Cardiac Resynchronization Therapy

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Individualized cardiac resynchronization therapy: current status

Individualized cardiac resynchronization therapy: current status

Abstract: Cardiac resynchronization therapy (CRT) has shown a substantial reduction in heart failure patient morbidity and mortality, with improvement in quality of life as well as symptoms. The therapy is, however, limited to approximately 10%–15% of heart failure patients and, typi- cally, 30% do not derive benefit from the device. For optimal outcomes with CRT, the correct selection of patients is of paramount importance. The first parameter is depressed left ventricular systolic function, and the second is a wide QRS complex. Different nuances among clinical tri- als have rendered guidelines pragmatic and compromising, but also conflicting and confusing. A large proportion of real-life CRTs are implanted in patients where the evidence for benefit is scarce or not present. Further, for optimal benefit, patients require evidence-directed medi- cal therapy at maximal doses, effective placement of ventricular leads, and high biventricular pacing percentages, along with optimized atrioventricular (AV) and interventricular interval device programming. These items, as well as specific clinical characteristics, such as AV block and atrial fibrillation, in the context of CRT indications, are discussed. This review focuses on these issues to guide the clinician through guidelines, with an evidence-based update on the current status of CRT.
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Improvement in circulating endothelial progenitor cells pool after cardiac resynchronization therapy: increasing the list of benefits

Improvement in circulating endothelial progenitor cells pool after cardiac resynchronization therapy: increasing the list of benefits

ACE-inhibitors: Angiotensin-converting enzyme inhibitors; ASA: Aspirin; CRT: Cardiac resynchronization therapy; DCM: Dilated cardiomyopathy (non- ischemic cardiomyopathy); EDTA: Ethylenediaminetetraacetic acid; EPCs: Endothelial progenitor cells; FITC: Fluorescein isothiocyanate; HF: Heart failure; HFrEF: Heart failure with reduced ejection fraction; ICM: Ischemic cardiomyopathy; IL: Interleukin; LVEDV: Left ventricular end-diastolic volume; LVEF: Left ventricular ejection fraction; LVESV: Left ventricular end-systolic vol- ume; NYHA: New York Heart Association; NOS: Nitric oxide synthase; PE: Phycoerythrin; SDF-1: Stromal cell-derived factor 1; TNF: Tumor necrosis factor; VEGF-R2: Type 2 vascular endothelial growth factor receptor
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Cardiac resynchronization therapy pacemaker: critical appraisal of the adaptive CRT-P device

Cardiac resynchronization therapy pacemaker: critical appraisal of the adaptive CRT-P device

Abstract: Cardiac resynchronization therapy (CRT) is an effective and well-established therapy for patients suffering with heart failure, left ventricular (LV) systolic dysfunction (ejection frac- tion #35%), and electrical dyssynchrony, demonstrated by a surface QRS duration of $120 ms. Patients undergoing treatment with CRT have shown significant improvement in functional class, quality of life, LV ejection fraction, exercise capacity, hemodynamics, and reverse remodeling of LV, and ultimately, morbidity and mortality. However, 30%–40% of patients who receive a CRT device may not show improvement, and they are termed as non responders. The nonresponders have a poor prognosis; several methods have been developed to try to enhance response to CRT. Echocardiography-guided optimization of CRT has not resulted in significant clinical benefit, since it is done at rest with the patient in supine position. An ideal optimiza- tion strategy would provide continuous monitoring and adjustment of device pacing to provide maximal cardiac resynchronization, under a multitude of physiologic states. Intrinsic activation of the right ventricle (RV) with paced activation of the RV, even in the setting of biventricular (BiV) pacing, may result in an adverse effect on cardiac performance. With this physiology, the use of LV-only pacing may be preferred and may enhance CRT. Adaptive CRT is a novel device-based algorithm that was designed to achieve patient-specific adjustment in CRT so as to provide appropriate BiV pacing or LV-only pacing. This article will review the goals of CRT optimization, and implementation and outcomes associated with adaptive CRT.
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Successful Treatment of Cardiac Failure Due to Cardiomyopathy in Propionic Acidemia by Cardiac Resynchronization Therapy and Hemodialysis in a Young Adult

