Cardiac Resynchronization Therapy Treatment Research Articles

Investigating the clinical utility of global and regional myocardial work parameters in predicting response to cardiac resynchronization therapy in patients with heart failure and reduced ejection fraction.

Previous studies have indicated that despite adhering to current patient selection guidelines, there remains a 30% to 40% subset of patients who do not experience improvement in heart failure (HF) after receiving cardiac resynchronization therapy (CRT). We aim to utilize echocardiographic myocardial work parameters to serve as predictors of responsiveness to CRT in patients with heart failure and reduced ejection fraction (HFrEF). We prospectively recruited patients who underwent CRT at Sun Yat-sen Memorial Hospital from June 2019 to September 2022. Comprehensive preoperative information, clinical laboratory data, conventional echocardiographic parameters and myocardial work were collected for all participants, as well as follow-up data 6 months after CRT. Twenty-five patients (67.6%) showed response to CRT treatment, while twelve patients (32.4%) had no response. Compared with the non-response group, the response group had larger region constructive work [RCW: the sum of constructive work (CW) in the 9 segments of the basal, mid, and apical segments of the anterior, lateral, and posterior walls], region wasted work [RWW: the sum of wasted work (WW) in the 6 segments of the basal and mid segments of the anterior septum, posterior septum and anterior walls], and the combination of RCW and RWW (RCW + RWW) in baseline (RCW: 9,695.68±2,955.40 vs. 5,219.50±2,207.68 mmHg%, P<0.001; RWW: 3,612.08±1,723.80 vs. 1,674.33±995.23 mmHg%, P=0.001; RCW + RWW: 13,307.76±3,857.71 vs. 6,893.83±2,592.83 mmHg%, P<0.001). Furthermore, global constructive work (GCW), global wasted work (GWW), GCW + GWW, RCW, RWW, and RCW + RWW had areas under the receiver operating characteristic curve (AUCs) of 0.870, 0.770, 0.860, 0.890, 0.870, and 0.910, respectively, for predicting CRT responsiveness. The global and regional myocardial work parameters are associated with CRT response in CRT candidates. Particularly regional myocardial work parameters appear to be promising parameters to improve selection for CRT of patients with HFrEF.

The Utility of Low-Dose-Dobutamine Stress Echocardiography in Patients with Heart Failure with Reduced Ejection Fraction: An Update.

Despite significant advancements in medical therapy, heart failure with reduced ejection fraction (HFrEF) continues to be a significant cause of death and disability. Reversible ischaemic left ventricular dysfunction due to viable myocardium is one such contributing factor. In these cases, coronary revascularization has shown promise in improving left ventricular function and prognosis. For patients with HFrEF and wide QRS, cardiac resynchronization therapy (CRT) is an effective option to address electromechanical dyssynchrony. However, approximately 30% of patients do not respond positively to CRT, highlighting the need to refine candidate selection for this treatment. In some patients with reduced HFrEF, there is a condition known as classical low-flow, low-gradient aortic stenosis (AS) that may be observed. This condition is characterized by a low transaortic flow, which leads to reductions in both the transaortic mean gradient and aortic valve area. Decision-making regarding revascularization, CRT, and pharmacological treatment play a crucial role in managing HFrEF. Cardiac imaging can be valuable in guiding decision-making processes and assessing the prognosis of patients with HFrEF. Among the imaging modalities, dobutamine stress echocardiography has come a long way in establishing itself as a feasible, safe, effective, relatively cheap non-invasive technique. The aim of this review is to explore the current literature on the utility of low-dose stress echocardiography in diagnosing and prognosticating patients with HFrEF.

Variations of coronary sinus tributaries among patients undergoing cardiac resynchronisation therapy.

