Cardiac resynchronization therapy in mildly symptomatic heart failure: the earlier the better

A new era is emerging in the field of complex pacing as a treatment for heart failure. Cardiac resynchronization therapy (CRT) is already established as an effective therapy to improve mortality and functional capacity in patients with moderate-severe heart failure, left ventricular systolic impairment and conduction delay (prolonged QRS duration on surface ECG). Recent evidence has demonstrated that CRT is also an effective treatment for patients with mild heart failure. As the indications for CRT expand, cardiologists face the exciting prospect of exploring where pacemaker technology can help improve patient outcomes across the entire heart failure disease continuum. Enthusiasm for future application needs to be tempered with the practicalities of delivering safe and effective care within the confines of finite healthcare resources.     

Cardiac Resynchronization Therapy in Pediatric and Congenital Heart Disease

Cardiac resynchronization therapy (CRT) is an emerging option for treating dyssynchrony-associated heart failure in patients with pediatric or congenital heart disease. CRT has proved beneficial for both the acute manipulation of cardiac output after surgery for congenital heart defects and for the management of chronic systemic ventricular failure. Although there are no prospective and randomized trial data, retrospective series show that CRT is similarly effective for managing dyssynchrony-associated heart failure in this younger population as it is for treating adults with ischemic and idiopathic dilated cardiomyopathy. The heterogeneity of anatomical and functional substrates in which CRT shows efficacy calls for further studies defining the usefulness of CRT in specific subgroups of patients.     

Cardiac resynchronization therapy and the role of nuclear cardiology

Cardiac resynchronization therapy (CRT) is an accepted treatment modality in patients with endstage heart failure despite optimal pharmacologic therapy. Although considerable benefit of CRT has been demonstrated in large clinical trials, a substantial cohort of patients failed to respond to CRT. Accordingly, studies have focused on potential predictors for CRT response, and the relative merits of left ventricular dyssynchrony, viability, and scar tissue for CRT response have been demonstrated. Nuclear cardiology techniques can provide this information, particularly gated myocardial perfusion single photon emission CT with phase analysis, and this technique can be used to improve selection of CRT candidates. Also, nuclear imaging can be used to evaluate effects of CRT (changes in blood flow, oxidative metabolism, glucose utilization, and sympathetic innervation). The use of nuclear imaging in selection of CRT patients, and evaluation of CRT effects, are reviewed here.     

Antiinflammatory effects of cardiac resynchronization therapy in patients with chronic heart failure

BACKGROUND: Cardiac resynchronization therapy (CRT) pacing has been proposed as an additional treatment to medical therapy to improve heart failure patients with left ventricular asynchrony. The aim of this study was to evaluate the influence of CRT treatment on proinflammatory cytokines in patients with heart failure. METHODS: Twenty patients, with a mean age 64 +/- 2 years, with severe chronic heart failure NYHA class II-IV (mean ejection fraction 25 +/- 2%), were included in the study. Patients were treated with CRT pacing, after failure of optimal therapy. Blood samples were taken at baseline, 3 months after pacing therapy, and after a subsequent 3-month period of no pacing for the assessment of proinflammatory cytokines TNF-alpha and its receptors (sTNFR-I, sTNFR-II), IL-6, adhesion molecules sICAM-1 and sVCAM-1, and the apoptotic indices sFas and sFas-Ligand. RESULTS: Levels of TNF-alpha, sTNFR-I, and sTNFR-II were reduced at the end of 3 months of CRT therapy and further reduced at the end of the no pacing period (P < 0.05, compared to baseline). Levels of IL-6 also declined after 3 months of CRT pacing (from 8.9 +/- 2.5 pg/mL to 4.7 +/- 1.3 pg/mL, P < 0.05) and this was maintained during the no pacing period (3.9 +/- 1.1 pg/mL P < 0.05 compared to baseline). The adhesion molecule sICAM-1 levels also reduced (from 265 +/- 17 ng/mL to 235 +/- 12, P < 0.05) after 3 months of CRT pacing and remained unchanged at the end of the no pacing period (219 +/- 12 ng/mL, P < 0.05 compared to baseline values). CONCLUSION: Major proinflammatory cytokines and the adhesion molecule sICAM-1 are reduced with CRT therapy and this effect is maintained for at least 3 months after discontinuation of pacing.     

