Therapeutic potential of conduction system pacing as a method for improving cardiac output during ventricular tachycardia.

BACKGROUND: Ventricular tachycardia (VT) reduces cardiac output through high heart rates, loss of atrioventricular synchrony, and loss of ventricular synchrony. We studied the contribution of each mechanism and explored the potential therapeutic utility of His bundle pacing to improve cardiac output during VT. METHODS: Study 1 aimed to improve the understanding of mechanisms of harm during VT (using pacing simulated VT). In 23 patients with left ventricular impairment, we recorded continuous ECG and beat-by-beat blood pressure measurements. We assessed the hemodynamic impact of heart rate and restoration of atrial and biventricular synchrony. Study 2 investigated novel pacing interventions during clinical VT by evaluating the hemodynamic effects of His bundle pacing at 5 bpm above the VT rate in 10 patients. RESULTS: In Study 1, at progressively higher rates of simulated VT, systolic blood pressure declined: at rates of 125, 160, and 190 bpm, -22.2%, -42.0%, and -58.7%, respectively (ANOVA p < 0.0001). Restoring atrial synchrony alone had only a modest beneficial effect on systolic blood pressure (+ 3.6% at 160 bpm, p = 0.2117), restoring biventricular synchrony alone had a greater effect (+ 9.1% at 160 bpm, p = 0.242), and simultaneously restoring both significantly increased systolic blood pressure (+ 31.6% at 160 bpm, p = 0.0003). In Study 2, the mean rate of clinical VT was 143 ± 21 bpm. His bundle pacing increased systolic blood pressure by + 14.2% (p = 0.0023). In 6 of 10 patients, VT terminated with His bundle pacing. CONCLUSIONS: Restoring atrial and biventricular synchrony improved hemodynamic function in simulated and clinical VT. Conduction system pacing could improve VT tolerability and treatment.

Catheter Ablation for Ventricular Tachycardia After MI: A Reconstructed Individual Patient Data Meta-analysis of Randomised Controlled Trials.

Background: The prognostic impact of ventricular tachycardia (VT) catheter ablation is an important outstanding research question. We undertook a reconstructed individual patient data meta-analysis of randomised controlled trials comparing ablation to medical therapy in patients developing VT after MI. Methods: We systematically identified all trials comparing catheter ablation to medical therapy in patients with VT and prior MI. The prespecified primary endpoint was reconstructed individual patient assessment of all-cause mortality. Prespecified secondary endpoints included trial-level assessment of all-cause mortality, VT recurrence or defibrillator shocks and all-cause hospitalisations. Prespecified subgroup analysis was performed for ablation approaches involving only substrate modification without VT activation mapping. Sensitivity analyses were performed depending on the proportion of patients with prior MI included. Results: Eight trials, recruiting a total of 874 patients, were included. Of these 874 patients, 430 were randomised to catheter ablation and 444 were randomised to medical therapy. Catheter ablation reduced all-cause mortality compared with medical therapy when synthesising individual patient data (HR 0.63; 95% CI [0.41-0.96]; p=0.03), but not in trial-level analysis (RR 0.91; 95% CI [0.67-1.23]; p=0.53; I2=0%). Catheter ablation significantly reduced VT recurrence, defibrillator shocks and hospitalisations compared with medical therapy. Sensitivity analyses were consistent with the primary analyses. Conclusion: In patients with postinfarct VT, catheter ablation reduces mortality.

Left bundle branch pacing with and without anodal capture: impact on ventricular activation pattern and acute haemodynamics.

AIMS: Left bundle branch pacing (LBBP) can deliver physiological left ventricular activation, but typically at the cost of delayed right ventricular (RV) activation. Right ventricular activation can be advanced through anodal capture, but there is uncertainty regarding the mechanism by which this is achieved, and it is not known whether this produces haemodynamic benefit. METHODS AND RESULTS: We recruited patients with LBBP leads in whom anodal capture eliminated the terminal R-wave in lead V1. Ventricular activation pattern, timing, and high-precision acute haemodynamic response were studied during LBBP with and without anodal capture. We recruited 21 patients with a mean age of 67 years, of whom 14 were males. We measured electrocardiogram timings and haemodynamics in all patients, and in 16, we also performed non-invasive mapping. Ventricular epicardial propagation maps demonstrated that RV septal myocardial capture, rather than right bundle capture, was the mechanism for earlier RV activation. With anodal capture, QRS duration and total ventricular activation times were shorter (116 ± 12 vs. 129 ± 14 ms, P < 0.01 and 83 ± 18 vs. 90 ± 15 ms, P = 0.01). This required higher outputs (3.6 ± 1.9 vs. 0.6 ± 0.2 V, P < 0.01) but without additional haemodynamic benefit (mean difference -0.2 ± 3.8 mmHg compared with pacing without anodal capture, P = 0.2). CONCLUSION: Left bundle branch pacing with anodal capture advances RV activation by stimulating the RV septal myocardium. However, this requires higher outputs and does not improve acute haemodynamics. Aiming for anodal capture may therefore not be necessary.