In cardiac resynchronisation therapy (CRT), the coronary venous system is used for left ventricular pacing electrode placement. Despite the well- -known anatomy of the coronary sinus and its tributaries, heart failure patients' remodelled and enlarged left ventricles may impede the successful lead placement because of acquired anatomical obstacles. Fifty-five patients qualified for CRT treatment were divided into ischaemic and non-ischaemic cardiomyopathy. Forty-four control groups without heart failure underwent dual-source computed tomography (CT). Rendered reconstructions of cardiac coronary systems were compared. The presence of main tributaries was comparable in all groups. The left marginal vein, small cardiac vein, and oblique vein of the left atrium were present in 63%, 60%, and 51% of the hearts in all the groups. CRT referred CTs had significantly longer distances between posterior and lateral cardiac veins over the left ventricle (p < 0.05), wider angles of tributaries (p = 0.03), and smaller lumen of coronary sinus (p = 0.03). In the non-ischaemic group, the posterior interventricular and great cardiac veins are more extensive than in the control group. Age-related analysis of vessel size shows a moderate correlation between age and diminishing mean vessel size in all the groups studied. The general structure of the coronary heart system is consistent in patients with and without heart failure. The variance of the general structure, or the presence of adequate veins, is an individual variation. The use of CT and analysis of the coronary veins allow better planning of the CRT-D implantation procedure and may reduce the risk of ineffective left ventricular electrode implantation.

Subclinical hypothyroidism and its relationship with therapy failure in patients underwent cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) is used in patients with heart failure (HF), an important problem in cardiology practice, with reduced left ventricular systolic dysfunctions and left ventricular dyssynchrony to improve morbidity and mortality. Thyroid diseases have undeniable effects on cardiac functions. So, we aimed to evaluate the effect of subclinical hypothyroidism on CRT response in HF patients in this study. After the exclusion, 386 consecutive patients who received first-time CRT-defibrillator (CRT-D) or CRT-pacemaker (CRT-P) were retrospectively included. Known overt hypothyroidism or hyperthyroidism patients were excluded. The response of CRT was defined as a relative increase (≥15%) or absolute increase (≥10%) in left ventricular ejection fraction (LVEF) from implantation to one-year after follow-up. Diabetes mellitus, atrial fibrillation and coronary artery disease ratios were similar between responder vs. non-responder groups. Thyroid stimulating hormone (TSH) levels were higher (p <0.005) in non-responder group. Responder group had higher baseline LVEF (p <0.001), and follow-up LVEF (p <0.001) and longer baseline QRS interval (p =0.004), but similar post-implant QRS interval duration (p >0.005) with non-responder group. Baseline QRS interval (p =0.002), baseline LVEF (p <0.001) and the presence of subclinical hypothyroidism (SCH) (p =0.001) were independent predictors of CRT response. Adding SCH as a risk factor to our baseline risk modelling has an independent prognostic impact to predict non-responder patients (p =0.01). Presence of the SCH may be an important predictor of non-response in patients undergoing CRT. Evaluating the risk factors associated with non-response to CRT may be logical in identifying patients who obtain maximum benefit from CRT treatment.

Coronary artery disease is a stronger predictor of mortality than left ventricular ejection fraction among newly diagnosed patients with heart failure

Abstract Background Heart failure (HF) prevalence remains high and prognosis is poor despite improvements in both medical treatment and implantation of primary prophylactic implantable cardioverter-defibrillator (ICD) and cardiac resynchronisation therapy (CRT) devices. At present, classification of HF and treatment algorithms are determined by the left ventricular ejection fraction (LVEF). However, in patients with LVEF &amp;lt;50% and newly diagnosed HF, evidence remains sparse as to whether LVEF per se or presence of CAD provide independent prognostic information on mortality. Methods Using the Western Denmark Heart Registry, we identified newly diagnosed patients with HF and LVEF 10–49% undergoing first-time coronary angiography (CAG) from 2003 to 2016 referred due to HF. Patients were stratified by LVEF (10–35% vs. 36–49%, according as to whether primary prophylactic ICD and CRT treatment should be considered) and presence of coronary artery disease (CAD). Maximum follow-up was 10 years. We estimated 10-year cumulative incidence of death and calculated hazard ratios (HR) adjusted for relevant comorbidities and risk factors. Results Of 154,186 Western Danish residents undergoing CAG, 3,620 patients had HF and LVEF 10–49%. Among these, 2,780 (77%) patients had LVEF 10–35% and 840 (23%) patients had LVEF 36–49%. CAD was present in 1,592 (44%) patients. There was a potential association in 10-year mortality when comparing patients with HF and LVEF 36–49% to those with LVEF 10–35% (37.3% vs. 42.1%, HR 1.15; 95% CI 0.99–1.34) (Figure 1A), with point estimates of mortality ranging from being 1% reduced to 24% increased. This result was not strongly influenced by the presence of CAD (HR 1.11; 95% CI 0.91–1.35) or absence of CAD (HR 1.24; 95% CI 0.97–1.57) (Figure 1B). There was no trend between LVEF categorized by 5-percentiles and mortality (p for trend = 0.24) (Table 1). In contrast, CAD was more strongly associated with increased 10-year mortality (55.0% vs. 31.5%, HR 1.43; 95% CI 1.25–1.64) irrespective of LVEF (Figure 1B). Conclusion Among newly diagnosed patients with HF and LVEF 10–49%, presence of CAD impacts mortality substantially more than LVEF per se. These results emphasize that assessment of CAD is pivotal for prognostication of newly diagnosed patients with HF and LVEF 10–49%. Funding Acknowledgement Type of funding sources: None.

