Ventricular dyssynchrony imaging, echocardiographic and clinical outcomes of left bundle branch pacing and biventricular pacing.

BACKGROUND: Left bundle branch pacing (LBBP) is a novel physiological pacing technique which may serve as an alternative to cardiac resynchronization therapy (CRT) by biventricular pacing (BVP). This study assessed ventricular activation patterns and echocardiographic and clinical outcomes of LBBP and compared this to BVP. METHODS: Fifty consecutive patients underwent LBBP or BVP for CRT. Ventricular activation mapping was obtained by ultra-high-frequency ECG (UHF-ECG). Functional and echocardiographic outcomes and hospitalization for heart failure and all-cause mortality after one year from implantation were evaluated. RESULTS: LBBP resulted in greater resynchronization vs BVP (QRS width: 170 ± 16 ms to 128 ± 20 ms vs 174 ± 15 to 144 ± 17 ms, p = 0.002 (LBBP vs BVP); e-DYS 81 ± 17 ms to 0 ± 32 ms vs 77 ± 18 to 16 ± 29 ms, p = 0.016 (LBBP vs BVP)). Improvement in LVEF (from 28 ± 8 to 42 ± 10 percent vs 28 ± 9 to 36 ± 12 percent, LBBP vs BVP, p = 0.078) was similar. Improvement in NYHA function class (from 2.4 to 1.5 and from 2.3 to 1.5 (LBBP vs BVP)), hospitalization for heart failure and all-cause mortality were comparable in both groups. CONCLUSIONS: Ventricular dyssynchrony imaging is an appropriate way to gain a better insight into activation patterns of LBBP and BVP. LBBP resulted in greater resynchronization (e-DYS and QRS duration) with comparable improvement in LVEF, NYHA functional class, hospitalization for heart failure and all-cause mortality at one year of follow up.

Ultra-High-Frequency ECG in Cardiac Pacing and Cardiac Resynchronization Therapy: From Technical Concept to Clinical Application.

Identifying electrical dyssynchrony is crucial for cardiac pacing and cardiac resynchronization therapy (CRT). The ultra-high-frequency electrocardiography (UHF-ECG) technique allows instantaneous dyssynchrony analyses with real-time visualization. This review explores the physiological background of higher frequencies in ventricular conduction and the translational evolution of UHF-ECG in cardiac pacing and CRT. Although high-frequency components were studied half a century ago, their exploration in the dyssynchrony context is rare. UHF-ECG records ECG signals from eight precordial leads over multiple beats in time. After initial conceptual studies, the implementation of an instant visualization of ventricular activation led to clinical implementation with minimal patient burden. UHF-ECG aids patient selection in biventricular CRT and evaluates ventricular activation during various forms of conduction system pacing (CSP). UHF-ECG ventricular electrical dyssynchrony has been associated with clinical outcomes in a large retrospective CRT cohort and has been used to study the electrophysiological differences between CSP methods, including His bundle pacing, left bundle branch (area) pacing, left ventricular septal pacing and conventional biventricular pacing. UHF-ECG can potentially be used to determine a tailored resynchronization approach (CRT through biventricular pacing or CSP) based on the electrical substrate (true LBBB vs. non-specified intraventricular conduction delay with more distal left ventricular conduction disease), for the optimization of CRT and holds promise beyond CRT for the risk stratification of ventricular arrhythmias.

Extraction of non-infected redundant pacing and defibrillator leads does not result in better patient outcomes.

The introduction of dedicated tools for pacing and defibrillator lead extraction has resulted in relatively high success and low complication rates. The confidence this elicits has broadened the indications from device infections to non-functional or redundant leads and the latter make up an increasing share of extraction procedures. Proponents of extracting these leads point to the higher complication burden of lead extraction in patients with longstanding abandoned leads when compared one-to-one with extraction when these leads become redundant. However, this does not translate into better patient outcomes on a population level: complications are rare with properly abandoned leads and thus most patients will never be subjected to an extraction procedure and the ensuing complications. Therefore, not extracting redundant leads minimises the risk for the patients and avoids many expensive procedures.

