Role Of Cardiac Resynchronization Therapy Research Articles

Effects on the timing of left ventricular pressure rise when pacing the right ventricular free wall in cardiac resynchronization therapy

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Norwegian Research Council. Background/Introduction The timing of left ventricular pressure rise (Td) is associated with dispersion of regional work distribution and prolongs with dyssynchrony and dyssynergistic contractions. Synergistic contractions shorten Td and result from effective biventricular pacing (BIVP). Attempts have been made to optimize right ventricular (RV) lead position with septal lead placement away from the apex. In this study we attempted to study the effects from RV free wall (RVfw) compared to septal/ apical RV (RVsept) lead positioning on Td. Purpose RVfw pacing results in activation of RVfw before LV activation with a delay that may hamper the myocardial synergy resulting from biventricular pacing. This effect has not yet been demonstrated and may play an important role to understand non-response to CRT. Methods 9 mongrel dogs were included in the study and handled according to ethics committee approved protocol/GLP. Pacing electrodes were placed epicardial on the left atrial appendage, the RVfw and LV, and endocardial in the septum. Pressure was measured with a Micro-tip pressure sensor (Millar Inc.) in the LV. BIVP was performed from LV combined with RVsept or RVfw. Td was measured from 10 consecutive beats. Mixed models were utilized for the repeated measurements. Results The average Td with BiVP-RVfw, BIVP-RVsept and LV pacing only was 116ms (95% CI: 110, 122), 114ms (95% CI: 108, 120), and 118ms (95% CI: 112, 124) respectively (p<0.001). BiVP with RVsept shortened Td by 4.1 ms (95% confidence interval (CI): -5.3, -2.9, p<0.001), whereas BiVP with RVfw pacing location shorten Td by 1.8 ms (95% CI: -2.8, -0.8, p<0.001), compared to LVP. The SD from 10 beats was on average 0.8ms (range 0-1.6ms). Conclusion(s) Myocardial Synergy with shortening of Td compared to LV only pacing was demonstrated with BIVP regardless of RV position. The synergistic effect from BIVP is more pronounced with BIVP-RVsept than from BIVP-RVfw. RV lead position may play an important role in cardiac resynchronization therapy that can be revealed when measuring the time-course of LV pressure rise.

Resynchronization of the left atrium may play an important role in cardiac resynchronization therapy

Abstract Introduction Left atrial (LA) dyssynchrony is a predictor of response to cardiac resynchronization therapy (CRT). It is unknown, however, if LA resynchronization contributes to response to CRT. We hypothesize that there is a relationship between correction of LA dyssynchrony and response to CRT. Purpose To investigate the association between LA resynchronization and response to CRT. Methods In a prospective study of 171 heart failure patients with LBBB, myocardial strain was measured by speckle-tracking echocardiography, before and 6 months after CRT. As indicated by the white arrows in Figure 1, LA dyssynchrony was measured as the time delay between onset systolic stretch of the interatrial septum and the LA lateral wall. Response to CRT was defined as at least 15% reduction in left ventricular (LV) end systolic volume at 6 months follow up. Results 119 (70%) patients responded to CRT. The panels in Figure 1 shows LA strain traces in a representative LBBB patient that did respond (upper panels), and a patient that did not respond (lower panels). The white arrows in the left panels indicate that both the responder and the non-responder had marked LA dyssynchrony before CRT (198 and 171 ms, respectively). However, after 6 months with CRT, there was recovery of LA synchrony only in the responder (time delay −40 ms), and still marked LA dyssynchrony of 191 ms in the non-responder (right panels). Figure 2 confirms similar results for the whole study population: CRT response was associated with marked reduction of LA dyssynchrony (p=0.0001). In the CRT non-responders there was, however, only a modest, non-significant reduction of LA dyssynchrony. Conclusions Positive CRT response was associated with resynchronization of the left atrium. These findings suggest LA resynchronization as a potential additional target for CRT. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Institute for Surgical Research, Oslo University HospitalThe Intervention Centre, Oslo University Hospital

