Jan Nemec

University of Alabama at Birmingham, Birmingham, Alabama, United States

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Publications (31)103.86 Total impact

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    ABSTRACT: Dofetilide is a class III antiarrhythmic agent approved for the maintenance of sinus rhythm in patients with persistent atrial fibrillation (AF). The goal of this study was to determine if chemical cardioversion (CCV) suggests a greater sensitivity to dofetilide and, therefore, portends a higher risk of proarrhythmia. We analyzed 99 consecutive patients with persistent AF who were loaded on dofetilide before cardioversion. CCV occurred after 2 ± 1.5 doses of dofetilide in 46 patients whereas electrical cardioversion (ECV) was required in the remaining 53 patients after 4.7 ± 1.3 doses. During index hospitalization, there were higher rates of dofetilide discontinuation because of QT prolongation or torsades de pointes (TdP) in the CCV group compared with the ECV group (24% vs 2%, p = 0.001). All patients with CCV requiring drug discontinuation converted after a single dose of dofetilide. Additionally, all 3 patients with TdP were in the CCV group. Furthermore, 15 of the 21 patients with CCV (71%) who converted after the first dose of dofetilide developed significant QT prolongation, requiring dose adjustment or discontinuation of drug. Among patients discharged on drug, AF recurrence and drug discontinuation rates were similar between groups at 2-year follow-up. In patients hospitalized for initiation of dofetilide, CCV occurs in almost 50% and is associated with higher rates of pathologic QT prolongation and TdP compared with those who require ECV. Once discharged on dofetilide, safety and efficacy is similar in both groups. In conclusion, patients with CCV may require closer monitoring for proarrhythmia.
    The American journal of cardiology 05/2013; · 3.58 Impact Factor
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    ABSTRACT: Introduction and Objectives: Bradycardia prolongs action potential durations (APD-adaptation), enhances dispersion-of-repolarization (DOR) and promotes tachyarrhythmias. Yet, the mechanisms responsible for enhanced DOR and tachyarrhythmias remain largely unexplored. Methods: Ca(2+) transients (CaiT) and APs were measured optically from Langendorff rabbit hearts at high (150x150µm(2)) or low (1.5x1.5cm(2)) magnification while pacing at a physiological (120-beats/min) or a slow heart rate (SHR=50-beats/min). Western blots and pharmacological interventions were used to elucidate the regional effects of bradycardia. Results: Bradycardia (SHR=50-beats/min) increased APDs gradually (time-constant τf→s =48±9.2s) and caused a secondary Ca(2+) release (SCR) from the sarcoplasmic reticulum (SR) during AP plateaus, occurring at the base on average 184.4±9.7 ms after the CaiT upstroke. In subcellular imaging, SCRs were temporally synchronous and spatially homogeneous within myocytes. In diastole, SHR elicited variable asynchronous SR Ca(2+) release events leading to subcellular Ca(2+)-waves, detectable only at high-magnification. SCR was regionally heterogeneous, correlated with APD prolongation (p<0.01, n=5), enhanced DOR (r=0.9277±0.03, n=7) and was gradually reversed by pacing at 120-beats/min along with APD shortening (p<0.05, n=5). A stabilizer of leaky ryanodine receptors (RyR2), K201 (1µM) suppressed SCR and reduced APD at the base, thereby reducing DOR (p<0.02, n=5). Ventricular ectopy induced by bradycardia (n=5/15) was suppressed by K201. Western blots revealed spatial differences of Cav1.2α, NCX1, Nav1.5 and RERG (but not RyR2 or SERCA2a) that correlate with the SCR distribution and explain the molecular basis for SCR heterogeneities. Conclusions: Acute bradycardia elicits synchronized subcellular SCRs of sufficient magnitude to overcome the 'source-sink' mismatch and to promote afterdepolarizations and tachyarrhythmias.
