CRT Implantation Research Articles

The impact of QRS complex fragmentation status before and after cardiac resynchronization therapy with defibrillator implantation: Is it a predictor of arrhythmic events?

Abstract Introduction Cardiac resynchronization therapy with an implantable cardioverter defibrillator (CRT-D) has demonstrated efficacy in reducing mortality, hospitalization for heart failure (HF), and sudden cardiac death among subgroups of patients with HF with reduced ejection fraction (HFrEF). However, this population is highly heterogeneous, necessitating risk stratification. Several clinical findings, including QRS complex fragmentation (QRSf), have been identified as potential prognostic factors for arrhythmic risk. Nonetheless, evidence supporting the prognostic significance of QRSf in patients undergoing CRT-D remains limited. Purpose The aim of this study is to assess whether alterations in QRSf status, before and after CRT-D implantation, can predict arrhythmic events (AE) in patients with HFrEF. Methods This study included consecutive patients underwent CRT-D implantation at our center from October 2009 to December 2022. Demographic, clinical, electrocardiographic and echocardiographic data were obtained from electronic medical records and telephone interviews. QRSf was defined by the presence of various RSR′ patterns, including additional R waves (R′) or notching of the R and S wave in two contiguous leads corresponding to a primary coronary artery territory on a 12-lead electrocardiogram conducted before and after CRT-D implantation. An AE was characterized by appropriate ICD therapy (antitachycardia pacing or shock) for a ventricular arrhythmia or sustained ventricular arrhythmia without the need for ICD therapy. Results A total of 176 patients were included (mean age 69.9 ± 9.6 years with 80.6% male). Ischemic etiology accounted for 54.6% of cases of LV systolic dysfunction, with a mean baseline LVEF of 23.6%. CRT-D was indicated as secondary prevention in 18 patients. At baseline, 114 patients (64.8%) presented QRSf. Following CRT implantation, 17 patients (9.8%) without previous QRSf developed QRSf, while 26 patients (14.9%) resolved QRSf. The median follow-up was 43.6 months (interquartile range 19.5-81.1). During follow-up, 90 patients died and 29 AE occurred (16.5%). Among these, 23 patients had QRSf before and after CRT, whereas 6 AE occurred in patients without QRSf. Multivariate survival analysis using Cox regression demonstrated that the presence of QRSf before and after CRT-D was an independent predictor of AE (HR 3.56; 95% CI 1.00-12.70). Univariate and multivariate Cox regression analyses are presented in Table 1. Kaplan-Meier curves for AE in relation to QRSf status before and after CRT-D are illustrated in Figure 1. Conclusions Our findings suggest that the presence of QRSf and its persistence following CRT-D implantation appears to be an independent predictor of AE after CRT-D implantation in patients with HFrEF. Therefore, these patients would benefit from closer monitoring as they exhibit a heightened risk of arrhythmic events. Nevertheless, further research is warranted to validate these results.Table 1.Cox Regression Analysis.

Lateral QRS amplitude is independently associated with outcome after cardiac resynchronization therapy: Advancing patient selection?

BackgroundCardiac resynchronization therapy (CRT) is a cornerstone in the treatment of selected heart failure patients. However, a relevant proportion of patients do not show beneficial response. Identification of simple, additive, and outcome-relevant selection criteria may improve selection of patients. ObjectiveWe sought to determine whether baseline QRS amplitude is associated with outcome in CRT. MethodsQuantification of intrinsic, pre–CRT implantation QRS amplitude was performed in an observational multinational 2-center retrospective cohort analysis (derivation cohort Zurich, n = 178, 2000–2015; validation cohort Leuven, n = 183, 1999–2016) with a composite end point of all-cause mortality, ventricular assist device implantation, or heart transplantation at 5 years. ResultsHigher baseline to peak amplitude in lateral leads (lead I and V6) was associated with a lower risk of reaching the composite end point (lead I: hazard ratio, 0.86 [95% confidence interval, 0.78–0.95] per millivolt, P = .002; lead V6: hazard ratio, 0.94 [95% confidence interval, 0.88–1.00] per millivolt, P = .043). Concordance index–based comparison of quartile, spline, and receiver operating characteristic curve analysis suggested cutoff values of 6 mV for lead I and 3 mV for V6 for optimal discrimination of outcome. External validation confirmed the cutoff of 3 mV in lead V6 as a highly significant discriminator of outcome (P < .001) associated with a risk reduction of 65%. ConclusionLow QRS amplitude in lateral electrocardiogram leads is associated with higher risk of poor outcome in CRT patients. A cutoff of 3 mV in lead V6 proved highly discriminative. Further studies need to confirm the additive value of QRS amplitude in selection of patients for CRT and to assess whether CRT may be made available to more patients.

QRS length/left ventricular mass index: a novel predictive factor of response to cardiac resynchronization therapy