Successful Treatment of Cardiac Failure Due to Cardiomyopathy in Propionic Acidemia by Cardiac Resynchronization Therapy and Hemodialysis in a Young Adult

Propionic acidemia is an autosomal recessive disorder that is due to deficiency in the enzyme propionyl-CoA carboxylase. Cardiomyopathy is a well-known phenomenon in propionic acidemia that it may rapidly progress to death. Here we describe a case of propionic acidemia in a 27-year- old man who developed adult-onset secondary dilated cardiomyopathy. In early infancy he was diagnosed with propionic acidemia and was later noted to have mild mental retardation, mild renal failure, and optic nerve atrophy. Although he was in good energy status with a low-protein diet and carnitine supplementation, he was admitted to our university hospital with decompen- sate heart failure, which resulted in low-output cardiac syndrome with massive mitral regurgita- tion and left ventricular dyssynchrony. Cardiac resynchronization therapy (CRT) and continuous hemodiafiltration followed by hemodialysis (HD) dramatically improved his clinical status.
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Pacing in heart failure: focus on risk stratification and patient selection
for cardiac resynchronization therapy

Pacing in heart failure: focus on risk stratification and patient selection for cardiac resynchronization therapy

2. Brignole M, Auricchio A, Baron-Esquivias G, Bordachar P, Boriani G, Breithardt OA, Cleland J, Deharo JC, Delgado V, Elliott PM, Gorenek B, Israel CW, Leclercq C, Linde C, Mont L, Pade- letti L, Sutton R, Vardas PE, Guidelines ESCCfP, Zamorano JL, Achenbach S, Baumgartner H, Bax JJ, Bueno H, Dean V, Deaton C, Erol C, Fagard R, Ferrari R, Hasdai D, Hoes AW, Kirch- hof P, Knuuti J, Kolh P, Lancellotti P, Linhart A, Nihoyannopoulos P, Piepoli MF, Ponikowski P, Sirnes PA, Tamargo JL, Tendera M, Torbicki A, Wijns W, Windecker S, Document R, Kirch- hof P, Blomstrom-Lundqvist C, Badano LP, Aliyev F, Bansch D, Baumgartner H, Bsata W, Buser P, Charron P, Daubert JC, Dobreanu D, Faerestrand S, Hasdai D, Hoes AW, Le Heuzey JY, Mavrakis H, McDonagh T, Merino JL, Nawar MM, Nielsen JC, Pieske B, Poposka L, Ruschitzka F, Tendera M, Van Gelder IC, Wilson CM. 2013 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy: the Task Force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA). Eur Heart J 2013; 34: 2281-2329.
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Speckle tracking echocardiography analyses of myocardial contraction efficiency predict response for cardiac resynchronization therapy

Speckle tracking echocardiography analyses of myocardial contraction efficiency predict response for cardiac resynchronization therapy

heterogeneity parameters correlated better with acute re- sponse than the mechanical dyssynchrony parameters, so it’s consist with our conclusion of ECR but not ECTR was one of the predictor for CRT response. Besides, Eschalier R, Lumens J et al. [34, 35] show that Left bun- dle branch block (LBBB) leads to prolonged left ven- tricular total activation time (TAT) and ventricular electrical uncoupling (VEU; mean LV activation time minus mean right ventricular [RV] activation time); both have been shown to be preferential targets for cardiac resynchronization therapy (CRT), our study show the prolonged TCT at baseline in responder group, and it may can be further explained in the electrophysiology of LBBB.
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Pre-implant right ventricular function might be an important predictor of the response to cardiac resynchronization therapy

Pre-implant right ventricular function might be an important predictor of the response to cardiac resynchronization therapy

Objective: Cardiac resynchronization therapy is proven efficacious in patients with heart failure (HF). Presence of biventricular HF is associated with a worse prognosis than having only left ventricular (LV) HF and pacing might deteriorate heart function. The aim of the study was to assess a possible significance of right ventricular (RV) pre- implant systolic function to predict response to CRT.

