Kalyanam Shivkumar

Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, United States

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Publications (249)1168.37 Total impact

  • William A Huang, Kalyanam Shivkumar, Marmar Vaseghi
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    ABSTRACT: 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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    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; DOI:10.1161/CIRCEP.115.002721 · 5.42 Impact Factor
  • Heart rhythm: the official journal of the Heart Rhythm Society 03/2015; DOI:10.1016/j.hrthm.2015.03.038 · 4.92 Impact Factor
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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; DOI:10.1002/mrm.25601 · 3.40 Impact Factor
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    ABSTRACT: -It is not known if the most delayed late potentials are functionally most specific for scar-related ventricular tachycardia (VT) circuits. -Isochronal late activation maps (ILAM) were constructed to display ventricular activation during sinus rhythm over eight isochrones. Analysis was performed at successful VT termination sites and prospectively tested. 33 patients with 47 scar-related VTs where a critical site was demonstrated by termination of VT during ablation were retrospectively analyzed. In those that underwent mapping of multiple surfaces, 90% of critical sites were on the surface that contained the latest late potential. However, only 11% of critical sites were localized to the latest isochrone (87.5-100%) of ventricular activation. The median percentage of latest activation at critical sites was 78% at a distance from the latest isochrone of 18 mm. Sites critical to reentry were harbored in regions with slow conduction velocity, where 3 isochrones were present within a 1 cm radius. 10 consecutive patients underwent ablation prospectively guided by ILAM, targeting concentric isochrones outside of the latest isochrone. Elimination of the targeted VT was achieved in 90%. Termination of VT was achieved in 6 patients at a mean ventricular activation percentage of 78%, with only 1 requiring ablation in the latest isochrone. -Late potentials identified in the latest isochrone of activation during sinus rhythm are infrequently correlated with successful ablation sites for VT. The targeting of slow conduction regions propagating into the latest zone of activation may be a novel and promising strategy for substrate modification.
    Circulation Arrhythmia and Electrophysiology 03/2015; DOI:10.1161/CIRCEP.114.002637 · 5.42 Impact Factor
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    ABSTRACT: Modulation of human cardiac mechanical and electrophysiologic function by direct stellate ganglion stimulation has not been performed. Our aim was to assess the effect of low-level left stellate ganglion (LSG) stimulation (SGS) on arrhythmias, hemodynamic, and cardiac electrophysiological indices. Patients undergoing ablation procedures for arrhythmias were recruited for SGS. A stimulating electrode was placed next to the LSG under fluoroscopy and ultrasound imaging; and SGS (5-10 Hz, 10-20 mA) was performed. We measured hemodynamic, intracardiac and ECG parameters, and activation recovery intervals (ARIs) (surrogate for action potential duration) from a duodecapolar catheter in the right ventricular outflow tract. Five patients underwent SGS (3 males, 45 ± 20 years). Stimulating catheter placement was successful, and without complication in all patients. SGS did not change heart rate, but increased mean arterial blood pressure (78 ± 3 mmHg to 98 ± 5 mmHg, P < 0.001) and dP/dt max (1148 ± 244 mmHg/sec to 1645 ± 493 mmHg/sec, P = 0.03). SGS shortened mean ARI from 304 ± 23 msec to 283 ± 17 msec (P < 0.001), although one patient required parasympathetic blockade. Dispersion of repolarization (DOR) increased in four patients and decreased in one, consistent with animal models. QT interval, T-wave duration and amplitude at baseline and with SGS were 415 ± 15 msec versus 399 ± 15 msec (P < 0.001); 201 ± 12 msec versus 230 ± 28 msec; and 0.2 ± 0.09 mV versus 0.22 ± 0.08 mV, respectively. At the level of SGS performed, no increase in arrhythmias was seen. Percutaneous low-level SGS shortens ARI in the RVOT, and increases blood pressure and LV contractility. These observations demonstrate feasibility of percutaneous SGS in humans. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
    03/2015; 3(3). DOI:10.14814/phy2.12328
  • Roderick Tung, Eric Buch, Noel Boyle, Kalyanam Shivkumar
    Journal of the American College of Cardiology 03/2015; 65(10):A428. DOI:10.1016/S0735-1097(15)60428-4 · 15.34 Impact Factor
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    ABSTRACT: Myocardial infarction (MI) induces remodeling in stellate ganglion neurons (SGNs). We investigated whether infarct site has any impact on the laterality of morphological changes or neuropeptide expression in stellate ganglia. Yorkshire pigs underwent left circumflex artery (LCX, n=6) or right coronary artery (RCA, n=6) occlusion, to create left and right-sided MI, respectively (control: n=10). 5±1weeks post-MI, left and right stellate ganglia (LSG and RSG, respectively) were collected to determine neuronal size, tyrosine hydroxylase (TH) and neuropeptide Y (NPY) immunoreactivity. Compared to control, LCX and RCA MI increased mean neuronal size in the LSG (451±25µm² vs. 650±34µm² vs. 577±55 µm², respectively, p=0.0012); and RSG (433±22 µm² vs. 646±42 µm² vs. 530±41µm², respectively, p=0.002). TH-immunoreactivity was present in the majority of SGNs. Both LCX and RCA MI were associated with significant decrease in the percentage of TH-negative SGNs; from 2.58±0.2% in controls to 1.26±0.3% and 0.7±0.3% in LCX and RCA MI respectively for LSG (p=0.001); and from 3.02±0.4 in controls to 1.36±0.3% and 0.68±0.2% in LCX and RCA MI respectively for RSG (p=0.002). Both TH-negative and TH-positive neurons increased in size following LCX and RCA MI. Neuropeptide Y immunoreactivity was also significantly increased by LCX and RCA MI in both ganglia. Left and right-sided MI equally induced morphologic and neurochemical changes in LSG and RSG neurons, independent of infarct site. These data indicate that afferent signals transduced following MI result in bilateral changes, and provide a rationale for bilateral interventions targeting the sympathetic chain for arrhythmia modulation. Copyright © 2015. Published by Elsevier Inc.
