Dyssynchronous Ventricular Contraction Research Articles

Mechanocardiography detects improvement of systolic function caused by resynchronization pacing.

Objective.Cardiac resynchronization therapy (CRT) is commonly used to manage heart failure with dyssynchronous ventricular contraction. CRT pacing resynchronizes the ventricular contraction, while AAI (single-chamber atrial) pacing does not affect the dyssynchronous function. This study compared waveform characteristics during CRT and AAI pacing at similar pacing rates using seismocardiogram (SCG) and gyrocardiogram (GCG), collectively known as mechanocardiogram (MCG).Approach.We included 10 patients with heart failure with reduced ejection fraction and previously implanted CRT pacemakers. ECG and MCG recordings were taken during AAI and CRT pacing at a heart rate of 80 bpm. Waveform characteristics, including energy, vertical range (amplitude) during systole and early diastole, electromechanical systole (QS2) and left ventricular ejection time (LVET), were derived by considering 6 MCG axes and 3 MCG vectors across frequency ranges of >1 Hz, 20-90 Hz, 6-90 Hz and 1-20 Hz.Main results.Significant differences were observed between CRT and AAI pacing. CRT pacing consistently exhibited higher energy and vertical range during systole compared to AAI pacing (p< 0.05). However, QS2, LVET and waveform characteristics around aortic valve closure did not differ between the pacing modes. Optimal differences were observed in SCG-Y, GCG-X, and GCG-Y axes within the frequency range of 6-90 Hz.Significance.The results demonstrate significant differences in MCG waveforms, reflecting improved mechanical cardiac function during CRT. This information has potential implications for predicting the clinical response to CRT. Further research is needed to explore the differences in signal characteristics between responders and non-responders to CRT.

Dyssynchrony Induced by Ventricular Preexcitation: A Risk Factor for the Development of Dilated Cardiomyopathy

Background: Significant left ventricular dysfunction may arise in right-sided accessory pathways with ventricular preexcitation in the absence of recurrent or incessant tachycardia. This has just been realized and not enough attention has been paid to it. Methods: In the last 7 years, we identified 12 consecutive children with a diagnosis of ventricular preexcitation–induced dilated cardiomyopathy. This report describes the clinical and echocardiographic characteristics of the patients before and after ablation. Results: Dyssynchronous ventricular contraction was observed by M-mode echocardiography and two-dimensional strain analysis in all patients. The basal and middle segments of the interventricular septum became thin and moved similarly to an aneurysm, with typical bulging during the end of systole. The locations of the accessory pathways were the right-sided septum (n=5) and the free wall (n=7). Left ventricular synchrony was obtained shortly after ablation. The left ventricular function recovered to normal and the left ventricular end-diastolic diameter decreased gradually during follow-up. Conclusions: A causal relationship between ventricular preexcitation and the development of dilated cardiomyopathy is supported by the complete recovery of left ventricular function and reversed left ventricular remodeling after the loss of ventricular preexcitation. Preexcitation-related dyssynchrony was thought to be the crucial mechanism. Ventricular preexcitation–induced dilated cardiomyopathy is an indication for ablation with a good prognosis.

Metabolic remodeling in moderate synchronous versus dyssynchronous pacing-induced heart failure: integrated metabolomics and proteomics study.