Relationship Between Left Ventricular Strain Assessment by Cardiac Magnetic Resonance Imaging and Response to Cardiac Resynchronization Therapy.

Although cardiac resynchronization therapy (CRT) is an established treatment for heart failure with reduced ejection fraction, 30 to 50% patients are non-responders. In this retrospective single-centre study, 19 patients underwent cardiac MRI pre-CRT, and global left ventricular (LV) strain and late gadolinium enhancement (LGE) were measured by a blinded reader. LV reverse remodeling was independently assessed using transthoracic echocardiogram before and after CRT implant. Both LV strain and extent of LGE correlated significantly with measures of reverse LV remodeling (reduction in LV volume and improvement in LV ejection fraction). These findings suggest that CMR derived strain analysis and scar evaluation may be useful preimplant predictors of response to CRT. Larger prospective multi-center studies are needed to confirm these findings and to further evaluate the role of CMR strain imaging in guiding CRT treatment decisions.

Quadripolar leads are associated with better results according to bipolar leads in cardiac resynchronization therapy in one-year follow-up: Multicenter, retrospective study

Aim: In this study, we compared patients who were performed cardiac resynchronization therapy with quadripolar left ventricle lead or bipolar left ventricle lead in one-year follow-up. We investigated the relationship between the improvements of New York Heart Association classification, electrocardiography and echocardiography parameters according to lead type at one-year follow-up after CRT treatment. Materials and Methods: In this study, 91 patients were enrolled respectively as bipolar left ventricle lead and quadripolar left ventricle lead. 40 patients are quadripolar left ventricle lead and 51 patients are bipolar left ventricle lead. Results: After cardiac resynchronization therapy treatment in one year follow-up, patients with ≥1 NYHA improvement was 80% vs 56.8%, p=0.006 and left ventricular ejection fraction ≥5% was 77.5% vs 54.9%, p=0.031 and QRS duration 140.4±11.7 vs 151.7±19.4 ms, p=0.018 in quadripolar and bipolar left ventricle lead respectively. The univariable regression analysis revealed that left ventricular ejection fraction (OR:1.082 95%CI [1.005–1.165], p=0.037), QRS duration (OR:0.980 95%CI [0.961–0.999], p=0.038), NYHA class (OR:1.107 95%CI [0.075–0.682], p=0.008) and left ventricular ejection fraction improvement (OR:2.959 95%CI [1.083–8.086], p=0.034) were better response cardiac resynchronization therapy with quadripolar left ventricle rather than bipolar left ventricle lead. Conclusion: Qdp LVL can be considered instead of BiP LVL to shorten QRS duration and better improve LVEF and NYHA in patients undergoing CRT in long-term follow-up

The diagnostic value of different criteria in predicting the response of LBBB patients: a systematic review and meta-analysis