    AJP Heart and Circulatory Physiology 01/2013; · 4.01 Impact Factor
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    ABSTRACT: BACKGROUND: The Riata implantable cardioverter-defibrillator lead was recalled by the Food and Drug Administration because of an increased rate of failure associated with cable externalization. Because of its mechanical separation, the Riata lead may be challenging to extract. We therefore examined the experience with Riata lead extractions at our institution. METHODS: All patients implanted with the Riata lead underwent detailed review of their electronic medical records and operative notes. Procedural complications were ascertained by reviewing the medical records up to 30 days after Riata extraction. RESULTS: From a total of 627 patients implanted with the Riata lead at our institution, 20 patients (age at time of extraction, 57 ± 11 years; 85 % men; lead dwell time, 48 ± 27 months) underwent lead extraction. Extraction was successful in 19 of 20 (95 %) patients and required the use of laser-powered sheaths in 18 (90 %) patients. Over a 30-day follow-up period, 1 of 20 (5 %) patients had a minor procedure-related complication consisting of a new pericardial effusion that did not require drainage. CONCLUSIONS: Extraction of the Riata lead seems to be successful and safe and frequently requires the use of powered sheaths.
    Journal of Interventional Cardiac Electrophysiology 11/2012; · 1.39 Impact Factor
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    ABSTRACT: The Food and Drug Administration recently issued a class I recall of the St. Jude Medical Riata implantable cardioverter-defibrillator lead presumably because of increased risk of electric failure and mechanical separation via inside-out abrasion. We sought to examine the incidence and time dependence of inside-out abrasion in asymptomatic patients implanted with the Riata lead. Asymptomatic patients implanted with the Riata lead at our institution were offered voluntary fluoroscopic screening in 3 views. Electric testing of the Riata lead with provocative isometric muscle contraction was performed at the time of fluoroscopic screening. Of the 245 patients undergoing fluoroscopic screening, 53 (21.6%) patients showed clear evidence of lead separation. Of these externalized leads, 0%, 13%, and 26% had a dwell time of <3 years, 3 to 5 years, and >5 years, respectively (P=0.037). Externalized leads had a significantly pronounced decrease in R-wave amplitude (-1.7±2.9 mV versus +0.35±2.5 mV; P<0.001), and more patients with externalized leads had ≥25% decrease in R-wave amplitude from baseline (28.0% versus 8.1%; P=0.018). One patient with externalization exhibited new noise on near-field electrogram. The Riata lead exhibits time-dependent high rates of cable externalization exceeding 20% at >5 years of dwell time. Externalized leads are associated with a more pronounced decrease in R-wave amplitude, which may be an early marker of future electric failure. The use of fluoroscopic and electric screening of asymptomatic patients with the Riata lead remains controversial in the management of patients affected by the recent Food and Drug Administration recall.
    Circulation Arrhythmia and Electrophysiology 07/2012; 5(4):809-14. · 5.95 Impact Factor
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    Jong J. Kim, Jan Nemec, Guy Salama
    Journal of The American College of Cardiology - J AMER COLL CARDIOL. 01/2011; 57(14).
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    ABSTRACT: 52-year-old patient presented with palpitation and well tolerated monomorphic ventricular tachycardia. He had normal echocardiogram and coronary angiogram 3 months prior to presentation. Surface EKG revealed regular wide-complex tachycardia with right bundle branch block morphology and right inferior axis. In conjunction with recent negative cardiac evaluation, this suggested idiopathic focal ventricular tachycardia from anterolateral basal left ventricle. CARTO based activation mapping confirmed the presence of VT focus in that area. Radiofrequency ablation at the site of perfect pacemap resulted in a partial suppression of the focus. Echocardiogram was subsequently performed because of progressive dyspnea. It revealed asymmetrical thickening of posterolateral left ventricle, with delayed enhancement on contrast magnetic resonance imaging. Fine needle aspiration of abdominal fat stained with Congo red confirmed the diagnosis of systemic AL amyloidosis due to IgG lambda-light chain deposition. Consequently, the patient underwent placement of implantable defibrillator and hematopoetic stem cell transplantation. He remains in excellent functional status 18 months after presentation.
