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Functional mitral regurgitation (MR) describes valve leakage in the absence of disease or damage to the mitral leaflets or subvalvular apparatus. Significant, new functional MR after cardiopulmonary bypass (CPB) may result from a number of intraoperative processes, including left ventricular (LV) ischemia and enlargement, left atrial enlargement secondary to increased filling pressure, and systolic anterior motion of the mitral valve after mitral repair. Assessment of new MR after CPB is important because it may direct hemodynamic maneuvers or prompt reinitiation of CPB if surgical intervention is deemed necessary. Described extensively in the electrophysiology literature but underreported as a cause of MR after CPB, LV dyssynchrony represents another possible mechanism of functional MR, in which resynchronization of conduction via pacing maneuvers may prove beneficial. Herein, a series of 4 patients in whom new MR was found after non-mitral valve cardiac surgery in the setting of normal LV systolic function is presented, and LV dyssynchrony is proposed as a major contributing factor. The findings suggested that the concomitant observation of new or worsened functional MR, together with normal global and regional LV systolic function, should lead the clinician to consider ventricular dyssynchrony as a possible cause. Attempts to improve or alter ventricular conduction should be considered before contemplating a return to CPB for mitral valve intervention.

–: The benefits of CRT in select subsets of systolic heart failure patients with LBBB are proven. We prospectively evaluated conventional and newer echocardiographic parameters of left ventricular dyssynchrony in 35 patients who underwent CRT and were followed up after 6 months. Of the 33 surviving patients, 21 were echocardiographic responders and 24 were clinical responders. The parameters in clinical responders and non-responders were compared. The anatomic M Mode parameters of delays improved, while the radial strain and the mitral valve velocity time integral (MVVTI) did not show any significant change after CRT.

This study aimed to evaluate left ventricular dyssynchrony with QRS width on ECG in patients with systolic heart failure. 100 study patients were classified into two groups. Narrow QRS group-N- QRS (80-119 msec) and Wide QRS group-W- QRS (120-160 msec). Out of each 50 patients in W- QRS group, 38(76%) had LV dyssynchrony and 18 (36%) in N- QRS group had ventricular dyssynchrony. Dyssynchrony in narrow QRS patients with heart failure also needs attention as a therapeutic target in future studies.

Recently, cases of pharmacological resynchronization for Wolff–Parkinson–White syndrome (WPWS) in children with left ventricular dyssynchrony (LVD) were reported, but an appropriate pharmacological therapy has not yet been established. A 3-month-old, previously healthy female patient was referred to our hospital due to supraventricular tachycardia (SVT). After resolution of the SVT, 12-lead electrocardiography (ECG) showed ventricular pre-excitation. Transthoracic echocardiography showed LVD with no findings of congenital heart disease or cardiomyopathy. To prevent SVT recurrence, oral propranolol administration was started, but the SVT recurred one month later. To prevent further recurrences, oral flecainide administration was started, as the patient’s body weight was insufficient for catheter ablation to be performed safely. When the flecainide dosage was increased to 50 mg/m(2)/day, the pre-excitation resolved, and the LVD improved. Holter ECG showed that the resolution of pre-excitation depended on the serum concentration of flecainide. There are only few reports on pharmacological resynchronization in WPWS patients with LVD (LVD-WPWS). The present report is the first to examine the efficacy of flecainide in patients with recurrent SVT. Flecainide may be a safe and effective alternative resynchronization therapy for LVD-WPWS patients, especially for children in whom catheter ablation cannot be performed safely due to insufficient body weight.

Cardiac resynchronization therapy (CRT) via biventricular pacing has demonstrated clinical benefits in patients with heart failure (HF) and ventricular dyssynchrony. Other approaches of CRT is little known.The purpose of this study was to assess the feasibility, safety, and efficacy of left bundle branch area pacing (LBBAP) in patients with HF and left bundle branch block (LBBB).Eleven consecutive patients with HF, reduced left ventricular ejection fraction and LBBB and indicated for CRT were recruited. LBBAP was achieved via transventricular septal approach and characterized by narrower QRS duration, shortened peak left ventricular activation time, and right bundle branch conduction delay on the electrocardiogram. Electrocardiogram, echocardiogram, and cardiac function were evaluated at baseline and follow-up. Interventricular mechanical delay and 3-dimensional tissue synchronization imaging during LBBAP and intrinsic LBBB status were measured by echocardiography at follow-up.LBBAP significantly shortened QRS duration (from baseline 180.00 ± 15.86 ms to 129.09 ± 15.94 ms; P.01) and left ventricular activation time (from baseline 108.18 ± 15.54 ms to 80.91 ± 9.95 ms; P.01). Interventricular mechanical delay and the standard deviation of tissue synchronization imaging of 12 left ventricular (LV) segments were significantly shorter during LBBAP than in intrinsic LBBB status (both with P.01). At a mean follow-up period of 6.7 months, New York Heart Association functional class, plasma level of B-type natriuretic peptide, LV end-systolic diameter, and left ventricular ejection fraction were significantly improved (all with P.05 vs baseline).The study demonstrates that LBBAP is clinically feasible in patients with systolic HF and LBBB. LBBAP can be a new CRT technique to correct LBBB, provide ventricular synchrony, and improve clinical symptoms with LV reverse remodeling.

Right ventricular pacing causes electric and mechanical dyssynchrony, which is associated with an increased risk for heart failure and atrial fibrillation. Cardiac resynchronization therapy with biventricular pacing reduces ventricular dyssynchrony and results in clinical benefits in subsets of patients with heart failure with QRS prolongation. Recently, His bundle pacing has increased in use as a physiological pacing modality but is limited by difficult implantation, lower success rates in patients with QRS prolongation, and high, often unstable, pacing capture threshold. Thus, the concept of pacing the conduction system distal to the His bundle to bypass the region of conduction block was proposed. Early clinical studies demonstrated the procedural feasibility of left bundle branch pacing using a transventricular septal approach that generates narrow paced QRS duration, fast synchronized left ventricular activation, and correction of left bundle branch block. The current status and future direction of left bundle branch pacing are summarized in this paper.

