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5. Diagnostic procedures and techniques in Heart Rhythmology and Clinical EP (rationale, materials and equipment, techniques and procedures, complications, result interpretation, indications and contraindications, ESC Guidelines)

Clinical evaluation (history and physical examination)

  • Thavendiranathan P, Bagai A, Khoo C, Dorian P, Choudhry NK. Does this patient with palpitations have a cardiac arrhythmia? JAMA 2009;302:2135-2143.
    # This review nicely describes the the accuracy of historical features, physical examination, and cardiac testing for the diagnosis of cardiac arrhythmia in patients with palpitations. A sudden onset more likely points towards AVNRT or AVRT, although an AT may also present in this way. 
  • Thrall G, Lane D, Carroll D, Lip GY. Quality of life in patients with atrial fibrillation: a systematic review. Am J Med 2006;119:448.e1–19.
    # Review describing that AF patients have a poorer quality of life than controls and that they experience lethargy, palpitations, dyspnea, chest tightness, sleeping difficulties, and psychosocial distress.
  • Abe H, Nagatomo T, Kobayashi H, Miura Y, Araki M, Kuroiwa A, Nakashima Y. Neurohumoral and hemodynamic mechanisms of diuresis during atrioventricular nodal reentrant tachycardia. Pacing Clin Electrophysiol 1997;20:2783-2788.
    # Some patients can experience polyuria during AVNRT due to atrial stretch-induced ANP activity.
  • Zimetbaum P, Josephson ME. Evaluation of patients with palpitations. N Engl J Med. 1998;338:1369-1373.
    # This manuscript describes the impact of supraventricular arrhythmias: palpitations, fatigue, light-headedness, chest discomfort, dyspnea, and altered consciousness. Dyspnea, or other clinical signs and symptoms of heart failure, can occur when the patient has developed tachycardiomyopathy. Older patients more often present with (pre)syncope.
  • Porter MJ, Morton JB, Denman R, Lin AC, Tierney S, Santucci PA, Cai JJ, Madsen N, Wilber DJ. Influence of age and gender on the mechanism of supraventricular tachycardia. Heart Rhythm 2004;1:393–396.
    # This article tells us that women are more likely to affected by AVNRT as opposed to men. Men are more affected by AVRT. The proportion of patients with AVRT decreases with age, whereas the incidence of AT and AVNRT increases with age.
  • Kirchhof P, Auricchio A, Bax J, Crijns H, Camm J, Diener HC, Goette A, Hindricks G, Hohnloser S, Kappenberger L, Kuck KH, Lip GY, Olsson B, Meinertz T, Priori S, Ravens U, Steinbeck G, Svernhage E, Tijssen J, Vincent A, Breithardt G. Outcome parameters for trials in atrial fibrillation: executive summary. Eur Heart J 2007;28:2803–2817.
    # This paper describes the modified EHRA symptom scale to describe symptom severity in AF patients.  
  • Gonzalez-Torrecilla E, Almendral J, Arenal A, Atienza F, Atea LF, del Castillo S, Fernandez Aviles F. Combined evaluation of bedside clinical variables and the electrocardiogram for the differential diagnosis of paroxysmal atrioventricular reciprocating tachycardias in patients without pre-excitation. J Am Coll Cardiol 2009;53:2353–2358.
    # Physical examination, more specifically the ‘frog sign’ points to competing influences of atrial and ventricular contraction on the tricuspid valve in AVNRT.
  • Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest 2010;137:263–272.
    # CHADS-VASc score for stroke risk prediction in AF.
  • Digby GC, Baranchuk A. Sleep apnea and atrial fibrillation; 2012 update. Curr Cardiol Rev 2012;8:265–272.
    # This review enlightens the association between AF and obstructive sleep apnoea; further elaboration on pathophysiological mechanisms.
  • Skov MW, Rasmussen PV, Ghouse J, Hansen SM, Graff C, Olesen MS, Pietersen A, Torp-Pedersen C, Haunsø S, Køber L, Svendsen JH, Holst AG, Nielsen JB. Electrocardiographic preexcitation and risk of cardiovascular morbidity and mortality. Results from the Copenhagen ECG Study. Circ Arrhythm Electrophysiol 2017;10:e004778.
    # Generally, risks due to SVT are small, although patients with WPW and AF have a higher risk of SCD.
  • Brignole M, Moya A, de Lange FJ, Deharo JC, Elliott PM, Fanciulli A, Fedorowski A, Furlan R, Kenny RA, Martín A, Probst V, Reed MJ, Rice CP, Sutton R, Ungar A, van Dijk JG; ESC Scientific Document Group. Practical instructions for the 2018 ESC guidelines for the diagnosis and management of syncope. The Task Force for the diagnosis and management of syncope of the European Society of Cardiology (ESC). Eur Heart J 2018;39:e43–e80.
    # Syncope occurring during strenuous exercise, while sitting or in the supine position should always raise the suspicion of a cardiac cause, while other situational events may indicate vasovagal syncope or postural hypotension.
  • Jouven X, Desnos M, Guerot C, Ducimetiere P. Predicting sudden death in the population: the Paris Prospective Study I. Circulation 1999;99:1978–1983.
  • Friedlander Y, Siscovick DS, Weinmann S, Austin MA, Psaty BM, Lemaitre RN, Arbogast P, Raghunathan TE, Cobb LA. Family history as a risk factor for primary cardiac arrest. Circulation 1998;97:155–160.
    # Both manuscripts are seminal as they demonstrated that a positive family history of SCD is a strong independent predictor of susceptibility to VA and SCD.
  • Costantino G, Sun BC, Barbic F, Bossi I, Casazza G, Dipaola F, McDermott D, Quinn J, Reed MJ, Sheldon RS, Solbiati M, Thiruganasambandamoorthy V, Beach D, Bodemer N, Brignole M, Casagranda I, Del Rosso A, Duca P, Falavigna G, Grossman SA, Ippoliti R, Krahn AD, Montano N, Morillo CA, Olshansky B, Raj SR, Ruwald MH, Sarasin FP, Shen WK, Stiell I, Ungar A, Gert van Dijk J, van Dijk N, Wieling W, Furlan R. Syncope clinical management in the emergency department: a consensus from the first international workshop on syncope risk stratification in the emergency department. Eur Heart J. 2016 May 14;37(19):1493-1498.

Electrocardiography (ECG)

Conventional 12-lead ECG

  • Wellens HJ, Schwartz PJ, Lindemans FW, Buxton AE, Goldberger JJ, Hohnloser SH, Huikuri HV, Kaab S, La Rovere MT, Malik M, Myerburg RJ, Simoons ML, Swedberg K, Tijssen J, Voors AA, Wilde AA. Risk stratification for sudden cardiac death: current status and challenges for the future. Eur Heart J 2014;35:1642–1651.
    # This review also nicely wraps up ECG features, next to other parameters, related to SCD risk prediction.
  • Enriquez A, Baranchuk A, Briceno D, Saenz L, Garcia F. How to use the 12-lead ECG to predict the site of origin of idiopathic ventricular arrhythmias. Heart Rhythm. 2019;16:1538-1544.
    # In this review, a stepwise anatomical approach for the localization of idiopathic ventricular arrhythmias is provided based on sequential analysis of the most relevant ECG features.
  • Eranti A, Aro AL, Kenttä T, Holkeri A, Tikkanen JT, Junttila MJ, Huikuri HV. 12-Lead electrocardiogram as a predictor of sudden cardiac death: from epidemiology to clinical practice. Scand Cardiovasc J. 2016;50:253-259.
    # In this review, the current knowledge of the prognostic significance of ECG predictors of SCD in the general population, and in patients with coronary heart disease, heart failure, cardiomyopathies, and in inheritable arrhythmia syndromes is described. Also, insights into the novel digital ECG signal processing techniques are provided.
  • Straus SMJM, Kors JA, De Bruin ML, van der Hooft CS, Hofman A, Heeringa J, Deckers JW, Kingma JH, Sturkenboom MCJM, Stricker BHC, Witteman JCM. Prolonged QTc interval and risk of sudden cardiac death in a population of older adults. J Am Coll Cardiol 2006;47:362–367.
    # Paper on QTc analysis and SCD risk prediction: subjects > 55 years of age a prolonged QTc >450 ms in men and >470 ms in women is associated with a 3-fold increase risk of SCD.
  • Tikkanen JT, Anttonen O, Junttila MJ, Aro AL, Kerola T, Rissanen HA, Reunanen A, Huikuri HV. Long-term outcome associated with early repolarization on electrocardiography. N Engl J Med 2009;361:2529–2537.
    # Prevalence and prognostic significance of early repolarization in the inferior/lateral leads of the 12-lead ECG over a mean follow-up of 30 years was determined. When stratified according to the degree of J-point elevation (≥0.2 mV) in inferior and/or lateral leads, there was a three-fold higher risk for both death from cardiac causes and from arrhythmias.
  • Aro AL, Anttonen O, Tikkanen JT, Junttila MJ, Kerola T, Rissanen H, Reunanen A, Huikuri HV. Intraventricular conduction delay in a standard 12-lead electrocardiogram as a predictor of mortality in general population. Circ Arrhythm Electrophysiol 2011;4:704–710.
    # Prolonged QRS duration in a standard 12-lead ECG is associated with increased mortality in a general population, with intraventricular conduction delay being most strongly associated with an increased risk of arrhythmic death.
  • Aro AL, Anttonen O, Kerola T, Tikkanen JT, Junttila MJ, Rissanen H, Reunanen A, Huikuri HV. Prevalence and prognostic significance of T-wave inversions in right precordial leads of a 12-lead electrocardiogram in the middle-aged subjects. Circulation 2012;125:2572–2577.
    # T-wave inversions in right precordial leads are relatively rare in the general population, and are not associated with adverse outcome. Increased mortality risk associated with inverted T waves in other leads may reflect the presence of an underlying structural heart disease.
  • Aro AL, Huikuri HV, Tikkanen JT, Junttila MJ, Rissanen HA, Reunanen A, Anttonen O. QRS-T angle as a predictor of sudden cardiac death in a middle-aged general population. Europace 2012;14:8710–8712.
    # In a middle-aged general population, Frontal QRS-T angle ≥ 100° increases the risk of arrhythmic death.
  • Aro AL, Anttonen O, Kerola T, Junttila MJ, Tikkanen JT, Rissanen HA, Reunanen A, Huikuri HV. Prognostic significance of prolonged PR interval in the general population. Eur Heart J. 2014;35:123-129.
    # In the middle-aged general population, prolonged PR interval normalizes in a substantial proportion of subjects during the time course, andit is not associated with an increased risk of all-cause or cardiovascular mortality.
  • Fitzmaurice DA, Hobbs FD, Jowett S, Mant J, Murray ET, Holder R, Raftery JP, Bryan S, Davies M, Lip GY, Allan TF. Screening versus routine practice in detection of atrial fibrillation in patients aged 65 or over: cluster randomised controlled trial. BMJ 2007;335:383.
    # Active screening for atrial fibrillation detects additional cases over current practice. The preferred method of screening in patients aged 65 or over in primary care is opportunistic pulse taking with follow-up electrocardiography.

ECG monitoring (Holter, event monitoring, implantable event and loop monitoring) 

  • Giada F, Bertaglia E, Reimers B, Noventa D, Raviele A. Current and emerging indications for implantable cardiac monitors. Pacing Clin Electrophysiol 2012;35:1169-1178.
    # Review on indications for implantable loop recorders: symptomatic and asymptomatic arrhythmias, syncope, VT, syncope.
  • Giancaterino S, Lupercio F, Nishimura M, Hsu JC. Current and future use of insertable cardiac monitors. JACC: Clinical Electrophysiology 2018;4:1383-1396.
    # This review outlines the current use of ICM for syncope and AF detection, summarizes the latest guidelines and evidence, and describe future implications of ICM use specifically for detection of subclinical AF in patients with cryptogenic stroke.
  • Krahn AD, Klein GJ, Yee R, Skanes AC. Randomized assessment of syncope trial: conventional diagnostic testing versus a prolonged monitoring strategy. Circulation 2001;104:46-51.# Randomized controlled trial demonstrating a diagnosis in 55% of patients in the ICM arm compared with 19% in the control arm.
  • Edvardsson N, Frykman V, van Mechelen R, et al. Use of an implantable loop recorder to increase the diagnostic yield in unexplained syncope: results from the PICTURE registry. Europace 2011;13:262-269.
    # ICMs assisted in diagnosis in 30% of patients.
  • Volosin K, Stadler RW, Wyszynski R, Kirchhof P. Tachycardia detection performance of implantable loop recorders: results from a large ‘real-life’ patient cohort and patients with induced ventricular arrhythmias. Europace 2013;15:1215–1222.
    # ILR are useful in syncopes that are infrequent and that are suspected to be related to arrhythmias.
  • Sanna T, Diener HC, Passman RS, et al. Cryptogenic stroke and underlying atrial fibrillation. N Engl J Med 2014:2478-2486.
    # The development of long-term ECG monitoring through insertable cardiac monitors has greatly improved the ability to detect AF after cryptogenic stroke, evidenced most notably in the landmark CRYSTAL-AF (Cryptogenic Stroke and Underlying Atrial Fibrillation) study.
  • de Asmundis C, Conte G, Sieira J, Chierchia GB, Rodriguez-Manero M, Di Giovanni G, Ciconte G, Levinstein M, Baltogiannis G, Saitoh Y, Casado-Arroyo R, Brugada P. Comparison of the patient-activated event recording system vs. traditional 24 h Holter electrocardiography in individuals with paroxysmal palpitations or dizziness. Europace 2014;16:1231–1235.
    # Cardiac event recorders are recommended to investigate whether symptoms as palpitations or dizziness are attributable to transient arrhythmias.
  • A. Moya, R. Sutton, F. Ammirati, et al. Guidelines for the diagnosis and management of syncope (version 2009) Eur Heart J 2009;30;2631-2671.
    # Insertable cardiac monitors are useful in patients with recurrent unexplained syncope and carry Class I and II recommendations for this indication from major society guidelines.
  • Brignole M, Vardas P, Hoffman E, et al. Indications for the use of diagnostic implantable and external ECG loop recorders. Europace 2009;11:671-687.
    # EHRA 2009 position paper on indications for the use of diagnostic implantable and external ECG loop recorders provided a Class IIA recommendation for ICM use in select cases of severe infrequent palpitations when other ECG monitoring systems fail to document cause.

