Impact of QRS Duration and Ventricular Pacing on Clinical and Arrhythmic Outcomes in Continuous Flow Left Ventricular Assist Device Recipients: A Multicenter Study

ObjectivesWide QRS duration and ventricular pacing are common in recipients of continuous-flow left ventricular assist devices (CF-LVADs) but their impact on outcomes remains unclear. We assessed the clinical and arrhythmic outcomes of CF-LVAD patients with wide QRS or right ventricular (RV) pacing at baseline, compared with those with narrow QRS and those with continued cardiac resynchronization therapy (CRT).Methods and ResultsA total of 520 patients (57 ± 13 years) with an implantable cardioverter-defibrillator (ICD) (n = 240) or CRT-defibrillator (n = 280) who underwent CF-LVAD implantation at 5 centers in 2007–2015 were studied. Patients were divided into 3 groups: ICD-N (QRS ≤120 ms; n = 134), ICD-W (QRS >120 ms; n = 106), and CRT (n = 280). Mortality, hospitalization, and ventricular arrhythmia (VA) incidence were compared among the groups. Baseline QRS duration was different among the groups (100 ± 13 [ICD-N] vs 155 ± 26 [ICD-W] vs 159 ± 29 ms [CRT]; P < .0001). In the ICD-W group, 37 (35%) had >80% RV pacing at baseline. Median biventricular pacing in the CRT group was 96%. Over 523 days of CF-LVAD support, Kaplan-Meier analysis showed no difference in survival among groups (log rank P = .9). According to multivariate Cox regression, wide QRS duration and RV pacing were not associated with survival. QRS narrowed during CF-LVAD support in the ICD-W and CRT groups but was not associated with improved survival (P = .9). No differences were noted among the groups in hospitalizations (P = .9), VA (P = .2), or ICD shocks (P = .06).ConclusionsIn this large CF-LVAD cohort, a wide QRS duration, high percentage of RV pacing at baseline, and changes in QRS duration after LVAD implantation were not associated with survival. Continued CRT after CF-LVAD implantation also was not associated with improved survival or HF hospitalizations.     

Iron Deficiency Is Associated With Impaired Biventricular Reserve and Reduced Exercise Capacity in Patients With Unexplained Dyspnea

BackgroundIron deficiency (ID) is frequent and associated with diminished exercise capacity in heart failure (HF), but its contribution to unexplained dyspnea without a HF diagnosis at rest remains unclear.Methods and ResultsConsecutive patients with unexplained dyspnea and normal echocardiography and pulmonary function tests at rest underwent prospective standardized cardiopulmonary exercise testing with echocardiography in a tertiary care dyspnea clinic. ID was defined as ferritin of <300 µg/L and a transferrin saturation of <20% and its impact on peak oxygen uptake (peakVO₂), biventricular response to exercise, and peripheral oxygen extraction was assessed. Of 272 patients who underwent cardiopulmonary exercise testing with echocardiography, 63 (23%) had ID. For a similar respiratory exchange ratio, patients with ID had lower peakVO₂ (14.6 ± 7.6 mL/kg/minvs 17.8 ± 8.8 mL/kg/min; P = .009) and maximal workload (89 ± 50 watt vs 108 ± 56 watt P = .047), even after adjustment for the presence of anemia. At rest, patients with ID had a similar left ventricular and right ventricular (RV) contractile function. During exercise, patients with ID had lower cardiac output reserve (P < .05) and depressed RV function by tricuspid s' (P = .004), tricuspid annular plane systolic excursion (P = .034), and RV end-systolic pressure-area ratio (P = .038), with more RV–pulmonary artery uncoupling measured by tricuspid annular plane systolic excursion/systolic pulmonary arterial pressure ratio (P = .023). RV end-systolic pressure-area ratio change from rest to peak exercise, as a load-insensitive metric of RV contractility, was lower in patients with ID (2.09 ± 0.72 mm Hg/cm² vs 2.58 ± 1.14 mm Hg/cm²; P < .001). ID was associated with impaired peripheral oxygen extraction (peakVO₂/peak cardiac output; P = .036). Cardiopulmonary exercise testing with echocardiography resulted in a diagnosis of HF with preserved ejection fraction in 71 patients (26%) based on an exercise E/e' ratio of >14, with equal distribution in patients with (28.6%) or without ID (25.4%, P = .611). None of these findings were influenced in a sensitivity analysis adjusted for a final diagnosis of HFpEF as etiology for the unexplained dyspnea.ConclusionsIn patients with unexplained dyspnea without clear HF at rest, ID is common and associated with decreased exercise capacity, diminished biventricular contractile reserve, and decreased peripheral oxygen extraction.     