    Heart rhythm: the official journal of the Heart Rhythm Society 01/2015; DOI:10.1016/j.hrthm.2015.01.045 · 4.92 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.
    01/2015; 29(1):56-60. DOI:10.7555/JBR.29.20140161
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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 01/2015; 6:90. DOI:10.3389/fphys.2015.00090
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    ABSTRACT: -T-peak to T-end interval (Tp-e) is an independent marker of sudden cardiac death. Modulation of Tp-e by sympathetic nerve activation and circulating norepinephrine (NE) is not well understood. The purpose of this study was to characterize endocardial and epicardial dispersion of repolarization (DOR) and its effects on Tp-e with sympathetic activation. -In Yorkshire pigs (n=13), a sternotomy was performed and the heart and bilateral stellate ganglia (SG) were exposed. A 56-electrode sock and 64-electrode basket catheter were placed around the epicardium and in the left ventricle (LV), respectively. Activation recovery interval (ARI), dispersion of repolarization (DOR), defined as variance in repolarization time, and Tp-e were assessed before and after left, right, and bilateral SG stimulation and NE infusion. LV endocardial and epicardial ARIs significantly decreased, and LV endocardial and epicardial DOR increased during sympathetic nerve stimulation. There were no LV epicardial vs. endocardial differences in ARI during sympathetic stimulation and regional endocardial ARI patterns were similar to the epicardium. Tp-e prolonged during left (from 40.4±2.2 ms to 92.4±12.4 ms; P<0.01), right (from 47.7±2.6 ms to 80.7±11.5 ms; P<0.01), and bilateral (from 47.5±2.8 ms to 78.1±9.8 ms; P<0.01) stellate stimulation and strongly correlated with whole heart DOR during stimulation (P<0.001, R=0.86). Of note, NE infusion did not increase DOR or Tp-e. -Regional patterns of LV endocardial sympathetic innervation are similar to that of LV epicardium. Tp-e correlated with whole heart DOR during sympathetic nerve activation. Circulating NE did not affect DOR or Tp-e.
    Circulation Arrhythmia and Electrophysiology 12/2014; 8(1). DOI:10.1161/CIRCEP.114.002195 · 5.42 Impact Factor
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    ABSTRACT: Accessory pathways can lie near or within the coronary sinus (CS). Radiofrequency catheter ablation of accessory pathways is a well-established treatment option, but this procedure can cause damage to adjacent coronary arteries. The purpose of this study was to evaluate the anatomical relationship between the coronary arteries and the CS. Retrospective data of patients who underwent catheter ablation of supraventricular tachycardia between 6/2011 and 8/2013 was reviewed. In addition, detailed analysis of coronary CT angiography (CTA) data from 50 patients was performed. Between 6/2011 and 8/2013, 427 patients underwent catheter ablation of supraventricular tachycardia, of which 105 (age 28±17, 60% male) had accessory pathway mediated tachycardia. Of these, 23 patients had accessory pathways near the CS and 60% (N=14) underwent concurrent coronary angiography. In four patients, the posterolateral (inferolateral) branch (PLA) of the right coronary artery was in close proximity to the CS, and two patients (18%) had stenosis of PLA at the site of ablation. On CTA at their closest proximity, the PLA was 1.9±1.3 mm and the LCx was 2.0±0.8 mm from the body of the CS, in right and left coronary artery dominant patients, respectively. CS ostium and PLA were 3.6±1.9 mm apart. In left dominant patients, LCx and CS ostium were 3.8±1.2 mm apart. The PLA and LCx are in close proximity to the antero-inferior aspect of the CS ostium and proximal CS. The relationship of the CS and coronary arteries should be evaluated prior to ablation at these sites. Copyright © 2014. Published by Elsevier Inc.
    Heart rhythm: the official journal of the Heart Rhythm Society 12/2014; 12(3). DOI:10.1016/j.hrthm.2014.11.035 · 4.92 Impact Factor
  • Jason S Bradfield, Kalyanam Shivkumar
    Circulation Arrhythmia and Electrophysiology 12/2014; 7(6):1000-2. DOI:10.1161/CIRCEP.114.002390 · 5.42 Impact Factor
  • Indian pacing and electrophysiology journal 11/2014; 14(6):311-2.
