Left bundle branch area pacing results in more physiological ventricular activation than biventricular pacing in patients with left bundle branch block heart failure.

Biventricular pacing (Biv) and left bundle branch area pacing (LBBAP) are methods of cardiac resynchronization therapy (CRT). Currently, little is known about how they differ in terms of ventricular activation. This study compared ventricular activation patterns in left bundle branch block (LBBB) heart failure patients using an ultra-high-frequency electrocardiography (UHF-ECG). This was a retrospective analysis including 80 CRT patients from two centres. UHF-ECG data were obtained during LBBB, LBBAP, and Biv. Left bundle branch area pacing patients were divided into non-selective left bundle branch pacing (NSLBBP) or left ventricular septal pacing (LVSP) and into groups with V6 R-wave peak times (V6RWPT) < 90 ms and ≥ 90 ms. Calculated parameters were: e-DYS (time difference between the first and last activation in V1-V8 leads) and Vdmean (average of V1-V8 local depolarization durations). In LBBB patients (n = 80) indicated for CRT, spontaneous rhythms were compared with Biv (39) and LBBAP rhythms (64). Although both Biv and LBBAP significantly reduced QRS duration (QRSd) compared with LBBB (from 172 to 148 and 152 ms, respectively, both P < 0.001), the difference between them was not significant (P = 0.2). Left bundle branch area pacing led to shorter e-DYS (24 ms) than Biv (33 ms; P = 0.008) and shorter Vdmean (53 vs. 59 ms; P = 0.003). No differences in QRSd, e-DYS, or Vdmean were found between NSLBBP, LVSP, and LBBAP with paced V6RWPTs < 90 and ≥ 90 ms. Both Biv CRT and LBBAP significantly reduce ventricular dyssynchrony in CRT patients with LBBB. Left bundle branch area pacing is associated with more physiological ventricular activation.

A randomized comparison of HBP versus RVP: Effect on left ventricular function and biomarkers of collagen metabolism.

BACKGROUND: Right ventricular pacing (RVP) can result in pacing-induced cardiomyopathy (PICM). It is unknown whether specific biomarkers reflect differences between His bundle pacing (HBP) and RVP and predict a decrease in left ventricular function during RVP. AIMS: We aimed to compare the effect of HBP and RVP on the left ventricular ejection fraction (LVEF) and to study how they affect serum markers of collagen metabolism. METHODS: Ninety-two high-risk PICM patients were randomized to HBP or RVP groups. Their clinical characteristics, echocardiography, and serum levels of transforming growth factor ß1 (TGF-ß1), matrix metalloproteinase 9 (MMP-9), suppression of tumorigenicity 2 interleukin (ST2-IL), tissue inhibitor of metalloproteinase 1 (TIMP-1), and galectin 3 (Gal-3) were studied before pacemaker implantation and six months later. RESULTS: Fifty-three patients were randomized to the HBP group and 39 patients to the RVP group. HBP failed in 10 patients, who crossed over to the RVP group. Patients with RVP had significantly lower LVEF compared to HBP patients after six months of pacing (-5% and -4% in as-treated and intention-to-treat analysis, respectively). Levels of TGF-ß1 after 6 months were lower in HBP than RVP patients (mean difference -6 ng/ml; P = 0.009) and preimplant Gal-3 and ST2-IL levels were higher in RVP patients, with a decline in LVEF ≥5% compared to those with a decline of <5% (mean difference 3 ng/ml and 8 ng/ml; P = 0.02 for both groups). CONCLUSION: In high-risk PICM patients, HBP was superior to RVP in providing more physiological ventricular function, as reflected by higher LVEF and lower levels of TGF-ß1. In RVP patients, LVEF declined more in those with higher baseline Gal-3 and ST2-IL levels than in those with lower levels.

Left bundle branch area pacing outcomes: the multicentre European MELOS study.

