Right Ventricular Pacing Burden Research Articles

Left ventricular global longitudinal strain is a long-term predictor of pacemaker-associated cardiomyopathy

Abstract Background Implantation of a permanent pacemaker is an effective treatment for symptomatic bradycardia. However, chronic right ventricular pacing (RVP) may lead to compromised left ventricular (LV) function, atrial fibrillation, heart failure, and increased mortality via pacing induced electrical and mechanical dyssynchrony. A decrease in LV ejection fraction (LVEF) of ≥ 10% with a baseline LVEF > 50% prior to RVP and no alternative explanation for the decline in LVEF is termed pacing-induced cardiomyopathy (PICM). Predictive clinical and imaging-derived measures to identify patients at high risk for pacemaker induced cardiomyopathy (PMIC) are lacking, but essential. Objective The study is a prospective, single center, double-blinded trial evaluating the impact of right ventricular pacing on left ventricular function and clinical outcome. Methods In 105 patients (59 male / 46 female), who underwent a dual-chamber pacemaker implantation at the Charité Campus Virchow Klinikum, RVP burden, LVEF and left ventricular global longitudinal strain (LV-GLS) were obtained. Mean follow-up per patient was 29.6 ±13.9 months. We used a stepwise analytic approach including ROC analysis, univariate testing, binary regression as well as Cox-regression models and Kaplan-Meier analysis to compare low RVP burden (< 30%) and high RVP burden (≥ 30%) cohorts according to change in echocardiographic parameters and clinical outcome (all-cause mortality). Results Mean LVEF was 61 ± 6% and mean LV-GLS was 18 ± 4% at baseline. We identified 7 patients with a LVEF decline in the course of the study. In Pearson’s Chi-squared test, patients with a high RVP burden were more likely to develop LVEF and LV-GLS deterioration (6 patients versus 1 patient for LVEF, p<0.05; 28 versus 16 patients for LV-GLS, p<0.001). In multivariable binary logistic regression, LV-GLS (OR: 1.410, 95% CI: 1.201-1.610, p<0.001) deterioration was significantly associated with a LVEF decline and a high RVP burden ≥ 30% (OR: 1.358, 95% CI: 1.160-1.534, p<0.01). In a log-rank test, time to LVEF decline was significantly shorter in patients with a RVP burden ≥ 30% compared to a RVP burden < 30% (45.2±2.9 versus 55.7±1.0 months, p<0.05). In the Cox-regression analysis, LV-strain decline within 12 months (HR: 7.210, 95% CI: 4.239-9.516, p<0.05) was a significant predictor for a later LVEF decline. In a log-rank test, time to LVEF deterioration was significantly shorter in patients with LV-strain decline within 12 months compared to those without (34.7 ± 4.2 versus 53.7 ± 1.4 months, p<0.001). No significant difference in all-cause mortality between patients with a high RVP burden compared to those with low RVP burden (log-rank test, p=0.2). Conclusion A decline in LV-GLS is a sensitive long-term parameter of subsequent LVEF deterioration in patients with normal preimplant LVEF, who require RVP ≥ 30%. and is associated with a poor clinical outcome.

The effect of cardiac resynchronisation therapy upgrade from right ventricular pacing on symptoms and functional clinical outcomes, results from the BUDAPEST-CRT Upgrade trial

Abstract Background Based on the results of the BUDAPEST-CRT Upgrade trial, in patients with intermittent or permanent right ventricular (RV) pacing and reduced left ventricular ejection fraction (HFrEF) upgrade to cardiac resynchronization therapy (CRT) reduces morbidity and mortality. Purpose Whether the substantial treatment effect of the CRT upgrade could also be detected in a better functional and exercise capacity is scarcely investigated. We examined the changes of the prespecified tertiary endpoints such as symptoms, quality of life (QoL), exercise capacity and natriuretic peptide measurement from baseline to 12 months. Methods In the BUDAPEST CRT Upgrade trial 360 HFrEF patients with a priorly implanted PM or ICD and >20% of RV pacing burden were randomly assigned to CRT-D upgrade (n=215) or ICD (n=145) in a 3:2 ratio. The prespecified tertiary endpoints were changes in quality of life measured by EQ-5D-3L, New York Heart Association (NYHA) functional class, 6-minute walk test (6-MWT), and NT-proBNP. When data of trial patients were unavailable due to death at 12 months, imputed values were used as 0 (6MWT) and 0 score (EQ-5D-3L) or a 5th grade (NYHA class). Responders were defined as >15% change of left ventricular end-systolic volume at 12 months. Results From baseline to 12 months, NYHA functional class improved in the CRT-D upgrade arm compared with the ICD only group [adjusted odds ratio (OR) 0.50; 95% CI 0.32-0.80; P=0.003]. According to the adjusted model there was a statistically significant decrease in the NT-proBNP [adjusted difference -1257 pg/mL; 95% CI -2287 – (-228); P=0.017]. In responders, the changes in NT-proBNP levels were significantly greater than in non-responders [adjusted difference -1635 pg/mL; 95% CI -2811 - (-459); P=0.007]. The progression of worsening of QoL attributed to ageing was moderated only by CRT-D upgrade [EQ-5D-3L difference by age -0.01; 95% CI -0.02 - (-0.003); P=0.004; interaction P=0.003]. 6MWT did not improve significantly in either group. Conclusions Patients receiving CRT upgrade showed a substantial improvement in symptoms and a significant decrease in natriuretic peptide levels, as compared to ICD alone, which was more pronounced in responders. Moreover, CRT-D upgrade could moderate the progression of worsening of quality of life attributed to ageing in this vulnerable, older patient population.

