Ischemic Cardiomyopathy Research Articles

Effect of Intravenous Iron on Functional Capacity in Patients with Ischemic Cardiomyopathy

Background: Iron deficiency is common in heart failure with reduced ejection fraction. Intravenous (IV) iron supplementation has been found to reduce morbidity in heart failure. However, the effect of IV iron on Bangladeshi patients with heart failure are not known. Objects: The study was done to see the effect of IV iron on functional capacity in Bangladeshi patients with ischaemic cardiomyopathy (ICM) and iron deficiency. Methodology: In this quasi-experimental study, out of 80 hospitalized patients with ICM and iron deficiency, 40 were given IV ferric carboxymaltose (FCM) in addition to standard therapy of heart failure, while another 40 were randomized to standard therapy alone. Primary outcome measure was changes in six-minute walk test (6MWT) distance, while secondary outcome measures were changes in New York Heart Association (NYHA) functional class, left ventricular ejection fraction (LVEF) and plasma NT-proBNP at Weeks 4 and 12. Results: 6MWT distance improved significantly in patients receiving IV iron therapy compared to the patients not receiving IV iron. LVEF improved and plasma NT-proBNP decreased significantly in IV irontreated patients than in patients receiving standard therapy. However, improvement in NYHA functional class was not statistically significant. Conclusion: In Bangladeshi patients with ICM and iron deficiency, IV FCM on top of standard heart failure therapy was associated with improved functional capacity. J Inv Clin Cardiol 2023; 5(2): 32-37

Coronary artery bypass grafting vs. percutaneous coronary intervention in severe ischaemic cardiomyopathy: long-term survival

Abstract Background and Aims The optimal revascularization strategy in patients with ischaemic cardiomyopathy remains unclear with no contemporary randomized trial data to guide clinical practice. This study aims to assess long-term survival in patients with severe ischaemic cardiomyopathy revascularized by either coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI). Methods Using the Australian and New Zealand Society of Cardiac and Thoracic Surgeons and Melbourne Interventional Group registries (from January 2005 to 2018), patients with severe ischaemic cardiomyopathy [left ventricular ejection fraction (LVEF) <35%] undergoing PCI or isolated CABG were included in the analysis. Those with ST-elevation myocardial infarction and cardiogenic shock were excluded. The primary outcome was long-term National Death Index–linked mortality up to 10 years following revascularization. Risk adjustment was performed to estimate the average treatment effect using propensity score analysis with inverse probability of treatment weighting (IPTW). Results A total of 2042 patients were included, of whom 1451 patients were treated by CABG and 591 by PCI. Inverse probability of treatment weighting–adjusted demographics, procedural indication, coronary artery disease extent, and LVEF were well balanced between the two patient groups. After risk adjustment, patients treated by CABG compared with those treated by PCI experienced reduced long-term mortality [adjusted hazard ratio 0.59, 95% confidence interval (CI) 0.45–0.79, P = .001] over a median follow-up period of 4.0 (inter-quartile range 2.2–6.8) years. There was no difference between the groups in terms of in-hospital mortality [adjusted odds ratio (aOR) 1.42, 95% CI 0.41–4.96, P = .58], but there was an increased risk of peri-procedural stroke (aOR 19.6, 95% CI 4.21–91.6, P < .001) and increased length of hospital stay (exponentiated coefficient 3.58, 95% CI 3.00–4.28, P < .001) in patients treated with CABG. Conclusions In this multi-centre IPTW analysis, patients with severe ischaemic cardiomyopathy undergoing revascularization by CABG rather than PCI showed improved long-term survival. However, future randomized controlled trials are needed to confirm the effect of any such benefits.

Comparing outcomes in cardiogenic shock patients with ischemic versus nonischemic cardiomyopathy: A nationwide retrospective observational study

Abstract Introduction Ischemic and non-ischemic cardiomyopathy are common causes of heart failure. In our study, we compare the in-hospital outcomes between these two groups of patients with cardiogenic shock. Methods Data was obtained from the Nationwide Inpatient Sample database between January 2016 to December 2020. The study included all adult patients who were in cardiogenic shock and either ischemic cardiomyopathy (ICM) or non-ischemic cardiomyopathy (NICM). The primary outcome was inpatient mortality. Secondary outcomes were cardiac arrest, arrhythmias, acute respiratory failure, and acute renal failure, as well as the need for ventilators, dialysis, and ECMO. Results Among 168,591 adult patients who had cardiogenic shock during their hospitalization, 72,538 patients had either ischemic cardiomyopathy or nonischemic cardiomyopathy. Among them, 31,854 (43.9%) had ischemic cardiomyopathy (ICM) vs 40,684 (56.1%) who had nonischemic cardiomyopathy (NICM). Patients with NICM had higher in-patient mortality (24.6% vs 26.1, aOR: 1.12; 95% CI: 1.08-1.16, p<0.001); when adjusted for age, sex, race, and Charlson comorbidity index. Furthermore, patients with NICM also had a higher risk of respiratory failure (54.1% vs 53.8%, aOR:1.11, 95% CI: 1.07-1.14, p<0.001) and required more life-saving treatments like pressors (1.6% vs 0.7%, aOR: 1.14; 95% CI: 1.10-1.20, p< 0.001) and dialysis (12.7.1% vs 11.3%, aOR:1.20, 95% CI: 1.14-1.26, p<0.001). However, these patients with NICM had a lower risk of cardiac arrest (7.2% vs 7.8%, aOR: 0.88; 95% CI: 0.84-0.94, p< 0.001) and ventricular arrhythmias (29.5% vs 32.2%, aOR: 0.82; 95% CI: 0.80-0.86, p<0.001) as well as lower ECMO utilization (2.5 vs 2.1, aOR:0.82; 95% CI: 0.73-0.92, p <0.001) and blood transfusions (9.8% vs 11.7%, aOR:0.839; 95% CI: 0.80-0.88, p< 0.001). There was no significant difference in the ventilator use between the 2 groups (40.3% vs 39.7%, aOR:1.01, 95% CI: 0.97-1.04, p=0.714). Conclusion The findings of this study underscore the higher in-patient mortality among patients with non-ischemic cardiomyopathy (NICM) presenting with cardiogenic shock. These results emphasize the need for tailored treatment approaches targeting NICM-CS, warranting dedicated diagnostic and therapeutic strategies to improve prognosis in this vulnerable patient subset.Odd's ratios for NICM-CS vs ICM-CS

Larger QRS but better hemodynamic function after high output His bundle pacing in patients with heart failure and narrow QRS. A paradox or a new concept?

