Kalyanam Shivkumar

Loma Linda University, لوما ليندا، كاليفورنيا, California, United States

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Publications (265)1301.79 Total impact

  • O.A. Ajijola · L. Shahabi · S. Khalsa · B.D. Naliboff · K. Shivkumar
  • Eric Buch · Kalyanam Shivkumar
    Journal of the American College of Cardiology 09/2015; 66(12):1361-3. DOI:10.1016/j.jacc.2015.07.056 · 16.50 Impact Factor
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    ABSTRACT: Aims: Vagal nerve stimulation (VNS) has been shown to have anti-arrhythmic effects, but many of these benefits were demonstrated in the setting of vagal nerve decentralization. The purpose of this study was to evaluate the role of afferent fiber activation during VNS on efferent control of cardiac hemodynamic and electrophysiological parameters. Methods and results: In 37 pigs a 56-electrode sock was placed over the ventricles to record local activation recovery intervals (ARIs), a surrogate of action potential duration. In 12 of 37 animals atropine was given systemically. Right and left VNS were performed under six conditions: both vagal trunks intact (n=25), ipsilateral right (n=11), ipsilateral left (n=14), contralateral right (n=7), contralateral left (n=10), and bilateral (n=25) VNTx. Unilateral VNTx significantly affected heart rate, PR interval, Tau, and global ARIs. Right VNS after ipsilateral VNTx had augmented effects on hemodynamic parameters and increase in ARI, while subsequent bilateral VNTx did not significantly modify this effect (% change in ARI in intact condition: 2.2±0.9% vs. ipsilateral VNTx: 5.3±1.7% and bilateral VNTx: 5.3±0.8%, p<0.05). Left VNS after left VNTx tended to increase its effects on hemodynamics and ARI response (p=0.07), but only after bilateral VNTx did these changes reach significance (intact 1.1±0.5% vs. ipsilateral VNTx 3.6±0.7% and bilateral VNTx 6.6±1.6%, p<0.05 vs. intact). Contralateral VNTx did not modify VNS response. Effect of atropine on ventricular ARI was similar to bilateral VNTx. Conclusions: VNS activates afferent fibers in the ipsilateral vagal nerve, which reflexively inhibit cardiac parasympathetic efferent electrophysiological and hemodynamic effects.
    AJP Heart and Circulatory Physiology 09/2015; DOI:10.1152/ajpheart.00558.2015 · 3.84 Impact Factor
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    ABSTRACT: Selective, bilateral cervicothoracic sympathectomy has proven to be effective for managing ventricular arrhythmias in the setting of structural heart disease. The procedure currently employed removes the caudal portions of both stellate ganglia, along with thoracic chain ganglia down to T4 ganglia. To define the relative contributions of T1-T2 and the T3-T4 paravertebral ganglia in modulating ventricular electrical function. In anesthetized vagotomised porcine subjects (n=8), the heart was exposed via sternotomy along with right and left paravertebral sympathetic ganglia to the T4 level. A 56-electrode epicardial sock was placed over both ventricles to assess epicardial activation recovery intervals (ARI) in response to individually stimulating right and left stellate vs T3 paravertebral ganglia. Responses to T3 stimuli were repeated following surgical removal of the caudal portions of stellate ganglia and T2 bilaterally. In intact preparations, stellate ganglion vs T3 stimuli (4Hz, 4ms duration) were titrated to produce equivalent decreases in global ventricular ARIs (right-side 85±6 vs 55±10 ms; left-side 24±3 vs 17±7 ms). Threshold of stimulus intensity applied to T3 ganglia to achieve threshold was 3 times that of T1 threshold. ARIs in unstimulated states were unaffected by bilateral stellate-T2 ganglion removal. Following acute decentralization, T3 stimulation failed to change ARIs. Preganglionic sympathetic efferents arising from the T1-T4 spinal cord that project to the heart transit through stellate ganglia via the paravertebral chain. T1-T2 surgical excision is thus sufficient to functionally interrupt central control of peripheral sympathetic efferent activity. Copyright © 2015. Published by Elsevier Inc.