    Indian pacing and electrophysiology journal 01/2010; 10(3):143-7.
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    Journal of The American College of Cardiology - J AMER COLL CARDIOL. 01/2010; 55(10).
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    ABSTRACT: The recently published Ventricular Arrhythmia Suppression Trial (VAST) found no effect of rate-smoothing (RS) algorithm on frequency of ventricular tachycardia (VT) episodes in patients with implantable defibrillator. A similar recent trial reported an opposite result. In order to determine possible reasons for the discrepancy between the trials and achieve better understanding of events preceding VT onset, we analyzed stored device electrograms preceding 162 VT episodes from 50 VAST trial patients with dual-chamber devices. In this analysis, short-long sequences were more common prior to polymorphic VTs than before monomorphic VTs. The proportion of VT episodes preceded by short-long sequences was lower during randomization to RS ON (5.3% vs 31.3%, P < 0.001). For patients with multiple episodes of monomorphic VT, there was higher interpatient than intrapatient variability in preceding RR intervals. When adjusting for this similarity of RR interval sequences preceding VT onset in individual patients, the difference in proportion short-long sequences between RS ON and RS OFF programming was no longer significant. Episodes of VT were preceded by stereotypic, patient-specific sequences of RR intervals in several VAST trial patients. RS reduced the percentage of VTs preceded by short-long sequences, but did not change overall VT incidence.
    Journal of Cardiovascular Electrophysiology 12/2008; 20(5):545-50. · 3.48 Impact Factor
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    ABSTRACT: National trends in chronic lead extractions from cardiac rhythm management (CRM) devices are on the rise. The main objective of the study was to identify the predictors of complications of chronic lead extractions. All patients who underwent endovascular chronic CRM lead extraction at our institution between 2002 and 2008 were included in this analysis. Demographic data as well as details of the extraction procedure and its complications within the ensuing 30 days were collected on all patients. Data of 212 consecutive patients (456 leads, age = 65 +/- 17 years, men 75%, left ventricular ejection fraction = 36 +/- 16%, coronary artery disease 80%, defibrillators 49%) were analyzed. There were a total of 26 (11.8%) complications in 25 patients including 9 (4.2%) major complications (death 1, hemothorax 4, pneumothorax 2, tamponade 1, stroke 1) and 17 (8.0%) minor complications. Independent predictors of any complications included a higher number of explanted right ventricular leads (HR = 3.51, P = 0.013). Explantation of ICD as opposed to a pacemaker device showed a strong trend toward significance (HR = 2.57, P = 0.053). An elevated white blood cell count also predicted major complications (HR = 1.52, P = 0.005). Predictors of complications after lead extraction procedures include a higher number of extracted leads and the presence of defibrillator as opposed to pacemaker leads. A new paradigm of the removal of all leads not connected to a device may, therefore, reduce the risk of complications from lead extraction procedures and deserves to be tested prospectively.
    Journal of Cardiovascular Electrophysiology 10/2008; 20(2):171-5. · 3.48 Impact Factor
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    ABSTRACT: We present a case of a patient with lymphoma in an ICD pocket in the setting of posttransplant immune suppression. Infection of the ICD system was suspected and the correct diagnosis was established by biopsy.