Abstract Background QRS duration is an important factor in determining Cardiac Resynchronisation Therapy (CRT) response and a useful surrogate for electromechanical dyssynchrony. However, we don’t have studies confirming this concept in conduction system pacing. Purpose We performed His Bundle Pacing (HBP) with high output (3.5V/1msec) in HF patients with dilated or ischemic cardiomyopathy and narrow QRS to evaluate hemodynamic benefit independent of the QRS duration or AV delay shortening. Methods 14 patients with dilated (7 patients) or ischemic (7 patients) cardiomyopathy (EF<35%) and narrow QRS (<120ms) were referred for implantation of a defibrillator. We implanted an ICD- HBP system, and we collected clinical, echocardiographic, and electrocardiographic data. Results We obtained HBP in all 14 patients successfully. PQ after implantation was shorter from 172±48 to 143±16 (P=0.048) so as to pace the ventricle. Baseline QRS duration increased after pacing from 110±15 to 123±16ms (P=0.008) as measured by ECG analyzer. Despite this increase in QRS duration basal mean EF increased from 30±4% to 46±10% (P<0.001) after a median follow-up of 17 months. Left ventricular end-diastolic diameter and left ventricular end-diastolic volume decreased from 62±5 to 57±5mm (P=0.013) and from 195±69 to 126±27ml (P<0.001), respectively. Left ventricular end-systolic volume decreased from 139±58 to 69±27 (P<0.001). TAPSE increased from 19±4 to 27±4. NYHA class decreased by one class in every patient after only one month. HBP threshold was 1.05V±0.7/1msec and raised to 1.33±0.93/1msec (due mainly to 2 patients with very high threshold). The impedance was 588±109 and decreased to 484±69 Ohms. R-wave at implant was 3.2±1.8mV. In 2 out of 14 patients, threshold increased but was still less than 3.5V/1msec. Conclusions HBP in HF patients with dilated or ischemic cardiomyopathy and narrow QRS improves hemodynamic function in right and left ventricle and decreases NYHA class. This benefit appears to be produced by a higher stimulation output despite a larger QRS after pacing. We exclude that a very short AV delay could be favorable, by measuring acute EF changes only after increasing the pacing output without AV delay modifications. To our knowledge these are the first cases of beneficial HBP in HF patients with narrow QRS. Interestingly, larger QRS corresponds to higher EF in patients with high output HIs Bundle Pacing.

Single cell multi-omics analysis unveils a distinct mechanism of exercise-mediated cardioprotection in ischemic cardiomyopathy

Abstract Background Exercise is pivotal in heart disease prevention, with proven cardioprotective effects in clinical trials. However, its precise molecular mechanisms remain elusive. Recent advancements in single-cell omics have revealed cellular heterogeneity within heart tissues, offering a deeper understanding of the pathophysiology of cardiac diseases. Purpose To investigate the exercise-induced physiological changes in heart tissue at the single-cell level and elucidate the molecular mechanisms underlying its cardioprotective effect on ischemic cardiomyopathy. Methods Murine myocardial infarction (MI) model was established by ligating the left ascending coronary artery, and a six-week voluntary wheel running exercise regimen was implemented to investigate the effect of aerobic exercise on ischemic cardiomyopathy. Integrated multi-omics analyses of single-cell DNA methylation profiling, single-nucleus assay for transposase-accessible chromatin sequencing (snATAC-seq) and single-nucleus RNA sequencing (snRNA-seq) were conducted to clarify the molecular mechanism of exercise-mediated cardioprotection at single-cell resolution. Overexpression and short hairpin RNA-mediated knockdown of gene X were conducted for murine MI model using cardiomyocyte-specific Myo-AAV2a vector. snRNA-seq of heart tissues from heart failure patients was performed to validate the clinical significance of the expression of gene X in cardiomyocytes. Results Exercise attenuates pathological cardiac remodeling, inducing physiological hypertrophy in non-infarcted areas while suppressing pathological remodeling of cardiomyocytes in infarct border zones. Single-cell epigenetic analysis unveiled intricate molecular mechanisms underlying exercise-induced transcriptome changes, providing insights into the gene regulatory networks modulated by exercise in the heart. In addition, integrated with snRNA-seq, we identified exercise-specific cardiomyocyte clusters, highlighting the substantial role of gene X in the molecular mechanism of exercise. Functional studies confirmed the essential role of gene X in exercise-induced cardioprotection, as its overexpression suppressed the adverse remodeling after MI and knockdown abolished the beneficial effects of exercise. Furthermore, snRNA-seq of heart failure patients revealed that higher expression of gene X was associated with ventricular reverse remodeling and favorable clinical outcomes, underscoring its significance in the pathophysiology of patients with heart failure. Conclusion Our study elucidates exercise-specific gene expression regulation networks in ischemic cardiomyopathy by unraveling the cellular heterogeneity and molecular changes associated with exercise. We identified gene X as a central player in exercise-mediated cardioprotection and further confirmed its significance in clinical settings, providing a potential therapeutic target for heart failure.

Triglyceride-glucose index predicts the prognosis of patients with ischemic cardiomyopathy

Abstract Objective A large number of studies have provided strong statistical evidence that the Triglyceride-glucose (TYG) index is associated with the development and prognosis of cardiovascular disease. However, little is known about the predictive value of TYG index for ischemic cardiomyopathy (ICM). This study aimed to investigate the predictive value of TYG index in patients with ICM. Methods Hospitalized patients ICM in our Hospital from April 2014 to December 2017 were included in this study. Inclusion criteria: previous definite diagnosis of coronary atherosclerotic heart disease (coronary angiography found one or more vessels stenosis > 50%) and echocardiography showed LVEF < 45 percent. In addition, the TYG index was calculated as follows :LN[fasting triglycerides (mg /dl)× fasting blood glucose (mg /dl)x1/2]. The endpoint of the study was MACE events, including all-cause death, myocardial infarction, ischemia-induced revascularization and heart failure (HF) rehospitalization. Results A total of 688 patients were included in this study and followed up for 1 year. In the multivariate Cox proportional hazards model, TYG index (adjusted HR 2.33 [95% CI: 1.30-4.20], P<0.01) were associated with an increased risk of MACE events, and the area under the ROC curve (AUC) was 0.604 (95%CI: 0.528-0.680, p <0.05). A total of 197 ICM patients with previously diagnosed diabetes were screened for analysis. We found that TYG index (adjusted HR 6.63 [95% CI: 2.15-20.47], P<0.01), and the AUC was 0.691 (95%CI: 0.562-0.820, p<0.05). Conclusion TYG index can predict the poor prognosis of ICM patients, and the predictive value of TyG index for ICM patients with diabetes is more significant.

