Non-ischemic Cardiomyopathy Patients Research Articles

Prognostic impact of late gadolinium enhancement granularity in non-ischemic dilated cardiomyopathy.

We aimed to assess the additional prognostic value of the concept of "late gadolinium enhancement (LGE) granularity" in non-ischemic dilated cardiomyopathy (DCM) patients to predict all-cause death. Between 2008 and 2021, we conducted a bicentric retrospective study including all consecutive DCM patients referred for Cardiovascular Magnetic Resonance (CMR). The primary outcome was all-cause death. Cox regressions were performed to determine the prognostic value of LGE findings. Of 1668 DCM patients recruited (age 52 ± 8 years, 54% male), 268 (16%) died after a median (interquartile range) follow-up of 9 (7-12) years. In DCM patients with LGE (N = 472), the LGE extent, the septal location, and its presence in multiple areas were independently associated with death after adjustment for all prognostic variables (adjusted hazard ratio (HR): 4.27, 95% CI: 2.22-8.22; HR: 5.74, 95% CI: 3.35-9.85; and HR: 4.38, 95% CI: 2.08-9.22 respectively; all p < 0.001). The LGE granularity model combining all these LGE features showed the best improvement in model discrimination and reclassification over traditional prognostic variables, including the left ventricular ejection fraction (LVEF) value (C-statistic improvement: 0.14; net reclassification improvement = 64.3%; integrative discrimination index = 29.0%; all p < 0.05). In a large cohort of DCM patients, a LGE granularity model combining LGE extent, location and multiple areas had additional prognostic value above traditional prognostic variables including the LVEF value to predict all-cause death. Question Assessment of late gadolinium enhancement (LGE) is recommended in non-ischemic dilated. cardiomyopathy (DCM) patients to stratify the risk of death, but other LGE characteristics are not currently considered. Findings The concept of "LGE granularity," including the extent, location, and number of areas, provides additional prognostic value, especially in predicting all-cause mortality. Clinical relevance "LGE granularity" could play a crucial role not only in guiding the decision to implant a defibrillator in DCM patients but also in providing more personalized management, such as enhanced cardioprotective treatments, for those with high-risk LGE characteristics.

Right ventricular dysfunction in ischemic vs nonischemic dilated cardiomyopathy

Abstract Background Non-ischemic cardiomyopathy (NICM) and ischemic cardiomyopathy (ICM) can both lead to right ventricular (RV) dysfunction. Data on direct head to head comparisons of the two entities regarding RV size and function using state-of-the-art imaging techniques is sparse. Such a comparison may help to better understand the underlying pathophysiology of RV dysfunction in both NICM and ICM. Also, differentiation between the two etiologies for cardiomyopathy has important therapeutic implications because ICM may benefit from coronary revascularization. Purpose The aim of this study was to investigate RV function using conventional transthoracic and tissue Doppler echocardiography in patients with dilated cardiomyopathy (ICM and NICM groups) and compare the various parameters of the RV assessment in both the groups and correlate with etiology of cardiomyopathy. Methods 35 patients with NICM and 35 patients with ICM, both groups with LVEF&amp;lt;35% evaluated at our center were included in the study. Transthoracic echocardiography was done for all of them for assessment of Right ventricular volumes and function using conventional and Tissue Doppler parameters. Results Baseline LVEF was similar in the two groups with mean LVEF of 28% in ICM group and 27% in NICM group [p=0.71]. RV dysfunction was seen in 22 (62.9%) patients in ICM group as compared to 25 (71.4%) patients in NICM group [p=0.445]. PAH was present in 31(44.3%) patients, with presence of PAH more common in NICM group (n=18, 51.4%) as compared to ICM group (n=13, 37.1%) [p=0.009]. There was a significant positive correlation between LVEF &amp; RV Basal S’ velocity (R2 0.33, p=0.02) and LVEF &amp; TAPSE (R2 0.309, p=0.03) in the ICM group. Presence of more than mild MR (p=0.047), TAPSE &amp;lt; 1.5 cm (p&amp;lt;0.001) and RV Basal S’ velocity &amp;lt; 8.6 cm/s (p=0.02) were significant predictors of RV dysfunction in these patients. Conclusion RV dysfunction is common in both NICM and ICM patients. However, there is no significant association of underlying cause of LV dysfunction with presence of RV dysfunction in these patients. Pulmonary artery hypertension was more common in patients in NICM group.