Impact of cardiac resynchronisation therapy in patients with cardiac sarcoidosis

Abstract Background Implantation of a device is usually required in cardiac sarcoidosis (CS) patients presenting with advanced conduction abnormalities or ventricular arrhythmias. A cardiac resynchronisation therapy (CRT) device is often chosen in patients with concomitant left ventricular systolic impairment. The role of CRT in CS is not well established. Purpose To describe the cohort of CS patients with CRT device in situ in our hospital focusing on the short-term effect in serial echocardiography and long-term outcomes on morbidity and mortality. Methods All consecutive CS patients with a CRT device in situ were identified in our CS database (2005–2022). A confident CS diagnosis was provided after review of all relevant clinical and imaging baseline data in our CS multi-disciplinary meeting and a consensus decision for CRT-D implantation was made based on international guidelines. All patients were followed up for at least 6 months with serial echocardiography. Serial data regarding symptoms, rhythm disturbance and echocardiographic parameters were obtained and comparisons were performed using Wilcoxon signed rank test. Results A total of 51 CS patients with CRT-D were identified (mean age: 57±10 years old). Patients were male predominant (64.7%) and Caucasian in origin (86.2%). Extra-cardiac sarcoidosis was confirmed histologically in 33 (64.7%) patients. The prevalence of smoking, diabetes, hypertension and ischaemic heart disease was 27.5%, 21.6%, 49.0% and 7.8% respectively. At the time of device implantation or during follow-up, 43 (84.3%) patients were found to have active cardiac sarcoidosis on cardiac PET. Post CRT implantation there was a significant difference in LV ejection fraction (35.9±15.0% vs 42.2±14.1%, p<0.001), LV end-systolic diameter (4.90±1.46 cm vs 4.62±1.32 cm, p=0.012) and LV end-diastolic diameter (5.99±1.18 cm vs 5.66±1.06 cm, p<0.001). No significant changes were observed in the right ventricular function (p=0.09) and severity of mitral regurgitation (p=0.40). There was one patient who experienced acute heart failure decompensation admission within six months of CRT-D implantation. The New York Heart Association (NYHA) class improved in 26 patients (51.0%), worsened in 4 (7.8%) patients and remained the same in 21 (41.2%) patients at 6 months post CRT-implantation. During the mean follow up of 47.6 months, the composite end-point of death and cardiac transplantation was reached in 9 (17.6%) patients (8 deaths and 1 cardiac transplantation). 5 patients had major complications including a large haematoma, a small atrio-septal defect, haemothorax, device associated endocarditis and lead fracture. Minor wound infections were seen in 3 patients and 4 patients received inappropriate shock or anti-tachycardia pacing. Conclusions CRT in cardiac sarcoidosis patients is associated with short-term improvement in LV remodelling and functional status but over a four year follow up, morbidity and mortality are common. Funding Acknowledgement Type of funding sources: None.

The Role of Cardiac Resynchronization Therapy for the Management of Functional Mitral Regurgitation.

Valve leaflets and chordae structurally normal characterize functional mitral regurgitation (FMR), which in heart failure (HF) setting results from an imbalance between closing and tethering forces secondary to alterations in the left ventricle (LV) and left atrium geometry. In this context, FMR impacts the quality of life and increases mortality. Despite multiple medical and surgical attempts to treat FMR, to date, there is no univocal treatment for many patients. The pathophysiology of FMR is highly complex and involves several underlying mechanisms. Left ventricle dyssynchrony may contribute to FMR onset and worsening and represents an important target for FMR management. In this article, we discuss the mechanisms of FMR and review the potential therapeutic role of CRT, providing a comprehensive review of the available data coming from clinical studies and trials.

The response to cardiac resynchronization therapy in LMNA cardiomyopathy.