Optimizing Patient Selection for Physiological Pacing in Bradyarrhythmia: Factors Associated With High Ventricular Pacing Burden.

Right ventricular (RV) pacing is established as the most common ventricular pacing (VP) strategy for patients with symptomatic bradyarrhythmia. Some patients with high VP burden suffer deterioration of left ventricular (LV) function, termed pacing-induced cardiomyopathy (PICM). Patients who pace > 20% of the time from the RV apex are at increased risk of PICM, but independent predictors of increased RV pacing burden have not been elucidated in those who have a permanent pacemaker (PPM) inserted for bradyarrhythmia. We aimed to identify factors that are associated with increased VP burden > 20%, hence determining those at risk for resultant PICM. In this retrospective cohort study, we identified the most recent 300 consecutive cardiac implantable electronic device (CIED) implants in our center and collected past medical history, electrocardiogram (ECG), echo, medication and pacemaker check data. A total of 236 individuals met inclusion criteria. Of the patients, 35% had RV pacing burden < 20%, while 65% had VP burden ≥ 20%; 96.2% of patients with complete heart block (CHB) paced > 20% (P = 0.002). Utilization of DDD or VVI (75.2% and 89.2% of patients, respectively) without mode switch algorithms was associated with VP > 20% (P < 0.001). Male or previous coronary artery bypass grafting (CABG) patients also statistically paced > 20%. Other factors trending towards significance included prolonged PR interval, atrial fibrillation or more advanced age. High-grade atrioventricular (AV) block was associated with an RV pacing burden > 20% over 3 years but this was not consistent in patients with only transient episodes of high-grade AV block. We found a significant association between high VP% and male sex, previous CABG and the absence of mode switching algorithms.

Prediction of pacemaker-induced cardiomyopathy using a convolutional neural network based on clinical findings prior to pacemaker implantation

Risk factors for pacemaker-induced cardiomyopathy (PICM) have been previously reported, including a high burden of right ventricular pacing, lower left ventricular ejection fraction, a wide QRS duration, and left bundle branch block before pacemaker implantation (PMI). However, predicting the development of PICM remains challenging. This study aimed to use a convolutional neural network (CNN) model, based on clinical findings before PMI, to predict the development of PICM. Out of a total of 561 patients with dual-chamber PMI, 165 (mean age 71.6 years, 89 men [53.9%]) who underwent echocardiography both before and after dual-chamber PMI were enrolled. During a mean follow-up period of 1.7 years, 47 patients developed PICM. A CNN algorithm for prediction of the development of PICM was constructed based on a dataset prior to PMI that included 31 variables such as age, sex, body mass index, left ventricular ejection fraction, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, left atrial diameter, severity of mitral regurgitation, severity of tricuspid regurgitation, ischemic heart disease, diabetes mellitus, hypertension, heart failure, New York Heart Association class, atrial fibrillation, the etiology of bradycardia (sick sinus syndrome or atrioventricular block) , right ventricular (RV) lead tip position (apex, septum, left bundle, His bundle, RV outflow tract), left bundle branch block, QRS duration, white blood cell count, haemoglobin, platelet count, serum total protein, albumin, aspartate transaminase, alanine transaminase, estimated glomerular filtration rate, sodium, potassium, C-reactive protein, and brain natriuretic peptide. The accuracy, sensitivity, specificity, and area under the curve of the CNN model were 75.8%, 55.6%, 83.3% and 0.78 respectively. The CNN model could accurately predict the development of PICM using clinical findings before PMI. This model could be useful for screening patients at risk of developing PICM, ensuring timely upgrades to physiological pacing to avoid missing the optimal intervention window.

Cardiac resynchronization therapy for pacing induced cardiomyopathy: Role of baseline right ventricular pacing burden.

Cardiac resynchronization therapy (CRT) is indicated for patients with heart failure with reduced left ventricular ejection fraction (LVEF) and chronic right ventricular (RV) pacing burden ≥40% (pacing-induced cardiomyopathy, PICM). It is uncertain whether baseline RV pacing burden impacts response to CRT. We conducted a retrospective study of all CRT upgrades for PICM at our hospital from January 2017 to December 2018. Univariate and multivariable-adjusted changes in LVEF, and echocardiographic response (≥10% improvement in LVEF) at 3-12 months post-CRT upgrade were compared in those with RV pacing burden ≥90% versus<90%. We included 75 patients (age 74±11years, 71% male) who underwent CRT upgrade for PICM. The baseline RV pacing burden was ≥90% in 56 patients (median 99% [IQR 98%-99%]), and<90% in 19 patients (median 79% [IQR 73%-87%]). Improvement in LVEF was greater in those with baseline RV pacing burden ≥90%versus<90% (15.7±9.3%vs. 7.5±9.6%, p=.003). Baseline RV pacing burden ≥90% was a strong predictor of an improvement in LVEF ≥10% after CRT upgrade both in univariate and multivariate-adjusted models (p=.005 and .02, respectively). A higher baseline RV pacing burden predicts a greater improvement in LVEF after CRT upgrade for PICM.