Rescue left bundle branch area pacing in coronary venous lead failure or nonresponse to biventricular pacing: Results from International LBBAP Collaborative Study Group.

BACKGROUND: Cardiac resynchronization therapy (CRT) using biventricular pacing (BVP) is effective in patients with heart failure, left bundle branch block (LBBB), and reduced left ventricular function. Left bundle branch area pacing (LBBAP) has been reported as an alternative option for CRT. OBJECTIVE: The purpose of this study was to assess the feasibility and outcomes of LBBAP in patients who failed conventional BVP because of coronary venous (CV) lead complications or who were nonresponders to BVP. METHODS: At 16 international centers, LBBAP was attempted in patients with conventional CRT indication who failed BVP because of CV lead complications or lack of therapeutic response to BVP. Heart failure hospitalization (HFH) and death, echocardiographic outcomes, procedural data, pacing parameters, and lead complications including CV lead failure are reported. RESULTS: LBBAP was successfully performed in 200 patients (CV lead failures 156; nonresponders 44) (age 68 ± 11 years; female 35%; LBBB 55%; right ventricular pacing 23%; ischemic cardiomyopathy 28%; nonischemic cardiomyopathy 63%; left ventricular ejection fraction [LVEF] ≤35% in 80%). Procedural duration was 119.5 ± 59.6 minutes, and fluoroscopy duration was 25.7 ± 18.5 minutes. LBBAP threshold and R-wave amplitudes were 0.68 ± 0.35 V @ 0.45 ms and 10.4 ± 5 mV at implant, respectively, and remained stable during mean follow-up of 12 ± 10.1 months. LBBAP resulted in significant QRS narrowing from 170 ± 28 ms to 139 ± 25 ms (P <.001) with V6 R-wave peak times of 85 ± 17 ms. LVEF improved from 29% ± 10% at baseline to 40% ± 12% (P <.001) during follow-up. The risk of death or HFH was lower in those with CV lead failure than in nonresponders (hazard ratio 0.357; 95% confidence interval 0.168-0.756; P = .007) CONCLUSION: LBBAP is a viable alternative to CRT in patients who failed conventional BVP due to CV lead failure or who were nonresponders.

Feasibility, safety and outcomes of upgrading to left bundle branch pacing in patients with right ventricular pacing induced cardiomyopathy.

BACKGROUND: Right ventricular pacing (RVP) induces abnormal electrical activation and asynchronous ventricular contraction and leads to pacing induced cardiomyopathy (PICM) in 10%-20% of patients. Cardiac resynchronization therapy (CRT) utilizing biventricular pacing (BVP) is the recommended treatment. Left bundle branch pacing (LBBP) is a novel physiological pacing technique which may serve as an alternative to CRT. This study assessed feasibility and outcomes of LBBP delivered CRT in patients with PICM. METHODS: Total 20 consecutive patients with PICM who received an upgrade of their pacemaker to LBBP were prospectively studied. Acute success rate, complications, functional and echocardiographic response, and hospitalization for heart failure within 6 months from implantation were evaluated. RESULTS: LBBP was successfully delivered in all patients. Median duration of RVP before upgrade to LBBP was 3.8 years and the RVP was 99%. LBBP resulted in significant QRS narrowing (from 193 ± 18 ms to 130 ± 17 ms [p < .001]), improvement in LVEF (from 32% ± 6 % to 47% ± 8% [p < .001]) and NYHA class (from 2.8 ± 0.4 to 1.4 ± 0.5 [p < .001]) at 6 months. No LBBP-related complications occurred. No patients were hospitalized for heart failure or died. CONCLUSION: LBBP is feasible and safe in delivering CRT in PICM. Preliminary analyses demonstrated significant electrical resynchronization and favorable improvement in LV function and NYHA functional class at short term follow-up. Data needs to be validated in large randomized controlled trials.

