Imperial College London

DrZacharyWhinnett

Faculty of MedicineNational Heart & Lung Institute

Reader in Cardiac Electrophysiology
 
 
 
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z.whinnett

 
 
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South- NHLI Cardiovascular ScienceBlock B Hammersmith HospitalHammersmith Campus

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138 results found

Arnold A, Howard J, Chiew K, Kerrigan W, de Vere F, Johns H, Churilov L, Ahmad Y, Keene D, Shun-Shin M, Cole G, Kanagaratnam P, Sohaib S, Varnava A, Francis D, Whinnett Zet al., 2019, Right ventricular pacing for hypertrophic obstructive cardiomyopathy: meta-analysis and meta-regression of clinical trials, European Heart Journal - Quality of Care and Clinical Outcomes, Vol: 5, Pages: 321-333, ISSN: 2058-5225

AimsRight ventricular pacing for left ventricular outflow tract gradient reduction in hypertrophic obstructive cardiomyopathy remains controversial. We undertook a meta-analysis for echocardiographic and functional outcomes.Methods and resultsThirty-four studies comprising 1135 patients met eligibility criteria. In the four blinded randomized controlled trials (RCTs), pacing reduced gradient by 35% [95% confidence interval (CI) 23.2–46.9, P < 0.0001], but there was only a trend towards improved New York Heart Association (NYHA) class [odds ratio (OR) 1.82, CI 0.96–3.44; P = 0.066]. The unblinded observational studies reported a 54.3% (CI 44.1–64.6, P < 0.0001) reduction in gradient, which was a 18.6% greater reduction than the RCTs (P = 0.0351 for difference between study designs). Observational studies reported an effect on unblinded NYHA class at an OR of 8.39 (CI 4.39–16.04, P < 0.0001), 450% larger than the OR in RCTs (P = 0.0042 for difference between study designs). Across all studies, the gradient progressively decreased at longer follow durations, by 5.2% per month (CI 2.5–7.9, P = 0.0001).ConclusionRight ventricular pacing reduces gradient in blinded RCTs. There is a non-significant trend to reduction in NYHA class. The bias in assessment of NYHA class in observational studies appears to be more than twice as large as any genuine treatment effect.

Journal article

Keene D, Arnold A, Jastrzębski M, Burri H, Zweibel S, Crespo E, Chandrasekaran B, Bassi S, Joghetaei N, Swift M, Moskal P, Francis D, Foley P, Shun-Shin M, Whinnett Zet al., 2019, His bundle pacing, learning curve, procedure characteristics, safety, and feasibility: Insights from a large international observational study, Journal of Cardiovascular Electrophysiology, Vol: 30, Pages: 1984-1993, ISSN: 1045-3873

BackgroundHis‐bundle pacing (HBP) provides physiological ventricular activation. Observational studies have demonstrated the techniques feasibility however, data has come from a limited number of centres.ObjectivesWe set out to explore contemporary global practise in HBP focusing on learning curve, procedural characteristics and outcomes.MethodsThis is a retrospective, multi‐centre observational study of patients undergoing attempted HBP at seven centres. Pacing indication, fluoroscopy time, HBP thresholds and lead re‐intervention and deactivation rates were recorded. Where centres had systematically recorded implant success rates from the outset, these were collated.Results529 patients underwent attempted HBP during the study period (2014‐19) with mean follow‐up of 217±303 days. Most implants were for bradycardia indications.In the three centres with systematic collation of all attempts, overall implant success rate was 81% which improved to 87% after completion of 40 cases.All seven centres reported data on successful implants. Mean fluoroscopy time was 11.7±12.0 minutes, His‐bundle capture threshold at implant was 1.4±0.9V at 0.8±0.3 ms and was 1.3±1.2V at 0.9±0.2ms at last device check.HBP lead re‐intervention or deactivation (for lead displacement or rise in threshold) occurred in 7.5% of successful implants.There was evidence of a learning curve: fluoroscopy time and HBP capture threshold reduced with greater experience, plateauing after ~30‐50 cases.ConclusionWe found that it is feasible to establish a successful HBP program, using the currently available implantation tools. For physicians who are experienced at pacemaker implantation the steepest part of the learning curve appears to be over the first 30‐50 cases.

Journal article

Shun-Shin MJ, Leong KMW, Ng FS, Linton NWF, Whinnett ZI, Koa-Wing M, Qureshi N, Lefroy DC, Harding SE, Lim PB, Peters NS, Francis DP, Varnava AM, Kanagaratnam Pet al., 2019, Ventricular conduction stability test: a method to identify and quantify changes in whole heart activation patterns during physiological stress, EP-Europace, Vol: 21, Pages: 1422-1431, ISSN: 1099-5129

AIMS: Abnormal rate adaptation of the action potential is proarrhythmic but is difficult to measure with current electro-anatomical mapping techniques. We developed a method to rapidly quantify spatial discordance in whole heart activation in response to rate cycle length changes. We test the hypothesis that patients with underlying channelopathies or history of aborted sudden cardiac death (SCD) have a reduced capacity to maintain uniform activation following exercise. METHODS AND RESULTS: Electrocardiographical imaging (ECGI) reconstructs >1200 electrograms (EGMs) over the ventricles from a single beat, providing epicardial whole heart activation maps. Thirty-one individuals [11 SCD survivors; 10 Brugada syndrome (BrS) without SCD; and 10 controls] with structurally normal hearts underwent ECGI vest recordings following exercise treadmill. For each patient, we calculated the relative change in EGM local activation times (LATs) between a baseline and post-exertion phase using custom written software. A ventricular conduction stability (V-CoS) score calculated to indicate the percentage of ventricle that showed no significant change in relative LAT (<10 ms). A lower score reflected greater conduction heterogeneity. Mean variability (standard deviation) of V-CoS score over 10 consecutive beats was small (0.9 ± 0.5%), with good inter-operator reproducibility of V-CoS scores. Sudden cardiac death survivors, compared to BrS and controls, had the lowest V-CoS scores post-exertion (P = 0.011) but were no different at baseline (P = 0.50). CONCLUSION: We present a method to rapidly quantify changes in global activation which provides a measure of conduction heterogeneity and proof of concept by demonstrating SCD survivors have a reduced capacity to maintain uniform activation following exercise.