Cardiac implantable electronic device (CIED) therapy is fundamental to the management of LMNA cardiomyopathy due to the high frequency of atrioventricular block and ventricular tachyarrhythmias. We aimed to define the role of cardiac resynchronization therapy (CRT) in impacting heart failure in LMNA cardiomyopathy. From nine referral centres, LMNA cardiomyopathy patients who underwent CRT with available pre- and post-echocardiograms were identified retrospectively. Factors associated with CRT response were identified (defined as improvement in left ventricular ejection fraction [LVEF] ≥5% 6 months post-implant) and the associated impact on the primary outcome of death, implantation of a left ventricular assist device or cardiac transplantation was assessed. We identified 105 patients (mean age 51 ± 10 years) undergoing CRT, including 70 (67%) who underwent CRT as a CIED upgrade. The mean change in LVEF ∼6 months post-CRT was +4 ± 9%. A CRT response occurred in 40 (38%) patients and was associated with lower baseline LVEF or a high percentage of right ventricular pacing prior to CRT in patients with pre-existing CIED. In patients with a European Society of Cardiology class I guideline indication for CRT, response rates were 61%. A CRT response was evident at thresholds of LVEF ≤45% or percent pacing ≥50%. There was a 1.3year estimated median difference in event-free survival in those who responded to CRT (p=0.04). Systolic function improves in patients with LMNA cardiomyopathy who undergo CRT, especially with strong guideline indications for implantation. Post-CRT improvements in LVEF are associated with survival benefits in this population with otherwise limited options.

Arrhythmias in adults with congenital heart disease and heart failure.

Arrhythmias and heart failure are among the most common complications encountered by adults with congenital heart disease (CHD). In this contemporary review, we explore the interactions between arrhythmias and heart failure and discuss management strategies. Major knowledge gaps are highlighted throughout. Interactions between arrhythmias and heart failure are complex and bidirectional, with one begetting the other. Arrhythmias can provoke heart failure through various mechanisms: conduction disturbances may contribute to inefficient ventricular filling and contraction patterns; bradyarrhythmias and tachyarrhythmias can result in a reduction in cardiac output; hypoxemia may be exacerbated by right-to-left shunting; and tachycardia-induced cardiomyopathy has potentially devastating consequences if the diagnosis is delayed. In turn, heart failure promotes arrhythmogenesis through various structural (eg, fibrosis, chamber dilation, hypertrophy) and electrical remodeling effects that include changes to ion currents and channels and connexin expression, along with shortening of atrial and ventricular refractory periods with increased heterogeneity. Several shared comorbidities can contribute to, and modulate the impact of, arrhythmias and heart failure. Preemptive arrhythmia management can potentially mitigate effects on heart failure exacerbations. Similarly, optimal heart failure control could curtail its impact on arrhythmogenesis. Treatment strategies to prevent or treat heart failure in adults with CHD encompass pharmacological agents, catheter ablation, and device therapies including defibrillators, cardiac resynchronization therapy, and His bundle pacing. High-priority research avenues with major knowledge gaps include tachycardia-induced cardiomyopathy, catheter ablation of atrial fibrillation, defibrillator indications in high-risk subsets, and the role of cardiac resynchronization therapy and His bundle pacing in diverse forms of CHD.

Cardiac resynchronisation therapy in anthracycline-induced cardiomyopathy

IntroductionChemotherapy-induced cardiomyopathy has been increasingly recognised as patients are living longer with more effective treatments for their malignancies. Anthracyclines are known to cause left ventricular (LV) dysfunction. While heart failure...

Future research prioritization in cardiac resynchronization therapy

Although cardiac resynchronization therapy (CRT) is effective for some patients with heart failure and a reduced left ventricular ejection fraction (HFrEF), evidence gaps remain for key clinical and policy areas. The objective of the study was to review the data on the effects of CRT for patients with HFrEF receiving pharmacological therapy alone or pharmacological therapy and an implantable cardioverter-defibrillator (ICD) and then, informed by a diverse group of stakeholders, to identify evidence gaps, prioritize them, and develop a research plan. Relevant studies were identified using PubMed and EMBASE and ongoing trials using clinicaltrials.gov. Forced-ranking prioritization method was applied by stakeholders to reach a consensus on the most important questions. Twenty-six stakeholders contributed to the expanded list of evidence gaps, including key investigators from existing randomized controlled trials and others representing different perspectives, including patients, the public, device manufacturers, and policymakers. Of the 18 top-tier evidence gaps, 8 were related to specific populations or subgroups of interest. Seven were related to the comparative effectiveness and safety of CRT interventions or comparators, and 3 were related to the association of CRT treatment with specific outcomes. The association of comorbidities with CRT effectiveness ranked highest, followed by questions about the effectiveness of CRT among patients with atrial fibrillation and the relationship between gender, QRS morphology and duration, and outcomes for patients either with CRT plus ICD or with ICD. Evidence gaps presented in this article highlight numerous, important clinical and policy questions for which there is inconclusive evidence on the role of CRT and provide a framework for future collaborative research.