Heart failure (HF) is accompanied by complex alterations in myocardial energy metabolism. Up to 40% of HF patients have dyssynchronous ventricular contraction, which is an independent indicator of mortality. We hypothesized that electromechanical dyssynchrony significantly affects metabolic remodeling in the course of HF. We used a canine model of tachypacing-induced HF. Animals were paced at 200 bpm for 6 weeks either in the right atrium (synchronous HF, SHF) or in the right ventricle (dyssynchronous HF, DHF). We collected biopsies from left ventricular apex and performed comprehensive metabolic pathway analysis using multi-platform metabolomics (GC/MS; MS/MS; HPLC) and LC-MS/MS label-free proteomics. We found important differences in metabolic remodeling between SHF and DHF. As compared to Control, ATP, phosphocreatine (PCr), creatine, and PCr/ATP (prognostic indicator of mortality in HF patients) were all significantly reduced in DHF, but not SHF. In addition, the myocardial levels of carnitine (mitochondrial fatty acid carrier) and fatty acids (12:0, 14:0) were significantly reduced in DHF, but not SHF. Carnitine parmitoyltransferase I, a key regulatory enzyme of fatty acid ß-oxidation, was significantly upregulated in SHF but was not different in DHF, as compared to Control. Both SHF and DHF exhibited a reduction, but to a different degree, in creatine and the intermediates of glycolysis and the TCA cycle. In contrast to this, the enzymes of creatine kinase shuttle were upregulated, and the enzymes of glycolysis and the TCA cycle were predominantly upregulated or unchanged in both SHF and DHF. These data suggest a systemic mismatch between substrate supply and demand in pacing-induced HF. The energy deficit observed in DHF, but not in SHF, may be associated with a critical decrease in fatty acid delivery to the ß-oxidation pipeline, primarily due to a reduction in myocardial carnitine content.

Adverse effects of type B ventricular pre-excitation on ventricular wall motion and left ventricular function: clinical analysis of 9 cases

To analyze the adverse effects of type B ventricular pre-excitation on ventricular wall motion and left ventricular function and its clinical characteristic. The clinical, electrophysiological and echocardiographic characteristics of the 9 cases with type B ventricular pre-excitation before and after ablation seen between March 2011 and March 2013 were analyzed. The patients aged from 3 to 16 years. Five of them were female. Dyschronous left ventricular contraction was demonstrated by M-Mode echocardiography in all of the cases. The basal segments of the interventricular septum turned thin and moved in a manner similar to that of an aneurysm, with typical bulging during end-systole, which was observed in six cases. All patients received successful RFCAs. The locations of the accessory pathways (APs) were the right-sided anteroseptum (n = 2) and the free wall (n = 7). Their physical activities and growth improved greatly in the four cases with coexisting dilated cardiomyopathy (DCM). The echocardiographic data demonstrated that their LV contraction recovered to synchrony shortly after the ablation, LVEF recovered to normal and LVED decreased to almost normal gradually during the follow-up. Overt right-sided APs may have adverse effects on ventricular wall motion and left ventricular function. They can even result in DCM. Dyssynchronous ventricular contraction induced by right-sided overt accessory pathway may be the vital mechanism. Such kinds of cases are indication for ablation with good prognosis.

Dyssynchronous ventricular contraction in Wolff–Parkinson–White syndrome: a risk factor for the development of dilated cardiomyopathy

Emerging evidence suggests that significant left ventricular dysfunction may arise in right-sided septal or paraseptal accessory pathways (APs) with Wolff-Parkinson-White syndrome, even in the absence of recurrent or incessant tachycardia. During 1 year and 9 months, we identified four consecutive female children with median age of 8 years diagnosed as having dilated cardiomyopathy (DCM) combined with overt right-sided APs several years ago. Incessant or recurrent tachycardia as the cause of DCM could be excluded. Anti-heart failure chemotherapy did not produce satisfactory effects. The patients underwent radiofrequency ablations (RFCAs). This report describes the clinical and echocardiographic characteristics of the cases before and after the ablation. Dyssynchronous ventricular contraction was observed in all patients. The locations of the APs were the right-sided anteroseptum and the free wall (n = 2 each). All patients received successful RFCAs. Their physical activities and growth improved greatly, and the echocardiographic data demonstrated that their left ventricular (LV) contraction recovered to synchrony shortly after the ablation and that their LV function recovered to normal gradually during the follow-up. A causal relationship between overt ventricular preexcitation and the development of DCM is supported by the complete recovery of LV function and reversed LV remodeling after the loss of ventricular preexcitation. Preexcitation-related dyssynchrony was probably the crucial mechanism. Not only right-sided septal or paraseptal but also free wall overt APs may induce LV dysfunction and even DCM. AP-induced DCM is an indication for ablation with a good prognosis.