Abstract 17657: The Effect of Medical Therapy on Reducing the Risk of Pacing Induced Cardiomyopathy

Introduction: Right ventricular (RV) pacing results in left ventricular dyssynchrony that can lead to pacing induced cardiomyopathy (PICM). The risk of PICM increases with RV pacing burden. No prior trials have investigated the effect of medical therapy on preventing PICM in patients with high RV pacing burden. The goal of this study was to investigate whether ACE inhibitors (ACEI), angiotensin receptor blockers (ARB), and beta blockers (BB) reduce the risk of PICM in patients with high RV pacing burden. Methods: This was a retrospective study which included patients with normal ejection fraction (EF) and complete heart block who underwent single- or dual-chamber pacemaker placement at Wake Forest Baptist Medical Center between 1992 - 2013. Exclusion criteria were age &lt;18 and myocardial infarction. The medical therapy group included patients who received ACEI/ARB, BB, or both. The control group included patients who received neither ACEI/ARB nor BB. The primary endpoint was PICM, which was defined as upgrade to a biventricular device or reduction in EF by ≥10% without another etiology identified. Follow-up was 10 years or until development of PICM. Kaplan-Meier and multivariable Cox proportional hazards ratio survival analysis was performed. Results: The study included 642 patients. Average age was 71 ± 14. Females were 51%. ACEI/ARB only was prescribed for 80 (12%), BB only was prescribed for 55 (9%), and both were prescribed for 114 (18%). PICM occurred in 12 out of a total of 249 in the medical therapy group (4.8%) and 28 out of a total of 393 in the control group (7.1%). The risk of PICM was significantly lower in the medical therapy group compared to the control group (HR 0.34, 95% CI 0.16 - 0.71, P&lt;0.01) in a model fully adjusted for age, sex, hypertension, diabetes mellitus, chronic kidney disease, and atrial fibrillation. Conclusions: In patients who have high RV pacing burden, medical therapy with ACEI/ARB and BB appears to reduce the risk of PICM.

Association of leadless pacing with ventricular and valvular function.

Traditional transvenous pacemakers are associated with worsening tricuspid valve function due to lead-related leaflet impingement, as well as ventricular dysfunction related to electromechanical dyssynchrony from chronic right ventricular (RV) pacing. The association of leadless pacing with ventricular and valvular function has not been well established. We aimed to assess the association of leadless pacemaker placement with changes in valvular regurgitation and ventricular function. Echocardiographic features before and after leadless pacemaker implant were analyzed in consecutive patients who received a leadless pacemaker with pre- and postprocedure echocardiography at Duke University Hospital between November 2014 and November 2019. Valvular regurgitation was graded ordinally from 0 (none) to 3 (severe). Among 54 patients, the mean age was mean age was 70.1 ± 14.3 years, 24 (44%) were women, and the most frequent primary pacing indication was complete heart block in 24 (44%). The median RV pacing burden was 45.4 (interquartile range [IQR] 3.5-97.0). On echocardiogram performed 8.9 months (IQR 4.5-14.5) after implant, there was no change in the average severity of tricuspid regurgitation (mean change 0.07 ± 1.15, p = .64) from pre-procedure echocardiogram. We observed a decrease in the average left ventricular ejection fraction (LVEF) (52.3 ± 9.3 to 47.9 ± 12.1, p = .0019) and tricuspid annular plane systolic excursion (TAPSE) (1.8 ± 0.6 to 1.6 ± 0.4, p = .0437). Thirteen patients (24%) had absolute drop in LVEF of ≥10%. We did not observe short term worsening valvular function in patients with leadless pacemakers. However, consistent with the pathophysiologic impact of RV pacing, leadless pacing was associated with a reduction in biventricular function.

Upgrade of right ventricular pacing to cardiac resynchronization therapy in heart failure: a randomized trial.