Normal parameters of right ventricular mechanics with exertion in healthy individuals: a tissue Doppler imaging study

IntroductionTissue Doppler imaging (TDI) has been a useful tool to evaluate of resting right ventricular (RV) function; however, the response of the RV to exercise has not been well established. This study attempts to determine RV mechanics at rest and immediately after exercise in healthy subjects using TDI and to define normal values.MethodsThe authors studied 30 patients (mean age: 46 ± 14 years) who underwent a treadmill stress echocardiogram and had a normal exercise response without cardiac abnormalities. RV end-diastolic and end-systolic areas and RV fractional area change were measured. In addition, longitudinal RV strain and velocity generation were measured.ResultsImmediately postexertion, a significant decrease in RV end-systolic area (6.4 ± 2.5 cm² versus 4.6 ± 1.5 cm², P < 0.001), increase in RV end-diastolic area (14.1 ± 4.5 cm² versus 15.3 ± 3.8 cm², P = 0.05) and a higher RV fractional area change (54 ± 6.9% versus 69 ± 7.7%, P < 0.001) were observed. RV strain increased significantly with exercise at both the base (—18.4 ± 7.7% versus —26.2 ± 10.9%, P = 0.005) and mid-RV lateral wall (—29.9 ± 8.7% versus —40.2 ± 11%, P < 0.001). RV velocity also increased significantly at both the base (8.3 ± 2.1 cm/sec versus 12.7 ± 2.5 cm/sec, P < 0.001) and mid-RV lateral wall (4.4 ± 1.6 cm/sec versus 8.1 ± 4.1 cm/sec, P = 0.001).ConclusionImmediately postexercise, TDI seems to be a useful tool for assessing RV mechanics and function. Whether RV velocity and strain may be used to detect subclinical RV dysfunction during exercise will require further study.     

Effects of simultaneous and optimized sequential cardiac resynchronization therapy on myocardial oxidative metabolism and efficiency

Introduction: Cardiac resynchronization therapy (CRT) can improve left ventricular (LV) hemodynamics and function. Recent data suggest the energy cost of such improvement is favorable. The effects of sequential CRT on myocardial oxidative metabolism (MVO₂) and efficiency have not been previously assessed. Methods and Results: Eight patients with NYHA class III heart failure were studied 196 ± 180 days after CRT implant. Dynamic [¹¹C]acetate positron emission tomography (PET) and echocardiography were performed after 1 hour of: 1) AAI pacing, 2) simultaneous CRT, and 3) sequential CRT. MVO₂ was calculated using the monoexponential clearance rate of [¹¹C]acetate (k_mono). Myocardial efficiency was expressed in terms of the work metabolic index (WMI). P values represent overall significance from repeated measures analysis. Global LV and right ventricular (RV) MVO₂ were not significantly different between pacing modes, but the septal/lateral MVO₂ ratio differed significantly with the change in pacing mode (AAI pacing = 0.696 ± 0.094 min^?1, simultaneous CRT = 0.975 ± 0.143 min^?1, and sequential CRT = 0.938 ± 0.189 min^?1; overall P = 0.001). Stroke volume index (SVI) (AAI pacing = 26.7 ± 10.4 mL/m², simultaneous CRT = 30.6 ± 11.2 mL/m², sequential CRT = 33.5 ± 12.2 mL/m²; overall P < 0.001) and WMI (AAI pacing = 3.29 ± 1.34 mmHg*mL/m²*10⁶, simultaneous CRT = 4.29 ± 1.72 mmHg*mL/m²*10⁶, sequential CRT = 4.79 ± 1.92 mmHg*mL/m²*10⁶; overall P = 0.002) also differed between pacing modes. Compared with simultaneous CRT, additional changes in septal/lateral MVO₂, SVI, and WMI with sequential CRT were not statistically significant on post hoc analysis. Conclusion: In this small selected population, CRT increases LV SVI without increasing MVO₂, resulting in improved myocardial efficiency. Additional improvements in LV work, oxidative metabolism, and efficiency from simultaneous to sequential CRT were not significant.     

Effect of Transcatheter Aortic Valve Replacement on Right Ventricular–Pulmonary Artery Coupling