Late Gadolinium Enhancement Magnetic Resonance Imaging (MRI) for Predicting Left Ventricular Reverse Remodeling in Non-Ischemic Cardiomyopathy: A Systematic Review and Meta-Analysis

Background/Objectives: Late gadolinium enhancement (LGE)-MRI has proven utility in prognosticating outcomes in patients with non-ischemic cardiomyopathy (NICM). However, evidence regarding its ability to predict responsiveness to optimal medical therapy remains insufficient. This study conducted a meta-analysis to evaluate the predictive utility of LGE-MRI for left ventricular reverse remodeling (LVRR) in response to pharmacological therapy. Methods: Data from 1092 NICM patients across 13 studies were included in the analysis. To assess the predictive ability of LGE-MRI for LVRR following optimal medical therapy, a pooled odds ratio was calculated using an inverse variance random-effects meta-analysis. Subgroup analyses were performed by stratifying patients based on the presence or absence of left ventricular dilation and by LVEF (&lt;30% vs. ≥30%). Results: The pooled odds ratio of the absence of LGE for predicting LVRR in NICM was 3.72 (95% CI: 2.83–4.90, I2 = 0, P for heterogeneity = 0.54). A comparison of pooled odds ratios between dilated cardiomyopathy (DCM) and NICM showed no significant difference (p = 0.16). A subgroup analysis in NICM based on the left ventricular ejection fraction (LVEF) demonstrated no significant difference in odds ratios between patients with LVEF &lt;30% (OR: 2.96, 95% CI: 1.80–4.87) and those with LVEF ≥30% (OR: 3.97, 95% CI: 2.97–5.31), (p = 0.13). Conclusions: This meta-analysis suggested that LGE-MRI serves as a reliable predictor of LVRR in patients with NICM, regardless of left ventricular dilation or baseline LVEF classification.

Implantable Cardioverter Defibrillator in Nonischemic Versus Ischemic Cardiomyopathy: Real-World Primary Prevention Study.

The evidence in the primary prevention of sudden cardiac death (SCD) by using implantable cardioverter defibrillators (ICD) in patients with ischemic cardiomyopathy (ICM) is well-established but remains controversial for those with nonischemic cardiomyopathy (NICM). This study evaluates whether prognostic differences exist between ICM and NICM patients after ICD implantation. Patients initially undergoing ICD implantation as primary SCD prevention were retrospectively enrolled from January 2017 to May 2023. Malignant ventricular arrhythmic and/or SCD were set as the primary endpoint, whereas all-cause mortality was the secondary endpoint. Patients were grouped by heart failure etiology (ICM vs. NICM) and then by primary endpoint events occurrence. Outcomes analyses were performed between the NICM and ICM patients. The final cohort had 342 patients, 213 (62.3%) with NICM and 129 (37.7%) with ICM. At a median follow-up of 23.0 (10.7, 33.2) months, 51 patients (14.9%) encountered primary endpoint events. No statistically significant disparities in primary endpoint events (log rank p = 0.413), all-cause death (log rank p = 0.208), cardiovascular mortality (log rank p = 0.218), or appropriate ICD therapy (log rank p = 0.250) between the two groups were indicated by Kaplan-Meier survival analysis. Moreover, the COX-adjusted models further demonstrated the absence of any significant differences between the two groups. In real-world settings, primary prevention of SCD with ICD implantation yields similar outcomes for ICM and NICM patients, including probabilities of SCD and/or malignant ventricular arrhythmias, all-cause mortality, appropriate ICD therapy, and cardiovascular mortality.

Sequential CMR imaging in a nonischemic cardiomyopathy patient with an ICD before and after radio-frequency ablation

Sequential CMR imaging in a nonischemic cardiomyopathy patient with an ICD before and after radio-frequency ablation

Preprocedural imaging guiding ventricular tachycardia ablation in structural heart disease.

Integration of preprocedural imaging techniques in ventricular tachycardia (VT) ablation may improve the identification of arrhythmogenic substrates, particularly relevant for patients with nonischemic cardiomyopathy (NICM) with sub-optimal outcomes. We assessed the impact of advanced preprocedural imaging on the safety and long-term efficacy of radiofrequency catheter ablation (RCA) for VT, comparing patients with NICM and ischemic cardiomyopathy (ICM). In this prospective, single-center study, consecutive patients referred for scar-related VT ablation underwent multidetector computed tomography (MDCT) and late gadolinium enhancement cardiac magnetic resonance (LGE-CMR). Images were segmented with ADAS 3D software and integrated into mapping systems. Substrate map collection targeted the imaging-predicted area of interest and the ablation aimed at eliminating all local abnormal ventricular activities. Procedural safety was evaluated with 30-day mortality. Long-term efficacy was assessed by survival free from appropriate ICD shocks at 36 months. 102 patients were included (67 ± 11 years, 94% male; 75 ICM, 27 NICM). All patients underwent MDCT and 35% also underwent LGE-CMR. Procedural safety (4% 30-day mortality, p = .95) and 36-month efficacy were similar in both groups (88.0% vs. 74.1%, HR 2.09; p = .13 in ICM and NICM). Efficacy was higher in patients when VT activation mapping with VT isthmus ablation complemented substrate ablation compared to substrate-based ablation alone (94.5% vs. 80.6%, HR 4.00; p < .05). A preprocedural imaging protocol integrated into the invasive mapping system may improve safety and long-term efficacy, with NICM patients exhibiting outcomes comparable to those with ICM. Activation mapping of the VT on top of substrate ablation may improve prognosis.