Left bundle branch-optimized cardiac resynchronization therapy (LOT-CRT): Results from an international LBBAP collaborative study group.

BACKGROUND: Cardiac resynchronization therapy (CRT) based on the conventional biventricular pacing (BiV-CRT) technique sometimes results in broad QRS complex and suboptimal response. OBJECTIVE: We aimed to assess the feasibility and outcomes of CRT based on left bundle branch area pacing (LBBAP, in lieu of the right ventricular lead) combined with coronary venous left ventricular pacing in an international multicenter study. METHODS: LBBAP-optimized CRT (LOT-CRT) was attempted in nonconsecutive patients with CRT indications. Addition of the LBBA (or coronary venous) lead was at the discretion of the implanting physician, who was guided by suboptimal paced QRS complex, and/or on clinical grounds. RESULTS: LOT-CRT was successful in 91 of 112 patients (81%). The baseline characteristics were as follows: mean age 70 ± 11 years, female 22 (20%), left ventricular ejection fraction 28.7% ± 9.8%, left ventricular end-diastolic diameter 62 ± 9 mm, N-terminal pro-B-type natriuretic peptide level 5821 ± 8193 pg/mL, left bundle branch block 47 (42%), nonspecific intraventricular conduction delay 25 (22%), right ventricular pacing 26 (23%), and right bundle branch block 14 (12%). The procedure characteristics were as follows: mean fluoroscopy time 27.3 ± 22 minutes, LBBAP capture threshold 0.8 ± 0.5 V @ 0.5 ms, and R-wave amplitude 10 mV. LOT-CRT resulted in significantly greater narrowing of QRS complex from 182 ± 25 ms at baseline to 144 ± 22 ms (P < .0001) than did BiV-CRT (170 ± 30 ms; P < .0001) and LBBAP (162 ± 23 ms; P < .0001). At follow-up of ≥3 months, the ejection fraction improved to 37% ± 12%, left ventricular end-diastolic diameter decreased to 59 ± 9 mm, N-terminal pro-B-type natriuretic peptide level decreased to 2514 ± 3537 pg/mL, pacing parameters were stable, and clinical improvement was noted in 76% of patients (New York Heart Association class 2.9 vs 1.9). CONCLUSION: LOT-CRT is feasible and safe and provides greater electrical resynchronization as compared with BiV-CRT and could be an alternative, especially when only suboptimal electrical resynchronization is obtained with BiV-CRT. Randomized controlled trials comparing LOT-CRT and BiV-CRT are needed.

Cephalic vein access by modified Seldinger technique for lead implantations.

BACKGROUND: Venous access for cardiac implantable electronic devices (CIED) is commonly performed by cephalic venous cut down, or axillary or subclavian vein puncture. The latter technique carries a risk of complications such as pneumothorax or lead crush. Cephalic venous cut down is free of these complications but often less successful due to technical difficulties. We report a highly successful, simplified cephalic venous access with a modified Seldinger technique. METHODS: We prospectively studied 221 patients undergoing de novo implantation of a one, two, or three lead device system performed over a 1-year period at our center, and assessed the efficacy of the cephalic vein access including the number of leads successfully placed for each procedure. RESULTS: In 83% of patients undergoing CIED implantation, a suitable cephalic vein was present. In respectively 98% and 99% of patients undergoing single- or dual-chamber CIED implantation, lead placement could be performed exclusively via the cephalic vein and in 72% of cardiac resynchronization therapy implants, all three leads were placed via cephalic access. CONCLUSION: A novel, technically simple cephalic venous catheterization technique provides high success rates for any CIED lead implantation.

A Possible Role for Pacing the Left Ventricular Septum in Cardiac Resynchronization Therapy.