Journal article

Keene D, Shun-Shin M, Arnold A, Howard J, Lefroy D, Davies W, Lim PB, Ng FS, Koa-Wing M, Qureshi N, Linton N, Shah J, Peters N, Kanagaratnam P, Francis D, Whinnett Zet al., 2019, Quantification of Electromechanical Coupling to Prevent Inappropriate Implantable Cardioverter-Defibrillator Shocks, JACC: Clinical Electrophysiology, Vol: 5, Pages: 705-715, ISSN: 2405-500X

Objective To test specialised processing of laser Doppler signals for discriminating ventricular fibrillation(VF) from common causes of inappropriate therapies.BackgroundInappropriate ICD therapies remain a clinically important problem associated with morbidity and mortality.Tissue perfusion biomarkers, to assist automated diagnosis of VF, suffer the vulnerability of sometimes mistaking artefact and random noise for perfusion, which could lead to shocks being inappropriately withheld. MethodsWe developed a novel processing algorithm that combines electrogram data and laser Doppler perfusion monitoring, as a method for assessing circulatory status. We recruited 50 patients undergoing VF induction during ICD implantation. We recorded non-invasive laser Doppler and continuous electrograms, during both sinus-rhythm and VF. For each patient we simulated two additional scenarios that may lead to inappropriate shocks: ventricular-lead fracture and T-wave oversensing. We analysed the laser Doppler using three methods for reducing noise: (i)Running Mean, (ii)Oscillatory Height, (iii)a novel quantification of Electro-Mechanical coupling which gates laser Doppler against electrograms. We additionally tested the algorithm during exercise induced sinus tachycardia.ResultsOnly the Electro-mechanical coupling algorithm found a clear perfusion cut-off between sinus rhythm and VF (sensitivity and specificity 100%). Sensitivity and specificity remained 100% during simulated lead fracture and electrogram oversensing. (AUC: Running Mean 0.91, Oscillatory Height 0.86, Electro-Mechanical Coupling 1.00). Sinus tachycardia did not cause false positives.ConclusionsQuantifying the coupling between electrical and perfusion signals increases reliability of discrimination between VF and artefacts that ICDs may interpret as VF. Incorporating such methods into future ICDs may safely permit reductions of inappropriate shocks.

Journal article

ShunShin MJ, Miyazawa AA, Keene D, Sterliński M, Sokal A, Heuverswyn F, Rinaldi CA, Cornelussen R, Stegemann B, Francis DP, Whinnett Zet al., 2019, How to deliver personalized Cardiac Resynchronization Therapy through the precise measurement of the acute hemodynamic response: insights from the iSpot trial, Journal of Cardiovascular Electrophysiology, ISSN: 1045-3873

IntroductionNew pacing technologies offer greater choice of left ventricular pacing sites and greater personalization of cardiac resynchronization therapy (CRT). The effects on cardiac function of novel pacing configurations are often compared using multi‐beat averages of acute hemodynamic measurements. In this analysis of the iSpot trial we explore whether this is sufficient.MethodsThe iSpot trial was an international, prospective, acute hemodynamic trial that assessed seven CRT configurations: Standard CRT, Multispot (posterolateral vein), and Multivein (anterior and posterior vein) pacing. Invasive and non‐invasive blood pressure, and LV dP/dtmax were recorded. Eight beats were recorded before and after an alternation from AAI to the tested pacing configuration and vice‐versa. Eight alternations were performed for each configuration at each of the 5 AV delays.Results25 patients underwent the full protocol of 8 alternations. Only 4 (16%) patients had a statistically significant >3mmHg improvement over conventional CRT configuration (posterolateral vein, distal electrode). However, if only one alternation was analyzed (standard multi‐beat averaging protocol), 15 (60%) patients falsely appeared to have a superior non‐conventional configuration. Responses to pacing were significantly correlated between the different hemodynamic measures: invasive SBP versus non‐invasive SBP r=0.82 (p<0.001); invasive SBP versus LV dP/dt r=0.57, r2=0.32 (p<0.001).ConclusionsCurrent standard multi‐beat acquisition protocols are unfortunately unable to prevent false impressions of optimality arising in individual patients. Personalization processes need to include distinct repeated transitions to the tested pacing configuration in addition to averaging multiple beats. The need is not only during research stages, but also during clinical implementation.

Journal article

Howard J, Fisher L, Shun-Shin M, Keene D, Arnold A, Ahmad Y, Cook C, Moon J, Manisty C, Whinnett Z, Cole G, Rueckert D, Francis Det al., 2019, Cardiac rhythm device identification using neural networks, JACC: Clinical Electrophysiology, Vol: 5, Pages: 576-586, ISSN: 2405-5018

BackgroundMedical staff often need to determine the model of a pacemaker or defibrillator (cardiac rhythm devices) quickly and accurately. Current approaches involve comparing a device’s X-ray appearance with a manual flow chart. We aimed to see whether a neural network could be trained to perform this task more accurately.Methods and ResultsWe extracted X-ray images of 1676 devices, comprising 45 models from 5 manufacturers. We developed a convolutional neural network to classify the images, using a training set of 1451 images. The testing set was a further 225 images, consisting of 5 examples of each model. We compared the network’s ability to identify the manufacturer of a device with those of cardiologists using a published flow-chart.The neural network was 99.6% (95% CI 97.5 to 100) accurate in identifying the manufacturer of a device from an X-ray, and 96.4% (95% CI 93.1 to 98.5) accurate in identifying the model group. Amongst 5 cardiologists using the flow-chart, median manufacturer accuracy was 72.0% (range 62.2% to 88.9%), and model group identification was not possible. The network was significantly superior to all of the cardiologists in identifying the manufacturer (p < 0.0001 against the median human; p < 0.0001 against the best human).ConclusionsA neural network can accurately identify the manufacturer and even model group of a cardiac rhythm device from an X-ray, and exceeds human performance. This system may speed up the diagnosis and treatment of patients with cardiac rhythm devices and it is publicly accessible online.