De novo implanted cardiac resynchronization therapy with defibrillator (CRT-D) reduces the risk of morbidity and mortality in patients with left bundle branch block, heart failure and reduced ejection fraction (HFrEF). However, among HFrEF patients with right ventricular pacing (RVP), the efficacy of CRT-D upgrade is uncertain. In this multicentre, randomized, controlled trial, 360 symptomatic (New York Heart Association Classes II-IVa) HFrEF patients with a pacemaker or implantable cardioverter defibrillator (ICD), high RVP burden ≥ 20%, and a wide paced QRS complex duration ≥ 150 ms were randomly assigned to receive CRT-D upgrade (n = 215) or ICD (n = 145) in a 3:2 ratio. The primary outcome was the composite of all-cause mortality, heart failure hospitalization, or <15% reduction of left ventricular end-systolic volume assessed at 12 months. Secondary outcomes included all-cause mortality or heart failure hospitalization. Over a median follow-up of 12.4 months, the primary outcome occurred in 58/179 (32.4%) in the CRT-D arm vs. 101/128 (78.9%) in the ICD arm (odds ratio 0.11; 95% confidence interval 0.06-0.19; P < .001). All-cause mortality or heart failure hospitalization occurred in 22/215 (10%) in the CRT-D arm vs. 46/145 (32%) in the ICD arm (hazard ratio 0.27; 95% confidence interval 0.16-0.47; P < .001). The incidence of procedure- or device-related complications was similar between the two arms [CRT-D group 25/211 (12.3%) vs. ICD group 11/142 (7.8%)]. In pacemaker or ICD patients with significant RVP burden and reduced ejection fraction, upgrade to CRT-D compared with ICD therapy reduced the combined risk of all-cause mortality, heart failure hospitalization, or absence of reverse remodelling.

Reduction of left ventricular global longitudinal strain in patients with permanent pacemakers as a predictor of heart failure and mortality outcomes.

Frequent right ventricular (RV) pacing is associated with cardiomyopathy. The impact of RV pacing on left ventricular (LV) global longitudinal strain (GLS) and clinical outcomes is unclear. We analyzed GLS via two-dimensional speckle tracking and LV ejection fraction (EF) on pre- and post-implantation transthoracic echocardiograms of patients undergoing dual chamber pacemaker implantation. We collected long-term data on strain, LVEF, and clinical outcomes. One hundred and ten patients (mean age 76±12years; 59 [54%] female) were followed for mean 23±17months. Mean baseline LVEF was 58±11% and mean GLS was -17±4%. Twenty-four (22%) patients had an absolute decrease in LVEF>10% and 43 (39%) patients had a relative reduction of GLS>15%. Among patients with a reduction of GLS, a larger proportion of patients had RV pacing burden ≥20% (67% vs. 46%; p=.048). Compared to patients without GLS reduction, more patients with a reduction in GLS reached a composite endpoint of HF hospitalization, CRT upgrade or death (47% vs. 16%; p=.001). Reduction in LV GLS was seen in nearly four in 10 patients undergoing pacemaker implantation and was significantly associated with increased RV pacing burden. LV GLS reduction was associated with increased risk of adverse outcomes. LV GLS may have utility in predicting outcomes among patients with RV pacing.

Ventricular conduction abnormality in patients with mild to moderate cardiomyopathy.

In mild-to-moderate cardiomyopathy, cardiac resynchronization therapy (CRT) is indicated in patients with high burden of right ventricular pacing but not in those with intrinsic ventricular conduction abnormalities. We hypothesized that CRT positively impacts outcomes of patients with intrinsic ventricular conduction delay and left ventricular ejection fraction (LVEF) of 36%-50%. Of 18 003 patients with LVEF ≤ 50%, 5966 (33%) patients had mild-to-moderate cardiomyopathy, of whom 1741 (29%) have a QRS duration ≥120 ms. Patients were followed to the endpoints of death and heart failure (HF) hospitalization. Outcomes were compared between patients with narrow versus wide QRS. Of the 1741 patients with mild-to-moderate cardiomyopathy and wide QRS duration, only 68 (4%) were implanted with a CRT device. Over a median follow-up of 3.35 years, 849 (51%) died and 1004 (58%) had a HF hospitalization. The adjusted risk of death (hazard ratio (HR) = 1.11, p = 0.046) and of death or HF hospitalization (HR = 1.10, p = 0.037) were significantly higher in patients with wide versus narrow QRS duration. In patients with wide QRS complex, CRT was associated with reduction in the adjusted risk of death (HR = 0.47, p = 0.020) and of death or HF hospitalization (HR = 0.58, p = 0.008). Patients with mild-to-moderate cardiomyopathy and wide QRS duration are rarely implanted with CRT devices and have worse outcomes compared to those with narrow QRS. Randomized trials are needed to examine if CRT has salutary effects in this population.

Clinical impact of right ventricular pacing burden in patients with post-transcatheter aortic valve replacement permanent pacemaker implantation.

Patients who undergo permanent pacemaker (PPM) implantation after transcatheter aortic valve replacement (TAVR) have a worse outcome. The aim of this study was to identify risk factors of worse outcomes in patients with post-TAVR PPM implantation. This is a single-centre, retrospective study of consecutive patients who underwent post-TAVR PPM implantation from 11 March 2011 to 9 November 2019. Clinical outcomes were evaluated by landmark analysis with cut-off at 1 year after the PPM implantation. Of the 1389 patients underwent TAVR during the study duration and a total of 110 patients were included in the final analysis. Right ventricular pacing burden (RVPB) ≥ 30% at 1 year was associated with a higher likelihood of heart failure (HF) readmission [adjusted hazard ratio (aHR): 6.333; 95% confidence interval [CI]: 1.417-28.311; P = 0.016] and composite endpoint of overall death and/or HF (aHR: 2.453; 95% CI: 1.040-5.786; P = 0.040). The RVPB ≥30% at 1 year was associated with higher atrial fibrillation burden (24.1 ± 40.6% vs. 1.2 ± 5.3%; P = 0.013) and a decrease in left ventricular ejection fraction (-5.0 ± 9.8% vs. + 1.1 ± 7.9%; P = 0.005). The predicting factors of the RVPB ≥30% at 1 year were the presence of RVPB ≥40% at 1 month and the valve implantation depth measured from non-coronary cusp ≥4.0 mm (aHR: 57.808; 95% CI: 12.489-267.584; P < 0.001 and aHR: 6.817; 95% CI: 1.829-25.402; P = 0.004). The RVPB ≥30% at 1 year was associated with worse outcomes. Clinical benefit of minimal RV pacing algorithms and biventricular pacing needs to be investigated.