ObjectivesThe aim of this study was to test the hypothesis that the acute left ventricular (LV) unloading effect of transcatheter aortic valve replacement (TAVR) would improve right ventricular (RV) function and RV–pulmonary artery (PA) coupling in patients with severe aortic stenosis (AS).BackgroundRV dysfunction is an ominous prognostic marker in patients undergoing TAVR, suggesting that relief of obstruction might be less beneficial in this cohort. However, the left ventricle and right ventricle influence each other through ventricular interaction, which could lead to improved RV function through LV unloading.MethodsProspective invasive hemodynamic measurements with simultaneous echocardiography were performed in symptomatic patients with severe AS before and immediately after TAVR.ResultsForty-four patients (mean age 81 ± 8 years, 27% women) with severe AS underwent TAVR. At baseline, right atrial, PA mean (27 ± 7 mm Hg), and pulmonary capillary wedge (16 ± 4 mm Hg) pressures were mildly elevated, with a low normal cardiac index (2.3 l/min/m²). Pulmonary vascular resistance was mildly elevated (222 ± 133 dynes · s/cm⁵) and PA compliance mildly reduced (3.4 ± 01.4 ml/mm Hg). Following TAVR, aortic valve area increased (from 0.8 ± 0.3 to 2.7 ± 1.1 cm²; p < 0.001) with a reduction in mean aortic gradient (from 37 ± 11 to 7 ± 4 mm Hg; p < 0.001) and an increase in cardiac index (from 2.3 ± 0.5 to 2.5 ± 0.6 l/min/m²; p = 0.03). LV stroke work, end-systolic wall stress, and systolic ejection period decreased by 23% to 27% (p < 0.001 for all), indicating substantial LV unloading. RV stroke work (from 16 ± 7 to 18 ± 7 mm Hg · ml; p = 0.04) and tricuspid annular systolic velocities (from 9.5 ± 2.0 to 10.4 ± 3.5 cm/s; p = 0.01) increased, along with a decrease in PVR (194 ± 113 dynes · s/cm⁵; p = 0.03), indicating improvement in RV-PA coupling. Increased RV stroke work following TAVR directly correlated with the magnitude of increase in aortic valve area (r = 0.58; p < 0.001).ConclusionsAcute relief in obstruction to LV ejection with TAVR is associated with improvements in RV function and RV-PA coupling. These findings provide new insights into the potential benefits of LV unloading with TAVR on RV dysfunction in patients with severe AS.     

Right ventricular dysfunction is a strong predictor of developing atrial fibrillation in acutely decompensated heart failure patients, ACAP-HF data analysis

BackgroundHeart failure and atrial fibrillation (AFib) are the twin epidemics of modern cardiovascular disease. The incidence of new-onset AFib in acute decompensated heart failure (ADHF) patients is difficult to predict and the short- and long-term outcomes of AFib in a cohort of patients admitted with ADHF are unknown.Methods and ResultsA total of 904 patients admitted with ADHF were studied. Incidence of AFib on admission was recorded and a multivariate analysis was performed using echocardiographic parameters to specify the predictors of AFib incidence in this cohort. In 904 ADHF patients (57% male, mean age 69 ± 14 years), 81% had history of hypertension, 40% were diabetics, and 51% were smokers. A total of 63% of the patients had known heart failure (HF) with mean ejection fraction of 34% ± 21%, and 33% of the patients had ischemic cardiomyopathy as the etiology of HF. Echocardiographic parameters were: left atrial (LA) diameter 4.5 ± 0.8 cm, left ventricular end-systolic 4.1 ± 1.3 cm, left ventricular end-diastolic 5.3 ± 1.1 cm. Right ventricular dysfunction (RVD) was present in 34% of the patients. A total of 191 (21%) patients subsequently developed AFib with two thirds of the cases occurring in patients with RVD. Using a univariate analysis, older age (OR 1.02; P < .0001), history of HF (OR 2.93; P < .0001), LA dilation (OR 1.58; P < .0001), the presence of left ventricular hypertrophy (OR 3.01, P < .0001), and RVD (OR 4.93; P < .00001) were the strongest predictors for AFib. Controlling for LA size and left ventricular hypertrophy using a forward stepwise regression, RVD remained the strongest predictor (OR 4.45; P < .0001). Patients with RVD had more events (cardiac readmission and mortality) than those with normal RV (56% versus 38%; P < .00001), notably; all-cause mortality was 4.7%/year in the abnormal RV group versus 2.9%/year in the normal RV group; P < .05. RV function analyses by echocardiography further risk stratified these patients based on their rhythm categorizing those patients with abnormal RV and AFib as the ones with the worse prognosis.ConclusionRV dysfunction is a strong predictor for developing AFib in acutely decompensated systolic failure patients. Patients with AFib and RVD have the worse outcome specially when is combined with LV dysfunction, therefore; evaluation of RV function may substantiate the difference in HF prognosis.     

Short-Term Hemodynamic and Electrophysiological Effects of Cardiac Resynchronization by Left Ventricular Septal Pacing