    Heart rhythm: the official journal of the Heart Rhythm Society 08/2015; DOI:10.1016/j.hrthm.2015.08.022 · 5.08 Impact Factor
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    ABSTRACT: The incidence of myocardial inflammation in patients with unexplained cardiomyopathy referred for ventricular arrhythmias (VA) is unknown. To report fasting PET scan findings in consecutive patients referred with unexplained cardiomyopathy and VA. 18-FDG PET/CT scans with a >16 hour fasting protocol were prospectively ordered for patients referred for VA and unexplained cardiomyopathy (EF<55%). Patients with focal myocardial FDG uptake were labeled as arrhythmogenic inflammatory cardiomyopathy (AIC) and classified into four groups based on the presence of lymph node uptake (AIC+) and perfusion abnormalities (early vs late stage). Over a 3-year period, 103 PET scan were performed with 49% (AIC+=17, AIC=33) exhibiting focal FDG uptake. The mean age was 52±12 years with an EF of 36±16%. Patients with AIC were more likely to have a history of pacemaker (32% vs 6%, p=0.002) compared to those with normal PET. When biopsy was performed, histologic diagnosis revealed non-granulomatous inflammation in 6 patients and sarcoidosis in 18 patients. 90% of patients with AIC/AIC+ were prescribed immunosuppressive therapy and 58% underwent ablation. Correlation between areas of perfusion abnormalities and FDG uptake with electro-anatomic mapping was observed in 79% patients and MRI findings matched in only 33%. Nearly 50% of patients referred with unexplained cardiomyopathy and VA demonstrate ongoing focal myocardial inflammation on FDG PET. These data suggests that a significant proportion of patients labeled "idiopathic" may have occult arrhythmogenic inflammatory cardiomyopathy, which may benefit from early detection and immunosuppressive medical therapy. Copyright © 2015. Published by Elsevier Inc.
    Heart rhythm: the official journal of the Heart Rhythm Society 08/2015; DOI:10.1016/j.hrthm.2015.08.014 · 5.08 Impact Factor
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    Una Buckley · Kalyanam Shivkumar · Jeffrey L Ardell
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    ABSTRACT: Autonomic regulation therapy (ART) is a rapidly emerging therapy in the management of congestive heart failure secondary to systolic dysfunction. Modulation of the cardiac neuronal hierarchy can be achieved with bioelectronics modulation of the spinal cord, cervical vagus, baroreceptor, or renal nerve ablation. This review will discuss relevant preclinical and clinical research in ART for systolic heart failure. Understanding mechanistically what is being stimulated within the autonomic nervous system by such device-based therapy and how the system reacts to such stimuli is essential for optimizing stimulation parameters and for the future development of effective ART.
    Current Heart Failure Reports 06/2015; 12(4). DOI:10.1007/s11897-015-0263-7
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    ABSTRACT: Afferent and efferent cardiac neurotransmission via the cardiac nerves intricately modulates nearly all physiological functions of the heart (chronotropy, dromotropy, lusitropy, and inotropy). Afferent information from the heart is transmitted to higher levels of the nervous system for processing (intrinsic cardiac nervous system, extracardiac-intrathoracic ganglia, spinal cord, brain stem, and higher centers), which ultimately results in efferent cardiomotor neural impulses (via the sympathetic and parasympathetic nerves). This system forms interacting feedback loops that provide physiological stability for maintaining normal rhythm and life-sustaining circulation. This system also ensures that there is fine-tuned regulation of sympathetic-parasympathetic balance in the heart under normal and stressed states in the short (beat to beat), intermediate (minutes to hours), and long term (days to years). This important neurovisceral/autonomic nervous system also plays a major role in the pathophysiology and progression of heart disease, including heart failure and arrhythmias leading to sudden cardiac death. Transdifferentiation of neurons in heart failure, functional denervation, cardiac and extracardiac neural remodeling has also been identified and characterized during the progression of disease. Recent advances in understanding the cellular and molecular processes governing innervation and the functional control of the myocardium in health and disease provide a rational mechanistic basis for the development of neuraxial therapies for preventing sudden cardiac death and other arrhythmias. Advances in cellular, molecular, and bioengineering realms have underscored the emergence of this area as an important avenue of scientific inquiry and therapeutic intervention.