Left bundle branch area pacing as a first line pacing strategy, which patients should we consider?

Abstract Background A higher right ventricular (RV) pacing burden in those with permanent pacemakers results in accelerated pacing induced cardiomyopathy, in addition to increased incidence of heart failure and mortality [1–3]. This process may necessitate upgrade to a biventricular system in time, as the cardiomyopathy progresses. Physiological conduction system pacing targets such as His-bundle pacing (HBP) or Left Bundle Branch Area Pacing (LBBAP) have been shown to generate comparatively narrower QRS complexes and thus mitigate this cardiomyopathy development [4,5]. The 2021 ESC guidelines have a class 2b indication for consideration of HBP as an alternative to RV pacing in those with AV block and left ventricular ejection fraction &amp;gt;40%, who are anticipated to have &amp;gt;20% ventricular pacing burden [6]. Purpose To retrospectively identify ECG, echocardiographic, permanent pacemaker (PPM) setting and patient factors associated with high RV pacing burden that may aid selection of those who may benefit from conduction system pacing (CSP). Methods We retrospectively identified 300 consecutive patients who underwent cardiac implantable electronic device insertion in our Electrophysiology Lab from the years 2017–2018. We excluded patients who underwent generator replacements, in addition to those who had biventricular devices or implantable cardioverter defibrillators inserted. We collated ECG, echo, past medical history and pacing data for each patient over a three-year follow up period. Data were analysed using SPSS v.26. Results 160 patients met inclusion criteria. Those with an RV pacing burden &amp;gt;20% were categorised group one (n=85) and those with &amp;lt;20% in group two (n=75). Baseline characteristics of these two groups are compared in Table 1 and Table 2. Our analysis showed that significant differences between these groups included a lower mean HR (Table 1) (55.1±17.8 vs 57.63±17.4) with a more prolonged PR interval (225.7ms ± 8.34 vs. 188.6ms ± 6.62) or atrial fibrillation/flutter (AF/AFL) on admission ECG. There were more males with a greater mean age (High Ventricular Paced (VP) = 76.6 years ± 8.4 vs Low VP = 71.23 years ± 12.3) in the higher VP group, and they demonstrated more incidence of dilated RA/RV on echo (Enlarged RA = 30.5%; Enlarged RV = 23.6% vs 10% and 8.4% respectively). There were significant differences in PPM indications and setting between groups (Table 2), with the higher VP groups having PPM inserted for persistent high-grade AV block (CHB = 31.5% vs 4.9% and Mobitz 2 = 9.6% vs 0%) and had less MVP mode activated (Mode switch algorithm = 13.3% vs 71%). Conclusion Our data suggests that those with persistent high grade AV block such as Mobitz 2 or CHB should be considered for CSP. Other considerations include older age, male sex, dilated RV/RA, prolonged PR, lower intrinsic HR or AF/AFL on admission ECG. PPM mode switching settings to reduce RV pacing burden should be utilised where possible. Funding Acknowledgement Type of funding sources: None.

Can left ventricle mass index predict pacemaker-induced cardiomyopathy in patients with dual chamber permanent pacemakers implanted due to complete atrioventricular block?

Abstract Background Pacing induced cardiomyopathy (PICM) occurs due to high-burden right ventricular pacing. In patients with complete atrioventricular (AV) block, it is presumed to have a higher burden of right ventricular pacing. There is a lack of data regarding the relationship between PICM and pre-implantation left ventricular mass index (LVMI). Purpose This study aims to investigate the effect of LVMI on PICM in patients with implanted dual chamber permanent pacemakers (PPM) due to complete AV block. Methods PPM implanted 577 patients were divided into three groups according to admission LVMI. Mean duration of follow-up was 57±38 months. The baseline characteristics, laboratory and echocardiographic variables were compared between the groups. The independent predictors of PICM incidence and the effect LVMI on PICM were evaluated. Results Age, post-implantation QRS duration, left atrium anteroposterior diameter and LVMI were determined to predict long-term PICM. After adjustment for confounding baseline variables, tertile with highest LVMI had 1.9 times higher rates of long-term PICM compared to tertile with lowest LVMI, which was used as the reference group. A ROC analysis showed that the optimal cut-off value of the LVMI to predict long-term PICM was 109.8 mg/m2 with 71% sensitivity and 62% specificity (AUC: 0.68; 95% CI: 0.60–0.76; p&amp;lt;0.001), Conclusion Pre-implantation LVMI plays an important prognostic role in predicting PICM in patients with implanted dual chamber PPM due to complete AV block. Funding Acknowledgement Type of funding sources: None.