BackgroundCardiac resynchronization therapy (CRT) is usually performed by biventricular (BiV) pacing. Previously, feasibility of transvenous implantation of a lead at the left ventricular (LV) endocardial side of the interventricular septum, referred to as LV septal (LVs) pacing, was demonstrated.ObjectivesThe authors sought to compare the acute electrophysiological and hemodynamic effects of LVs with BiV and His bundle (HB) pacing in CRT patients.MethodsTemporary LVs pacing (transaortic approach) alone or in combination with right ventricular (RV) (LVs+RV), BiV, and HB pacing was performed in 27 patients undergoing CRT implantation. Electrophysiological changes were assessed using electrocardiography (QRS duration), vectorcardiography (QRS area), and multielectrode body surface mapping (standard deviation of activation times [SDAT]). Hemodynamic changes were assessed as the first derivative of LV pressure (LVdP/dtmax).ResultsAs compared with baseline, LVs pacing resulted in a larger reduction in QRS area (to 73 ± 22 μVs) and SDAT (to 26 ± 7 ms) than BiV (to 93 ± 26 μVs and 31 ± 7 ms; both p < 0.05) and LVs+RV pacing (to 108 ± 37 μVs; p < 0.05; and 29 ± 8 ms; p = 0.05). The increase in LVdP/dtmax was similar during LVs and BiV pacing (17 ± 10% vs. 17 ± 9%, respectively) and larger than during LVs+RV pacing (11 ± 9%; p < 0.05). There were no significant differences between basal, mid-, or apical LVs levels in LVdP/dtmax and SDAT. In a subgroup of 16 patients, changes in QRS area, SDAT, and LVdP/dtmax were comparable between LVs and HB pacing.ConclusionsLVs pacing provides short-term hemodynamic improvement and electrical resynchronization that is at least as good as during BiV and possibly HB pacing. These results indicate that LVs pacing may serve as a valuable alternative for CRT.     

Left Bundle Branch Pacing for Cardiac Resynchronization Therapy: Nonrandomized On-Treatment Comparison With His Bundle Pacing and Biventricular Pacing

BackgroundLeft bundle branch pacing (LBBP) is a novel method for delivering cardiac resynchronization therapy (CRT). We compared on-treatment outcomes with His bundle pacing (HBP) and biventricular pacing (BVP) in this nonrandomized observational study.MethodsConsecutive patients with left-ventricular ejection fraction (LVEF) ≤ 40% and typical left bundle branch block (LBBB) referred for CRT received BVP, HBP, or LBBP. QRS duration, pacing threshold, LVEF, and New York Heart Association (NYHA) class were assessed.ResultsOne hundred thirty-seven patients were recruited: 49 HBP, 32 LBBP, and 54 BVP; 2 did not receive CRT. The majority of patients had nonischemic cardiomyopathy. Mean paced QRS duration was 100.7 ± 15.3 ms, 110.8 ± 11.1 ms, and 135.4 ± 20.2 ms during HBP, LBBP, and BVP, respectively. HBP and LBBP demonstrated a similar absolute increase (Δ) in LVEF (+23.9% vs +24%, P = 0.977) and rate of normalized final LVEF (74.4% vs 70.0%, P = 0.881) at 1-year follow-up. This was significantly higher than in the BVP group (Δ LVEF +16.7% and 44.9% rate of normalized final LVEF, P < 0.005). HBP and LBBP also demonstrated greater improvements in NYHA class compared with BVP. LBBP was associated with higher R-wave amplitude (11.2 ± 5.1 mV vs 3.8 ± 1.9 mV, P < 0.001) and lower pacing threshold (0.49 ± 0.13 V/0.5 ms vs 1.35 ± 0.73 V/0.5 ms, P < 0.001) compared with HBP.ConclusionLBBP appears to be a promising method for delivering CRT. We observed similar improvements in symptoms and LV function with LBBP and HBP. These improvements were significantly greater than those seen in patients treated with BVP in this nonrandomized study. These promising findings justify further investigation with randomized trials.     

Clinical outcomes with biventricular versus right ventricular pacing in patients with atrioventricular conduction defects

There have been increasing concerns about the unexpected effects of right ventricular (RV) pacing. We aimed to systematically evaluate the effect of biventricular (BiV) versus RV pacing on clinical events in patients with impaired AV conduction. We searched PubMed, EMBASE, and Cochrane Library for studies comparing BiV pacing with RV pacing in patients with AV block, through April 2017. We selected randomized controlled trials (RCTs) reporting data on mortality, hospitalization for heart failure (HF), and/or 6-min walk distance (6MWD). A total of 12 RCTs were finally included. Pooled analysis suggested that BiV pacing was associated with a significantly reduced all-cause mortality in contrast to RV pacing (risk ratio (RR)?=?0.77, 95% confidence interval (CI) 0.62 to 0.95, I²?=?9.6%). BiV pacing, compared with RV pacing, significantly reduced the rate of HF hospitalization (RR?=?0.74, 95% CI 0.59 to 0.93, I²?=?10.1%). Sensitivity analyses by excluding studies with AV nodal ablation showed that BiV pacing still had a lower mortality and non-significant reduced HF hospitalization. Patients in BiV and RV pacing mode had a similar 6WMD at follow-up (mean difference?=?4.99 m, 95% CI ??11.34 to 21.33 m, I²?=?0%). Meta-regression analysis showed that the effect size of all-cause mortality or HF hospitalization was not significantly associated with mean LVEF value at baseline. In patients with impaired AV conduction that need frequent ventricular pacing, BiV pacing was associated with reduced mortality and hospitalization for HF, compared with traditional RV pacing mode.     