Journal article

Sharp A, Sohaib A, Shun-Shin M, Pabari P, Wilson K, Rajkumar C, Hughes A, Kanagaratnam P, Mayet J, Whinnett Z, Kyriacou A, Francis Det al., 2019, Improving haemodynamic optimization of cardiac resynchronization therapy for heart failure., Physiol Meas

Objective&#13; Optimization of cardiac resynchronization therapy using non-invasive haemodynamic parameters, produces reliable optima when performed at high atrial paced heart rates. Here we investigate whether this is a result of increased heart rate or atrial pacing itself.&#13; &#13; Approach&#13; 43 patients with cardiac resynchronization therapy underwent haemodynamic optimization of AV delay using non-invasive beat-to-beat systolic blood pressure in three states: rest (atrial-sensing, 66±11bpm), slow atrial pacing (73±12bpm), and fast atrial pacing (94±10bpm). A 20-patient subset underwent a fourth optimization, during exercise (80±11bpm). &#13; &#13; Main results&#13; Intraclass correlation coefficient (ICC, quantifying information content mean ±SE) was 0.20±0.02 for resting sensed optimization, 0.45± 0.03 for slow atrial pacing (p&lt;0.0001 versus rest-sensed), and 0.52±0.03 for fast atrial pacing (p=0.12 versus slow-paced). 78% of the increase in ICC, from sinus rhythm to fast atrial pacing, is achieved by simply atrially pacing just above sinus rate.&#13; &#13; Atrial pacing increased signal (blood pressure difference between best and worst AV delay) from 6.5±0.6 mmHg at rest to 13.3±1.1 mmHg during slow atrial pacing (p&lt;0.0001) and 17.2±1.3 mmHg during fast atrial pacing (p=0.003 versus slow atrial pacing). &#13; &#13; Atrial pacing reduced noise (average SD of systolic blood pressure measurements) from 4.9±0.4mmHg at rest to 4.1±0.3mmHg during slow atrial pacing (p=0.28). At faster atrial pacing the noise was 4.6±0.3mmHg (p=0.69 versus slow-paced, p=0.90 versus rest-sensed). &#13; &#13; In the exercise subgroup ICC was 0.14±0.02 (p=0.97 versus rest-sensed).&#13; &#13; Significance&#13; Atrial pacing, rather than the increase in heart rate, contributes to ~80% of the observed in

Journal article

Lewis AJM, Foley P, Whinnett Z, Keene D, Chandrasekaran Bet al., 2019, His bundle pacing: a new strategy for physiological ventricular activation, Journal of the American Heart Association : Cardiovascular and Cerebrovascular Disease, Vol: 8, Pages: e010972-e010972, ISSN: 2047-9980

The specialized fibers of the His‐Purkinje system are essential for the maintenance of the coordinated, synchronous ventricular contraction via endocardial to epicardial and apical to basal electrical activation. The right ventricle has been the most commonly used site to deliver artificial pacemaker stimuli since the 1950s, although pacing from both right ventricular (RV) apical and septal positions causes ventricular dyssynchrony, which is in turn associated with deleterious consequences including impaired myocardial perfusion,1 mitral and tricuspid regurgitation,2 an increased risk of atrial fibrillation, and systolic contractile dysfunction.3 As a result, the risk of hospitalization for heart failure was strikingly increased in patients receiving a higher proportion of ventricular pacing in the DAVID (Dual Chamber and VVI Implantable Defibrillator) trial 4, 5 and MOST (Mode Selection Trial)6 alongside an increased risk of ventricular tachycardia/fibrillation.7 Current guidelines8 and pacemaker algorithms9 therefore promote the minimization of right ventricular pacing wherever possible; however, excessive restriction of RV pacing with, for example, long atrioventricular delays impairs atrioventricular synchrony, increasing the risk of atrioventricular block at higher atrial rates and predisposing to mitral regurgitation. Furthermore, current strategies for the reduction of RV pacing have not improved clinical outcomes.10

Journal article

Burri H, Keene D, Whinnett Z, Zanon F, Vijayaraman Pet al., 2019, Device Programming for His Bundle Pacing, CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY, Vol: 12, ISSN: 1941-3149

Journal article

Arnold A, Shun-Shin M, Keene D, Howard J, Sohaib S, wright I, Cole G, Qureshi N, lefroy D, Koa-Wing M, Linton N, Lim P, Peters N, Davies D, muthumala A, Tanner M, ellenbogen K, Kanagaratnam P, Francis D, Whinnett Zet al., 2018, His resynchronization versus biventricular pacing in patients with heart failure and left bundle branch block, Journal of the American College of Cardiology, Vol: 72, Pages: 3112-3122, ISSN: 0735-1097

Background His bundle pacing is a new method for delivering cardiac resynchronization therapy (CRT).Objectives The authors performed a head-to-head, high-precision, acute crossover comparison between His bundle pacing and conventional biventricular CRT, measuring effects on ventricular activation and acute hemodynamic function.Methods Patients with heart failure and left bundle branch block referred for conventional biventricular CRT were recruited. Using noninvasive epicardial electrocardiographic imaging, the authors identified patients in whom His bundle pacing shortened left ventricular activation time. In these patients, the authors compared the hemodynamic effects of His bundle pacing against biventricular pacing using a high-multiple repeated alternation protocol to minimize the effect of noise, as well as comparing effects on ventricular activation.Results In 18 of 23 patients, left ventricular activation time was significantly shortened by His bundle pacing. Seventeen patients had a complete electromechanical dataset. In them, His bundle pacing was more effective at delivering ventricular resynchronization than biventricular pacing: greater reduction in QRS duration (−18.6 ms; 95% confidence interval [CI]: −31.6 to −5.7 ms; p = 0.007), left ventricular activation time (−26 ms; 95% CI: −41 to −21 ms; p = 0.002), and left ventricular dyssynchrony index (−11.2 ms; 95% CI: −16.8 to −5.6 ms; p < 0.001). His bundle pacing also produced a greater acute hemodynamic response (4.6 mm Hg; 95% CI: 0.2 to 9.1 mm Hg; p = 0.04). The incremental activation time reduction with His bundle pacing over biventricular pacing correlated with the incremental hemodynamic improvement with His bundle pacing over biventricular pacing (R = 0.70; p = 0.04).Conclusions His resynchronization delivers better ventricular resynchronization, and greater improvement in hemodynamic parameters, than biventricular pacing.