Role of nuclear cardiology for guiding device therapy in patients with heart failure

Heart failure is a dynamic condition with high morbidity and mortality and its prognosis should be reassessed frequently, particularly in patients for whom critical treatment decisions may depend on the results of prognostication. In patients with heart failure, nuclear cardiology techniques are useful to establish the etiology and the severity of the disease, while fewer studies have explored the potential capability of nuclear cardiology to guide cardiac resynchronization therapy(CRT) and to select patients for implantable cardioverter defibrillators(ICD). Left ventricular synchrony may be assessed by radionuclide angiography or gated singlephoton emission computed tomography myocardial perfusion scintigraphy. These modalities have shown promise as predictors of CRT outcome using phase analysis. Combined assessment of myocardial viability and left ventricular dyssynchrony is feasible using positron emission tomography and could improve conventional response prediction criteria for CRT. Preliminary data also exists on integrated positron emission tomography/computed tomography approach for assessing myocardial viability, identifying the location of biventricular pacemaker leads, and obtaining left ventricular functional data, including contractile phase analysis. Finally, cardiac imaging with autonomic radiotracers may be useful in predicting CRT response and for identifying patients at risk for sudden cardiac death, therefore potentially offering a way to select patients for both CRT and ICD therapy. Prospective trials where imaging is combined with image-test driven therapy are needed to better define the role of nuclear cardiology for guiding device therapy in patients with heart failure.     

Geometrical and electrical predictors of cardiac resynchronization therapy response

Several studies have demonstrated the beneficial effect of cardiac resynchronization therapy (CRT) in patients with drug-refractory heart failure. A variable proportion, up to 30%, of CRT patients do not benefit from treatment. The lack of response to CRT has a variety of potential causes. The implantation process is fundamental to the success of CRT, since little can subsequently be done to improve the CRT response. The authors reviewed all the geometrical and electrical parameters that could guide the CRT implant and predict its response.     

Use of Triple-Site Ventricular Pacing in a Patient with Severe Congestive Heart Failure and Atrial Fibrillation

Cardiac resynchronization therapy (CRT) has become an accepted treatment for selected patients with drug-resistant heart failure. Data for patients in atrial fibrillation (AF) remains limited but suggests benefit in these patients too. We report the case of an 82-year-old patient with heart failure, VVIR permanent pacemaker, and permanent AF who had an upgrade to triple-site CRT implantation with good clinical response. Triple-site ventricular pacing may enhance the chance of response and LV reverse remodeling and should be considered in AF patients undergoing CRT implantation.     

Magnetic resonance criteria for future trials of cardiac resynchronization therapy.

Current patient selection criteria for Cardiac Resynchronization Therapy (CRT), an efficacious treatment for heart failure, include no measure of disconjugate cardiac contractility other than prolonged QRS on electrocardiogram. Using cardiac magnetic resonance imaging, we examined the roles of cardiac asymmetry, asynchrony, and circumferential strain in DCC with the principal aim of generating a robust numerical index for use in future trials of CRT. Standard cardiac magnetic resonance imaging was done on a GE 1.5 Tesla Signa LX MRI clinical scanner (GE Healthcare, Milwaukee, WI, USA) and analyzed by MASS Analysis (MEDIS, Leiden, The Netherlands). The methods were evaluated in eleven patients with advanced heart failure due to ischemic and non-ischemic cardiomyopathy, who did not qualify under current criteria for CRT, five CRT candidates pre-op and eleven normal subjects. Using t-test and standardized differences (SD = sd/diff, Power (N) = number of patients to reach p < .05) we determined efficacy. Indices of asymmetry and asynchrony (Ism and Isn, respectively) could be measured with accuracy and provided excellent statistical power when used as surrogate markers to delineate heart failure and CRT patients from control subjects. Asymmetry and asynchrony in heart contraction are both critical components of dilated cardiomyopathy that can be improved by CRT. Magnetic resonance asynchrony is efficacious in screening patients and should now be compared with recently published echocardiography data to improve outcome for this costly but valuable therapy.     