Background His bundle pacing (HBP) can be achieved in 2 ways: selective HBP (S-HBP), where the His bundle is captured alone, and nonselective HBP (NS-HBP), where local myocardium is also captured, resulting a pre-excited electrocardiogram appearance. Objective We assessed the impact of this ventricular pre-excitation on left and right ventricular dyssynchrony. Methods We recruited patients who displayed both S-HBP and NS-HBP. We performed noninvasive epicardial electrical mapping for left and right ventricular activation time (LVAT and RVAT) and pattern. Results Twenty patients were recruited. In the primary analysis, the mean within-patient change in LVAT from S-HBP to NS-HBP was -5.5 ms (95% confidence interval: -0.6 to -10.4, noninferiority P < .0001). NS-HBP did not prolong RVAT (4.3 ms, -4.0 to 12.8, P = .296) but did prolong QRS duration (QRSd, 22.1 ms, 11.8 to 32.4, P = .0003). In patients with narrow intrinsic QRS (n = 6), NS-HBP preserved LVAT (-2.9 ms, -9.7 to 4.0, P = .331) but prolonged QRS duration (31.4 ms, 22.0 to 40.7, P = .0003) and mean RVAT (16.8 ms, -5.3 to 38.9, P = .108) compared to S-HBP. Activation pattern of the left ventricular surface was unchanged between S-HBP and NS-HBP, but NS-HBP produced early basal right ventricular activation that was not seen in S-HBP. Conclusion Compared to S-HBP, local myocardial capture during NS-HBP produces pre-excitation of the basal right ventricle resulting in QRS duration prolongation. However, NS-HBP preserves the left ventricular activation time and pattern of S-HBP. Left ventricular dyssynchrony is not an important factor when choosing between S-HBP and NS-HBP in most patients., Graphical abstract

The goal of this study was to examine whether diastolic dyssynchrony, measured by using gated single-photon emission computed tomography (GSPECT) myocardial perfusion imaging (MPI) in patients with coronary artery disease (CAD), is independently associated with adverse outcomes.Systolic left ventricular dyssynchrony is known to be associated with worse clinical outcome in patients with CAD.This study included patients who presented to Duke University for GSPECT MPI between 2003 and 2009. Patients had at least 1 major epicardial obstruction ≥50%. Dyssynchrony was assessed by using Emory Cardiac Toolbox software and compared with a control population without CAD. Abnormal degree of diastolic/systolic dyssynchrony was defined as values above 2 SDs above mean of mechanical dyssynchrony parameters. Using Cox proportional hazards modeling, the adjusted association between dyssynchrony and outcomes, including all-cause and cardiovascular death, was assessed.Among 1,310 patients with a median age of 64 years (interquartile range: 55 to 72 years), 69.7% were male and 2.6% had left bundle branch block. Overall, 241 (18.4%) and 238 (18.2%) patients had significant systolic and diastolic mechanical dyssynchrony, respectively, and 211 (16.1%) had both. After a median follow-up of 7.1 years, 543 deaths occurred. At 5 years, the mortality estimate was 21.2% among patients with a normal degree of diastolic left ventricular mechanical dyssynchrony (LVMD) and 41.7% among those with an abnormal degree of LVMD (p 0.001). When added to clinical comorbidities, electrical dyssynchrony, and systolic LVMD, diastolic dyssynchrony was incrementally associated with cardiovascular mortality (global chi-square statistic of 211.9 vs. 222.8; 2 degrees of freedom; p = 0.004). In a model that also includes left ventricular ejection fraction, the addition of diastolic dyssynchrony to systolic dyssynchrony maintained an incremental prognostic benefit (global chi-square statistic of 234.8 vs. 241.8; p = 0.030). Adjustment for baseline ischemia and scar burden did not change this relationship.Systolic and diastolic left ventricular dyssynchrony, as measured by using GSPECT MPI, were associated with adverse outcomes. Moreover, diastolic dyssynchrony appears to provide incremental predictive value to clinical history, electrical dyssynchrony, and left ventricular function.

Investigative works of the past 20 years have compiled extensive data on the effectiveness and implications of cardiac resynchronization therapy (CRT) in patients with heart failure. Since then, CRT has become a well-accepted and widely adapted adjunctive therapy for patients with heart failure with ventricular dyssynchrony. This overview discusses the updated knowledge on the benefits afforded with CRT and reviews the major clinical trials that have established CRT at its current practice. Based on the data, the indications of CRT and the timing of appropriate implant of CRT devices with respect to heart failure status will be presented.

Permanent His bundle pacing (PHBP) has shown significant clinical benefits in patients requiring ventricular pacing compared with conventional right ventricular pacing. There is an emerging role for PHBP in patients with interventricular dyssynchrony. This article reviews the mechanisms and the available data on the use of PHBP in overcoming dyssynchrony.

Idiopathic or iatrogenic left bundle branch block (LBBB) is a unique model of electro-mechanical ventricular dyssynchrony with concordant changes in electrical activation sequence and mechanical ventricle synchronization. In chronic animal models, isolated LBBB induces structural remodeling with progressive left ventricular (LV) dysfunction. Most abnormalities can be reverted after cardiac resynchronization therapy (CRT). In humans, 2 principal models of LBBB dyssynchronopathy can be observed: the chronic model of isolated LBBB and an acute iatrogenic model of new-onset LBBB after aortic valve interventions. Although epidemiological evidence and clinical data need to be strengthened, there is a strong presumption that they may lead to LBBB-induced cardiomyopathy and benefit from CRT to prevent progression to heart failure. A large cohort study with prospective follow-up would be required to better define actual incidence, evolution over time, and predisposing factors. Parallel randomized CRT clinical trials should be conducted in selected at-risk populations: namely, patients with persistent LBBB after transcatheter aortic valve replacement.