    Pacing and Clinical Electrophysiology 07/2008; 31(6):769-71. · 1.75 Impact Factor
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    ABSTRACT: Advisories for implanted devices present a challenging management problem since no specific guidelines exist for device replacement under these circumstances. Since the rate and severity of complications is an important factor in the decision-making, we sought to review our experience with replacement of devices under advisory. Medical records of patients with devices under advisory were reviewed. A total of 237 patients (age 68+/-13 years, men 71%, implantable cardioverter-defibrillator (ICD) 87%) underwent device replacement in response to advisories (Medtronic Inc. 43% and Guidant Inc. 57%) at our institution between February 2005 and June 2006. The mean time from original device implantation to replacement was 31+/-16 months (3-73 months). During a mean follow-up of 198+/-103 days, there was a 5.5% overall rate of complications related to the procedure. Major complications requiring re-operation affected 2.1% of patients. There were no deaths associated with device replacement. Device failure prior to replacement was documented in 1.7% of patients, with syncope occurring in one patient. A history of diabetes mellitus (23%), peripheral vascular disease (4%), obstructive lung disease (7%), end-stage renal disease (2%), or use of anticoagulation (44%) did not predict the occurrence of complications after advisory device replacement. This single center experience shows a lower major complication rate from replacement of devices under advisory than previously reported. Experience from this center and others may be useful in guiding future management of patients in the setting of device advisories.
    International journal of cardiology 04/2008; 134(1):42-6. · 6.18 Impact Factor
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    ABSTRACT: A patient with advanced ischemic cardiomyopathy underwent implantation of a vagal stimulator in an attempt to control recurrent drug refractory ventricular arrhythmia. Electrical storm was exacerbated after the implant and continued after neurostimulation was discontinued. The report aims to provide a cautionary note to application of vagal stimulation for control of cardiac arrhythmia.
    Clinical Autonomic Research 01/2008; 17(6):385-90. · 1.48 Impact Factor
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    ABSTRACT: The muscarinic-gated atrial potassium channel IKACh has been well characterized functionally, and has been an excellent model system for studying G protein/effector interactions. Complementary DNAs encoding the composite subunits of IKACh have been identified, allowing direct probing of structural and functional features of the channel. Here, we highlight recent approaches taken in our laboratory to determine the oligomeric structure of native cardiac IKACh, the mechanism of activation of IKACh by G proteins, and the relevance of IKACh to cardiac physiology.
    Annals of the New York Academy of Sciences 02/2006; 868(1):386 - 398. · 4.38 Impact Factor
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    ABSTRACT: The heart rate dependence of QT interval duration is abnormal in patients with congenital long QT syndrome. Patients with LQT1 have a defective I(Ks) current, a major determinant of QT response to heart rate. We studied the heart rate dependence of QT interval duration in different long QT syndrome genotypes and control subjects using computerized QT measurements obtained from Holter recordings. The dependence of QT duration on heart rate is steeper in long QT syndrome than in control subjects (0.347 +/- 0.263 vs 0.162 +/- 0.083 at heart rate 100 beats/min; P < 0.05). In addition, QT interval is significantly longer in LQT2 and LQT3 than in LQT1 patients at slow (533 +/- 23 ms vs 468 +/- 30 ms at heart rate 60 beats/min; P < 0.0001) but not at rapid heart rate. The heart rate dependence of QT interval is steeper in LQT2 and LQT3 than in LQT1 (0.623 +/- 0.245 vs 0.19 +/- 0.079 at heart rate 100 beats/min; P < 0.05). For a given heart rate, the QT intervals vary more in LQT2 and LQT3 than in LQT1 patients (25.98 +/- 11.18 ms vs 14.39 +/- 1.55 ms; P < 0.01). Individual long QT syndrome genotypes differ with respect to QT interval dependence on heart rate. These differences may relate to the propensity of LQT2 and LQT3 patients to develop arrhythmias during bradycardia.