Heart rate variability and baroreflex sensitivity

  • Stein KM. Noninvasive riskstratification for sudden death: signal-averaged electrocardiography, nonsustained ventricular tachycardia, heart rate variability, baroreflex sensitivity, and QRS duration. Prog Cardiovasc Dis 2008;51:106-117.
  • # This review focusses on several proposed noninvasive methods for SCD risk stratification: signal-averaged electrocardiography (SAECG), detection of nonsustained ventricular tachycardia (NSVT), measurement of heart rate variability (HRV) and baroreflex sensitivity (BRS).
  • Chen PS, Chen LS, Fishbein MC, Lin SF, Nattel S. Role of the autonomic nervous system in atrial fibrillation: pathophysiology and therapy. Circ Res 2014;114:1500-1515.
  • # This review focusses on the relationship between the autonomic nervous system and the pathophysiology of AF and the potential benefit and limitations of neuromodulation in the management of this arrhythmia.
  • Goldberger JJ, Subačius H, Patel T, Cunnane R, Kadish AH. Sudden cardiac death risk stratification in patients with nonischemic dilated cardiomyopathy. J Am Coll Cardiol 2014;63:1879-1889.
    # Meta-analysis to estimate the performance of different techniques incorporating functional parameters, depolarization abnormalities, repolarization abnormalities, and arrhythmic markers for SCD risk stratification: only modest risk stratification for sudden cardiac death is found in patients with nonischemic dilated cardiomyopathy. 
  • Schwartz PJ, Vanoli E, Stramba-Badiale M, De Ferrari GM, Billman GE, Foreman RD. Autonomic mechanisms and sudden death. New insights from analysis of baroreceptor reflexes in conscious dogs with and without a myocardial infarction. Circulation 1988;78:969-979.
    # This study demonstrates that the presence of a reduced BRS is associated with a greater susceptibility to ventricular fibrillation during subsequent ischemic episodes. BRS is reduced after an MI. The results in 192 conscious dogs with a healed MI indicate that analysis of BRS is a powerful tool for risk stratification not only after, but even before, the occurrence of an MI.
  • La Rovere MT, Bigger JT Jr, Marcus FI, Mortara A, Schwartz PJ. Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction. ATRAMI (Autonomic Tone and Reflexes After Myocardial Infarction) Investigators. Lancet 1998;351:478-484.
  • # ATRAMI provides clinical evidence that after myocardial infarction the analysis of vagal reflexes has significant prognostic value independently of LVEF and of ventricular arrhythmias and that it significantly adds to the prognostic value of heart-rate variability.
  • La Rovere MT, Pinna GD, Hohnloser SH, Marcus FI, Mortara A, Nohara R, Bigger JT Jr, Camm AJ, Schwartz PJ; ATRAMI Investigators. Autonomic Tone and Reflexes After Myocardial Infarction. Baroreflex sensitivity and heart rate variability in the identification of patients at risk for life-threatening arrhythmias: implications for clinical trials. Circulation 2001;103:2072-2077.
    # BRS and HRV contribute importantly and additionally to risk stratification. Particularly when LVEF is depressed, the analysis of BRS identifies a large number of patients at high risk for cardiac and arrhythmic mortality who might benefit from implantable cardioverter defibrillator therapy without disproportionately increasing the number of false-positives.
  • Malik M, Camm AJ, Janse MJ, Julian DG, Frangin GA, Schwartz PJ. Depressed heart rate variability identifies postinfarction patients who might benefit from prophylactic treatment with amiodarone: a substudy of EMIAT (the European Myocardial Infarct Amiodarone Trial). J Am Coll Cardiol 2000;35:1263–1275.
  • # Measurement of HRV in a large set of centrally processed Holter recordings is feasible with robust methods of assessment. Patients with LVEF < or =40% and depressed HRV benefit from prophylactic antiarrhythmic treatment with amiodarone. 
  • Schwartz PJ1, Vanoli E, Crotti L, Spazzolini C, Ferrandi C, Goosen A, Hedley P, Heradien M, Bacchini S, Turco A, La Rovere MT, Bartoli A, George AL Jr, Brink PA. Neural control of heart rate is an arrhythmia risk modifier in long QT syndrome. J Am Coll Cardiol 2008;51:920-929.
    # Lower resting HR and "relatively low" BRS are protective factors in KCNQ1-A341V carriers. 
  • Huikuri HV, Exner DV, Kavanagh KM, Aggarwal SG, Mitchell LB, Messier MD, Becker D, Sheldon RS, Bloch Thomsen PE; CARISMA and REFINE Investigators. Attenuated recovery of heart rate turbulence early after myocardial infarction identifies patients at high risk for fatal or near-fatal arrhythmic events. Heart Rhythm 2010;7:229-235.
    # Attenuated recovery of autonomic function early after MI consistently predicts a higher risk of fatal or near-fatal arrhythmic events. 
  • Crotti L, Spazzolini C, Porretta AP, Dagradi F, Taravelli E, Petracci B, Vicentini A, Pedrazzini M, La Rovere MT, Vanoli E, Goosen A, Heradien M, George AL Jr, Brink PA, Schwartz PJ. Vagal reflexes following an exercise stress test: a simple clinical tool for gene-specific risk stratification in the long QT syndrome. J Am Coll Cardiol 2012;60:2515-2524.
  • # This manuscript demonstrates that heart rate reduction post-exercise identifies LQT1 patients at high or low arrhythmic risk, independently of β-blocker therapy, and contributes to risk stratification. Intense exercise training, which potentiates vagal reflexes, should probably be avoided by LQT1 patients.

Signal-averaged ECG 

  • Stein KM. Noninvasive risk stratification for sudden death: signal-averaged electrocardiography, nonsustained ventricular tachycardia, heart rate variability, baroreflex sensitivity, and QRS duration. Prog Cardiovasc Dis 2008;51:106-117.
  • # This review focusses on several proposed noninvasive methods for SCD risk stratification: signal-averaged electrocardiography (SAECG), detection of nonsustained ventricular tachycardia (NSVT), measurement of heart rate variability (HRV) and baroreflex sensitivity (BRS).
  • Darbar D, Jahangir A, Hammill SC, Gersh BJ. P wave signal-averaged electrocardiography to identify risk for atrial fibrillation. Pacing Clin Electrophysiol 2002;25:1447–1453.
  • # This review demonstrates that the combination of P wave duration with other predictors for AF improves the diagnostic value of P wave SAECG.
  • Blomström-Lundqvist C, Hirsch I, Olsson SB, Edvardsson N. Quantitative analysis of the signal-averaged QRS in patients with arrhythmogenic right ventricular dysplasia. Eur Heart J 1988;9:301–312.
    # This manuscript describes aberrant parameters of temporal signal averaging of the surface QRS in ARVC patients.
  • Leclerq JF, Coumel P. Late potentials in arrhythmogenic right ventricular dysplasia. Prevalence, diagnostic and prognostic values. Eur Heart J 1993;14: 80–83.
    # Prevalence of late potentials was 75% (39/52) in patients with ARVD, 19% (25/132) in patients with apparently idiopathic ventricular arrhythmias, and 4% (4/45) in controls (P < 0.01). In ARVD, no relationship was found between LP and age, type of ventricular arrhythmia (sustained or not), or extent of the disease on angiography. 
  • Abe Y, Fukunami M, Yamada T, Ohmori M, Shimonagata T, Kumagai K, Kim J, Sanada S, Hori M, Hoki N.Prediction of transition to chronic atrial fibrillation in patients with paroxysmal atrial fibrillation by signal-averaged electrocardiography: a prospective study. Circulation 1997;96:2612-2616.
    # This prospective study of 122 AF patients shows that P-wave-triggered signal-averaged ECG (P-SAE) is useful for the prediction of the transition to CAF in patients with PAF.
  • Yamada T, Fukunami M, Shimonagata T, Kumagai K, Sanada S, Ogita H, Asano Y, Hori M, Hoki N. Dispersion of signal-averaged P wave duration on precordial body surface in patients with paroxysmal atrial fibrillation. Eur Heart J 1999;20:211-220.
    # Increased dispersion of signal-averaged P wave duration plays an important role in generating paroxysmal atrial fibrillation.
  • Nava A, Folino AF, Bauce B, Turrini P, Buja GF, Daliento L, Thiene G. Signal-averaged electrocardiogram in patients with arrhythmogenic right ventricular cardiomyopathy and ventricular arrhythmias. Eur Heart J 2000;21:58–65.
    # The signal averaged ECG was abnormal in 94.4% of patients with the extensive form of the disease, in 77.7% of patients with the moderate form and in 31.8% of patients with the minor form, demonstrating good correlation with the extent of the disease.
  • Blanche C, Tran N, Rigamonti F, Burri H, Zimmermann M. Value of P-wave signal averaging to predict atrial fibrillation recurrences after pulmonary vein isolation. Europace 2013;15:198-204.
    # A filtered P-wave duration >140 ms is a marker of AF recurrences after RFCA-PVI and probably reflects the extent of atrial remodeling.

T-wave and micro-T wave alternans 

  • Aro AL, Kenttä TV, Huikuri HV. Microvolt T-wave Alternans: Where are we now? Arrhythm Electrophysiol Rev 2016;5:37-40.
    # Short and snappy overview of TWA, the method and it’s clinical implementation.
  • Verrier RL, Klingenheben T, Malik M, et al. Microvolt T-wave alternans physiological basis, methods of measurement, and clinical utility--consensus guideline by International Society for Holter and Noninvasive Electrocardiology. J Am Coll Cardiol 2011;58:1309–1324.
    # The spectral method has demonstrated TWA to be predictive of future cardiovascular events in >8,000 patients mostly with ischaemic heart disease and prior MI, but also in non-ischaemic cardiomyopathy and heart failure. The prognostic significance of the MMA method has been demonstrated in >6,000 patients with reduced and preserved LVEF, including those with coronary artery disease and prior MI. 
  • Nieminen T, Lehtimaki T, Viik J, et al. T-wave alternans predicts mortality in a population undergoing a clinically indicated exercise test. Eur Heart J 2007;28:2332–2337.
    # Time-domain TWA analysis powerfully predicts mortality in a general population undergoing a clinical exercise test.
  • Merchant FM, Ikeda T, Pedretti RF, et al. Clinical utility of microvolt T-wave alternans testing in identifying patients at high or low risk of sudden cardiac death. Heart Rhythm 2012;9:1256–1264.
    # In a pooled cohort of patients with EF ≤35 % but no ICD therapy, negative TWA was associated with a low incidence of SCD, compared with substantial SCD risk associated with both positive TWA and indeterminate TWA.
  • Chow T, Kereiakes DJ, Onufer J, et al. Does microvolt T-wave alternans testing predict ventricular tachyarrhythmias in patients with ischemic cardiomyopathy and prophylactic defibrillators? The MASTER (Microvolt T Wave Alternans Testing for Risk Stratification of Post-Myocardial Infarction Patients) trial. J Am Coll Cardiol 2008;52:1607–1615.
    # In the Microvolt T Wave Alternans Testing for Risk Stratification of Post MI Patients (MASTER I) study, which enrolled MADIT-II (Second Multicenter Automated Defibrillator Implantation Trial) type ICD-patients with LVEF ≤30 %, risk of ventricular arrhythmias did not differ according to TWA classification, despite differences in total mortality rates.
  • Gold MR, Ip JH, Costantini O, et al. Role of microvolt T-wave alternans in assessment of arrhythmia vulnerability among patients with heart failure and systolic dysfunction: Primary results from the T-wave alternans sudden cardiac death in heart failure trial substudy. Circulation 2008;118:2022–2028.
    # In the SCD-HeFT ICD-study (Sudden Cardiac Death in Heart Failure Trial), TWA could not predict arrhythmic events or mortality.
  • Costantini O, Hohnloser SH, Kirk MM, et al. The ABCD (alternans before cardioverter defibrillator) trial: Strategies using T-wave alternans to improve efficiency of sudden cardiac death prevention. J Am Coll Cardiol 2009;53:471–479.
    # In the ABCD (Alternans Before Cardioverter Defibrillator) study, event rates were over twofold higher both among patients with positive TWA and positive electrophysiological study at the pre-specified 1-year endpoint. However, TWA did not predict endpoint events at 2 years. 