Recently, permanent His bundle pacing (HBP) has emerged as a viable pacing strategy for chronic ventricular pacing. It allows for recruitment of the native His Purkinje system thereby preventing pacing-induced ventricular dyssynchrony seen in traditional right ventricular pacing. Current tools allow for relatively good success rates for implantation. Understanding the various responses to HBP is crucial for long-term success. With better tools and unique pacing and sensing algorithms designed specifically for this form of pacing, HBP is likely to increase as a tool for long-term pacing therapy.

Permanent His bundle pacing prevents ventricular dyssynchrony in patients who depend on ventricular pacing and can provide an alternative means to implementing cardiac resynchronization therapy in patients with bundle branch disease and congestive heart failure. Adoption of His bundle pacing, however, has lagged in part due to perceived and real challenges in performing the procedure well and durably. This article focuses on what is required to get on the learning curve and developing technical competence.

His bundle pacing (HBP) prevents ventricular dyssynchrony and its long-term consequences by preserving normal electrical activation of the ventricles. Since the original description of permanent HBP in 2000, the adoption of HBP has increased over the past several years. However, the reporting of procedural and clinical outcomes to date is not uniform. This article is a collaboration between several implanters with significant experience in HBP to establish a uniform set of definitions encompassing the different forms of HBP as well as define a standardized approach to gathering data end points to ensure consistency in reported outcomes.

Left ventricular dyssynchrony can be assessed with phase parameters from radionuclide ventriculography (RNVG), including approximate entropy ( ApEn ). The input values used to calculate ApEn will affect the results significantly, so it is essential to optimise ApEn for the application. However to date, no optimisation for ApEn applied to images has been published. In this paper, generated data were used to simulate patient phase images, allowing the input parameters for ApEn to be tested and optimised in a controlled environment. Clinical images were then used to confirm that the selected parameters were appropriate. The results demonstrate the effect of input parameters for ApEn and the most appropriate use with RNVG phase images. This work demonstrates the importance of optimisation and standardisation when using ApEn as a measure of dyssynchrony.

One of the key aspects of heart failure management is whether patients should be considered for device therapy. Clinical trials, which have employed QRS duration and morphology as measures of left ventricular dyssynchrony, have demonstrated the morbidity and mortality benefit of cardiac resynchronization therapy. Women, however, are underrepresented in these trials, the basis of which current guidelines and standards of care are derived. Despite low enrollment of women, several studies highlight the statistically significant improvement in risk reduction that women gain from cardiac resynchronization therapy compared to men. This review discusses the foundation for current guidelines and the building evidence that women may reap more benefit from cardiac resynchronization therapy than men. Given these data, a more individualized approach should be considered in prescribing this device therapy in the future, particularly in women.

Background: Left ventricular dyssynchrony has been studied extensively, but this is not the case with right ventricular (RV) dyssynchrony. Our aim was to investigate RV dyssynchrony through 2D speckle strain imaging in patients with chronic thromboembolic pulmonary hypertension (CTEPH) before and after pulmonary thromboendarterectomy (PTE).Methods: We measured 2D peak RV strain (%) of the RV free-wall and time to peak strain (ms) of its three freewall segments (base, mid, and apex) in 127 consecutive CTEPH patients (51 ± 14 years, 59% female) with adequate images pre- and post-PTE. RV strain was calculated using Epsilon Imaging EchoInsight® software. RV dyssynchrony was measured using two methods: the standard deviation of peak systolic strain and the standard deviation of time (ms) to peak strain (RVDT) between the three RV free-wall segments.Results: Mean RV free wall strain did not change significantly after PTE (−11.4 ± 5.7 to −11.2 ± 5.6%, p = 0.67). However, RV dyssynchrony improved dramatic...

Background RV dyssynchrony has been described in patients with pulmonary hypertension (PH) and is an independent predictor of clinical worsening; however, the optimal method for measuring RV dyssynchrony has not been fully established. This study aimed to investigate whether RV dyssynchrony is correlated with hemodynamics and prognosis in PH patients and to identify the best parameter for evaluating RV dyssynchrony. Methods This study assessed 100 PH patients, measuring mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), and cardiac index (CI) by right heart catheterization (RHC). RV strain curves were obtained using two-dimensional speckle-tracking echocardiography (2DSTE), and time from QRS onset to maximum peak longitudinal strain (T max ) or time to first peak (T first ) was measured. Difference in time between the earliest and the latest segment (TD) and standard deviation (SD) of T in 6 segments with RV apex (−SD6) and 4 segments without RV apex (−SD4) were also assessed. Results Among all RV dyssynchrony parameters, T max -SD6 showed the strongest correlation with RV hemodynamics such as mPAP (R 2 =0.27, P 2 =0.22, P max -SD6 significantly correlated with and independently predicted event-free survival in patients with PH. Conclusions RV dyssynchrony is a useful index for RV function and an independent predictor of clinical outcomes in patients with PH. In addition, the inclusion of apical motion is essential for the optimal assessment of RV dyssynchrony.

In the second part of this 2-part series on pacemakers, we present recent advances in pacemakers and preview future developments. Cardiac resynchronization therapy (CRT) is a potent treatment for heart failure in the setting of ventricular dyssynchrony. Successful CRT using coronary venous pacing depends on appropriate patient selection, lead implantation, and device programming. Despite optimization of these factors, nonresponse to CRT may occur in one-third of patients, which has led to a search for alternative techniques such as multisite pacing, His bundle pacing, and endocardial left ventricular pacing. A paradigm shift in pacemaker technology has been the development of leadless pacemaker devices, and on the horizon is the development of batteryless devices. Remote monitoring has ushered in an era of greater safety and the ability to respond to device malfunction in a timely fashion, improving outcomes.