Reversal of pulmonary vein remodeling after catheter ablation of atrial fibrillation

Background Pulmonary veins (PV) and the atria undergo electrical and structural remodeling in atrial fibrillation (AF). This study aimed to determine PV and left atrial (LA) reverse remodeling after catheter ablation for AF assessed by chest computed tomography (CT). Methods PV electrophysiologic studies and catheter ablation were performed in 63 patients (68% male; mean ± SD age: 56 ± 10 years) with symptomatic AF (49% paroxysmal, 51% persistent). Chest CT was performed before and 3 months after catheter ablation. Results At baseline, patients with persistent AF had a greater LA volume (91 ± 29 cm³ vs. 66 ± 27 cm3; P = 0.003) and mean PV ostial area (241 ± 43 mm² vs. 212 ± 47 mm²; P = 0.03) than patients with paroxysmal AF. There was no significant correlation between the effective refractory period and the area of the left superior PV ostium. At 3 months of follow-up after ablation, 48 patients (76%) were AF free on or off antiar?rhythmic drugs. There was a significant reduction in LA volume (77 ± 31 cm³ to 70 ± 28 cm³; P < 0.001) and mean PV ostial area (224 ± 48 mm² to 182 ± 43 mm²; P < 0.001). Patients with persistent AF had more reduction in LA volume (11.8 ± 12.8 cm³ vs. 4.0 ± 11.2 cm³; P = 0.04) and PV ostial area (62 mm² vs. 34 mm²; P = 0.04) than those who have paroxysmal AF. The reduction of the averaged PV ostial area was significantly correlated with the reduction of LA volume (r = 0.38, P = 0.03). Conclusions Catheter ablation of AF improves structural remodeling of PV ostia and left atrium. This finding is more apparent in patients with persistent AF treated by catheter ablation.     

Upgrading to biventricular pacing guided by pressure-volume loop analysis during implantation

Pressure–Volume Loop Analyses during CRT Implants. Introduction: cardiac resynchronization therapy (CRT) may improve prognosis in patients with chronic right ventricular (RV) pacing, and optimal lead position can decrease nonresponders. We evaluated the clinical and echocardiographic response to CRT in patients with previous chronic RV pacing, using pressure–volume loop analyses to determine the optimal left ventricular (LV) lead position during implantation. Methods and Results: In this single‐blinded, randomized, controlled crossover study, 40 patients with chronic RV apical pacing and symptoms of heart failure, decreased LV ejection fraction (LVEF) or dyssynchrony were included. During implantation, stroke work (SW), LVEF, cardiac output, and LV dP/dt_max were assessed by a conductance catheter. Clinical and echocardiographic response was studied during a 3‐month period of RV pacing (RV period, LV lead inactive) and a 3‐month period of biventricular pacing (CRT period). At the optimal LV lead position, SW (37 ± 41%), LVEF (16 ± 13%), cardiac output (29 ± 16%), and LV dP/dt_max increased (11 ± 11%) significantly during biventricular pacing compared to baseline. Additional benefit could be achieved by pressure–volume loop guided selection of the best left‐sided pacing location. RV outflow tract pacing did not improve hemodynamics. During follow‐up, symptoms improved during CRT, VO_2,max increased 10% and significant improvements in LVEF, LV volumes, and mitral regurgitation were observed as compared to the RV period. Conclusions: CRT in patients with chronic RV pacing causes significant improvement of both LV function as measured by pressure–volume loops during implantation and clinical and echocardiographic improvement during follow‐up. Pressure–volume loops during implantation may facilitate selection of the most optimal pacing site . (J Cardiovasc Electrophysiol, Vol. 22, pp. 677‐683, June 2011)     

Acute Effects of Withdrawal of Cardiac Resynchronization Therapy on Left and Right Ventricular Function,Dyssynchrony, and Contractile Function in Patients With New York Heart Association Functional Class I/II Heart Failure: MADIT-CRT

BackgroundCardiac resynchronization therapy (CRT) improves left ventricular (LV) function, size, mitral regurgitation, and clinical outcomes. Whether these improvements are due to the short-term effects of improvement in synchrony or contractile performance, or to long-term improvement in ventricular structure and function remains insufficiently elucidated.Methods and ResultsWe used echocardiographic data from 63 patients enrolled in the MADIT-CRT trial who, after 1 year of CRT therapy, underwent echocardiographic evaluation with CRT turned both on and off within minutes. LV volumes, LV ejection fraction, left atrial (LA) volumes, and right ventricular function were assessed at baseline and in the on and off modes within a 5-minute time-frame at 12 months. Speckle-tracking strain analysis was used to assess LV dyssynchrony and contractile function. Interruption of long-term CRT resulted in acute deterioration of LV and RV function and acute increase in LV and LA volumes, although not to baseline. Acute withdrawal was also associated with increased dyssynchrony (SD time to peak transverse strain 178 ± 68 ms vs 195 ± 62 ms; P = .16; and SD time to peak longitudinal strain 108 ± 46 ms vs 125 ± 55 ms; P = .046). However, there was no deterioration in contractile function (global longitudinal strain), which had improved with CRT (?9.8 ± 4.3% vs ?10.0 ± 3.7%; P = .93).ConclusionsDespite substantial LV reverse remodeling with CRT, interruption of long-term CRT after 12 months resulted in an acute worsening of LV size and function, LA volumes, and right ventricular function, with concomitant worsening of ventricular synchrony despite minimal change to the observed improvement in LV strain measures of contractile function. These findings suggest that the beneficial reverse remodeling associated with CRT may be mostly dependent on active pacing, although intrinsic improvements in contractile function may persist beyond termination of pacing.     