Body surface mapping and ECGI

  • Rudy Y. Noninvasive electrocardiographic imaging of arrhythmogenic substrates in humans. Circ Res 2013;112:863-874.
    # Review on electrocardiographic imaging of human hearts with examples of heart failure, myocardial infarction, atrial fibrillation and abnormal ventricular repolarization including a brief description of the ECGI methodology.
  • Cluitmans M, Brooks DH, MacLeod R, Dössel O, Guillem MS, van Dam PM, Svehlikova J, He B, Sapp J, Wang L, Bear L. Validation and opportunities of electrocardiographic imaging: from technical achievements to clinical applications. Front Physiol 2018;9:1305.
    # Comprehensive translational review on technical aspects, validation, clinical applications including personalized medicine.
  • Ramanathan C, Jia P, Ghanem R, Ryu K, Rudy Y. Activation and repolarization of the normal human heart under complete physiological conditions. Proc Natl Acad Sci U S A 2006;103:6309-6314.
    # Comprehensive evaluation of normal activation and repolarization of healthy human heart under physiological conditions.
  •   Cuculich PS, Zhang J, Wang Y, Desouza KA, Vijayakumar R, Woodard PK, Rudy Y. The electrophysiological cardiac ventricular substrate in patients after myocardial infarction: noninvasive characterization with electrocardiographic imaging. J Am Coll Cardiol 2011;58:1893-1902.
    # This paper demonstrates the correlation between myocardial scar detected with ECGI and DE-MRI/SPECT.
  • Vijayakumar R, Silva JN, Desouza KA, Abraham RL, Strom M, Sacher F, Van Hare GF, Haïssaguerre M, Roden DM, Rudy Y. Electrophysiologic substrate in congenital long QT syndrome: Noninvasive mapping with electrocardiographic imaging (ECGI). Circulation 2014;130:1936-1943.
    # This paper is the first to describe steep epicardial repolarization gradients in LQTS patients, being more  pronounced in symptomatics. 
  • Zhang J, Sacher F, Hoffimayer K, O’Hara T, Strom M, Cuculich P, Silva J, Cooper D, Faddis M, Hocini M, Haïssagueree M, Scheinman M, Rudy Y. The Cardiac electrophysiologic substrate underlying the ECG phenotype and electrogram abnormalities in Brugada syndrome patients. Circulation 2015;131:1950-1959.
    # This paper demonstrated that Brugada patients have a combination of slow discontinuous conduction and steep gradients dispersion of repolarization in the RVOT.
  • Ramanathan C, Ghanem RN, Jia P, Ryu K, Rudy Y. Noninvasive electrocardiographic imaging for cardiac electrophysiology and anatomy. Nature Med 2004;10:422-428.
    # This article provides ECGI recorded atrial and ventricular activation during normal SR, RBBB, RV/LV pacing and atrial flutter.
  • Jia P, Ramanathan C, Ghanem RN, Ryu K, Varma N, Rudy Y. Electrocardiographic imaging of cardiac resynchronization therapy in heart failure: observation of variable electrophysiologic responses. Heart Rhythm 2006;3:296-310.
    # This manuscript demonstrates heterogeneous activation patterns in LBBB and the efficacy of multisite pacing. 
  • Cuculich PS, Wang Y, Lindsay BD, Faddis MN, Schuessler RB, Damiano RJ Jr, Li L, Rudy Y. Noninvasive characterization of epicardial activation in humans with diverse atrial fibrillation patterns. Circulation 2010;122:1364-1372.
    # This paper highlights heterogenous and complex epicardial activation patterns in AF patients.
  • Cluitmans M, Bonizzi P, Karel JMH, Das M, Kietselaer BLJH, de Jong MMJ, Prinzen FW, Peeters RLM, Westra RL, Volders PGA. In vivo validation of electrocardiographic imaging. JACC Clin Electrophysiol 2017;3:232-242.
    # Experimental epicardial validation of ECGI and contact mapping showing a 10-mm precision of activation localization.
  • Cochet H, Dubois R, Yamashita S, Jefairi N, Berte B, Sellal JM, Hooks D, Frontera A, Amraoui S, Zemoura A, Denis A, Derval N, Sacher F, Corneloup O, Latrabe V, Clément-Guinaudeau S, Relan J, Zahid S, Boyle P, Trayanova N, Bernus O, Montaudon M, Laurent F, Hocini M, Haïssaguerre M, Jaïs P. Relationship between fibrosis detected on late gadolinium-enhanced cardiac magnetic resonance and re-entrant activity assessed with electrocardiographic imaging in human persistent atrial fibrillation. JACC Clin Electrophysiol 2018;4:17-29.
    # In this paper the relation is found between number of re-entrant regions on ECGI and extent of LGE on CMR.
  • Duchateau J, Sacher F, Pambrun T, Derval N, Chamorro-Servent J, Denis A, Ploux S, Hocini M, Jaïs P, Bernus O, Haïssaguerre M, Dubois R. Performance and limitations of noninvasive cardiac activation mapping. Heart Rhythm. 2019 Mar;16(3):435-442.
    # The manuscript highlights the challenges in obtaining accurate ECGI in clinical settings.

ECG-pharmacological tests

Type I drugs for His-Purkinje system challenge

  • Englund A, Bergfeldt L, Rosenqvist M. Pharmacological stress testing of the His-Purkinje system in patientswith bifascicular block. PACE-Pacing Clin Electrophysiol 1998;21:1979–1987.
    # This literature review, based mainly on the English-language literature, focuses on pharmacological stress testing of the His-Purkinje system (using ajmaline, procainamide, disopyramide and flecainide) as part of an invasive electrophysiological study. 
  • Gronda M, Magnani A, Occhetta E, Sauro G, D’Aulerio M, Carfora A, Rossi P. Electrophysiological study of atrio-ventricular block and ventricular conduction defects. Prognostic and therapeutical implications. G Ital Cardiol 1983;14:768-773.
    # This article describes the prognostic value of ajmaline induced HV prolongation >120 ms or development of 2nd or 3rd degree AVB in a relatively large patient population.
  • Twidale N, Heddle WF, Tonkin AM. Procainamide administration during electrophysiology study–utility as a provocative test for intermittent atrioventricular block. Pacing Clin Electrophysiol 1988;11:1388-1397.
    # Procainamide in patients with intermittent AV block has limited value.
  • Kaul U, Dev V, Narula J, Malhotra AK, Talwar KK, Bhatia ML. Evaluation of patients with bundle branch block and ‘unexplained’ syncope: a study based on comprehensive electrophysiological testing and ajmaline stress. Pacing Clin Electrophysiol 1988;11:289-297.
    # This paper shows that ajmaline provocation is useful to unmask infra-His block.
  • Bergfeldt L, Edvardsson N, Rosenqvist M, Vallin H, Edhag O. Atrioventricular block progression in patients with bifascicular block assessed by repeated electrocardiography and a bradycardia-detecting pacemaker. Am J Cardiol 1994;74:1129-1132.
    # This study reports on the prognostic information of disopyramide stress testing in patients with bifascicular block and syncope.
  • Pentimalli F, Bacino L, Ghione M, Siri G, Gazzarata M, Bellotti P. Ajmaline challenge to unmask infrahisian disease in patients with recurrent and unexplained syncope, preserved ejection fraction, with or without conduction abnormalities on surface ECG. J Atr Fibrillation 2016;9:37–42.
    # Ajmaline challenge can unmask infrahisian disease if an HV interval of < 70 ms prolongs to more than 100 ms after the class I challenge.
  • Roca-Luque I, Francisco-Pasqual J, Oristrell G, Rodríguez-García J, Santos-Ortega A, Martin-Sanchez G, Rivas-Gandara N, Perez-Rodon J, Ferreira-Gonzalez I, García-Dorado D, Moya-Mitjans A. Flecainide versus procainamide in electrophysiological study in patients with syncope and wide QRS duration. JACC Clin Electrophysiol 2019;5:212-219.
    # Direct comparison of procainamide and flecainide demonstrates that the latter has a higher diagnostic yield to stress the His-Purkinje system in syncope patients with BBB but normal baseline HV interval.

Type I drugs for Brugada ECG unmasking

  • Brugada R, Brugada P, Brugada J. Electrocardiogram interpretation and class I blocker challenge in Brugada syndrome. J Electrocardiol 2006;39:S115-S118.
    # Detailed review describing in detail electrocardiographic changes present in the Brugada syndrome at rest, during sodium channel blockers and it’s value for risk assessment.
  • Sarquella-Brugada G, Campuzano O, Arbelo E, Brugada J, Brugada R. Brugada syndrome: clinical and genetic findings. Genet Med 2016;18:3-12.
    # Comprehensive review incorporating detailed information on pharmalogical provocation to unmask the Brugada syndrome: indications, different class IC antiarrhythmic agents, false-negative results.
  • Poli S, Toniolo M, Maiani M, Zanuttini D, Rebellato L, Vendramin I, Dametto E, Bernardi G, Bassi F, Napolitano C, Livi U, Proclemer A. Management of untreatable ventricular arrhythmias during pharmacologic challenges with sodium channel blockers for suspected Brugada syndrome. Europace 2018;20(2):234-242.
    # This review elaborates on potential life-threatening proarrhythmic deterioration during pharmacologic challenge with Class I AAD.
  • Hong K, Brugada J, Oliva A, Berruezo-Sanchez A, Potenza D, Pollevick GD, Guerchicoff A, Matsuo K, Burashnikov E, Dumaine R, Towbin JA, Nesterenko V, Brugada P, Antzelevitch C, Brugada R. Value of electrocardiographic parameters and ajmaline test in the diagnosis of Brugada syndrome caused by SCN5A mutations. Circulation 2004;110:3023–3027.
    # Nearly 25% of drug-induced test appeared false-negative in SCN5A mutation carriers.
  • Wolpert C, Echternach C, Veltmann C, Antzelevitch C, Thomas GP, Spehl S, Streitner F, Kuschyk J, Schimpf R, Haase KK, Borggrefe M. Intravenous drug challenge using flecainide and ajmaline in patients with Brugada syndrome. Heart Rhythm. 2005;2:254–260.
    # The purpose of this study was to compare the effect of intravenous flecainide and ajmaline with respect to their ability to induce or accentuate the typical ECG pattern of Brugada syndrome. The ajmaline seemed to be more effective.
  • Morita H, Zipes DP, Wu J. Brugada syndrome: insights of ST elevation, arrhythmogenicity, and risk stratification from experimental observations. Heart Rhythm 2009;6:S34–S43.
    # This study demonstrates the unequal response to IV administration of flecainide and ajmaline, suggesting ajmaline is better at unmasking the ECG pattern. 
  • Probst V, Wilde AA, Barc J, Sacher F, Babuty D, Mabo P, Mansourati J, Le Scouarnec S, Kyndt F, Le Caignec C, Guicheney P, Gouas L, Albuisson J, Meregalli PG, Le Marec H, Tan HL, Schott JJ. SCN5A mutations and the role of genetic background in the pathophysiology of Brugada syndrome. Circ Cardiovasc Genet 2009;2:552-557.
    # This study shows that SCN5A negative family members of Brugada syndrome patients can have positive ajmaline provocation tests, highlighting the importance of genetic background.
  • Conte G, Dewals W, Sieira J, de Asmundis C, Ciconte G, Chierchia GB, Di Giovanni G, Baltogiannis G, Saitoh Y, Levinstein M, La Meir M, Wellens F, Pappaert G, Brugada P. Drug-induced brugada syndrome in children: clinical features, device-based management, and long-term follow-up. J Am Coll Cardiol 2014;63:2272–2279.
    # This manuscript demonstrated that children <12 years have a higher rate of ajmaline-induced major ventricular arrhythmias.
  • Gandjbakhch E, Fressart V, Duthoit G, Marquié C, Deharo JC, Pousset F, Hebert JL, Simon F, Himbert C, Klug D, Charron P, Hidden-Lucet F. Malignant response to ajmaline challenge in SCN5A mutation carriers: experience from a large familial study. Int J Cardiol 2014;172:256-258. 
    # This study identified conduction abnormalities as risk factor for ventricular arrhythmias.
  • Conte G, Sieira J, Sarkozy A, de Asmundis C, Di Giovanni G, Chierchia GB, Ciconte G, Levinstein M, Casado-Arroyo R, Baltogiannis G, Saenen J, Saitoh Y, Pappaert G, Brugada P. Life-threatening ventricular arrhythmias during ajmaline challenge in patients with Brugada syndrome: incidence, clinical features and prognosis. Heart Rhythm 2013;10:1869-1874.
    # This study identified that sinus node dysfunction is associated with increased risk of major arrhythmias.
  • Therasse D, Sacher F, Babuty D, Mabo P, Mansourati J, Kyndt F, Redon R, Schott JJ, Barc J, Probst V, Gourraud JB. Value of the sodium-channel blocker challenge in Brugada syndrome. Int J Cardiol 2017;245:178-180.
    # Large registry of consecutive patients showing that ajmaline challenge has an excellent sensitivity to rule out Brugada syndrome; flecainide is inferior.
  • Miyazaki T, Mitamura H, Miyoshi S, Soejima K, Aizawa Y, Ogawa S. Autonomic and antiarrhythmic drug modulation of ST segment elevation in patients with Brugada syndrome. J Am Coll Cardiol 1996;27:1061-1070.
    # Modulation of ST segment by selective stimulation of alpha-adrenoceptors or by class IA drugs. Mitigation by beta-adrenergic stimulation.
  • Wilde AA, Antzelevitch C, Borggrefe M, et al. Proposed diagnostic criteria for the Brugada syndrome: consensus report. Circulation 2002;106:2514. 
  • Antzelevitch C, Brugada P, Borggrefe M, et al. Brugada syndrome: report of the second consensus conference: endorsed by the Heart Rhythm Society and the European Heart Rhythm Association. Circulation 2005;111:659–670.
    # Suggests to adopt cautious protocols interrupting the sodium channel blocker test as soon as Brugada pattern type I emerges, QRS broadens to ≥130% of baseline or frequent PVCs appear.
  • Priori SG, Wilde AA, Horie M,, Cho Y, Behr ER, Berul C et al. Executive summary: HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes. Europace 2013;15:389–406.
    # Suggests to monitor the patient with right precordial leads positioned also in the upper intercostal spaces (third and second), as it is normal practice for baseline-ECG identification of Brugada type I.