Abstract 4137113: The Effectiveness of Cardiac Resynchronization Therapy in Patients with Cardiac Sarcoidosis: A Retrospective Analysis

Background: Cardiac sarcoidosis (CS) manifests in a wide range of clinical presentations, including conduction system abnormalities, ventricular arrhythmias, and systolic heart failure. Although cardiac resynchronization therapy (CRT) has shown efficacy in treating select nonischemic cardiomyopathy patients, its specific impact on CS patients remains less explored. This study aimed to evaluate the outcomes of CRT therapy in CS patients, focusing on implantable cardioverter defibrillator (ICD) therapies, heart failure (HF) hospitalizations and mortality. Methods: We retrospectively reviewed all patients with a clinical or histological diagnosis of CS who underwent device implantation (ICD or Permanent Pacemaker (PPM)) with or without CRT therapy at Johns Hopkins Hospital between 2004 and 2024. Baseline characteristics and echocardiographic parameters were assessed. Heart failure hospitalizations, the frequency of ATP (Anti-Tachycardia Pacing) or ICD shocks, and all-cause mortality were also evaluated as the outcomes. Results: The study included 212 patients (40.1% female, average age 52.8 ± 11.1 years). Eighty-five patients underwent CRT implantation (82 CRT-D and 3 CRT-P), whereas the rest received either an ICD or a PPM without CRT therapy. Most CRT devices (58.82%) were upgrades from an initial PPM or ICD. Over a follow-up of 6.15 ± 4.43 years, 27 (12.74%) patients were hospitalized for heart failure (HF), 86 (40.56%) experienced ATP or ICD shocks, and 17 (8.02%) died. The composite outcome was observed in 103 patients (48.5%), with no significant differences between CRT and non-CRT groups ( P = .51). Survival analysis indicated significantly reduced freedom from HF hospitalizations in the CRT group compared to non-CRT group ( P = .01). However, ATP/ICD shocks did not have a significant difference. CRT recipients showed an improvement in left ventricular ejection fraction (LVEF) from 35.3 ± 12.6% to 38.9 ± 13.6% at 6 months ( P = .01). Non-recipients showed no significant change in LVEF ( P = .43). Conclusions: Over an average six-year follow-up period, CRT upgrade does not appear to affect ATP/ICD shock and mortality in CS patients, although it is associated with significantly higher rates of heart failure (HF) hospitalizations compared to CS patients with an ICD or PPM alone. These findings underscore the complex response of CS patients to CRT, highlighting the need for further research to optimize treatment strategies within this subgroup.

The Role of Cardiac Magnetic Resonance to Predict Response to Cardiac Resynchronization Therapy: A Systematic Review and Meta-analysis.

Cardiac resynchronization therapy (CRT) has revolutionized heart failure (HF) management, offering benefits in morbidity, mortality, and symptom alleviation. However, optimal response rates are not universally achieved, necessitating enhanced patient-selection strategies. Myocardial scar patterns, quantified by delayed-enhancement cardiac magnetic resonance (DE-CMR), have been implicated in CRT outcomes. We conducted a meta-analysis of observational studies assessing CRT responses by performing a systematic literature search using PubMed, Embase, Ovid MEDLINE, Scopus, the Cochrane Library, ScienceDirect, and the Web of Science. Scar burden, left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and left ventricular end-diastolic volume (LVEDV) were evaluated. CRT response rates among ischemic and non-ischemic cardiomyopathy patients were also explored. This meta-analysis incorporated eight studies meeting the eligibility criteria. CRT responders exhibited a significantly lower scar burden (-11.7%; 95% confidence interval, 6.6%-16.8%) compared to non-responders, supporting the predictive value of scar quantification (I 2 = 95.25%; P < .001). Responders demonstrated an increased mean LVEF (from 25.2% to 31.9%), while non-responders showed modest changes (from 23.3% to 24.4%). Responders experienced a decrease in mean LVESV from 158.8 to 132.8 mL, contrasting with a more stable mean LVESV value in non-responders (reduction from 160.9 to 157.6 mL). Responders experienced a reduced mean LVEDV from 219.4 to 196.7 mL, while non-responders showed more minimal changes (from 213.4 to 210.6 mL). Limited data suggested a CRT response rate of 34.7% in ischemic cardiomyopathy; non-ischemic data were insufficient. In conclusion, DE-CMR, assessing the scar burden, emerges as a valuable tool for predicting the CRT response. A lower scar burden correlates with improved responses, supporting the role of DE-CMR in refining patient selection for CRT. This meta-analysis contributes insights into personalized CRT strategies, emphasizing the potential of imaging modalities to enhance therapeutic outcomes in HF patients. Further research is warranted to solidify these findings and refine clinical applications.