Acute Effects of Multisite Left Ventricular Pacing on Mechanical Dyssynchrony in Patients Receiving Cardiac Resynchronization Therapy

BackgroundA novel quadripolar left ventricular (LV) pacing lead has the ability to deliver multisite LV pacing (MSLV). We set out to characterize the safety and changes in acute mechanical dyssynchrony with MSLV in cardiac resynchronization therapy (CRT) patients.Methods and ResultsProspective multicenter study in 52 patients receiving CRT. An acute pacing protocol comprising 8 MSLV configurations covering a range of delays was compared with conventional CRT (baseline). Transthoracic tissue Doppler imaging (TDI) was used to measure the standard deviation of time to peak contraction of 12 LV segments (Ts-SD) and delayed longitudinal contraction. No ventricular arrhythmia occurred in any of the 52 patients. Complete TDI datasets were collected in 41 patients. Compared with baseline: 1) The mean Ts-SD was significantly lower for the optimal MSLV configuration (35.3 ± 36.4 vs 50.2 ± 29.1 ms; P < .001); 2) at least 1 MSLV configuration exhibited a significant dyssynchrony improvement in 63% of patients; and 3) the mean number of LV segments with delayed longitudinal contractions was significantly reduced with the optimal MSLV configuration (0.37 ± 7.99 vs 2.20 ± 0.19; P < .001).ConclusionsAcute MSLV was acutely safe, and a proportion of MSLV vectors resulted in a significant reduction in echocardiographic dyssynchrony compared with conventional CRT.     

Right Ventricular Function and Prognosis in Stable Heart Failure Patients

BackgroundRight ventricular ejection fraction (RVEF) is a mortality predictor in heart failure (HF) patients. There are controversial results regarding the influence of RVEF on other important prognostic variables. The purpose of this study was to investigate the effect of RVEF on exercise parameters obtained during cardiopulmonary exercise testing (CPET), creatinine and B-type natriuretic peptide (BNP) levels, and a composite outcome of death, heart transplantation, or ventricular assist device implantation in ambulatory HF patients.Methods and ResultsThis retrospective cohort study included 246 ambulatory HF patients with CPET and RVEF evaluated with the use of first-pass radionuclide angiography. We analyzed the impact of RVEF on other prognostic factors with the use of multivariable linear regression. The mean age was 49 ± 12 years. The mean peak VO₂ was 16.4 ± 5.7 mL kg⁻¹ min⁻¹, mean peak VE/VCO₂ 34.1 ± 9.1, mean creatinine 1.17 ± 0.40 mg/dL, and median BNP 158 pg/mL (interquartile range 374 pg/mL). The mean left ventricular ejection fraction was 35 ± 12% and the mean RVEF 38 ± 10%. For every 10% decrease in RVEF, peak VO₂ decreased 0.97 mL kg⁻¹ min⁻¹ (P < .05), creatinine increased 0.12 mg/dL (P < .01), and log BNP increased 0.26 (P < .05).ConclusionsWe found an independent association between RVEF and prognostic markers in HF patients. Worsening RV function may exert its negative effect on prognosis through increasing congestion (elevated BNP), affecting renal blood flow (increased creatinine) and limiting left ventricular preload, thereby reducing exercise tolerance.     

The right ventricular septum presents the optimum site for maximal electrical separation during left ventricular pacing

Septum Presents the Optimum Site for Maximal Electrical Separation. Cardiac resynchronization therapy (CRT) benefits selected heart failure (HF) patients. The optimal placement of the right ventricle (RV) lead during biventricular pacing has not been assessed. Greater electrical separation (ES) between left ventricle (LV) and RV leads has been associated with better clinical outcomes. The site of maximal electrical separation(MES) in the RV is unknown. Methods: Prospective study of 50 CRT patients. The LV lead was placed in a postero‐lateral branch of the coronary sinus. ES was recorded at 6 sites within the RV during LV pacing at 600 milliseconds cycle length (CL). The median ES was recorded with a roving deflectable catheter at the RV outflow tract (RVOT), high septum, inflow septum, mid‐septum, apical septum and apex. Results: Mean age was 67 ± 7 years, 39 were male (78%). Thirty had ischemic etiology (60%). Mean left ventricular ejection fraction (LVEF) was 25 ± 7%, QRS duration pre and post was 165 ± 26 milliseconds and 138.5 ± 15.6 milliseconds (P < 0.001). Mapping ES showed a difference between 20 and 50 milliseconds distributed across the RV in the majority of patients (40/49). However, 7 subjects demonstrated delay distribution of between 50 and 82 milliseconds. ES was significant greater in the RV mid‐septum (161.2 ± 23.7 milliseconds) compared with RVOT (154.1 ± 20.8 milliseconds) and apex (148.0 ± 25.5 milliseconds; P < 0.001). The site of Maximal ES was most commonly found at the mid‐septum (40 patients, 80%) and only rarely at the RVOT (5, 10%) and apex (5, 10%; P < 0.01). Conclusion: MES was observed most commonly at the RV septum and rarely at the RV apex. Better correction of electrical and mechanical dyssynchrony by CRT may be achieved by placing the RV lead in a site outside of the apex in the majority of patients. Clinical studies exploring RV septal pacing in CRT seem warranted.     

