Basal Asynchrony and Resynchronization with Biventricular Pacing Predict Long-Term Improvement of LV Function in Heart Failure Patients (original) (raw)
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Mechanisms by Which Cardiac Resynchronization Therapy Improves Cardiac Performance in Heart Failure
Journal of the American College of Cardiology, 2011
This thesis assesses the mechanisms by which biventricular and left ventricular pacing improves cardiac performance in patients with heart failure. We demonstrated for the first time that CRT results in an improvement in acute haemodynamic variables in heart failure patients with a narrow QRS duration that is comparable to the effects seen in heart failure patients with a broad QRS duration. In addition, we have shown that both biventricular (BIVP) and left ventricular pacing (LVP) significantly reduce external constraint to left ventricular filling, resulting in an increase in effective filling pressure. In heart failure patients with evidence of external constraint at rest, the acute haemodynamic benefits of both BIVP and LVP were principally due to the relief of external constraint and preload recruitment. However, in those patients with evidence of electrical dyssynchrony and a broad QRS duration, a significant haemodynamic benefit was derived from an enhancement in left ventricular contractility, presumably as a result of a reduction in left ventricular dyssynchrony. Patients with external constraint appear to derive a greater haemodynamic benefit from pacing due to the significant increase in stroke work that is associated with relief of external constraint and preload recruitment, in addition to the increase in stroke work derived from enhanced contractility due to a reduction in dyssynchrony. These findings will inform better patient selection for this therapy and also optimisation of pacing strategy in individual patients. STATEMENT OF CONTRIBUTION I undertook screening (with echocardiography, ECG and metabolic exercise testing) and recruitment of potential participants with a narrow QRS duration, as well as recruiting patients undergoing implantation of a biventricular pacemaker with a broad QRS duration. I undertook the acquisition of the invasive haemodynamic data in 85% of all patients, and completed analysis of the data in all cases recruited. I was also involved in the collection and analysis of all echocardiographic data included in this thesis.
Circulation, 2011
Background— Left ventricular (LV) pacing alone may theoretically avoid deleterious effects of right ventricular pacing. Methods and Results— In a multicenter, double-blind, crossover trial, we compared the effects of LV and biventricular (BiV) pacing on exercise tolerance and LV remodeling in patients with an LV ejection fraction ≤35%, QRS ≥120 milliseconds, and symptoms of heart failure. A total of 211 patients were recruited from 11 centers. After a run-in period of 2 to 8 weeks, 121 qualifying patients were randomized to LV followed by BiV pacing or vice versa for consecutive 6-month periods. The greatest improvement in New York Heart Association class and 6-minute walk test occurred during the run-in phase before randomization. Exercise duration at 75% of peak V o 2 (primary outcome) increased from 9.3±6.4 to 14.0±11.9 and 14.3±12.5 minutes with LV and BiV pacing, respectively, with no difference between groups ( P =0.4327). LV ejection fraction improved from 24.4±6.3% to 31.9±1...
Biventricular and novel pacing mechanisms in heart failure
Current Heart Failure Reports, 2009
Biventricular pacing, often referred to as cardiac resynchronization therapy (CRT), improves subjective and objective measures and promotes reverse ventricular remodeling in patients with chronic New York Heart Association (NYHA) class III or IV heart failure despite optimal medical therapy, QRS duration of more than 130 ms, and left ventricular ejection fraction of less than 35%. However, there are many nonresponders
Pace-pacing and Clinical Electrophysiology, 2007