Adrenaline for congenital long QT syndrome unmasking 

  • Vyas H, Ackerman MJ. Epinephrine QT stress testing in congenital long QT syndrome. J Electrocardiol 2006;39:S107-113.
    # Comprehensive review on the epinephrine QT stress test, explaining the pathological basis of differential responses among patients and healthy individuals, and describing the methodology for conducting the test and the interpretation of the responses. It also highlights the differences between the two major LQTS epinephrine QT stress test protocols, the Mayo protocol and the Shimizu protocol.
  • Ackerman MJ, Khositseth A, Tester DJ, Hejlik JB, Shen WK, Porter CB. Epinephrine-induced QT interval prolongation: a gene-specific paradoxical response in congenital long QT syndrome. Mayo Clin Proc 2002;77:413-421.
    # Low-dose epinephrine infusion discriminated LQTS1 patients from controls.
  • Noda T, Takaki H, Kurita T, Suyama K, Nagaya N, Taguchi A, Aihara N, Kamakura S, Sunagawa K, Nakamura K, Ohe T, Horie M, Napolitano C, Towbin JA, Priori SG, Shimizu W. Gene-specific response of dynamic ventricular repolarization to sympathetic stimulation in LQT1, LQT2 and LQT3 forms of congenital long QT syndrome. Eur Heart J 2002;23:975-983.
    # There is a dynamic response of ventricular repolarization to sympathetic stimulation, which is different between LQT1, LQT2 and LQT3.
  • Shimizu W, Noda T, Takaki H, Kurita T, Nagaya N, Satomi K. Epinephrine unmasks latent mutation carriers with LQT1 form of congenital long-QT syndrome. J Am Coll Cardiol 2003;41:633–642.
    # The study shows that epinephrine challenge is a powerful test to establish electrocardiographic diagnosis in silent LQT1 mutation carriers.
  • Shimizu W, Noda T, Takaki H, Nagaya N, Satomi K, Kurita T, Yoshimasa Y, Nakamura K, Ohe T, Towbin JA, Priori SG, Kamakura S. Diagnostic value of epinephrine test for genotyping LQT1, LQT2, and LQT3 forms of congenital long QT syndrome. Heart Rhythm 2004; 1:276-283.
    # Epinephrine infusion is powerful to predict the underlying LQT genotype.
  • Vyas H, Hejlik J, Ackerman MJ. Epinephrine QT stress testing in the evaluation of congenital long-QT syndrome: diagnostic accuracy of the paradoxical QT response. Circulation 2006;113:1385–1392.
    # This paper confirmed the efficiency of epinephrine in unmasking LQT1 syndrome, for the other types of LQT it was not significant.
  • Clur SA, Chockalingam P, Ackerman MJ, Filippini LH, Widyanti AP, Van Cruijsen M, Blom NA, Alders M, Hofman N, Wilde AA. The role of epinephrine test in the diagnosis and management of children suspected of having congenital long QT syndrome. Pediatr Cardiol. 2010;31:462-468.
    # This study used the Shimizu protocol of infusion of epinephrine to unmask LQT in children: it enables better management of therapy.
  • Churet M, Luttoo K, Hocini M, Haïssaguerre M, Sacher F, Duchateau J. Diagnostic reproducibility of epinephrine drug challenge interpretation in suspected long QT syndrome. J Cardiovasc Electrophysiol 2019;30:896-901.
    #  Moderate inter- and intraobserver agreement in the interpretation of the epinephrine provocation.

Adrenaline(isoproterenol?)/atropine for sinus node dysfunction 

  • Das G. Therapeutic review. Cardiac effects of atropine in man: an update. Int J Clin Pharmacol Ther Toxicol 1989;27:473-477.
    # This review discusses the basic pharmacology of atropine and addresses the paradoxical effects at the SA and AV node.
  • Mandel WJ, Hayakawa H, Allen HN, Danzig R, Kermaier AI. Assessment of sinus node function in patients with the sick sinus syndrome. Circulation 1972;46:761-769.
    # This article addresses the effect of isoproterenol and atropine in patients with SND.
  • Dhingra RC, Amat-Y-Leon F, Wyndham C, Denes P, Wu D, Miller RH, Rosen KM. Electrophysiologic effects of atropine on sinus node and atrium in patients with sinus nodal dysfunction. Am J Cardiol 1976;38:848-855.
    # This paper the effects of atropine on atrial electrophysiologic parameters in patients with SND and controls is described.
  • Jordan JL, Yamaguchi I, Mandel WJ. Studies on the mechanism of sinus node dysfunction in the sick sinus syndrome. Circulation 1978;57:217-223.
    # This article describes the use of atropine (and propranolol) to distinguish between extrinsic and intrinsic SND.
  • Bergfeldt L, Vallin H, Rosenqvist M, Insulander P, Nordlander R, Aström H. Sinus node recovery time assessment revisited: role of pharmacologic blockade of the autonomic nervous system. J Cardiovasc Electrophysiol 1996;7:95-101.
    # This article reports on the assessment of sinus node recovery time after pharmacologic blockade of the autonomic nervous system (atropine and propranol), increasing the sensitivity in patients with suspected SND.
  • Vavetsi S, Nikolaou N, Tsarouhas K, Lymperopoulos G, Kouzanidis I, Kafantaris I, Antonakopoulos A, Tsitsimpikou C, Kandylas J. Consecutive administration of atropine and isoproterenol for the evaluation of asymptomatic sinus bradycardia. Europace. 2008;10:1176–1181.
    # In this paper we learn that a step wise use of atropine and isoproterenol can better detect patients that may require pacemaker.

Adenosine/ATPA for sinus node and AV node dysfunction

  • Watt AH: Sick sinus syndrome: an adenosine-mediated disease. Lancet 1985;1:786-788.
    # Review article on adenosine sensitivity of SND.
  • Parry SW, Nath S, Bourke JP, Bexton RS, Kenny RA. Adenosine test in the diagnosis of unexplained syncope: marker of conducting tissue disease or neurally mediated syncope? Eur Heart J 2006;27:1396-1400.
    # Review on the possible mechanisms underlying a positive adenosine test, its safety, and a comprehensive examination of the literature supporting each of the putative causal diagnoses.
  • Drury AN, Szent-Gyorgyi A. The physiological activity of adenine compounds with especial reference to their action upon the mammalian heart. J Physiol 1929;68:213-237.
    # First report that adenosine significantly slowed sinus rhythm, produced atrioventricular block, and facilitated both atrial flutter and atrial fibrillation by shortening the refractory period.
  • West GA, Belardinelli L. Correlation of sinus slowing and hyperpolarization caused by adenosine in sinus node. Pflugers Arch 1985;403:75-81.
    # This manuscript demonstrates that adenosine in SAN pacemaker cells activates a potassium outward current as well as suppresses the inward calcium current and hyperpolarization-activated current (“funny” current).
  • Brignole M, Menozzi C, Alboni P, Oddone D, Gianfranchi L, Gaggioli G, Lolli G, Paparella N. The effect of exogenous adenosine in patients with neurally-mediated syncope and sick sinus syndrome. Pacing Clin Electrophysiol 1994;17:2211-2216.
    # Patients with intrinsic SND have an abnormal adenosine mediated sinus arrest. The clinical meaning of ATP induced AVB remains uncertain.
  • Lin JM, Lin JL, Lai LP, Huang SK. Usefulness of single-bolus adenosine test for confirming sinus node dysfunction and correlation with atrial overdrive suppression test. Am J Cardiol 2004;94:1569-1572.
    # This article demonstrates that a bolus injection of adenosine suppresses SAN function and produces pauses especially in patients with SAN dysfunction.
  • Fragakis N, Iliadis I, Sidopoulos E, Lambrou A, Tsaritsaniotis E, Katsaris G. The value of adenosine test in the diagnosis of sick sinus syndrome: susceptibility of sinus and atrioventricular node to adenosine in patients with sick sinus syndrome and unexplained syncope. Europace. 2007;9:559-562.
    # Adenosine test is comparable with CSNRT in making the diagnosis of SSS and may be considered as an alternative non-invasive test for confirmation of suspected SSS. No difference in the susceptibility of AVN to adenosine between the pts with syncope in the presence of SSS and those with unexplained syncope was found, suggesting that adenosine test cannot be used to diagnose atrioventricular block as the cause of syncope.
  • Fragakis N, Antoniadis AP, Korantzopoulos P, Kyriakou P, Koskinas KC, Geleris P. Sinus nodal response to adenosine relates to the severity of sinus node dysfunction. Europace 2012;14:859-864.
    # A bolus injection of adenosine suppresses SAN function and produces pauses especially in patients with SAN dysfunction.
  • Lou Q, Glukhov AV, Hansen B, Hage L, Vargas-Pinto P, Billman GE, Carnes CA, Federov VV. Tachy-brady arrhythmias: the critical role of adenosine-induced sinoatrial conduction block in post-tachycardia pauses. Heart Rhythm 2013;10:110-118.
    # Experimental SAN preparation that demonstrates that adenosine induces post-tachycardia atrial pauses via suppression of SAN conduction rather than by slowing pacemaker automaticity.
  • Belhassen B, Fish R, Glikson M, Glick A, Eldar M, Laniado S, Viskin S. Noninvasive diagnosis of dual AV node physiology in patients with AV nodal reentrant tachycardia by administration of adenosine-5'-triphosphate during sinus rhythm. Circulation.1998 Jul 7;98:47-53.
    # Very interesting, in this paper we find another method to detect AV node duality. Indeed, using adenosine in sinus rhythm can help us to perform the diagnosis of AVNRT.


  • Obeyesekere MN, Klein GJ, Modi S, Leong-Sit P, Gula LJ, Yee R, Skanes AC, Krahn AD. How to perform and interpret provocative testing for the diagnosis of Brugada syndrome, long-QT syndrome, and catecholaminergic polymorphic ventricular tachycardia. Circ Arrhythmia Electrophysiol 2011;4:958–964.
    # This review is quite complete. It highlights the clinical utility of provocative testing and describe how to perform and interpret provocative testing for the diagnosis of Brugada syndrome, LQTS, and CPVT.
  • Narla VA, Badhwar N. Provocative drug testing in the electrophysiology lab. In Practical Cardiac Electrophysiology, Editors Kartikeya Bhargava, Samuel J Asirvatham. Jaypee Broth Med Pub 2017.
    # Here we are a review of different situations for pharmacological testing. We can find also the protocols used. 