Preferred left ventricular lead position for upgrade from right ventricular pacing to cardiac resynchronization therapy

Introduction

Cardiac resynchronization therapy (CRT) is well-established for treating symptomatic heart failure with electrical dyssynchrony. The left ventricular (LV) lead position is recommended at LV posterolateral to lateral sites in patients with left bundle branch block; however, its preferred region remains unclear in patients being upgraded from right ventricular (RV) apical pacing to CRT. This study aimed to identify the preferred LV lead position for upgrading conventional RV apical pacing to CRT.

Methods

We used electrode catheters positioned at the RV apex and LV anterolateral and posterolateral sites via the coronary sinus (CS) branches to measure the ratio of activation time to QRS duration from the RV apex to the LV anterolateral and posterolateral sites during RV apical pacing. Simultaneous biventricular pacing was performed at the RV apex and each LV site, and the differences in QRS duration and LV dP/dt_max from those of RV apical pacing were measured.

Results

Thirty-seven patients with anterolateral and posterolateral LV CS branches were included. During RV apical pacing, the average ratio of activation time to QRS duration was higher at the LV anterolateral site than at the LV posterolateral site (0.90 ± 0.06 vs. 0.71 ± 0.11, p < .001). The decreasing ratio of QRS duration and the increasing ratio of LV dP/dt_max were higher at the LV anterolateral site than at the posterolateral site (45.7 ± 18.0% vs. 32.0 ± 17.6%, p < .001; 12.7 ± 2.9% vs. 3.7 ± 8.2%, p < .001, respectively) during biventricular pacing compared with RV apical pacing.

Conclusion

The LV anterolateral site is the preferred LV lead position in patients being upgraded from conventional RV apical pacing to CRT.     

The ischemic etiology of heart failure in diabetics limits reverse left ventricular remodeling after cardiac resynchronization therapy

Aim of the StudyThe aim of this study was to evaluate reverse volumetric left ventricular (LV) remodeling after cardiac resynchronization therapy (CRT) in patients with heart failure (HF) with vs. without diabetes mellitus (DM).MethodsThe study comprised 130 consecutive patients with HF (mean age, 61±12 years) who underwent CRT. Thirty patients (23%) had DM [mean glycated haemoglobin (HbA_1c), 7.2±3.4%; 13 (43%) on insulin therapy]. Echocardiography, including tissue Doppler measurements, was performed before CRT and between 3 and 6 months after CRT. Echocardiographic response was defined as a >15% reduction in LV end-systolic volume (ESV).ResultsPatients with DM had more often hypertension (60% vs. 29%, P<.05) and ischemic HF etiology (87% vs. 51%, P<.05), but similar pre-CRT echocardiographic findings. After CRT, patients with DM had equal reductions in QRS duration and lateral-to-septal mechanical delay, but less improvement in LV ESV, mitral annular tissue velocity, the myocardial performance (or Tei) index and the E/E′ ratio (ratio of early transmitral peak filling velocity to early mitral annular peak diastolic velocity, an indicator of LV filling pressure). Patients without reverse volumetric LV remodeling had more often DM [hazard ratio (HR), 1.897; P=.042] and an ischemic HF etiology (HR, 2.308; P=.006). An ischemic HF etiology (HR, 2.119; P=.018) was the only independent predictor of poor reverse volumetric LV remodeling.ConclusionIschemic etiology of HF is an independent predictor of poor echocardiographic response to CRT. Patients with DM and HF have a relatively poor echocardiographic response to CRT most probably due to a high incidence of ischemic etiology of HF.     