Improving prognostic accuracy in ischemic cardiomyopathy: the CMR-LGE score

Abstract Background There is a need for accurate prognostic stratification tools in patients with ischemic cardiomyopathy (ICM). Several studies have shown the considerable impact of cardiac magnetic resonance (CMR) imaging findings notably late gadolinium enhancement (LGE) but an easy interpretable score to guide clinical practice is lacking. Purpose To determine the CMR parameters most predictive of mortality in a cohort of ICM patients with left ventricular ejection fraction (LVEF) less than 50%, and then to develop a readily interpretable score based on these parameters. Methods Between 2008 and 2022, all consecutive patients with a history of ICM with LVEF<50% and presence of ischemic LGE on viability CMR examination, were recruited by two independent centers. The primary outcome was all-cause death using French National Registry of Death. The first center (N=2,900) was designated as the derivation cohort for variable selection and score development, and the second center (N=691) was used as the validation cohort to evaluate the performance of the final score. Thirty-two variables (17 clinical and 15 CMR) were initially assessed. Automatic feature selection was performed using a machine-learning approach with a Random Survival Forest (RSF) algorithm. Using the selected variables, our proposed score, the CMR-LGE score, was derived from coefficients of the Cox regression. Performance evaluation on the validation cohort was conducted using Harrel’s C index compared with traditional prognostic factors associated with poor outcomes in ICM. Categories for the prognostic score were identified using a survival conditional inference tree analysis on the derivation cohort, aiming to maximize the log-rank score. Results Among the 3,591 patients included (mean age 65±12 years; 75% male; mean LVEF 44±6%), 549 (15.3%) died over a median follow-up of 9 (interquartile range: 7–12) years. Feature selection with RSF highlighted that the most important variables to predict death were LGE variables: the extent, the location (septal and anterior) and the transmurality of ischemic LGE as well as the extent of additional midwall LGE (Figure 1). Following these findings, we developed the CMR-LGE score by rounding the coefficient of a Cox regression (Figure 2A). Harrel’s C index of CMR-LGE score outperformed traditional prognostic factors, including LVEF (0.88 vs 0.69). Finally, based on our CMR-LGE score, we identified a low-risk population (CMR-LGE score below 6) and a high-risk population (CMR-LGE above 8), validated using survival curves in the validation cohort (Figure 2B). Conclusion Using RSF, we identified that the 5 most important CMR variables to predict mortality in ICM were all LGE features. Our CMR-LGE score showed excellent performance to stratify patient risk compared to traditional prognostic factors including LVEF.Variable selectionModel building and evaluation

Prognostic impact of mitral valve geometry in patients with secondary mitral regurgitation: a secondary analysis of the MITRA-FR trial

Abstract Background Mitral valve (MV) transcatheter edge-to-edge repair (TEER) has emerged as a second line therapy on top of guidelines-directed medical treatment (GDMT) in heart failure (HF) patients with severe secondary mitral regurgitation (SMR). Following the disparate results of the COAPT and MITRA-FR pivotal trials, echocardiographic markers of LV remodeling and MR severity have been proposed to select patients most likely to benefit from MV-TEER. The characterization of MV geometry arises as a potential tool to stratify risk of outcomes in SMR patients, who underwent classical surgery or MV-TEER intervention. However, it remains unknown whether MV geometry parameters were associated with prognosis in MITRA-FR patients and whether MV-TEER could modulate their impact on outcomes. Purpose To evaluate the association between MV geometry and outcomes of HF patients with SMR in the MITRA-FR trial, as well as the impact of SMR treatment modality. Methods Thirteen MV geometry parameters were assessed from baseline transthoracic echocardiograms in patients from the MITRA-FR trial. The prognostic impact of MV geometry parameters was studied on top of the baseline clinical variables used in the primary analysis of MITRA-FR (i.e. age, atrial fibrillation [AF], ischemic cardiomyopathy, myocardial infarction, left ventricular ejection fraction [LVEF] and effective regurgitant orifice area [EROA]). The primary endpoint was the composite of all-cause mortality or HF hospitalization (HFH) within 2 years. The effect of treatment arms (MV-TEER plus GDMT vs. GDMT alone) on this association was also evaluated. Results Among the 307 patients included in the pivotal trial, 272 were analyzed in the present study (i.e. 135 from the GDMT group and 137 from the GDMT + MV-TEER group). Mean age was 70±10, 74% male. 50% had ischemic cardiomyopathy and 34% AF. LVEF was 33±7% and EROA was 31±11 mm². MV geometry parameters were presented for the whole population and according to the randomization group in the Table. Among these parameters, only MV tenting area remained independently associated with the primary endpoint (Hazard Ratio (HR) = 1.22 per 1 cm², Confidence Interval (CI) = 1.01-1.47; p=0.041) after multivariate analysis (Figure). Tenting height was independently associated with the risk of HFH (HR=1.07 per 1 mm, CI=1.00-1.14, p=0.037), but no MV geometry variable was associated with all-cause death. These findings remained consistent in both treatment arms (p>0.20 for interaction). Conclusion In HF patients with SMR included in the MITRA-FR trial, MV tenting area and MV tenting height were independently associated with the risk of HFH or all-cause mortality and HFH respectively, without any difference according to treatment arms. These data suggest that MV tethering provides an incremental prognostic value beyond classical echocardiographic variables, including EROA, and then should be considered in the risk stratification of patients with HF and SMR.Table of MV geometry parameters featuresMultivariate analysis (Forrest-plots)