Summary Background The relationship between electrical and mechanical indices of cardiac dyssynchronization in systolic heart failure (HF) remains poorly understood. Objectives We examined retrospectively this relationship by using the daily practice tools in cardiology in recipients of cardiac resynchronization therapy (CRT) systems. Methods We studied 119 consecutive patients in sinus rhythm and QRS ≥ 120 ms (mean: 160 ± 17 ms) undergoing CRT device implantation. P wave duration, PR, e PR (end of P wave to QRS onset), QT, RR–QT, JT and QRS axis and morphology were putative predictors of atrioventricular (diastolic filling time [DFT]/RR), interventricular mechanical dyssynchrony (IVMD) and left intraventricular mechanical dyssynchrony (left ventricular pre-ejection interval [PEI] and other measures) assessed by transthoracic echocardiography (TTE). Correlations between TTE and electrocardiographic measurements were examined by linear regression. Results Statistically significant but relatively weak correlations were found between heart rate ( r = −0.5), JT ( r = 0.3), QT ( r = 0.3), RR–QT intervals ( r = 0.5) and DFT/RR, though not with PR and QRS intervals. Weak correlations were found between: (a) QRS ( r = 0.3) and QT interval ( r = 0.3) and (b) IVMD > 40 ms; and between (a) e PR ( r = −0.2), QRS ( r = 0.4), QT interval ( r = 0.3) and (b) LVPEI, though not with other indices of intraventricular dyssynchrony. Conclusions The correlations between electrical and the evaluated mechanical indices of cardiac dyssynchrony were generally weak in heart failure candidates for CRT. These data may help to explain the discordance between electrocardiographic and echocardiographic criteria of ventricular dyssynchrony in predicting the effect of CRT.

Although cardiac resynchronization therapy (CRT) is an important treatment of symptomatic heart failure patients in sinus rhythm with low left ventricular ejection fraction and ventricular dyssynchrony, its role is not well defined in patients with atrial fibrillation (AF). CRT is not as effective in patients with AF because of inadequate biventricular capture and loss of atrioventricular synchrony. Both can be addressed with catheter ablation of AF. It is still unclear if these therapies offer additive benefits in patients with ventricular dyssynchrony. This article discusses the role and techniques of catheter ablation of AF in patients with heart failure, and its application in CRT recipients.

Cardiac resynchronization therapy (CRT) or biventricular pacing (BIVP) has become a common procedure for the treatment of ventricular dyssynchrony in patients with heart failure, particularly in those with bundle branch block patterns (QRS durations150ms) on the electrocardiogram (ECG). However, a large group of non-responders are made up of patients with dyssynchrony and QRS duration below 130ms. Recent studies have introduced permanent His bundle pacing as another method for achieving normalization of the QRS duration even in a majority of patients with right or left bundle branch block pattern on the ECG.We hypothesize 1. Biventricular pacing, (BIVP) performed as the standard procedure for CRT is inherently abnormal, spatially, at the right and left ventricular apex, and temporally, in regard to the timing of normal activation of the interventricular conduction system. Corollary 1. Permanent, selective, His bundle pacing (PHBP) is the most physiological form of ventricular pacing which replicates the normal activation of the interventricular conduction system. Corollary 2. An appropriately powered, prospective, crossover trial comparing PHBP with BIVP will show that the former is associated with the same benefits in patients with heart failure and QRS durations130ms and would improve, rather than worsen, outcomes in heart failure patients with QRS duration130ms. We present experimental and clinical evidence in support of these hypotheses.

Background Left bundle branch block (LBBB) causes left ventricular (LV) dyssynchrony that can lead to a subsequent cardiomyopathy (CMP). Objectives Among patients with LBBB and an initially preserved LV ejection fraction (EF), we evaluated the relationship between LV dyssynchrony assessed by echocardiography and the future development of LV systolic dysfunction. Methods Subjects were taken from a database of LBBB patients with an initially preserved LVEF (≥45%) without clinically relevant coronary disease or other identifiable cause of CMP. From the initial echocardiogram obtained after diagnosis of LBBB in which the LVEF was preserved, we compared LVEF and LV dimensions in patients who maintained a preserved LVEF (pEF - N=40) with those who developed LV systolic dysfunction (EF≤40%; subsequent CMP - N=28) over a mean follow up period of 58.0±37.8 mos. We also quantified dyssynchrony from this echocardiogram using two methods: 1) time delay between the earliest peak septal and peak posterior wall contraction by M-mode; and 2) time difference between peak posterior wall contraction and onset of transmitral E-wave on pulsed-wave Doppler, for which a value above zero indicates significant dyssynchrony. Results (data are means±sd) There were no significant differences among clinical variables (including age, gender, and other comorbidities). Echocardiographic data are shown in the table below. The subsequent CMP group exhibited a slightly lower mean LVEF compared to the pEF group with the LV end diastolic diameters (LVEDD) and end systolic diameters (ESD) being correspondingly and significantly increased. However, we observed no statistically significant differences with either measure of dyssynchrony. Conclusions Among LBBB patients with an initially preserved LVEF, the degree of LV dyssynchrony assessed through these two echocardiographic measures was not different between those who maintained a preserved EF versus those who developed a subsequent CMP. These data indicate that dyssynchrony itself does not predict future LV systolic dysfunction in patients with patients with LBBB, and support the notion that the mechanisms contributing to LBBB-associated cardiomyopathy are complex and perhaps not driven by dyssynchrony alone.