Transvenous versus open chest lead placement for resynchronization therapy in patients with heart failure: comparison of ventricular electromechanical synchronicity

Background Transvenous lead placement is the standard approach for left ventricular (LV) pacing in cardiac resynchronization therapy (CRT), while the open chest access epicardial lead placement is currently the most frequently used second choice. Our study aimed to compare the ventricular electromechanical synchronicity in patients with heart failure after CRT with these two different LV pacing techniques. Methods We enrolled 33 consecutive patients with refractory heart failure secondly to dilated cardiomyopathy who were eligible for CRT in this study. Nineteen patients received transvenous (TV group) while 14 received open chest (OP group) LV lead pacing. Intra- and inter-ventricular electromechanical synchronicity was assessed by tissue Doppler imaging (TDI) before and one year after CRT procedure. Results Before CRT procedure, the mean QRS-duration, maximum time difference to systolic peak velocity among 12 left ventricle segments (LV Ts-12), standard deviation of time difference to systolic peak velocity of 12 left ventricle segments (LV Ts-SD), and inter-ventricular mechanical delay (IVMD) in OP and TV group were 166 ± 17 ms and 170 ± 21 ms, 391 ± 42 ms and 397 ± 36 ms, 144 ± 30 ms and 148 ± 22 ms, 58 ± 25 ms and 60 ± 36 ms, respectively (all P > 0.05). At one year after the CRT, the mean QRS-duration, LV Ts-12, LV Ts-SD, and IVMD in TV and OP group were 128 ± 14 ms and 141 ± 22 ms (P = 0.031), 136 ± 37 ms and 294 ± 119 ms (P = 0.023), 50 ± 22 ms and 96 ± 34 ms (P = 0.015), 27 ± 11 ms and 27 ± 26 ms (P = 0.86), respectively. The LV lead implantation procedure time was 53.4 ± 16.3 min for OP group and 136 ± 35.1 min for TV group (P = 0.016). The mean LV pacing threshold increased significantly from 1.7 ± 0.6 V/0.5 ms to 2.3 ± 1.6 V/0.5 ms (P < 0.05) in TV group while it remained stable in the OP group. Conclusions Compared to conventional endovascular approach, open chest access of LV pacing for CRT leads to better improvement of the intraventricular synchronization.     

Endothelial Dysfunction is a Marker of Systemic Response to the Cardiac Resynchronization Therapy in Heart Failure

BackgroundCardiac resynchronization therapy (CRT) induces a significant improvement in patients with heart failure (HF), who are often characterized by the presence of endothelial dysfunction (ED) with impaired flow-mediated vasodilation (FMD). We aimed to study the ED in patients with HF candidates to CRT with defibrillator (CRT-D).Methods and ResultsWe studied 57 consecutive patients affected by HF and undergoing CRT-D. At the baseline we recorded a high prevalence of ED (64.9%) with impaired FMD (4.1 ± 3.8%). After 12 months of CRT, we reported a marked increase of the mean FMD (8.8 ± 4.8% vs 4.1 ± 3.8%; P < .05) along with significant improvement of left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), New York Heart Association (NYHA) functional class, and 6-minute walk test (6MWT); 42 patients (73.7%) were classified as responders according to standard criteria. FMD was related to LVEF (r = 0.169; P < .05), LVESV (r = ?0.169; P < .05), NYHA functional class (r = ?0.27; P < .051), and 6MWT (r = 0.360; P < .01).ConclusionsED is not an independent predictor of CRT response, but it is able to intercept the systemic effects of CRT and is an affordable marker of response to CRT, especially in patients unable to perform the 6MWT.     

Gabapentin therapy improves heart rate variability in diabetic patients with peripheral neuropathy

PurposeDiabetic cardiac neuropathy, which is characterized by reduced heart rate variability (HRV), frequently coexists with peripheral neuropathy. Gabapentin has been used for the treatment of diabetic neuropathy. We aimed to evaluate the possible effect of gabapentin treatment on autonomic function in patients with type 2 diabetes via HRV.MethodsThirty patients with type 2 diabetes mellitus and peripheral neuropathy and 28 age- and sex-matched healthy controls were consecutively registered. Each patient underwent HRV measurements, and diabetic patients were administered gabapentin. After 3 months of gabapentin therapy, HRV parameters were measured again.ResultsBaseline HRV parameters were blunted in patients with diabetes mellitus according to the controls [standard deviation of all NN intervals (SDNN, ms): 106.3±29.9 vs. 148.8±36.5, P=.001; power spectrum of the high-frequency band (HF, ms²): 133.6±98.3 to 231.4±197.6, P=.02; power spectrum of the low-frequency band (LF, ms²): 341.8±247.8 to 511.5±409.4, P=.048; LF/HF ratio: 3.3±2.4 to 2.6±1.5, P=.33]. After 3 months of treatment with gabapentin, some HRV parameters showed some improvement. SDNN (106.2±29.8 to 119.4 ± 25, P=.016) and HF (133.6±98.3 to 167.6±118.3, P=.021) increased significantly. LF/HF ratio decreased (from 3.3±2.4 to 2.3±1.9, P=.039) and LF remained unchanged (341.8±247.8 to 352.3±228.9, P=.88).ConclusionsTherapeutic doses of gabapentin not only alleviate neuropathic symptoms but also improve cardiac autonomic function in diabetic patients with peripheral neuropathy.