Journal article

Sharma PS, Naperkowski A, Bauch TD, Chan JYS, Arnold AD, Whinnett ZI, Ellenbogen KA, Vijayaraman Pet al., 2018, Permanent His Bundle Pacing for Cardiac Resynchronization Therapy in Patients With Heart Failure and Right Bundle Branch Block, CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY, Vol: 11, ISSN: 1941-3149

Journal article

Arnold AD, Shun-Shin MJ, Sohaib A, Chiew K, Howard JP, Keene D, Leong K, Ahmad Y, Cole G, Lefroy D, Kanagaratnam P, Varnava A, Francis DP, Whinnett ZIet al., 2018, Automated, high-precision echocardiographic and haemodynamic assessment of the effect of atrioventricular interval during right ventricular pacing in obstructed hypertrophic cardiomyopathy, European-Society-of-Cardiology Congress, Publisher: OXFORD UNIV PRESS, Pages: 729-729, ISSN: 0195-668X

Conference paper

Ali N, Keene D, Arnold A, Shun-Shin M, Whinnett ZI, Sohaib SMAet al., 2018, His bundle pacing: a new frontier in the treatment of heart failure, Arrhythmia & electrophysiology review, Vol: 7, Pages: 103-110, ISSN: 2050-3369

Biventricular pacing has revolutionised the treatment of heart failure in patients with sinus rhythm and left bundle branch block; however, left ventricular-lead placement is not always technically possible. Furthermore, biventricular pacing does not fully normalise ventricular activation and, therefore, the ventricular resynchronisation is imperfect. Right ventricular pacing for bradycardia may cause or worsen heart failure in some patients by causing dyssynchronous ventricular activation. His bundle pacing activates the ventricles via the native His-Purkinje system, resulting in true physiological pacing, and, therefore, is a promising alternate site for pacing in bradycardia and traditional CRT indications in cases where it can overcome left bundle branch block. Furthermore, it may open up new indications for pacing therapy in heart failure, such as targeting patients with PR prolongation, but a narrow QRS duration. In this article we explore the physiology, technology and potential roles of His bundle pacing in the prevention and treatment of heart failure.

Journal article

Whinnett Z, Sohaib SMA, Mason M, Duncan E, Tanner M, Lefroy D, Al-Obaidi M, Ellery S, Leyva-Leon F, Betts T, Dayer M, Foley P, Swinburn J, Thomas M, Khiani R, Wong T, Yousef Z, Rogers D, Kalra P, Dhileepan V, March K, Howard J, Kyriacou A, Mayet J, Kanagaratnam P, Frenneaux M, Hughes A, Francis Det al., 2018, Multicenter randomized controlled crossover trial comparing hemodynamic optimization against echocardiographic optimization of AV and VV delay of Cardiac Resynchronization Therapy: The BRAVO Trial, JACC: Cardiovascular Imaging, ISSN: 1936-878X

ObjectivesBRAVO (British Randomized Controlled Trial of AV and VV Optimization) is a multicenter, randomized, crossover, noninferiority trial comparing echocardiographic optimization of atrioventricular (AV) and interventricular delay with a noninvasive blood pressure method.BackgroundCardiac resynchronization therapy including AV delay optimization confers clinical benefit, but the optimization requires time and expertise to perform.MethodsThis study randomized patients to echocardiographic optimization or hemodynamic optimization using multiple-replicate beat-by-beat noninvasive blood pressure at baseline; after 6 months, participants were crossed over to the other optimization arm of the trial. The primary outcome was exercise capacity, quantified as peak exercise oxygen uptake. Secondary outcome measures were echocardiographic left ventricular (LV) remodeling, quality-of-life scores, and N-terminal pro–B-type natriuretic peptide.ResultsA total of 401 patients were enrolled, the median age was 69 years, 78% of patients were men, and the New York Heart Association functional class was II in 84% and III in 16%. The primary endpoint, peak oxygen uptake, met the criterion for noninferiority (pnoninferiority = 0.0001), with no significant difference between the hemodynamically optimized arm and echocardiographically optimized arm of the trial (mean difference 0.1 ml/kg/min). Secondary endpoints for noninferiority were also met for symptoms (mean difference in Minnesota score 1; pnoninferiority = 0.002) and hormonal changes (mean change in N-terminal pro–B-type natriuretic peptide -10 pg/ml; pnoninferiority = 0.002). There was no significant difference in LV size (mean change in LV systolic dimension 1 mm; pnoninferiority < 0.001; LV diastolic dimension 0 mm; pnoninferiority <0.001). In 30% of patients the AV delay identified as optimal was more than 20 ms from the nominal setting of 120 ms.ConclusionsOptimization of cardiac resynchronization therapy

Journal article

Luther V, Qureshi N, Lim PB, Koa-Wing M, Jamil-Copley S, Ng FS, Whinnett Z, Davies DW, Peters NS, Kanagaratnam P, Linton Net al., 2018, Isthmus sites identified by Ripple Mapping are usually anatomically stable: A novel method to guide atrial substrate ablation?, Journal of Cardiovascular Electrophysiology, Vol: 29, Pages: 404-411, ISSN: 1045-3873

BACKGROUND: Postablation reentrant ATs depend upon conducting isthmuses bordered by scar. Bipolar voltage maps highlight scar as sites of low voltage, but the voltage amplitude of an electrogram depends upon the myocardial activation sequence. Furthermore, a voltage threshold that defines atrial scar is unknown. We used Ripple Mapping (RM) to test whether these isthmuses were anatomically fixed between different activation vectors and atrial rates. METHODS: We studied post-AF ablation ATs where >1 rhythm was mapped. Multipolar catheters were used with CARTO Confidense for high-density mapping. RM visualized the pattern of activation, and the voltage threshold below which no activation was seen. Isthmuses were characterized at this threshold between maps for each patient. RESULTS: Ten patients were studied (Map 1 was AT1; Map 2: sinus 1/10, LA paced 2/10, AT2 with reverse CS activation 3/10; AT2 CL difference 50 ± 30 ms). Point density was similar between maps (Map 1: 2,589 ± 1,330; Map 2: 2,214 ± 1,384; P  =  0.31). RM activation threshold was 0.16 ± 0.08 mV. Thirty-one isthmuses were identified in Map 1 (median 3 per map; width 27 ± 15 mm; 7 anterior; 6 roof; 8 mitral; 9 septal; 1 posterior). Importantly, 7 of 31 (23%) isthmuses were unexpectedly identified within regions without prior ablation. AT1 was treated following ablation of 11/31 (35%) isthmuses. Of the remaining 20 isthmuses, 14 of 16 isthmuses (88%) were consistent between the two maps (four were inadequately mapped). Wavefront collision caused variation in low voltage distribution in 2 of 16 (12%). CONCLUSIONS: The distribution of isthmuses and nonconducting tissue within the ablated left atrium, as defined by RM, appear concordant between rhythms. This could guide a substrate ablative approach.