    Journal of Cardiovascular Electrophysiology 06/2004; 15(5):550-6. · 3.48 Impact Factor
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    ABSTRACT: Macrovoltage T wave alternans (TWA) has been described in congenital long QT syndrome (LQTS). Microvoltage T wave alternans (microV-TWA) at low heart rate (HR) is a marker of arrhythmogenic risk in many conditions, but its significance in LQTS has not been established. Twenty-three genotypically heterogeneous patients with LQTS and 16 control subjects were studied at rest and during phenylephrine and dobutamine provocation. Genotyping was established by PCR amplification and DNA sequencing of the three most common LQTS genes; KCNQ1/KVLQT1 (LQT1), KCNH2/HERG (LQT2), and SCN5A (LQT3). microV-TWA was determined using Fast Fourier transform. Precluded by ectopy, microV-TWA could not be assessed in 8 of 23 patients with LQTS. In the remaining 15 patients with LQTS, microV-TWA occurred at lower HR in LQTS than in controls (117 +/- 49 vs 153 +/- 37 beats/min; P < 0.05). Patients with LQTS developed microV-TWA at HR < 150 beats/min more often than controls (10/15 vs 2/16; P = 0.003). However, microV-TWA was not detected in the 3 individuals with a history of out-of-hospital cardiac arrest including a 14-year-old male with an F339del-KVLQT1 mutation (LQT1) who had dobutamine-provoked polymorphic ventricular tachycardia requiring external defibrillation. Catecholamine-provoked microV-TWA occurs at lower HR in patients with LQTS than in healthy people but does not identify high risk subjects.
    Pacing and Clinical Electrophysiology 08/2003; 26(8):1660-7. · 1.75 Impact Factor
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    ABSTRACT: Syncope and sudden death are associated with sympathetic stimulation in LQT1 while LQT2 patients are more susceptible to arrhythmias during nonexertional states. Abnormal spatial (QTd)- and transmural (TDR)-dispersion of repolarization may indicate increased arrhythmogenicity. This study compares the effect of phenylephrine on QTd and TDR in genotyped LQTS to control (C). Seventeen LQT1, 12 LQT2, and 18 age- and sex-matched normal controls received 2 mcg/kg of phenylephrine intravenously. At baseline and peak phenylephrine effect, BP, QT, RR, Bazett's QTc, precordial QTd (QTmax-QTmin), and T-peak to T-end (Tp-e) intervals were determined blinded to the patient's clinical and genotype status. Baseline QT intervals and QTc were significantly longer in LQT1 and LQT2 compared to C. Baseline QTd and Tp-e were greater in LQT2 than either LQT1 or C: QTd=79+/-29 ms (LQT2), 53+/-26 (LQT1), and 45+/-15 (C) and Tp-e=120+/-30 ms (LQT2), 99+/-20 (LQT1), and 90+/-11 (C). Overall, phenylephrine exerted no significant effect on either QTd or Tp-e except with subgroup analysis of symptomatic LQTS where LQT1 and LQT2 patients had a divergent response with TDR. Phenylephrine-induced bradycardia decreased TDR in symptomatic LQT1 but increased TDR in symptomatic LQT2. The observed effects of phenylephrine are consistent with the protective effect of beta-blocker in LQT1 and the increased arrhythmogenicity noted during nonexertional states in LQT2.
    Annals of Noninvasive Electrocardiology 08/2003; 8(3):208-14. · 1.08 Impact Factor
  • Jan Nemec, Win-Kuang Shen
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    ABSTRACT: Properties of several new antiarrhythmic drugs are summarised in this review article. Recent concepts concerning their safety and efficacy of antiarrhythmics are discussed. A brief perspective on possible future strategies for pharmacotherapy of arrhythmias is provided.
    Expert Opinion on Investigational Drugs 04/2003; 12(3):435-53. · 4.74 Impact Factor
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    ABSTRACT: To determine the effects of phenylephrine and dobutamine on repolarization lability in patients with genotyped long QT syndrome (LQTS). Between December 1998 and August 2000, 23 patients with genotyped LQTS (13 LQT1, 7 LQT2, and 3 LQT3) and 16 controls underwent electrocardiographic stress testing at the Mayo Clinic in Rochester, Minn. Aperiodic repolarization lability was quantified from digitized electrocardiograms recorded during catecholamine stress testing with phenylephrine and dobutamine. T-wave lability was quantified as a root-mean-square of the differences between corresponding signal values of subsequent beats. The magnitude of aperiodic T-wave lability was quantified by using a newly derived T-wave lability index (TWLI). The TWLI was significantly greater in patients with LQTS than in controls (0.0945 +/- 0.0517 vs 0.0445 +/- 0.0123; P < .003). Marked T-wave lability (TWLI > or = 0.095) was detected in all 3 LQTS genotypes (10/23) but in no controls (P < .003). There was no correlation between the TWLI and the baseline corrected QT interval. All high-risk patients having either a history of out-of-hospital cardiac arrest or syncope had a TWLI of 0.095 or greater. Beat-to-beat nonalternating T-wave lability occurs in LQT1, LQT2, and LQT3 patients during catecholamine provocation and is associated with a history of prior cardiac events. The quantification of this novel phenomenon may assist in identifying LQTS patients with increased risk of sudden cardiac death.
