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.     

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.     

Imaging techniques in cardiac resynchronization therapy

Cardiac resynchronization therapy is a high cost therapeutic option with proven efficacy on improving symptoms of ventricular failure and for reducing both hospitalization and mortality. However, a significant number of patients do not respond to cardiac resynchronization therapy that is due to various reasons. Identification of the optimal pacing site is crucial to obtain the best therapeutic result that necessitates careful patient selection. Currently, using echocardiography for mechanical dyssynchrony assessment performs patient selection. Multi-Detector-Row Computed Tomography (MDCT) and Magnetic Resonance Imaging (MRI) are new imaging techniques that may assist the cardiologist in patient selection. These new imaging techniques have the potential to improve the success rate of cardiac resynchronization therapy, due to pre-interventional evaluation of the venous coronary anatomy, to evaluation of the presence of scar tissue, and to improved evaluation of mechanical dyssynchrony. In conclusion, clinical issues associated with heart failure in potential candidates for cardiac resynchronization therapy, and the information regarding this therapy that can be provided by the imaging techniques echocardiography, MDCT, and MRI, are reviewed.     

Cardiac CT: Imaging of and Through Cardiac Devices

For patients with cardiac devices, cardiac computed tomography (CT) remains the mainstay for imaging due to its superior resolution as compared with echocardiography and nuclear studies and no contraindication to metal as with cardiac magnetic resonance imaging. This review focuses on the evaluation and pitfalls of coronary arterial imaging in patients with devices, such as pacemakers, implantable defibrillators, cardiac resynchronization therapy (CRT), as well as complications such as lead perforation and safety concerns of CT interference. We discuss both pre- and post-procedural CRT assessment for coronary venous imaging and pre-procedural myocardial scar assessment to localize regions of scar and peri-infarct zone to facilitate ventricular tachycardia ablation in patients with devices. We describe potential new research on dyssynchrony and integration with myocardial scar and site of latest activation for patients with or being considered for CRT. We detail the utility of CT for the assessment of proper function and complications in patients with left ventricular assist device implantation.     

The role of multi modality imaging in selecting patients and guiding lead placement for the delivery of cardiac resynchronization therapy

Introduction: Cardiac resynchronization therapy (CRT) is an effective pacemaker delivered treatment for selected patients with heart failure with the target of restoring electro-mechanical synchrony. Imaging techniques using echocardiography have as yet failed to find a metric of dyssynchrony to predict CRT response. Current guidelines are thus unchanged in recommending prolonged QRS duration, severe systolic function and refractory heart failure symptoms as criteria for CRT implantation. Evolving strain imaging techniques in 3D echocardiography, cardiac MRI and CT may however, overcome limitations of older methods and yield more powerful CRT response predictors.

Areas covered: In this review, we firstly discuss the use of multi modality cardiac imaging in the selection of patients for CRT implantation and predicting the response to CRT. Secondly we examine the clinical evidence on avoiding areas of myocardial scar, targeting areas of dyssynchrony and in doing so, achieving the optimal positioning of the left ventricular lead to deliver CRT. Finally, we present the latest clinical studies which are integrating both clinical and imaging data with X-rays during the implantation in order to improve the accuracy of LV lead placement.

Expert commentary: Image integration and fusion of datasets with live X-Ray angiography to guide procedures in real time is now a reality for some implanting centers. Such hybrid facilities will enable users to interact with images, allowing measurement, annotation and manipulation with instantaneous visualization on the catheter laboratory monitor. Such advances will serve as an invaluable adjunct for implanting physicians to accurately deliver pacemaker leads into the optimal position to deliver CRT.     

Noninvasive Assessment of Myocardial Dyssynchrony Prior to Cardiac Resynchronization Therapy

Cardiac resynchronization therapy (CRT) has proven to be of benefit in patients with heart failure and evidence of dyssynchrony. QRS duration is the most widely applied measure of dyssynchrony but this is accepted to be an imperfect measure. There has been much focus on the use of imaging, particularly echocardiography, in identifying mechanical dyssynchrony but results from multi-center studies have proved disappointing. Cardiac magnetic resonance (CMR) imaging has inherent advantages over echocardiography in terms of image resolution and there have been several studies looking at the use of both simple and complex CMR measures as markers of dyssynchrony. In this review, we describe the advances in CMR assessment of dyssynchrony.     