AIMS: Permanent transseptal left bundle branch area pacing (LBBAP) is a promising new pacing method for both bradyarrhythmia and heart failure indications. However, data regarding safety, feasibility and capture type are limited to relatively small, usually single centre studies. In this large multicentre international collaboration, outcomes of LBBAP were evaluated. METHODS AND RESULTS: This is a registry-based observational study that included patients in whom LBBAP device implantation was attempted at 14 European centres, for any indication. The study comprised 2533 patients (mean age 73.9 years, female 57.6%, heart failure 27.5%). LBBAP lead implantation success rate for bradyarrhythmia and heart failure indications was 92.4% and 82.2%, respectively. The learning curve was steepest for the initial 110 cases and plateaued after 250 cases. Independent predictors of LBBAP lead implantation failure were heart failure, broad baseline QRS and left ventricular end-diastolic diameter. The predominant LBBAP capture type was left bundle fascicular capture (69.5%), followed by left ventricular septal capture (21.5%) and proximal left bundle branch capture (9%). Capture threshold (0.77 V) and sensing (10.6 mV) were stable during mean follow-up of 6.4 months. The complication rate was 11.7%. Complications specific to the ventricular transseptal route of the pacing lead occurred in 209 patients (8.3%). CONCLUSIONS: LBBAP is feasible as a primary pacing technique for both bradyarrhythmia and heart failure indications. Success rate in heart failure patients and safety need to be improved. For wider use of LBBAP, randomized trials are necessary to assess clinical outcomes.

The Efficacy and Safety of Hybrid Ablations for Atrial Fibrillation.

OBJECTIVES: This study sought to comprehensively determine the procedural safety and midterm efficacy of hybrid ablations. BACKGROUND: Hybrid ablation of atrial fibrillation (AF) (thoracoscopic ablation followed by catheter ablation) has been used for patients with nonparoxysmal AF; however, accurate data regarding efficacy and safety are still limited. METHODS: Patients with nonparoxysmal AF underwent thoracoscopic, off-pump ablation using the COBRA Fusion radiofrequency system (Estech) followed by a catheter ablation 3 months afterward. The safety of the procedure was assessed using sequential brain magnetic resonance and neuropsychological examinations at baseline (1 day before), postoperatively (2-4 days for brain magnetic resonance imaging or 1 month for neuropsychological examination), and at 9 months after the surgical procedure. Implantable loop recorders were used to detect arrhythmia recurrence. Arrhythmia-free survival (the primary efficacy endpoint) was defined as no episodes of AF or atrial tachycardia while off antiarrhythmic drugs, redo ablations or cardioversions. RESULTS: Fifty-nine patients (age: 62.5 ± 10.5 years) were enrolled, 37 (62.7%) were men, and the mean follow-up was 30.3 ± 10.8 months. Thoracoscopic ablation was successfully performed in 55 (93.2%) patients. On baseline magnetic resonance imaging, chronic ischemic brain lesions were present in 60.0% of patients. New ischemic lesions on postoperative magnetic resonance imaging were present in 44.4%. Major postoperative cognitive dysfunction was present in 27.0% and 17.6% at 1 and 9 months postoperatively, respectively. The probability of arrhythmia-free survival was 54.0% (95% CI: 41.3-66.8) at 1 year and 43.8% (95% CI: 30.7-57.0) at 2 years. CONCLUSIONS: The thoracoscopic ablation is associated with a high risk of silent cerebral ischemia. The midterm efficacy of hybrid ablations is moderate.

Ventricular activation pattern assessment during right ventricular pacing: Ultra-high-frequency ECG study.

BACKGROUND: Right ventricular (RV) pacing causes delayed activation of remote ventricular segments. We used the ultra-high-frequency ECG (UHF-ECG) to describe ventricular depolarization when pacing different RV locations. METHODS: In 51 patients, temporary pacing was performed at the RV septum (mSp); further subclassified as right ventricular inflow tract (RVIT) and right ventricular outflow tract (RVOT) for septal inflow and outflow positions (below or above the plane of His bundle in right anterior oblique), apex, anterior lateral wall, and at the basal RV septum with nonselective His bundle or RBB capture (nsHBorRBBp). The timings of UHF-ECG electrical activations were quantified as left ventricular lateral wall delay (LVLWd; V8 activation delay) and RV lateral wall delay (RVLWd; V1 activation delay). RESULTS: The LVLWd was shortest for nsHBorRBBp (11 ms [95% confidence interval = 5-17]), followed by the RVIT (19 ms [11-26]) and the RVOT (33 ms [27-40]; p < .01 between all of them), although the QRSd for the latter two were the same (153 ms (148-158) vs. 153 ms (148-158); p = .99). RV apical capture not only had a longer LVLWd (34 ms (26-43) compared to mSp (27 ms (20-34), p < .05), but its RVLWd (17 ms (9-25) was also the longest compared to other RV pacing sites (mean values for nsHBorRBBp, mSp, anterior and lateral wall captures being below 6 ms), p < .001 compared to each of them. CONCLUSION: RVIT pacing produces better ventricular synchrony compared to other RV pacing locations with myocardial capture. However, UHF-ECG ventricular dysynchrony seen during RVIT pacing is increased compared to concomitant capture of basal septal myocytes and His bundle or proximal right bundle branch.