Abstract Introduction The length of QRS interval is an extensively studied predictor of response to CRT. There is little evidence of the probability of response in patients with QRS between 130 and 150 ms and its relationship with LV mass. (1,2) Objective Evaluation of the QRS length/LV mass index (QRS/LVMi) as a "relative dyssynchrony" marker and its correlation to response after CRT implantation. Methods Retrospective study that included patients over 18 years of age with HFrEF (LVEF ≤ 35%) and CRT implantation between years 2018 – 2022 (n = 92). QRS length (ms) was measured with CardioLab 3.0 Software and divided by LV mass (g), according to Deveraux equation using echocardiography measurements. Primary outcome was response to CRT defined by: Improvement of at least 1-point in NYHA functional class + (i) increase of at least 5% in LVEF or (ii) decrease of at least 15% in LVESD. Results QRS/LVMi value ≥ 0.6 was associated with a higher frequency of response to CRT than values &amp;lt; 0.6 (83% responders vs 17% non responders; OR 5.1; CI 2.7–12.1, p &amp;lt; 0.05). There was no difference in response to CRT between QRS &amp;gt; 150 ms and 130 – 150 ms in patients with QRS/LVMi ≥ 0.6 (80% vs 82% of responders, p = 0.8). A multivariate analysis showed a significantly higher probability of response to CRT in patients with QRS/LVMi ≥ 0.6 compared to other known predictive factors (OR 4.1; CI 1.2–12, p &amp;lt; 0.05). Conclusions The use of QRS/LVMi was associated with a better prediction of response to CRT than other traditional factors. There was no difference in response between QRS &amp;gt; 150 ms and 130 - 150 ms in patients with QRS/LVMi ≥ 0.6, suggesting the efficacy of CRT in patients with shorter QRS interval length and less LV mass, highlighting the importance of the concept of relative dyssynchrony.Total Response according QRS/LMViMultivariate analysis

Feasibility and effectiveness of left bundle branch area pacing after TAVR: the single center experience

Abstract Introduction Transcatheter aortic valve replacement (TAVR) is a safe alternative to open-heart surgery in patients with symptomatic severe aortic stenosis and high surgical risk due to multiple comorbidities, advanced age, and severe left ventricle dysfunction. Due to anatomical considerations of the atrioventricular node, conduction abnormalities requiring the implantation of a pacemaker are common findings after TAVR. High-grade atrioventricular block and new-onset left bundle branch block (LBBB) are the most commonly reported conduction abnormalities after TAVR. Purpose The aim of our study was to assess the feasibility, success rates, and effectiveness of LBBAP in patients requiring pacing after TAVR. Methods A total of 302 patients underwent the TAVR procedure in our institution in the period from January 2022 to November 2023. In this cohort, 38 patients required ventricular pacing in the postoperative period. 16 patients who underwent permanent pacing using LBBAP were included in this observational study. Patients undergoing traditional right ventricular pacing biventricular pacing or leadless pacemaker implantation were excluded from the study. Results LBBAP was successfully performed in 16 patients (89%). 2 patients underwent conventional CRT implantation (1 cardiac resynchronization therapy pacemaker and 1 cardiac resynchronization therapy defibrillator) in order to severe calcification and presence of fibrotic tissue in the target area. The mean age was 60.5±2.74 years, and 10 patients (62.5%) were women. According to the patient’s medical history, 14 patients (84%) had hypertension; coronary artery disease – 2 (12.5%), 2 (12.5%) patients had atrial fibrillation and atrial flutter, and 7 (43.5%) patients had diabetes mellitus. The mean left ventricle ejection fraction (LVEF) was 46.2±14.7%. Interventricular septal thickness 11.8 ± 1.9 mm. Type of conduction diseases: Infranodal AV block and LBBB were present in 9 (56.5%) patients. 5 (31,25%) patients had persistent complete AV block and 2 (12,25%) had Mobitz II AV block. In 2 patients we observed congestive heart failure combined with LBBB. Pre-TAVR QRS morphology was normal in 15 (93%), and RBBB morphology in 1 (7%). The mean QRS duration at baseline was 105±20 ms. Pre-implant QRS duration 135±52 ms. The single-chamber pacemaker was implanted in 1 patient, dual-chamber pacemaker - 13 patients, and cardiac resynchronization therapy defibrillators in 2 patients. Procedural duration and fluoroscopy times were 105. ± 31.9 min and 18 ± 11 min, respectively. Conclusion Complete AV block and new-onset LBBB after TAVR is still an important issue. LBBB correction using conduction system pacing technology is an effective strategy for this type of patient. LBBAP is one of the most exciting developments in pacing therapy over the last few years. Long-term clinical outcomes and safety of physiological pacing data are limited and require further investigations

Left atrial strain measurement in patients with heart failure and atrial fibrillation compared to a control group

Abstract Background Left atrial (LA)-strain measurement is a non-invasive and widely available echocardiographic method to detect atrial cardiomyopathy as a process of structural and functional remodeling. The aim of this study is to measure LA-strain in patients with heart failure (HF) and atrial fibrillation (AF), compared to patients without structural heart disease and to evaluate whether or not LA-Strain could be part of a multi-modality assessment that influences therapy strategies and prognosis in patients suffering AF. Methods This study includes 18 patients with HF in sinus rhythm who underwent CRT implantation (HF group), 25 patients with persistent AF and preserved ejection fraction (EF) who underwent left atrial catheter ablation (AF group) and 22 patients without structural heart disease or AF who underwent electrophysiological study (control group). All subjects received measurement of reservoir (LASr), conduit (LAScd) and contraction (LASct) LA strain imaging using two-dimensional speckle tracking echocardiography (2D-STE). Results Patient characteristics in the HF-group showed mean age 68y (SD 10,6), mean EF 29% (SD 6,8), 66% male compared to the AF-group with mean age 66y (SD 8.0), mean EF 60% (SD 5.1), 68% male. The control-group showed mean age 55y (SD 13.8), mean EF 60% (SD 5.4), 55% male. For LASr we found normal values in the control groups and reduced values in the HF und AF group (HF: mean 20% [9 – 45%], AF: mean 24% [7 – 52%], control: mean 42% [30 – 67%]). In LASr, LAScd and LASct there was a statistically significant difference between the HF and the control group (p &amp;lt; 0.001) as well as the AF and control group (p &amp;lt; 0.001), whereas there was no difference between AF and HF group (p = 0.444). Discussion Patients with persistent AF show similar LA-strain compared to patients with HF and patients without structural heart disease present significant better LA strains. The findings of this study suggest, that LA strain analysis might contribute to comprehensive assessment of patients with AF especially as a simple imaging method. A limitation of our results could be the significant younger age of our control group (p = 0.004) as fibrotic remodeling increases in advanced age. It remains to be analyzed whether early AF treatment could prevent further fibrotic remodeling and whether measuring LA strain could provide further information for risk stratification and the definition of therapeutic intervention strategies.