Specific strain echocardiogram and electrocardiogram (ECG) measures of mechanical and electrical ventricular dyssynchrony correlate in certain disease states. We hypothesized that strain and ECG measures of dyssynchrony would correlate in patients who develop a new left bundle branch block (LBBB) or

Objectives The aim of the present study was to assess the short term prognostic significance of N-terminal pro BNP (NT-proBNP), 3D left atrial volume (LAV) and left ventricular (LV) dyssynchrony in patients of acute ST-elevation myocardial infarction (STEMI) who underwent primary Percutaneous intervention (PCI). Background NT-proBNP, LV dyssynchrony and LAV in patients with acute coronary syndrome have been associated with PCI outcomes and predict the short and long-term prognosis. Methods This study consisted of 142 patients with a first STEMI who underwent primary PCI. Baseline echocardiographic data was collected at admission and at 6 months follow up. Left ventricular dyssynchrony was measured by tissue Doppler imaging and LAV by real time 3D-echocardiography, plasma NT-proBNP levels were estimated between 72 and 96 h of admission. Results During study period 3 patients expired and 4 developed congestive heart failure (CHF). Baseline NT-proBNP and LV dyssynchrony correlated with LV size and LV ejection fraction (LVEF) at baseline and during follow up. Patients with higher NT-proBNP levels and higher LV dyssynchrony showed significant increase in LV size with decrease in LVEF during follow-up. Baseline Left atrial volume index (LAVI) showed significant correlation with LV size but no association with LVEF at baseline and during follow-up. Conclusions Higher levels of NT-proBNP and higher LV dyssynchrony can predict patients with increase in LV size, worsening of LV systolic and diastolic function during follow-up. Patients with higher NT-proBNP levels at baseline developed CHF during follow-up.

Objectives: Our study aimed to demonstrate the early negative impact of right ventricular apical pacing induced by single (VVI) and dual chamber (DDD) pacemakers on LV functions in patients with preserved EF. And to assess that single brain natriuretic peptide (BNP) after 2 months of implantation is correlated to ventricular dyssynchrony. Methods: 40 patients with implanted VVI and DDD pacemakers were examined before implantation and again after 2 and 6 months of implantation for BNP, left ventricular (LV) systolic and diastolic functions by echocardiography and pulsed tissue Doppler. After 6 months, patients with DDD pacemakers were crossed over to VVI mode of pacing for 2 weeks with lower rate programed to 60 beat per minute then sample for BNP was collected again. Results: There was no statistically significant difference in LV systolic and diastolic functions except for myocardial performance index (MPI) with (P value of 0.03). Mean BNP level in VVI pacing was higher than DDD pacing after two months with P value = 0.001 while comparison after 6 months showed P value = 0.023. There was a statistically significant difference between both groups in results of aortic preejection delay (APED) (P value of

The role of atherosclerosis in the progression of global left ventricular dysfunction and cardiovascular events has been well recognized. Left ventricular (LV) dyssynchrony is a measure of regional myocardial dysfunction. Our objective was to investigate the relationship of subclinical atherosclerosis with mechanical LV dyssynchrony in a population-based asymptomatic multi-ethnic cohort.Participants of the Multi-Ethnic Study of Atherosclerosis (MESA) at exam 5 were evaluated using 1.5T cardiac magnetic resonance (CMR) imaging, carotid ultrasound (n = 2062) for common carotid artery (CCA) and internal carotid artery (ICA) intima-media thickness (IMT), and cardiac computed tomography (n = 2039) for coronary artery calcium (CAC) assessment (Agatston method). Dyssynchrony indices were defined as the standard deviation of time to peak systolic circumferential strain (SD-TPS) and the difference between maximum and minimum (max-min) time to peak strain using harmonic phase imaging in 12 segments (3-slices × 4 segments). Multivariable regression analyses were performed to assess associations after adjusting for participant demographics, cardiovascular risk factors, LV mass, and ejection fraction. In multivariable analyses, SD-TPS was significantly related to measures of atherosclerosis, including CCA-IMT (8.7 ms/mm change in IMT, p = 0.020), ICA-IMT (19.2 ms/mm change in IMT, p0.001), carotid plaque score (1.2 ms/unit change in score, p0.001), and log transformed CAC+1 (0.66 ms/unit log-CAC+1, p = 0.018). These findings were consistent with other parameter of LV dyssynchrony i.e. max-min.In the MESA cohort, measures of atherosclerosis are associated with parameters of subclinical LV dyssynchrony in the absence of clinical coronary event and left-bundle-branch block.

Rightventricular(RV)apicalpacingcreatesanabnormalventricularactivation pattern inducing cardiac dyssynchrony, ventricular dysfunc-tion,andanincreasedmortalityrisk[1–3].Atrial-basedpacingtomain-tainatrioventricular(AV)synchronycandecreasetheincidenceofatrialfibrillation (AF), heart failure and overall mortality rates [1]. However,evenwhenAV-nodefunctionispreserved,dual-chamber(DDD)pacingoften results in frequent ventricular pacing [3]. Previous analyses linkthefrequencyofRVpacedbeatstoincreasedrisksofAFandheartfailurein patients with sinus-node disease [4].To overcome the limitations of pacing-induced asynchronouselectricalactivation,devicealgorithmshavebeendevelopedtopromotenormal AV synchrony by preserving the physiologic ventricular activa-tion sequence [2].Specifically, intrinsic conduction search (ICS) hasbeen shown to lead to a decrease in unnecessary RV pacing and itsadverse consequences on left ventricular function [5,6].Moreover,pulsegeneratorlongevityisanimportant issueinthecareof pacemaker patients [7]. One of the determinants of pacemaker lon-gevityisthe energy consumption ofthepulsegenerator,whichdependson programmable variables, including output parameters of the system(voltage and pulse width), and the frequency and percentage of pacing.A previous study using an algorithm to preserve normal AV synchrony