OBJECTIVES: The purpose of this study was to investigate whether stimulation at the left ventricular (LV) septum (LVs), alone or in combination with another site, could be an alternative way to apply cardiac resynchronization therapy (CRT) that avoids the coronary sinus and phrenic nerve stimulation and may create more physiological sequence of activation. BACKGROUND: In CRT, biventricular pacing is commonly performed from the right ventricle (RV) and the epicardium of the LV lateral wall (LVlat). In the left bundle branch block (LBBB), half of the electrical delay occurs due to impulse conduction across the septum. METHODS: Experiments were performed in 13 dogs with LBBB, 7 of them with chronic myocardial infarction (LBBB + MI). Pacing leads were positioned in the right atrium, RV, LVs, and at the LVlat epicardium. LV pump function was measured using conductance catheter and synchrony of electrical activation of the ventricles using epicardial mapping and from surface electrocardiogram. In 12 CRT patients, LV pump function was measured during temporary RV + LVs pacing and compared to RV + LVlat and RV + LVlat endo pacing. RESULTS: In the animals, electrical and hemodynamic benefits of LVs and RV + LVs pacing were comparable to those during conventional biventricular pacing and were comparable in LBBB and LBBB + MI hearts. Dispersion of repolarization was reduced by LVs stimulation, but not by LVlat pacing. In patients, hemodynamic benefits of RV + LVs, RV + LVlat and RV + LVlat endo pacing were similar. CONCLUSIONS: The use of the LVs as LV pacing site in CRT improves synchronization and acute hemodynamics comparably to conventional biventricular pacing in dyssynchronous canines and in patients. In addition, LVs stimulation may reduce dispersion of repolarization compared to epicardial pacing.

Mid-term haemodynamic and clinical results after aortic valve replacement using the Freedom Solo stentless bioprosthesis versus the Carpentier Edwards Perimount stented bioprosthesis.

OBJECTIVES: The aim of this study was to investigate the mid-term haemodynamic and clinical results after aortic valve replacement (AVR) using the Sorin Freedom Solo (SFS) stentless bioprosthesis, compared with the standard Carpentier Edwards Perimount (CEP) stented bioprosthesis. METHODS: In this retrospective cohort study of prospectively collected data, 116 patients were included in the SFS group (53 males; median age 74 years, range 56-85 years), and 122 patients in the CEP group (85 males; median age 73 years, range 43-88 years) between July 2007 and January 2013. Echocardiography was performed at 6 weeks after surgery in our centre, and the most recent echocardiography (in our centre or in referring cardiology departments) was requested. Between September 2013 and April 2014, all patients were called by the same researcher to gain clinical follow-up data. RESULTS: Mid-term mortality was 16.4% in the SFS group (19 patients) and 21.3% in the CEP group (26 patients); (P = 0.3). The mean transvalvular gradient was 7.4 ± 3.1 mmHg in the SFS group, and 11.6 ± 3.2 mmHg in the CEP group at 6 weeks postoperatively (P < 0.001). When stratified by labelled valve size, mean gradients were significantly lower in the SFS group for every size (P ≤ 0.03). After 3.3 ± 1.4 years of follow-up, the mean gradient was still significantly lower in the SFS group than that in the CEP group (P < 0.001). Clinical follow-up showed relatively low complication rates. CONCLUSION: These data suggest that the Sorin Freedom Solo stentless bioprosthesis is as safe as the Carpentier Edwards bioprosthesis, and provides better short- and mid-term haemodynamic performance than the Carpentier Edwards bioprosthesis.

Mid-term follow up of thromboembolic complications in left ventricular endocardial cardiac resynchronization therapy.