Journal article

Leong KMW, chow J-J, Ng FS, Falaschetti E, Qureshi N, Koa-Wing M, Linton N, Whinnett Z, Lefroy D, Davies DW, Lim PB, Peters N, Kanagaratnam P, Varnava Aet al., 2017, Comparison of the Prognostic Usefulness of the European Society of Cardiology and American Heart Association/American College of Cardiology Foundation Risk Stratification Systems for Patients With Hypertrophic Cardiomyopathy, American Journal of Cardiology, Vol: 121, Pages: 349-355, ISSN: 0002-9149

Implantable cardio-defibrillators (ICDs) have proven benefit in preventing sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HC), making risk stratification essential. Data on the predictive accuracy on the European Society of Cardiology (ESC) risk scoring system has been conflicting. We independently evaluated the ESC risk scoring system in our cohort of HC patients from a large tertiary centre and compared this to previous guidance by the American College of Cardiology Foundation and Heart Association (ACCF/AHA). Risk factor profiles, 5-year SCD risk estimates and ICD recommendations as defined by the ACCF/AHA and ESC guidelines, were retrospectively ascertained for 288 HC patients with and without SCD or equivalent events at our centre. In the SCD group (n=14), a significantly higher proportion of patients would not have met the criteria for an ICD implant using the ESC scoring algorithm than ACCF/AHA guidance (43%vs7%, p=0.029). In those without SCD events (n=274), a larger proportion of individuals not requiring an ICD was identified using the ESC risk score model compared to the ACCF/AHA model (82%vs57%; p<0.0001). Based on risk stratification criteria alone, 5 more individuals with a previously aborted SCD event would not have received an ICD with the ESC risk model than the ACCF/AHA risk model. In conclusion, we found that the current ESC scoring system potentially leaves more high-risk patients unprotected from sudden death in our cohort of patients.

Journal article

Leong KMW, Ng FS, Roney C, Cantwell C, Shun-Shin M, Linton N, Whinnett Z, Lefroy D, Davies DW, Harding S, Lim PB, Francis D, Peters N, Varnava A, Kanagaratnam Pet al., 2017, Repolarization abnormalities unmasked with exercise in sudden cardiac death survivors with structurally normal hearts, Journal of Cardiovascular Electrophysiology, Vol: 29, Pages: 115-126, ISSN: 1045-3873

BACKGROUND: Models of cardiac arrhythmogenesis predict that non-uniformity in repolarization and/or depolarization promotes ventricular fibrillation and is modulated by autonomic tone, but this is difficult to evaluate in patients. We hypothesize that such spatial heterogeneities would be detected by non-invasive ECG imaging (ECGi) in sudden cardiac death (SCD) survivors with structurally normal hearts under physiological stress. METHODS: ECGi was applied to 11 SCD survivors, 10 low-risk Brugada Syndrome patients (BrS) and 10 controls undergoing exercise treadmill testing. ECGi provides whole heart activation maps and > 1200 unipolar electrograms over the ventricular surface from which global dispersion of activation recovery interval (ARI) and regional delay in conduction were determined. These were used as surrogates for spatial heterogeneities in repolarization and depolarization. Surface ECG markers of dispersion (QT and Tpeak-end intervals) were also calculated for all patients for comparison. RESULTS: Following exertion, the SCD group demonstrated the largest increase in ARI dispersion compared to BrS and control groups (13±8 ms vs 4±7 ms vs 4±5 ms; p = 0.009), with baseline dispersion being similar in all groups. In comparison, surface ECG markers of dispersion of repolarisation were unable to discriminate between the groups at baseline or following exertion. Spatial heterogeneities in conduction were also present following exercise but were not significantly different between SCD survivors and the other groups. CONCLUSION: Increased dispersion of repolarization is apparent during physiological stress in SCD survivors and is detectable with ECGi but not with standard ECG parameters. The electrophysiological substrate revealed by ECGi could be the basis of alternative risk-stratification techniques. This article is protected by copyright. All rights reserved.

Journal article

Su J, Manisty C, Parker KH, Simonsen U, Nielsen-Kudsk JE, Mellemkjaer S, Connolly S, Lim PB, Whinnett ZI, Malik IS, Watson G, Davies JE, Gibbs S, Hughes AD, Howard Let al., 2017, Wave Intensity Analysis Provides Novel Insights Into Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension., Journal of the American Heart Association, Vol: 6, ISSN: 2047-9980

BACKGROUND: In contrast to systemic hypertension, the significance of arterial waves in pulmonary hypertension (PH) is not well understood. We hypothesized that arterial wave energy and wave reflection are augmented in PH and that wave behavior differs between patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). METHODS AND RESULTS: Right heart catheterization was performed using a pressure and Doppler flow sensor-tipped catheter to obtain simultaneous pressure and flow velocity measurements in the pulmonary artery. Wave intensity analysis was subsequently applied to the acquired data. Ten control participants, 11 patients with PAH, and 10 patients with CTEPH were studied. Wave speed and wave power were significantly greater in PH patients compared with controls, indicating increased arterial stiffness and right ventricular work, respectively. The ratio of wave power to mean right ventricular power was lower in PAH patients than CTEPH patients and controls. Wave reflection index in PH patients (PAH: ≈25%; CTEPH: ≈30%) was significantly greater compared with controls (≈4%), indicating downstream vascular impedance mismatch. Although wave speed was significantly correlated to disease severity, wave reflection indexes of patients with mildly and severely elevated pulmonary pressures were similar. CONCLUSIONS: Wave reflection in the pulmonary artery increased in PH and was unrelated to severity, suggesting that vascular impedance mismatch occurs early in the development of pulmonary vascular disease. The lower wave power fraction in PAH compared with CTEPH indicates differences in the intrinsic and/or extrinsic ventricular load between the 2 diseases.