Abstract 19162: Metabolites Reporting on Mitochondrial Function Predict Response to Biventricular Pacing

Background. Biventricular pacing has been shown to improve morbidity and mortality in patients with impaired systolic left ventricular function and congestive heart failure who have evidence of dyssynchronous ventricular contraction. However, a significant percentage of patients implanted with a biventricular pacer will not have a beneficial response. Novel molecular technologies may help identify biomarkers to better predict who will benefit most from this therapy. Methods. Individuals undergoing biventricular pacemaker implantation were selected from the ElectroPhysiology GENetics (EPGEN) biorepository (N=120). Targeted, quantitative mass-spectrometry based metabolomic profiling of 63 metabolites was performed on baseline, frozen, fasting plasma samples collected at the time of the index procedure. Positive response to pacing was defined as a 5% improvement in left ventricular ejection fraction or a ≥1 class improvement in New York Heart Association functional class at six months after device implantation. Principal components analysis (PCA) was used to reduce the large number of individual metabolites into a smaller set of uncorrelated factors. Logistic regression was used to test the association between PCA-derived factors and response. Results. A positive response to biventricular pacing was observed in 55 individuals at 6 months (N=65 showing no positive response). PCA identified 13 metabolite factors clustering in biologically plausible pathways. Of these, factor 1 (composed of medium and long chain acylcarnitines, medium and long chain dicarboxylacylcarnitines, ketones and β-hydroxybutyrate) was associated with positive response to pacing (p=0.007). Analyses of the individual metabolites composing this factor showed similar results (p=0.03-0.003). Conclusions. We have identified a cluster of metabolites, many of which are derived from mitochondrial metabolism, that predict a positive response to biventricular pacing. These novel biomarkers may assist in better risk stratification and patient selection for this therapy.

Basic Science of Cardiac Resynchronization Therapy

Electromechanical dyssynchrony can markedly worsen heart failure (HF) morbidity and mortality, independent of traditional risk factors.1–4 Depending on the metric used, current estimates of the prevalence of dyssynchrony vary from 25–30% in patients with HF (based on QRS widening) up to 60%, based on tissue Doppler or MRI measures of dyssynchronous contraction of the left ventricle (LV).5,6 Cardiac resynchronization therapy (CRT) or biventricular pacing has emerged as a promising option to treat patients with HF and dyssynchronous contraction.7–9 The past few decades have seen the rise of pharmacotherapy, primarily through agents that antagonize the effect of excessive concentrations of circulating neurohormones, yet, HF-related morbidity and mortality remain high.3–6 Biventricular stimulation has been demonstrated to improve contractile performance in patients with mechanical dyssynchrony acutely and chronically while also prolonging long-term survival—something not yet achieved by drug therapy.10 Although the clinical and mechanical effectiveness of CRT are well described, 30% of patients do not benefit from CRT and clinical criteria to identify CRT nonresponders remain elusive8,11,12 Currently, the most widely used predictor of reverse remodeling is the presence of marked mechanical dyssynchrony before CRT, as indexed by the width of the QRS.13 Mechanical dyssynchrony seems important, yet imaging-based measures have not predicted response well14 and even improvement in dyssynchrony after initiation of CRT only weakly predicts chronic response.15 Limited understanding of the molecular mechanisms underlying reverse cardiac remodeling induced by CRT has hampered the selection of potential responders. In this review, we focus on the electrophysiological aspects and molecular networks underlying the benefits of CRT. We will review how CRT homogenizes regional differences in stress kinase signaling and electric remodeling and then review its global effect on myocyte function and its …

Clinical Predictors of Chronic Cardiac Resynchronization Pacing Efficacy in the Failing Congenital Heart

Cardiac resynchronization pacing therapy (CRT) is an effective mode of therapy in adults with advanced heart failure(HF) and dyssynchronous ventricular contraction. CRT has been helpful in patients(pts) with congenital heart disease (CHD) as well. But the adult criteria for pt selection is not applicable to CHD pts. QRS duration varies with age, dyssnchrony can exist with a narrow QRS, and accurate ejection fraction estimation is difficult with CHD. Selection criteria for CRT in CHD are not established.