BACKGROUND: Endocardial left ventricular (LV) pacing for cardiac resynchronization therapy (CRT) has been proposed as an alternative to traditional LV transvenous epicardial pacing with equal or superior cardiac performance. The risks of cerebral thromboembolism and possible interference with mitral valve function moderate its clinical application. OBJECTIVE: The purpose of this study was to investigate cerebral thromboembolic complications after LV endocardial lead placement. Mitral regurgitation (MR) was the secondary outcome measure. METHODS: CRT candidates with a failed coronary sinus approach or nonresponders to conventional CRT underwent endocardial LV lead implantation (45 atrial transseptal, 6 transapical). Coumarin was prescribed with a targeted international normalized ratio between 3.5 and 4.5. Patient records were checked and general practitioners were contacted regarding cerebral thromboembolic complications. MR was evaluated by echocardiography at baseline and after 6 months. RESULTS: In 7 patients, 6 ischemic strokes and 2 transient ischemic attacks occurred, corresponding to 6.1 thromboembolic events per 100 patient-years (95% confidence interval 3.4-15.8). One patient refused hospital admission; all other patients had a subtherapeutic anticoagulation level at the time of the event. No major bleeding complications occurred. There was no change in the grade of MR (grade 2, P = .727) after 6 months. CONCLUSION: Endocardial LV lead placement in patients with advanced heart failure is associated with thromboembolic risk. However, all but 1 patient had a subtherapeutic level of anticoagulation. Endocardial LV lead placement is not associated with aggravation of MR.

Vectorcardiography as a tool for easy optimization of cardiac resynchronization therapy in canine left bundle branch block hearts.

BACKGROUND: In cardiac resynchronization therapy (CRT), optimization of left ventricular (LV) stimulation timing is often time consuming. We hypothesized that the QRS vector in the vectorcardiogram (VCG) reflects electric interventricular dyssynchrony, and that the QRS vector amplitude (VAQRS), halfway between that during left bundle branch block (LBBB) and LV pacing, reflects optimal resynchronization, and can be used for easy optimization of CRT. METHODS AND RESULTS: In 24 canine hearts with LBBB (12 acute, 6 with heart failure, and 6 with myocardial infarction), the LV was paced over a wide range of atrioventricular (AV) delays. Surface ECGs were recorded from the limb leads, and VAQRS was calculated in the frontal plane. Mechanical interventricular dyssynchrony (MIVD) was determined as the time delay between upslopes of LV and right ventricular pressure curves, and systolic function was assessed as LV dP/dtmax. VAQRS and MIVD were highly correlated (r=0.94). The VAQRS halfway between that during LV pacing with short AV delay and intrinsic LBBB activation accurately predicted the optimal AV delay for LV pacing (1 ms; 95% CI, -5 to 8 ms). Increase in LV dP/dtmax at the VCG predicted AV delay was only slightly lower than the highest observed LV dP/dtmax (-2.7%; 95% CI, -3.6 to -1.8%). Inability to reach the halfway value of VAQRS during simultaneous biventricular pacing (53% of cases) was associated with suboptimal hemodynamic response, which could be corrected by sequential pacing. CONCLUSIONS: The VAQRS reflects electric interventricular dyssynchrony and accurately predicts optimal timing of LV stimulation in canine LBBB hearts. Therefore, VCG may be useful as a reliable and easy tool for individual optimization of CRT.

Endocardial left ventricular pacing improves cardiac resynchronization therapy in chronic asynchronous infarction and heart failure models.

BACKGROUND: Studies in canine hearts with acute left bundle branch block (LBBB) showed that endocardial left ventricular (LV) pacing improves the efficacy of cardiac resynchronization therapy (CRT) compared with conventional epicardial LV pacing. The present study explores the efficacy of endocardial CRT in more compromised hearts and the mechanisms of such beneficial effects. METHODS AND RESULTS: Measurements were performed in 22 dogs, 9 with acute LBBB, 7 with chronic LBBB combined with infarction (embolization; LBBB plus myocardial infarction, and concentric remodeling), and 6 with chronic LBBB and heart failure (rapid pacing, LBBB+HF, and eccentric remodeling). A head-to-head comparison was performed of the effects of endocardial and epicardial LV pacing at 8 sites. LV activation times were measured using ≈100 endocardial and epicardial electrodes and noncontact mapping. Pump function was assessed from right ventricular and LV pressures. Endocardial CRT resulted in better electric resynchronization than epicardial CRT in all models, although the benefit was larger in concentrically remodeled LBBB plus myocardial infarction than in eccentrically remodeled LBBB+HF hearts (19% versus 10%). In LBBB and LBBB+HF animals, endocardial conduction was ≈50% faster than epicardial conduction; in all models, transmural impulse conduction was ≈25% faster when pacing from the endocardium than from the epicardium. Hemodynamic effects were congruent with electric effects. CONCLUSIONS: Endocardial CRT improves electric synchrony of activation and LV pump function compared with conventional epicardial CRT in compromised canine LBBB hearts. This benefit can be explained by a shorter path length along the endocardium and by faster circumferential and transmural impulse conduction during endocardial LV pacing.