Exercise tests 

  • Beckerman J, Wu T, Jones S, Froelicher VF. Exercise test-induced arrhythmias. Prog Cardiovasc Dis 2005;47:285-305.
  • Morise AP. Exercise testing in nonatherosclerotic heart disease: hypertrophic cardiomyopathy, valvular heart disease, and arrhythmias. Circulation 2011;123:216-225.
    # Nice review article on value of exercise testing in various arrhythmia disorders.
  • Refaat MM, Hotait M, Tseng ZH. Utility of the exercise electrocardiogram testing in sudden cardiac death risk stratification.  Ann Noninvasive Electrocardiol 2014;19:311-318.
    # This review article focuses on the role of exercise testing beyond the diagnosis and prognostic evaluation of patients with ischemic heart disease. Through a systematic review of the literature, they analyse the role of exercise testing in sudden cardiac death risk stratification. 
  • Lee V, Perera D, Lambiase P. Prognostic significance of exercise-induced premature ventricular complexes: a systematic review and meta-analysis of observational studies. Heart Asia. 2017;9:14-24.
    # Exercise-induced PVCs are correlated with a higher risk of all cause death or cardiovascular events in the long term. This risk is elevated in asymptomatic patients without clinical heart disease and in patients with symptomatic heart disease. The fact that only EI-PVCs during recovery, and not during exercise, have poor prognostic value suggests that autonomic dysfunction may play a role in this association.
  • Coumel P. Catecholamine-induced severe ventricular arrhythmias with Adams- Stokes syndrome in children: a report of four cases. Br Heart J 1978;40:28–37.
    # Exercise testing in adrenergic-dependent rhythm disturbances, including monomorphic VT and polymorphic VT such as CPVT. CPVT is diagnosed in the presence of a structurally normal heart, normal ECG and exercise- or emotion-induced bidirectional or polymorphic VT. 
  • Podrid PJ, Graboys TB. Exercise stress testing in the management of cardiac rhythm disorders. Med Clin North Am 1984;68:1139–1152.
    # Exercise stress testing is recommended in patients with known or suspected exercise-induced VA, including CPVT, to achieve a diagnosis and define prognosis. 
  • Young DZ, Lampert S, Graboys TB, Lown B. Safety of maximal exercise testing in patients at high risk for ventricular arrhythmia. Circulation 1984; 70:184–191.
    # This paper describes exercise test–related complications were defined as the occurrence of ventricular fibrillation, ventricular tachycardia, or bradycardia requiring immediate medical treatment. These arrhythmic complications were seen in 24 patients (9.1%) during 32 exercise tests (2.3%).
  • Jouven X, Zureik M, Desnos M, Courbon D, Ducimetière P. Long-term outcome in asymptomatic men with exercise-induced premature ventricular depolarizations. N Engl J Med 2000;343:826-833.
    # Exercise-induced ventricular ectopic beats increase the likelihood of future cardiac death.
  • Lerman BB, Stein KM, Markowitz SM, Mittal S, Slotwiner DJ. Ventricular arrhythmias in normal hearts. Cardiol Clin 2000;18:265-291.
    # Review that also describes exercise-induced outflowtracts VTs.
  • Sumitomo N, Harada K, Nagashima M, Yasuda T, Nakamura Y, Aragaki Y, Saito A, Kurosaki K, Jouo K, Koujiro M, Konishi S, Matsuoka S, Oono T, Hayakawa S, Miura M, Ushinohama H, Shibata T, Niimura I. Catecholaminergic polymorphic ventricular tachycardia: electrocardiographic characteristics and optimal therapeutic strategies to prevent sudden death. Heart 2003; 89:66–70.
    # Importance of exercise-stress testing in CPVT patients.
  • Eckart RE, Field ME, Hruczkowski TW, Forman DE, Dorbala S, DiCarli MF, Albert CE, Maisel WH, Epstein LM, Stevenson WG. Association of electrocardiographic morphology of exercise-induced ventricular arrhythmia with mortality. Ann Intern Med 2008; 149:451–460.
    # Right bundle-branch block morphology ectopic beats are associated with increased mortality and left bundle-branch block morphology beats are not.
  • GimenoJ R, Tome-Esteban M, Lofiego C, Hurtado J, Pantazis A, Mist B, Lambiase P, McKenna WJ, Elliott PM. Exercise-induced ventricular arrhythmias and risk of sudden cardiac death in patients with hypertrophic cardiomyopathy. Eur Heart J 2009; 30:2599–2605.
    # Documented NSVT during or immediately following exercise is very rare, but may be associated with a higher risk of SCD in HCM. 
  • Hayashi M, Denjoy I, Extramiana F, Maltret A, Buisson NR, Lupoglazoff JM, Klug D, Hayashi M, Takatsuki S, Villain E, Kamblock J, Messali A, Guicheney P, Lunardi J, Leenhardt A. Incidence and risk factors of arrhythmic events in catecholaminergic polymorphic ventricular tachycardia. Circulation 2009;119:2426-2434.
    # CPVT therapy with beta-blockers should be considered for genetically positive family members, even after a negative exercise test. 
  • Wong JA, Gula LJ, Klein GJ, Yee R, Skanes AC, Krahn AD. Utility of treadmill testing in identification and genotype prediction in long QT syndrome. Circ Arrhythm Electrophysiol 2010;3:120–125.
    # changes in the QT interval with exercise can be useful in identifying and risk stratifying patients with the long-QT syndrome.
  • Van Gelder IC, Groenveld HF, Crijns HJ, Tuininga YS, Tijssen JG, Alings AM, Hillege HL, Bergsma-Kadijk JA, Cornel JH, Kamp O, Tukkie R, Bosker HA, Van Veldhuisen DJ, Van den Berg MP, RACE II Investigators. Lenient versus strict rate control in patients with atrial fibrillation. N Engl J Med 2010;362:1363–1373.
    # Criteria for rate control of AF vary with patient age but usually involve achieving ventricular rates between 90 and 115 bpm during moderate exercise.
  • Horner JM, Horner MM, Ackerman MJ. The diagnostic utility of recovery phase QTc during treadmill exercise stress testing in the evaluation of long QT syndrome. Heart Rhythm 2011;8:1698-1704.
    # This review demonstrates that treadmill stress testing can unmask patients with concealed LQT1.
  • Marine JE, Shetty V, Chow GV, Wright JG, Gerstenblith G, Najjar SS, Lakatta EG, Fleg JL. Prevalence and prognostic significance of exercise-induced nonsustained ventricular tachycardia in asymptomatic volunteers: BLSA (Baltimore Longitudinal Study of Aging). J Am Coll Cardiol 2013;62:595–600.
    # Exercise-induced non-sustained VT was reported in nearly 4% of asymptomatic middle-age adults and was not associated with an increased risk of total mortality.
  • Masrur S, Memon S, Thompson PD. Brugada syndrome, exercise, and exercise testing. Clin Cardiol 2015 May;38(5):323-326.
    # Review article highlighting that exercise can unmask a Brugada electrocardiographic pattern. Exercise is associated with syncope and ST augmentation after exercise and may be helpful in unmasking Brugada syndrome. 
  • Gibbons RJ, Balady GJ, Bricker JT, Chaitman BR, Fletcher GF, Froelicher VF, Mark DB, McCallister BD, Mooss AN, O’Reilly MG, Winters WL, Gibbons RJ, Antman EM, Alpert JS, Faxon DP, Fuster V, Gregoratos G, Hiratzka LF, Jacobs AK, Russell RO, Smith SC. ACC/AHA 2002 guideline update for exercise testing: summary article. A report of the American College of Cardiology/Ameri- can Heart Association Task Force on Practice Guidelines (Committee to Update the 1997 Exercise Testing Guidelines). J Am Coll Cardiol 2002;40:1531–1540.
    # ACC/AHA guidelines for exercise testing referred to by ESC guidelines on management of ventricular arrhythmias.
  • Pelliccia A, Zipes DP, Maron BJ. Bethesda Conference
    #36 and the European Society of Cardiology Consensus recommendations revisited: a comparison of U.S. and European criteria for eligibility and disqualification of competitive athletes with cardiovascular abnormalities. J Am Coll Cardiol 2008;52:1990–1996.
  • Priori SG, Wilde AA, Horie M, Cho Y, Behr ER, Berul C, Blom N, Brugada J, Chiang CE, Huikuri H, Kannankeril P, Krahn A, Leenhardt A, Moss A, Schwartz PJ, Shimizu W, Tomaselli G, Tracy C. Executive summary: HRS/ EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes. Europace 2013;15:1389–1406. 

General knowledge in imaging techniques (fluoroscopy, echocardiography, magnetic resonance imaging (MRI), computed tomography (CT), nuclear imaging, angiograms, and other)

  • Farré J, Anderson RH, Cabrera JA, Sánchez-Quintana D, Rubio JM, Benezet-Mazuecos J, del Castillo S, Macía E. Cardiac anatomy for the interventional arrhythmologist: I. Terminology and Fluoroscopic projections. PACE 2010;33:497-507.
    # In this paper anatomy of the heart is extensively revised with special focus on those issues that are relevant for electrophysiological interventions. Terminology is updated according to most recent recommendations. Images are of great quality and belong to The Visible Human Slice and Surface Server, an open-access, web-based software. They are depicted in the different fluoroscopic projections, so that the reader can easily understand how to place a catheter in a desired location and the relationship of the catheter with the surrounding structures. The later is important to be aware of possible complications during ablations. 
  • Heidbuchel H, Whittkampf FH, Vano E, Ernst S, Schilling R, Picano E, Mont L, Jais P, de Bono J, Piorkowski C, Saad E, Femenia F. Practical ways to reduce radiation dose for patients and staff during device implantations and electrophysiological procedures. Europace 2014;16:946-964.
    # The proposed document represents an EHRA Practical Guide focused on risks of radiation exposure and most importantly, the way they can be reduced during implantations and electrophysiological procedures. 
  • Bucciarelli-Ducci C, Baritussio A, Auricchio A. Cardiac MRI anatomy and function as substrate for arrhythmias. Europace 2016;18:iv130-iv135.
    # This paper highlights the role of cardiac MRI in the diagnostic work-up of patients with cardiomyopathies with especial focus on its capability to perform an accurate tissue characterization, which is useful in the detection of arrhythmic substrates and risk stratification. Some technical aspects of late gadolinium enhancement imaging are revised. It offers also a brief summary of the role of MRI in the detection of atrial fibrosis. Highly recommended as a first contact with the role of cardiac MRI in EP labs/procedures. Among its references, the reader can find the most relevant ones in the field.  
  • Mukherjee RK, Whitaker J, Williams SE, Razavi R, O´Neill MD. Magnetic resonance imaging guidance for the optimization of ventricular tachycardia ablation. Europace 2018;20:1721-1732.
    # This paper focuses on the role of MR imaging to identify substrate causing VT in structural heart disease (scar and border-zone scar). The authors address its limitations (with special focus on image integration with electro-anatomic maps) and the new developments that can improve its ability to define targets for ablation. They also revise the potential for a real-time MRI guided ablation procedure, i.e. visualize soft tissues, guide catheters to a desired position or lesion assessment.  
  • Enriquez A, Saenz LC, Rosso R, Silvestry FE, Callans D, Marchlinsky FE, Garcia F. Use of intracardiac echocardiography in Interventional Cardiology. Circulation 2018;137:2278-2294.
    # This paper provides an outstanding review of the main uses of intracardiac echocardiography (ICE) in catheter-based structural and electrophysiological procedures.. 
  • Muser D, Santageli P, Selvanayagam JB, Nucifora G. Role of cardiac magnetic resonance imaging in patients with idiopathic ventricular arrhythmias. Curr Cardiol Rev 2019;15:12-23.
    # This is a recently published review focused on the role of CMR in the evaluation of patients with suspected idiopathic ventricular arrhythmias. 
  • Pontecorboli G, Figueras I, Ventura RM, Carlosena A, Benito E, Prat-Gonzalez S, Padeletti L, Mont L. Use of delayed-enhancement magnetic resonance imaging for fibrosis detection in the atria: a review. Europace 2017;19:180-189.
    # This paper presents a review of the different approaches to detect and quantify fibrosis in MR images.  Blomström Lundqvist C, Auricchio A, Brugada J, Boriani G, Bremerich J, Cabrera JA et al. The use of imaging for electrophysiological and devices procedures: a report from the First European Heart Rhythm Policy Conference, jointly organized with the European Association of Cardiovascular Imaging (EACVI), the Council of Cardiovascular Imaging and the European Society of Cardiac Radiology. Europace 2013;15(7): 927-936.# This EHRA consensus statement focuses on the main uses of each imaging technique according to the type of procedure or substrate. A good starting point. 
  • Haugaa KH, Basso C, Badano LP, Bucciarelli-Ducci C, Cardim N, Gaemperli O, Galderisi M, Habib G, Knuuti J, Lancellotti P, McKenna W, Neglia D, Popescu BA and Edvardsen T. Comprehensive multi-modality imaging approach in arrhythmogenic cardiomyopathy-an expert consensus document of the European Association of Cardiovascular Imaging. European heart journal cardiovascular Imaging. 2017;18:237-253.
    # Summary of ARVC disease and recommendations of imaging and follow up intervals.
  • Donal E, Lip GYH, Galderisi M, Goette A, Shah D, Marwan M, Lederlin M, Mondillo S, Edvardsen T, Sitges M, Grapsa J, Garbi M, Senior R, Gimelli A, Potpara TS, Van Gelder IC, Gorenek B, Mabo P, Lancellotti P, Kuck KH, Popescu BA, Hindricks G, Habib G. EACVI/EHRA Expert Consensus Document on the role of multi-modality imaging for the evaluation of patients with atrial fibrillation. Eur Heart J 2016;17:355-383.
  • Sarkozy A, De Potter T, Heidbuchel H, Ernst S, Kosiuk J, Vano E, Picano E, Arbelo E, Tedrow  U. ESC Scientific Document Group. Occupational radiation exposure in the electrophysiology laboratory with a focus on personnel with reproductive potential and during pregnancy: A European Heart Rhythm Association (EHRA) consensus document endorsed by the Heart Rhythm Society (HRS). Europace 2017;19(12):1909-1922.

Autonomic nervous system evaluation

  • Brignole M, Moya A, de Lange FJ, Deharo JC, Elliot PM, Fanciulli A, Fedorowski A, et al. Practical instructions for the 2018 ESC Guidelines for the diagnosis and management of syncope. Eur Heart J 2018;39:e47-e80.
    # This document is part of the supplementary materials of the 2018 ESC Guidelines for the diagnosis and management of syncope. It describes the way the different diagnostic tests should be done and interpreted. It contains illustrations and figures that are quite useful.

Carotid sinus massage

  • Krediet CTP, Parry SW, Jardine DL, Benditt DG, Brignole M, Wieling W. The history of diagnosing carotid sinus hypersensitivity: why are the current criteria too sensitive? Europace 2011;13:14-22.
    # This review paper focuses on carotid sinus hypersensitivity (bradycardia and/or hypotension elicit by carotid sinus massage) and carotid sinus syndrome (syncope triggered by carotid sinus manipulation). It is mainly an expert and critical review of the criteria used to define carotid sinus hypersensitivity. The authors review the historical backgrounds that are behind the three types of haemodynamic responses and the reference values that we use in daily practice. 
  • Pasquier M, Clair M, Pruvot E, Hugli O, Carron PN. Carotid sinus massage. N Engl J Med 2017;377:e21.
    # This supplement reviews the information provided in the video on the indications for carotid sinus massage, the contraindications, and the equipment and techniques required to perform the procedure safely in adults.
  • Schweitzer P, Teichholz LE. Carotid sinus massage: its diagnostic and therapeutic value in arrhythmias. Am J Med 1985;78:645-654.
    # This article states that carotid sinus massage may help to clarify the type and origin of narrow-complex tachycardia.
  • Brignole M, Alboni P, Benditt DG, et al. Guidelines on management (diagnosis and treatment) of syncope — update 2004. Europace2004;6:467-537.
    # Cardioinhibitory response is defined as a pause of 3 seconds or more without a drop in blood pressure of 50 mm Hg or more, the vasodepressor response is defined as a decrease in blood pressure of 50 mm Hg or more without a pause of 3 seconds or more, and the mixed response is defined as the association of a pause of 3 seconds or more with a drop in blood pressure of 50 mm Hg.
  • The task force for the diagnosis and management of syncope of the European Society of Cardiology (ESC). Guidelines for the diagnosis and management of syncope (version 2009). Eur Heart J 2009;30:2631-2671.

Supine to orthostatism for orthostatic hypotension evaluation

  • Mar PL, Raj SR. Orthostatic hypotension for the cardiologist. Curr Opin Cardiol 2018;33(1):66-72# This review focuses on orthostatic hypotension (OH), the second more frequent cause of syncope. 
  • Frith J, Parry SW. New horizons in orthostatic hypotension. Age Ageing 2017;46(2):168-174
    # This recent review offers a comprehensive overview on orthostatic hypotension (OH), with special focus on elderly patients. 
  • Ricci F, De Caterina R, Fedorowski A. Orthostatic hypotension: epidemiology, prognosis, and treatment. J Am Coll Cardiol 2015;66:848-860.
    # This review outlines the etiology and prevalence of OH in the general population, summarizes its relationship with morbidity and mortality, propose a diagnostic and therapeutic algorithm, and delineate current challenges and future perspectives.
  • Freeman R, Wieling W, Axelrod FB, Benditt DG, Benarroch E, Biaggioni I, Cheshire WP, Chelimsky T, Cortelli P, Gibbons CH, Goldstein DS, Hainsworth R, Hilz MJ, Jacob G, Kaufmann H, Jordan J, Lipsitz  LA, Levine BD, Low PA, Mathias C, Raj SR, Robertson D, Sandroni P, Schatz I, Schondorff R, Stewart JM, van Dijk JG. Consensus Statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clin Auton Res 2011;21:69-72.
    # This consensus statement establishes the diagnostic criteria that are currently used for diagnosing of orthostatic hypotension, including a different cut-off value for hypertensive patients and the definition of supine hypertension. It also provides a definition for the postural orthostatic tachycardia syndrome. 