Cardiac resynchronization therapy

Despite recent advances in pharmacologic treatment for heart failure, the prognosis of patients with chronic heart failure remains poor. One third of patients with chronic heart failure have intraventricular conduction delay. The ventricular mechanical dyssynchrony based on intraventricular conduction delay worsen ventricular systolic dysfunction. Cardiac resynchronization therapy(CRT) through biventricular pacing significantly improves symptoms, exercise tolerance, hemodynamics, hospitalization for heart failure and mortality. However, it is estimated that 30 % of patients do not respond to CRT. A direct assessment of mechanical dyssynchrony with echocardiography seems more important than QRS duration in selecting appropriate patients for CRT.     

Reverse remodeling with resynchronization in an asymptomatic patient with dilated hypokinetic cardiomyopathy

Cardiac resynchronization therapy (CRT) is a validated treatment for selected heart failure patients who remain highly symptomatic despite optimal drug treatment. Yet there is currently no indication for CRT in patients with few or no symptoms. We report a spectacular "reverse remodeling" effect after CRT in an asymptomatic patient with hypokinetic dilated myocardiopathy who needed pacing for atrio-ventricular conduction disorder. CRT was chosen to prevent deterioration of left ventricular function by conventional right apical pacing. Thus, CRT could be indicated in patients with hypokinetic dilated myocardiopathy before the appearance of symptoms.     

Recent advances in cardiac resynchronization therapy: echocardiographic modalities,patient selection,optimization, non-responders—all you need to know for more efficient CRT

Cardiac Resynchronization Therapy (CRT) constitutes an established way of treatment for patients suffering from severe heart failure. However, this technologically based and expensive mode of therapy may not be effective for a substantial number of individuals. Recent research and advanced echocardiographic modalities have provided new insight on the proper patient selection, lead implantation, optimization and reasons for non-response. Based on this evidence, an overall assessment of parameters that appear to contribute significantly to the outcome of CRT in addition to electrical or mechanical dyssynchrony, seems to be a reasonable approach for more effective resynchronization therapy.     

Biventricular pacing for treating heart failure in children: A case report and review of the literature

BACKGROUND Cardiac resynchronization therapy(CRT) can be used as an escalated therapy to improve heart function in patients with cardiac dysfunction due to long-term right ventricular pacing. However, guidelines are only targeted at adults. CRT is rarely used in children.CASE SUMMARY This case aimed to implement biventricular pacing in one child with heart failure who had a left ventricular ejection fraction < 35% at 4 years after implantation of an atrioventricular sequential pacemaker due to atrioventricular block.Postoperatively, echocardiography showed atrial sensing ventricular pacing and QRS wave duration of 120-130 ms, and cardiac function significantly improved after upgrading pacemaker.CONCLUSION Patients whose cardiac function is deteriorated to a level to upgrade to CRT should be upgraded to reverse myocardial remodeling as soon as possible.     

Cardiac resynchronisation therapy for heart failure

Cardiac resynchronisation therapy (CRT) reduces symptoms and improves left ventricular function in chronic heart failure (CHF) patients with left ventricular systolic dysfunction and prolonged QRS duration. Recent studies have demonstrated a reduction in mortality associated with CRT. When combined with an implantable cardioverter defibrillator (ICD) reduction in mortality is likely to reduce further. Cardiac resynchronisation therapy is well tolerated and free from compliance issues and therefore should be considered for all suitable patients. Identifying patients who will derive maximum benefit requires further study and has health economic implications. We review here the CRT trial evidence as well as the implantation technique and complications. We also describe a case report where an intra-aortic balloon pump was used successfully as a bridge to CRT to treat a patient with end-stage heart failure.     