Journal article

Leong KMW, Ng FS, yao C, Roney C, Linton N, Whinnett Z, lefroy D, Davies DW, Lim PB, Harding S, Peters N, Kanagaratnam P, Varnava Aet al., 2017, ST-Elevation Magnitude Correlates With Right Ventricular Outflow Tract Conduction Delay in Type I Brugada ECG, Circulation: Arrhythmia and Electrophysiology, Vol: 10, ISSN: 1941-3084

Background: The substrate location and underlying electrophysiological mechanisms that contribute to the characteristic ECG pattern of Brugada syndrome (BrS) are still debated. Using noninvasive electrocardiographical imaging, we studied whole heart conduction and repolarization patterns during ajmaline challenge in BrS individuals.Methods and Results: A total of 13 participants (mean age, 44±12 years; 8 men), 11 concealed patients with type I BrS and 2 healthy controls, underwent an ajmaline infusion with electrocardiographical imaging and ECG recordings. Electrocardiographical imaging activation recovery intervals and activation timings across the right ventricle (RV) body, outflow tract (RVOT), and left ventricle were calculated and analyzed at baseline and when type I BrS pattern manifested after ajmaline infusion. Peak J-ST point elevation was calculated from the surface ECG and compared with the electrocardiographical imaging–derived parameters at the same time point. After ajmaline infusion, the RVOT had the greatest increase in conduction delay (5.4±2.8 versus 2.0±2.8 versus 1.1±1.6 ms; P=0.007) and activation recovery intervals prolongation (69±32 versus 39±29 versus 21±12 ms; P=0.0005) compared with RV or left ventricle. In controls, there was minimal change in J-ST point elevation, conduction delay, or activation recovery intervals at all sites with ajmaline. In patients with BrS, conduction delay in RVOT, but not RV or left ventricle, correlated to the degree of J-ST point elevation (Pearson R, 0.81; P<0.001). No correlation was found between J-ST point elevation and activation recovery intervals prolongation in the RVOT, RV, or left ventricle.Conclusions: Magnitude of ST (J point) elevation in the type I BrS pattern is attributed to degree of conduction delay in the RVOT and not prolongation in repolarization time.

Journal article

Sau A, Sikkel MB, Luther V, Wright I, Guerrero F, Koa-Wing M, Lefroy D, Linton N, Qureshi N, Whinnett Z, Lim PB, Kanagaratnam P, Peters NS, Davies DWet al., 2017, The sawtooth EKG pattern of typical atrial flutter is not related to slow conduction velocity at the cavotricuspid isthmus., Journal of Cardiovascular Electrophysiology, Vol: 28, Pages: 1445-1453, ISSN: 1045-3873

INTRODUCTION: We hypothesized that very high density mapping of typical atrial flutter (AFL) would facilitate a more complete understanding of its circuit. Such very high density mapping was performed with the Rhythmia mapping system using its 64 electrode basket catheter. METHODS AND RESULTS: Data were acquired from 13 patients in AFL. Functional anatomy of the right atrium (RA) was readily identified during mapping including the Crista Terminalis and Eustachian ridge. The leading edge of the activation wavefront was identified without interruption and its conduction velocity (CV) calculated. CV was not different at the cavotricuspid isthmus (CTI) compared to the remainder of the RA (1.02 vs. 1.03 m/s, p = 0.93). The sawtooth pattern of the surface EKG flutter waves were compared to the position of the dominant wavefront. The downslope of the surface EKG flutter waves represented on average, 73% ± 9% of the total flutter cycle length. During the downslope the activation wavefront travelled significantly further than during the upslope (182 ± 21 ms vs. 68 ± 29 ms, p < 0.0001) with no change in conduction velocity between the two phases (0.88 vs. 0.91 m/s, p = 0.79). CONCLUSION: CV at the CTI is not slower than other RA regions during typical AFL. The gradual downslope of the sawtooth EKG is not due to slow conduction at the CTI suggesting that success of ablation at this site relates to anatomical properties rather than presence of a "slow isthmus". This article is protected by copyright. All rights reserved.

Journal article

Luther V, Sikkel M, Bennett N, Guerrero F, Leong K, Qureshi N, Ng FS, Hayat SA, Sohaib SMA, Malcolme-Lawes L, Lim E, Wright I, Koa-Wing M, Lefroy DC, Linton NWF, Whinnett Z, Kanagaratnam P, Davies W, Peters NS, Lim PBet al., 2017, Visualizing Localized Reentry With Ultra-High Density Mapping in Iatrogenic Atrial Tachycardia Beware Pseudo-Reentry, CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY, Vol: 10, ISSN: 1941-3149

Background—The activation pattern of localized reentry (LR) in atrial tachycardia remains incompletely understood. We used the ultra–high density Rhythmia mapping system to study activation patterns in LR.Methods and Results—LR was suggested by small rotatory activations (carousels) containing the full spectrum of the color-coded map. Twenty-three left-sided atrial tachycardias were mapped in 15 patients (age: 64±11 years). 16 253±9192 points were displayed per map, collected over 26±14 minutes. A total of 50 carousels were identified (median 2; quartiles 1–3 per map), although this represented LR in only n=7 out of 50 (14%): here, rotation occurred around a small area of scar (<0.03 mV; 12±6 mm diameter). In LR, electrograms along the carousel encompassed the full tachycardia cycle length, and surrounding activation moved away from the carousel in all directions. Ablating fractionated electrograms (117±18 ms; 44±13% of tachycardia cycle length) within the carousel interrupted the tachycardia in every LR case. All remaining carousels were pseudo-reentrant (n=43/50 [86%]) occurring in areas of wavefront collision (n=21; median 0.5; quartiles 0–2 per map) or as artifact because of annotation of noise or interpolation in areas of incomplete mapping (n=22; median 1, quartiles 0–2 per map). Pseudo-reentrant carousels were incorrectly ablated in 5 cases having been misinterpreted as LR.Conclusions—The activation pattern of LR is of small stable rotational activations (carousels), and this drove 30% (7/23) of our postablation atrial tachycardias. However, this appearance is most often pseudo-reentrant and must be differentiated by interpretation of electrograms in the candidate circuit and activation in the wider surrounding region.