Left Ventricular Endocardial Pacing/Leadless Pacing

Several clinical trials have established the role of cardiac resynchronization therapy in patients with heart failure, impaired left ventricular function and dyssynchrony. Challenges to traditional therapy include coronary sinus anatomy and failure to respond. Left ventricular endocardial pacing could overcome anatomic constraints, provide more flexibility, and allow for more physiologic activation. Cases and case series have demonstrated the promise of the approach. Preclinical studies support the superior hemodynamic effects of left ventricular endocardial pacing. Leadless left ventricular endocardial pacing is a recent innovation that is undergoing prospective testing. Successful delivery may be associated with clinical response and positive cardiac structural remodeling.

Role of Cardiac Resynchronization Therapy in Patients with Left Ventricular Assist Support

Role of Cardiac Resynchronization Therapy in Patients with Left Ventricular Assist Support

Prospective Randomized Evaluation of Implantable Cardioverter‐Defibrillator Programming in Patients With a Left Ventricular Assist Device

BackgroundVentricular arrhythmias are common in patients with left ventricular assist devices (LVADs) but are often hemodynamically tolerated. Optimal implantable cardioverter defibrillator (ICD) tachy‐programming strategies in patients with LVAD have not been determined. We sought to determine if an ultra‐conservative ICD programming strategy in patients with LVAD affects ICD shocks.Methods and ResultsAdult patients with an existing ICD undergoing continuous flow LVAD implantation were randomized to standard ICD programming by their treating physician or an ultra‐conservative ICD programming strategy utilizing maximal allowable intervals to detection in the ventricular fibrillation and ventricular tachycardia zones with use of ATP. Patients with cardiac resynchronization therapy (CRT) devices were also randomized to CRT ON or OFF. Patients were followed a minimum of 6 months. The primary outcome was time to first ICD shock. Among the 83 patients studied, we found no statistically significant difference in time to first ICD shock or total ICD shocks between groups. In the ultra‐conservative group 16% of patients experienced at least one shock compared with 21% in the control group (P=0.66). There was no difference in mortality, arrhythmic hospitalization, or hospitalization for heart failure. In the 41 patients with CRT ICDs fewer shocks were observed with CRT‐ON but this was not statistically significant: 10% of patients with CRT‐ON (n=21) versus 38% with CRT‐OFF (n=20) received shocks (P=0.08).ConclusionsAn ultra‐conservative programming strategy did not reduce ICD shocks. Programming restrictions on ventricular tachycardia and ventricular fibrillation zone therapy should be reconsidered for the LVAD population. The role of CRT in patients with LVAD warrants further investigation.Clinical Trial RegistrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT01977703.

073_16781-K3 NYHA Functional Class or Left Ventricle Ejection Fraction: Who Should we Rely on to Predict Mortality in Cardiac Resynchronization Therapy?

Despite the indisputable role of cardiac resynchronization therapy (CRT) in heart failure, the prognostic significance of clinical or echocardiographic responses to CRT are less well defined. We aimed to evaluate the impact of either clinical or echocardiographic response to CRT on long-term

Cardiac resynchronization therapy for the treatment of mild heart failure: A review of the clinical data

Cardiac resynchronization therapy (CRT) was originally established as an effective treatment for patients with systolic heart failure (HF) with New York Heart Association Class III–IV symptoms, reduced left ventricular ejection fraction and prolonged QRS duration ≥120 ms. Subsequent studies expanded the role of CRT to the treatment of patients with mildly symptomatic HF as these patients experienced similar improvement in clinical symptoms and reverse remodeling of the left ventricle. These clinical trial results were incorporated into the 2013 guidelines on cardiac pacing and CRT from the European Society of Cardiology and the 2012 American College of Cardiology Foundation/American Heart Association/Heart Rhythm Society Focused Update on Device-based Therapy of Cardiac Rhythm Abnormalities. Additional data from careful post hoc and substudy analyses as well as long-term follow-up of the original study cohorts have been performed. These results attempt to identify subgroups more likely to benefit from CRT, to define the association between response and QRS morphology/duration and to demonstrate the sustained benefit of CRT in this population. More importantly, these results highlight that patients with mildly symptomatic HF who respond to CRT not only have improvement in clinical symptoms but also receive a therapy that may prevent or delay progression of HF. A review of the clinical trials in mildly symptomatic HF and the results of subsequent post hoc analysis are summarized herein.