Abstract Funding Acknowledgements Type of funding sources: None. Background The left bundle branch has emerged as an essential part of the cardiac conduction system. However, many patients with conventional left bundle branch block (LBBB) QRS morphology appeared to have a poor response to cardiac resynchronization therapy (CRT) therapy; these might be due to they were non-LBBB patients who met the conventional diagnostic criteria but failed to meet the strict LBBB standard. There are different criteria to select appropriate CRT patients currently. Several studies have reported that patients with complete LBBB had worse ventricular synchronization and worse prognosis. Thus, it is of great clinical significance to distinguish between complete LBBB and non-LBBB. Purpose To compare the difference in mortality and CRT response between complete LBBB and non-LBBB patients. Methods This meta-analysis has been registered on the International Prospective Register of Systematic Reviews (ID: CRD42021242318). A systematic search on PubMed, Cochrane library, Embase databases was conducted before July 2021. All the included studies were screened and identified based on the specific inclusion and exclusion criteria. Relevant data, including time to event data for different outcomes (e.g., hazard ratio, HR), responders, electrocardiogram parameters, and echocardiographic changes, were extracted for meta-analysis. Results A total of 15 studies were ultimately involved in this meta-analysis. A random-effect model was conducted due to the substantial heterogeneity. The results showed that patients who received CRT treatment in the complete LBBB group had a 35% reduction in mortality than in the non-LBBB group (HR 0.65, 95% CI 0.56 to 0.77, P =0.000). The subgroup analysis showed that when stratified by the Strauss criteria, the survival was much higher in complete LBBB patients (HR 0.58, 95% CI 0.43 to 0.77, P =0.000), compared with other criteria, including ESC, AHA, Marriot, and conventional (HR 0.72, 95% CI 0.63 to 0.82, P =0.000). The pooled results suggested that the patient survival rate was significantly better under the Strauss criteria than other standards. Conclusions Present criteria differentiating complete LBBB and non-LBBB have good predictive value for survival. Among those, Strauss criteria may provide the most valuable information on the predictive effects of mortality and survival rate. This meta-analysis indicates that the use of Strauss criteria correlated independently with the response and prognosis of CRT patients with LBBB.

Prevalence of left bundle branch block and CRT treatment in a large regional unselected ECG database

Abstract Introduction Heart failure is a clinical syndrome in which signs and symptoms are due to functional and/or structural abnormalities of the heart which prevent the necessary supply of oxygenated blood or do so at the expense of high filling pressures. It has a prevalence of 1–2% in the western world and increasing prevalence with increasing age. While the prognosis for coronary heart disease has improved significantly, the same does not apply for heart failure, perhaps because some effective treatment methods have not been sufficiently implemented in health care. One effective but underutilized heart failure treatment is the cardiac resynchronisation therapy (CRT), that coordinates the contraction of the left and right ventricles via a pacemaker (PM). CRT treatment is an evidence based treatment recommended by among other the ESC guidelines for heart failure. Clinical studies have suggested decreases in mortality, hospitalization, morbidity and improvements in quality of life for heart failure patients receiving a CRT. Purpose To find a new clinical pathway to improve CRT implementation and to evaluate if it might be optimized through ECG-based surveillance and thus improving prognosis. Methods In a population of approximately 2.5 million people in our region we investigated the University Hospital's ECG database between 2000 and 2018. During which time 432 108 adult patients with 1 482 489 ECG's presented to the hospital. We searched and found 5 511 unique patients with the following ECG criteria: QRS ≥150 ms at any time, LBBB and Non pace. According to the Pacemaker Registry we excluded 771 patients that had previously received a PM/CRT. We also identified patients with diagnosis of heart failure by using the ICD-10 codes (I42.0 and I50). Results Our final cohort consists of 4 740 patients. The median age was 75 (19–112) years, 34.5% were female and 14.9% were subsequently implanted with a CRT (60% with CRT-D). The median time to CRT implantation from the first ECG with LBBB was 244 (IQR 994) days. Of the 4 740 patients 20.6% had a previous hospitalistion for heart failure with a median delay from the hospitalisation to CRT implantation of 5 (IQR 5.4) years. Conclusions Our observational data from a large real-life regional ECG database show there is a considerable number of heart failure patients that could benefit from CRT treatment. Using an existing ECG database could be useful in finding patients with indication for CRT implantation. This could possibly influence morbidity and mortality in a regional heart failure population by minimizing the delay of CRT treatment. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Karolinska University Hospital Research Fund

Underlying causes of under-utilization of cardiac resynchronization therapy in real-world heart failure settings