The Contemporary Role of Echocardiography in Improving Patient Response to Cardiac Resynchronization Therapy

Cardiac resynchronization therapy (CRT) is an important therapy for heart failure patients with widened electrocardiographic QRS complexes and depressed ejection fractions, however, approximately one-third do not respond. This article presents a practical contemporary approach to the utility of echocardiography to improve CRT patient response by assessing mechanical dyssynchrony, optimizing left ventricular lead positioning, and performing appropriate echo-Doppler optimization, along with future potential roles. Specifically, recent long-term outcome data are presented that demonstrates that baseline dyssynchrony is a powerful marker associated with CRT response, in particular for patients with narrower QRS duration or non left bundle branch block morphology. Advances in speckle tracking echocardiography to tailor delivery of CRT by guiding LV lead position is discussed, including data from randomized clinical trials supporting targeting the LV lead toward the site of latest activation. In addition, an update on the current role of Doppler echocardiographic device optimization after CRT implantation is reviewed.     

Prevalence of mechanical dyssynchrony in heart failure patients with different QRS durations

BACKGROUND: Cardiac resynchronization therapy (CRT) has emerged as an established therapy for congestive heart failure. However, up to 30% of patients fail to respond to CRT despite prolonged QRS. OBJECTIVES: This study aimed at defining the prevalence of interventricular and intraventricular dyssynchrony in heart failure patients with different QRS durations. METHODS: A total of 123 consecutive patients with severe heart failure (LVEF < 35% and NYHA class III-IV) were prospectively evaluated using 12-lead electrocardiogram and complete echocardiographic examination including tissue Doppler imaging. RESULTS: According to the QRS duration, 56 patients had a QRS duration < or = 120 ms (Group 1), 33 patients had a QRS duration between 120 and 150 ms (Group 2), and 34 patients had a QRS duration > or = 150 ms (Group 3). Intraventricular dyssynchrony was present in 36% of Group 1 patients, in 58% of Group 2 patients, and in 79% of Group 3 patients (P < 0.000). Linear regression demonstrated a weak relation between QRS and intraventricular dyssynchrony. A greater proportion of patients with interventricular dyssynchrony was observed in Group 3 or Group 2 compared to patients with normal QRS duration (32% in Group 1 vs. 51.5% in Group 2 vs. 76.5% in Group 3, P < 0.000). Linear regression demonstrated a significant relation between QRS duration and interventricular mechanical delay. CONCLUSIONS: Although both interventricular and intraventricular dyssynchrony increased with the increasing QRS duration, the correlation between intraventricular mechanical and electrical dyssynchrony was weak. The lack of intraventricular dyssynchrony in a fraction of patients with standard CRT indication by QRS duration may provide us insight into the nonresponders rates.     

Biventricular upgrading in patients with conventional pacing system and congestive heart failure: results and response predictors

BACKGROUND: 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 > or = 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 > or = 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.     

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.     

Prediction of Response to Cardiac Resynchronization Therapy: The Selection of Candidates for CRT (SCART) Study

Background: The aim of this study was to evaluate the ability of baseline clinical and echocardiographic parameters to predict a positive response to CRT.
Methods: We analyzed 6-month data from the first 133 consecutive patients enrolled in a multicenter prospective study. These patients had symptomatic heart failure (HF) refractory to pharmacological therapy (NYHA class II–IV), left ventricular ejection fraction (LVEF) ≤35%, and prespecified electrocardiographic, echocardiographic or tissue Doppler imaging markers of left ventricular (LV) dyssynchrony.
Results: After a follow-up period of 6 months, 1 patient died and 13 were hospitalized for worsening HF. There were significant (P < 0.01) clinical, functional, and echocardiographic improvements that included: New York heart Association Class, Quality-of-Life Score, QRS duration, LVEF, LV end-diastolic and end-systolic diameter (LVESD), and severity of mitral regurgitation A positive response was documented in 90/133 (68%) patients who presented an improved clinical composite score associated to an increase in LVEF ≥ 5 units. A multivariate analysis identified that a smaller LVESD (OR = 0.957, 95% CI 0.920–0.996; P = 0.030) and longer interventricular mechanical delay (IVMD) (OR = 1.017, 95% CI 1.005–1.029, P = 0.007) as independent predictors of a positive response. Receiver-operating curve analysis showed that a positive response to CRT may be predicted in patients with IVMD > 44 ms (with a sensitivity of 66% and a specificity of 55%) or with LVESD < 60 mm (with a sensitivity of 66% and a specificity of 61%).
Conclusions: Our results confirm the limited value of QRS duration in the selection of patients for CRT.
A less-advanced stage of disease and echocardiographic evidence of interventricular dyssynchrony demonstrated to predict response to CRT, while intraventricular dyssynchrony did not predict response.     