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    ABSTRACT: Background Ablation has become an important option for treatment of ventricular tachycardia (VT). The influence of procedure duration on outcomes remains unexamined. Objective To report the influence of procedure duration on outcomes and complications over an 8-year period Methods Patients referred for scar-mediated VT ablation from 2004-2011 were retrospectively analyzed. Procedure duration was defined as the time from the insertion of catheters through the femoral vein to the time of their withdrawal. Procedure duration was analyzed in relationship with: baseline and intraoperative covariates, acute procedural outcomes, complications, and 6-month clinical outcomes. Results 148 patients underwent VT ablation with mean procedure duration of 5.7 ± 1.8 hours. VT recurrence and survival at 6 months were 46% and 82%, respectively, and were not associated with procedure duration. Hospital mortality increased with intraoperative intra-aortic balloon pump insertion (adjusted OR 13.7, 95% CI 2.35-79.94, p=0.004), and was improved with successful ablation of the clinical VT as a procedural endpoint (adjusted OR 0.13, 95% Cl 0.03-0.54, p=0.005). The association between procedure duration and hospital mortality remained after adjusting for significant baseline variables (adjusted OR 1.75, 95% CI 1.14-2.68, p=0.0098) and intraoperative variables (adjusted OR 1.6, 95% CI 1.12-2.29, p=0.0104). Conclusion Hospital mortality was significantly increased by unsuccessful clinical VT ablation as a procedural endpoint and intraoperative IABP insertion. However, after adjusting for significant baseline and intraoperative covariates, procedure duration was still associated with increased hospital mortality. Procedure duration had no impact on VT recurrence and survival at 6 months.
    Heart Rhythm 10/2014; DOI:10.1016/j.hrthm.2014.10.004 · 4.92 Impact Factor
  • Cardiac electrophysiology clinics 09/2014; DOI:10.1016/j.ccep.2014.05.007
  • Heart Rhythm 08/2014; 11(10). DOI:10.1093/europace/euu194 · 4.92 Impact Factor
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    ABSTRACT: Vagal nerve stimulation (VNS) has been proposed as a cardio-protective intervention. However, regional ventricular electrophysiological effects of VNS are not well characterized. The purpose of this study was to evaluate effects of right and left VNS on electrophysiological properties of the ventricles and hemodynamic parameters. In Yorkshire pigs, a 56-electrode sock was used for epicardial (n=12) and a 64-electrode catheter for endocardial (n=9) activation recovery interval (ARI) recordings at baseline and during VNS. Hemodynamic recordings were obtained using a conductance catheter. Right and left VNS decreased heart rate (84±5 to 71±5 bpm, and 84±4 to 73±5 bpm), LV pressure (89±9 to 77±9 mmHg, and 91±9 to 83±9 mmHg), dP/dt max (1660±154 to 1490±160 mmHg/s, and 1595±155 to 1416±134 mmHg/s) and prolonged ARI (327±18 to 350±23 ms, and 327±16 to 347±21 ms), respectively, p < 0.05 vs. baseline for all parameters, p = NS for right vs. left VNS. No anterior-posterior-lateral regional differences in prolongation of ARI during right or left VNS were found. However, endocardial ARI prolonged more than epicardial, and apical ARI more than basal ARI during both right and left VNS. Changes in dP/dt max showed the strongest correlation with ventricular ARI effects (R(2) = 0.81, p < 0.0001) than either heart rate (R(2) = 0.58, p < 0.01), or LV pressure (R(2)=0.52, p < 0.05). Therefore, right and left VNS have similar effects on ventricular ARI in contrast to sympathetic stimulation that shows regional differences. Decrease in inotropy correlates best with ventricular electrophysiological effects.
    AJP Heart and Circulatory Physiology 07/2014; 307(5). DOI:10.1152/ajpheart.00279.2014 · 4.01 Impact Factor
  • Jason S. Bradfield, Marmar Vaseghi, Kalyanam Shivkumar
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    ABSTRACT: The autonomic nervous system is known to play a significant role in the genesis and persistence of arrhythmias. Neuromodulation has become a new therapeutic strategy for the treatment of ventricular arrhythmias. Catheter based renal denervation (RDN) is being studied as a treatment option for drug-refractory hypertension. Ablation within the renal arteries, by altering efferent and afferent signaling, has the potential to improve blood pressure as well as heart failure, atrial, and ventricular tachyarrhythmias.
    Trends in Cardiovascular Medicine 07/2014; 24(5). DOI:10.1016/j.tcm.2014.05.006 · 2.07 Impact Factor
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    ABSTRACT: Objective The goal of this study was to examine the association between ECG repolarization parameters and mortality in Chagas disease (CD) patients living in the United States. Methods CD patients with cardiomyopathy (CM) and bundle branch block (BBB) or BBB alone were compared to age- and sex-matched controls. QT interval, QT dispersion (QTd), T wave peak to T wave end duration (Tp-Te) and T wave peak to T wave end dispersion ((Tp-Te)d) were measured. Presence of fractionated QRS (fQRS) was also assessed. The main outcome measure was the association between ECG parameters and mortality or need for cardiac transplant. Results A total of 18 CM and 13 BBB CD patients were studied with 97% originating from Mexico or Central America. QTd (60.0±15.0 ms vs 43.5±9.8 ms, P=0.0002), Tp-Te (102.6±29.3 ms vs 77.1±11.0 ms, P=0.0002) and (Tp-Te)d (39.5±9.4 ms vs 22.7±7.6 ms, P<0.0001) were prolonged in CD CM patients compared to CM controls. Chagas CM patients had more fQRS then controls (84.2±0.10% vs 33.3±0.11%, p=0.0005). QTd (59.9±15.0 ms vs 29.5±6.9 ms, P=0.0001) and (Tp-Te)d (40.0±15.9 ms vs 18.5±5.4 ms, p<0.0001) were longer in the CD BBB group compared to BBB controls. Univariate analysis showed QTd (56.9±15.0 ms vs 46.5±17.3 ms, p=0.0412) and (Tp-Te)d (36.8±13.5 ms vs 28.5±13.3 ms, p=0.0395) were associated with death and/or need for cardiac transplant. Conclusion Our results indicate that P-max and PD are useful electrocardiographic markers for identifying the β-TM-high-risk patients for AF onset, even when the cardiac function is conserved.
    Indian pacing and electrophysiology journal 07/2014; 14(4):171-80.