Abstract Background Despite well-established effectiveness of cardiac resynchronization therapy (CRT) in patients with heart failure (HF), it remained significantly under-utilized. The underlying causes are still not well described. Aim To investigate how many patients with HF were eligible for CRT and determine underlying causes why CRT was abstained for these patients in real life settings. Methods Retrospective review of medical data was carried out in all patients hospitalized for newly diagnosed HF from January 1, 2016 to December 31, 2019. Patients were identified from the local university hospital register with three afiliations by use of international classification of disease (ICD)-10 codes I50.0-I50.9. Medical journals, including electrocardiograms and echocardiograms, were reviewed. The indication for CRT was evaluated three months after mineralocorticoid receptor antagonists (MRA) were initiated as addition to angiotensin converting enzyme inhibitor /angiotensin-receptor blockers and beta-blocker treatment according to European guidelines for heart failure from 2016. Follow-up was minimum one year and up to two years after HF diagnosis. Results In 3456 patients with HF, 642 (18.6%) were patients hospitalized for new onset of HF with ejection fraction (EF) &amp;lt;40%. Out of those, 104 (16.2%) patients were excluded because of incomplete medical record as a result of referral to primary care. Finally, 538 were included in this study. Overall, 163 patients (30.3%) met CRT criteria with 22.5%, 2.6%, 1.9% complying with recommendation IA, IIA, IIB respectively, and 3.9% had more than 50% right ventricular pacing. Only 52 (9.7%) of patients received CRT with mean age 69.3±11.5 years, and 69.2% men and EF 31.9% ± 7.6. In all these patients with HF eligible for CRT, no difference was found in baseline data including hypertension, ischemic heart disease, atrial fibrillation, valvular heart disease, diabetes mellitus, stroke, cancer and renal failure nor medical treatment between those received CRT and those without CRT. Among underlying causes of under-utilization of CRT, 24.3% were due to multiple concomitant comorbidities, 4.5% due to patient's own wish, 12.5% due to other reasons such as socioeconomic problems and 58.6% with unknown reasons. Mortality rates were 20.7% in patients without treatment with CRT compared with 7.7% in those who received CRT (p=0.037). Conclusion In this real world HF cohort, 1/3 patients were eligible for CRT treatment. However only 1/3 received CRT and 58.6% had no contraindication but did not receive CRT, which emphasize urgent need for structured implementation methods for device treatment in patients with HF. Funding Acknowledgement Type of funding sources: None.

Atrial fibrillation associated with heart failure treated by a 2-lead CRT-DX system (BIO-AffectDX): Study design and clinical protocol.

BackgroundEvidence to support use of cardiac resynchronization therapy (CRT) among patients with both heart failure (HF) and atrial fibrillation (AF) is largely limited to retrospective or post hoc subanalyses. Data from a prospectively enrolled and contemporary cohort are needed.ObjectiveWe aim to better characterize the changes from baseline in HF patients with concomitant AF subsequently implanted with a 2-lead CRT-DX system capable of sensing in the atrium, aggregating diagnostics, and delivering CRT therapy. The primary objective of this study is to evaluate the percentage of all HF subjects with an improvement in a clinical composite score from pre-CRT implant to 12 months.MethodsThe study is a US-based, prospective, observational multicenter clinical trial conducted at up to 50 sites and enrolling approximately 400 subjects with a follow-up period of 1 year. Multiple subject assessments, atrial rhythm status, and device interrogation will be collected at follow-up visits occurring at 3, 6, and 12 months postimplant.ResultsA Clinical Events Committee will adjudicate subject HF events, arrhythmia events, death events, and all device-classified ventricular tachycardia and ventricular fibrillation episodes with treatment that are collected throughout the follow-up period. Their decisions are based on independent physician review of the data from sites and device interrogation.ConclusionThe BIO-AffectDX study aims to provide further insight into the expected outcomes from CRT treatment in patients with HF and AF.

Cardiac resynchronization therapy in paediatric patients with congenital heart disease: single centre with 10 years of experience.