Targeting ventricular tachycardia originating from the anterolateral papillary muscle with stereotactic body radioablation therapy

Abstract Background Ventricular Tachycardia (VT) is prevalent in the setting of non-ischaemic cardiomyopathy (NICM), a heterogeneous group of conditions characterized by myocardial dysfunction in the absence of coronary artery disease. Challenges of catheter ablation to treat VT in NICM patients are well known, and recurrence rates can be as high as 58%. Stereotactic body radioablation therapy (SBRT) involves precise delivery of radiation to arrhythmogenic substrates, and represents a novel treatment to reduce recurrent implantable cardioverter defibrillator (ICD) therapies in patients with refractory VT. Though SBRT has shown preliminary effectiveness in reducing VT episodes, its effectiveness in NICM patients has not been widely evaluated. Purpose To evaluate SBRT effectiveness in NICM patients with scars at the basal anterolateral papillary muscle at a tertiary care center between November-December 2022. Methods Eligible patients had their VT substrate mapped using a single-use ECGI vest and a 4D-CT simulation scan. In addition, MRI scans were used to aid anatomical identification of the anterolateral papillary muscle which could not be seen on the non-contrast diagnostic CTs. SBRT was delivered in a single fraction of 25 Gy under image guidance. Effectiveness of the treatment was evaluated as changes in frequencies of total antitachycardia pacing (ATP) and ICD shock episodes from 6 months pre-, and within to 3, 6, and 12 months follow up post SBRT. Results Participants were 3 males with NICM, aged 56, 60, and 73 with previous dual chamber ICD implantation, 2 of whom had a history of VT ablation/ VT storm and paroxysmal atrial fibrillation. All participants had basal lateral scar, and were receiving beta blockers, mexiletine, and amiodarone with refractory VT before SBRT treatment. Prior to SBRT, ICD device interrogation showed a total of 119 (77, 7, and 35 in patients 1-3 respectively) ATPs, and 27 (10, 1, and 16 in patients 1-3 respectively) ICD shocks delivered. At 12 month follow-up, none of the participants experienced any episodes of ATP or ICD shock. Ejection fraction remained consistent pre-post SBRT. Conclusion SBRT showed remarkable success in reducing ATP and ICD shock episodes, facilitating uncomplicated 1 year follow-up in 3 male patients with NICM and VT from the anterolateral papillary muscle.

Regional cardiac denervation predicts sustained ventricular arrhythmias in non-ischemic cardiomyopathy patients without LGE on CMR imaging

Abstract Background In patients with non-ischemic cardiomyopathy (NICM) and no late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR), risk prediction for the occurrence of sustained ventricular arrhythmias (VA) is challenging. Global and regional sympathetic denervation has been associated with VA in patients with ischemic cardiomyopathy. Its prognostic relevance in NICM is unknown. Purpose To assess the risk prediction of sympathetic denervation for the occurrence of VA in NICM patients without LGE. Methods Consecutive patients from the ‘Leiden Nonischemic Cardiomyopathy Study’, who underwent programmed electrical stimulation, LGE-CMR and 123I- MIBG imaging between 2011-2018 were included. The presence of LGE and global and regional sympathetic denervation on 123I- MIBG was evaluated and patients were followed for occurrence of VA. Global denervation was assessed using the heart-to-mediastinum ratio. Regional denervation was evaluated by calculating the number of denervated segments (DS), the ratio of DS, the summed defect score and the weighted denervation size. Results Of 75 included patients (63 years [52-68], 79% male, LVEF 36% [27-44], 37% inducible for VA) 35 had no LGE. During 4.5±1.6 years follow-up, VA occurred in 8/35 (23%) patients without LGE and in 18/40 (45%) patients with LGE. Among patients without LGE, those with VA had greater regional sympathetic denervation (number of DS 8 [8-10] vs. 2 [1-5], P=0.004; ratio of DS 0.5 [0.5-0.7] vs. 0.2 [0.1-0.4], P=0.007; defect score 36 [31-41] vs. 18 [14-24], P=0.01; weighted denervation size 47 [39-53] vs. 22 [16-30], P=0.01). In univariable analysis the number of DS (HR 1.25, 95% CI 1.06–1.46, P=0.006) was associated with the occurrence of VA in patients without LGE. Denervation of ≥ 7 segments identified patients without LGE at risk for VA (AUC: 0.83, sensitivity: 88%; specificity: 89%). Among patients with LGE, innervation state was not associated with VA during follow-up. Conclusions In NICM patients without LGE the extent of regional denervation may contribute to risk stratification for VA.Graphical Abstract

Prognostic impact of the concept of late gadolinium enhancement granularity in non-ischaemic dilated cardiomyopathy

