Nonischemic Heart Research Articles

Reverse electrical remodeling after cardiac resynchronization therapy in a patient undergoing left bundle branch area pacing: a case report

Abstract Background Left bundle branch area pacing (LBBAP) has been introduced as an alternative to biventricular pacing in cardiac resynchronization therapy (CRT). Several studies describe echocardiographic reverse remodeling after LBBAP. Reverse electrical remodeling after LBBAP has not yet been described. Case summary A 77-year-old female with non-ischemic heart failure with reduced ejection fraction (LVEF 30-35%), left bundle branch block (QRS duration 164ms) and symptomatic atrial fibrillation irresponsive to pharmacological therapy was evaluated for CRT with LBBAP and AV node ablation. Successful LBBAP implantation resulted in confirmed left bundle branch capture. Immediately after implantation paced QRS duration was 194ms with a long stimulus-V6RWPT (time to peak R wave in V6) of 93ms, suggesting distal conduction system disease. Patient showed an echocardiographic improvement (LVEF 35% to 50%) and improvement in symptoms (NYHA III to NYHA II) at one year follow-up. Moreover, an improvement in conduction delays was found present. Paced QRS duration improved to 159ms and stimulus-V6RWPT improved to 78ms. This improvement might be due to reverse electrical remodeling. Discussion This case demonstrates that left bundle branch area pacing can induce reverse electrical remodeling, even in the presence of distal conduction system disease. With the current availability of different pacing strategies in CRT (i.e. biventricular CRT, LBBAP, left bundle branch-optimized CRT) more research on patient selection and pacing strategy selection is needed.

Donor age and ischemic time in heart transplantation –implications for organ preservation

IntroductionThe Organ Care System and Non-ischemic Heart Preservation methods have emerged as significant advancements in heart transplantation, designed to mitigate ischemic injury and extend preservation times. However, their high costs and logistical complexities necessitate strategic utilization. MethodsWe evaluated data from 83,761 heart transplants registered in the International Society for Heart and Lung Transplantation registry from 1988 to 2018. Utilizing a Cox proportional hazards model, we explored the influence of donor age and ischemic time on transplant survival. A key innovation of our study is the development of a nomogram to predict post-transplant survival, incorporating both traditional and advanced statistical methods. ResultsThe median age of recipients was 52 years (22% female) and 33 years (31% female) for donors. Analysis revealed a median ischemic time of 3 hours and median survival of 11.5 years across the cohort. The nomogram showed a decline in survival probabilities with increasing donor age, notably from age 40 and more significantly with ischemic times >4 hours. Ischemic times ≥4 hours versus <2 hours were associated with hazard ratio (HR) of 1.2 (95% CI, 1.1-1.3) for donors aged 40-59, a disparity that escalated for donors aged ≥60 (HR: 2.0; 95% CI, 1.5-2.7). ConclusionThis study highlights the importance of careful donor selection and indicates that certain groups, particularly older donors with prolonged ischemic times, might benefit from ex-vivo preservation techniques. The developed nomogram offers a practical tool for clinicians, enhancing decision-making by providing detailed insights into the relationship between donor age, ischemic time, and post-transplant mortality.

Global longitudinal strain measurement in the modern era - is artificial intelligence the answer ?