Introduction The main objective of research in pacemaker therapy has been to provide the best physiologic way to pace the heart. Despite the good results provided by right ventricular pacing minimization and by biventricular pacing in specific subsets of heart failure patients, these options present many limitations for standard pacemaker recipients. In these patients, pacing the right ventricle at alternative sites could result in a lower degree of left intraventricular dyssynchrony. Despite the lack of strong evidence and the difficulty in placing and accurately classifying the final lead position, pacing at alternative right ventricular sites seems to have become a standard procedure at many implanting centers. Material and methods The RIGHT PACE study is a multi-center, prospective, single-blind, double-arm, intervention-control trial comparing right ventricular pacing from the apex and from the septal site in terms of left intraventricular dyssynchrony. A total of 408 patients with indications for cardiac pacing but without indications for ICD and/or CRT will be enrolled. Investigators will be divided on the basis of their prior experience of selective site pacing lead implantation and patients will be treated according to the clinical practice of the centers. After device implantation, they will be followed up for 24 months through evaluation of clinical, echocardiographic and safety/system-performance variables. Discussion This study might provide important information about the impact of the right ventricular pacing on the left ventricular dyssynchrony, and about acute and chronic responses to selective site pacing, as adopted in current clinical practice. This trial is registered at ClinicalTrials.gov (ID: NCT01647490 ). Trial registration Right Ventricular Lead Placement in a Pacemaker Population: Evaluation of apical and alternative position. ClinicalTrials.gov : NCT01647490 .

Background Severe mitral regurgitation (MR) ≥3+ and left ventricular dyssynchrony in heart failure patients are markers of CRT non response. The MitraClip (MC) implantation is a therapy for MR ≥3+ in patients with high surgical risk of mitral valve reconstruction. Methods and results We investigated 42 patients with CRT and MR ≥3+ who received an MC device at our center. One and two year mortality rates were compared with the predicted mortality by Seattle Heart Failure Model (SHFM) and meta-analysis global group in chronic heart failure (MAGGIC), using the baseline characteristics of patients at the time of MC implantation. The median time interval between CRT and MC implantation was 20.1 (4.5–43.3) months. In 19 patients we observed a functional regurgitation with normal leaflets and in 23 patients a degenerative mechanism for mitral regurgitation. There was no change in mean QRS duration by biventricular pacing or MC implantation. The use of MC led to significant reductions in: median N-terminal pro-brain natriuretic peptide (NT-proBNP) level (pg/ml) from 3923 to 2636 ( p =0.02), tricuspid regurgitation pressure gradient (TRPG) from 43 to 35mmHg ( p =0.019) and in left ventricular end-diastolic volume (LVEDV) by MC ( p =0.008). At the 2year follow-up interval the all-cause mortality was 25%. Conclusion MC implantation leads to an improvement of NT-proBNP level, TRPG and LVEDV in both functional and degenerative MR but does not influence QRS duration. Two year all-cause mortality was 25% and did not differ significantly from that predicted by SHFM and MAGGIC.

Mechanical dyssynchrony (MD) is associated with poor outcomes in many different populations. However, the predictors for the development of MD after chronic right ventricular (RV) pacing are not well known.Pacing QRS morphology and MD using echocardiography was analyzed in 175 consecutive patients that have pacemaker implantation during a 7.6 year median follow-up. Predictive score for MD was constructed using QRS morphology variables and calculated by summing the points of the 4 variables: duration (≥150 ms, 1 point), transition (1 point), notching (2 points), and left-axis deviation (1 point), based on a multivariate-adjusted risk relationship with MD.Sixty-eight (38.9%) patients developed MD. Patients with MD had worsened left ventricular systolic function (ejection fraction from 64.6±10.6% to 59.1±10.4%, p0.001) and heart failure symptoms (New York Heart Association functional class increase from 1.1±0.3 to 1.9±0.8, p0.001). In an electrocardiographic analysis, QRS duration≥150 ms, the presence of precordial axis transition, notching, and left-axis deviation were strongly associated with MD. Predictive score for MD using QRS morphology parameters displayed an excellent graded relationship with MD (score 0: 3.4% vs. 1: 12.5% vs. 2: 22.6% vs. 3: 45.0% vs. 4: 57.9% vs. 5: 72.7%, linear p0.001) (model performance c-static 0.78, 95% confidence interval 0.72-0.85, p0.001).Patients with MD experienced a decline in left ventricular systolic function and an increase in heart failure symptoms after chronic RV pacing. A new scoring system using QRS morphology is considered a simple and efficient tool for predicting the development of MD after chronic RV pacing.

The number of patients with severe aortic stenosis getting treated with transcatheter aortic valve replacement (TAVR) is rapidly growing and the outcome after the procedure is very good. However, the incidence of new persistent left bundle branch block (LBBB) following the TAVR procedure is high and the impact of this new conduction disturbance has been studied in four major studies with divergent result. This review investigates the differences between these studies that might explain the divergent results and concludes that future studies are needed to characterize whether or not new LBBB after TAVR fulfills the new strict LBBB criteria, whether these new LBBB patients develops left ventricular dyssynchrony, and which, if any, might benefit from cardiac resyncronization therapy (CRT).

The present case report describes a 53-year-old man with drug-resistant heart failure. Electrocardiogram showed complete right-bundle branch block and left anterior fascicular block. A cardiac resynchronization therapy (CRT) device was implanted in him because echocardiography showed obvious left ventricular dyssynchrony between septal and lateral walls. After CRT implantation, dyssynchrony was improved and ejection fraction was increased. Evaluation of coexisting left hemiblock and left ventricular dyssynchrony may be needed in patients with atypical indications for CRT.