Evaluation of synchronized left ventricular pacing rate over biventricular pacing in cardiac resynchronization therapy

BackgroundThe adaptive cardiac resynchronization therapy (aCRT) algorithm enables synchronized left ventricular pacing (sLVP) to achieve fusion with intrinsic right ventricular activation. Although sLVP presents benefits over biventricular pacing, the adequate sLVP rate for better clinical outcomes remains unclear. We aimed to assess the association between sLVP rates and clinical outcomes. MethodsOur study cohort included 271 consecutive patients, who underwent CRT implantation between April 2016 and August 2021. ResultsWe evaluated 63 patients on whom we applied the aCRT algorithm [48 men, mean age: 64 ± 14 years; median follow-up period: 316 days (interquartile range: 212–809 days)]. At the 6-month follow-up after CRT implantation, the frequency of CRT responders was 71 % (n = 45). The sLVP rate was significantly higher in responders than in non-responders (75 ± 30 % vs. 47 ± 40 %, p = 0.003). Receiver operating characteristics curve analysis revealed that the optimal cut-off value during the sLVP rate was 59.4 % for the prediction of CRT responders (area under the curve, 0.70; sensitivity, 80 %; specificity, 61 %; positive predictive value, 84 %; and negative predictive value, 55 %). Kaplan–Meier analysis demonstrated that the higher-sLVP group (sLVP ≧59.4 %, n = 43) had a better prognosis (cardiac death and heart failure hospitalization) than the lower-sLVP group (sLVP <59.4 %, n = 20) (log-rank p < 0.001). Multivariate Cox hazard analysis revealed that a higher sLVP rate was associated with a good prognosis (p < 0.001). ConclusionssLVP was associated with CRT response, and a higher sLVP rate (≧59.4 %) was important for good prognosis in patients with aCRT.

Clinical characteristics and outcome of cardiac resynchronization therapy for heart failure in National Hospital of Sri Lanka from year 2005 to 2020 – a retrospective observational study

BackgroundCardiac resynchronization therapy (CRT) has been a well-established treatment modality for moderate to severe left ventricular systolic dysfunction with left ventricular desynchrony. This is the pioneering study that analyses the cohort who underwent CRT implantation at the National Hospital of Sri Lanka (NHSL) in Colombo from 2005 to 2020.ObjectivesThis study was carried out to describe socio-demographic factors, improvements in clinical outcome (symptoms, electrocardiographic, and echocardiographic features), and post-CRT complications in the study population, as well as to determine the efficacy of CRT in heart failure.MethodA retrospective observational study was conducted on all the living patients who had undergone CRT implantation from 2005 to 2020. The data was gathered from all the consented patients who visited the device programming clinic using a physician-administered questionnaire and clinical records. Data was analyzed using SPSS 25, and significant statistics were assessed with the McNemer test, the Student T test, and the Chi-Squared test.ResultsThe study included 50 patients with a mean age of 52.82+/− 11.66 years and female predominance (56%, n = 28). Idiopathic dilated cardiomyopathy (50%, n = 25) was the leading etiological factor, followed by ischemic cardiomyopathy (28%, n = 14). Clinical symptoms have improved significantly with CRT implantation (p < 0.001). A significant improvement was found in NYHA functional class (p < 0.001, 95% CI = 0.072 to 0.284), QRS width (p < 0.001, 95% CI = 0.229 to 0.534), ejection fraction (p < 0.001, 95% CI = − 16.437 to − 8.504), and LV EDD (p < 0.001, 95% CI = 2.89 to 9.24). Post-CRT complications included lead malfunction (6%, n = 3) and chronic (14%, n = 7), bleeding or hematoma (2%, n = 1), pocket erosion or infection (6%, n = 3), and infective endocarditis (2%, n = 1).ConclusionAccording to the study, CRT significantly improves both clinical and functional outcomes in patients with moderate to severe heart failure.

Navigating Heart Failure: Unveiling Sex Disparities in Guideline-Directed Medical Therapy Combinations