Epicardial application of an amiodarone-releasing hydrogel to suppress atrial tachyarrhythmias.

BACKGROUND: Amiodarone is currently the most effective antiarrhythmic drug for sinus rhythm maintenance. However, due to serious extracardiac adverse effects, prophylactic amiodarone therapy is only appropriate for patients at high risk for postoperative atrial fibrillation (AF). We hypothesized that epicardial application of an amiodarone-releasing hydrogel would produce therapeutic myocardial drug concentrations, while systemic levels would remain low. METHODS: Goats were fitted with right atrial epicardial patch electrodes. A poly(ethylene glycol)-based hydrogel with amiodarone (1mg/kg bw) (n=10) or without drug (n=6) was applied to the right atrial epicardium. Atrial effective refractory period (AERP), conduction time and atrial response to burst pacing (rapid atrial response, RAR) were assessed up to 28days in awake goats. Myocardial, plasma and extracardiac tissue amiodarone concentrations were analysed by high-performance liquid chromatography. RESULTS: The amiodarone-loaded hydrogel produced therapeutic drug concentrations in the right atrium up to 21days after application. In this period, AERP and conduction time were prolonged, while RAR inducibility was reduced (P<0.05) compared to animals treated with drug-free hydrogel. Mean amiodarone concentrations in the right atrium were 1 order of magnitude higher than in other heart chambers and 2 orders of magnitude higher than in extracardiac tissues. Plasma amiodarone levels remained below the detection limit (<10ng/mL) during the 28-day follow-up. CONCLUSIONS: Epicardial application of an amiodarone-releasing hydrogel reduces atrial vulnerability to tachyarrhythmias up to 3weeks, while extracardiac drug levels remain low. Therefore, amiodarone-releasing hydrogel could be applied during cardiac surgery to prevent postoperative AF at minimal risk for extracardiac adverse side effects.

Transient midventricular ballooning syndrome. an atypical presentation of takotsubo cardiomyopathy.

A 72-year-old woman without cardiovascular history presented with acute substernal chest pain and dyspnoea. The electrocardiogram was normal, but the blood test analyses showed an elevated troponin T level. Emergency coronary angiography revealed normal epicardial coronary arteries, but the left ventriculogram demonstrated midventricular dilatation and akinesis with well-preserved contractility of the apex and base. The patient was diagnosed as having an atypical presentation of takotsubo cardiomyopathy. She was treated with a beta blocker and an ACE inhibitor and recovered well. A follow-up echocardiogram at 2 months showed normalization of the wall motion abnormality.

Myocardial infarction does not preclude electrical and hemodynamic benefits of cardiac resynchronization therapy in dyssynchronous canine hearts.