Clinical impact of “minimal” right ventricular pacing on atrial arrhythmias: results from the prospective multi-center worldwide EMERALD study

Abstract Background/Introduction Unnecessary right ventricular pacing (RVP), typically the result of pacing forced by the atrio-ventricular delay (AVD), can have deleterious effects such as atrial arrhythmias (AA) and heart failure (HF). Previous studies have shown that these increased risks occur when unnecessary RVP exceeds 40%, leading to the development of pacing modes to reduce the amount of unnecessary RVP and minimize these risks. Purpose The EMERALD (AssEssment of CoMorbiditiEs &amp; Atrial ArRhythmiA Burden In DuaL-Chamber PaceD Patients) Study was a real-world registry designed to assess the impact of RVP burden on the risk of developing AA. The primary endpoint was the difference in incidence of persistent/permanent AA in subjects with high (&amp;gt;40%) and low (&amp;lt;40%) RVP. Methods EMERALD was a non-interventional, prospective, observational, multi-center registry conducted at 186 centers in 12 countries. The study enrolled subjects without a previous history of persistent or permanent AA implanted with a dual-chamber (DR) pacemaker according to ESC or ACC/AHA/HRS guidelines. Devices could be implanted as de-novo therapy, generator replacement or an upgrade in therapy. All implanted devices were approved for commercial use by local regulatory authorities. Programming was left to the investigators' discretion. Subjects were followed for at least 24 months. Persistent/permanent AA was defined as: a) &amp;gt;22 hours/day of AA for &amp;gt;7 consecutive days; b) permanent/persistent AA diagnosed during any follow-up visit; c) an AA-related ablation carried-out; d) a cardioversion performed during any follow-up visit. Results Eligible follow-up data were available for n=3477 subjects with a RVP value. The population was nearly evenly split between High RVP (47.7%) and Low RVP (52.3%). In the High RVP group, 11.7% fulfilled at least one criterion for persistent/permanent AA versus 9.1% in the Low RVP group (p=0.006). The primary endpoint was met. A reanalysis of the data was performed first looking at quartiles of %RVP. Based on this, the threshold of RVP was changed from 40% to 1% (High RVP&amp;gt;1%; Low RVP&amp;lt;1%). Using this new RVP threshold, 13.1% of patients in the High RVP group fulfilled at least 1 criterion for persistent/permanent AA versus 3.4% in the Low RVP group (p&amp;lt;0.0001). Conclusions The EMERALD Study confirmed the results of previous studies showing that limiting unnecessary RVP to &amp;lt;40% is beneficial in reducing the risk of AA in unselected DR pacemaker patients. Moreover, it showed for the first time that even small amounts of unnecessary RVP (&amp;gt;1%) significantly increases the risk of AAs, underlining the need to target very low RVP with efficient modes to reduce RVP. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): MicroPort CRM (Clamart, France)

Dual-chamber paced patients without high-degree AV block at baseline are at higher risk of atrial arrhythmias when inappropriately paced in the right ventricle: a sub-analysis of the EMERALD study

Abstract Background/Introduction Unnecessary right ventricular pacing (RVP) can have deleterious effects including an increased risk of atrial arrhythmia (AA) and heart failure during follow-up (FU) in dual-chamber (DR) paced patients. While previous studies have shown that these increased risks occur with RVP&amp;gt;40%, the EMERALD Study demonstrated an increased risk for RVP&amp;gt;1%. Few data exist on the interaction between the amount of RVP and the presence/absence of high-degree atrio-ventricular block (AVB) as a pacing indication at baseline. Purpose The EMERALD (AssEssment of CoMorbiditiEs &amp; Atrial ArRhythmiA Burden In DuaL-Chamber PaceD Patients) Study was a real-world registry designed to assess the impact of RVP burden on the risk of developing persistent/permanent AA (Pers-AA) over 2-year FU. The primary endpoint was the difference in Pers-AA in subjects with high (&amp;gt;40%) and low (&amp;lt;40%) RVP. This sub-analysis aimed to identify the interaction between RVP and the presence/absence of high-degree AVB at baseline in relation to the incidence of Pers-AA. Methods EMERALD was a non-interventional, prospective, multi-center registry conducted at 186 centers in 12 countries. Enrolled subjects were implanted with a DR pacemaker according to ESC or ACC/AHA/HRS guidelines. Subjects were excluded if they had a history of Pers-AA. Devices could be implanted as de-novo, replacement or upgrade therapy. Programming was left to the investigators' discretion. Subjects were followed for at least 24 months. Pers-AA was defined as: &amp;gt;22 h/day of AA for &amp;gt;7 consecutive days; Pers-AA diagnosed during any FU visit; AA-related ablation or cardioversion carried out in the FU period. We compared the incidence of Pers-AA between subjects with (n=1529) and without (n=1948) high-degree AVB as a baseline pacing indication. Results Eligible FU data were available for n=3477 subjects. The overall population was nearly evenly split - High RVP (47.7%) and Low RVP (52.3%). In the High RVP group, 11.7% experienced at least one Pers-AA episode versus 9.1% in the Low RVP group (p=0.006). In this sub-analysis, the prevalence of RVP&amp;gt;40% was higher in patients with high-degree AVB at baseline (74% vs 26%). Although the incidence of Pers-AA was similar in the group with high-degree AVB at baseline (High RVP 8.7% vs Low RVP 7.4%), in the group without high-degree AVB at baseline, those with High RVP developed a significantly higher incidence of Pers-AA (High RVP 18.2% vs Low RVP 9.5%, p value for interaction 0.0275; Figure 1). An analysis with a newly identified RVP threshold of 1% confirmed a high incidence of Pers-AA only in the group without high-degree AVB at baseline (18% vs 3.5%, p value for interaction 0.2265; Figure 2). Conclusions The baseline pacing indication sub-analysis of the EMERALD Study shows that patients without high-degree AVB as a baseline indication are at highest risk of Pers-AA. Efforts should be made to avoid any unnecessary RVP in this subgroup of patients. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): MicroPort CRM (Clamart, France)