Long-standing aortic stenosis (AS) results in fibrotic changes that often persist after transcatheter aortic valve replacement (TAVR). Fibrosis in AS preferentially affects the left ventricular (LV) basal segments and can lead to ventricular dyssynchrony. We hypothesize that basal longitudinal

Introduction Increased QRS duration (QRSd) and left ventricular dyssynchrony are associated with worse outcomes in heart failure (HF). The implication of QRSd on left ventricular ejection fraction (LVEF) trajectories among patients with severe decompensated systolic HF is unclear. Methods Patients hospitalized with HF between 2014-2018 with an LVEF ≤ 35% and at least two echocardiograms with LVEF assessments were included. Patients received guideline-directed medical and device therapies. Survival was assessed for up to 4 years after the index admission. LVEF trajectory was defined as the difference between the lowest LVEF and the highest LVEF, multiplied by -1 if the lowest LVEF was more recent than the highest LVEF. Linear regression was used to evaluate the association between LVEF trajectory and QRSd, and logistic regression was used to assess survival based on QRSd and LVEF trajectory. Results Among 1,674 patients (65.3 ± 14.2 years, 35.9 % female), 39% had QRSD > 120 ms. The lowest LVEF was 26.7% ± 9.7%, the highest LVEF was 45.5% ± 14.5%, and the LVEF trajectory had a median of 5% with an interquartile range of -10% to +25%. The frequency of QRSd less than 120 ms, 120-149 ms, and greater than or equal to 150 ms were 60.5%, 20.5%, and 19.5% respectively. Increasing QRSd was associated with more negative LVEF trajectories (r = -0.24, p Conclusions Increasing QRS duration in HF is associated with worsening LVEF trajectories and increased mortality despite contemporary guideline-directed medical and device therapy. The effect of QRS duration on survival appears to be mediated both by its impact on LVEF trajectory and mechanisms independent of the LVEF trajectory.

Introduction Asymptomatic Diaphragmatic Stimulation (ADS) is a novel device-based HF therapy under investigation. Prior studies have shown that ADS transiently modulates intrathoracic pressure, thereby reducing intra-cardiac pressures and increasing stroke volume. Hypothesis Chronic ADS therapy using a novel system delivered via a trans-abdominal laparoscopic approach improves heart failure function and exercise tolerance in patients with HFrEF but without ventricular dyssynchrony. Methods Patients with moderately severe symptoms, LVEF ≤35% but no evidence of ventricular dyssynchrony underwent laparoscopic implantation of the VisONE ADS system (NCT03484780). Post implant in-clinic tests were conducted to determine the acute effects of ADS on cardiac function at stimulation levels imperceptible to the patient. At discharge, therapy was programmed to chronically deliver ADS. Patients will be followed for 12 months to assess measures of cardiac function, HF status, diaphragmatic function, and standard safety measures. Baseline and one month data are reported as median [IQR]. Results Fifteen men (60 [56, 67] years, EF 27 [23, 33] %, NYHA class II (53%)/III (47%), 100% sinus rhythm) received implants. Temporary activation of ADS post implant while conscious increased CO (4.8 [4.0, 5.4] vs. 5.7 [4.5, 5.9] l/min, p Conclusions These data suggest that the ADS system can be implanted safely with a short in-hospital stay. Acute improvements to cardiac output and key measures of heart failure after 1 month without ADS related events are encouraging. Further investigation of ADS in randomized clinical trials should be considered.

Background Right ventricular pacing (RVP) is the main treatment of symptomatic bradycardia. But it is well established that cardiac pacing induces electrical and mechanical left ventricular dyssynchrony. Purpose Evaluate the effect of RVP on the incidence of heart failure (HF) in patients implanted for symptomatic bradycardia. Methods The study was prospective, observational, including all consecutive patients implanted in our center between 2009 January and 2014 December for symptomatic bradycardia. HF diagnosis was based on clinical data, natriuretic peptides dosage and echocardiography. The follow up was done every 6 months. The cumulative HF rates were estimated using the Kaplan-Meier method, and variables associated with the risk of HF were identified by the Cox model. Results We included 986 patients, with a mean age of 74.6 ± 8.3 years, and 58.6% of men. A total of 675 (68.4%) had a second or third atrioventricular block and the others a sinus node dysfunction. The proportions of NYHA class I, II, III and IV at inclusion were 28.6%, 49.7%, 17.4% and 4.3% respectively. The mean left ventricular ejection fraction (LVEF) was 0.51 ± 0.10. After a median follow-up of 47.8 months, the cumulative rate of HF was 13.6% (CI 95%: 11.2%–16.0%). Predictive factors of HF occurrence were NYHA class (HR: 3.08; CI 95%: 2.45–4.41, for class II to IV versus class I); history of HF (HR: 2.10; CI 95%: 1.60–2.90); LVEF (HR: 2.13; CI 95%: 1.56–3.02, for LVEF ≤ 0.40 versus > 0.40); history of atrial fibrillation (HR: 1.48; CI 95%: 1.1–2.25); the percentage of ventricular pacing (HR: 3.26; CI 95%: 2.11–5.43; for %VP ≥ 90% versus Conclusions RVP is independently associated with the risk of HF. Using algorithms minimizing unnecessary RVP and cardiac resynchronization therapy in some cases could reduce the incidence of the “pacing induced cardiomyopathy”.

Background: CRT is indicated for patients with severely impaired left ventricular systolic function and ventricular dyssynchrony who remain symptomatic despite optimal medical therapy. CRT is an expensive treatment with a significant non-responder rate. Objective: To ensure appropriate use of this treatment modality, we decided to investigate whether clinical parameters can predict response to CRT in our patients. Methods: We retrospectively reviewed all CRT patients under responder based on pre-specified ECHO and clinical criteria. An ECHO response would be: relative improvement from baseline left ventricular ejection fraction (EF) of N 15%; and a decrease in End Diastolic Volume index (EDVi) or End Systolic Volume index (ESVi) of N 15%. Clinical response was defined as an improvement of at least 1 NYHA functional class. Patients who fulfil both ECHO and clinical criteria are considered responders our follow-up since 2014. We classified them as responder or non.