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A prospective evaluation of cardiovascular magnetic resonance measures of dyssynchrony in the prediction of response to cardiac resynchronization therapy

A prospective evaluation of cardiovascular magnetic resonance measures of dyssynchrony in the prediction of response to cardiac resynchronization therapy

Cardiac resynchronization therapy (CRT) is established as an effective treatment in selected heart failure patients with evidence of dyssynchrony, improving both morbidity and mortality [1]. Despite advances in imaging and device technology, the clinical non-responder rate has remained static at approximately 30% [2], whilst the proportion failing to demonstrate left ventricular (LV) reverse remodeling (RR) is closer to 40-50% [3]. QRS duration (QRSd) is the most widely utilized marker of dyssynchrony but it is only a moderate predictor of CRT response [4] and does not always correlate with mechanical dyssyn- chrony [5]. The mechanics of myocardial contraction and relaxation are complex with multiple methods currently used to investigate dyssynchrony. This has led to extensive, but ultimately unsuccessful, work in the field of echocardiography to develop imaging based mechanical dyssynchrony measures that improve patient selection [3]. It is not entirely clear if the concept of mechanical dyssynchrony is flawed or if the most widely used method of measuring it (echocardiography) is the limiting factor. There are inherent limitations with echocardiography such as sub-optimal image quality and associated problems with reproducibility and these may impact the integrity of any data acquired. Addition- ally, analysis methods based on echo Doppler largely look at two-dimensional longitudinal motion and this may over-simplify the complex mechanisms involved in myo- cardial contraction. Newer echocardiographic techniques that use speckle tracking to measure strain have been advocated as better methods of measuring mechanical dysynchrony and CRT response but this has yet to be demonstrated in a multi-center setting [6,7].
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Techniques for Identification of Left Ventricular Asynchrony for Cardiac Resynchronization Therapy in Heart Failure

Techniques for Identification of Left Ventricular Asynchrony for Cardiac Resynchronization Therapy in Heart Failure

The most recent treatment option of medically refractory heart failure includes cardiac resynchronization therapy (CRT) by biventricular pacing in selected patients in NYHA functional class III or IV heart failure. The widely used marker to indicate left ventricular (LV) asynchrony has been the surface ECG, but seems not to be a sufficient marker of the mechanical events within the LV and prediction of clinical response. This review presents an overview of techniques for identification of left ventricular intra- and interventricular asynchrony. Both manuscripts for electrical and mechanical asynchrony are reviewed, partly predicting response to CRT. In summary there is still no gold standard for assessment of LV asynchrony for CRT, but both traditional and new echocardiographic methods have shown asynchronous LV contraction in heart failure patients, and resynchronized LV contraction during CRT and should be implemented as additional methods for selecting patients to CRT.
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Cardiac resynchronization therapy improves heart failure in one patient with acromegaly induced cardiomyopathy: a case report

Cardiac resynchronization therapy improves heart failure in one patient with acromegaly induced cardiomyopathy: a case report

for management of heart failure following the current guidelines [7]; in the meantime, octreotide (200 μg/day) was administered for the control of GH excess. After good compliance of pharmacotherapy and a regular medical examination regimen for nearly half a year, the serum GH and IGF-1 concentrations decreased from 32.50 ng/ml to 1.98 ng/ml and 627.00 ng/ml to 229.10 ng/ml, re- spectively, but the patient was hospitalized again be- cause of uncontrollable cardiac failure. Accompanied by the normalization of GH and IGF-1 levels, the pa- tient’s cardiac function did not seem to take a favorable turn upon readmission. Though echocardiography showed a recovered EF value from 16% to 28%, a significant ven- tricular mechanical dyssynchrony was detected as formerly. Electrophysiological study was performed using a non- aggressive stimulation protocol, which revealed a non- sustained ventricular monomorphic tachycardia [8]. In the presence of overt ventricular dyssynchrony, complete LBBB, LVEF< 35%, inducible ventricular tachycardia, and symptomatic heart failure despite guideline-directed med- ical therapy, surgical indication was rarely assessed by neu- rosurgeons, and stereotactic radiosurgery together with pharmacotherapy produced infinitesimal effects. Therefore, we boldly recommended cardiac resynchronization therapy with defibrillator (CRT-D) implantation based on device implantation official guidelines [7, 9]. The patient under- went CRT insertion finally and was discharged to home 5 days later, pharmacotherapy continued as usual (Fig. 3).
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Hemodynamic device-based optimization in cardiac resynchronization therapy: concordance with systematic echocardiographic assessment of AV and VV intervals