Septal scar as a barrier to left bundle branch area pacing.

BACKGROUND: The use of left bundle branch area pacing (LBBAP) for bradycardia pacing and cardiac resynchronization is increasing, but implants are not always successful. We prospectively studied consecutive patients to determine whether septal scar contributes to implant failure. METHODS: Patients scheduled for bradycardia pacing or cardiac resynchronization therapy were prospectively enrolled. Recruited patients underwent preprocedural scar assessment by cardiac MRI with late gadolinium enhancement imaging. LBBAP was attempted using a lumenless lead (Medtronic 3830) via a transeptal approach. RESULTS: Thirty-five patients were recruited: 29 male, mean age 68 years, 10 ischemic, and 16 non-ischemic cardiomyopathy. Pacing indication was bradycardia in 26% and cardiac resynchronization in 74%. The lead was successfully deployed to the left ventricular septum in 30/35 (86%) and unsuccessful in the remaining 5/35 (14%). Septal late gadolinium enhancement was significantly less extensive in patients where left septal lead deployment was successful, compared those where it was unsuccessful (median 8%, IQR 2%-18% vs. median 54%, IQR 53%-57%, p < .001). CONCLUSIONS: The presence of septal scar appears to make it more challenging to deploy a lead to the left ventricular septum via the transeptal route. Additional implant tools or alternative approaches may be required in patients with extensive septal scar.

Comparison of methods for delivering cardiac resynchronization therapy: an acute electrical and haemodynamic within-patient comparison of left bundle branch area, His bundle, and biventricular pacing.

AIMS: Left bundle branch area pacing (LBBAP) is a promising method for delivering cardiac resynchronization therapy (CRT), but its relative physiological effectiveness compared with His bundle pacing (HBP) is unknown. We conducted a within-patient comparison of HBP, LBBAP, and biventricular pacing (BVP). METHODS AND RESULTS: Patients referred for CRT were recruited. We assessed electrical response using non-invasive mapping, and acute haemodynamic response using a high-precision haemodynamic protocol. Nineteen patients were recruited: 14 male, mean LVEF of 30%. Twelve had time for BVP measurements. All three modalities reduced total ventricular activation time (TVAT), (ΔTVATHBP -43 ± 14 ms and ΔTVATLBBAP -35 ± 20 ms vs. ΔTVATBVP -19 ± 30 ms, P = 0.03 and P = 0.1, respectively). HBP produced a significantly greater reduction in TVAT compared with LBBAP in all 19 patients (-46 ± 15 ms, -36 ± 17 ms, P = 0.03). His bundle pacing and LBBAP reduced left ventricular activation time (LVAT) more than BVP (ΔLVATHBP -43 ± 16 ms, P < 0.01 vs. BVP, ΔLVATLBBAP -45 ± 17 ms, P < 0.01 vs. BVP, ΔLVATBVP -13 ± 36 ms), with no difference between HBP and LBBAP (P = 0.65). Acute systolic blood pressure was increased by all three modalities. In the 12 with BVP, greater improvement was seen with HBP and LBBAP (6.4 ± 3.8 mmHg BVP, 8.1 ± 3.8 mmHg HBP, P = 0.02 vs. BVP and 8.4 ± 8.2 mmHg for LBBAP, P = 0.3 vs. BVP), with no difference between HBP and LBBAP (P = 0.8). CONCLUSION: HBP delivered better ventricular resynchronization than LBBAP because right ventricular activation was slower during LBBAP. But LBBAP was not inferior to HBP with respect to LV electrical resynchronization and acute haemodynamic response.

Upgrading right ventricular pacemakers to biventricular pacing or conduction system pacing: a systematic review and meta-analysis.