Journal article

Shun-Shin MJ, Zheng S, Cole G, Howard J, Whinnett Z, Francis Det al., Implantable cardioverter defibrillators for primary prevention of death in left ventricular dysfunction with and without ischaemic heart disease: a meta-analysis of 8567 patients in the 11 trials, European Heart Journal, Vol: 38, Pages: 1738-1746, ISSN: 1522-9645

AimsPrimary prevention implantable cardioverter defibrillators (ICDs) are established therapy for reducing mortality in patients with left ventricular systolic dysfunction and ischaemic heart disease (IHD). However, their efficacy in patients without IHD has been controversial. We undertook a meta-analysis of the totality of the evidence.Methods We systematically identified all RCTs comparing ICD versus no ICD in primary prevention. Eligible RCTs were those that recruited patients with left ventricular dysfunction, reported all-cause mortality, and presented their results stratified by the presence of IHD (or recruited only those with or without). Our primary endpoint was all-cause mortality.ResultsWe identified 11 studies enrolling 8567 participants with left ventricular dysfunction, including 3128 patients without IHD and 5439 patients with IHD. In patients without IHD, ICD therapy reduced mortality by 24% (HR 0.76, 95% CI 0.64 to 0.90 p=0.001). In patients with IHD, ICD implantation (at a dedicated procedure), also reduced mortality by 24% (HR 0.76, 95% CI 0.60 to 0.96, p=0.02).ConclusionsUntil now, it has never been explicitly stated that the patients without IHD in COMPANION showed significant survival benefit from adding ICD therapy (to a background of CRT). Furthermore, even with only the trials before DANISH, meta-analysis shows reduced mortality. DANISH is consistent with these data.With a significant 24% mortality reduction in both aetiologies, it may no longer be necessaryto distinguish between them when deciding on primary prevention ICD implantation.

Journal article

Jones S, Lumens J, Sohaib SMA, Finegold JA, Kanagaratnam P, Tanner M, Duncan E, Moore P, Leyva F, Frenneaux M, Mason M, Hughes AD, Francis D, Whinnett ZI, the BRAVO Investigators, on behalf of the BRAVO Investigatorset al., 2016, Cardiac Resynchronisation Therapy: mechanisms of action and scope for further improvement in cardiac function, Europace, Vol: 19, Pages: 1178-1186, ISSN: 1532-2092

BackgroundCardiac resynchronisation therapy(CRT) may exert its beneficial hemodynamic effect by improving ventricular synchrony and improving atrioventricular(AV) timing.Aims To establish the relative importance of the mechanisms through which CRT improves cardiac function and explore the potential for additional improvements with improved ventricular resynchronisation. Methods We performed simulations using the CircAdapt haemodynamic model and performed haemodynamic measurements while adjusting AV delay, at low and high heart rates, in 87 patients with CRT devices. We assessed QRS duration, presence of fusion and haemodynamic response.ResultsThe simulations suggest intrinsic PR interval and the magnitude of reduction in ventricular activation determine the relative importance of the mechanisms of benefit. For example, if PR interval is 201ms and LV activation time is reduced by 25ms (typical for current CRT methods) then AV delay optimisation is responsible for 69% of overall improvement. Reducing LV activation time by an additional 25ms produced an additional 2.6mmHg increase in BP (30% of effect size observed with current CRT).In the clinical population, ventricular fusion significantly shortened QRS duration (∆-27±23ms, P <0.001), and, improved SBP (mean 2.5 mmHg increase). Ventricular Fusion was present in 69% of patients, yet in 40% of patients with fusion, shortening AV delay (to a delay where fusion was not present) produced the optimal haemodynamic response.ConclusionsImproving LV preloading by shortening AV delay is an important mechanism through which cardiac function is improved with CRT. There is substantial scope for further improvement if methods for delivering more efficient ventricular resynchronisation can be developed.

Journal article

Leong KMW, Ng FS, Yao C, Yates S, Taraborrelli P, Linton NW, Whinnett Z, LeFroy D, Davies DW, Lim PB, Peters NS, Harding SE, Kanagaratnam P, Varnava Aet al., 2016, Contribution of Conduction and Repolarisation Abnormalities to the Type I Brugada Pattern: A Study Using Non-Invasive Electrocardiographic Imaging, Annual Conference of the British Cardiovascular Society (BCS) on Prediction and Prevention, Publisher: BMJ Publishing Group, Pages: A105-A106, ISSN: 1468-201X

Conference paper

Leong KMW, Chow J-J, Ng FS, Yates S, Wright I, Luther V, David L, Qureshi N, Koa-Wing M, Whinnett Z, Linton NW, Davies DW, Lim PB, Peters NS, Kanagaratnam P, Varnava Aet al., 2016, Risk Stratification in Hypertrophic Cardiomyopathy: Evaluation of the European Society of Cardiology Sudden Cardiac Death Risk Scoring System, Annual Conference of the British Cardiovascular Society (BCS) on Prediction and Prevention, Publisher: BMJ Publishing Group, Pages: A104-A105, ISSN: 1355-6037

Conference paper

Luther V, Linton NW, Jamil-Copley S, Koa-Wing M, Qureshi N, Ng F, Lim PB, Whinnett Z, Davies DW, Peters NS, Kanagaratnam Pet al., 2016, RIPPLE MAPPING THE VENTRICULAR SCAR: A NOVEL APPROACH TO SUBSTRATE ABLATION OF POST-INFARCT VENTRICULAR TACHYCARDIA TO PREVENT IMPLANTABLE DEFIBRILLATOR THERAPY, Annual Conference of the British-Cardiovascular-Society (BCS) on Prediction and Prevention, Publisher: BMJ PUBLISHING GROUP, Pages: A49-A50, ISSN: 1355-6037

Conference paper

Luther V, Linton NW, Jamil-Copley S, Koa-Wing M, Lim PB, Qureshi N, Ng FS, Hayat S, Whinnett Z, Davies DW, Peters NS, Kanagaratnam Pet al., 2016, A prospective study of ripple mapping the post-infarct ventricular scar to guide substrate ablation for ventricular tachycardia, Circulation-Arrhythmia and Electrophysiology, Vol: 9, ISSN: 1941-3084