Cardiac resynchronization therapy in patients with end-stage hypertrophic cardiomyopathy.

A dilated/end-stage phase of hypertrophic cardiomyopathy (HCM) is rare but well-recognized. The role for cardiac resynchronization therapy (CRT) in this subset of patients remains unexplored. We aimed to clarify the impact of bi-ventricular pacing CRT in dilated/end-stage HCM. The Mayo Clinic HCM database was interrogated to identify patients with ejection fraction (EF) <50% and CRT. Control subjects were identified in 1:1 manner. Clinical outcomes were determined. Of 2073 patients with HCM, 9 (8 male) had EF <50% and received CRT. The average age at CRT-D implant was 44.8 ± 14.8 years, an average of 17.3 ± 10.3 years after HCM diagnosis. The indication for CRT was based on New York Heart Association class ≥II symptoms (mean 2.7 ± 0.4) and EF <50% in all patients (EF 34.7 ± 7.1% at implant), with electrocardiographic evidence of abnormal ventricular conduction. At 6-month, 12-month, and long-term follow-up, EF was 39.9 ± 8.4%, 37.9 ± 9.8%, and 33.3 ± 7.6%, respectively (P > 0.05 for all). There was no difference in the combined end-point of left ventricular assist device (LVAD), cardiac transplant, or death between groups (P = 0.90). At last follow-up [mean duration 12.9 ± 8.3 (median 10.7) years], 8 (89%) in the CRT group were alive. Three and 2 patients underwent LVAD implantation and cardiac heart transplantation, respectively, 15.0 ± 10.1 years from HCM diagnosis and 2.6 ± 0.9 years from CRT implant. In the control group, 4 (44.4%) patients were alive at last follow-up [mean duration 12.0 ± 7.1 (median 12.7) years]. One patient each had LVAD and cardiac transplant. CRT in patients with dilated/end-stage HCM does not appear to confer a salutary effect on ventricular function. In medium-term follow-up, however, left ventricular function did not appear to deteriorate further, yet advanced heart failure therapy was common in this group.

Right Ventricular Versus Biventricular Pacing for Heart Failure and Atrioventricular Block.

The use of cardiac resynchronization therapy (CRT) is well accepted as an important option for the treatment of patients with systolic heart failure and prolonged QRS duration. CRT for patients with narrow QRS complexes is reserved for patients who are undergoing implantation of new or replacement pacemakers or implantable cardioverter defibrillators with an anticipated significant requirement for ventricular pacing. The Biventricular versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block (BLOCK HF) Trial examined the role of CRT in heart failure patients with atrioventricular block and demonstrated significantly better outcomes with CRT compared to right ventricular pacing. On the other hand, conflicting preliminary data were reported by the Biventricular Pacing for Atrioventricular Block to Prevent Cardiac Desynchronization (BioPace) Trial investigators. In this review, we will discuss the adverse consequences of chronic right ventricular pacing, the options of alternate pacing sites in the right ventricle versus biventricular pacing, and the findings from the BLOCK HF Trial as well as the preliminary data from the BioPace Trial. Our goal is to explore the role of biventricular pacing in patients with atrioventricular block.

Cardiac Resynchronization Therapy Leads to Improvements in Handgrip Strength.