Guidelines recommend patients undergoing a first pacemaker implant who have even mild left ventricular (LV) impairment should receive biventricular or conduction system pacing (CSP). There is no corresponding recommendation for patients who already have a pacemaker. We conducted a meta-analysis of randomized controlled trials (RCTs) and observational studies assessing device upgrades. The primary outcome was the echocardiographic change in LV ejection fraction (LVEF). Six RCTs (randomizing 161 patients) and 47 observational studies (2644 patients) assessing the efficacy of upgrade to biventricular pacing were eligible for analysis. Eight observational studies recruiting 217 patients of CSP upgrade were also eligible. Fourteen additional studies contributed data on complications (25 412 patients). Randomized controlled trials of biventricular pacing upgrade showed LVEF improvement of +8.4% from 35.5% and observational studies: +8.4% from 25.7%. Observational studies of left bundle branch area pacing upgrade showed +11.1% improvement from 39.0% and observational studies of His bundle pacing upgrade showed +12.7% improvement from 36.0%. New York Heart Association class decreased by -0.4, -0.8, -1.0, and -1.2, respectively. Randomized controlled trials of biventricular upgrade found improvement in Minnesota Heart Failure Score (-6.9 points) and peak oxygen uptake (+1.1 mL/kg/min). This was also seen in observational studies of biventricular upgrades (-19.67 points and +2.63 mL/kg/min, respectively). In studies of the biventricular upgrade, complication rates averaged 2% for pneumothorax, 1.4% for tamponade, and 3.7% for infection over 24 months of mean follow-up. Lead-related complications occurred in 3.3% of biventricular upgrades and 1.8% of CSP upgrades. Randomized controlled trials show significant physiological and symptomatic benefits of upgrading pacemakers to biventricular pacing. Observational studies show similar effects between biventricular pacing upgrade and CSP upgrade.

Laser Doppler flow for the hemodynamic differentiation of tachycardia.

BACKGROUND: Implantable cardioverter defibrillators (ICDs) offer effective therapy for the prevention of sudden cardiac death (SCD) due to ventricular arrhythmias. However, inappropriate shocks have detrimental effects on survival and quality of life. The addition of hemodynamic monitoring may be useful in discriminating clinically important ventricular arrhythmias. OBJECTIVE: In this study, we assess the ability of laser Doppler flowmetry to assess the hemodynamic effect of paced atrial and ventricular arrhythmias using mean arterial blood pressure as the reference. METHODS: In this acute human study in patients undergoing an elective electrophysiological study, laser Doppler flowmetry, arterial blood pressure, and surface ECG were acquired during high-rate atrial and ventricular pacing to simulate supraventricular and ventricular tachycardias. RESULTS: Arterial blood pressure and laser Doppler flow signals correlated well during atrial and ventricular pacing (rho = 0.694, p < .001). The hemodynamic impairment detected by both methods was greater during ventricular pacing than atrial pacing (-1.0% vs. 19.0%, p < .001). Laser Doppler flowmetry performed better than rate alone to identify hemodynamic impairments. CONCLUSION: In this acute study, laser Doppler flowmetry tissue perfusion served as a good surrogate measure for arterial pressure, which could be incorporated into future ICDs.

Basic Principles of Hemodynamics in Pacing.

Pacing therapy aims to improve overall cardiac function by normalizing cardiac electrical activation. Although hemodynamic measurements allow the impact of cardiac pacing on cardiac function to be quantified, the protocol is crucial to minimize the effect of noise and achieve greater precision. Multiple steps can be undertaken to optimize accuracy of hemodynamic measurements. These include comparing with a reference state, using an average of a set number of beats, making repeated measurements, ensuring all beats are included, and pacing at faster heart rates. These measurements can aid comparison between different pacing modalities and guide optimal programming.

Optimizing atrio-ventricular delay in pacemakers using potentially implantable physiological biomarkers.

BACKGROUND: Hemodynamically optimal atrioventricular (AV) delay can be derived by echocardiography or beat-by-beat blood pressure (BP) measurements, but analysis is labor intensive. Laser Doppler perfusion monitoring measures blood flow and can be incorporated into future implantable cardiac devices. We assess whether laser Doppler can be used instead of BP to optimize AV delay. METHODS: Fifty eight patients underwent 94 AV delay optimizations with biventricular or His-bundle pacing using laser Doppler and simultaneous noninvasive beat-by-beat BP. Optimal AV delay was defined using a curve of hemodynamic response to switching from AAI (reference state) to DDD (test state) at several AV delays (40-320 ms), with automatic quality control checking precision of the optimum. Five subsequent patients underwent an extended protocol to test the impact of greater numbers of alternations on optimization quality. RESULTS: 55/94 optimizations passed quality control resulting in an optimal AV delay on laser Doppler similar to that derived by BP (median absolute deviation 12 ms). An extended protocol with increasing number of replicates consistently improved quality and reduced disagreement between laser Doppler and BP optima. With only five replicates, no optimization passed quality control, and the median absolute deviation would be 29 ms. These improved progressively until at 50 replicates, all optimizations passed quality control and the median absolute deviation was only 13 ms. CONCLUSIONS: Laser Doppler perfusion produces hemodynamic optima equivalent to BP. Quality control can be automatic. Adding more replicates, consistently improves quality. Future implantable devices could use such methods to dynamically and reliably optimize AV delays.