Prognostic value of additional midwall late gadolinium enhancement in patients with ischemic cardiomyopathy

Abstract Background Although several studies have reported the additional presence of midwall late gadolinium enhancement (LGE) using cardiac magnetic resonance (CMR) in patients with ischemic cardiomyopathy (ICM), its prognostic value is not well established. Purpose To assess the prognostic value of the additional presence of midwall-LGE in a large cohort of patients with ICM and reduced left ventricular ejection fraction (LVEF). Methods Between 2008 and 2022, all consecutive patients referred for myocardial viability assessment using CMR with an history of ICM (≥70% stenosis in ≥1 epicardial coronary vessel on angiography and/or history of myocardial infarction and/or coronary revascularization) and LVEF <50% were included. Midwall-LGE was defined by non-ischemic LGE corresponding to non-specific myocardial fibrosis. All patients with a history of acute myocarditis and/or sub-epicardial LGE were excluded. The primary outcome was all-cause death. Nested Cox proportional hazard models were used to assess the prognostic value of additional midwall-LGE including its location (lateral and/or septal and other location) and extent (1 or ≥2 segments), above the presence of ischemic-LGE and traditional prognostic factors. The incremental prognostic value of midwall-LGE extent and location was assessed by the C-statistic increment, the continuous net reclassification improvement (NRI), the integrative discrimination index (IDI) and the global Chi-2. Results Among the 6,082 included patients (65±12 years, 73% males), 702 (11.5%) had an additional midwall-LGE. During a median follow-up of 9 (IQR, 7-12) years, 652 (11%) patients died. The presence of midwall-LGE alone was strongly associated with the risk of death compared to patients without midwall-LGE (p<0.001, Figure 1A). Among these patients with midwall-LGE (N=702), survival curves showed an increased risk for midwall-LGE in lateral and/or septal location (p<0.001), for larger extent (p<0.001) and the presence of ischemic-LGE (p<0.001, Figure 1B). In this population with midwall-LGE (N=702), after adjustment for risk factors and extent of ischemic-LGE, midwall-LGE with septal and/or lateral location (adjusted HR: 2.6; 95%CI: 1.8-3.6) and extent ≥2 segments (adjusted HR: 2.6; 95%CI: 1.8-3.7, both p<0.001) were independently associated with all-cause death. A comprehensive LGE model combining all the characteristics of midwall-LGE showed the best improvement in model discrimination and reclassification above traditional prognosticators (C-statistic improvement: 0.13; NRI=46%; IDI=19%, Chi-2 global=261, all p<0.05; LR-test p<0.001, Figure 2). Conclusion In a large cohort of ICM patients, the presence of an additional non-ischemic midwall-LGE is an independent prognosticator of all-cause death, particularly for larger extent or when present in the septal and/or lateral location.Prognostic value of midwall-LGEIncremental prognostic value

Role of ventricular tachycardia cycle length in the outcomes after catheter ablation or antiarrhythmic drugs in the SURVIVE-VT trial

Abstract Background It has been suggested that antiarrhythmic drugs (AAD) are less effective and safe in slow ventricular tachycardia (VT) due to their effect on conduction velocity, which could stabilize reentry. Conversely, catheter ablation aims to disrupt the VT circuit. Because of the distinct mechanisms of action of AAD and catheter ablation on the VT circuit, VT cycle length (VT-CL) may play a crucial role in determining their therapeutic efficacy. Therefore, VT-CL could be important in selecting VT treatment. Purpose The aim of this study was to assess the impact of VT-CL on outcomes following catheter ablation or antiarrhythmic drugs in AAD-naïve patients with ischemic cardiomyopathy presenting with VT. Methods This is a post hoc analysis of the previously published Substrate Ablation vs Antiarrhythmic Drug Therapy for Symptomatic Ventricular Tachycardia (SURVIVE-VT) trial. In summary, 144 patients with ischemic cardiomyopathy and symptomatic VT were randomized to receive either catheter ablation (N=71) or AAD (N=73) as first-line therapy. We analyzed VT recurrence, implantable cardioverter-defibrillator (ICD) therapies, and the incidence of slow/incessant VT/VT storm using Cox proportional hazard models, with treatment and VT-CL interaction terms, adjusted for age. Missing VT-CL data for five patients were imputed using the median value. Results In patients with chronic ischemic heart disease and VT treated with either AAD or catheter ablation, a significant interaction was observed between clinical VT-CL and treatment effect on VT recurrence (p=0.016 for the interaction). Specifically, slower VT cycle lengths were associated with higher rates of VT recurrence (hazard ratio per 10 ms [HR] 1.094, 95% confidence interval [CI] 1.015, 1.179; p=0.037) in patients treated with AAD, while no significant effect was observed in those undergoing catheter ablation (see Figure 1). Survival freedom from VT recurrence in patients with VT-CL ≥300ms was significantly higher in patients treated with catheter ablation (78.8% vs 58.1%, log-rank p=0.044, see Figure 2). As expected, VT-CL was significantly associated with a higher risk of slow/incessant VT/VT storm (HR per 10 ms 1.115, 95% CI 1.017-1.222, p=0.047) but was not associated with ICD therapies (HR per 10 ms 1.082, 95% CI 0.994-1.178, p=0.102). Conclusion VT-CL significantly influences treatment outcomes, with slower VT cycles associated with an increased risk of VT recurrence in patients treated with AAD, but not in those undergoing catheter ablation. Therefore, VT-CL should be taken into consideration when selecting the optimal therapy for patients with ischemic cardiomyopathy and VT.Figure 1Figure 2

The prevalence and prognostic impact of low voltage zone in patients with cardiomyopathy after catheter ablation for atrial fibrillation