Can QRS morphology be used to differentiate between true septal vs. apparently septal lead placement? An analysis of ECG of real mid-septal, apparent mid-septal, and apical pacing.

The location of the pacemaker lead is based on the shape of the lead on fluoroscopy only, typically in the left and right anterior oblique positions. However, these fluoroscopy criteria are insufficient and many leads apparently considered to be in septum are in fact anchored in anterior wall. Periprocedural ECG could determine the correct lead location. The aim of the current analysis is to characterize ECG criteria associated with a correct position of the right ventricular (RV) lead in the mid-septum. Patients with indications for a pacemaker had the RV lead implanted in the apex (Group A) or mid-septum using the standard fluoroscopic criteria. The exact position of the RV lead was verified using computed tomography. Based on the findings, the mid-septal group was divided into two subgroups: (i) true septum, i.e. lead was found in the mid-septum, and (ii) false septum, i.e. lead was in the adjacent areas (anterior wall, anteroseptal groove). Paced ECGs were acquired from all patients and multiple criteria were analysed. Paced ECGs from 106 patients were analysed (27 in A, 36 in true septum, and 43 in false septum group). Group A had a significantly wider QRS, more left-deviated axis and later transition zone compared with the true septum and false septum groups. There were no differences in presence of q in lead I, or notching in inferior or lateral leads between the three groups. QRS patterns of true septum and false septum groups were similar with only one exception of the transition zone. In the multivariate model, the only ECG parameters associated with correct lead placement in the septum was an earlier transition zone (odds ratio (OR) 2.53, P = 0.001). ECGs can be easily used to differentiate apical pacing from septal or septum-close pacing. The only ECG characteristic that could help to identify true septum lead position was the transition zone in the precordial leads. ClinicalTrials.gov identifier: NCT02412176.

Both selective and nonselective His bundle, but not myocardial, pacing preserve ventricular electrical synchrony assessed by ultra-high-frequency ECG.

BACKGROUND: Right ventricular myocardial pacing leads to nonphysiological activation of heart ventricles. Contrary to this, His bundle pacing preserves their fast activation. Ultra-high-frequency electrocardiography (UHF-ECG) is a novel tool for ventricular depolarization assessment. OBJECTIVE: The purpose of this study was to describe UHF-ECG depolarization patterns during myocardial and His bundle pacing. METHODS: Forty-six patients undergoing His bundle pacing to treat bradycardia and spontaneous QRS complexes without bundle branch block were included. UHF-ECG recordings were performed during spontaneous rhythm, pure myocardial para-Hisian capture, and His bundle capture. QRS duration, QRS area, depolarization time in specific leads, and the UHF-ECG-derived ventricular dyssynchrony index were calculated. RESULTS: One hundred thirty-three UHF-ECG recordings were performed in 46 patients (44 spontaneous rhythm, 28 selective His bundle, 43 nonselective His bundle, and 18 myocardial capture). The mean QRS duration was 117 ms for spontaneous rhythm, 118 ms for selective, 135 ms for nonselective, and 166 ms for myocardial capture (P < .001 for nonselective and myocardial capture compared to each of the other types of ventricular activation). The calculated dyssynchrony index was shortest during spontaneous rhythm (12 ms; P = .02 compared to selective and P = .09 compared to nonselective), and it did not differ between selective and nonselective His bundle capture (16 vs 15 ms; P > .99) and was longest during myocardial capture of the para-Hisian area (37 ms; P < .001 compared to each of the other types of ventricular activation). CONCLUSION: In patients without bundle branch block, both types of His bundle, but not myocardial, capture preserve ventricular electrical synchrony as measured using UHF-ECG.