Major heart failure (HF) trials remain insufficient in terms of assessing the differences in clinical characteristics, biomarkers, treatment efficacy, and safety because of the under-representation of women. The study aimed to present sex-related disparities in HF management, including differences in demographics, co-morbidities, cardiac biomarkers, prescribed medications, and treatment outcomes. The study utilized anonymized data from the Turkish Ministry of Health's National Electronic Database between January 1, 2016, and December 31, 2022. The cohort analysis included 2,501,231 adult patients with HF. Specific therapeutic combinations were analyzed using a Cox regression model to obtain relative risk reduction for all-cause death. The primary end point was all-cause mortality. In the cohort, 48.7% (n = 1,218,911) were male, whereas 51.3% (n = 1,282,320) were female. Female patients exhibited a higher median age (71 vs 68 years) and manifested higher prevalence of diabetes mellitus, anemia, atrial fibrillation, anxiety, and ischemic stroke. Male patients demonstrated higher rates of previous myocardial infarction, dyslipidemia, chronic obstructive pulmonary disease, and chronic kidney disease. Higher concentrations of natriuretic peptides were observed in female patients. Renin-angiotensin aldosterone inhibitor, β blockers, mineralocorticoid receptor antagonists, sodium/glucose cotransporter 2 inhibitor (SGLT2i), and ivabradine were more commonly prescribed in male patients, whereas loop diuretics, digoxin, and ferric carboxymaltose were more frequent in female patients. Male patients had higher rates of cardiac resynchronization therapy and implantable cardioverter defibrillator implantation rates. All-cause mortality and hospitalization rates were higher in male patients. Compared with monotherapy, all combinations, including SGLT2i, showed a beneficial effect on all-cause mortality in both female and male patients with HF. In hospitalized patients with HF, the addition of digoxin to renin-angiotensin aldosterone inhibitor, mineralocorticoid receptor antagonists, and β blockers was superior to monotherapy regarding all-cause mortality in female patients with HF compared with male patients with HF. In conclusion, this study highlights that sex-specific responses to HF medication combinations compared with monotherapy and differences in co-morbidities underscore the importance of tailored management strategies. Digoxin showed a contrasting effect on all-cause mortality between both sexes after hospitalization, whereas SGLT2i exhibited a consistent beneficial effect in both sexes when added to all combinations.

Outcomes of cardiac resynchronization therapy in congenital heart disease: A meta-analysis and systematic review.

Cardiac resynchronization therapy (CRT) is a standard treatment for patients with heart failure with reduced ejection fraction. However, there is still a gap of evidence in congenital heart disease (CHD) patients regarding resynchronization therapy. We performed a meta-analysis and systematic review of CHD patients who received CRT implantation. We comprehensively searched the databases of MEDLINE, EMBASE, and Cochrane database from inception to June 2023. Studies that reported response rate to CRT, total mortality rate, change in QRS duration, change in left ventricular ejection fraction, and change in New York Heart Association functional class were included. A total of 14 studies were included in the study. There were 10 studies that reported response rates after implantation. The overall response rate to CRT in CHD patients was 68% (95% confidence interval [CI] 61%-75%, I2 32%). The response rates in patients with systemic right ventricle (RV), systemic left ventricle (LV), and single ventricle were 58% (95% CI 46%-70%, I2 0%), 80% (95% CI 74%-86% I2 14%), and 67% (95% CI 49%-80% I2 0%). Response to CRT in systemic RV was inferior to systemic LV with an odds ratio of 0.38 (95% CI 0.15-0.95, I2 38%). The total mortality rate from sevenstudies was 12% (95% CI 8%-18%, I2 55%). The parameters which represented ventricular dyssynchrony improved after CRT implantation. The overall response rate to CRT in CHD was 68%. Patients with systemic RV had a lower response rate to CRT when compared to patients with systemic LV. The total mortality rate after CRT implantation was 12%.

Role of fragmented QRS complex in the prognosis of patients undergoing cardiac resynchronization therapy. A new red flag to look for?

Abstract Introduction Cardiac resynchronization therapy (CRT) has demonstrated to reduce mortality and hospitalization for heart failure in selected patients with heart failure with reduced ejection fraction (HFrEF). However, there is a significant percentage of readmissions for heart failure (HF) after implantation. In the recent years, several biomarkers and electrocardiographic findings possibly related with prognosis in this group of patients have been identified. Fragmentation of QRS complex (fQRS) has been related with worse prognosis in various cardiac diseases, but the evidence in patients undergoing CRT is limited. Purpose The objective of this study is to evaluate if the presence of pre-implantation fragmented QRS complex has a prognostic role in patients undergoing cardiac resynchronization therapy in terms of hospitalization for HF. Methods Consecutive patients undergoing CRT were prospectively included from October 2009 to December 2022. Demographic clinical, electrocardiographic and echocardiographic variables were recorded. Prospective follow-up variables were collected from electronic clinical records and telephone interview. Fragmentation of the QRS complex was defined by the presence of different RSR′ patterns including an additional R-wave (R′), notching of the R-wave and S-wave or the presence of more than 1R′ in two contiguous leads corresponding to a main coronary artery territory. Results 244 patients were included. Mean age at the implantation of the device was 71.8 years (standard deviation, SD ±9.8 years), 79.5% were male and 40.2% were diabetic. Mean LVEF was 24.9% (SD ±8.9) and the aetiology was non-ischaemic in 50.8% of the patients and ischaemic in 49.2%. 40.2% had prior history of acute myocardial infarction. Pre-implantation fragmented QRS complex was found in 58.6% of the patients and mostly in inferior leads of the surface ECG. Mean QRS duration was 157.9ms and 82.0% had left-bundle branch block morphology. CRT with defibrillator implantation was performed in 71.4% of the patients. The median follow-up time was 27.4 month. After device implantation, mean LVEF was 33.2% and 76.6% presented NYHA class I-II. During this period, 28.7% of the patients died. Additionally, 29.1% of the patients presented at least one hospitalization for heart failure (HF), 22.5% with fQRS and 6.6% without fQRS. A multivariate survival study using Cox regression showed that the presence of pre-implantation fQRS was an independent predictor of HF hospitalization events (HR 2.24; 95% CI 1.20-4.18). Figure 1 presents Kaplan-Meier curves for hospitalization for HF. Conclusions According to our results, pre-implantation fQRS is a strong independent predictor of hospitalization for HF after CRT implantation. Thus, patients with fQRS could benefit from a more rigorous follow-up as they present higher risk of decompensation. Further research is needed to confirm our findings.Figure 1.Kaplan-Meier curves

Long-term outcome after upgrade to cardiac resynchronization therapy: A propensity score-matched analysis.