    Circulation Research 06/2015; 116(12):2005-2019. DOI:10.1161/CIRCRESAHA.116.304679 · 11.02 Impact Factor
  • JACC Clinical Electrophysiology 06/2015; 1(3):116-123. DOI:10.1016/j.jacep.2015.04.005
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    ABSTRACT: The impact of catheter ablation of ventricular tachycardia (VT) on all-cause mortality remains unknown. To examine the association between VT recurrence after ablation and survival in patients with scar-related VT. Analysis of 2,061 patients with structural heart disease referred for catheter ablation of scar-related VT from 12 international centers was performed. Data on clinical and procedural variables, VT recurrence, and mortality were analyzed. Kaplan-Meier analysis was used to estimate freedom from recurrent VT, transplant, and death. Cox proportional hazards frailty models were used to analyze the effect of risk factors on VT recurrence and mortality. One-year freedom from VT recurrence was 70% (72% in ischemic and 68% in non-ischemic cardiomyopathy). 57 (3%) patients underwent cardiac transplantation and 216 (10%) died during follow-up. At one year, the estimated rate of transplant and/or mortality was 15% (same for ischemic and non-ischemic cardiomyopathy). Transplant-free survival was significantly higher in patients without VT recurrence compared to those with recurrence (90% vs. 71%, p<0.001). In multivariable analysis, recurrence of VT after ablation showed the highest risk for transplant and/or mortality (HR 6.9 (5.3-9.0); p<0.001). In patients with EF<30% and across all NYHA classes, improved transplant-free survival was seen in those without VT recurrence. Catheter ablation of VT in patients with structural heart disease results in 70% freedom from VT recurrence, with an overall transplant and/or mortality rate of 15% at 1 year. Freedom from VT recurrence is associated with improved transplant-free survival, independent of heart failure severity. Copyright © 2015. Published by Elsevier Inc.
    Heart rhythm: the official journal of the Heart Rhythm Society 05/2015; 12(9). DOI:10.1016/j.hrthm.2015.05.036 · 5.08 Impact Factor
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    Una Buckley · Kalyanam Shivkumar
    Trends in cardiovascular medicine 05/2015; DOI:10.1016/j.tcm.2015.05.001 · 2.91 Impact Factor
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    Una Buckley · Kalyanam Shivkumar
    European Heart Journal 05/2015; 36(26). DOI:10.1093/eurheartj/ehv158 · 15.20 Impact Factor
  • William A Huang · Kalyanam Shivkumar · Marmar Vaseghi
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    ABSTRACT: Opinion statement: Vagal nerve stimulation (VNS) has shown promise as an adjunctive therapy for management of cardiac arrhythmias by targeting the cardiac parasympathetic nervous system. VNS has been evaluated in the setting of ischemia-driven ventricular arrhythmias and atrial arrhythmias, as well as a treatment option for heart failure. As better understanding of the complexities of the cardiac autonomic nervous system is obtained, vagal nerve stimulation will likely become a powerful tool in the current cardiovascular therapeutic armamentarium.