Abstract Background The prognostic stratification of non-ischaemic dilated cardiomyopathy (DCM) to predict the risk of death is mainly driven by the left ventricular ejection fraction (LVEF). Indeed, LVEF&amp;lt;35% is currently the only indication for primary prevention with implantable cardioverter-defibrillator (ICD) in these patients. Beyond LVEF, several cardiac magnetic resonance imaging (MRI) studies have suggested the strong prgnostic impact of late gadolinium enhancement (LGE), and particularly its extent and location. Therefore, we assumed that a more granular approach combining detailed LGE findings including extent, location and pattern could improve risk stratification in this population. Purpose To assess the additional prognostic value of the concept of "Late Gadolinium Enhancement (LGE) Granularity" that includes extent, location, and pattern in non-ischaemic dilated cardiomyopathy (DCM) patients to predict all-cause death. Methods Between 2008-2021, all consecutive patients with DCM without ICD or history of sustained ventricular arrythmia referred for cardiac MRI were included in two French centres. In line with the current ESC and AHA guidelines, DCM was defined by the LV dilation and LVEF&amp;lt; 50% using cardiac MRI. All patients with history of coronary artery disease or clinical history of myocarditis were excluded. The primary outcome was all-cause death using the French National Registry of Death. Cox regressions were performed to determine the prognostic value of each LGE findings. The additional prognostic value of the LGE granularity was assessed by the C-statistic increment, the continuous net reclassification improvement (NRI), and the integrative discrimination index (IDI). Results Of 1,668 DCM patients (age 52±8 years, 54% males), 268 (16%) died after a median (interquartile range) follow-up of 9 (7-12) years. With a median LVEF value of 39% (30-46), 472 (28%) patients had non-ischemic LGE. Using survival curves, patients with LVEF&amp;gt;35% but the LGE septal location showed a higher risk of death compared to all patients with LVEF≤35% with or without LGE (except for the septal location, all p&amp;lt;0.001). In DCM patients with LGE (N=472), LGE extent (adjusted HR: 4.27, 95% CI: 2.22-8.22), septal location (HR: 5.74, 95% CI: 3.35-9.85) and multiple areas of LGE (HR: 4.38, 95% CI: 2.08-9.22; all p&amp;lt;0.001) were all independently associated with death after adjustment for prognosticators. The concept of "LGE granularity" combining all these LGE features showed the best improvement in model discrimination and reclassification over traditional prognosticators including LVEF (C-statistic improvement: 0.14; net reclassification improvement=64.3%; integrative discrimination index=29.0%; all p&amp;lt;0.05). Conclusion In a large cohort of DCM patients, the concept of "LGE granularity" combining LGE extent, location and the presence of multiple areas had an additional prognostic value above traditional prognosticators including LVEF to predict all-cause death.

Global myocardial work index is an independent predictor of functional capacity on 6-minute walk test in stable non-ischaemic cardiomyopathy

Abstract Background Reduction in 6-minute walk test distance (6MWD) in heart failure (HF) is associated with impaired quality of life and adverse cardiovascular outcomes. Myocardial work (MW) indices are novel non-invasive measures of left ventricular (LV) function which characterise myocardial contractile efficiency and energy utility. Purpose We aim to assess the predictive capacity of MW indices for functional capacity in stable non-ischaemic cardiomyopathy (NICM). Methods We prospectively recruited consecutive patients with stable NICM from our HF service from January 2021 to December 2023. All patients received optimal guideline direct therapy (OGDT) for 3-months before undergoing a comprehensive transthoracic echocardiogram and functional assessment with 6-minute walk test (6MWT). We excluded patients with prior cardiac surgery, severe airways disease, valvular heart disease, and those in atrial fibrillation (AF) or had mechanical limitations to their mobility at time of 6MWT. We collected demographic, clinical, and echocardiographic factors to identify the determinates of reduced 6MWD defined as &amp;lt;300 metres. Results Of 249-patients included (69.9% male; age 57.3±16.5yrs), 65-patients had reduced 6MWD. They were significantly older (62.3±17.2 vs 55.5±16.0yrs, p=0.005), had shorter height (166.3±10.3 vs 171.3±9.8cm, p=0.001), higher prevalence of AF history (39.1 vs 21.4%, p=0.001), lower LV-ejection-fraction (38.1±13.3 vs 43.3±10.2%, p=0.001), lower LV-global-longitudinal-strain (LV-GLS; 10.5±4.4 vs 12.7±3.9%, p&amp;lt;0.001), lower global-work-index (GWI; 943±487 vs 1230±455mmHg%, p&amp;lt;0.001), lower global-constructive-work (GCW; 1286±561 vs 1590±494mmHg%, p&amp;lt;0.001), lower global-work-efficiency (GE; 81.2±9.9 vs 85.4±8.1mmHg%, p=0.04), larger indexed left atrial volume (LAV; 45.0±18.4 vs 40.1±24.5ml/m2, p=0.038), higher E/e’ ratio (14.6±8.9 vs 11.8±6.0, p=0.003), and lower right-ventricular-free-wall-strain (RV-FWS; 19.2±6.7 vs 21.8±6.4, p=0.008; Table 1.). On receiver-operating-characteristics-curve analysis, GWI best predicted 6MWD reduction (Figure 1; AUC 0.68) compared to GCW, GE, LVEF and LVGLS (AUC: 0.62, 0.40, 0.62, and 0.62 respectively). Accounting for covariates, our multiple regression was run to predict 6MWD from age, height, AF history, LAV, E/e’, GWI and RV-FWS. These variables statistically significantly predicted 6MWD, F(4,239)=23.5, p&amp;lt;0.001, R2=0.34). With each 100mmHg% rise in GWI being independently associated with a 6.5m increase in 6MWD. Conclusion GWI was independently associated with 6MWD in our cohort of NICM patients on OGDT. MW indices provide some mechanistic insights into exercise capacity in patients with NICM.Table 1.Baseline CharacteristicsFigure 1.ROC of GWI Discriminating 6MWD