Abstract Background Global longitudinal strain (GLS) enhances the assessment of left ventricular (LV) function beyond ejection fraction (EF) in 2D echocardiography (Echo). However, manual GLS measurement, the most common technique, is operator dependent. A novel vendor-independent artificial intelligence (AI)-based software streamlines automated 2D-Echo exam evaluation and GLS calculation. Purpose We sought to evaluate the ability of the AI to automatically identify LV 4-, 2-, and 3-chamber views (CV) from 2D-Echo exams and to validate GLS against the conventional manual method. Methods 540 patients underwent standard 2D-Echo exams. The server-based AI recognized the optimal LV CVs from 2D-Echo exams and automatically calculated triplane GLS by endocardial delineation (n=489, 91%). Manual LV GLS was performed independently by accredited cardiologists. Pearson’s correlation (R) and Bland-Altman analysis were performed to assess bias and limits of agreement (LOA) for GLS. Multivariate between-method regression was performed using ordinary least squares to disclose possible sources of possible bias. Significance was defined as a 2-tailed P value &amp;lt; 0.05. Results Patients’ median age was 70 years [18-93], 59% were males. The 2D-Echo indications were coronary artery disease (36%), valvular heart disease (15%), non-ischemic heart failure (15%) and others (34%). The feasibility of the AI to calculate GLS was 91% (n=489) due to endocardial border delineation issues. AI correctly classified all CVs. An excellent correlation (r=0.92, p&amp;lt;0.001) was observed between AI and manual GLS, with low bias (0.5%) and narrow LOAs (-3.1 and +4.2%) (Figure 1, top row). We identified LV end-diastolic volume and EF as statistically significant confounders (p &amp;lt; 0.05) with only small effect as depicted in Figure 1 (bottom row). Neither sex, age, acoustic window, body mass index, nor heart rate, along with the interaction with sex, end-diastolic volume, or EF, were significant (p &amp;gt; 0.23). Conclusion AI-based LV GLS calculation in 2D-Echo shows promising feasibility and accuracy. Strong agreement between AI-derived GLS and manual measurements supports its reliability. The AI's ability to identify optimal LV views underscores its robustness. Further validation and refinement are warranted, highlighting the transformative potential of AI in advancing cardiovascular diagnostics.

Comprehensive stress echocardiography uncovers the heterogenity of phenotypes in non-ischemic heart failure with abnormal ejection fraction

Abstract Background Heart failure (HF) with abnormal left ventricular (LV) ejection fraction (EF) manifests in multiple phenotypes, each presenting distinct and potentially actionable therapeutic targets. This study aimed to assess the potential of the ABCDE+ stress echocardiography (SE) protocol in uncovering different phenotypes of non-ischemic HF. Methods With a retrospective analysis of prospectively acquired data, we identified 265 patients (mean age: 65.7±12.6 years; 154 males, 59.9%) with non-ischemic HF with EF&amp;lt;50% (mean =41.4±7.5) enrolled by 23 certified laboratories between 2021 and 2023. Ischemic origin was excluded based on data of angiography and medical history. ABCDE-SE was evaluated with exercise (n=98, 37.0%), dobutamine (n=50, 18.9%), or vasodilators (n=117, 44.1%). The protocol consisted of several steps: A assessed regional wall motion abnormality (RWMA); B evaluated number of B-lines; C measured left ventricular contractile reserve; Step D with coronary flow velocity reserve (CFVR) in the left anterior descending artery (LAD) was completed in 102 patients (38.5%); step E assessed heart rate reserve. Additionally, step F (evaluated in 188 patients at rest and 107 at peak stress) noted the presence of rest or stress-induced moderate-to-severe secondary mitral regurgitation. The SE response was graded on a scale from 0 (all steps normal) to 5 (all ABCDE+ steps abnormal). Results The mean ABCDE score was 1.5±1.2, ranging from 0 (n=59, 22.3%) to 5 (n=2, 0.8%) (see distribution of scores in Figure 1A). Abnormal results were observed in 21 subjects (7.9%) for A, 86 (32.5 %) for B, 147 (55.5%) for C, 42/102 (41.2%) for D, and 101 (38.1%) for E steps. Step F was abnormal in 22/188 (11.8%) at rest and in 16/107 (14.9%) at peak stress. The predominant "solitary phenotypes" (only one step abnormal) were impaired LV contractile function phenotype (step C in 47, 51.1%) followed by chronotropic insufficiency (step E in 17, 18.5%) and congestive phenotype (step B in 17, 18.5%) (see Figure 1B). The most frequent combined phenotype was BCE – congestive phenotype with impaired ventricular and heart rate reserves (28 [62.2%]). Notably, 38 patients (14.3%) demonstrated improved regional contractility, while 27 patients (10.2%) showed new regional wall motion abnormality (see Table). Conclusion Non-ischemic HF patients with abnormal EF exhibit a broad spectrum of phenotypes. Impaired left ventricular contractility, interstitial congestion, and chronotropic insufficiency are the most frequent abnormalities detected by ABCDE-SE. Up to one-quarter of such patients demonstrate normal SE results. This comprehensive approach paves the way for personalized, SE-guided therapy.