Echocardiographic Modeling of Cardiac Dyssynchrony Before and During Multisite Stimulation: A Prospective Study

CAZEAU, S., et al.: Echocardiographic Modeling of Cardiac Dyssynchrony Before and During Multisite Stimulation: A Prospective Study. Multisite biventricular pacing therapy offers significant clinical improvement in some stimulated patients with electrocardiographic criteria of cardiac dyssynchrony. However, observational data increasingly suggest that patients suffering from congestive heart failure in presence of modest QRS widening may also derive benefit from cardiac resynchronization therapy (CRT), and that some patients can be significantly improved clinically after system implantation despite no apparent change in QRS width. This pilot study explored the value of an echocardiographic model to identify cardiac electromechanical dyssynchrony parameters (EDP) in candidates for CRT, and their potential correction after implantation. The study included 66 consecutive CRT recipients of CRT in NYHA functional class III or IV who had one or more atrioventricular, interventricular or intraventricular dyssynchrony criteria. An immediate improvement was observed in 85% of the population with a partial or total correction of their EDP. However, the modifications in EDP differed considerably between recipients of de novo CRT systems and patients with previously implanted standard pacing systems upgraded with the implantation of a left ventricular lead. EDP measurements appear to identify potential candidates for CRT, and to confirm the success of system implantation. (PACE 2003; 26[Pt. II]:137–143)     

SPECT and Cardiac Resynchronization Therapy

Cardiac resynchronization therapy (CRT) has proven benefits in patients with refractory heart failure including improved symptoms, exercise capacity, quality of life, and left ventricular (LV) function, and mortality benefits. At present, CRT is recommended in patients with severe refractory heart failure (New York Heart Association class III or IV), LV ejection fraction ≤ 35%, QRS duration ≥ 120 ms, and sinus rhythm. When selected based on these standard indications, 20% to 40% of patients fail to respond to CRT. Important parameters for predicting CRT response, such as LV mechanical dyssynchrony, myocardial scar, and LV pacing lead position, have been studied using phase analysis of gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). This review aims to describe the role of gated SPECT MPI for the comprehensive assessment of those parameters for selection of patients for CRT.     

Nuclear Cardiology for the Prediction of Response to Cardiac Resynchronization Therapy

Purpose of Review

About one-third patients selected for cardiac resynchronization therapy (CRT) based on conventional criteria do not show favourable response. Assessment of cardiac mechanical dyssynchrony by nuclear medicine techniques has generated considerable interest in recent years as an additional tool to improve the outcome of patients submitted to CRT.

Recent Findings

Several studies in recent years have shown the utility of equilibrium radionuclide angiography (ERNA) and gated myocardial perfusion SPECT (GMPS) in predicting response to CRT. Both ERNA and GMPS can assess cardiac mechanical dyssynchrony quantitatively; GMPS in addition can also provide information on the presence of scar and site of the latest mechanical activation, thereby determining the optimal site of lead placement. Limited studies have also shown the utility of gated blood-pool SPECT, gated myocardial PET and cardiac autonomic imaging in predicting response to CRT.

Summary

Nuclear medicine techniques are useful for prediction of response to CRT.

     

Cardiac resynchronization therapy for heart failure management

Heart failure (HF) is responsible for an immense burden on our healthcare system. The prevalence of this disease continues to increase as a result of an aging population, successful treatment of acute coronary syndrome, and the use of new pharmacotherapies. Although pharmacotherapy with angiotensin converting enzyme inhibitors and beta-blockers shows improvement in morbidity and mortality, the overall prognosis of these patients remains poor. Cardiac transplant has limited applicability. Conduction disturbances are frequent in patients with advanced heart failure and may cause worsening systolic function and ventricular dyssynchrony. Biventricular pacing to achieve cardiac resynchronization is a recent and promising therapy for HF patients with an intraventricular conduction defect. Randomized clinical trials have substantiated that cardiac resynchronization therapy (CRT) through biventricular pacing offers significant benefit in morbidity and mortality in a select group of HF patients. Because of the high incidence of sudden cardiac death in patients with severe HF, the combination biventricular pacing with implantable cardioverter defibrillator therapy will provide additional benefit. This article provides an overview of CRT with the intent of describing ventricular dyssynchrony, the benefits of CRT, and the implications for advanced practice nurses.     