Cardiac Resynchronization Therapy for Treatment of Heart Failure

Conduction abnormalities, commonly seen in systolic heart failure, lead to delayed activation of the myocardium as the electrical impulse spreads slowly without the aid of healthy conduction tissue. The resulting dyssynchronous ventricular contraction is mechanically less efficient, reducing systolic function and impairing diastolic filling. Simultaneous pacing of the right and left ventricles (i.e., biventricular pacing) reduces ventricular dyssynchronous contraction, overcoming these consequences of conduction delay. An important role for implantable rhythm-management devices providing cardiac resynchronization therapy has emerged in the optimization of ventricular function in heart failure. Long-term benefits in patient outcomes have been well established. With increasing use, understanding of cardiac resynchronization therapy devices and the principles behind the therapy are important for physicians providing perioperative and intensive care for patients with heart failure.

Cardiac resynchronization therapy.

Systolic heart failure is a major problem for Americans today, with 550,000 new cases diagnosed per year, and ultimately contributes to 287,000 deaths annually. While pharmacologic therapy has drastically improved outcomes in patients with systolic heart failure, hospitalizations from systolic heart failure continue to increase and remain a major cost burden. In response to this unmet need, recent years have seen dramatic improvements in device-based therapy targeting one cause of systolic dysfunction: dyssynchronous ventricular contraction. Cardiac resynchronization therapy aims to restore mechanical synchrony by electrically activating the heart in a synchronized manner. This review summarizes the rationale for cardiac resynchronization therapy, evidence for its use, current guidelines, and ongoing and future directions for research.

Quantification of Regional Left Ventricular Dyssynchrony by Magnetic Resonance Imaging

Cardiac resynchronization therapy is an established treatment in patients with symptomatic heart failure and intraventricular conduction delay. Electrical dyssynchrony is typically adopted to represent myocardial activation dyssynchrony, which should be compensated by cardiac resynchronization therapy. One third of the patients, however, does not respond to the therapy. Therefore, imaging modalities aimed at the mechanical dyssynchrony estimation have been recently proposed to improve patient selection criteria. This paper presents a novel fully automated method for regional mechanical left ventricular dyssynchrony quantification in short-axis magnetic resonance imaging. The endocardial movement is described by time-displacement curves with respect to an automatically determined reference point. Different methods are proposed for time-displacement curve analysis aimed at the regional contraction timing estimation. These methods were evaluated in two groups of subjects with (nine patients) and without (six patients) left bundle branch block. The contraction timing standard deviation showed a significant increase for left bundle branch block patients with all the methods. A novel method based on phase spectrum analysis may be however preferred due to a better specificity (99.7%) and sensitivity (99.0%). In conclusion, this method provides a valuable prognostic indicator for heart failure patients with dyssynchronous ventricular contraction and it opens new possibilities for regional timing analysis.

Predicting outcome in severe heart failure. Who will benefit from device therapy (CRT)?

Dyssynchronous ventricular contraction in severe heart failure contributes to low cardiac output, worsening symptoms, and poor prognosis. Recognition of the effect of dyssynchrony in heart failure, and the possibility of manipulating the sequence of electrical cardiac activation to improve the efficiency of mechanical events, led Cazeau et al. to attempt four-chamber pacing in 1994.1 This early system could stimulate both atria and both ventricles extrinsically, and could dictate the temporal relationship between atrial systole and ventricular systole, and the ventriculo-ventricular relationship. Modern cardiac resynchronization therapy (CRT), involving pacing of the right and left ventricles, with right atrial pacing to optimize atrio-ventricular delay, has evolved rapidly from this beginning. Left bundle branch block (LBBB) on the surface electrocardiogram (ECG) has been considered a marker of mechanical dyssynchrony as it represents a delay in conduction of depolarization to the left ventricle, with the greatest delay usually being in the lateral free wall. The presence of LBBB, seen in about one-third of patients with heart failure,2 is associated with a poorer outcome than when LBBB is not present.3,4 Furthermore, the wider the QRS complex in LBBB, the worse the prognosis. The presence of a broad QRS complex with LBBB morphology has been an important entry criterion to most of the trials of CRT, which has now been evaluated in randomized clinical trials involving > 4000 patients.5–9 The European Society of Cardiology has now incorporated recommendations for use in clinical practice guidelines.10 The patients for whom CRT is recommended in these guidelines are those who represent a similar group to those involved in the randomized controlled trials, where in most cases the objective evidence of dyssynchrony was a broad QRS complex on the 12-lead ECG. The pharmacological and device-based therapies recommended in … *Corresponding author. Tel: +64 9 373 7599 ext. 89804; fax: +64 9 367 7146. E-mail address: r.doughty{at}auckland.ac.nz

Physiology of cardiac resynchronization.