In recent years, cardiac resynchronization therapy (CRT) has also started to be performed in the paediatric and CHD population. This study aimed to evaluate the efficacy of CRT in children with CHD. Patients with CHD who underwent CRT treatment in our paediatric cardiology clinic between January, 2010 and January, 2020 were included in the study. Demographic findings, 12-lead electrocardiograms, echocardiograms, clinical characteristics, management strategies, and outcomes were reviewed systematically. The study population consisted of 18 CHD patients who had been treated with CRT for 10 years in our institution. The median age was 11 years (2.2-18 years) and the median weight was 39 kg (10-81 kg). Systemic ventricle was left ventricle in 13 patients, right ventricle in 4 patients, and 1 patient had single-ventricle physiology. CRT implantation indications were as follows: dysfunction after permanent pacemaker in 11 patients, dysfunction after left bundle branch block in 4 patients, and systemic ventricular dysfunction in 3 patients. CRT implantation techniques were epicardial (n = 13), hybrid (n = 4), and transvenous (n = 1) methods. QRS duration significantly decreased after CRT implantation (160 versus 124 m/second, p < 0.05). Median systemic ventricle ejection fraction (EF) significantly increased after the procedure (30 versus 50%, p < 0.05). Fourteen patients (78%) were responders, two patients (11%) were superresponders, and two patients (11%) were non-responders after the CRT treatment. One patient deceased during follow-up. Median follow-up duration was 40 months (6-117 months). When electromechanical dyssynchrony occurs in paediatric cases with CHD and developing heart failure, patients should be evaluated in terms of CRT to improve ventricular function. Alternative CRT therapy will be beneficial in these cases that do not improve clinically despite optimal medical treatment.

Evaluation of effects of cardiac resynchronization on coronary blood flow by coronary flow reserve and in patients with İdiopathic dilated cardiomyopathy: Does it predict the response?

Background: The results of previous studies evaluating the effects of cardiac resynchronization therapy (CRT) on myocardial blood flow (MBF) and their relation with the response to CRT are conflicting. Materials and Methods: Sixty-one patients diagnosed with idiopathic dilated cardiomyopathy (IDC), a functional capacity (New York Heart Association [NYHA]) Class II or III, and left bundle branch block (LBBB) (QRS width >150 ms) were enrolled in the study. We aimed to evaluate the effects of CRT on MBF in patients with IDC and LBBB by coronary flow reserve (CFR) measurements and thereby tried to predict the responders. Results: Sixty-one patients with IDC were enrolled. CFR and hyperemic fractional flow reserve (FFR) increased after CRT. The only parameter affecting the increase in CFR was the change in FFR after CRT. Then, 44 patients who responded to the CRT treatment at 6 months were compared with 17 patients who did not. Left ventricle outflow tract time-velocity integral (LVOT-TVI), stroke volume (SV) and cardiac output index (COi) was detected significantly higher also left ventricular end-diastolic pressure (LVEDP) was lower in the CRT responders. However, there were no significant differences in coronary flow velocity measurements between the two groups. Moreover the regression analysis revealed that the baseline NYHA class, LVOT TVI, SV, COi, and LVEDP, which were changed due to increased blood flow after CRT implantation, is not associated with response to CRT. Conclusions: Our results suggest that MBF increased after CRT in patients with IDC probably by improving microvascular functions. However, the response to CRT treatment is not related to the changes in the coronary blood flow velocities after CRT.

Cardiac Resynchronization Therapy Guided by Echocardiography, MRI, and CT Imaging: ARandomized Controlled Study.

This study evaluated if selecting the left ventricular (LV) target segment by echocardiography-derived late mechanical activation, with access to multimodality imaging for scar and venous anatomy, could help to increase responder rates to cardiac resynchronization therapy (CRT). LV lead placement is important for clinical outcome, but the optimal strategy for LV lead placement in CRT is still debated. This study conducted a prospective, blinded randomized controlled trial on 102 patients with indication for CRT (27% women, 46% with ischemic cardiomyopathy, 63% in New York Heart Association functional class III, 74% with left bundle branch block, and with mean ejection fraction of 23%). Optimal LV lead location was defined as the latest mechanically activated available segment (free of transmural scar), determined by radial strain echocardiography, cardiac computed tomography, and cardiac magnetic resonance (n=70). The primary endpoint was reduction of LV end-systolic volume by≥15% at 6months post-implantation. Patients were followed for 47 ± 21months. Based on imaging, optimal or adjacent lead placement was feasible in 96% of all cases and was obtained in 83% of the intervention group versus 80% of the control group. Fifty-six percent of the patients were LV end-systolic volume responders compared with the control group (55%) (p=0.96), and 71% improved≥1 New York Heart Association functional class (74% vs. 67%; p=0.43). Death or heart failure hospitalization within 2 years occurred in 6% (2% of the intervention group vs. 10% of the control group; p=0.07). Radial strain-guided LV lead placement, in combination with multimodality imaging, did not result in increased clinical or echocardiographic response, nor in a significant reduction of death or heart failure hospitalization. (Combining Myocardial Strain and Cardiac CT to Optimize Left Ventricular Lead Placement in CRT Treatment [CRT Clinic]; NCT01426321).