Cardiac resynchronization therapy (CRT) is a cornerstone in the management of chronic heart failure in patients with a broad or paced QRS. However, data on long-term outcome after upgrade to CRT are scarce. This international, multicentre retrospective registry included 2275 patients who underwent a de novo or upgrade CRT implantation with a mean follow-up of 3.6 ± 2.7 years. The primary composite endpoint included all-cause mortality, heart transplantation, or ventricular assist device implantation. The secondary endpoint was first heart failure admission. Multivariable Cox regression and propensity score matching (PSM) analyses were performed. Patients who underwent CRT upgrade (n = 605, 26.6%) were less likely female (19.7% vs. 28.8%, p < 0.001), more often had ischeemic cardiomyopathy (49.8% vs. 40.2%, p < 0.001), and had worse renal function (median estimated glomerular filtration rate 50.3 ml/min/1.73 m2 [35.8-69.5] vs. 59.9 ml/min/1.73 m2 [43.0-76.5], p < 0.001). The incidence rate of the composite endpoint was 10.8%/year after CRT upgrade versus 7.1%/year for de novo implantations (p < 0.001). PSM for the primary endpoint resulted in 488 pairs. After propensity score matching, upgrade to CRT was associated with a higher chance to reach the composite endpoint (multivariable hazard ratio [HR] 1.35, 95% confidence interval [CI] 1.08-1.70), for both upgrade from pacemaker (multivariable HR 1.33, 95% CI 1.03-1.70) and implantable cardioverter-defibrillator (ICD) (multivariable HR 1.40, 95% CI 1.01-1.95). PSM for the secondary endpoint resulted in 277 pairs. After PSM, upgrade to CRT was associated with a higher chance for heart failure admission (HR 1.74, 95% CI 1.26-2.41). In this retrospective analysis, the outcome of patients who underwent upgrades to CRT differed significantly from patients who underwent de novo CRT implantation, particularly for upgrades from ICD. Importantly, this difference in outcome does not imply a causal relation between therapy and outcome but rather a difference between two different patient populations.

The predictive role of left ventricular cathode topography relative to CMR-determined latest mechanical activation and scar segments on response to cardiac resynchronisation therapy

Abstract Background Cardiac resynchronisation therapy (CRT) is still burdened by considerable rates of non-response. Herein left ventricular cathode (LVC) positioning has the greatest room for optimisation. Nonetheless, a purely CMR-based approach exploring LVC topography relative to both mechanical delay and tissue viability is yet to be investigated. Purpose To retrospectively analyse the effect on reverse remodelling of CMR-determined LVC topography relative to latest mechanical activation (LMA) and scar segments in a CRT population. Methods This is a retrospective single-centre analysis of 104 CRT-D/P consecutive patients with CMR performed within 6 months before implantation. Electrical delay (Q-LV time) was mapped on all suitable veins with LV lead positioning and cathode programming set in the region of latest electrical activation. Through CART-Tech® software analysis of CMR images, 36-segment 3D anatomical models of radial strain and scar were superimposed on their corresponding fluoroscopy images (Figure 1). Patients were then stratified based on LVC concordance (within), semi-concordance (adjacent) or non-concordance (at least one segment away) with LMA and scar segments (defined as segments with &amp;gt;50% scar transmurality). Follow-up echocardiography was performed at least 6 months after implantation and the degree of reverse remodelling expressed as percentage reduction in end-systolic volume (ESV). Results Of the 104 patients, 36 were excluded due to suboptimal CMR quality (8), switch to conduction system pacing (5), loss to follow-up (18) or death within 6 months of implantation (5), leaving a total of 68 (63 CRT-D and 5 CRT-P). LVC concordance with LMA was associated with a statistically significant improvement in reverse remodelling (Figure 2, A), while the contrary occurred with regards to scar (Figure 2, B). A greater impact of distance from scar compared to LMA proximity was observed, thus a combined analysis of LVC topography relative to both was developed accordingly. Patients were stratified into 4 categories of LVC optimality: optimal (LVC-LMA concordance + LVC-scar non-concordance), semi-optimal (LVC-LMA semi-concordance + LVC-scar non-concordance), suboptimal (LVC-LMA non-concordance + LVC-scar non-concordance), and unfavourable (LVC-scar semi-concordance or concordance regardless of LVC-LMA). The unfavourable group had higher rates of atrial fibrillation, non-LBBB QRS morphology and higher scar burden, while no significant differences were observed in the other 3 groups. This classification appears to predict the degree of reverse remodelling, ESV reduction being more pronounced the more optimal the group (Figure 2, C). Conclusions CMR-determined LVC topography relative to LMA and scar segments predicts left ventricular reverse remodelling in Q-LV-guided CRT implants. Optimisation of CRT response may thus benefit from a CMR-based approach assessing mechanical delay and tissue viability to guide LVC positioning.Figure 1Figure 2

Association of echocardiography-derived hemodynamic force parameters with left ventricular reverse remodeling after cardiac resynchronization in non-ischemic cardiomyopathy