Abstract Background The low voltage zone (LVZ) in left atrium (LA) was observed in 20-30% of patients undergoing catheter ablation of atrial fibrillation (AF). Furthermore, LVZ was associated with not only AF recurrence but also prognosis. However, the prevalence and prognostic impact of LVZ in patients diagnosed with cardiomyopathy remained unclear. Purpose In this study, we focused on the patients with cardiomyopathy after AF ablation and investigated the prevalence and prognostic impact of LVZ after AF ablation. Methods This study is a single-center retrospective observational study. We enrolled 125 patients diagnosed with cardiomyopathy. All patients underwent voltage mapping after pulmonary vein isolation. LVZ was defined as regions where bipolar peak-to-peak voltage was <0.5mV. We set 5 cm² as the cutoff of the presence of LVZ. The etiology of cardiomyopathy was divided into arrhythmia-induced cardiomyopathy (AICM) and non-AICM consisting of idiopathic dilated cardiomyopathy (iDCM), hypertrophic cardiomyopathy (HCM), ischemic cardiomyopathy (ICM), transthyretin amyloidosis wild type (ATTRwt) and others (1 Fabry disease, 1 cardiac sarcoidosis, 1 restrictive cardiomyopathy). AICM was defined as patient whose LVEF was recovered above 50% after maintenance of sinus rhythm. We investigated the proportion of LVZ by etiology, and the association between LVZ and the composite endpoint consisting of all cause death, heart failure hospitalization, ventricular assisting device implantation, ventricular arrhythmia and stroke. Results Out of 125 patients [age 68 (58-73), female 32 (25%), LVEF 34.0 (25-43)], 51 (41%) had LVZ. Sixty-four patients were AICM etiology (LVEF pre to post: 30.7±10.7% to 61.1±6.7% ) and 61 was Non-AICM etiology (LVEF: 40.7 ± 18.1 to 44.7±15.7, P=0.0062). The presence of LVZ was lower in AICM than in non-AICM group (20.3% vs. 62.3%, P<0.0001). The etiology of non-AICM was consisting of 26 iDCM, 18 HCM, 7 ICM, 7 ATRRwt and 3 other etiology. The prevalence of LVZ was lower in AICM than in non-AICM (20.3 vs. 62.3%, P<0.0001). Detail is shown in Figure 1. Next, the incidence of composite endpoint was higher in patients with LVZ than in those without (HR 4.6, 95%CI 2.1-10.0, P=0.0001) (Figure 2A). Among 4 groups stratified by AICM/non-AICM and with/without LVZ, there was significant difference in the incidence of the composite endpoint (Figure 2B, P<0.0001). After adjusted with age, gender, Non-AICM, LVZ, LVZ tended to have association with composite endpoint (2.21, 0.87-5.65, P=0.097) and Non-AICM showed strong association (5.58, 1.55-20.12, P=0.0086). LVZ was associated with HF hospitalization (4.35, 1.21-15.61, P=0.024). Conclusions The prevalence of LVZ was 60% in Non-AICM, while it was 20% in AICM. LVZ tended to be associated with poor prognosis of cardiomyopathy after AF ablation. LVZ was associated with HF hospitalization in patients with cardiomyopathy. LVZ might be the marker for poor prognosis in cardiomyopathy cohort.

Comparative study of the effects of preferential left ventricular and biventricular pacing on echocardiographic and cardiorespiratory indices and clinical status of heart failure patients: preliminary

Abstract Introduction Nonresponse to cardiac resynchronization therapy (CRT) has been related with right ventricular dysfunction. Preferential left ventricular pacing (pLV-P) can achieve left ventricle resynchronization allowing for intrinsic activation of the right side, and benefit cardiac output while reducing atrial fibrillation occurrence. Moreover, the AdaptivCRT® algorithm also automatically adjusts interventricular (V-V) delay every minute. Methods We evaluated the effects of a pLVP algorithm on 100 systolic heart failure patients ( all Caucasians, 49% male; 67 +/- 8 years old; 51% ischemic cardiomyopathy; 44% diabetics; NYHA II-III) following randomization to standard biventricular pacing and pLVP, on echocardiographic and cardiopulmonary exercise test indices of functional status. Device programming was based on echocardiography-evaluated maximization of stroke volume and subsequent interventricular and atrioventricular delay adjustments delegated to the device. The follow-up consisted of 6 and 12-months visits; after the 1rst month of optimizing maximum CRT response. Results Significant comparative effects of pLV-P over optimized CRT were noted regarding right ventricle systolic velocity in TDI at 12-months from baseline (mean (SE); 4.5(0.8), p=0.035); decrease in end-diastolic volume of left ventricle (mean (SE); 11.33(7), p=0.035); decrease in right ventricle strain mean ((SE); 9.2(2.1), p=0.03). According to other echocardiographic indices, again taking into account baseline levels, patients in pLV-P group exhibited lower E/e value at 6-months (mean (SE); 8.390(4,3), p=0.04), and at 12 -months (mean (SE); 7.45(3.9), p=0.035); improved values in left atrium contractility strain at 12-months (mean (SE); 8.390(0.8), p=0.04); a borderline improvement in left ventricular ejection fraction (mean (SE); 8.7(433), p=0.05) at 12-months; and borderline improvement in left ventricular longitudinal strain at 6-months (mean (SE); 4.9(2.6), p=0.035), compared to optimized CRT. In CPET, taking into account baseline levels, patients in the pLVP group showed higher METs at 12-months (mean (SE); 1,16(0.8), p=0.03) compared to opt CRT group; higher predicted Ventilation rate (%) even from 6-months (mean (SE); 8.167(5,7), p=0.03) and higher predicted peak VO2 (%) at 6 months (mean (SE); 34,13(14), p=0.03) and borderline significance at 12 months (mean (SE); 4.88(3), p=0.08), compared to opt CRT. Conclusions In the preliminary findings of READAPT study, it seems that pLVP optimized by a standardized echocardiographic protocol in patients with preserved AV conduction and LBBB, can achieve improvement in parameters of right ventricular and left atrium structure and function, as well as in survival-predictive parameters of CPET compared to optimized CRT during the 12-months of follow-up.