ST2 in patients with severe aortic stenosis and heart failure.

BACKGROUND: ST2 is a circulating biomarker that is well established for predicting outcome in heart failure (HF). This is the first study to look at ST2 concentrations in optimally treated patients with stable but significant left ventricular systolic dysfunction (LVSD) compared to patients with severe aortic stenosis (AS). METHODS: Two cohorts were retrospectively studied: 94 patients undergoing transcatheter aortic valve implantation for severe AS (63 with normal ejection fraction [EF] and 31 with reduced EF), and 50 patients with severe LVSD from non-valvular causes. ST2 pre-procedural samples were taken, and repeated again at 3 and 6 months. Patients were followed-up for 2 years. Data was analyzed using SPSS software. RESULTS: Baseline concentrations of soluble ST2 did not differ significantly between the HF group and AS group with normal EF (EF ≥ 50%). However, in the AS group with a low EF (EF < 50%) ST2 concentrations were significantly higher that the HF group (p = 0.009). New York Heart Association class IV HF, baseline N-terminal pro-B-type natriuretic peptide and gender were all independent predictors of soluble ST2 (sST2) baseline concentrations. CONCLUSIONS: Raised ST2 concentrations in the context of severe AS may be a marker for subclinical or clinical left ventricular dysfunction. More research is required to assess its use for assessment of prognosis and response to treatment.

Electrocardiographic predictors of successful resynchronization of left bundle branch block by His bundle pacing.

BACKGROUND: His bundle pacing (HBP) is an alternative to biventricular pacing (BVP) for delivering cardiac resynchronization therapy (CRT) in patients with heart failure and left bundle branch block (LBBB). It is not known whether ventricular activation times and patterns achieved by HBP are equivalent to intact conduction systems and not all patients with LBBB are resynchronized by HBP. OBJECTIVE: To compare activation times and patterns of His-CRT with BVP-CRT, LBBB and intact conduction systems. METHODS: In patients with LBBB, noninvasive epicardial mapping (ECG imaging) was performed during BVP and temporary HBP. Intrinsic activation was mapped in all subjects. Left ventricular activation times (LVAT) were measured and epicardial propagation mapping (EPM) was performed, to visualize epicardial wavefronts. Normal activation pattern and a normal LVAT range were determined from normal subjects. RESULTS: Forty-five patients were included, 24 with LBBB and LV impairment, and 21 with normal 12-lead ECG and LV function. In 87.5% of patients with LBBB, His-CRT successfully shortened LVAT by ≥10 ms. In 33.3%, His-CRT resulted in complete ventricular resynchronization, with activation times and patterns indistinguishable from normal subjects. EPM identified propagation discontinuity artifacts in 83% of patients with LBBB. This was the best predictor of whether successful resynchronization was achieved by HBP (logarithmic odds ratio, 2.19; 95% confidence interval, 0.07-4.31; p = .04). CONCLUSION: Noninvasive electrocardiographic mapping appears to identify patients whose LBBB can be resynchronized by HBP. In contrast to BVP, His-CRT may deliver the maximum potential ventricular resynchronization, returning activation times, and patterns to those seen in normal hearts.

How to deliver personalized cardiac resynchronization therapy through the precise measurement of the acute hemodynamic response: Insights from the iSpot trial.

INTRODUCTION: New pacing technologies offer a 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. MATERIALS AND METHODS: The 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 noninvasive blood pressure, and left ventricular (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 five atrioventricular delays. RESULTS: Twenty-five patients underwent the full protocol of eight alternations. Only four (16%) patients had a statistically significant >3 mm Hg 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 nonconventional configuration. Responses to pacing were significantly correlated between the different hemodynamic measures: invasive systolic blood pressure (SBP) vs noninvasive SBP r = 0.82 (P < .001); invasive SBP vs LV dP/dt r = 0.57, r2 = 0.32 (P < .001). CONCLUSIONS: Current standard multibeat 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.