BackgroundA reduction in skeletal muscle performance measured by handgrip strength is common in heart failure. No trial has investigated the role of cardiac resynchronization therapy, which leads to improvements in cardiac performance, on the function of skeletal muscle in patients with heart failure.MethodsNineteen patients were recruited, 18 male, age 69 ± 8 years, New York Heart Association class II-IV, QRS duration 173 ± 21 ms and left ventricular ejection fraction 26±8%. Handgrip strength was measured at baseline before, and 6 and 12 months, following cardiac resynchronization therapy. Response was assessed using quality of life questionnaire, 6-minute walk distance, left ventricular end-diastolic volume, and cardiopulmonary exercise testing at the same time points.ResultsFourteen patients were identified as responders, demonstrating significant improvements in all four markers of response. There was no significant difference at baseline in left or right handgrip strength between responders and non-responders. Compared to baseline, handgrip strength significantly increased in responders during follow-up, left (34.4 ± 11.4 to 40.3 ± 11.3 kgf, P < 0.001) and right (35.7 ± 12.5 to 42.2 ± 11.5 kgf, P < 0.001) at 12 months. No such improvement was seen in non-responders.ConclusionsThis study demonstrates that positive response to cardiac resynchronization therapy is associated with significant gains in handgrip strength, suggesting that cardiac resynchronization therapy may indirectly lead to secondary gains in skeletal muscle function.

The role of cardiac resynchronization therapy in permanent atrial fibrillation patients: current indications to treat heart failure

The role of cardiac resynchronization therapy in permanent atrial fibrillation patients: current indications to treat heart failure

Abstract 15322: Pacinchagas-crt: A Cohort Study of Cardiac Resynchronization Therapy in Patients With Chronic Chagas Cardiomyopathy

Background: Cardiac resynchronization therapy (CRT) is an established procedure for patients with heart failure (HF). However, trials evaluating its efficacy did not include patients with chronic Chagas cardiomyopathy (CCC), an important cause of HF in endemic countries. We aimed to assess the role of CRT in a cohort of patients with CCC. Methods: This was a retrospective study of consecutive CCC patients who underwent CRT between January 2005 and December 2012. We compared the outcomes of CCC patients who underwent CRT (CCC-CRT group) with those of ischemic and dilated cardiomyopathy patients who underwent CRT (CRT-control group) in the same period and with those of CCC patients with induced left bundle branch block (LBBB) who did not undergo CRT (CCC-control group). The primary endpoint was all-cause mortality and the secondary endpoint was echocardiographic changes, at least 24 months after CRT. Results: There were 115 patients in the CCC-CRT group, 311 in the CRT-control group, and 16 in the CCC-control group. The annual mortality rates were 25.4%, 10.9%, and 42.9%, respectively. Multivariate analysis adjusted for potential confounders showed that the CCC-CRT group had a two-fold (hazard ratio [HR] 2.11 [1.56-2.86], P&lt;0.001) higher risk of death compared to the CRT-control group, and that the CCC-control group had an almost three-fold (HR 2.78 [1.09-7.01], P=0.032) higher risk of death compared to the CCC-CRT group. Conclusions: This cohort study showed that CRT has a favorable impact in patients with CCC, despite their worse prognosis compared to patients with other cardiomyopathies who undergo CRT.

Cardiac resynchronization as rescue therapy for ventilator-dependent heart failure

The role of cardiac resynchronization therapy (CRT) in treating non-ambulatory patients with severe heart failure (HF) remains controversial. We present 2 cases in which CRT was successfully utilized in patients with very poor prognosis that had failed multiple attempts at weaning from the ventilator. Both patients improved rapidly, and were successfully weaned shortly after implant. One patient is still alive, living independently without HF symptoms, 23 months after implant. The other patient died 19.5 months after implant due to an unrelated condition. These cases demonstrate that CRT can be successfully employed as rescue therapy in selected ventilator-dependent HF patients.

Cardiac Resynchronization Therapy in 2015: Lessons Learned

Over 20 years of research has led to the now widely accepted role of cardiac resynchronization therapy (CRT) in medically refractory, mild to severe systolic heart failure (HF) with increased QRS duration. In addition to conferring a mortality benefit, CRT has been shown to reduce HF hospitalization rates and improve functional status in this population. However, not all patients consistently demonstrate a positive response to CRT. Efforts to improve response to CRT have focused on improving patient selection and optimizing device implantation and follow-up, thereby correcting electrical and mechanical dyssynchrony. In this article we review the pathobiology of cardiac dyssynchrony, the rationale for the use of CRT, the history and the state of the art of CRT, and guidelines and recommendations for CRT, while also focusing on the areas of controversy and potential future applications.