Predictor of wasted implantable cardioverter defibrillator for secondary prevention

Abstract Background ICD is the first line treatment to prevent sudden cardiac death from recurrence of VT/VF. However, patients with organic heart disease have many comorbidities, and some patients die without history of appropriate ICD therapy in lifetime. Purpose The aim of this study is to examine the predictors of death without appropriate ICD therapy in lifetime, among ICD patients for secondary prevention with organic heart disease. Methods We enrolled consecutive patients implanted with ICD/CRT-D for secondary prevention between 2000 and 2022. We excluded patients without organic heart disease, and alive patients without history of appropriate ICD therapy. Inappropriate candidate (Wasted-group) for defibrillator was defined as the patient who died without history of appropriate ICD therapy or died within one year from appropriate ICD therapy. Appropriate candidate (Appropriate-group) was defined as the patient who had been alive over one year from appropriate ICD therapy (Wasted-group:36, Appropriate-group:131). Results During a follow-up of 8.3 ± 5.3 years, a total of 93 (56%) patients died, including 6 (4%) patients died within one year from ICD/CRT-D implantation. Among the 36 patients of Wasted-group, 28 patients died without history of appropriate ICD therapy. Higher age, ischemic cardiomyopathy, non-ARVC, a past history of VF, diabetes mellitus, and higher serum creatinine was the predictor of Wasted-group (P<0.05). Wasted ICD risk score was constructed with the summation of these predictors for predicting candidates of Wasted-group. When the Wasted ICD risk score was ≥3, positive predictive value and negative predictive value were 39.7% and 89.4%, respectively (AUC=0.77, P<0.001). Conclusion Patients with a Wasted ICD risk score <3 is likely to receive appropriate ICD therapy in lifetime. Therefore, Wasted ICD risk score might be useful to decide to need for ICD therapy, regarding elderly patients who would be hesitant to have ICD implanted.Wasted ICD risk score

Impact of HF etiology on the sustainability of favorable response after LVAD weaning: A VAD Wean Registry analysis

Abstract Background A subset of heart failure (HF) patients can experience significant improvement of their cardiac structure and function while on left ventricular assist device (LVAD) support. Purpose We sought to investigate the impact of HF etiology on the durability of cardiac improvement and favorable outcomes after LVAD weaning. Methods We studied 324 HF patients enrolled in the international multicenter VAD Wean Registry who received a durable continuous-flow LVAD and underwent device support weaning (Figure 1). Indications for VAD weaning included: structural/functional cardiac improvement meeting institutional criteria for "myocardial recovery" (responders) or LVAD-related complications accompanied by variable degrees of cardiac improvement (partial responders). Patients were divided into seven categories based on HF etiology: ischemic cardiomyopathy (CM) (n=30), post-myocarditis CM (n=65), peripartum CM (n=53), valvular CM (n=12), chemotherapy-induced CM (n=14) and idiopathic CM (n=150). The primary outcome was 2-year survival free of transplant or LVAD re-implantation. The secondary outcome was the LVEF, measured by echocardiography at 3, 6, 12 and 24 months post-LVAD weaning. Results Patients with idiopathic, peripartum and post-myocarditis CM had higher rate of 2-year survival free of transplant or LVAD re-implantation compared to patients with chemotherapy-induced CM (Figure 2-Panel A) (p-values: 0.009, 0.004, 0.001, respectively). Patients with post-myocarditis CM were also more likely to achieve the primary outcome compared to those with ischemic CM (ICM) (p-value, 0.009). The LVEF changes over time are depicted in the Figure 2-Panel B. Conclusions In this multicenter analysis the etiology of HF appears to impact the durability of favorable response after LVAD weaning. The degree of reverse remodeling achieved before VAD weaning and its impact on the durability of response in different HF etiologies warrants further investigation in studies with larger patient population and power.

Atrial rates during treated ventricular tachycardia in patients with implantable cardioverter defibrillators: clinical implications of a vagal sinus node response

Abstract Introduction Autonomic tone plays an important role in the genesis and sustenance of ventricular tachycardia (VT). Whilst sympathetic hyperactivity is an established driver of ventricular arrhythmias, sinus node response during VT varies broadly between patients, and can be paradoxical. Purpose We hypothesized that device-detected changes in sinus node rate could be an important surrogate of the autonomic response to VT, and may exert significant – and potentially modifiable – haemodynamic consequences independent of ventricular activity. Methods Device electrograms were analysed from consecutive patients with dual chamber implantable cardioverter defibrillators (ICDs) requiring anti-tachycardia pacing (ATP) or defibrillation for sustained monomorphic VT. Atrial rates were measured before VT onset (‘baseline’) and again at the point of detection by the device. Sinus node response was characterized as ‘stable’ (atrial rate remained within 10% of baseline), ‘sympathetic’ (atrial rate increased >10%) or ‘vagal’ (atrial rate decreased >10%). Patients who did not maintain ventriculoatrial dissociation or who presented in atrial tachyarrhythmia were excluded. Symptoms and electrical response to ICD therapies were recorded. Results 172 treated episodes of VT were included from 97 patients (median age: 69 years, 65% male, 31% ischaemic cardiomyopathy, median ventricular rate: 205bpm, median ejection fraction: 30%). Sinus node response was stable in 55%, sympathetic in 24% and vagal in 21%. A vagal response was associated with ATP-refractory VT (OR: 2.2 (1.1-4.8) p=0.03) and, when adjusting for ventricular rate, was independently associated with symptoms of presyncope or syncope (adjusted OR: 6 (2.7-13.7), p<0.0001). Conclusions This preliminary analysis suggests that a vagal sinus node response during VT is associated with adverse outcomes in ICD patients. Vagolytic therapy has recently been demonstrated to improve haemodynamic tolerance during VT ablation; whether supportive atrial pacing during VT could mitigate symptoms and potentiate arrhythmia termination in ICD patients warrants further exploration. Figure 1: Change in sinus node rate during sustained monomorphic ventricular tachycardia in patients with dual chamber ICDs, stratified by the occurrence of presyncopal symptoms or syncopeFigure 1

Nationwide trends in utilization and safety of ventricular arrythmia ablation in patients with hypertrophic cardiomyopathy