Dyssynchronous ventricular contraction, often associated with delayed electrical activation, contributes to worsened clinical status in patients with chronic dilated heart failure. There are three levels of impaired electromechanical synchrony that can be recognized and potentially improved with pacing methods. Prolonged atrioventricular (AV) delay can promote presystolic mitral regurgitation and impaired left ventricular (LV) filling. Interventricular conduction delay with right ventricular (RV) activation preceding LV activation often occurs in the setting of left bundle branch block or RV apical pacing, and can result in impeded LV filling and ejection. Activation delays within the LV itself (intraventricular dyssynchrony) can cause decreased efficiency of contraction, increased mitral regurgitation, and abnormal ventricular remodeling. Cardiac resynchronization therapy (CRT) can improve ventricular performance in two thirds of patients selected based on QRS duration alone. Improved understanding of the pathophysiology of cardiac dyssynchrony will aid in patient selection and in assessment and optimization of response to CRT.

Clinical experience of contrast venography guided axillary vein puncture in biventricular pacing R1

Background and Objectives: Biventricular pacing is a new modality of treatment for patients with drug-refractory heart failure and ECG evidence of dyssynchronous ventricular contraction. A third lead is required to be placed in a coronary vein through the coronary sinus for left ventricular pacing, in addition to the atrial and right ventricular leads. Subclavian crush phenomenon is associated with lead placement using subclavian puncture. Cephalic venous cutdown, free of this complication, provides vascular access which is probably too small for multiple leads placement in biventricular pacing. Contrast venography guided axillary vein puncture (AP) is an alternative approach. This study reports on clinical experience of this technique in biventricular pacing. Methods: AP is the method of choice for biventricular pacing in Princess Margaret Hospital and Stanford University Medical Center. Patients’ clinical characteristics, effectiveness and safety of the technique were analysed. Results: AP was performed in 35 patients, 29 male and six female with mean age 57.1±14.7 years from 1 January 2000 to 30 June 2001. Six patients had biventricular pacing alone and 29 patients had biventricular implantable cardioverter defibrillator (ICD) implanted. Twelve (34.3%) patients have ischaemic cardiomyopathy, 22 (62.9%) patients have dilated cardiomyopathy and one (2.9%) patient has hypertrophic cardiomyopathy. Six (17.1%) patients were in NYHA Class II heart failure, 21 (60.0%) patients were in Class III and eight (22.9%) patients were in Class IV. The mean EF was 23.1±7.6%. AP was attempted for placement of all three leads in all patients. AP was successful in 34 (97.1%) patients. The single failure was due to small size of the axillary vein. There were no AP, lead or contrast-related complications with a follow up of 12 months. Conclusions: AP is both effective and safe for biventricular pacing. It may be the method of choice in biventricular pacing.

Frequency and associations of symptomatic deterioration after dual-chamber defibrillator implantation in patients with ischemic or idiopathic dilated cardiomyopathy