心脏再同步治疗起搏器与心脏再同步治疗除颤器对心力衰竭患者预后影响的荟萃分析

目的 比较心脏再同步治疗起搏器(cardiac resynchronization therapy,CRT)与心脏再同步治疗除颤器(cardiac resynchronization therapy -defibrillator,CRT-D)对心力衰竭患者预后的影响.方法 通过计算机和手工检索MEDLINE、Cochrane临床试验中心登记库、EMBASE和中国万方、中国知网(CNKI)数据库,收集1990年1月1日至2011年9月30日CRT与CRT-D对心力衰竭患者生存疗效影响的随机对照研究、前瞻观察性研究和病例对照研究.按纳入标准与排除标准选择文献,提取资料,采用RevMan 5.0软件对患者全因病死率、心脏猝死率和心衰病死率数据进行荟萃分析.结果 共纳入7项研究3404例患者,结果提示CRT-D组全因病死率低于CRT组(OR =0.61,95％ CI:0.47～0.79,P=0.01),亚组分析显示随访时间≤1年差异无统计学意义(OR =0.76,95％ CI:0.54 ～ 1.06,P=0.11),随访时间＞1年差异有统计学意义(OR=0.56,95％ CI:0.41～0.77,P=0.0004).CRT-D组心源性猝死(OR=0.20,95％ CI:0.07～0.59,P=0.003)和心衰病死(OR =0.72,95％ CI:0.54～0.96,P=0.02)也分别低于CRT组.结论 CRT-D对心力衰竭患者的预后可能优于CRT.     

Patient-specific electromechanical models of the heart for the prediction of pacing acute effects in CRT: a preliminary clinical validation

Cardiac resynchronisation therapy (CRT) is an effective treatment for patients with congestive heart failure and a wide QRS complex. However, up to 30% of patients are non-responders to therapy in terms of exercise capacity or left ventricular reverse remodelling. A number of controversies still remain surrounding patient selection, targeted lead implantation and optimisation of this important treatment. The development of biophysical models to predict the response to CRT represents a potential strategy to address these issues. In this article, we present how the personalisation of an electromechanical model of the myocardium can predict the acute haemodynamic changes associated with CRT. In order to introduce such an approach as a clinical application, we needed to design models that can be individualised from images and electrophysiological mapping of the left ventricle. In this paper the personalisation of the anatomy, the electrophysiology, the kinematics and the mechanics are described. The acute effects of pacing on pressure development were predicted with the in silico model for several pacing conditions on two patients, achieving good agreement with invasive haemodynamic measurements: the mean error on dP/dt_max is 47.5 ± 35 mm Hg s⁻¹, less than 5% error. These promising results demonstrate the potential of physiological models personalised from images and electrophysiology signals to improve patient selection and plan CRT.     

Economic analysis of a randomized trial of biventricular pacing in Canada

BACKGROUND: Congestive heart failure (CHF) has been shown to affect 5% of the Canadian adult population, and leads to 9.5 deaths per 100 cardiac-related hospitalizations in Canada. The economic outcomes from biventricular pacing for heart failure are not well understood. This study analyzes resource utilization and related costs associated with CHF for patients who receive standard implantable cardiac defibrillators (ICDs) versus those who receive ICD plus biventricular pacing or cardiac resynchronization therapy (CRT). METHODS: The Canadian analysis of resynchronization therapy in heart failure (CART-HF) study included 72 patients with New York Heart Association class II-IV CHF requiring an ICD. Patients were randomized to receive either ICD + CRT treatment or ICD treatment alone. Medical resource utilization data were collected for 6 months following treatment and were applied to representative costs for the provinces of Quebec and Ontario. Resource utilization was subcategorized into pharmacological therapy, physician visits, hospitalizations, adverse events, and productivity losses. RESULTS: Post-treatment, per patient costs for the CRT + ICD treatment group were less than the follow-up costs for patients receiving ICD treatment only in each province. Mean savings for patients receiving biventricular therapy were CAD 2,420 dollars in Quebec and CAD 2,085 dollars in Ontario during the 6-month follow-up. CONCLUSIONS: These analyses indicate that savings in post-implant health-care utilization (hospitalizations and pharmacological therapy) can offset some of the device and procedural costs associated with CRT devices.     