Abstract Background Catheter ablation for ventricular arrhythmias, including ventricular tachycardia (VT) and premature ventricular complexes (PVC) is increasingly utilized across the nation, while data on its safety in Hypertrophic Cardiomyopathy (HCM) patients is sparse. Purpose To analyze the nationwide trends in utilization and complications of inpatient ventricular arrhythmia ablations in patients with HCM. Methods This study is a retrospective analysis of hospitalizations, in HCM patients 18 years of age and older, who underwent an inpatient VA ablation in the U.S., between 2016 and 2020. We drew data from the National Inpatient Sample (NIS) database. Patients without HCM undergoing the CA for VA were used as controls. Baseline sociodemographic and clinical data, procedural complications, mortality and length of stay were analyzed. Multivariable analysis was performed to identify independent predictors of procedural complications. Results Among a weighted total of 2880 patients hospitalized between 2016 and 2020, who underwent VA ablations, the median age was 67 years (IQR 56-74), 60% were male, and 73% were white. The HCM group had similar age distribution but more women (64.5% vs 33.6%, p<0.001) and more African Americans (13.2% vs. 7.3%, p=0.03). The non-HCM cohort had significantly higher rates of prior myocardial infarction (22% vs 12.4%, p=0.026), ischemic cardiomyopathy (30.1% vs 0.8%, p<0.001), heart failure (70.5% vs 39.7%, p<0.001), and peripheral vascular disease (PVD, 42.9% vs 18.2%, p<0.001). This was reflected in higher Deyo Comorbidity Index in the non-HCM cohort (score of ≥ 2 in 66.6% vs 43%, p<0.001). Overall, the real-world peri-procedural complication rate in the entire cohort was 15.3%, including 6.4% hemorrhagic, 4.5% pericardial, and 2.3% vascular complications. There was a trend for lower complication rate in the HCM group (9.9% vs. 16.7%, p = 0.08). The in-hospital mortality didn’t defer (1.7% vs. 4.2%, p=0.28) and the length of stay was shorter in the HCM group (3.5 vs. 6.4 days, p < 0.001). Multivariable logistic regression analysis showed obesity (OR 2.06; 95%CI: 1.59 - 2.67; p<0.001) and PVD (OR 2.19; 95%CI: 1.34-3.53; p=0.001) to be independent predictors of complications while HCM was not (OR 0.76, 95% CI 0.51-1.14, p = 0.195). Conclusion Real-world data from a nationwide inpatient database shows comparable safety for VA ablation in HCM patients with similar mortality and lower length of stay, compared to non-HCM patients.

Heart failure hospitalization reduction and long-term safety with remote pulmonary artery pressure monitoring: results of the CardioMEMS HF System OUS Post-Market Study

Abstract Background Heart failure (HF) is increasing in prevalence and is responsible for frequent hospitalization and readmissions, despite current guideline recommended therapies. Hemodynamic guided HF management using frequently remotely obtained pulmonary artery (PA) pressure information using a permanently implanted PA sensor (CardioMEMSTM HF System, Abbott) consistently reduced HF hospitalizations (HFH) in multiple healthcare settings. The safety and efficacy of the CardioMEMS HF System has been shown previously in several clinical studies, which reported significant reductions in HFH compared to a control (CHAMPION: 33%, 18M; GUIDE-HF: 28%, 1 yr; and MONITOR-HF: 44%, 1 yr) and longitudinally (MEMS-HF: 62%, 1 yr; and CardioMEMS US PAS: 57%, 1 yr) across varying health systems. Purpose The CardioMEMS HF System OUS Post-Market Study (COAST) aimed to evaluate the safety and effectiveness of hemodynamic guided HF management in patients with NYHA Class III HF in varying health systems across Europe and Australia. Methods COAST is a prospective, multi-centre, open-label clinical trial that consented 321 patients at 38 European and Australian centres. The primary endpoint is a combination of safety (freedom from DSRCs and freedom from pressure sensor failure at 2 years after implant) and efficacy endpoints (annualized HFH rate at 1-year vs the HFH rate in the year prior to enrolment). In this analysis we report these primary results of the study. Results Out of 321 consented patients, 17 subjects were withdrawn before implant, while the PA sensor was implanted successfully in 299 out of 304 patients who underwent the procedure (98.3% success rate). Seventy-three percent (73%) of the patients were male, the mean age was 68.4±11.7 years with ischemic cardiomyopathy in 45.4%. At baseline, all patients had NYHA Class III symptoms and an average EQ-5D-5L VAS score of 60.0±21.6. After 2 years follow-up there was 100% freedom from DSRCs and 99.7% freedom from pressure sensor failure. The annualized HFH rate after 1 year decreased by 69%, from 1.586 (pre-implant) to 0.488 (post-implant) (p<0.0001). The patient’s quality of life (EQ-5D-5L VAS) increased 8.1 units (68.2 ± 20.1, p=0.0008). Conclusion The COAST Study demonstrated that hemodynamic-guided remote HF management using PA pressure information is both safe and effective, with consistent implant safety and low risk for long-term sensor failure. At 1 year post implant, HFH were significantly reduced and quality of life improved. These results are also consistent with long-term clinical follow-up (2 yr) in other geographies with no late-stage adverse events or adverse events from sensor implant, demonstrating the generalizability of this type of hemodynamic-guided HF management.

A mcgyvering way to left bundle branch area pacing : using the treadmill test machine ECG system and modified V1 / V6 leads connected to the pacing system analyser for left bundle branch area pacing

Abstract Background Left bundle branch area pacing (LBBaP) is a novel pacing modality which provides physiological synchronisation of both the ventricles. However, its use and adoption requires the presence of a standardised electrophysiological (EP) system with 12 lead ECG to show left bundle branch area capture. Purpose The aim of the study was to assess the feasibility and outcomes of using the conventional treadmill test (TMT) machine 12 lead ECG system and modified V1 and V6 leads connected to the pacing system analyser (PSA) to demonstrate conduction system capture during left bundle branch area pacing (LBBaP). Methods LBBaP was attempted by a single operator in a mixed cohort of patients at peripheral hospitals lacking the standardised EP system. The presence of LBB area capture was tested with the aid of the 12 lead ECG system connected to the standard TMT machine (1). Conduction system capture was also assessed using modified V1 and V6 leads connected to the PSA for measurement of V6 left ventricular activation time (LVAT)(2) . The baseline clinical, procedural, pacing, electrocardiographic parameters, echocardiographic response (> 10% improvement in ejection fraction {EF}) and clinical response to LBBaP were assessed. Results LBBaP was attempted in 19 patients and was successful in 18 patients (94.7%). Patient characteristics include age 66.7 +/- 11.47 years, female 47.37%, male 52.63%, ischaemic cardiomyopathy 10.52% and non-ischaemic cardiomyopathy 5.26% .The mean baseline EF and QRS duration was 45%+/-14% and 130.18 +/-10.45 milliseconds(ms) respectively. LBBaP threshold was 0.59 +/-0.168 volts and R wave amplitude was 12+/-3.5 millimetres , which remained stable during the mean follow up of 15.9 +/-13.67 months. The mean fluoroscopic duration was 11.57 +/-2.58 minutes and procedural time was 108.78+/-29.20 minutes. LBBaP resulted in impressive narrowing of the QRS duration to 102.39 +/-10.55 ms (p<0.001) with LVAT of 68.94 +/-9.94 ms. LVEF improved in the patients with cardiomyopathy from 33.4 +/- 5.77 % to 48.2+/-12.37 % (p=0.028) .Clinical and echocardiographic response was noted in 87.5% of patients with cardiomyopathy. Conclusion The 12 lead ECG system with the standardised TMT machine in conjunction with the modified V1 and V6 leads connected to the PSA is a feasible alternative to the EP system to perform successful left bundle branch area pacing.ECG leads connected during LBBapClinical profile of patients