Analysis factors influencing left ventricular thrombus in patients with non-ischemic heart failure

Objective: To explore the influencing factors of left ventricular thrombus (LVT) in patients with non-ischemic heart failure (NIHF) and to construct a nomogram prediction model for NIHF patients with LVT. Methods: This study was a case-control study. A total of 2 592 patients with NIHF hospitalized in Beijing Anzhen Hospital affiliated to Capital Medical University from January 2018 to July 2022 were selected. Fifty-one patients with LVT identified by echocardiography and cardiac magnetic resonance were classified into LVT group. One hundred and sixty patients were selected as the non-LVT group using a 1∶3 propensity score matching based on age and gender. Multivariate logistic regression analysis was used to explore the influencing factors of LVT in patients with NIHF. A nomogram prediction model was constructed, and the area under (AUC) the receiver operating characteristic (ROC) curve was calculated to evaluate the predictive effect of the model. Results: A total of 211 patients were enrolled, with a median age of 40 years old and 160 males (76%). Compared with non-LVT group, LVT group had lower systolic blood pressure ((112±20) mmHg vs. (120±19) mmHg; 1 mmHg=0.133 kPa), lower left ventricular ejection fraction (LVEF; (27±12)% vs. (39±14)% ), lower proportion of patients with history of hypertension (28% (14/51) vs. 44% (70/160)) and atrial fibrillation (8% (4/51)vs.39% (62/160)), higher proportion of patients with New York Heart Association functional class Ⅲ to Ⅳ (class Ⅲ: 59% (30/51) vs. 41% (66/160); class Ⅳ: 28% (14/51) vs. 19% (31/160)), and larger left ventricular end-systolic diameter (LVESD; (56±14) mm vs. (50±15) mm). The levels of hemoglobin ((152±23) g/L vs. (142±30) g/L), D-dimer (508 (300, 1 105) μg/L vs. 158 (68, 379) μg/L), and N-terminal pro-brain natriuretic peptide (3 429 (2 462, 4 734) ng/L vs. 1 288 (422, 2 544) ng/L) were higher in LVT group than in non-LVT group (P all<0.05). LVT group had a higher proportion of patients using beta-blockers (92% (47/51) vs. 78% (124/160)), angiotensin-converting enzyme inhibitors or angiotensin receptor blockers or angiotensin receptor neprilysin inhibitors (88% (45/51) vs. 72% (115/160)), and anticoagulant drugs (98% (50/51) vs. 32% (51/160)) than non-LVT group (all P <0.05). Multivariate logistic regression showed that reduced LVEF (OR=1.08, 95%CI 1.02-1.15, P=0.008), decreased LVESD (OR=1.07, 95%CI 1.01-1.12, P=0.013), and increased D-dimer levels (OR=5.40, 95%CI 1.98-14.74, P=0.001) were independent influencing factors for LVT in patients with NIHF. The ROC curve showed that the AUC of the nomogram for predicting LVT in patients with NIHF was 0.793 (95%CI 0.710-0.876, P<0.001). Conclusion: Reduced LVEF, decreased LVESD, and elevated D-dimer are associated with LVT in NIHF patients. The predictive model developed based on the above indicators has certain value in predicting LVT in NIHF patients.

The emerging role of clonal haematopoiesis in the pathogenesis of dilated cardiomyopathy.