Sequential atrioventricular (AV) pacing has been proposed as a treatment for congestive heart failure (CHF) due to its ability to maintain chronotropic competence and optimal AV synchrony 1 Auricchio A. Sommariva L. Salo R.W. Scafuri A. Chiariello L. Improvement of cardiac function in patients with severe congestive heart failure and coronary artery disease by dual chamber pacing with shortened AV delay. Pacing Clin Electrophysiol. 1993; 16: 2034-2043 Crossref PubMed Scopus (131) Google Scholar , 2 Hochleitner M. Hortnagl H. Hortnagl H. Fridrich L. Gschnitzer F. Long-term efficacy of physiologic dual-chamber pacing in the treatment of end-stage idiopathic dilated cardiomyopathy. Am J Cardiol. 1992; 70: 1320-1325 Abstract Full Text PDF PubMed Scopus (170) Google Scholar ; it is increasingly being used in this patient population. Controlled studies have failed to confirm a significant improvement in left ventricular (LV) systolic function. 3 Innes D. Leitch J.W. Fletcher P.J. VDD pacing at short atrioventricular intervals does not improve cardiac output in patients with dilated heart failure. Pacing Clin Electrophysiol. 1994; 17: 959-965 Crossref PubMed Scopus (81) Google Scholar , 4 Gold M.R. Feliciano Z. Gottlieb S.S. Fisher M.L. Dual-chamber pacing with a short atrioventricular delay in congestive heart failure a randomized study. J Am Coll Cardiol. 1995; 26: 967-973 Abstract Full Text PDF PubMed Scopus (223) Google Scholar , 5 Linde C. Gadler F. Edner M. Nordlander R. Rosenqvist M. Rydén L. Results of atrioventricular synchronous pacing with optimized delay in patients with severe congestive heart failure. J Am Coll Cardiol. 1995; 75: 919-923 Abstract Full Text PDF Scopus (214) Google Scholar Anecdotal evidence exists that an exacerbation of symptomatic cardiac dysfunction may occur with right ventricular (RV) apical pacing, presumably due to dyssynchronous ventricular contraction. Although ventricular pacing is rarely used with single-chamber implantable cardioverter defibrillators, with dual-chamber systems many patients are paced in the ventricular chamber for much of the time. In this study we evaluated the effects of RV apical pacing in patients with heart failure who received dual-chamber defibrillators.

Hemodynamically optimized temporary cardiac pacing after surgery for congenital heart defects.

Disturbance of normal AV synchrony and dyssynchronous ventricular contraction may be deleterious in patients with otherwise compromised hemodynamics. This study evaluated the effect of hemodynamically optimized temporary dual chamber pacing in patients after surgery for congenital heart disease. Pacing was performed in 23 children aged 5 days to 7.7 years (median 7.3 months) with various postoperative dysrhythmias, low cardiac output, and/or high inotropic support and optimized to achieve the highest systolic and mean arterial pressures. The following four pacing modes were used: (1) AV synchronous or AV sequential pacing with individually optimized AV delay in 11 patients with first- to third-degree AV block; (2) AV sequential pacing using transesophageal atrial pacing in combination with a temporary DDD pacemaker for atrial tracking and ventricular pacing in three patients with third-degree AV block and junctional ectopic tachycardia, respectively, who had poor signal and exit block on atrial epicardial pacing wires; (3) R wave synchronized atrial pacing in eight patients with junctional ectopic tachycardia and impaired antegrade AV conduction precluding the use of atrial overdrive pacing; (4) Atrio-biventricular sequential pacing in two patients. Pressures measured during optimized pacing were compared to baseline values at underlying rhythm (13 patients with first-degree AV block or junctional ectopic tachycardia) or during pacing modes commonly used in the given clinical situation: AAI pacing (1 patient with slow junctional rhythm and first-degree AV block during atrial pacing), VVI pacing (2 patients with third-degree AV block and exit block and poor sensing on epicardial atrial pacing wires) and dual-chamber pacing with AV delays set to 100 ms (atrial tracking) or 150 ms (AV sequential pacing) in 7 patients with second- to third-degree AV block and functional atrial pacing wires. Optimized pacing led to a significant increase in arterial systolic (mean) pressure from 71.5 +/- 12.5 (52.3 +/- 9.0) to 80.5 +/- 12.2 (59.7 +/- 9.1) mmHg (P < 0.001 for both) and a decrease in central venous (left atrial) pressure from 12.3 +/- 3.4 (10.5 +/- 3.2) to 11.0 +/- 3.0 (9.2 +/- 2.7) mmHg (P < 0.001 and < 0.005, respectively). In conclusion, several techniques of individually optimized temporary dual chamber pacing leading to optimal AV synchrony and/or synchronous ventricular contraction were successfully used to improve hemodynamics in patients with heart failure and selected dysrhythmias after congenital heart surgery.