Efficacy of native T1 mapping for patients with non-ischemic cardiomyopathy and ventricular functional mitral regurgitation undergoing transcatheter edge-to-edge repair

Abstract Background The objectives of this study were to investigate the efficacy of LV myocardial damage assessment by native T1 mapping obtained with cardiac magnetic resonance (CMR) for symptomatic heart failure (HF) patients with non-ischemic cardiomyopathy (NICM) and ventricular functional mitral regurgitation (VFMR) undergoing transcatheter edge-to-edge repair (TEER). Methods We studied 40 symptomatic HF patients with NICM and VFMR undergoing TEER. LV myocardial damage was defined as the native T1 Z-score which was converted from native T1 value obtained with CMR before TEER. The primary endpoint was defined as first re-hospitalization for HF or cardiovascular death over a median follow-up period of 12 months after TEER. Results Multivariable Cox-proportional hazards analysis showed that a native T1 Z-score was the only independent parameter associated with cardiovascular events (hazard ratio: 3.40, 95% confidential interval: 1.51-7.67), and patients with native T1 Z-score &amp;lt; 2.41 experienced significantly fewer cardiovascular events than those with a native T1 Z-score ≥ 2.41 (log-rank P = 0.001). Moreover, such a low native T1 Z-score and more severe VFMR in an effective regurgitant orifice area (EROA) ≥ 0.30 cm2 was associated with fewer cardiovascular events than for a high native T1 Z-score of ≥ 2.41 and less severe VFMR of EROA &amp;lt; 0.30 cm2 (log-rank P = 0.002). Conclusion Assessment of baseline LV myocardial damage by means of native T1 Z-score obtained with CMR without the use of gadolinium-based contrast media is a valuable additional parameter for better management of symptomatic NICM patients with reduced LVEF and VFMR following TEER.

ECGWiz: a unified and generalizable AI model for comprehensive ECG diagnosis

Abstract Background Deep learning has demonstrated diagnostic performance in electrocardiogram (ECG) analysis comparable to that of clinicians. However, existing models primarily excel in diagnosing common conditions such as arrhythmias and heart blocks, which are easily identifiable using standard predictor variables. Conversely, models aiming to uncover novel insights, such as detecting structural changes or the presence of myocardial scar, often lack generalizability due to insufficient data, model architecture limitations, and other factors. Moreover, these models frequently encounter challenges, such as a decline in performance when applied to external datasets. To address these issues comprehensively, we propose the ECGWiz — a unified model capable of tackling diverse ECG-related problems with consistently high performance. Objective To develop a generalizable Foundation AI model for ECG diagnosis capable of detecting diverse cardiac abnormalities and diseases using few training samples. Methods We utilized publicly available datasets like PTB-XL, CPSC, etc. To build our model, totaling approximately 80,000 ECGs. These 12 lead ECGs are scaled and filtered before using them for training. The AI model is pretrained using Self Supervised Learning and Contrastive Learning strategies. Further, the model undergoes supervised training using a hierarchy of labels that increase in granularity, encompassing arrhythmias, heart blocks, other cardiac abnormalities, heart failure, sudden cardiac death and more. Lastly, the model is prepared for Few-Shot Learning — where the model learns from a minimal set of samples (5 to 10 ECGs) of the target disease. For testing the model, we are using unique datasets like PROSE which consists of non-ischemic cardiomyopathy patients with and without myocardial scaring detected using cardiac MRI imaging at the Johns Hopkins University. Results Our model, trained on a dataset of only 5 ECG recordings, demonstrated a 74% accuracy in identifying myocardial scarring as detected by LGE MRI, utilizing a standard 12-lead ECG. This performance is comparable to that of conventional deep learning methods, which necessitate datasets containing upwards of 120 ECG recordings. Conclusion Our model represents a promising stride in creating a unified and adaptable foundation AI model for comprehensive ECG-based diagnosis. Its capacity to learn from a minimal set of examples signifies a robust framework that can evolve and adapt to new challenges in ECG diagnosis. Ongoing improvements, particularly through dataset expansion, underscore its potential to enhance cardiovascular diagnostics, offering precise and efficient patient care.

Late gadolinium enhancement and outcome of cardiac resynchronization therapy in non-ischemic cardiomyopathy