Publication Stats

2k Citations
1,168.37 Total Impact Points

Institutions

  • 2014–2015
    • Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
      Torrance, California, United States
  • 2001–2015
    • University of California, Los Angeles
      • • Division of Cardiology
      • • Department of Medicine
      • • Cardiac Arrhythmia Center
      Los Ángeles, California, United States
    • University of Iowa Children's Hospital
      Iowa City, Iowa, United States
  • 2000–2014
    • Harbor-UCLA Medical Center
      Torrance, California, United States
  • 2012
    • University of California, Davis
      • Department of Biomedical Engineering
      Davis, CA, United States
    • Loma Linda University
      • Division of Pediatric Cardiology
      Loma Linda, California, United States
  • 2011
    • Stanford University
      Palo Alto, California, United States
  • 2010
    • Canadian Hemochromatosis Society
      Canada
    • Southlake Regional Health Centre
      Bradford West Gwillimbury, Ontario, Canada
  • 2007–2009
    • Oregon Health and Science University
      • Department of Diagnostic Radiology
      Los Angeles, CA, United States
  • 2002
    • Cedars-Sinai Medical Center
      • Division of Cardiology
      Los Angeles, California, United States
  • 1993–1996
    • Henry Ford Hospital
      • Department of Internal Medicine
      Detroit, Michigan, United States
    • Michigan State University
      Ист-Лансинг, Michigan, United States