    Current Treatment Options in Cardiovascular Medicine 05/2015; 17(5):379. DOI:10.1007/s11936-015-0379-9
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    Heart rhythm: the official journal of the Heart Rhythm Society 05/2015; 12(5):S522. DOI:10.1016/j.hrthm.2015.03.059 · 5.08 Impact Factor
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    ABSTRACT: -New approaches to ablation of atrial fibrillation (AF) include focal impulse and rotor modulation (FIRM) mapping, and initial results reported with this technique have been favorable. We sought to independently evaluate the approach by analyzing quantitative characteristics of atrial electrograms (AEGMs) used to identify rotors, and describe acute procedural outcomes of FIRM-guided ablation. -All FIRM-guided ablation procedures (n=24, 50% paroxysmal) at UCLA Medical Center were included for analysis. During AF, unipolar AEGMs collected from a 64-pole basket catheter were used to construct phase maps and identify putative AF sources. These sites were targeted for ablation, in conjunction with pulmonary vein isolation (PVI) in most patients (n=19, 79%). All patients had rotors identified (mean 2.3 ± 0.9 per patient, 72% in LA). Prespecified acute procedural endpoint was achieved in 12/24 (50%) patients: AF termination (n=1), organization (n=3), or >10% slowing of AF cycle length (n=8). Basket electrodes were within 1cm of 54% of LA surface area, and a mean of 31 electrodes per patient showed interpretable AEGMs. Offline analysis revealed no differences between rotor and distant sites in dominant frequency or Shannon entropy. Electroanatomic mapping showed no rotational activation at FIRM-identified rotor sites in 23/24 patients (96%). -FIRM-identified rotor sites did not exhibit quantitative AEGM characteristics expected from rotors, and did not differ quantitatively from surrounding tissue. Catheter ablation of these sites, in conjunction with PVI, resulted in AF termination or organization in a minority of patients (4/24, 17%). Further validation of this approach is necessary.
    Circulation Arrhythmia and Electrophysiology 04/2015; 8(3). DOI:10.1161/CIRCEP.115.002721 · 4.51 Impact Factor
  • Roderick Tung · Kalyanam Shivkumar
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    ABSTRACT: Epicardial mapping and ablation via a percutaneous subxiphoid technique has been instrumental in improving the working understanding of complex myocardial scars in various arrhythmogenic substrates. Endocardial ablation alone may not be sufficient in patients with ischemic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, hypertrophic cardiomyopathy, and Chagas disease to prevent recurrent ventricular tachycardia. Multiple observational studies have demonstrated greater freedom from recurrence with adjunctive epicardial ablation compared with endocardial ablation alone. While epicardial ablation is performed predominantly at tertiary referral centers, knowledge of the technical approach, clinical indications, and potential complications is imperative to maximizing clinical success and patient safety. In 1996, Sosa and colleagues modified the pericardiocentesis technique to enable percutaneous access to the pericardial space for mapping and catheter ablation of ventricular tachycardia.1 Originally developed for patients with epicardial scarring due to chagasic cardiomyopathy and patients with ischemic cardiomyopathy refractory to endocardial ablationm,2,3 this approach has since become an essential part of the armamentarium for the treatment of ventricular tachycardia. Myocardial scars are three-dimensionally complex with varying degrees of transmurality, and the ability to map and ablate the epicardial surface has contributed to a greater understanding of scar-related VT in postinfarction cardiomyopathy and nonischemic substrates including idiopathic dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, hypertrophic cardiomyopathy, and chagasic cardiomyopathy. In this review, we highlight the percutaneous approach and discuss clinical indications and potential complications.
    Methodist DeBakey cardiovascular journal 04/2015; 11(2):129-34. DOI:10.14797/mdcj-11-2-129
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    Olujimi A Ajijola · Noel G Boyle · Kalyanam Shivkumar
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    ABSTRACT: Atrial fibrillation (AF) is the most common arrhythmia prompting clinical presentation, is associated with significant morbidity and mortality. The incidence and prevalence of this arrhythmia is expected to grow significantly in the coming decades. Of the available pharmacologic and non-pharmacologic treatment options, the fastest growing and most intensely studied is catheter-based ablation therapy for AF. Given the varying success rates for AF ablation, the increasingly complex factors that need to be taken into account when deciding to proceed with ablation, as well as varying definitions of procedural success, accurate detection of arrhythmia recurrence and its burden is of significance. Detecting and monitoring AF recurrence following catheter ablation is therefore an important consideration. Multiple studies have demonstrated the close relationship between the intensity of rhythm monitoring with wearable ambulatory cardiac monitors, or implantable cardiac rhythm monitors and the detection of arrhythmia recurrence. Other studies have employed algorithms dependent on intensive monitoring and arrhythmia detection in the decision tree on whether to proceed with repeat ablation or medical therapy. In this review, we discuss these considerations, types of monitoring devices, and implications for monitoring AF recurrence following catheter ablation.