There are few studies on cardiac resynchronization therapy (CRT) in heart failure (HF) patients with preexisting right ventricular (RV) pacing. The purpose of this study was to determine the efficacy of CRT upgrading in RV-paced patients and the predictivity of electromechanical dyssynchrony parameters (EDP) evaluated by standard echocardiography (ECHO) and tissue Doppler imaging (TDI). Methods: Thirty-eight consecutive patients with HF [New York Heart Association (NYHA) class III or IV, LVEF < 35%], prior continuous RV pacing, and absence of atrial fibrillation were enrolled in the presence of a paced QRS ≥ 150 ms and evaluated by ECHO and TDI. A responder was defined as a patient with a favorable change in NYHA class and neither HF hospitalization nor death, plus an absolute increase of LVEF ≥ 10 units. Results: At six-months follow-up, the whole study population had significant improvement in symptoms, systolic function, and QRS duration (P < 0.001); 32 (84%) patients had a favorable clinical outcome, 25 (66%) were considered responders according to the previous definition. Postimplant QRS was similarly reduced in both responders and nonresponders, whereas EDP had a significant improvement only in responders (P < 0.05). Using EDP, 23 (79%) patients were responders compared with 2 (22%) patients without mechanical dyssynchrony (P = 0.002). Conclusions: In HF patients with previous RV pacing, CRT is effective to improve clinical, functional outcome, and LV performance and to reduce electromechanical dyssynchrony in a large proportion of patients. Dyssynchrony evaluated by standard and TDI ECHO can be useful for CRT selection of paced patients. (PACE 2007; 30:1096-1104 heart failure, ventricular dyssynchrony, cardiac resynchronization therapy, biventricular upgrading
Journal of the American College of Cardiology, 2001
We sought to investigate the impact of six months of cardiac resynchronization therapy (CRT) on echocardiographic variables of left ventricular (LV) function. BACKGROUND Cardiac resynchronization therapy has recently been introduced as a new therapeutic modality in patients with advanced heart failure (HF) and conduction abnormalities. However, most studies have only investigated the early hemodynamic effects of CRT. METHODS Twenty-five patients (12 women and 13 men; 59.8 Ϯ 5.1 years old) with advanced HF caused by ischemic (n ϭ 7) or idiopathic dilated cardiomyopathy (n ϭ 18) and a prolonged QRS complex were analyzed. All patients underwent early hemodynamic testing with a randomized testing protocol; echocardiographic measurements were compared before implantation and after six months of CRT. RESULTS Left ventricular end-diastolic and end-systolic diameters (LVEDD and LVESD, respectively) were significantly reduced after six months (LVEDD from 71 Ϯ 10 to 68 Ϯ 11 mm, p ϭ 0.027; LVESD from 63 Ϯ 11 to 58 Ϯ 11 mm, p ϭ 0.007), as were LV end-diastolic and end-systolic volumes (LVEDV from 253 Ϯ 83 to 227 Ϯ 112 ml, p ϭ 0.017; LVESV from 202 Ϯ 79 to 174 Ϯ 101 ml, p ϭ 0.009). Ejection fraction was significantly increased (from 22 Ϯ 7% to 26 Ϯ 9%, p ϭ 0.03). "Nonresponders," with regard to LV volume reduction, had significantly higher baseline LVEDV, compared with "responders" (351 Ϯ 52 vs. 234 Ϯ 74 ml, p ϭ 0.018). Overall, there was only mild mitral regurgitation at baseline, with a minor reduction by semiquantitative analysis. The results of early hemodynamic testing did not predict the volume response. CONCLUSIONS Cardiac resynchronization therapy may lead to a reduction in LV volumes in patients with advanced HF and conduction disturbances. Volume nonresponders have significantly higher baseline LVEDV.
Biventricular pacing and heterogeneity of ventricular repolarization in heart failure patients
Heart International, 2006
Objective: The aim of our study was to evaluate the effect of cardiac resyncronization therapy (CRT) on QT dispersion (QTd), JT dispersion (JTd) and transmural dispersion of repolarization (TDR), markers of heterogeneity of ventricular repolarization in a study population with severe heart failure. Methods and Results: Fifty patients (43 male, 7 female, aged 60.2 ± 3.1 years) suffering from congestive heart failure (N = 39 NYHA class III; N = 11 NYHA class IV) as a result of coronary artery disease (N = 19) or of dilated cardiomyopathy (N = 31), sinus rhythm, QRS duration >130 ms (mean QRS duration >156 ± 21 ms), an ejection fraction < 35%, left ventricular end-diastolic diameter >55 mm, underwent permanent biventricular DDDR pacemaker implantation. A 12-lead standard electrocardiogram was performed at baseline, during right-, left-, and biventricular pacing and QTd, JTd and TDR were assessed. Biventricular pacing significantly reduced QTd (73.93 ± 19.4 ms during BiVP vs 91 ± 6.7 ms at sinus rhythm, p = 0.004), JTd (73.18 ± 17.16 ms during BiVP vs 100.72 ± 39.04 at baseline p = 0.003), TDR (93.16 ± 15.60 vs 101.55 ± 19.08 at baseline; p<0.004), as compared to sinus rhythm. Right ventricular endocardial pacing and left ventricular epicardial pacing both enhanced QTd (RVendoP 94 ± 51 ms, p<0.03; LVepiP 116 ± 71 ms, p<0.02) and TDR (RVendoP 108.13 ± 19.94 ms; p<0.002; LVepiP 114.71 ± 26.1; p<0.05).There was no effect on JTd during right and left ventricular stimulation. Conclusions: Biventricular pacing causes a statistically significant reduction of ventricular heterogeneity of ripolarization and has an electrophysiological antiarrhythmic influence on arrhythmogenic substrate of dilatative cardiomiopathy. (Heart International 2006; 2: 27-32)