Baseline clinical characteristics of heart failure patients with reduced ejection fraction enrolled in the BUDAPEST-CRT Upgrade trial.

The BUDAPEST-CRT Upgrade study is the first prospective, randomized, multicentre clinical trial investigating the outcomes after cardiac resynchronization therapy (CRT) upgrade in heart failure (HF) patients with intermittent or permanent right ventricular (RV) pacing with wide paced QRS. This report describes the baseline clinical characteristics of the enrolled patients and compares them to cohorts from previous milestone CRT studies. This international multicentre randomized controlled trial investigates 360 patients having a pacemaker (PM) or implantable cardioverter defibrillator (ICD) device for at least 6 months prior to enrolment, reduced left ventricular ejection fraction (LVEF ≤35%), HF symptoms (New York Heart Association [NYHA] functional class II-IVa), wide paced QRS (&gt;150 ms), and ≥20% of RV pacing burden without having a native left bundle branch block. At enrolment, the mean age of the patients was 73 ± 8 years; 89% were male, 97% were in NYHA class II/III functional class, and 56% had atrial fibrillation. Enrolled patients predominantly had conventional PM devices, with a mean RV pacing burden of 86%. Thus, this is a patient cohort with advanced HF, low baseline LVEF (25 ± 7%), high N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (2231 pg/ml [25th-75th percentile 1254-4309 pg/ml]), and frequent HF hospitalizations during the preceding 12 months (50%). When compared with prior CRT trial cohorts, the BUDAPEST-CRT Upgrade study includes older patients with a strong male predominance and a high burden of atrial fibrillation and other comorbidities. Moreover, this cohort represents an advanced HF population with low LVEF, high NT-proBNP, and frequent previous HF events. ClinicalTrials.gov NCT02270840.

Effects of Left Bundle Branch Block and Pacemaker Implantation on Left Ventricular Systolic Function After Transcatheter Aortic Valve Implantation

Permanent pacemaker implantation (PPI) and left bundle branch block (LBBB) frequency after transcatheter aortic valve implantation (TAVI) and their effect on left ventricular ejection fraction (LVEF) remain controversial. We evaluated the incidence of PPI and new-onset LBBB after TAVI and their impact on LVEF at 6-month follow-up. Moreover, the impact of right ventricular (RV) pacing burden on changes in LVEF after TAVI was analyzed. The electrocardiograms of 377 patients (age 80 ± 7years, 52% male) treated with TAVI were collected at baseline, after the procedure, at discharge, and at each outpatient follow-up. LVEF was measured at baseline before TAVI and 6months after the procedure. Patients were divided into 3 groups according to the occurrence of LBBB, the need for PPI, or the absence of new conduction abnormalities. In patients with PPI, the influence of RV pacing burden on LVEF was analyzed. New-onset LBBB after TAVI occurred in 92 patients (24%), and PPI was required in 55 patients (15%). In patients without new conduction abnormalities, LVEF significantly increased during follow-up (56 ± 14% to 61 ± 12%, p &lt;0.001). Patients with a baseline LVEF ≤50% presented with a significant recovery in LVEF, although the recovery was less pronounced in patients with new-onset LBBB. Moreover, patients with a baseline LVEF ≤50% who received PPI showed an improvement in LVEF at 6months regardless of the RV pacing burden. New-onset LBBB hampers the recovery of LVEF after TAVI. Among patients with an LVEF ≤50%, pressure overload relief counteracts the effects of new-onset LBBB or RV pacing.