Hemodynamic device-based optimization in cardiac resynchronization therapy: concordance with systematic echocardiographic assessment of AV and VV intervals

Figure 2 View of hemodynamic sensor amplitude profile and automatic programming of AV + VV intervals during the first 6 months after CRT implant in a (A) super-responder patient ( , 73 years old, ischemic cardiomyopathy, baseline LVEF 34%, 6- months LVEF 55%); (B) View of hemodynamic sensor amplitude profile and automatic programming of AV + VV intervals during the first 6 months after CRT implant in a non-responder patient ( , 51 years old, dilated cardiomyopathy, baseline LVEF 24%, 6- months LVEF 26%) Abbreviations: AV, atrioventricular; VV, ventriculo-ventricular; CRT, cardiac resynchronization therapy; LVEF, left ventricular ejection fraction; RV, right ventricle; LV, left ventricle; ms, milliseconds; R, right; L, left.
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Predictors of clinical outcomes after cardiac resynchronization therapy in patients ≥75 years of age: a retrospective cohort study

Predictors of clinical outcomes after cardiac resynchronization therapy in patients ≥75 years of age: a retrospective cohort study

Cardiac resynchronization therapy (CRT) has become a standard therapy for patients with chronic heart failure (HF) related to reduced left ventricular ejection fraction (LVEF). Large clinical trials have demonstrated CRT benefits on symptoms, quality of life, as well as morbid- ity and mortality reduction [1–4]. The current guidelines recommend CRT for selected patients regardless of age status [5], but older patients, defined as individuals aged ≥65, especially those aged ≥75, have been underrepre- sented in these studies [6]. The prevalence of HF in- creases with age, and the European Survey on CRT reported that the median age of patients with HF was 70, with 31% of the patients being aged ≥75 [7] . A few reports have previously highlighted the feasibility and ef- ficiency of CRT in older patients, but little is known about the predictors of clinical responses in this popula- tion [8–12].
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Strain dyssynchrony index determined by three-dimensional speckle area tracking can predict response to cardiac resynchronization therapy

Strain dyssynchrony index determined by three-dimensional speckle area tracking can predict response to cardiac resynchronization therapy

Background: We have previously reported strain dyssynchrony index assessed by two-dimensional speckle tracking strain, and a marker of both dyssynchrony and residual myocardial contractility, can predict response to cardiac resynchronization therapy (CRT). A newly developed three-dimensional (3-D) speckle tracking system can quantify endocardial area change ratio (area strain), which coupled with the factors of both longitudinal and circumferential strain, from all 16 standard left ventricular (LV) segments using complete 3-D pyramidal datasets. Our objective was to test the hypothesis that strain dyssynchrony index using area tracking (ASDI) can quantify dyssynchrony and predict response to CRT.
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Implementation of seven echocardiographic parameters of myocardial asynchrony to improve the long-term response rate of cardiac resynchronization therapy (CRT)

Implementation of seven echocardiographic parameters of myocardial asynchrony to improve the long-term response rate of cardiac resynchronization therapy (CRT)