Drug and device therapy for patients with chronic heart failure

Untreated heart failure is a terminal illness with a poor prognosis. β-blockers are an established therapy used to reduce morbidity and mortality. Hypotension and bradycardia often hinder optimal β-blocker administration in patients with chronic heart failure. The efficacy of cardiac resynchronization therapy (CRT) in affecting favorable cardiac remodeling and reducing mortality in heart failure patients with electrical dyssynchrony has been demonstrated in landmark trials only in patients receiving optimal medical therapy. This paper demonstrates the favorable effects of CRT on cardiac hemodynamics facilitating uptitration of β-blocker therapy. It highlights the synergistic relationship of the two therapies and emphasizes the importance of optimizing medical therapy before and after CRT implantation.     

Assessing reverse remodeling in heart failure patients treated with cardiac resynchronization therapy and its impact on prognosis

Cardiac resynchronization therapy (CRT) has become an alternative for patients with systolic dysfunction and persistence of heart failure symptoms despite optimal medical therapy. The role of noninvasive cardiac imaging before device implantation still remains controversial, but they are essential to provide an objective evidence of reverse remodeling of the heart which is, in turn, also related to the outcome of patients treated with CRT. The objective of this review is to highlight the acute and long-term CRT benefits as assessed by imaging, with special focus in cardiac reverse remodeling and its impact on prognosis.     

Left ventricular dysfunction after cardiac resynchronization therapy in congenital heart disease patients with a failing systemic right ventricle

Background: Cardiac resynchronization therapy is rapidly emerging as an effective strategy for managing ventricular dysfunction and heart failure associated with congenital heart disease. Indications for therapy, optimal lead placement, and late outcomes are however lacking.
Methods: We present three patients, one with Mustard procedure and two with congenitally corrected transposition of great arteries, who developed subpulmonic ventricular dysfunction 3–6 months after biventricular pacing ± implantable cardioverter defibrillator implantation, despite initial favorable result of resynchronization therapy. Possible factors for adverse outcome are relatively high pacing rate, unfavorable alteration of torsional contraction, and increased atrioventricular valve regurgitation due to suboptimal placement of larger diameter defibrillation leads.
Results: Careful evaluation of patients, particularly indications for therapy, need to be rigorous; assessment of hemodynamic response at the time of implant and appropriate programming may improve the effectiveness of cardiac resynchronization therapy (CRT) in this patient population.
Conclusion: Our case series emphasizes the need for a registry in the absence of randomized controlled trials, in order to identify patients who benefit most from CRT, and, importantly, recognize subgroups that respond poorly.     

Continuously adjusting CRT therapy: clinical impact of adaptive cardiac resynchronization therapy

Cardiac resynchronization therapy (CRT) is a well-established therapy to reduce morbidity and mortality in patients with moderate and severe symptomatic congestive heart failure. Left ventricular (LV) pacing that fuses with intrinsic right ventricular (RV) conduction results in similar or even better cardiac performance compared to biventricular (Biv) pacing. Optimal programming of the atrio-ventricular (AV) and inter-ventricular (VV) delays is crucial to improve LV performance since suboptimal programming of AV and VV delays affect LV filling as well as cardiac output. CRT optimization using echocardiogram is resource-dependent and time consuming. Adaptive CRT (aCRT) algorithm provides a dynamic, automatic, ambulatory adjustment of CRT pacing configuration (Biv or LV pacing) and optimization of AV and VV delays. aCRT algorithm is safe and efficacious for CRT-indicated patients without permanent atrial fibrillation. It has been shown to improve CRT response and reduce morbidity and mortality for patients with normal AV conduction.