BackgroundIt is uncertain whether CRT with defibrillator (CRTD) is superior to CRT with pacemaker (CRTP) in NICM. Patients with low arrhythmic risk and high probability of response to CRT might be ideal candidates for CRTP.We aimed to evaluate predictors of ventricular arrhythmias and of echocardiographic response to cardiac resynchronization therapy (CRT) in non-ischemic cardiomyopathy (NICM). MethodsMulticenter, retrospective observational study of NICM patients with left ventricular ejection fraction (LVEF) ≤35 %, cardiac magnetic resonance with analysis of late gadolinium enhancement (LGE) available and de-novo CRT implant. Echocardiographic response to CRT was defined as an improvement in LVEF ≥10 %. The combined arrhythmic endpoint included sustained ventricular tachycardia, appropriate ICD therapy, resuscitated cardiac arrest and sudden death. ResultsWe included 167 patients, with a median follow-up of 63 months. LGE was present in 77 (46 %). Response to CRT occurred in 68 % of patients, more frequently in LGE- than in LGE+ (81 % vs 53 %, p < 0.001). Absence of LGE (OR 3.4, p = 0.002), was an independent predictor of response to CRT. The arrhythmic endpoint occurred in 19 patients (11 %). Among LGE- patients there were zero arrhythmic events as compared to a 25 % cumulative incidence in LGE+ (p < 0.001). Presence of LGE (HR 22.5, p < 0.001), was an independent predictor of the arrhythmic endpoint. ConclusionAbsence of LGE identifies patients at minimal arrhythmic risk and with high probability of response to CRT. Thus, they might be ideal candidates to CRT-P.

Prognostic value of left atrial size and function by cardiac magnetic resonance in non-ischemic cardiomyopathy.

To evaluate left atrial (LA) function and strain parameters by cardiac magnetic resonance imaging (CMR) in patients with non-ischemic cardiomyopathy (NICM) and evaluate the association of these parameters with long-term clinical outcomes. We retrospectively included 92 patients with NICM and 50 subjects with no significant cardiovascular disease (control group). We calculated LA volumes using the Simpson area-length method to derive LA ejection fraction and expansion index. LA reservoir (ƐR), conduit (ƐCD), and contractile strain (ƐCT) were measured using dedicated CMR software (cvi42, Circle Cardiovascular Imaging Inc., version 5.14). An adjusted multivariate regression analysis was performed to determine the association of LA parameters with death and heart failure hospitalization (HFH). NICM patients were older with male preponderance. The mean age for NICM patients was 59.6 ± 15.9 years, 64% males, and 73% whites versus 52.2 ± 12.4 years, 34% male and 64% white for controls. LA strain patterns were significantly lower in NICM patients when compared to controls. During a median follow-up of 58.9 months, 12 patients (13%) died and 33(35.9%) had a HFH. None of the clinical or CMR factors were significantly associated with death. On multivariate analysis, after adjusting for age and significant univariate variables, ƐR was the only variable significantly associated with the HFH (OR 0.98, CI 0.96-1.0). Unadjusted and adjusted Cox proportional hazard models divided by the median ƐR (~ 18%) showed a significant difference in HFH over time (χ2 statistic = 21.1; P value = 0.03). In NICM patients, all LA strain components were reduced. ƐR was found to be significantly associated with HFH.

Prognosis and predictors of right ventricular dysfunction by quantitative cardiac magnetic resonance in non-ischaemic cardiomyopathy.

Pathophysiology and prognostic implications of right ventricle (RV) dysfunction in heart failure are complex and incompletely elucidated. Cardiac magnetic resonance imaging (CMR) is the reference standard for RV quantification, but its clinical implications in non-ischaemic cardiomyopathy (NICM), in the context of myocardial fibrosis and functional mitral regurgitation are not well defined. We evaluated predictors, prognostic impact, and thresholds for defining significant RV dysfunction in NICM. NICM patients (n = 624) undergoing CMR assessment during 2002-2017 were retrospectively studied. CMR's quantification of right ventricular ejection fraction (RVEF) was evaluated against the primary outcome of all-cause mortality, heart transplant, and/or left ventricular assist device implantation in threshold and multivariable analyses. Mean RVEF was 43 ± 13%, and factors associated with reduced RVEF were male sex, New York Heart Association (NYHA) class III-IV, right bundle branch block, lower left ventricular ejection fraction, higher mitral regurgitant fraction (MR-RF) and right ventricle size in NICM. RVEF per 5% increase was independently associated with the primary endpoint hazards ratio (95% confidence interval) 0.80 (0.73-0.88), P < 0.001. RVEF ≤40% was the optimal threshold associated with worse prognosis, regardless of late gadolinium enhancement (LGE) or MR-RF quantification. On the other hand, higher LGE was associated with primary endpoint in patients with RVEF ≤40% only, while risk associated with MR-RF was significant dampened after adjusting for RVEF. RVEF provides powerful risk stratification, with RVEF ≤40% defining significant RV dysfunction associated with adverse outcomes in NICM. The integration of quantitative CMR measurements for RVEF, LGE, and MR-RF provides comprehensive NICM risk prognostication.

Inhibition of myeloperoxidase to treat left ventricular dysfunction in non-ischaemic cardiomyopathy.