Clinical phenotyping and treatment response in patients with chronic heart failure: a latent class analysis from a Japanese multicentre registry

Abstract Background There are diversities of pathophysiology and co-morbidities in patients with chronic heart failure (HF), irrespective of left ventricular ejection fraction (LVEF). Therefore, the identification of subgroups with different outcomes and treatment response patterns may help to tailor strategies to each individual HF patient. Purpose We sought to identify phenogroups of patients with different prognosis and response to medical therapies in patients with chronic HF. Methods A total of 1565 patients with a broad spectrum of LVEF in a prospective multicentre registry of patients with chronic HF were enrolled between January 2020 and December 2023. Latent class analysis was performed in each subgroup using 80 features including patients’ demographics, laboratory, and echocardiographic data. The optimal number of phenogroups was determined using the first minimum of the Bayesian information criterion. The primary outcome was a composite of all-cause death and hospitalisation due to worsening HF. Results The analysis subclassified patients into six phenogroups. Patients in phenogroup A (young non-ischaemic cardiomyopathy, n = 242, 15.5%) were the youngest and had lower LVEF and lowest prevalence of coronary artery disease (CAD) and other comorbidities. Phenogroup B (atrial fibrillation [AF] and small left atrium, n = 282, 18.0%) had higher proportion of AF but smaller left atrium volume. Phenogroup C (ischaemic cardiomyopathy, n = 204, 13.0%) had the highest proportion of CAD and lower LVEF. Phenogroup D (classical HF with preserved ejection fraction [HFpEF], n =308, 19.7%) had the highest age, proportion of female, LVEF and thickness of LV wall. Phenogroup E (elderly and AF , n = 235, 15.0%) had higher age, the highest proportion of AF and largest left atrium volume. Phenogroup F (biventricular failure and multiple comorbidities, n = 294, 18.8%) had the highest proportion of co-morbidities and the lowest LVEF, right ventricular systolic function and renal function. During a median follow-up period of 538 (interquartile range 286-701) days, the incidence of the primary outcome significantly differed among the phenogroups (P < 0.001, Figure 1). Regarding treatment response for renin-angiotensin system blockers and beta blockers, there were no significant associations between the use of renin-angiotensin system blockers and the risk of the primary outcome among the phenogroups whereas the use of beta-blockers was significantly associated with increased risk of the primary outcome in patients classified to phenogroup D (classical HFpEF) (hazard ratio 1.83 95% confidence interval 1.05-3.19) among the phenogroups (Figure 2). Conclusion We identified six phenogroups with distinct clinical outcomes in patients with chronic HF, and the use of beta-blockers might have unfavorable effect in the classical HFpEF phenogroup. This phenotyping provides novel risk stratification and may aid in clinical decision making.Clinical outcomes among the phenogroupsTreatment effect among the phenogroups

Outcomes of intra-aortic balloon pump in patients with advanced heart failure and cardiogenic shock undergoing heart transplantation

Abstract Background Intra-aortic balloon pump (IABP) is generally used as a short-term device to maintain adequate organ perfusion in patients with cardiogenic shock (CS). However, whether IABP improves clinical outcomes as a bridge therapy for heart transplant (HTx) remains controversial. Purpose Evaluate the survival rate 30 days after heart transplant (HTx) in patients with advanced heart failure (HF) and CS using IABP pre transplant compared to non-IABP group. Methods We retrospectively analyzed consecutive patients with advanced HF and CS, admitted in the cardiac intensive care unit (ICU) of a tertiary university center, between 2009 and 2020, who underwent HTx. Study group included patients submitted to IABP implantation before HTx, and a non-IABP group submitted to HTx without left ventricular mechanical support. Propensity Score Matching was used to pair the groups according to relevant clinical covariates. The primary outcome of survival rate 30 days after HTx was estimated by the Kaplan-Meier method. Results 326 were enrolled, 199 in IABP group and 127 in non-IABP group. For non-IABP and IABP group, respectively, the most frequent etiology was Chagas disease (29,9% and 47,2%, p=0,006) followed by idiopathic cardiomyopathy and ischemic cardiomyopathy, the majority of patients were male (63% and 61,3%, p=0,760), the mean age was 46,9 ± 14,4 and 46,5 ± 12 years (p=0,791) and mean left ventricular ejection fraction was 25,9 ± 9,5% and 23,5 ± 5,9% (p=0,010). The Simplified Acute Physiology Score 3 (SAPS 3) at ICU admission was compared in both groups, which was 36,8% ± 17,8% in non-IABP group and 32,6% ± 18,6% in IABP group (p=0,042). At 30 days after HTx, there was no statistical difference in overall survival (p=0,459) between the groups (IABP: 18,1% mortality; non-IABP: 14,2% mortality). Survival rate after HTx was also similar in patients with Chagas disease compared to the other etiologies in both study groups (IABP group: p=0,221; non-IABP group: p=0,421). Conclusion In patients with advanced HF and CS submitted to HTx, the survival rate 30 days after HTx was equivalent in the IABP and non-IABP groups. In patients with Chagas disease the survival was also similar compared to other etiologies in both groups.Characteristics according to groupsKaplan-Meier survival estimates