BACKGROUND: Post-infarct ventricular tachycardia is associated with channels of surviving myocardium within scar characterized by fractionated and low-amplitude signals usually occurring late during sinus rhythm. Conventional automated algorithms for 3-dimensional electro-anatomic mapping cannot differentiate the delayed local signal of conduction within the scar from the initial far-field signal generated by surrounding healthy tissue. Ripple mapping displays every deflection of an electrogram, thereby providing fully informative activation sequences. We prospectively used CARTO-based ripple maps to identify conducting channels as a target for ablation. METHODS AND RESULTS: High-density bipolar left ventricular endocardial electrograms were collected using CARTO3v4 in sinus rhythm or ventricular pacing and reviewed for ripple mapping conducting channel identification. Fifteen consecutive patients (median age 68 years, left ventricular ejection fraction 30%) were studied (6 month preprocedural implantable cardioverter defibrillator therapies: median 19 ATP events [Q1-Q3=4-93] and 1 shock [Q1-Q3=0-3]). Scar (<1.5 mV) occupied a median 29% of the total surface area (median 540 points collected within scar). A median of 2 ripple mapping conducting channels were seen within each scar (length 60 mm; initial component 0.44 mV; delayed component 0.20 mV; conduction 55 cm/s). Ablation was performed along all identified ripple mapping conducting channels (median 18 lesions) and any presumed interconnected late-activating sites (median 6 lesions; Q1-Q3=2-12). The diastolic isthmus in ventricular tachycardia was mapped in 3 patients and colocated within the ripple mapping conducting channels identified. Ventricular tachycardia was noninducible in 85% of patients post ablation, and 71% remain free of ventricular tachycardia recurrence at 6-month median follow-up. CONCLUSIONS: Ripple mapping can be used to identify conduction channels within scar to guide functional substrate

Journal article

Luther V, Linton NW, Koa-Wing M, Lim PB, Jamil-Copley S, Qureshi N, Ng FS, Hayat S, Whinnett Z, Davies DW, Peters NS, Kanagaratnam Pet al., 2016, A Prospective Study of Ripple Mapping in Atrial Tachycardias: A Novel Approach to Interpreting Activation in Low-Voltage Areas., Circulation: Arrhythmia and Electrophysiology, Vol: 9, ISSN: 1941-3149

BACKGROUND: Post ablation atrial tachycardias are characterized by low-voltage signals that challenge current mapping methods. Ripple mapping (RM) displays every electrogram deflection as a bar moving from the cardiac surface, resulting in the impression of propagating wavefronts when a series of bars move consecutively. RM displays fractionated signals in their entirety thereby helping to identify propagating activation in low-voltage areas from nonconducting tissue. We prospectively used RM to study tachycardia activation in the previously ablated left atrium. METHODS AND RESULTS: Patients referred for atrial tachycardia ablation underwent dense electroanatomic point collection using CARTO3v4. RM was played over a bipolar voltage map and used to determine the voltage "activation threshold" that differentiated functional low voltage from nonconducting areas for each map. Ablation was guided by RM, but operators could perform entrainment or review the isochronal activation map for diagnostic uncertainty. Twenty patients were studied. Median RM determined activation threshold was 0.3 mV (0.19-0.33), with nonconducting tissue covering 33±9% of the mapped surface. All tachycardias crossed an isthmus (median, 0.52 mV, 13 mm) bordered by nonconducting tissue (70%) or had a breakout source (median, 0.35 mV) moving away from nonconducting tissue (30%). In reentrant circuits (14/20) the path length was measured (87-202 mm), with 9 of 14 also supporting a bystander circuit (path lengths, 147-234 mm). In breakout tachycardias, splitting of wavefronts resulted in 2 to 4 incomplete circuits. RM-guided ablation interrupted the tachycardia in 19 of 20 cases with the first ablation set. CONCLUSIONS: RM helps to define activation through low-voltage regions and aids ablation of atrial tachycardias.

Journal article

Kim M-Y, Ng FS, Ariff B, Hanna GB, Whinnett Z, Kanagaratnam P, Tanner M, Lim PBet al., 2015, Extensive Intramural Esophageal Hematoma After Transesophageal Echocardiography During Atrial Fibrillation Ablation, CIRCULATION, Vol: 132, Pages: 1847-1849, ISSN: 0009-7322

Journal article

Sohaib SMA, Wright I, Lim E, Moore P, Lim PB, Koawing M, Lefroy DC, Lustgarten D, Linton NWF, Davies DW, Peters NS, Kanagaratnam P, Francis DP, Whinnett ZIet al., 2015, Atrioventricular Optimized Direct His Bundle Pacing Improves Acute Hemodynamic Function in Patients With Heart Failure and PR Interval Prolongation Without Left Bundle Branch Block, JACC: Clinical electrophysiology, Vol: 1, Pages: 582-591, ISSN: 2405-5018

ObjectivesThe purpose of this study was to investigate whether heart failure patients with narrow QRS duration (or right bundle branch block) but with long PR interval gain acute hemodynamic benefit from atrioventricular (AV) optimization. We tested this with biventricular pacing and (to deliver pure AV shortening) direct His bundle pacing.BackgroundBenefits of pacing for heart failure have previously been indicated by acute hemodynamic studies and verified in outcome studies. A new target for pacing in heart failure may be PR interval prolongation, which is associated with 58% higher mortality regardless of QRS duration.MethodsWe enrolled 16 consecutive patients with systolic heart failure, PR interval prolongation (mean, 254 ± 62 ms) and narrow QRS duration (n = 13; mean QRS duration: 119 ± 17 ms) or right bundle branch block (n = 3; mean, QRS duration: 156 ± 18 ms). We successfully delivered temporary direct His bundle pacing in 14 patients and temporary biventricular pacing in 14 participants. We performed AV optimization using invasive systolic blood pressure obtaining parabolic responses (mean R2: 0.90 for His, and 0.85 for biventricular pacing).ResultsThe mean increment in systolic BP compared with intrinsic ventricular conduction was 4.1 mm Hg (95% confidence interval [CI]: +1.9 to +6.2 mm Hg for His and 4.3 mm Hg [95% CI: +2.0 to +6.5 mm Hg] for biventricular pacing. QRS duration lengthened with biventricular pacing (change = +22 ms [95% CI: +18 to +25 ms]) but not with His pacing (change = +0.5 ms [95% CI: −2.6 to +3.6 ms).ConclusionsAV-optimized pacing improves acute hemodynamic function in patients with heart failure and long PR interval without left bundle branch block. That it can be achieved by single-site His pacing shows that its mechanism is AV shortening. The improvement is ∼60% of the effect size previously reported for biventricular pacing in left bundle branch block. Randomized, blinded trials are warranted to tes

Journal article

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