Non-ischaemic cardiomyopathy (NICMP), an incurable disease terminating in systolic heart failure (heart failure with reduced ejection fraction [HFrEF]), causes immune activation, however anti-inflammatory treatment strategies so far have failed to alter the course of this disease. Myeloperoxidase (MPO), the principal enzyme in neutrophils, has cytotoxic, pro-fibrotic and nitric oxide oxidizing effects. Whether MPO inhibition ameliorates the phenotype in NICMP remains elusive. Prognostic information from MPO was derived from proteomic data of a large human cardiovascular health cohort (n = 3289). In a murine model of NICMP, we studied the mechanisms of MPO in this disease. In a case series, the MPO inhibitor was also evaluated in NICMP patients. Individuals with increased MPO revealed higher long-term mortality and worsening of heart failure, with impaired prognosis when MPO increased during follow-up. MPO infusion attenuated left ventricular ejection fraction (LVEF) in mice with NICMP, whereas genetic ablation or inhibition of MPO decreased systemic vascular resistance (SVR, 9.4 ± 0.7 mmHg*min/ml in NICMP vs. 6.7 ± 0.8 mmHg*min/ml in NICMP/Mpo-/-mice, n = 8, p = 0.006, data expressed as mean ± standard error of the mean) and improved left ventricular function (LVEF 30.3 ± 2.2% in NICMP vs. 40.7 ± 1.1% in NICMP/Mpo-/- mice, n = 16, p < 0.0001). Four patients diagnosed with NICMP and treated with an MPO inhibitor over 12 weeks showed increase in LVEF, decline in natriuretic peptides and improved 6-min walking distance. MPO inhibitor-related changes in the proteome of NICMP patients predicted reduced mortality when related to the changes in the proteome of the above referenced cardiovascular health cohort. Myeloperoxidase predicts long-term outcome in HFrEF and its inhibition elicits systemic anti-inflammatory and vasodilating effects which translate into improved left ventricular function. MPO inhibition deserves further evaluation as a novel, complementary treatment strategy for HFrEF.

Survival benefit of ICD implantation for primary prevention in dilated cardiomyopathy

Objectives: Dilated cardiomyopathy (DCM) represents a significant cause of heart failure unrelated to ischemic heart disease, posing a high risk of sudden cardiac death (SCD) due to low left ventricular ejection fraction (LVEF). This study evaluates the survival benefits of implantable cardiac defibrillators (ICDs) for primary prevention in DCM patients. Methods: We enrolled 52 symptomatic non-ischemic cardiomyopathy patients (LVEF ≤ 35%, NYHA class II-III) eligible for ICD implantation in Afshar Hospital, Yazd, Iran, from 2014 to 2015. Exclusion criteria included those with ischemic indications or requiring cardiac resynchronization therapy. We divided patients into ICD recipients and those on a waiting list, collected the baseline data (age, functional class, LVEF), then followed up with patients to assess mortality rates. Results: Among 45 patients, 64.5% received ICDs while 35.5% were on the waiting list. The mean age was 57±13 years, predominantly male (67.3%). The ICD group had a significantly lower mortality rate (17.3%) than the waiting list group (42.7%, p = 0.54). Although age and functional class did not significantly predict outcomes, lower LVEF was a crucial factor for long-term survival. Despite some studies suggesting no survival benefit in non-ischemic heart failure, our findings highlight the efficacy of ICDs in reducing mortality among DCM patients. Conclusions: ICD implantation in DCM patients substantially reduces all-cause mortality compared to those awaiting the procedure, underscoring the importance of timely ICD deployment for primary prevention in this population.

Septal late enhancement by cardiac CT is associated with repeat ablation in nonischemic cardiomyopathy patients.

Scar substrate in nonischemic cardiomyopathy (NICM) patients is often difficult to identify. Advances in cardiac imaging, especially using late iodine-enhanced computed tomography (LIE-CT), allow better characterization of scars giving rise to ventricular tachycardia (VT). Currently, there are limited data on clinical correlates of CT-derived scar substrates in NICM. We sought assess the relationship between scar location on LIE-CT and outcomes after radiofrequency catheter ablation (RFCA) in NICM patients with VT. From 2020 to 2022, consecutive patients with NICM undergoing VT RFCA with integration of cardiac CT scar modeling (inHeart, Pessac, France) were included at two US tertiary care centers. The CT protocol included both arterial-enhanced imaging for anatomical modeling and LIE-CT for scar assessment. The distribution of substrate on CT was analyzed in relation to patient outcomes, with primary endpoints being VT recurrence and the need for repeat ablation procedure. Sixty patients were included (age 64 ± 12 years, 90% men). Over a median follow-up of 120 days (interquartile range [IQR]: 41-365), repeat ablation procedures were required in 32 (53%). VT recurrence occurred in 46 (77%), with a median time to recurrence of 40 days (IQR: 8-65). CT-derived total scar volume positively correlated with intrinsic QRS duration (r = .34, p = 0.008). Septal scar was found on CT in 34 (57%), and lateral scar in 40 (7%). On univariate logistic regression, septal scar was associated with increased odds of repeat ablation (odds ratio [OR]: 2.9 [1.0-8.4]; p = 0.046), while lateral scar was not (OR: 0.9 [0.3-2.7]; p = 0.855). Septal scar better predicted VT recurrence when compared to lateral scar, but neither were statistically significant (septal scar OR: 3.0 [0.9-10.7]; p = 0.078; lateral scar OR: 1.7 [0.5-5.9]; p = 0.391). In this tertiary care referral population, patients with NICM undergoing VT catheter ablation with septal LIE-CT have nearly threefold increased risk of need for repeat ablation.