Tilt testing

  • Tan MP, Duncan GW, Parry SW. Head-up tilt table testing: a state-of-the-art review. Minerva Med 2009 Aug;100(4):329-338.
  • Forleo C, Guida P, Iacoviello M, Resta M, Monitillo F, Sorrentino S, Favale S. Head-up tilt testing for diagnosing vasovagal syncope: a meta-analysis.  Int J Cardiol 2013;168:27-35.
    # This study is a meta-analysis on the diagnostic yield of head-up tilt testing in patients with syncope of unknown origin. For this purpose they included all articles aimed to establish sensibility and specificity of this diagnostic tool. A total of 55 articles were selected (4361 patients and 1791 controls). For the analysis, variables such as the influence of age, test duration, tilt angle and drug used in the provocation phase were considered. 
  • Brignole M, Menozzi C, Del Rosso A, Costa S, Gaggioli G, Bottoni N, Bartoli P, Sutton R. New classification of haemodynamics of vasovagal syncope: beyond the VASIS classification. Europace 2000;2:66-76.
    # Most of the authors of the previous paper, review the behaviour of blood pressure during tilt testing in the time preceding the development of the vasovagal reaction, with the hypothesis that this pattern can add some extra diagnostic information.  
  • Brignole M, Sutton R, Menozzi C, Garcia-Civera R, Moya A, Wieling W, Andresen D, Benditt DG, Grovale N, De Santo T, Vardas P. International Study on Syncope of Uncertain Etiology 2 (ISSUE-2) Group. Lack of correlation between the responses to tilt testing and adenosine triphosphate test and the mechanism of spontaneous neutrally mediated syncope. Eur Heart J 2006;27:2232-2239. 
     # This is a prospective evaluation of the correlation between the results of the tilt testing and the findings in the ILR during spontaneous recurrences in patients with a clinical diagnosis of neurally-mediated syncope included in the ISSUE-2 study. The ISSUE-2 study was a multicentre, prospective, observational study enrolling consecutive patients that underwent early ILR implantation for recurrent suspected neurally-mediated syncope. Among 392 included patients, 343 (88%) underwent a tilt-test, which was positive in 164 (48%). There were no differences in baseline characteristic, syncopal recurrence rate or mechanism of syncope among patients with positive or negative tilt testing. Among patients with positive tilt testing, the electrocardiographic patterns observed during the test were poorly correlated with those observed during spontaneous syncope. Asystolic pauses were more frequently found during spontaneous syncope than during tilt testing (45 vs. 21%, p=0,02). The authors conclude that in patients with neurally-mediated syncope, clinical characteristic, outcome, and mechanism of syncope are poorly correlated and no predicted by the results of tilt-testing and, as a consequence, this test has little value in guiding therapy.  
  • Ungar A, Sgobino P, Russo V, Vitale E, Sutton R, Melissano D, Beiras X, Bottoni N, Ebert HH, Gulizia M, Jorfida M, Moya A, Andresen D, Grovale N, Brignole M. International Study on Syncope of Uncertain Etiology 3 (ISSUE-3) Investigators. Diagnosis of neurally-mediated syncope at initial evaluation with tilt table testing compared with that revealed by prolonged ECG monitoring. An analysis from the Third International Study on Syncope Of Uncertain Etiology (ISSUE-3). Heart 2013;99:1825-1831.
    # Diagnosis of neurally-mediated syncope is based on the history as well as on the exclusion of competing diagnosis in the initial evaluation. This initial evaluation frequently includes a tilt testing.In this prospective, multicentre and observational study 504 patients with suspected neurally-mediated syncope were included. The patients were ≥ 40 years and had a previous history of recurrent syncopal episodes (3 or more episodes in the previous 2 years). They all received an ILR and were followed for 15 ± 11 months. The main objective was to compare the diagnosis of neurally-mediated syncope made at initial evaluation with tilt-testing with that obtained with the documentation of an spontaneous recurrence by ILR. A spontaneous episode could be documented in 187 patients, with a diagnostic yield of 47% at 3 years. In 162 cases (87%), the ILR findings were consistent with the initial diagnosis of presumed neurally-mediated syncope. In 25 (13%) patients, the ILR revealed another diagnosis (intrinsic cardiac arrhythmic cause or non-arrhythmic loss of consciousness). Initial tilt testing was positive in 56% of patients with presumed neurally-mediated syncope, but also in 21% of patients with other causes of syncope/transient loss of consciousness. The authors conclude that tilt testing was unable to accurately discriminate between presumed neurally-mediated syncope and non neurally-mediated syncope, with the exception of asystolic pauses (an asystolic response was documented in none of the patients with positive tilt testing and non neurally-mediated syncope).
  • Kenny RA, Ingram A, Bayliss J, Sutton R. Head-up tilt: an useful test for investigation unexplained syncope. Lancet 1986;1:1352-1355.
    # This paper is the first report of the use of head-up tilt test in patients with unexplained syncope despite clinical and electrophysiological assessment. A total of 15 symptomatic patients and 10 control subjects underwent 40 degrees head-up tilt for 60 minutes, with continuous monitoring of heart rate and blood pressure. 67% of patients and 1 control developed vasovagal syncope that reproduced symptoms previously experienced. Pacemaker was implanted in 7 of those patients, that remained symptoms free after a mean follow-up of 10 months. 
  • Sutton R, Petersen M, Brignole M, Raviele A, Menozzi C, Giani  P. Proposed classification for tilt induced vasovagal syncope. Eur J Cardiac Pacing Electrophysiol 1992;2:180-3.
    # In this classical paper the classification of vasovagal syncope is proposed on the basis of recordings of arterial pressure and heart rate during tilt-induced syncope. These include mixed, two variants of cardioinhibition and vasodepression categories. The interpretation of tilt testing is still made according to this proposal. By this classification the authors provided a more pathophysiological and less arbitrary basis for future therapeutic studies.
  • Bartoletti A, Alboni P, Ammirati F, Brignole M, Del Rosso A, Foglia Manzillo G, Menozzi C, Raviele A, Sutton R. “The Italian Protocol”: a simplified head-up tilt testing potentiated with oral nitroglycerin to assess patients with unexplained syncope. Europace 2000;2:339-342.
    # This paper established the best methodology to perform the head-up tilt test potentiated by nitroglicerine, which is the standard nowadays. It describes the following phases and issues: 1. Stabilization: with a minimum duration of 5 minutes. This period allow the patient to achieve a stable physical condition. 2. Tilt angle: the best angle is considered to be 60º.3. Passive phase: they advocated for a reduction of the duration of this phase to 20 minutes instead of 45 minutes (original protocol). This modification did not affect the final positivity rates nor the specificity of the test. 4. Active phase: based in the administration of 400 mcg oral spray preparation of nitroglicerine (increase sensitivity due to a higher dose and higher bioavailability than previous protocols) and with a reduced duration (15 minutes). 5. Criteria for interruption of the test: completion of the protocol without symptoms, syncope or progressive symptomatic orthostatic hypotension.
  • Kenny RA, Brignole M, Dan GA, Deharo JC, van Dijk JG, Doherty C, Hamdan M, Moya A, Parry SW, Sutton R, Ungar A, Wieling W. Syncope unit: rationale and requirement – the European Heart Rhythm Association position statement endorsed by the Heart Rhythm Society. Europace 2015;17:1325-1340.


  • Jones PK, Gibbons CH. The role of autonomic testing in syncope. Auton Neurosci 2014;184:40-45
    # This paper offers a review of the role of different approaches to autonomic testing in patients with syncope. Despite an extensive review of head-up tilt testing (already covered in other references), it also covers other tests like active standing, evaluation of heart rate variability with deep breathing or Valsalva maneuver. Authors state that autonomic testing is safe and should be part of the evaluation of patients, as it may lead to identification of autonomic causes of syncope. 

Transesophageal electrical evaluation 

  • Akin A, Özer S, Karagöz T, Aykan HH, Gülgün M, Özkutlu S, Alehan D, Celiker A. Sensitivity of tranesophageal electrophysiologic study in children with supraventricular tachycardia on electrocardiography. Pacing Clin Electrophysiol 2014;37(8):1002-1008.
    # Transesophageal electrophysiological study (TEEPS) represents an alternative to classical electrophysiological study. It is mainly used in pediatric population, with the advantage of being less invasive. In this paper, 85 patients with documented supraventricular tachycardia were included. Age ranged 1 month to 17 years old. Patients underwent an initial TEEPS that was followed by electrophysiological study in 40 patients. Inducibility in TEEPS was high (93%) and similar to inducibility achieved by classical electrophysiological study. There were only 3 patients non-inducible in TEEPS in which electrophysiological study could induce the documented tachycardia. TEEPS could also establish the mechanism of the tachycardia in most of the patients that were induced. 

Invasive EP studies 

Sinus node and atrial impulse formation and conduction disorders

  • Menozzi C, Brignole M, Alboni P, Boni L, Paparella N, Gaggioli G, Lolli G. The natural course of untreated sick sinus syndrome and identification of the variables predictive of unfavorable outcome. Am J Cardiol 1998. 82:1205–1209. DOI: 10.1016/S0002-9149(98)00605-5; Menozzi C, Brignole M, Alboni P, Boni L, Paparella N, Gaggioli G, Lolli G. The natural course of untreated sick sinus syndrome and identification of the variables predictive of unfavorable outcome. Am J Cardiol 1998. 82:1205–1209. DOI: 10.1016/S0002-9149(98)00605-5;
    # A prospective study in 35 untreated patients aged≥45yo, with a mean sinus rate less than 50 beats/min and/or intermittent sinoatrial block, and symptoms attributed to sinus node dysfunction (SND).. 
  • Sanders P, Morton JB, Kistler PM, Spence SJ, Davidson NC, Hussin A, Vohra JK, Sparks PB, Kalman JM. Electrophysiological and Electroanatomic Characterization of the Atria in Sinus Node Disease: evidence of diffuse atrial remodeling. Circulation. 2004 Mar 30;109(12):1514-22. Epub 2004 Mar 8.
    # This study showed that pts with SND have atrial enlargement, scarring, conduction delay and increased right atrial refractoriness. 
  • Gann D, Tolentino A, Samet P. Electrophysiologic evaluation of elderly patients with sinus bradycardia: a long-term follow-up study. Ann Intern Med. 1979;90:24–29.
    # A study on 103 pts with persistent sinus bradycardia. Were evaluated electrophysiologicaly and followed prospectively. Mean follow-up of 4.6 years. The survival rate was not significantly different for the general population with similar age and sex distribution, 74.8% with respect to 72%. Forty-one pts (40%) had abnormal c-SNRT. Accurary of abnormal c-SNRT in predicting serious sinus node disease was lower in symptomatic and asymptomatic patients vs. those with syncope. When considering conventional limits, of 500-550ms for c-SNRT, the sensitivity of the test in patients who will need a pacemaker in the future is only 50-65% and the survival rate seems to be similar to the general population.

AV nodal and His-Purkinje conduction disorders

  • Demosthenes G. Katritsis, Mark E Josephson. Electrophysiological testing for the investigation of bradycardias. Arrhythm Electrophysiol Rev. 2017 Apr; 6(1): 24–28. doi: 10.15420/aer.2016:34:2
    # 34 articles were used for this paper. In this review we find details about the anatomic site of the block, the incidence of complete block in bifascicular and trifascicular block patients and recommendations for electrophysiology study in selecting patients for permanent pacing. High-grade block occur anywhere in the AV conduction system and the width of the QRS complex has limited value in localising the site of of block. A wide QRS complex may occurs with A-V nodal or intra-His disease in the presence of coexistent bundle branch block. An HV interval˃70ms is a nonspecific predictor of development of high grade atrioventricular block. An HV˃100ms is highly predictive but insensitive marker.  
  • Moya A,Garcia-Civera R, Croci F, Menozzi C, Brugada J, Ammirati F, DelRosso A,  Bellver-Navarro A, Garcia-Sacristan J, Bortnik M, Mont L, Ruiz-Granell R, Navarro X. Diagnosis, management, and outcomes of patients with syncope and bundle branchblock. Eur Heart J 2011;32:1535–1541.
    # A prospective study on 323 pts with ≥1 syncope in the last 6 months and QRS duration ≥120ms. The study had three-phase diagnostic strategy. Phase I, initial evaluation; Phase II, electrophysiological study; Phase III, insertion of an implantable loop recorder. The aetiological diagnosis was established in 267 (82.7%) pts ( 102 at initial evaluation, 113 upon EPS study, and 52 upon ILR) with the following aetiologies: bradyarrhythmia (202), carotid sinus syndrome (20), ventricular tachycardia (18), neurally mediated (9), orthostatic hypotension (4), drug-induced (3), secondary to cardiopulmonary disease (2), supraventricular tachycardia (1), bradycardia-tachycardia (1), and non-arrhythmic (7). In 68.1% a pacemaker was implanted, in 5.8% a cardioverter defibrillator and radiofrequency catheter ablation in 3 pts. In this study a systematic diagnostic approach is proposed for the aetiological diagnosis and specific treatment in pts with syncope and BBB.   
  • Scheinman MM, Peters RW, Suave MJ, Desai J, Abbott JA, Cogan J, Wohl B, Williams K. Value of the H-Q interval in patients with bundle branch block and the role of prophylactic permanent pacing. Am J Cardiol 1982;50:1316–1322.
    # Scheinman at el. analized the progression rate to AV block at 4 years for 313 pts with bundle branch block. In pts with HV interval ˂70ms was ≤4%; HV interval of 70-100ms was 12%; HV interval ˃100ms was 24%. The development of intra or infraHis block at incremental atrial pacing is highly predictive of impending AV block.  A HV greater than or equal to 70 ms was an independent risk factor for progression and HV greater or equal to 100 ms identified a subgroup at particularly high risk for high degree AV block.   

