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Objectives The purpose of this study was to enhance understanding of the working mechanism of cardiac resynchronization therapy by comparing animal experimental, clinical, and computational data on the hemodynamic and electromechanical consequences of left ventricular pacing (LVP) and biventricular pacing (BiVP). Background It is unclear why LVP and BiVP have comparative positive effects on hemodynamic function of patients with dyssynchronous heart failure. Methods Hemodynamic response to LVP and BiVP (% change in maximal rate of left ventricular pressure rise [LVdP/dt max ]) was measured in 6 dogs and 24 patients with heart failure and left bundle branch block followed by computer simulations of local myofiber mechanics during LVP and BiVP in the failing heart with left bundle branch block. Pacing-induced changes of electrical activation were measured in dogs using contact mapping and in patients using a noninvasive multielectrode electrocardiographic mapping technique. Results LVP and BiVP similarly increased LVdP/dt max in dogs and in patients, but only BiVP significantly decreased electrical dyssynchrony. In the simulations, LVP and BiVP increased total ventricular myofiber work to the same extent. While the LVP-induced increase was entirely due to enhanced right ventricular (RV) myofiber work, the BiVP-induced increase was due to enhanced myofiber work of both the left ventricle (LV) and RV. Overall, LVdP/dt max correlated better with total ventricular myofiber work than with LV or RV myofiber work alone. Conclusions Animal experimental, clinical, and computational data support the similarity of hemodynamic response to LVP and BiVP, despite differences in electrical dyssynchrony. The simulations provide the novel insight that, through ventricular interaction, the RV myocardium importantly contributes to the improvement in LV pump function induced by cardiac resynchronization therapy.

Objectives The purpose of this study was to analyze left ventricular obstruction in patients with hypertrophic cardiomyopathy (HCM) during exercise echocardiography. Background Despite the association of symptoms with left ventricular outflow tract obstruction in HCM, there exist paradoxical situations in which significant intraventricular gradients (>50 mm Hg) at rest occur in conjunction with excellent exercise tolerance. Methods To examine this phenomenon, we performed exercise echocardiography and analyzed the clinical status of 107 HCM patients with and without resting obstruction. Results At rest, 69 patients had no obstruction and 38 exhibited an intraventricular gradient, 9 of whom exhibited a decrease in gradient of at least 30 mm Hg (99.4 ± 35.5 mm Hg to 30.2 ± 14.3 mm Hg, p Conclusions Our study reports a subgroup of HCM patients, designated PRE based on a decreased intraventricular gradient during exercise. The reduced exertional obstruction may account for the better functional class and trend toward fewer clinical events in PRE patients.

Objectives This study sought to investigate whether noninvasive electrocardiographic activation mapping is a useful method for predicting response to cardiac resynchronization therapy (CRT). Background One third of the patients appear not to respond to CRT when they are selected according to QRS duration. Methods We performed electrocardiographic activation mapping in 33 consecutive CRT candidates (QRS duration ≥120 ms). In 18 patients, the 12-lead electrocardiographic morphology was left bundle branch block (LBBB), and in 15, it was nonspecific intraventricular conduction disturbance (NICD). Three indexes of electrical dyssynchrony were derived from intrinsic maps: right and left ventricular total activation times and ventricular electrical uncoupling (VEU) (difference between the left ventricular [LV] and right ventricular mean activation times). We assessed the ability of these parameters to predict response, measured using a clinical composite score, after 6 months of CRT. Results Electrocardiographic maps revealed homogeneous patterns of activation and consistently greater VEU and LV total activation time (LVTAT) in patients with LBBB compared with heterogeneous activation sequences and shorter VEU and LVTAT in NICD patients (VEU: 75 ± 12 ms vs. 40 ± 22 ms; p l 0.001; LVTAT: 115 ± 21 ms vs. 91 ± 34 ms; p = 0.03). LBBB and NICD patients had similar right ventricular total activation times (62 ± 30 ms vs. 58 ± 26 ms; p = 0.7). The area under the receiver-operating characteristic curve indicated that VEU (area under the curve [AUC]: 0.88) was significantly superior to QRS duration (AUC: 0.73) and LVTAT (AUC: 0.72) for predicting CRT response (p l 0.05). With a 50-ms cutoff value, VEU identified CRT responders with 90% sensitivity and 82% specificity whether LBBB was present or not. Conclusions Ventricular electrical uncoupling measured by electrocardiographic mapping predicted clinical CRT response better than QRS duration or the presence of LBBB.