Novel ultra-high-frequency electrocardiogram tool for the description of the ventricular depolarization pattern before and during cardiac resynchronization.

INTRODUCTION: The present study introduces a new ultra-high-frequency 14-lead electrocardiogram technique (UHF-ECG) for mapping ventricular depolarization patterns and calculation of novel dyssynchrony parameters that may improve the selection of patients and application of cardiac resynchronization therapy (CRT). METHODS: Components of the ECG in sixteen frequency bands within the 150 to 1000 Hz range were used to create ventricular depolarization maps. The maximum time difference between the UHF QRS complex centers of mass of leads V1 to V8 was defined as ventricular electrical dyssynchrony (e-DYS), and the duration at 50% of peak voltage amplitude in each lead was defined as the duration of local depolarization (Vd). Proof of principle measurements was performed in seven patients with left (left bundle branch block) and four patients with right bundle branch block (right bundle branch block) before and during CRT using biventricular and His-bundle pacing. RESULTS: The acquired activation maps reflect the activation sequence under the tested conditions. e-DYS decreased considerably more than QRS duration, during both biventricular pacing (-50% vs -8%) and His-bundle pacing (-77% vs -13%). While biventricular pacing slightly increased Vd, His-bundle pacing reduced Vd significantly (+11% vs -36%), indicating the contribution of the fast conduction system. Optimization of biventricular pacing by adjusting VV-interval showed a decrease of e-DYS from 102 to 36 ms with only a small Vd increase and QRS duration decrease. CONCLUSIONS: The UHF-ECG technique provides novel information about electrical activation of the ventricles from a standard ECG electrode setup, potentially improving the selection of patients for CRT and application of CRT.

Close Proximity of Left Anterior Descending Artery to the Right Ventricular Lead Apparently Implanted into the Mid-septum.

Right ventricular (RV) mid-septal pacing should have fewer negative effects on left ventricular function compared to apical pacing. However, targeting the mid-septum may be technically challenging since it is usually done with two-dimensional fluoroscopy. The rotation of the heart and various shapes of the RV make it difficult to assess, whether the lead is really anchored in the septum. Many leads, apparently anchored in the septum, are in fact anchored in the anterior wall or anteroseptal groove, and some can get anchored in close proximity to the left anterior descending artery (LAD). We report three cases from our series of 51 patients, in whom the RV lead thought to be implanted in the mid-septum was in fact anchored in close proximity of LAD when assessed using computed tomography.

The insufficiency of left anterior oblique and the usefulness of right anterior oblique projection for correct localization of a computed tomography-verified right ventricular lead into the midseptum.

BACKGROUND: The aim of the study was to verify the correct anchoring location for the tip of the right ventricular lead using cardiac computed tomography and to assess the best fluoroscopic and ECG criteria associated with the correct location of the electrode into the midseptum. METHODS AND RESULTS: Patients indicated to pacemaker implantation were prospectively enrolled. The right ventricular lead was implanted into the midseptum according to standard criteria in left anterior oblique 40 view. The cardiac shadow on the right anterior oblique 30 was divided into 4 quadrants perpendicular to the lateral cardiac silhouette and the position of the lead tip was analyzed. The exact position of the lead tip was assessed using computed tomography. Of 51 patients, the right ventricular lead was anchored midseptum in 21 (41.2%; MS group). In 30 patients (58.8%; non-MS group), the lead was anchored in the adjacent anterior wall. The angle between the lead and horizontal axis on the left anterior oblique was similar in both groups. The non-MS group was associated with shorter distances between the tip and the cardiac contours in the right anterior oblique 30 (96.7% of leads in the non-MS group were in the outer quadrant versus 9.6% in the MS group; P<0.001). The presence of the lead in the middle or inferior quadrants was independently associated with correct midseptum placement with positive predictive value of 94.7%. CONCLUSIONS: Despite the optimal shape of the left anterior oblique, substantial numbers of leads were not anchored in the midseptum. Knowing the right anterior oblique 30 lead position can ensure proper midseptal placement.

Changes and prognostic impact of apoptotic and inflammatory cytokines in patients treated with cardiac resynchronization therapy.