Abstract Background Cardiac resynchronization therapy (CRT) improves outcome in selected heart failure patients and can induce left ventricular (LV) reverse remodeling. Echocardiography-derived hemodynamic forces (HDF) are a new clinical tool which provides insight in fluid dynamics. Purpose To evaluate whether baseline HDF parameters are associated with LV reverse remodeling at six months after CRT implantation in patients with non-ischemic cardiomyopathy. Methods From a CRT database, patients with LV ejection fraction &amp;lt;35%, QRS duration &amp;gt;130ms and left bundle branch block were included. At baseline, the following HDF parameters were measured for the complete heart cycle (Figure 1): 1) apical-basal strength, representing the magnitude of the longitudinal HDF, 2) lateral-septal strength, representing the magnitude of the transversal HDF and 3) the angle, representing the HDF orientation. In the systolic thrust (i.e. the positive part of systole in the apical-basal curve), the apical-basal impulse (AB impulse) and the systolic angle were measured. LV reverse remodeling was defined as a reduction of LV end-systolic volume ≥15% at six months. Results In total, 196 patients were included (age 64±11 years, 62% male). LV reverse remodeling was observed in 136 (69%) patients (i.e. responders). Baseline characteristics are presented in Table 1. Responders had a higher angle in the complete heart cycle (67.1 vs 64.1; p = 0.002) as compared to non-responders, indicating less deviation of HDF orientation in responders. Responders also had a higher AB impulse (5.0% vs. 3.4%, p = 0.012) and higher systolic angle (74.0 vs. 71.0), p&amp;lt;0.001), indicating larger magnitude of HDF and less deviation of HDF orientation in the systolic thrust. Univariable logistic regression showed a significant association of loop diuretic use, LV global longitudinal strain (LV GLS), left atrial volume index (LAVI), the angle, AB impulse and the systolic angle with LV reverse remodeling. To minimize collinearity, two multivariable models were built. Loop diuretic use, LV GLS, LAVI and AB impulse were inserted in both models, while the angle was inserted in the first model and the systolic angle in the second model. In the first model, the angle (HR 1.082 (95%CI 1.018, 1.150), p = 0.011) was independently associated with LV reverse remodeling while the systolic angle (HR 1.073 (95%CI 1.011, 1.140), p = 0.021) was independently associated with LV reverse remodeling in the second model. Conclusion At baseline, responders have better orientation of HDF in the complete heart cycle and larger magnitude and better orientation of HDF in the systolic thrust as compared to non-responders. The orientation of HDF in the complete heart cycle and systolic thrust is independently associated with LV reverse remodeling. As such, the angle and systolic angle of HDF have the potential to identify patients that are likely to experience LV reverse remodeling after CRT.Figure 1.HDF in non-ischemic CMPTable 1.Baseline characteristics

Non-progressors to cardiac resynchronization therapy show long-term mortality benefit compared to progressors

Abstract Introduction Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in selected patients with symptomatic heart failure with reduced ejection fraction (HFrEF) and prolonged QRS. However, approximately one-third of the implanted patients fail to show clinical improvement or reverse remodeling. The criteria by response have been recently changed, those patients with a minimal improvement in left ventricular ejection fraction (LVEF) are defined as "non-progressors" rather than as "non-responders", selecting from those patients in whom the progression could not be modified. Data are scarce regarding the long-term outcome of this patient population. Purpose We aimed to evaluate the long-term outcome of CRT patients by their response, comparing non-progressors with responders and progressors. Methods Altogether 1019 patients undergoing CRT implantation between 2000-2020 in our center were registered and analyzed retrospectively. Patients were divided into 4 groups according to their response status, which was defined on the basis of LVEF change in 12 months after CRT implantation as follows: super-responders ≥20% (n=113), responders 6-19% (n=448), non-progressors 0-5% (n=244), and progressors &amp;lt;0% (n=214). The primary endpoint was the composite of all-cause mortality, heart transplantation, or left ventricular assist device implantation. Results During the median follow-up time of 4.7 years 547 (54%) patients died, 35 (31%) super-responder, 223 (50%) responder, 133 (55%) non-progressor, and 156 (73%) progressor. The mean change in LVEF occurred as follows: super-responders 24.5% ± 4.1%, responders 11.5% ± 3.8%, non-progressors 2.8% ± 1.8%, and progressors -6.6% ± 4.5% (p&amp;lt;0.0001). Non-progressors were more commonly male, had worse NYHA functional status, worse renal function, higher baseline LVEF and serum creatinine levels, and more frequently had an ischemic etiology. Univariate Cox regression analysis revealed that non-progressors had similar outcome to responders (HR 1.17; 95%CI 0.94-1.45; p=0.15) and superior outcome to progressors (HR 0.60; 95%CI 0.48-0.76; p&amp;lt;0.0001), which was also confirmed by multivariate analysis after adjustment for age, gender, ischemic etiology, LVEF, and serum creatinine levels: nonprogressors vs. responders (HR 1.25; 95%CI 0.98-1.58; p=0.07) and nonprogressors vs. progressors (HR 0.62; 95%CI 0.47-0.80; p&amp;lt;0.0001). Conclusions In our current study, non-progressors to CRT had a similar long-term outcome to responders and superior outcome to progressors. These findings suggest that non-progressor patients would have continued to adversely remodel without CRT and CRT is beneficial for these patients by moderating the remodeling process rather than improving it. Our results support the fact that categorizing patients as "responders" or "non-responders" is inappropriate and patients could be grouped as super-responders, responders, non-progressors, and progressors.Probability of survival by CRT responseMultivariate analysis by response status

Behavior of coronary sinus oxygen saturation and cardiac output in systolic heart failure