Protective effects of cardiac resynchronization therapy in a canine model with experimental heart failure by improving mitochondrial function: a mitochondrial proteomics study.

Cardiac resynchronization therapy (CRT) is well acknowledged as an effective treatment for dyssynchronous heart failure. However, the molecular mechanism is unclear to date. Mitochondrial dysfunction and impaired energetic metabolism are two important mechanisms that lead to heart failure. Therefore, we aim to screen the changes of mitochondria-associated proteins and signaling pathways involved in heart failure and CRT treatment. A total of 24 beagle dogs were randomly assigned into control (CON), heart failure (HF), or CRT group. Myocardial mitochondria from the free wall of left ventricle was extracted for isobaric tags for relative and absolute quantitation (iTRAQ) labeling coupled with two-dimensional liquid chromatography tandem mass spectrometry analysis (2DLC-MS/MS). A total of 2190 proteins were identified, among which 234 proteins were differentially expressed in HF compared with CON group, 151 proteins were differentially expressed in CRT compared with HF group. A total of 192 of the 234 differentially expressed proteins in HF group were changed oppositely by CRT treatment, and 128 of the 151 CRT-induced differentially expressed proteins showed opposite trend of expression to HF/CON. Gene Ontology analysis of the 128 proteins revealed that 16 were localized in mitochondria, 17 were associated with calcium signaling, and 7 could be secreted extracellularly for cell-to-cell signaling. Calpain-1 (CAPN1), which is localized to mitochondria and related to calcium signaling, was upregulated in HF and downregulated after CRT treatment. CRT treatment also improved mitochondrial morphology and function and reduced collagen areas of both interstitial and perivascular fibrosis. CRT treatment significantly improved cardiac function, reduced myocardial fibrosis, and enhanced mitochondrial function in the failing heart through CAPN1 downregulation.

Functional mitral regurgitation and cardiac resynchronization therapy in the “era” of trans-catheter interventions: Is it time to move from a staged strategy to a tailored therapy?

Cardiac resynchronization therapy (CRT) has been associated to left ventricle (LV) remodelling, reduction of functional mitral regurgitation (FMR) and clinical improvement in patients with heart failure and reduced ejection fraction (HFrEF). The prevalence of significant FMR in patients with LV dyssynchrony that are candidate to CRT is up to 40%. Current approach in patients with FMR undergoing CRT consists of re-evaluation of the amount of FMR following a waiting period of at least 3 months after the implant. In case of persistent significant FMR despite CRT and guideline directed medical therapy, trancatheter Mitral Valve repair (TMVR) is an important option to improve quality of life and prognosis. This stepwise approach does not take into account the probability of the individual response to CRT and the availability of TMVR solutions that are safe and effective in high risk patients. We reviewed the effects of CRT on FMR, the prognostic role of persistence of FMR after CRT treatment and the impact of treatment of FMR in patients CRT non responders. We aimed to point out the limits of current step-wised approach in light on more recent evidence regarding FMR treatment. A new, “tailored” approached is proposed.

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.

Effects of exercise training on physical activity in heart failure patients treated with cardiac resynchronization therapy devices or implantable cardioverter defibrillators.

This study elucidated the effects of exercise training on physical activity, 6-min walk distance, and all-cause hospitalization rates in patients with chronic heart failure, and evaluated factors contributing to changes in physical activity. Prospective cohort observational study. Patients (n =62) who completed an exercise training programme after implantable cardioverter-defibrillator or cardiac resynchronization therapy treatment between May 2017 and May 2018 were included. Patients exercised for 20-50 min 3-5 times weekly for 3 months and were assigned to the active (≥ 10 min/day) or non-active (< 10 min/day) group based on changes in walking times between baseline and 3 months, as assessed by the International Physical Activity Questionnaire. The 6-min walk distance improved in both groups with exercise training. Physical activity level did not increase in some patients, despite improvements in exercise tolerance. Depression improved significantly in the active group, but no correlation was found with physical activity. Factors contributing to physical activity changes were not identified. The all-cause hospitalization rate was lower in the active group during follow-up (mean 10.5 months). Exercise training effectively increased 6-min walk distance regardless of physical activity. Non-active patients experienced increased all-cause hospitalizations. Increasing physical activity improves patient outcomes.

