddiqui, Saad, Schwartz, Peter J, Shivkumar, Kalyanam, and Ackerman, Michael J
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Genetics ,Cardiovascular ,Pediatric ,Infant Mortality ,Clinical Research ,Heart Disease ,Perinatal Period - Conditions Originating in Perinatal Period ,Aftercare ,Electrocardiography ,Fetus ,Genotype ,Humans ,Infant ,Newborn ,Long QT Syndrome ,Patient Discharge ,Retrospective Studies ,atrioventricular block ,cardiac sympathetic denervation ,fetal arrhythmia ,fetus ,genetic testing ,implantable cardioverter-defibrillator ,long QT syndrome ,magnetocardiography ,sudden cardiac death ,torsades de pointes ,Cardiorespiratory Medicine and Haematology ,Clinical Sciences - Abstract
ObjectivesThis study sought to determine the relationship between long QT syndrome (LQTS) subtype (LTQ1, LTQ2, LTQ3) and postnatal cardiac events (CEs).BackgroundLQTS presenting with 2:1 atrioventricular block or torsades de pointes in the fetus and/or neonate has been associated with risk for major CEs, but overall outcomes and predictors remain unknown.MethodsA retrospective study involving 25 international centers evaluated the course of fetuses/newborns diagnosed with congenital LQTS and either 2:1 atrioventricular block or torsades de pointes. The primary outcomes were age at first CE after dismissal from the newborn hospitalization and death and/or cardiac transplantation during follow-up. CE was defined as aborted cardiac arrest, appropriate shock from implantable cardioverter-defibrillator, or sudden cardiac death.ResultsA total of 84 fetuses and/or neonates were identified with LQTS (12 as LQT1, 35 as LQT2, 37 as LQT3). Median gestational age at delivery was 37 weeks (interquartile range: 35 to 39 weeks) and age at hospital discharge was 3 weeks (interquartile range: 2 to 5 weeks). Fetal demise occurred in 2 and pre-discharge death in 1. Over a median of 5.2 years, there were 1 LQT1, 3 LQT2, and 23 LQT3 CEs (13 aborted cardiac arrests, 5 sudden cardiac deaths, and 9 appropriate shocks). One patient with LQT1 and 11 patients with LQT3 died or received cardiac transplant during follow-up. The only multivariate predictor of post-discharge CEs was LQT3 status (LQT3 vs. LQT2: hazard ratio: 8.4; 95% confidence interval: 2.6 to 38.9; p
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- 2020
49. Ventricular Parasystole in Cardiomyopathy Patients: A Link Between His-Purkinje System Damage and Ventricular Fibrillation
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Do, Duc H., O’Meara, Kyle, Lee, Jiyoung, Meyer, Scott, Hanna, Peter, Mori, Shumpei, Fishbein, Michael C., Boyle, Noel G., Elizari, Marcelo V., Bradfield, Jason S., and Shivkumar, Kalyanam
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- 2023
- Full Text
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50. Recurrent ventricular tachycardia after cardiac sympathetic denervation: Prolonged cycle length with improved hemodynamic tolerance and ablation outcomes
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Hayase, Justin, Dusi, Veronica, Do, Duc, Ajijola, Olujimi A, Vaseghi, Marmar, Lee, Jay M, Yanagawa, Jane, Hoftman, Nir, Revels, Sha'Shonda, Buch, Eric F, Khakpour, Houman, Fujimura, Osamu, Krokhaleva, Yuliya, Macias, Carlos, Sorg, Julie, Gima, Jean, Pavez, Geraldine, Boyle, Noel G, Shivkumar, Kalyanam, and Bradfield, Jason S
- Subjects
Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Clinical Sciences ,Clinical Research ,Cardiovascular ,Heart Disease ,Adult ,Aged ,Arrhythmias ,Cardiac ,Catheter Ablation ,Female ,Heart ,Hemodynamics ,Humans ,Male ,Middle Aged ,Sympathectomy ,Tachycardia ,Ventricular ,Treatment Outcome ,autonomic nervous system ,cardiac sympathetic denervation ,catheter ablation ,stellate ganglion ,ventricular tachycardia ,Cardiorespiratory Medicine and Haematology ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology - Abstract
IntroductionCardiac sympathetic denervation (CSD) is utilized for the management of ventricular tachycardia (VT) in structural heart disease when refractory to radiofrequency ablation (RFA) or when patient/VT characteristics are not conducive to RFA.MethodsWe studied consecutive patients who underwent CSD at our institution from 2009 to 2018 with VT requiring repeat RFA post-CSD. Patient demographics, VT/procedural characteristics, and outcomes were assessed.ResultsNinety-six patients had CSD, 16 patients underwent RFA for VT post-CSD. There were 15 male and 1 female patients with mean age of 54.2 ± 13.2 years. Fourteen patients had nonischemic cardiomyopathy. A mean of 2.0 ± 0.8 RFAs for VT was unsuccessful before the patient undergoing CSD. The median time between CSD and RFA was 104 days (interquartile range [IQR] = 15-241). The clinical VT cycle length was significantly increased after CSD both spontaneously on ECG and/or ICD interrogation (355 ± 73 ms pre-CSD vs. 422 ± 94 ms post-CSD, p = .001) and intraprocedurally (406 ± 86 ms pre-CSD vs. 457 ± 88 ms post-CSD, p = .03). Two patients had polymorphic and 14 had monomorphic VT (MMVT) pre-CSD, and all patients had MMVT post-CSD. The proportion of mappable, hemodynamically stable VTs increased from 35% during pre-CSD RFA to 58% during post-CSD RFA (p = .038). At median follow-up of 413 days (IQR = 43-1840) after RFA, eight patients had no further VT.ConclusionRFA for recurrent MMVT post-CSD is a reasonable treatment option with intermediate-term clinical success in 50% of patients. Clinical VT cycle length was significantly increased after CSD with associated improvement in mappable, hemodynamically tolerated VT during RFA.
- Published
- 2020
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