BACKGROUND: Several studies suggest that patients with ischemic cardiomyopathy benefit less from cardiac resynchronization therapy. In a novel animal model of dyssynchronous ischemic cardiomyopathy, we investigated the extent to which the presence of infarction influences the short-term efficacy of cardiac resynchronization therapy. METHODS AND RESULTS: Experiments were performed in canine hearts with left bundle branch block (LBBB, n=19) and chronic myocardial infarction, created by embolization of the left anterior descending or left circumflex arteries followed by LBBB (LBBB+left anterior descending infarction [LADi; n=11] and LBBB+left circumflex infarction [LCXi; n=7], respectively). Pacing leads were positioned in the right atrium and right ventricle and at 8 sites on the left ventricular (LV) free wall. LV pump function was measured using the conductance catheter technique, and synchrony of electrical activation was measured using epicardial mapping and ECG. Average and maximal improvement in electric resynchronization and LV pump function by right ventricular+LV pacing was similar in the 3 groups; however, the site of optimal electrical and mechanical benefit was LV apical in LBBB hearts, LV midlateral in LBBB+LCXi hearts and LV basal-lateral in LBBB+LADi hearts. The best site of pacing was not the site of latest electrical activation but that providing the largest shortening of the QRS complex. During single-site LV pacing the range of atrioventricular delays yielding > or =70% of maximal hemodynamic effect was approximately 50% smaller in infarcted than noninfarcted LBBB hearts (P<0.05). CONCLUSIONS: Cardiac resynchronization therapy can improve resynchronization and LV pump function to a similar degree in infarcted and noninfarcted hearts. Optimal lead positioning and timing of LV stimulation, however, require more attention in the infarcted hearts.

Left ventricular septal and left ventricular apical pacing chronically maintain cardiac contractile coordination, pump function and efficiency.

BACKGROUND: Conventional right ventricular (RV) apex pacing can lead to adverse clinical outcome associated with asynchronous activation and reduced left ventricular (LV) pump function. We investigated to what extent alternate RV (septum) and LV (septum, apex) pacing sites improve LV electric activation, mechanics, hemodynamic performance, and efficiency over 4 months of pacing. METHODS AND RESULTS: After AV nodal ablation, mongrel dogs were randomized to receive 16 weeks of VDD pacing at the RV apex, RV septum, LV apex, or LV septum (transventricular septal approach). Electric activation maps (combined epicardial contact and endocardial noncontact) showed that RV apical and RV septal pacing induced significantly greater electric desynchronization than LV apical and LV septal pacing. RV apex and RV septal pacing also significantly increased mechanical dyssynchrony, discoordination (MRI tagging) and blood flow redistribution (microspheres) and reduced LV contractility, relaxation, and myocardial efficiency (stroke work/myocardial oxygen consumption). In contrast, LV apical and LV septal pacing did not significantly alter these parameters as compared with the values during intrinsic conduction. At 16 weeks, acute intrasubject comparison showed that single-site LV apical and LV septal pacing generally resulted in similar or better contractility, relaxation, and efficiency as compared with acute biventricular pacing. CONCLUSIONS: Acute and chronic LV apical and LV septal pacing maintain regional cardiac mechanics, contractility, relaxation, and efficiency near native levels, whereas RV apical or RV septal pacing diminish these variables. Acute LV apical and LV septal pacing tend to maintain or improve contractility and efficiency compared with biventricular pacing.

Left ventricular endocardial pacing improves resynchronization therapy in canine left bundle-branch hearts.

BACKGROUND: We investigated the benefits of the more physiological activation achieved by left ventricular (LV) endocardial pacing (ENDO) as compared with conventional epicardial (EPI) LV pacing in cardiac resynchronization therapy. METHODS AND RESULTS: In 8 anesthetized dogs with experimental left bundle-branch block, pacing leads were positioned in the right atrium, right ventricle, and at 8 paired (EPI and ENDO) LV sites. Systolic LV pump function was assessed as LVdP/dtmax and stroke work and diastolic function as LVdP/dtmin. Electrical activation and dispersion of repolarization were determined from 122 epicardial and endocardial electrodes and from analysis of the surface ECG. Overall, ENDO-biventricular (BiV) pacing more than doubled the degree of electrical resynchronization and increased the benefit on LVdP/dtmax and stroke work by 90% and 50%, respectively, as compared with EPI-BiV pacing. During single-site LV pacing, the range of AV intervals with a >10% increase in LV resynchronization (79+/-31 versus 32+/-24 ms, P<0.05) and LVdP/dtmax (92+/-29 versus 63+/-39 ms) was significantly longer for ENDO than for EPI pacing. EPI-BiV but not ENDO-BiV pacing created a significant (40+/-21 ms) transmural dispersion of repolarization. CONCLUSIONS: Data from this acute animal study indicate that the use of an endocardial LV pacing electrode may increase the efficacy of resynchronization therapy as compared with conventional epicardial resynchronization therapy.