553 Acute re-distribution of regional left ventricular work by cardiac resynchronization therapy determines long-term remodelling

Abstract Background In patients with dilated cardiomyopathy and left bundle branch block (LBBB), different regions of the left ventricle (LV) have been shown to perform different amounts of work. In this study, we investigate the acute impact of cardiac resynchronization therapy (CRT) on regional LV work distribution and its relation to long-term reverse-remodelling. Methods We recruited 140 heart failure patients, referred for CRT. Regional myocardial work was calculated from non-invasive echocardiographic segmental stress-strain-loop-area before and immediately after CRT. The magnitude of volumetric reverse-remodelling was determined from the change in LV end-systolic volume (ESV), 11 ± 3 months after implantation. Characteristics of patients with the lowest and highest quartile of LV ESV reverse remodelling (LV ESV reduction of less than 10% and LV ESV reduction of more than -48%) were compared. Results Before CRT, myocardial work showed significant differences among the walls of the LV (Figure A). CRT caused an acute re-distribution of myocardial work, on average with most increase in the septum and most decrease laterally (all walls p &amp;lt; 0.05) and lead to a homogeneous work distribution (Figure B). The acute change in the difference between lateral and septal wall work (Δ Lateral-to-septal work) correlated significantly with LV ESV reverse-remodelling (r = 0.63, p &amp;lt; 0.0001). The smallest changes in work were seen in the patients with the least LV ESV reverse remodelling (Figure C, red markers), while patients with the most LV ESV reverse remodelling showed the largest changes in work (Figure C, green markers). In multivariate linear regression analysis, including conventional parameters such as pre-implant QRS duration, LV ejection fraction, LV end-diastolic volume and global longitudinal strain, the re-distribution of work across the septal and lateral walls appeared as the strongest determinant of volumetric reverse-remodelling after CRT (R²=0.393, p &amp;lt; 0.0001). Conclusions The acute re-distribution of regional myocardial work between the septal and lateral wall of the left ventricle is an important determinant of long term reverse-remodelling after CRT-implantation. Our data suggest that modification of regional loading is the mode of action of CRT treatment. Abstract 553 Figure.

P1238Acute re-distribution of myocardial work by cardiac resynchronization therapy determines long-term remodelling of the left ventricle

Abstract Background In patients with dilated cardiomyopathy and left bundle branch block (LBBB), different regions of the left ventricle (LV) have been shown to perform different amounts of work. In this study, we investigate the acute impact of cardiac resynchronization therapy (CRT) on regional LV work distribution and its relation to long-term reverse-remodelling. Methods We recruited 130 heart failure patients, referred for CRT. Regional myocardial work was calculated from non-invasive echocardiographic segmental stress-strain-loop-area before and immediately after CRT. The magnitude of volumetric reverse-remodelling was determined from the change in LV end-systolic volume (ESV), 11±2 months after implantation. Characteristics of patients with the lowest and highest quartile of LV ESV reverse remodelling (ΔLV ESV &lt;−9% and ΔLV ESV &gt;−48%) were compared. Results Before CRT, myocardial work showed significant differences among the walls of the LV (Figure 1A). CRT caused an acute re-distribution of myocardial work, on average with most increase in the septum and most decrease laterally (all walls p&lt;0.05) and lead to a homogeneous work distribution (Figure 1B). The acute change in the difference between lateral and septal wall work (Δlateral − septal work) correlated best and significantly with LV ESV reverse-remodelling (r=0.62, p&lt;0.0001). The smallest changes in work were seen in the patients with the least LV ESV reverse remodelling (Figure 1C, red markers), while patients with the most LV ESV reverse remodelling showed the largest changes in work (Figure 1C, green markers). In a multivariate-linear-regression-analysis, including pre-implant QRS duration, LVEF, LV EDV and GLS, the re-distribution of work remained as the strongest determinant of volumetric reverse-remodelling after CRT (r=0.63, p&lt;0.0001). Figure 1 Conclusions The acute re-distribution of regional myocardial work between the septal and lateral wall of the left ventricle is the main determinant of long term reverse-remodelling after CRT-implantation. Our data suggest that modification of regional loading is the mode of action of CRT treatment.