OBJECTIVES: In patients with heart failure, increased apoptosis, inflammation and activation of the transforming growth factor (TGF)-ß cytokine system have been documented. The aim of the present study was to establish (i) whether cytokine concentrations decrease in patients who respond to cardiac resynchronization therapy (CRT), and (ii) whether pre-implant values have any prognostic value. METHODS: Eighty-one CRT candidates were prospectively studied. The success of CRT was assessed based on clinical and echocardiographic improvement 6 months after implantation. Mortality was assessed 2 years after implantation. Blood samples were drawn before and 6 months after implantation. Serum concentrations of Fas, TNF-related apoptosis-inducing ligand, tumor necrosis factor (TNF)-α, TNF-receptor 1, TGF-ß1 and interleukin (IL)-6 were measured using ELISA. RESULTS: At 6 months, 46 (56.8%) patients were classified as responders and 35 (43.2%) as nonresponders. Neither group differed with respect to baseline characteristics. In responders, the concentrations of IL-6, TNF-α and TGF-ß1 decreased significantly. In nonresponders, the concentration of TGF-ß1 even increased significantly. In multivariate analysis, the concentration of TGF-ß1 was a significant predictor of death during follow-up. CONCLUSIONS: The response to CRT implantation was associated with a decrease of TGF-ß1, IL-6 and TNF-α. Higher pre-implant concentrations of TGF-1ß were independently associated with a poor prognosis in CRT patients.

Deactivation of implantable cardioverter-defibrillators: results of patient surveys.

AIMS: The indications for implantable cardioverter-defibrillators (ICDs) have been expanding, especially for primary prevention of sudden cardiac death. Implantable cardioverter-defibrillator saves lives; however, in near end-of-life situations linked to incurable diseases, the question arises as to whether or not to turn off the ICD to avoid excessive numbers of shocks as the heart begins to fail. This study examined the wishes of a cohort of ICD recipients. METHODS AND RESULTS: Consecutive recipients of ICDs for primary or secondary prevention of sudden cardiac death were examined during a routine out-patient follow-up visit. Subjects completed a written survey about expected ICD benefits, feelings and circumstances under which they would want to deactivate the device. One hundred and nine patients fully completed the survey. Mean age was 67.6 ± 8.7 years, 91 (83.5%) were male and the mean systolic ejection fraction was 31.5 ± 10.9%. The severity of symptoms of heart failure according to the New York Heart Association classification was 2.1 ± 0.59 at implantation. Ninety-nine (90.8%) patients felt more secure and safe following ICD implantation and 66 (60.6%) patients reported a sense of improved health status after implantation. Thirty-one (28.4%) patients had experienced an ICD shock. Fifty (45.9%) patients indicated that they had never considered ICD deactivation during near end-of-life situations. This topic had been discussed with only eight (7.3%) patients. Forty-four (40.1%) patients wanted more information about ICD deactivation. On the other hand, 10 (41.7%) patients from secondary prevention and 19 (22.4%) from primary prevention groups categorically refused more information or further discussion on this topic (P = 0.058). CONCLUSION: Most ICD recipients felt safer following ICD implantation and most wanted more information regarding ICD deactivation. However, a significant number of patients (especially, secondary prevention patients) had no interest in receiving additional information about this topic.

Changes in cytokine concentrations following successful ablation of atrial fibrillation.

AIMS: Atrial fibrillation is associated with the activation of inflammatory processes [e.g. higher concentrations of pro-inflammatory cytokines interleukin-6 (IL-6), C-reactive protein (CRP)], as well as a pro-thrombotic state [e.g. increased concentration of serum pro-thrombotic markers P-selectin and CD40 ligand (CD40L)]. The aim of the present study was to establish, whether successful epicardial ablation of AF leads to decreased concentrations of traditional inflammatory and thrombotic markers. METHODS: Twenty-five patients with symptomatic paroxysmal or persistent AF were prospectively studied. All underwent epicardial isolation of pulmonary veins. The success of the ablation was assessed clinically and with three Holter recordings. Blood samples were drawn before, three and six months after surgery. Serum concentrations of IL-6, interleukin-10 (IL-10), CRP, CD40L and P-selectin were measured using ELISA. RESULTS: AF was successfully ablated in 15 patients (SR group). In the other 10 patients (AF group), AF re-occurred during follow-up. Neither group differed with respect to age, gender, left ventricular ejection fraction, or preoperative concentrations of measured molecules. The concentrations of IL-6, CRP and CD40L decreased in successfully ablated patients; however, there was no change in the concentrations of these molecules in the AF group. The concentrations of IL-10 and P-selectin were unchanged in both groups during follow-up. CONCLUSION: Successful ablation of AF, with sinus rhythm restoration and maintenance, is associated with decreased serum levels of markers of inflammation.