Cardiac resynchronization Therapy (CRT) is an effective therapy for chronic heart failure with beneficial hemody- namic effects and a reduction of morbidity and mortality [1-7]. Despite the overall favorable effect of CRT and a lack of a clear definition of hemodynamic benefit, pub- lished responder rates in the large CRT studies are low (43–69%) [8-10]. In the CARE-HF study, only about 50% of the patients responded clinically. The COMPANION study [1] did not publish responder rates (2004). In the CARE-HF study [6] with an observation period of 18 months, about half of the CRT patients had worsening of heart failure, 21% died (of any cause), and 13% had complications caused by CRT (e.g., lead displacement, pneumothorax, infection, dissection, and one implanta- tion-related death). Furthermore, as CRT is an expensive therapy with relatively high complication rates, careful patient selection and definition of predictors are needed. Accounting for the complexity of the parameters of asyn- chrony and the lack of a clear predictor, the indications for CRT in the current guidelines do not include echo param- eters of myocardial asynchrony [11] and an expert state- ment of the ASE justifies patient selection by echo only in borderline cases [12].
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Image guided left ventricular lead implantation for cardiac resynchronization therapy : assessment of the left phrenic nerve and coronary sinus

Image guided left ventricular lead implantation for cardiac resynchronization therapy : assessment of the left phrenic nerve and coronary sinus

Objective. Visualization and implementation of the left phrenic nerve (LPN) and the coronary sinus ostium in CARTBox3 to support left ventricular lead placement in cardiac resynchronization therapy. Introduction. Cardiac resynchronization therapy can be used to resynchronize a dyssynchronous ventricle contraction in patients with heart failure. The response rate of the therapy needs to be improved, since 30% of treated patients do not benefit from the therapy. One of the factors that can improve the response rate is optimal left ventricular lead position. CARTBox3 software was developed to determine an optimal lead position and provides image guided placement of the left ventricular lead to the optimal position during cardiac resynchronization therapy. To complete the CARTBox3 functionality, a way to visualize and segment the LPN course and coronary sinus ostium is developed. Method. A feasibility study of LPN visualization using MRI was performed. Based on the time planning and the availability of CT data it was chosen to develop and validate a method for LPN segmentation using contrast and non-contrast cardiac CTs. The LPN segmentation was implemented into CB3. Also from CT data, the ostium was determined by finding intersection points of segmented right atrium and coronary sinus volumes. Two segmentation methods were tested on contrast and non-contrast cardiac CTs.
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Strain-time curve analysis by speckle tracking echocardiography in cardiac resynchronization therapy: Insight into the pathophysiology of responders vs. non-responders

Strain-time curve analysis by speckle tracking echocardiography in cardiac resynchronization therapy: Insight into the pathophysiology of responders vs. non-responders

Background: Patients with non-ischemic heart failure etiology and left bundle branch block (LBBB) show better response to cardiac resynchronization therapy (CRT). While these patients have the most pronounced left ventricular (LV) dyssynchrony, LV dyssynchrony assessment often fails to predict outcome. We hypothesized that patients with favorable outcome from CRT can be identified by a characteristic strain distribution pattern. Methods: From 313 patients who underwent CRT between 2003 and 2006, we identified 10 patients who were CRT non-responders (no LV end-systolic volume [LVESV] reduction) with non-ischemic cardiomyopathy and LBBB and compared with randomly selected CRT responders ( n = 10; LVESV reduction ≥ 15 %). Longitudinal strain ( ε long )
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Double left ventricular pacing following accidental malpositioning of the right ventricular electrode during implantation of a cardiac resynchronization therapy device

Double left ventricular pacing following accidental malpositioning of the right ventricular electrode during implantation of a cardiac resynchronization therapy device

electrodes into the left ventricle (LV) [4,5]. Usually, the malplacement can be detected by the postprocedure twelve-lead electrocardiogram (ECG) exhibiting an un- expected right bundle branch block (RBBB) pattern in- stead of the usual left bundle branch (LBBB) appearance [4]. After successful cardiac resynchronization therapy (CRT) procedures, however, combined pacing of RV and LV usually results in a RBBB configuration and a misplaced RV-lead may therefore be missed. To our best knowledge, this problem has not been reported by case reports or recent review articles [4].