Atrial and thoracic vein ectopy and tachycardias  

  • Yi -Jen Chen, Shih-AnnChen. Thoracic Vein Arrhytmias. Circ J 2007; Suppl A: A-2—A-25.
    # This review summarises the basic and clinical electrophysiology of thoracic vein arrhythmias. 70 articles were taken into consideration and analyzed. The pulmonary veins have the highest arrhythmogenic activity but also other venous structures such as superior vena cava, coronary sinus and ligament of Marshall have arrhythmogenic potential. This venous structures contain cardiomyocytes with distinct electrical activities and complex anatomical structures. In this paper we find information about anatomy, mechanisms and factors determining arrhythmogenesis of PV, SVC, LOM, CS.  
  • Wang, X, Li, Z, Mao, J, He, B. Electrophysiological features and catheter ablation of symptomatic frequent premature atrial contractions. Europace. 2017; 19: 1535– 1541.
    # A study conducted on patients with symptomatic, frequent, and drug-refractory premature atrial contractions. Two groups, one with PACs alone, the other with PACs and atrial fibrillation. Coupling intervals of PACs were compared. Frequent PACs in the absence of AF were characterized as having their prediction sites and longer coupling intervals. The majority of them were at pulmonary vein (20%), crista terminalis (17%) and para-hissian area (17%). In the group with PACs and AF ectopic foci were in left-sided PV (60%), right sided PV (37%) and SVC (3%) and had the shortest coupling intervals.  
  • Kistler PM, Roberts-Thomson KC, Haqqani HM, Fynn SP, Singarayar S, Vohra JK, Morton JB, Sparks PB, Kalman JM.  P-wave morphology in focal atrial tachycardia development of an algorithm to predict the anatomic site of origin. J Am Coll Cardiol 2006;48:1010–7.
    # A study performed on 126 pts undergoing successful ablation of atrial tachycardias. Purpose of the study was to analyze the P wave morphology in tachycardia and construct and evaluate an algorithm for identification of the anatomic site of origin..  

Atrial flutter 

  • Laţcu DG, Bun SS, Casado Arroyo R, Wedn AM, Benaich FA, Hasni K, Enache B, Saoudi N. Scar identification, quantification, and characterization in complex atrial tachycardia: a path to targeted ablation? Europace. 2019 Jan 1;21(Supplement_1):i21-i26.
    # Identification of the critical isthmus of a scar-related atrial tachycardia is crucial in achieving successful catheter ablation. Often, this is a small area of viable conducting tissue within a low-voltage area. Achieving successful identification of the interesting low potentials depends on the signal-to-noise ratio and the properties of the diagnostic catheter giving high resolution. This article reviews the current status anno 2019 of using ultra-high density mapping with multipolar catheters with small and closely-spades electrodes.
  • Schaeffer B, Stevenson WG. Entrainment mapping: Theoretical considerations and practical implementation. J Cardiovasc Electrophysiol. 2018 Jan;29(1):204-213.
    # Despite current available high-density mapping techniques, entrainment mapping is still very helpful and remains one the most important maneuvers during electrophysiology testing. In this recent review, Dr. Schaeffer and Dr. Stevenson, summarize the theoretical aspects and the current practical implementation. Despite all modern techniques, this concept has to be well known by every electrophysiologist.
  • Manolis AS. Contemporary Diagnosis and Management of Atrial Flutter: A Continuum of Atrial Fibrillation and Vice Versa? Cardiol Rev. 2017 Nov/Dec;25(6):289-297.
    # This article gives a comprehensive overview of the mechanisms of typical and atypical atrial flutter. It is a complete review beginning from ECG diagnosis to electrophysiology mapping, ultimately leading to ablation. Besides, the author focus on the close interrelation with atrial fibrillation.
  • Asirvatham SJ. Correlative anatomy and electrophysiology for the interventional electrophysiologist: right atrial flutter. J Cardiovasc Electrophysiol. 2009 Jan;20(1):113-22.
    # Ablating the cavotricuspid istmus (CVTI) is most of the time a straightforward procedure but sometimes it can be very challenging.  Understanding the anatomy of the CVTI can help dealing with difficulties encountered during ablation. Prof. Asirvatham gives an overview of the normal anatomy of the CVTI and explains the anatomic basis for difficult electrograms found during the procedure.
  • De Ponti R, Verlato R, Bertaglia E, Del Greco M, Fusco A, Bottoni N, Drago F, Sciarra L, Ometto R, Mantovan R, Salerno-Uriarte JA.Treatment of macro-reentrant atrial tachycardia based on electroanatomic mapping: identificationand ablation of the mid-diastolic isthmus. Europace. 2007 Jul;9(7):449-57.
    # Identifying complex circuits of atypical flutters using electroanatomic mapping (EAM) together with entrainment mapping has been proved to be superior in achieving successful ablation. However, entrainment is not always achievable and mapping can provide confusing results. This article describes a method for calculating the window of interest to map the mid-diastolically activated isthmus of reentrant circuits as a region of interest for ablation.
  • Olgin JE, Kalman JM, Lesh MD. Conduction barriers in human atrial flutter: correlation of electrophysiology and anatomy. J Cardiovasc Electrophysiol 1996;7:1112-1126
    # The right atrium has an unique endocardial architecture with anatomic barriers around which reentry occurs. The importance and the role of this barriers is discussed in this article. Besides, the difference is described between fixed and functional barriers in atrial flutters and overview is given of the methodology for defining barriers. Knowledge of these barriers helps to understand the origin of atrial flutters. 
  • Waldo AL, MacLean WA, Karp RB, Kouchoukos NT, James TN. Entrainment and interruption of atrial flutter with atrial pacing: studies in man following open heart surgery. Circulation. 1977 Nov;56(5):737-45.
    # This is the original article describing the criteria for entrainment. Waldo et al. described that high right atrial pacing at increasing rates in patients with common atrial flutter could capture the atrium. If, after pacing, flutter returned to baseline cycle length (CL) and morphology, it was called transient entrainment.
  • Shah DC, Jaïs P, Takahashi A, Hocini M, Peng JT, Clémenty J, Haïssaguerre M. Dual loop intra-atrial reentry in man. Circulation 2000; 101(6): 631-639.
    # This study provides the first description of multi-loop reentrant tachycardias in man. Jaïs P, Shah DC, Haïssaguerre M, Hocini M, Peng JT, Takahashi A, Garrigue S, Le Métayer P, Clémenty J. Mapping and ablation of left atrial flutters. Circulation 2000; 101(25): 2928-2934.# This is the first publication describing the delineation of left atrial flutter (left atrial macroreentry) circuits and their ablation based on the analysis of the mapping data.
  • Ouyang F, Ernst S, Vogtmann T, Goya M, Volkmer M, Schaumann A, Bänsch D, Antz M, Kuck KH. Characterization of reentrant circuits in left atrial macroreentrant tachycardia: critical isthmus block can prevent atrial tachycardia recurrence. Circulation. 2002 Apr 23;105(16):1934-42.
    # This study describes the correlation of the achievement of critical isthmus conduction block with the prevention of recurrence of mainly left atrial reentrant tachycardias.
  • 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation. Calkins H, Hindricks G, Cappato R, Kim YH, Saad EB, Aguinaga L, et al. Europace. 2018 Jan 1;20(1):157-208.

Atrial fibrillation 

  • Santangeli P, Marchlinski FE. Techniques for the provocation, localization, and ablation of non-pulmonary vein triggers for atrial fibrillation. Heart Rhythm. 2017 Jul;14(7):1087-1096.
    # Pulmonary vein (PV) isolation is the cornerstone of ablating atrial fibrillation triggers. However, in more than 10% of the patients sustained atrial fibrillation remains demonstrated to be initiated from non-PV foci. This article gives a complete overview of the different potential triggers for atrial fibrillation.
  • Sim I, Bishop M, O'Neill M, Williams SE. Left atrial voltage mapping: defining and targeting the atrial fibrillation substrate. J interv Card Electrophysiol 2019 May 10. doi: 10.1007/s10840-019-00537-8. [Epub ahead of print]
    # Low atrial voltage areas are correlated with clinical outcomes after ablation for atrial fibrillation (AF). Results of trials targeting low voltages areas shows mixed success ratios.It is important to understand the voltage mapping techniques, the relation between the low voltage and the pathophysiology of AF and the limitations in voltage measurement. This review provides an analysis of the utility and limitations of voltage mapping
  • Narayan SM, Krummen DE, Shivkumar K, Clopton P, Rappel WJ, Miller JM. Treatment of atrial fibrillation by the ablation of localized sources: CONFIRM (Conventional Ablation for Atrial Fibrillation With or Without Focal Impulse and Rotor Modulation) trial. J Am Coll Cardiol. 2012 Aug 14;60(7):628-36.
    # Narayan et al. devised a technique to identify stable focal arrhythmias. The so called rotors are relatively stable in time and they are multiple. The authors could prove that targeted ablation of these sites resulted in termination of atrial fibrillation (AF). In a later study, they shows that the freedom of AF was greater relative to conventional ablation.
  • Siebermair J, Kholmovski EG, Marrouche N. Assessment of Left Atrial Fibrosis by Late Gadolinium Enhancement Magnetic Resonance Imaging: Methodology and Clinical Implications. JACC Clin Electrophysiol. 2017 Aug;3(8):791-802.
    # The presence of atrial fibrosis has an impact on the progression of atrial fibrillation (AF) and on the success-ratio of ablation. Determine the amount of fibrosis by late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) has prognostic values in predicting outcomes after AF ablation. This article reviews the current methodology of trial fibrosis imaging using LGE-MRI and it discusses the clinical implications and future challenges.
  • Narayan SM, Wright M, Derval N, Jadidi A, Forclaz A, Nault I, Miyazaki S, Sacher F, Bordachar P, Clémenty J, Jaïs P, Haïssaguerre M, Hocini M. Classifying fractionated electrograms in human atrial fibrillation using monophasic action potentials and activation mapping: evidence for localized drivers, rate acceleration, and nonlocal signal etiologies. Heart Rhythm. 2011 Feb;8(2):244-53.
    # Complex fractionated electrograms (CFAEs) detected during mapping of atrial substrate for atrial fibrillation are difficult to interpret. They can reflect local activation, wave collisions of far-field potentials. These article demonstrates that only a minority of CFAEs indicates localized rapid AF sites (later defined as rotors).
  • Pandit SV, Jalife J. Rotors and the dynamics of cardiac fibrillation. Circ Res. 2013 Mar 1;112(5):849-62.
    # The concept of focal drivers, so called rotors, is an important observation with important therapeutic implications. Pandit et al discuss this concept and describes the intrinsic properties. They give a review of the role of rotors and the accompanying spiral waves in the mechanism of atrial fibrillation. 
  • Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. Haissaguerre M, Jais P, Shah DC, Takahashi A, Hocini M, Quiniou G, et al. N Engl J Med 1998;339:659-666.
    # This landmark paper shows that the pulmonary veins (PV) often harbour the ectopic foci that are responsible for “focally-induced atrial fibrillation”. Ablation of these foci is able to prevent AF recurrences. The goal of this article was to ablate these foci. Nowadays, because of it risks. these technique is abundant and replaced by a full encircling of the ostia of the PV’s to achieve electrical isolation.
  • 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation. Calkins H, Hindricks G, Cappato R, Kim YH, Saad EB, Aguinaga L, et al. Europace. 2018 Jan 1;20(1):157-208.