Decreased apoptosis following successful ablation of atrial fibrillation.

OBJECTIVES: Increased apoptotic processes in tissue samples from hearts in atrial fibrillation (AF) have been previously documented in animals. Whether the restoration of sinus rhythm is associated with decreased apoptosis is not known. The aim of the present study was to establish whether successful epicardial ablation of AF leads to changes in the concentration of serum markers of apoptosis. METHODS: Twenty-five patients with AF were prospectively studied. All underwent epicardial isolation of pulmonary veins. The success of the ablation was assessed clinically and with 3 Holter recordings. Blood samples were drawn before surgery, and at 3 and 6 months after. Serum concentrations of Fas (apoptosis-stimulating fragment) and TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) were measured using ELISA. RESULTS: AF was successfully ablated in 15 patients (SR group). In the other 10 patients (AF group), AF recurred during follow-up. Neither group differed with respect to age, sex, left ventricular ejection fraction, or preoperative concentrations of measured molecules. While Fas decreased in successfully ablated patients, there was no change in the Fas concentration in the AF group. Similarly, the concentrations of TRAIL decreased in the SR group, but remained unchanged in the AF group. CONCLUSION: The ablation of AF is associated with decreased serum markers for apoptosis.

Higher platelet activity is present in patients with restenosis after percutaneous coronary intervention compared with patients with an occlusion of coronary artery bypass graft.

The aim of the study was to compare platelet activity between patients with an occlusion of bypass graft after coronary artery bypass graft surgery and restenosis after percutaneous coronary intervention (PCI); that is, between patients with reappearance of ischemia after two different kinds of coronary revascularization. Thirty patients were studied in a cross-sectional designed study. Fifteen of them were patients with the worst bypass graft patency from Prague-4 study (control protocol-driven coronary angiography performed at 1 year after surgery; originally 47 bypass grafts implanted, 94% of venous grafts occluded). The remaining 15 were patients with restenosis 3-12 months after PCI. Blood samples were drawn at least 12 weeks after coronary angiography. Platelet activity was determined by membrane expression of P-selectin (CD62P, % of positive cells) by flow cytometry, aggregability by ADP aggregometry. Data are expressed as mean +/- SEM. Both groups were similar with respect to age, BMI and presence of diabetes mellitus. No patient suffered from acute coronary syndrome. P-selectin expression was significantly higher in the patients with restenosis compared with patients with bypass graft occlusion (1.96 +/- 0.07 vs. 0.77 +/- 0.03, P < 0.001, Wilcoxon test). ADP aggregometry was not different between groups (55.5 +/- 1.1 vs. 56.1 +/- 0.8, P = NS). Higher platelet activity is present in the patients with restenosis after PCI compared with the patients with the occlusion of bypass graft. Platelet activity play more important role in the development of restenosis after PCI compared with the occlusion of bypass graft after coronary artery bypass graft surgery, at least in the period up to 1 year after revascularization.

In-hospital arrhythmias in patients with acute myocardial infarction - the relation to the reperfusion strategy and their prognostic impact.

Arrhythmias are frequent complication in patients with acute myocardial infarction (MI). The importance of accelerated idioventricular rhythm (AIVR), ventricular fibrillation or tachycardia (VF, VT), atrial fibrillation or flutter (AF) and bradycardias is considered and discussed in this review article. The value of the presence of AIVR as a marker of reperfusion is small, but in combination with other non-invasive markers (ST-segment resolution), its presence is connected with a high probability of successful reperfusion. Early ventricular arrhythmias are a serious complication of MI. However, if they are revealed and treated in time, they apparently do not represent a negative prognostic factor. Later occurred VF or VT are more a symptom of larger MI. AF, which is not directly life-threatening for the patients, frequently occurs in patients with larger MI and it is an independent predictor of a poor long-term prognosis of these patients. The early and successful reperfusion therapy is the best anti-arrhythmic therapeutic method in patients with MI.