The Micra VVI leadless pacemaker was designed to mitigate lead and pocket related complications associated with transvenous systems. We sought to understand patient selection and relationship to outcomes with this novel therapy. Successfully implanted patients from the Micra IDE trial were divided

Objectives We sought to evaluate the impact of the left ventricular (LV) pacing site on hemodynamic response to cardiac resynchronization therapy (CRT). Background CRT reduces morbidity and mortality in heart failure patients. However, 20% to 40% of eligible patients may not fully benefit from CRT device implantation. We hypothesized that selecting the optimal LV pacing site could be critical in this issue. Methods Thirty-five patients with nonischemic dilated cardiomyopathy referred for CRT device implantation were studied. Intraventricular dyssynchrony and latest activated LV wall were defined by tissue Doppler imaging analysis before the study. Eleven predetermined LV pacing sites were systematically assessed in random order: basal and mid-cavity (septal, anterior, lateral, inferior), apex, coronary sinus (CS), and the endocardial site facing the CS pacing site. For each patient, +dP/dTmax, −dP/dTmin, pulse pressure, and end-systolic pressure during baseline (AAI) and DDD LV pacing were compared. Two atrioventricular delays were tested. Results Major interindividual and intraindividual variations of hemodynamic response depending on the LV pacing site were observed. Compared with baseline, LV DDD pacing at the best LV position significantly improved +dP/dTmax(+31 ± 26%, p Conclusions The pacing site is a primary determinant of the hemodynamic response to LV pacing in patients with nonischemic dilated cardiomyopathy. Pacing at the best LV site is associated acutely with fewer nonresponders and twice the improvement in +dP/dTmaxobserved with CS pacing.

Objectives. The aim of this study was to assess the potential acute benefit of multisite cardiac pacing with optimized atrioventricular synchrony and simultaneous biventricular pacing in patients with drug-refractory congestive heart failure (CHF).Background. Prognosis and quality of life in severe CHF are poor. Various nonpharmacological therapies have been evaluated but are restricted in their effectiveness and applications. In the early 1990s, dual chamber pacing (DDD) pacing was proposed as primary treatment of refractory CHF but results were controversial. Recently, tests to evaluate the effect of simultaneous pacing of both ventricles have elicited a significant improvement of cardiac performance.Methods. Acute hemodynamic study was conducted in 18 patients with severe CHF (New York Heart Association class III and IV) and major intraventricular conduction block (IVCB) (QRS duration = 170 ± 37 ms). Using a Swan-Ganz catheter, pulmonary artery pressure, pulmonary capillary wedge pressure (PCWP) and cardiac index (CI) were measured in different pacing configurations: atrial pacing (AAI) mode, used as reference, single-site right ventricular DDD pacing and biventricular pacing with the right ventricular lead placed either at the apex or at the outflow tract.Results. The CI was significantly increased by biventricular pacing in comparison with AAI or right ventricular (RV). DDD pacing (2.7 ± 0.7 vs. 2 ± 0.5 and 2.4 ± 0.6 l/min/m2, p < 0.001). The PCWP also decreased significantly during biventricular pacing, compared with AAI (22 ± 8 vs. 27 ± 9 mm Hg; p < 0.001).Conclusions. This acute hemodynamic study demonstrated that biventricular DDD pacing may significantly improve cardiac performance in patients with IVCB and with severe heart failure, in comparison with intrinsic conduction and single-site RV DDD pacing.

The purpose of this study was to analyze left ventricular obstruction in patients with hypertrophic cardiomyopathy (HCM) during exercise echocardiography.Despite the association of symptoms with left ventricular outflow tract obstruction in HCM, there exist paradoxical situations in which significant intraventricular gradients (50 mm Hg) at rest occur in conjunction with excellent exercise tolerance.To examine this phenomenon, we performed exercise echocardiography and analyzed the clinical status of 107 HCM patients with and without resting obstruction.At rest, 69 patients had no obstruction and 38 exhibited an intraventricular gradient, 9 of whom exhibited a decrease in gradient of at least 30 mm Hg (99.4 ± 35.5 mm Hg to 30.2 ± 14.3 mm Hg, p0.001) during exercise (paradoxical response to exercise [PRE]). The PRE patients presented with a significantly lower New York Heart Association clinical class and higher left ventricular volumes and arterial pressure both at rest and during exercise than HCM patients in whom the gradient increased or did not change during stress echocardiography. Finally, PRE patients exhibited a trend toward a reduced rate of cardiac events.Our study reports a subgroup of HCM patients, designated PRE based on a decreased intraventricular gradient during exercise. The reduced exertional obstruction may account for the better functional class and trend toward fewer clinical events in PRE patients.