    Frontiers in Physiology 03/2015; 6:90. DOI:10.3389/fphys.2015.00090 · 3.53 Impact Factor
  • Heart rhythm: the official journal of the Heart Rhythm Society 03/2015; 12(7). DOI:10.1016/j.hrthm.2015.03.038 · 5.08 Impact Factor
  • Shams Rashid · Stanislas Rapacchi · Kalyanam Shivkumar · Adam Plotnik · J Paul Finn · Peng Hu
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    ABSTRACT: To study the effects of cardiac devices on three-dimensional (3D) late gadolinium enhancement (LGE) MRI and to develop a 3D LGE protocol for implantable cardioverter defibrillator (ICD) patients with reduced image artifacts. The 3D LGE sequence was modified by implementing a wideband inversion pulse, which reduces hyperintensity artifacts, and by increasing bandwidth of the excitation pulse. The modified wideband 3D LGE sequence was tested in phantoms and evaluated in six volunteers and five patients with ICDs. Phantom and in vivo studies results demonstrated extended signal void and ripple artifacts in 3D LGE that were associated with ICDs. The reason for these artifacts was slab profile distortion and the subsequent aliasing in the slice-encoding direction. The modified wideband 3D LGE provided significantly reduced ripple artifacts than 3D LGE with wideband inversion only. Comparison of 3D and 2D LGE images demonstrated improved spatial resolution of the heart using 3D LGE. Increased bandwidth of the inversion and excitation pulses can significantly reduce image artifacts associated with ICDs. Our modified wideband 3D LGE protocol can be readily used for imaging patients with ICDs given appropriate safety guidelines are followed. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Magnetic Resonance in Medicine 03/2015; 17(Suppl 1). DOI:10.1002/mrm.25601 · 3.57 Impact Factor
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    Roderick Tung · Kalyanam Shivkumar
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    ABSTRACT: In the hyperadrenergic state of VT storm where shocks are psychologically and physiologically traumatizing, suppression of sympathetic outflow from the organ level of the heart up to higher braincenters plays a significant role in reducing the propensity for VT recurrence. The autonomic nervous system continuously receives input from the heart (afferent signaling), integrates them, and sends efferent signals to modify or maintain cardiac function and arrhythmogenesis. Spinal anesthesia with thoracic epidural infusion of bupivicaine and surgical removal of the sympathetic chain including the stellate ganglion has been shown to decrease recurrences of VT. Excess sympathetic outflow with catecholamine release can be modified with catheter-based renal denervation. The insights provided from animal experiments and in patients that are refractory to conventional therapy have significantly improved our working understanding of the heart as an end organ in the autonomic nervous system.
    03/2015; 29(1):56-60. DOI:10.7555/JBR.29.20140161

Publication Stats

2k Citations
1,301.79 Total Impact Points


  • 2015
    • Loma Linda University
      لوما ليندا، كاليفورنيا, California, United States
  • 2004–2015
    • Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
      • Department of Medicine
      Torrance, California, United States
  • 2001–2015
    • University of California, Los Angeles
      • • Division of Cardiology
      • • Department of Medicine
      • • Department of Radiology
      • • Cardiac Arrhythmia Center
      Los Ángeles, California, United States
    • University of Iowa
      Iowa City, Iowa, United States
  • 2000–2014
    • Harbor-UCLA Medical Center
      Torrance, California, United States
  • 2011
    • Stanford University
      Palo Alto, California, United States
  • 2010
    • Canadian Hemochromatosis Society
    • Southlake Regional Health Centre
      Bradford West Gwillimbury, Ontario, Canada
  • 2009
    • Oregon Health and Science University
      • Department of Diagnostic Radiology
      Los Angeles, CA, United States
    • Keck School of Medicine USC
      Los Ángeles, California, United States
  • 2002
    • Cedars-Sinai Medical Center
      • Division of Cardiology
      Los Angeles, California, United States
  • 2001–2002
    • University of Iowa Children's Hospital
      Iowa City, Iowa, United States