To analyze whether left ventricular dyssynchrony (LVD) at baseline is predictive for long-term outcome in heart failure (CHF) patients with left ventricular (LV) dysfunction and conduction disturbances treated with cardiac resynchronization therapy (CRT).In 535 consecutive individuals with CHF scheduled for implantation of a CRT device, LVD was assessed by tissue Doppler imaging (TDI), defined as an electromechanical delay (EMD) difference of ≥40 ms in 2 opposed left ventricular wall regions (septal vs. lateral, anterior vs. inferior). All-cause mortality, heart transplantation, or assist device implantation was defined as combined primary end point. Secondary end points were measures of reverse LV remodeling and of symptomatic improvement.Mean follow-up was 68 ± 36 [range: 4-150] months. LVD at baseline was present in 308 patients (61%). Of these, 24% reached the combined primary endpoint in contrast to 58% of patients without LVD (p0.001). Furthermore, patients with LVD showed pronounced improvement of all secondary end point parameters. In our cohort LVD was an independent predictor for outcome (hazard ratio [95% CI]: 0.30 [0.21-0.42], p0.001).LVD at baseline as assessed by TDI is associated with a more pronounced clinical improvement and is a predictor for transplant-free long-term survival in CRT recipients.

In our study, we investigated the impact of papillary muscle systolic dyssynchrony (DYS-PAP) obtained by 2D speckle-tracking echocardiography (2D-STE) in the prediction of recurrent ischemic mitral regurgitation (MR) after restrictive annuloplasty.The study population consisted of 524 consecutive patients who survived coronary artery bypass grafting (CABG) and restrictive annuloplasty, performed between 2001 and 2010 at 3 different Institutions and who met inclusion criteria. The assessment of DYS-PAP was performed preoperatively and at follow-up (median 45.3 months [IQR 26-67]) by 2D-STE in the apical four-chamber view for the anterolateral papillary muscle (ALPM) and apical long-axis view for the posteromedial papillary muscle (PMPM).Recurrence of MR (≥ 2+ in patients with no/trivial MR at discharge) was found in 112 patients (21.3%) at follow-up. Compared to patients without recurrence of MR, these patients had higher DYS-PAP values at baseline (60.6 ± 4.4 ms vs. 47.2 ± 2.9 ms, p0.001) which significantly worsened at follow-up (74.4 ± 5.2 ms, p=0.002 vs. baseline). In contrast, in patients with no MR recurrence, DYS-PAP was significantly reduced (25.3 ± 4.4 ms, p=0.002 vs. baseline). At logistic regression analysis DYS-PAP (odds ratio [OR]: 4.8, 95% Confidence Interval [CI]: 3.4-8.2, p0.001), was the strongest predictor of recurrent MR with a cutoff ≥ 58 ms (95%CI 51-66 ms). The model showed an area under the Receiver Operating Characteristic (ROC) curve of 0.97 (CI 0.94-0.99 [optimism-corrected 0.94; CI 0.89-0.95]) with 98% sensitivity (CI 96-100% [optimism-corrected 95%; CI 91-96%]) and 90% specificity (CI 85-94% [optimism-corrected 87%; CI 82-90%]).DYS-PAP represents a reliable tool to identify patients with ischemic MR who can benefit from restrictive annuloplasty.

Left ventricular (LV) dyssynchrony reduces LV systolic function in patients with heart failure (HF). However, it remains unknown whether this relationship is independent of impaired LV myocardial perfusion.A total of 105 patients with chronic HF (age 71 ± 13 years; 71 men) were enrolled in the present study. (99m)Tc-sestamibi (MIBI) gated myocardial scintigraphy was performed at rest to assess LV myocardial perfusion as evaluated by the total defect score of perfusion Single Photon Emission Computed Tomography images (TDS-MIBI), LV systolic function as evaluated by LV ejection fraction (LVEF), and LV systolic dyssynchrony as evaluated by the maximal difference of time to end systole (MD-TES), which is the time lag between the earliest and the latest end systole among 17 LV segments analyzed with a novel program, "cardioGRAF". The mean ± SD (minimum and maximum range) of the MD-TES was 147.8 ± 117.5 (14.0-458.3)ms. The MD-TES was significantly higher in patients with LVEF45% (199.4 ± 117.6 ms) than in those with LVEF ≥ 45% (60.5 ± 41.2 ms, p0.001). In a multiple logistic regression analysis, the MD-TES showed an increased odds ratio for LVEF45% (2.46 [95% CI; 1.51-4.01] per increment in decile of MD-TES rank, p0.001), after adjusting for the TDS-MIBI, history of myocardial infarction, and other potential confounders.LV dyssynchrony is a significant determinant of LV systolic dysfunction in patients with HF, and this relationship is independent of impaired LV myocardial perfusion and history of myocardial infarction.

A 24-year-old male with Wolff-Parkinson-White syndrome developed systolic cardiomyopathy and severe heart failure following membranous ventricular septal defect repair and tricuspid valve replacement. Following successful catheter ablation of a right anterolateral accessory pathway (AP), complete AV block with junctional escape rhythm was noted. Patient subsequently underwent implantation of a biventricular ICD. Heart failure symptoms significantly improved soon after and left ventricular systolic function normalized 3months post-procedure. In this case, surgically acquired AV block likely explains development of postoperative cardiomyopathy by facilitating ventricular activation solely via the AP and thereby increasing the degree of ventricular dyssynchrony.