This study sought to investigate whether noninvasive electrocardiographic activation mapping is a useful method for predicting response to cardiac resynchronization therapy (CRT).One third of the patients appear not to respond to CRT when they are selected according to QRS duration.We performed electrocardiographic activation mapping in 33 consecutive CRT candidates (QRS duration ≥120 ms). In 18 patients, the 12-lead electrocardiographic morphology was left bundle branch block (LBBB), and in 15, it was nonspecific intraventricular conduction disturbance (NICD). Three indexes of electrical dyssynchrony were derived from intrinsic maps: right and left ventricular total activation times and ventricular electrical uncoupling (VEU) (difference between the left ventricular [LV] and right ventricular mean activation times). We assessed the ability of these parameters to predict response, measured using a clinical composite score, after 6 months of CRT.Electrocardiographic maps revealed homogeneous patterns of activation and consistently greater VEU and LV total activation time (LVTAT) in patients with LBBB compared with heterogeneous activation sequences and shorter VEU and LVTAT in NICD patients (VEU: 75 ± 12 ms vs. 40 ± 22 ms; p 0.001; LVTAT: 115 ± 21 ms vs. 91 ± 34 ms; p = 0.03). LBBB and NICD patients had similar right ventricular total activation times (62 ± 30 ms vs. 58 ± 26 ms; p = 0.7). The area under the receiver-operating characteristic curve indicated that VEU (area under the curve [AUC]: 0.88) was significantly superior to QRS duration (AUC: 0.73) and LVTAT (AUC: 0.72) for predicting CRT response (p 0.05). With a 50-ms cutoff value, VEU identified CRT responders with 90% sensitivity and 82% specificity whether LBBB was present or not.Ventricular electrical uncoupling measured by electrocardiographic mapping predicted clinical CRT response better than QRS duration or the presence of LBBB.

Biventricular resynchronization, a therapy recommended for patients presenting with left ventricular (LV) dysfunction and ventricular dyssynchrony, requires the implantation of an LV lead, usually placed in a lateral or posterolateral tributary of the coronary sinus. Despite important progress made in the development of dedicated instrumentation, the procedure remains sometimes challenging and unsuccessful in a minority of patients. In the rare instances of unsuccessful transvenous implantations occurring in the presence of major surgical contraindications, a few operators have implanted the LV lead transseptally, an approach limited by technical difficulties and by the thromboembolic risk associated with the presence of a lead inside the LV cavity. The interest in this approach was recently renewed by 2 studies in an animal model and in humans, respectively, which both found a distinctly superior hemodynamic performance associated with endocardial compared with epicardial stimulation. This review discusses the advantages and disadvantages of LV endocardial stimulation, examines the various techniques of LV endocardial stimulation, and projects their future applications in light of these highly promising recent results. The implementation of endocardial stimulation will ultimately depend on: 1) the development of safe, effective, and durable instrumentation, and reliable and reproducible intraprocedural methods to identify the optimal site of stimulation; and 2) the completion of controlled trials confirming the superiority of this technique compared with standard cardiac resynchronization therapy.

Objectives The purpose of this study was to enhance understanding of the working mechanism of cardiac resynchronization therapy by comparing animal experimental, clinical, and computational data on the hemodynamic and electromechanical consequences of left ventricular pacing (LVP) and biventricular pacing (BiVP). Background It is unclear why LVP and BiVP have comparative positive effects on hemodynamic function of patients with dyssynchronous heart failure. Methods Hemodynamic response to LVP and BiVP (% change in maximal rate of left ventricular pressure rise [LVdP/dt(max)]) was measured in 6 dogs and 24 patients with heart failure and left bundle branch block followed by computer simulations of local myofiber mechanics during LVP and BiVP in the failing heart with left bundle branch block. Pacing-induced changes of electrical activation were measured in dogs using contact mapping and in patients using a noninvasive multielectrode electrocardiographic mapping technique. Results LVP and BiVP similarly increased LVdP/dt(max) in dogs and in patients, but only BiVP significantly decreased electrical dyssynchrony. In the simulations, LVP and BiVP increased total ventricular myofiber work to the same extent. While the LVP-induced increase was entirely due to enhanced right ventricular (RV) myofiber work, the BiVP-induced increase was due to enhanced myofiber work of both the left ventricle (LV) and RV. Overall, LVdP/dt(max) correlated better with total ventricular myofiber work than with LV or RV myofiber work alone. Conclusions Animal experimental, clinical, and computational data support the similarity of hemodynamic response to LVP and BiVP, despite differences in electrical dyssynchrony. The simulations provide the novel insight that, through ventricular interaction, the RV myocardium importantly contributes to the improvement in LV pump function induced by cardiac resynchronization therapy.