Junctional and AV node ectopy and tachycardias 

  • Veenhuyzen GD, Quinn FR, Wilton SB, Clegg R, Mitchell LB. Diagnostic pacing maneuvers for supraventricular tachycardia: part 1. Pacing Clin Electrophysiol. 2011 Jun;34(6):767-82.
    # Diagnostic electrophysiological management of supraventricular arrhythmias remains one of the biggest challenges in the world of electrophysiology. Veenhuyzen et al reviews in a two-part manuscript the diagnostic pacing maneuvers. Part one describes the concept of ventricular overdrive pacing (VOP), including a review of post-VOP response, fusion during entrainment, the importance of the VOP site, quantitative results of entrainment such as the postpacing interval, differential entrainment, and new criteria derived from features found at the beginning of the VOP train.
  • Veenhuyzen GD, Quinn FR, Wilton SB, Clegg R, Mitchell LB. Pacing. Diagnostic pacing maneuvers for supraventricular tachycardia: part 2. Pacing Clin Electrophysiol 2012 Jun;35(6):757-69.
    # In part 2 of their manuscript, Veenhuyzen et al reviews other diagnostic pacing maneuvers that might be helpful when ventricular overdrive pacing is not diagnostic or appropriate. These include attempts to reset SVT with single atrial or ventricular beats, para-Hisian pacing, apex versus base pacing, and atrial overdrive pacing.
  • Veenhuyzen GD1, Quinn FR. Principles of entrainment: diagnostic utility for supraventricular tachycardia. Indian Pacing Electrophysiol J. 2008 Feb 1;8(1):51-65.
    # Entrainment is an important maneuver during electrophysiological testing. Knowledge of this concept is essential in the diagnostic approach of supraventricular tachycardia’s. These article provides an overview of how entrainment can be used to reach diagnosis. It proposes a simple algorithm for the application on complex circuits.
  • Asirvatham, The world of entrainment and stimulation manoeuvres for differentiating for SVT’s. EHRA 2017 (on
    # This is not an article but a very good presentation about a step-by-step diagnostic approach of supraventricular tachycardias.
  • Heidbüchel H, Jackman WM. Characterization of subforms of AV nodal reentrant tachycardia. Europace. 2004 Jul;6(4):316-29.
    # The aim of this article was to improve the classic definition of the three subforms of AVNRT: “Slow/Fast", "Slow/Slow" and "Fast/Slow". A reason for these approach is the identification of the retrograde pathway during AVNRT. This is based on the earliest activation and not on the H-A interval during tachycardia because this is partly defined by the antegrade conduction time over a lower common pathway (LCP).  Prof. Heidbuchel and Prof. Jackman distinguish different AVNRT types based on atrial activation sequence, timing interval and evidence for the presence of a LCP. 
  • Knight BP, Zivin A, Souza J, Flemming M, Pelosi F, Goyal R, Man C, Strickberger SA, Morady F. A technique for the rapid diagnosis of atrial tachycardia in the electrophysiology laboratory. J Am Coll Cardiol. 1999 Mar;33(3):775-81.
    # Ventricular overdrive pacing is an important to distinguish atrial tachycardia from other supraventricular arrhythmias despite multiple maneuvers. Knight et al describes the atrial – ventricular response relationship after ventricular overdrive pacing during supraventricular arrhythmias and reviewed the pitfalls.
  • Heart Rhythm. 2005 Jun;2(6):667-72. Para-Hisian pacing: useful clinical technique to differentiate retrograde conduction between accessory atrioventricular pathways and atrioventricular nodal pathways. Nakagawa H1, Jackman WM.
    # Parahisian pacing is useful in differentiating between retrograde conduction over an accessory pathway and retrograde conduction over the fast or slow AV nodal pathway. These article describes accurately how to perform these technique and how to interpret the ventricular-his-atrial respons during pacing. Despite, it gives an overview of possible pittfalls.
  • Miller JM, Rosenthal ME, Vassallo JA, Josephson ME: Atrioventricular nodal reentrant tachycardia: Studies on upper and lower ‘‘common pathways.” Circulation 1987;75:930–940.
    # This is the first description of the upper and lower common pathways.
  • Hirao K, Otomo K, Wang X, Beckman KJ, McClelland JH, Widman L, Gonzalez MD, Arruda M, Nakagawa H, Lazzara R, Jackman WM. Circulation. 1996 Sep 1;94(5):1027-35.Para-Hisian pacing. A new method for differentiating retrograde conduction over an accessory AV pathway from conduction over the AV node.
    # Parahisian pacing is useful in differentiating between retrograde conduction over an accessory pathway and retrograde conduction over the fast or slow AV nodal pathway. This is the first description of parahisian pacing
  • Katritsis DG, Boriani G, Cosio FG, Hindricks G, Jaïs P, Josephson ME, Keegan R, Kim YH, Knight BP, Kuck KH, Lane DA, Lip GY, Malmborg H, Oral H, Pappone C, Themistoclakis S, Wood KA, Blomström-Lundqvist C, Gorenek B, Dagres N, Dan GA, Vos MA, Kudaiberdieva G, Crijns H, Roberts-Thomson K, Lin YJ, Vanegas D, Caorsi WR, Cronin E, Rickard J. European Heart Rhythm Association (EHRA) consensus document on the management of supraventricular arrhythmias, endorsed by Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS), and Sociedad Latinoamericana de Estimulación Cardiaca y Electrofisiologia (SOLAECE). Europace. 2017 Mar 1;19(3):465-511.

Accessory pathway mediated tachycardias

  • Fox  DJ,  Klein  GJ,  Skanes  AC,  Gula  LJ,  Yee  R,  Krahn  AD.  How  to  identify  the location  of  an  accessory  pathway  by  the  12-lead  ECG.  Heart  Rhythm Dec 2008;5:1763-1766.
  • Nakagawa H, Jackman WM. Catheter ablation of paroxysmal supraventricular tachycardia. Circulation Nov 20 2007;116:2465-2478.
    # Comprehensive contemporary review on ablation of SVT
  • Haissaguerre  M,  Gaita  F,  Marcus  FI,  Clementy  J. Radiofrequency  catheter ablation   of   accessory   pathways:   a   contemporary   review.   J   Cardiovasc Electrophysiol Jun 1994;5:532-552.
    # Historical review on ablation of WPW
  • Arruda MS, McClella nd JH, Wang X, Beckman KJ, Widman LE, Gonzalez MD, Nakagawa  H,  Lazzara  R,  Jackman  WM.  Development  and  validation  of  an ECG  algorithm  for  identifying  accessory  pathway  ablation  site  in  Wolff-Parkinson-White syndrome. J Cardiovasc ElectrophysiolcJan 1998;9:2-12.
  • Calkins  H,  Kim  YN,  Schmaltz  S,  Sousa  J,  el-Atassi  R,  Leon  A,  Kadish  A, Langberg JJ, Morady F. Electrogram criteria for identification of appropriate target sites for radiofrequency catheter ablation of accessory atrioventricular connections. Circulation Feb 1992;85:565-573.
  • Fitzpatrick  AP,  Gonzales  RP,  Lesh  MD,  Modin  GW,  Lee  RJ,  Scheinman  MM. New algorithm for the localization of accessory atrioventricular connections using a baseline electrocardiogram. J Am Coll Cardiol Jan 1994;23:107-116.
    # Three classical algorithm papers to predict location of accessory pathway 
  • Borggrefe M, Budde T, Podczeck A, Breithardt G. High frequency alternating current  ablation  of  an  accessory  pathway  in  humans.  J  Am  Coll  Cardiol Sep 1987;10:576-582.
    # Landmark paper describing the very early experience in WPW ablation 
  • Jackman  WM,  Wang  XZ,  Friday  KJ,  Roman  CA,  Moulton  KP,  Beckman  KJ, McClelland  JH,  TwidaleN,  Hazlitt  HA,  Prior  MI,  et  al.  Catheter  ablation  of accessory atrioventricular pathways (Wolff-Parkinson-White syndrome) by radiofrequency current. N Engl J Med Jun 6 1991;324:1605-1611.
    # Landmark paper describing the very early experience in WPW ablation – from the US 
  • Kuck  KH,  Schluter  M,  Geiger  M,  Siebels  J,  Duckeck  W.  Radiofrequency current  catheter  ablation  of  accessory  atrioventricular  pathways.  Lancet Jun 29 1991;337:1557-1561.
    # Landmark paper describing the very early experience in WPW ablation – in Europe
  • Katritsis DG, Boriani G, Cosio FG, et al. European Heart Rhythm Association (EHRA)   consensus   document   on   the   management   of   supraventricular arrhythmias,  endorsed  by  Heart  Rhythm  Society  (HRS),  Asia-Pacific  Heart Rhythm  Society  (APHRS),  and  Sociedad  Latinoamericana  de  Estimulacion Cardiaca  y  Electrofisiologia  (SOLAECE).  Eur  Heart  J Apr  21  2018;39:1442-1445.
  • Cohen  MI,  Triedman  JK,  Cannon  BC,  et  al. PACES/HRS  expert  consensus statement  on  the  management  of  the  asymptomatic  young  patient  with  a Wolff-Parkinson-White (WPW, ventricular preexcitation) electrocardiographic   pattern:   developed   in    partnership between   the Pediatric  and  Congenital  Electrophysiology  Society  (PACES)  and  the  Heart Rhythm  Society  (HRS).  Endorsed  by  the  governing  bodies  of  PACES,  HRS, the American College of Cardiology Foundation (ACCF), the American Heart Association  (AHA),  the  American  Academy  of  Pediatrics  (AAP),  and  the Canadian Heart  Rhythm  Society  (CHRS).  Heart  Rhythm Jun  2012;9:1006-1024.
  • Al-Khatib  SM,  Arshad  A,  Balk  EM,  Das  SR,  Hsu  JC,  Joglar  JA,  Page  RL.  Risk Stratification  for  Arrhythmic  Events  in  Patients  With  Asymptomatic  Pre-Excitation:  A  Systematic  Review  for  the  2015  ACC/AHA/HRS  Guideline  for the  Management  of  Adult  Patients  With  Supraventricular  Tachycardia:  A Report  of  the  American  College  of  Cardiology/American  Heart  Association Task  Force  on  Clinical  Practice  Guidelines  and  the  Heart  Rhythm  Society. J Am Coll Cardiol Apr 5 2016;67:1624-1638.

Ventricular ectopy and tachycardias 

  • Dukkipati   SR,   Choudry   S,   Koruth   JS,   Miller  MA,   Whang   W,   Reddy   VY. Catheter Ablation of Ventricular Tachycardia in Structurally Normal Hearts: Indications,  Strategies,  and  Outcomes-Part  I.  J  Am  Coll  CardiolDec  12 2017;70:2909-2923.
  • Dukkipati   SR,   Koruth   JS,   Choudry   S,   Miller   MA,   Whang   W,   Reddy   VY. Catheter  Ablation  of  Ventricular  Tachycardia  in  Structural  Heart  Disease: Indications,  Strategies,  and  Outcomes-Part  II.  J  Am  Coll  CardiolDec  12 2017;70:2924-2941.
  • Tanawuttiwat  T,  Nazarian  S,  Calkins  H.  The  role  of  catheter  ablation  in  the management  of  ventricular  tachycardia.  Eur  Heart  JFeb  14  2016;37:594-609.
  • Kim  RJ,  Iwai  S,  Markowitz  SM,  Shah  BK,  Stein  KM,  Lerman  BB.  Clinical  and electrophysiological    spectrum   of   idiopathic   ventricular   outflow   tract arrhythmias. J Am Coll CardiolMay 22 2007;49:2035-2043.
  • Heeger  CH,  Hayashi  K,  Kuck  KH,  Ouyang  F.  Catheter  Ablation  of  Idiopathic Ventricular  Arrhythmias  Arising  From  the  Cardiac  Outflow  Tracts-Recent Insights  and  Techniques  for  the  Successful  Treatment  of  Common  and Challenging Cases. Circ JApr 25 2016;80:1073-1086.
  • Sung   RK,   Boyden   PA,   Scheinman   M.   Cellular   Physiology   and   Clinical Manifestations   of   Fascicular   Arrhythmias   in   Normal   Hearts.   JACC   Clin ElectrophysiolDec 11 2017;3:1343-1355.
  • Josephson   ME,   Callans   DJ.   Using   the   twelve-lead   electrocardiogram   to localize  the  site  of  origin  of  ventricular  tachycardia.  Heart  RhythmApr 2005;2:443-446.Marchlinski  FE,  Callans  DJ,  Gottlieb  CD,  Zado  E.  Linear ablation  lesions  for control  of  unmappable  ventricular  tachycardia  in  patients  with  ischemic and nonischemic cardiomyopathy. CirculationMar 21 2000;101:1288-1296.
  • Haqqani  HM,  Roberts-Thomson  KC.  Radiofrequency  catheter  ablation  for ventricular tachycardia. Heart Lung CircJun 2012;21:402-412.
  • Pedersen  CT,  Kay  GN,  Kalman  J,  et  al.  EHRA/HRS/APHRS  expert  consensus on ventricular arrhythmias. EuropaceSep 2014;16:1257-1283.
  • Corrado  D,  Wichter  T,  Link  MS,  et  al.  Treatment  of  arrhythmogenic  right ventricular     cardiomyopathy/dysplasia:     an     international     task     force consensus statement. Eur Heart JDec 7 2015;36:3227-3237.

Ventricular fibrillation  

  • Haissaguerre  M,  Vigmond  E,  Stuyvers  B,  Hocini  M,  Bernus  O.  Ventricular arrhythmias    and    the    His-Purkinje    system.    Nat    Rev    CardiolMar2016;13:155-166.
    # Contemporary review on the topic
  • Shah  AJ,  Hocini  M,  Denis  A,  Derval  N,  Sacher  F,  Jais  P,  Haissaguerre  M. Polymorphic  Ventricular  Tachycardia/Ventricular  Fibrillation  and  Sudden Cardiac    Death    in    the    Normal    Heart.    Card    Electrophysiol    ClinSep 2016;8:581-591.
    # Excellent contemporary review on the topic
  • Anderson  RD,  Kumar  S,  Kalman  JM,  Sanders  P,  Sacher  F,  Hocini  M,  Jais  P, Haisaguerre  M,  Lee  G.  Catheter  Ablation  of  Ventricular  Fibrillation.  Heart Lung CircJan 2019;28:110-122.
    # Very contemporary review on idiopathic VF ablation
  • Haissaguerre  M,  Shoda  M,  Jais  P,  et  al.  Mapping  and  ablation  of  idiopathic ventricular fibrillation. CirculationAug 20 2002;106:962-967.
    # Landmark paper introducing the concept of idiopathic VF ablation
  • Ozaydin M, Moazzami K, Kalantarian S, Lee H, Mansour M, Ruskin JN. Long-Term Outcome of Patients With Idiopathic Ventricular Fibrillation: A Meta-Analysis. J Cardiovasc ElectrophysiolOct 2015;26:1095-1104.
  • Itoh T, Yamada T. Multifocal Ventricular Arrhythmias Originating From the His-Purkinje  System:  Incidence,  Characteristics,  and  Outcome  of  Catheter Ablation. JACC Clin ElectrophysiolSep 2018;4:1248-1260.
  • Belhassen   B,   Shapira   I,   Shoshani   D,   Paredes   A,   Miller   H,   Laniado   S. Idiopathic ventricular fibrillation: inducibility and beneficial effects of class I antiarrhythmic agents. CirculationApr 1987;75:809-816.
    # Historical landmark paper on the topic
  • Haissaguerre M, Shah DC, Jais P, et al. Role of Purkinje conducting system in triggering of idiopathic ventricular fibrillation. LancetFeb 23 2002;359:677-678.
    # Historical landmark paper on the topic
  • Belhassen  B,  Glick  A,  Viskin  S.  Excellent  long-term  reproducibility  of  the electrophysiologic    efficacy    of    quinidine    in    patients    with    idiopathic ventricular  fibrillation  and  Brugada  syndrome.  Pacing  Clin  ElectrophysiolMar 2009;32:294-301.