Abstract Background CRT implantation is indicated in advanced systolic heart failure (LV-EF &amp;lt; 35%) on optimal medical therapy and left bundle branch block with wide QRS complex (QRS &amp;gt; 150 ms). This study investigates the influence of different variables on venous saturation in the coronary sinus during HFrEF. Methods In this study, blood gas analyses (BGA) of patients undergoing CRT implantation were performed at our center. Patients with an electrophysiological study but without structural heart disease served as a control group. In all patients a BGA from the coronary sinus was performed. Arterial and central venous saturation were used to determine cardiac output (CO) according to Fick's principle. Oxygen uptake was calculated from body surface area and age. Results In total, the study population included 19 patients in the CRT and 18 patients in the control group. The median age of the CRT group was 75 years (54-87 years) and in the control group 58 years (36-81 years). In the CRT group 53% had ischaemic cardiomyopathy. The saturation in the coronary sinus was 30.3% in CRT patients and was therefore significantly lower than in the control group (40.0%, p = 0.02). However, CO at rest did not differ in both groups (CRT 6.8 L/min vs. control 7.4 L/min.). It was observed that the coronary sinus saturation was independent of CO and the genesis of heart failure. In contrast, QRS width before CRT implantation was negatively correlated with saturation in the coronary sinus (r = - 0.58, p = 0.01). Conclusion In patients with systolic heart failure and despite a normal CO, a decreased oxygen saturation in the coronary sinus at rest was found compared to cardiac healthy subjects. CS saturation correlates negatively with the width of the QRS complex. It is not dependent on age, LV function and the genesis of heart failure.

Determinants and differences of delay in cardiac resynchronization therapy

Abstract Background Cardiac resynchronization therapy (CRT) is recommended for the treatment of heart failure (HF) patients with reduced ejection fraction and left bundle branch block (LBBB) but is still largely underused which may further deteriorate the HF condition. Studying the impact and factors related to delays in CRT with or without an Implantable cardioverter defibrillator (ICD) is fundamental to enhance CRT implementation in clinical practice. Methods We used a central ECG database together with National patient registries to identify LBBB patients with a QRS duration of more than 150 ms and estimated a class I indication for CRT based on a registered diagnosis of HF and ejection fraction &amp;lt; 35% (baseline date). We compared patient characteristics in those with CRT-D, CRT without defibrillator (CRT-P) and patients with an indication but without CRT. Factors associated with CRT-P or CRT-D were analyzed as well as factors related to delay in CRT utilization. Outcome parameters were HF hospitalization and combined total and CV mortality and the impact of the delay in CRT utilization on outcome was analysed. Results Of 5359 patients with LBBB and QRS &amp;gt; 150ms, 1268 (24%) developed a class I indication for CRT. Of these 31% received a CRT-P, 36% CRT-D and 33% were not implanted. Independent predictors for CRT-P were age &amp;gt; 75 years and for CRT-D ischemic heart failure aetiology, hypertension and male sex. Patients with CRT-D had similar HF hospitalization rate (hazard ratio (HR): 0.95, 95% (CI) 0.80-1.14) as patients with CRT-P. In contrast, patients indicated but not implanted with CRT had a significantly higher prevalence of HF hospitalization (HR: 1.65, CI 1.39-1.96). A delay in CRT use &amp;gt; 365 days (161 patients) from indication (baseline) was associated with increased risk of overall mortality and cardiovascular mortality compared to CRT implantation &amp;lt; 30 days from the indication (HR: 1.64, CI 1.05-2.55 and HR: 1.87, CI 1.10-3.18). Age &amp;gt; 75 years, male sex, paroxysmal atrial fibrillation, diabetes and ischemic heart disease were associated with significant delay in CRT use (&amp;gt;365 days). Conclusion In a large real-world setting, delay in CRT implantation was common and associated with increased mortality. The findings suggest a need for new methods to find and treat HF patients with an indication for CRT.

QRS width variation as a marker of prognosis after CRT implantation: getting slimmer is getting better

Abstract Introduction Cardiac resynchronization therapy (CRT) is a major therapeutic tool in the management of patients with systolic heart failure. However, controversy remains regarding who will most benefit from this device. The aim of the present study was to evaluate the impact of QRS duration on echocardiographic response and clinical outcomes. Methods We conducted a retrospective, observational, single-center study of patients submitted to CRT implantation. Only patients with electro and echocardiographic data on baseline and follow-up were included. CRT response was defined as an improvement of LVEF &amp;gt;10% or LVESV&amp;gt;5%. CRT superresponse was defined as an improvement of LVEF above the population 4th quartile (18%). Impact of QRS variables on CRT response was evaluated with ROC curve analysis. Clinical outcomes were defined as hospitalizations due to heart failure and all-cause mortality. Impact of QRS on clinical endpoints, response and superresponse was evaluated with survival analysis. Results From a total of 654 pts a total of 245 fulfilled the inclusion criteria. (57,3%% female, mean age). Most of the pts had a non-ischemic etiology (61,5%) and atrial fibrillation was present in 29.4%. The QRS characteristics were the following, baseline: 162+21ms, follow-up 159+28ms, mean QRS variation: 3+29ms. CRT response occurred in 69% of the pts and superresponse in 26%. QRS variation is the best predictor of CRT response (AUC =0,66, 95%CI 0,58-0,74, p&amp;lt;0,001). Interestingly, a QRS reduction above 8ms presented the best accuracy (S:70%;E:57%) for response to CRT. On multivariate analysis, after adjustment for gender, atrial fibrillation and cardiopathy etiology, only a QRS reduction above 8ms (p 0.028, HR 1.974 CI (1.075-3.623) and lower baseline LVEF (p = 0.02, 95% CI 0.943 (0.909-0.979) were significant independent predictors of CRT superresponse. Additionally, a QRS reduction higher than 8ms was a protective factor for long-term clinical outcomes during follow-up (p&amp;lt;0.001 HR (2,445) 1,553 a 3,849) – fig.1. Conclusion In pts with implanted CRT a reduction in QRS width, as small as 8ms, its a marker of improved LV function and a better clinical prognosis.