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Precision of a Parabolic Optimum Calculated from Noisy Biological Data, and Implications for Quantitative Optimization of Biventricular Pacemakers (Cardiac Resynchronization Therapy)

Precision of a Parabolic Optimum Calculated from Noisy Biological Data, and Implications for Quantitative Optimization of Biventricular Pacemakers (Cardiac Resynchronization Therapy)

In patients with heart failure and disordered intracardiac conduction of activation, doctors implant a biven- tricular pacemaker (“cardiac resynchronization therapy”, CRT) to allow adjustment of the relative timings of activation of parts of the heart. The process of selecting the pacemaker timings that maximize cardiac func- tion is called “optimization”. Although optimization—more than any other clinical assessment—needs to be precise, it is not yet conventional to report the standard error of the optimum alongside its value in clinical practice, nor even in research, because no method is available to calculate precision from one optimization dataset. Moreover, as long as the determinants of precision remain unknown, they will remain unconsidered, preventing candidate haemodynamic variables from being screened for suitability for use in optimization. This manuscript derives algebraically a clinically-applicable method to calculate the precision of the opti- mum value of x arising from fitting noisy biological measurements of y (such as blood flow or pressure) ob- tained at a series of known values of x (such as atrioventricular or interventricular delay) to a quadratic curve. A formula for uncertainty in the optimum value of x is obtained, in terms of the amount of scatter (irrepro- ducibility) of y, the intensity of its curvature with respect to x, the width of the range and number of values of x tested, the number of replicate measurements made at each value of x, and the position of the optimum within the tested range. The ratio of scatter to curvature is found to be the overwhelming practical determi- nant of precision of the optimum. The new formulae have three uses. First, they are a basic science for any- one desiring time-efficient, reliable optimization protocols. Second, asking for the precision of every re- ported optimum may expose optimization methods whose precision is unacceptable. Third, evaluating preci- sion quantitatively will help clinicians decide whether an apparent change in optimum between successive visits is real and not just noise.
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Impact of contractile reserve on acute response to cardiac resynchronization therapy

Impact of contractile reserve on acute response to cardiac resynchronization therapy

28. Ypenburg C, Schalij MJ, Bleeker GB, Steendijk P, Boersma E, Dibbets- Schneider P, Stokkel MP, Wall EE van der, Bax JJ: Extent of viability to predict response to cardiac resynchronization therapy in ischemic heart failure patients. J Nucl Med 2006, 47:1565-1570. 29. Chalil S, Foley PW, Muyhaldeen SA, Patel KC, Yousef ZR, Smith RE, Frenneaux MP, Leyva F: Late gadolinium enhancement-cardio- vascular magnetic resonance as a predictor of response to cardiac resynchronization therapy in patients with ischaemic cardiomyopathy. Europac 2007, 9:1031-1037.
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Cardiac resynchronization therapy guided by cardiovascular magnetic resonance

Cardiac resynchronization therapy guided by cardiovascular magnetic resonance

The first demonstration of a beneficial effect from car- diac resynchronization therapy (CRT) was provided by Cazeau et al who, in 1994, treated a 54 year old heart failure patient with four-chamber pacing [1]. Subse- quently, acute hemodynamic studies showed that CRT improves cardiac output [2,3]. The Multisite Stimulation in Cardiomyopathies (MUSTIC) study demonstrated that CRT led to an improvement in NYHA class, quality of life, exercise capacity and peak oxygen uptake, as well as to a reduction in heart failure hospitalizations [4]. By 2005, the Cardiac Resynchronization in Heart Failure (CARE-HF) study of patients with moderate-to-severe heart failure showed that CRT-pacing (CRT-P) led to a 36% relative reduction in total mortality [5]. The Com- parison of Medical Therapy, Pacing and Defibrillation in Heart Failure (COMPANION) study, which included a similar patient group, had previously shown that addi- tion of a cardioverter defibrillator (CRT-D) led to an additional survival benefit [6]. More recently, the Multi- center Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) trial has shown that compared with implantable cardioverter defibrillators (ICD) therapy alone, CRT-D therapy is associated with a dramatic reduction in the risk of heart-failure events in relatively asymptomatic (NYHA
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