Circulation, 2002
Background-Biventricular pacing has been proposed to improve symptoms and exercise capacity in patients with advanced heart failure and wide electrocardiographic wave complexes. This study investigated the effect of biventricular pacing on reverse remodeling and the underlying mechanisms. Methods and Results-Twenty-five patients with NYHA class III to IV heart failure and electrocardiographic wave complex duration Ͼ140 ms receiving biventricular pacing therapy were assessed serially up to 3 months after pacing and when pacing was withheld for 4 weeks. Tissue Doppler echocardiography was performed using a 6-basal, 6-mid segmental model to assess the time to peak sustained systolic contraction (T S). There was significant improvement of ejection fraction, dP/dt, and myocardial performance index; decrease in mitral regurgitation, left ventricular (LV) end-diastolic (205Ϯ68 versus 168Ϯ67 mL, PϽ0.01) and end-systolic volume (162Ϯ54 versus 122Ϯ42 mL, PϽ0.01); and improved 6-minute hall-walk distance and quality of life score after pacing for 3 months. The mechanisms of benefits were as follows: (1) improved LV synchrony, as evident by homogeneous delay of T S to a timing close to the latest (usually the lateral) segment abolishing the intersegmental difference in T S and decreasing the standard deviation of T S within the left ventricle (37.7Ϯ10.9 versus 29.3Ϯ8.3 ms, PϽ0.05); (2) improved interventricular synchrony; and (3) shortened isovolumic contraction time (122Ϯ57 versus 82Ϯ36 ms, PϽ0.05) but increased diastolic filling time. These benefits are pacing dependent, because withholding the pacing resulted in varying speeds in the loss of cardiac improvements. Conclusions-Biventricular pacing reverses LV remodeling and improves cardiac function. Improvement of LV mechanical synchrony seems to be the predominant mechanism. (Circulation. 2002;105:438-445.
A pilot experience with permanent biventricular pacing to treat advanced heart failure
American Heart Journal, 2000
at least it cannot correct the marked asynchrony of ventricular activation, contraction, and relaxation, which characterizes a number of patients with chronic left ventricular (LV) systolic dysfunction. Such is the case in particular in patients with intraventricular conduction delay (IVCD). Biventricular pacing (BVP), which simultaneously activates both ventricles, may contribute to correcting the asynchrony and thus improve cardiac performance. Several acute hemodynamic studies have shown that temporary biventricular pacing significantly improved hemodynamics. The aim of this prospective pilot but uncontrolled study was to assess the long-term clinical effects of permanent BVP in patients with drug-refractory heart failure secondary to advanced LV systolic dysfunction and IVCD.
Canadian Journal of Cardiology, 2017
Background: Studies comparing biventricular (BiV) cardiac resynchronization therapy (CRT) and left ventricular (LV) pacing alone have yielded conflicting results. We recently reported the results of the Greater Evaluation of Resynchronization Therapy for Heart Failure (GREATER-EARTH) trial demonstrating similar clinical benefits of BiV and LV-CRT on exercise tolerance. We report the prespecified secondary outcomes of the GREATER-EARTH trial, comparing the impact of BiV vs LV-CRT on structural and biochemical cardiac remodelling. Methods: Patients with a LV ejection fraction (LVEF) 35% and a QRS duration ! 120 ms were randomized to BiV-CRT or LV-CRT for a 6-month period, followed by crossover. The primary end point was a change in LV end-systolic volume (LVESV). Secondary end points included changes in LVEF, right ventricular (RV) dimensions and function, mitral regurgitation (MR), indices of diastolic function, systolic pulmonary artery pressure (sPAP), and disease-specific biomarkers. Results: One hundred twenty patients (60.9