Profiling cardiac resynchronization therapy patients: responders,non-responders and those who cannot respond—<Emphasis Type="Italic">The good,the bad and the ugly?</Emphasis>

Cardiac resynchronization therapy (CRT) is an effective option for the management of heart failure (HF) patients with left ventricular systolic dysfunction and prolongation of the QRS interval. Unfortunately, a variable proportion of eligible patients fail to benefit from this treatment, the so-called “non-responders”. Despite intensive investigations aimed at identifying reliable diagnostic tools, additional to standard criteria, for the selection of responders, partly due to the complexity and multi-factorial nature of the mechanism underlying response, no conclusive evidence is currently available about which of the many variables assessed may predict individual response and should be included in selection criteria. Accordingly, even if labeled as a non-responder, a patient should receive a CRT device being the certain risk of withholding the treatment more consistent than the potential risk of being a non-responder. However, a possible third profile of patients along with responders and non-responders is emerging consisting of a limited subset of individuals, mainly among those with HF of ischemic aetiology, who simply do not possess the anatomical requisite for conventional biventricular pacing to be effective. Such patients may be referred to as those who cannot respond to CRT and their identification is potentially feasible by integrating non-invasive imaging findings and of clinical relevance in the definition of the therapeutic strategy. In conclusion, this review will provide an analysis of gathered data about the selection of candidates to CRT beyond responders and non-responders with the perspective of the potential characterization of patients who cannot respond to CRT.     

CT冠状静脉成像与室壁运动评价用于心脏再同步化治疗

心脏再同步化治疗（CRT）在心力衰竭合并心室电-机械失同步的治疗中取得了令人满意的成就，但部分患者对CRT低反应或无反应。将左心室起搏电极置于心室最延迟收缩区域的冠状静脉属支内可避开瘢痕负荷过重区域，提高CRT应答率，最大限度提高临床获益。CRT术前较全面获取冠状静脉解剖及延迟收缩的心肌节段等信息，对确定左心室起搏电极植入部位有重要意义。本文针对CT冠状静脉成像及室壁运动评价用于CRT的进展进行综述。     

Male gender and chronic obstructive pulmonary disease predict a poor clinical response in patients undergoing cardiac resynchronisation therapy

Aims: Current guidelines advocate cardiac resynchronisation therapy (CRT) in patients with class III/IV New York Heart Association (NYHA) heart failure, depressed left ventricular function and a broad QRS. However, a significant proportion of patients do not derive any benefit from CRT. The aim of this study was to identify clinical, electrocardiographic and echocardiographic predictors of response to CRT. Methods: A retrospective analysis of patients undergoing CRT in our institution was performed. A favourable clinical response to CRT was defined as an improvement in NYHA Heart failure class of ≥ 1 and lack of hospitalisation with heart failure. Comparisons were made between responders and non‐responders in terms of baseline characteristics and potential predictors of CRT response (QRS width, presence of left bundle branch block, atrial fibrillation, evidence of mechanical dyssynchrony on echocardiography and LV lead position). Results: A total of 164 patients had full follow‐up data. The mean follow‐up was 293 days. Of patients undergoing CRT, 90 (58.9%) had a favourable clinical response to CRT. Predictors of a lack of clinical response to CRT were male gender (p = 0.012) and chronic obstructive pulmonary disease (COPD) (0.008). Pre‐implant echocardiographic dyssynchrony assessment appeared not to predict response to CRT (p = 0.87); however, there was a trend towards a positive response in those patients with significant dyssynchrony (p = 0.09) defined as interventricular delay > 40 ms or maximal LV delay of > 80 ms. Conclusion: Male gender and coexisting COPD were shown to be independent predictors of non‐response to CRT in this cohort of patients fulfilling current criteria for CRT.     

Cardiac resynchronization therapy guided by cardiovascular magnetic resonance

Cardiac resynchronization therapy (CRT) is an established treatment for patients with symptomatic heart failure, severely impaired left ventricular (LV) systolic dysfunction and a wide (> 120 ms) complex. As with any other treatment, the response to CRT is variable. The degree of pre-implant mechanical dyssynchrony, scar burden and scar localization to the vicinity of the LV pacing stimulus are known to influence response and outcome. In addition to its recognized role in the assessment of LV structure and function as well as myocardial scar, cardiovascular magnetic resonance (CMR) can be used to quantify global and regional LV dyssynchrony. This review focuses on the role of CMR in the assessment of patients undergoing CRT, with emphasis on risk stratification and LV lead deployment.