Intrapericardial delivery of amiodarone and sotalol: atrial transmural drug distribution and electrophysiological effects.

Amiodarone and sotalol are frequently used in the treatment of atrial fibrillation. However, oral and intravenous (IV) therapy with these drugs has suboptimal efficacy and is associated with serious extracardiac side effects. We hypothesized that intrapericardial (IPC) delivery produces antiarrhythmic effects at lower plasma drug concentrations than IV delivery. Goats (n = 27) were randomised into 5 groups receiving either IPC vehicle, amiodarone (IV or IPC) or dl-sotalol (IV or IPC). Epicardial and endocardial atrial effective refractory period and atrial response to burst pacing (rapid atrial response, RAR) were assessed before and after 3 hours of drug infusion at 2 mg.kg.h. IPC delivery produced steeply decreasing drug concentrations from epicardium to endocardium in both atria and ventricles. Plasma drug concentrations were significantly lower in IPC than in IV groups. IPC amiodarone and sotalol reduced epicardial RAR inducibility (-74% +/- 20% and -66% +/- 30%, respectively) compared with IV delivery (-11% +/- 17% and -17% +/- 28%, respectively; P < 0.05). Endocardial RAR inducibility was only reduced in the IPC amiodarone group (-70% +/- 17%, P < 0.05). In conclusion, IPC delivery of amiodarone and sotalol increases atrial drug concentration and antiarrhythmic effects at reduced plasma drug concentrations. These potential benefits are particularly prominent for IPC delivered amiodarone.

Stability of an autologous platelet clot in the pericardial sac: An experimental and clinical study.

OBJECTIVE: Autologous platelet clots serve as slow-release delivery systems for platelet-derived growth factors and cytokines. Their application to the pericardial sac might facilitate salvage and repair of ischemically injured myocardium. However, little is known about platelet clot stability in the pericardial sac. We investigated the stability of platelet clots in vitro and after administration to the pericardial sac in pigs and patients. METHODS: In 5 Yorkshire-Landrace pigs and 10 patients, in vitro manufactured autologous platelet gel (Medtronic Magellan Platelet Separator) and platelet-rich fibrin (Vivolution Vivostat System) were administered to the pericardial sac for 30 minutes. Two antifibrinolytics (tranexamic acid and aprotinin) were tested for their capacity to stabilize autologous platelet gel. In vitro clots, incubated at 37 degrees C for 48 hours, served as controls. Clot weight was measured before and after administration. RESULTS: In vitro, autologous platelet gel clots of either formula liquefied almost entirely within 60 minutes whereas platelet-rich fibrin clots remained intact. In the pig, platelet clot weight decreased to 16.7% +/- 7.8% (P < .05) and 66.4% +/- 3.2% (P < .05) of initial clot weight for autologous platelet gel and platelet-rich fibrin, respectively. Addition of antifibrinolytics to autologous platelet gel did not reduce clot degradation significantly. In patients, autologous platelet gel and platelet-rich fibrin clot weight remained 9.0% +/- 1.5% (P < .05) and 73.7% +/- 2.6% (P < .05) of initial clot weight, respectively. CONCLUSIONS: Autologous platelet gel is unstable both in vitro and in vivo, whereas platelet-rich fibrin remains intact in vitro and, compared with autologous platelet gel, is less subject to degradation in pigs and in patients.