Acute deterioration in dyssynchrony and systolic function from Lot-CRT to LBBB pacing

Abstract Background Better electrical synchronization and left ventricular (LV) systolic function was recently reported in left bundle branch–optimized cardiac resynchronization therapy ( Lot-CRT ) when compared with conventional CRT. The implantation of left bundle branch pacing (LBBP) is less expensive, easier to operate and has shorter exposure time to X-ray than Lot-CRT. Purpose To observe whether there are negative changes in dyssynchrony and LV systolic function when switched from Lot-CRT to LBBP. determine whether LBBP pacing alone can replace CRT therapy. Methods 30 patients (21 males, 64.4±9.5 years, 43% with persistent atrial fibrillation) who fulfilled the criteria of CRT implantation received Lot-CRT. The right atrial electrode of the patients with atrial fibrillation or the right ventricular electrode of those with sinus rhythm was implanted into the left bundle branch area. After six months, 20 patients whose LV ejection fraction (LVEF) increased by more than 5% and New York Heart Association functional class increased by at least 1 grade were selected for further investigation. Right and left ventricular pacemaker electrodes were programmed to shut off, leaving only the left bundle branch area pacing for one month. The LV size, systolic function, interventricular mechanical delay (IVMD), and LV mechanical dyssynchrony (LVMD) were compared by using two-dimensional speckle tracking echocardiography. Results It was found that QRS duration slightly widened, the LA size increased, the LV size slightly increased and LVEF decreased, p&amp;lt;0.05. There was no statistical significance in the IVMD (p=0.064). The LV mechanical dyssynchrony increased significantly, p&amp;lt;0.001. Conclusions Deteriotation of LV dyssynchrony and systolic function was recorded when Lot-CRT to LBBP for a short period in recovering patients with systolic dysfunction. It indicates that LBBP may not yet maintain the benefits of Lot-CRT in this group of patients.The comparison between Lot-CRT and LBBP

Assessment of fibrosis in heart failure and atrial fibrillation using TIMP- 1 serum levels

Abstract Background Tissue inhibitor of metalloproteinase- 1 (TIMP-1) levels are strongly associated with cardiac extracellular matrix accumulation and atrial fibrosis. The aim of this study was 1) to compare the TIMP-1 plasma levels in heart failure (HF) and atrial fibrillation (AF) patients and 2) to search for a local production in the heart. Methods This study included 13 patients with HF who underwent CRT implantation (CRT- group), 13 patients with persistent AF who underwent left atrial catheter ablation (AF- group) and 13 patients without structural heart disease or AF, who underwent electrophysiological study (control group). Blood was collected at the begin of the procedures from the coronary sinus (CS), superior vena cava (SVC) and aorta (Ao). Level of TIMP-1 in the CS (TIMP-1-CS), RA (TIMP-1-SVC) and aorta (TIMP-Ao) was measured. Results Patients characteristics: CRT- group: mean age 74y, 8 male, LV- EF 32%, 3 with a history of atrial fibrillation. AF- group: mean age 68y, 9 male, LV- EF 55%. Control- group: mean age 54y, 9 male, LV- EF 65%. The levels of TIMP-1 in the SVC was in the CRT group significantly higher 213 ± 70 ng/ml vs 160 ± 23 ng/ml in controls (p= 0,03). The level of TIMP-1 in the AF- group (191 ± 73 ng/ml) was not significantly different from the control group (p= 0,195) (figure 1). At the various collection sites (CS, SVC and aorta), no significant differences between the 3 groups were noted. Discussion: TIMP-1 serum levels in HF patients are significantly elevated compared to a control group without structural heart disease. No significant differences in levels of TIMP-1 were seen between AF patients and the control group. This is an expression of the advanced disease in the HF patients. The source of serum TIMP-1 are unclear as differences in the level of TIMP-1 between CS, SVC and aorta were not detectable.

Arrhythmic and mortality outcomes in patients with dilated cardiomyopathy receiving cardiac resynchronization therapy without defibrillator

IntroductionThe routine implantation of cardiac resynchronization therapy with defibrillators in all patients who are candidates for this treatment is now being negotiated, mainly in patients with dilated cardiomyopathy. ObjectiveWe investigated the arrhythmic and mortality outcomes following CRT implantation in DCM, as well as the necessity for defibrillator capabilities in that particular group of patients. Methodswe included 67- patients with DCM with EF ≤ 35%, QRS duration >130 msec and NYHA class II-IV, or those with EF ≤ 35% with indications of permanent pacing for implantation of CRT-P. Patients were followed to obtain good CRT response. Improved clinical outcomes were defined as improvement in at least one NYHA class, ≥5% increase in LVEF, and ≥15% reduction in left ventricular end-systolic volume versus baseline. Patients were classified into responder and non-responder. Patients were followed for 36 months regarding all-cause morbidity mainly ventricular tachycardia and all-cause mortality. ResultsCRT responder patients had better clinical outcomes than CRT non-responder patients (post NYHA, 1.3 ± 0.5 vs. 2.5 ± 0.6, p < 0.0001; post LVEF 30.0 ± 1.6 vs. 20.3 ± 2.2%, p < 0.0001; LVESV, 151.7 ± 7.6 vs. 190.4 ± 9.0 ml, p < 0.0001), with lower ventricular arrhythmia (p < 0.0001), lower mortality (p = 0.015) and lower all-cause morbidity (p < 0.001). This survival advantage may be related to the response to CRT response determined by clinical and echocardiographic parameters over a 36-month period of follow-up. ConclusionsOur findings suggest that CRT-P implantation without defibrillation backup is an encouraging treatment option for patients with DCM, principally those who responded to it. It may result in cost savings, a decrease in complications, and an improvement in all-cause morbidity, particularly ventricular arrhythmia and survival.