Predictors of right ventricular pacing-induced left ventricular dysfunction in pacemaker recipients with preserved ejection fraction

Pacing is an effective treatment in the management of patients with bradyarrhythmias. Chronic right ventricular pacing may cause electrical and mechanical dyssynchrony leading to adeterioration of left ventricular ejection fraction (LVEF). This deterioration of LVEF has been described as pacing-induced cardiomyopathy (PICM). The incidence of PICM has been described by many studies, ranging between 10% and 26%. Predictors for PICM are not yet established-studies were limited by variations in the definition of PICM and the follow-up period. The authors studied the incidence and predictors of PICM in patients with preserved LVEF who underwent pacemaker implantation. This retrospective study included 320patients that underwent single- or dual-chamber pacemaker implantation, with amean follow up period of 4.7 ± 2.0years. Implantable cardioverter defibrillator and cardiac resynchronization therapy patients were excluded from this study. Individuals that had abaseline LVEF ≥ 50% before implantation in transthoracic echocardiography were included in the study. Of the 320patients included in the study, 45% were male, with amean age 55.5years. The incidence of PICM was 7.5%. Wider native QRS duration, particularly > 140 ms (P < 0.001), wider paced QRS (pQRS) duration > 150 ms (P < 0.001), low normal ejection fraction < 56% pre-implantation (P = 0.023) and increased LV end diastolic diameter (LVEDD) > 53 mm and LV end systolic diameter (LVESD) > 38 mm (P < 0.001) predicted the development of PICM. There was no association between burden of right ventricular pacing (P = 0.782) or pacing site (P = 0.876) and the development of pacemaker-induced cardiomyopathy. Right ventricular pacing-induced left ventricular dysfunction is not uncommon, with an incidence of 7.5%. Wider native and paced QRS durations, low normal ejection fraction (< 56%) pre-implantation and increased LVEDD and LVESD post implantation are the most important predictors for the development of PICM.

The short term influence of right ventricular pacing burden on echocardiographic and spiroergometric parameters in patients with preserved left ventricular ejection fraction

BackgroundThe incidence of worsened clinical outcome due to high right ventricular (RV) pacing burden in patients with preserved left ventricular function remains controversial.ObjectiveTo investigate the impact of RV pacing on several echocardiographic and spiroergometric parameters.MethodsIn 60 pacemaker patients with preserved left ventricular ejection fraction (LVEF) serial echocardiographies and spiroergometries were performed over a time course of 12 months. Additionally, in 48 patients retrospective echocardiographic analyses of the LV- and RV function were carried out up to 24 months after pacemaker implantation.ResultsThe patients were divided into two groups: The high RV pacing burden group (hRVP: ≥ 40%) and the low RV pacing group (lRVP < 40%) according to the definitions in previous randomized MOST and DAVID trials. After a period of 12-month pacemaker therapy no changes to left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), LVEF, E/A-ratio; E/E′-ratio and tricuspid annular plane systolic excursion (TAPSE) could be revealed, independently of the RV pacing burden. Additionally, after 24-month long term follow-up there were no differences in LVEF and TAPSE in both groups. Accordingly, no relevant changes of peak exercise capacity, ventilatory anaerobic threshold or maximal oxygen consumption could be demonstrated independently of the RV pacing.ConclusionsIn pacemaker patients with preserved LVEF the burden of RV pacing has no adverse influence on several echocardiographic and spiroergometric surrogate parameters of pacemaker-induced cardiomyopathy after a follow-up of 12 to 24 month. Despite this, screening for pacemaker induced cardiomyopathy should be performed especially in the presence of new heart failure symptoms.

Risk factors for developing pacing induced LV dysfunction: Experience from a tertiary center in the UK.

The risk factors for developing pacing induced left ventricular dysfunction (LVD) in patients with high burden of right ventricular pacing (RVP) is poorly understood. Therefore, in the present study, we aimed to assess the determinants of pacing induced LVD. Our data were retrospectively collected from 146 patients with RVP>40% who underwent generator change (GC) or cardiac resynchronization therapy (CRT) upgrade between 2016 and 2019 who had left ventricular ejection fraction (EF) ≥50% at initial implant. A total of 75 patients had CRT upgrade due to pacing induced LVD (EF<50%) and 71 patients with preserved LV function (EF≥50%) had a GC. Primary indication for pacing in both groups was complete heart block. Male predominance (p=.008), prior myocardial infarction (MI) (p=.001), atrial fibrillation (AF) (p=.009), chronic kidney disease (CKD) (p=.005), and borderline low systolic function (BLSF) (EF 50%-55%) (p=.04) were more prevalent in the CRT upgrade group. Presence of AF (odds ratio [OR]=3.05, 95% confidence interval [CI] 1.42-6.58; p=.004), BLSF (OR=3.8, 95% CI 1.22-11.8; p=.02), and male gender (OR=2.41, 95% CI 1.14-5.08; p=.02) were independent predictors for RVP induced LVD. Age (OR=1.08, 95% CI 1.02-1.14; p=.005) and BLSF (OR=5.33, 95% CI 1.26-22.5; p=.023) were independent predictors of earlier development of LVD after implant. Our results suggested that AF, BLSF, and male gender are predictors for development of pacing induced LVD in patients with high RVP burden. LVD can occur at any time after pacemaker implant with BLSF and increasing age associated with earlier development of LVD.