    Mayo Clinic Proceedings 01/2003; 78(1):40-50. · 5.79 Impact Factor
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    ABSTRACT: We observed a change in the atrial activation sequence during radiofrequency (RF) energy application in patients undergoing left accessory pathway (AP) ablation. This occurred without damage to the AP and in the absence of a second AP or alternative arrhythmia mechanism. We hypothesized that block in a left atrial "isthmus" of tissue between the mitral annulus and a left inferior pulmonary vein was responsible for these findings. Electrophysiologic studies of 159 patients who underwent RF ablation of a left free-wall AP from 1995 to 1999 were reviewed. All studies with intra-atrial conduction block resulting from RF energy delivery were identified. Fluoroscopic catheter positions were reviewed. Intra-atrial conduction block was observed following RF delivery in 11 cases (6.9%). This was evidenced by a sudden change in retrograde left atrial activation sequence despite persistent and unaffected pathway conduction. In six patients, reversal of eccentric atrial excitation during orthodromic reciprocating tachycardia falsely suggested the presence of a second (septal) AP. A multipolar coronary sinus catheter in two patients directly demonstrated conduction block along the mitral annulus during tachycardia. An isthmus of conductive tissue is present in the low lateral left atrium of some individuals. Awareness of this structure may avoid misinterpretation of the electrogram during left AP ablation and may be useful in future therapies of atypical atrial flutter and fibrillation.
    Journal of Cardiovascular Electrophysiology 08/2001; 12(7):744-9. · 3.48 Impact Factor
  • J Nemec, W K Shen
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    ABSTRACT: Congenital long QT syndromes (LQTS) and Brugada syndrome are hereditary disorders of cardiac ion channels which result in life-threatening cardiac arrhythmias or sudden cardiac death in patients with anatomically normal hearts. The pathogenesis of these dramatic events has been partially elucidated with the identification of the individual ion channels involved and understanding of the effect of some disease-causing mutations on the membrane currents and action potential. The clinical spectrum of congenital LQTS is broader than previously thought and involves certain patients previously diagnosed with idiosyncratic drug-induced proarrhythmia. The initial treatment for congenital LQTS patients involves beta-blockers in most cases. Indications for implantable cardioverter-defibrillator (ICD) or pace-maker (PM) implantation in selected individuals continue to evolve.
    Expert Opinion on Pharmacotherapy 06/2001; 2(5):773-97. · 2.86 Impact Factor

Publication Stats

556 Citations
103.86 Total Impact Points

Institutions

  • 2013
    • University of Alabama at Birmingham
      Birmingham, Alabama, United States
  • 2008–2012
    • University of Pittsburgh
      • Division of General Internal Medicine
      Pittsburgh, Pennsylvania, United States
  • 2003
    • Charles University in Prague
      Praha, Praha, Czech Republic
  • 1999–2003
    • Mayo Clinic - Rochester
      • Department of Cardiovascular Diseases
      Rochester, Minnesota, United States
    • Howard Hughes Medical Institute
      Maryland, United States
  • 2000
    • Mayo Foundation for Medical Education and Research
      • Division of Cardiovascular Diseases
      Scottsdale, AZ, United States
  • 1998–1999
    • Harvard Medical School
      • Department of Neurobiology
      Boston, Massachusetts, United States