The increased sensitivity of novel DNA sequencing techniques has made it possible to identify somatic mutations in small circulating clones of haematopoietic stem cells. When the mutation affects a 'driver' gene, the mutant clone gains a competitive advantage and has the potential to expand over time, a phenomenon referred to as clonal haematopoiesis (CH), which is emerging as a new risk factor for various non-haematological conditions, most notably cardiovascular disease (e.g. heart failure). Dilated cardiomyopathy (DCM) is a form of non-ischaemic heart failure that is characterized by a heterogeneous aetiology. The first evidence is arising that CH plays an important role in the disease course in patients with DCM, and a strong association of CH with multiple aetiologies of DCM has been described (e.g. inflammation, chemotherapy, and atrial fibrillation). The myocardial inflammation induced by CH may be an important trigger for DCM development for an already susceptible heart, e.g. in the presence of genetic variants, environmental triggers, and comorbidities. Studies investigating the role of CH in the pathogenesis of DCM are expected to increase rapidly. To move the field forward, it will be important to report the methodology and results in a standardized manner, so results can be combined and compared. The accurate measurement of CH in patients with DCM can provide guidance of specific (anti-inflammatory) therapies, as mutations in the CH driver genes prime the inflammasome pathway.

Interpretable Clinical Decision-Making Application for Etiological Diagnosis of Ventricular Tachycardia Based on Machine Learning.

Background: Ventricular tachycardia (VT) can broadly be categorised into ischemic heart disease, non-ischemic structural heart disease, and idiopathic VT. There are few studies related to the application of machine learning for the etiological diagnosis of VT, and the interpretable methods are still in the exploratory stage for clinical decision-making applications. Objectives: The aim is to propose a machine learning model for the etiological diagnosis of VT. Interpretable results based on models are compared with expert knowledge, and interpretable evaluation protocols for clinical decision-making applications are developed. Methods: A total of 1305 VT patient data from 1 January 2013 to 1 September 2023 at the Arrhythmia Centre of Fuwai Hospital were included in the study. Clinical data collected during hospitalisation included demographics, medical history, vital signs, echocardiographic results, and laboratory test outcomes. Results: The XGBoost model demonstrated the best performance in VT etiological diagnosis (precision, recall, and F1 were 88.4%, 88.5%, and 88.4%, respectively). A total of four interpretable machine learning methods applicable to clinical decision-making were evaluated in terms of visualisation, clinical usability, clinical applicability, and efficiency with expert knowledge interpretation. Conclusions: The XGBoost model demonstrated superior performance in the etiological diagnosis of VT, and SHAP and decision tree interpretable methods are more favoured by clinicians for decision-making.

Metabolic cycles: A unifying concept for energy transfer in the heart

It is still debated whether changes in metabolic flux are cause or consequence of contractile dysfunction in non-ischemic heart disease. We have previously proposed a model of cardiac metabolism grounded in a series of six moiety-conserved, interconnected cycles. In view of a recent interest to augment oxygen availability in heart failure through iron supplementation, we integrated this intervention in terms of moiety conservation. Examining published work from both human and murine models, we argue this strategy restores a mitochondrial cycle of energy transfer by enhancing mitochondrial pyruvate carrier (MPC) expression and providing pyruvate as a substrate for carboxylation and anaplerosis. Metabolomic data from failing heart muscle reveal elevated pyruvate levels with a concomitant decrease in the levels of Krebs cycle intermediates. Additionally, MPC is downregulated in the same failing hearts, as well as under hypoxic conditions. MPC expression increases upon mechanical unloading in the failing human heart, as does contractile function. We note that MPC deficiency also alters expression of enzymes involved in pyruvate carboxylation and decarboxylation, increases intermediates of biosynthetic pathways, and eventually leads to cardiac hypertrophy and dilated cardiomyopathy. Collectively, we propose that an unbroken chain of moiety-conserved cycles facilitates energy transfer in the heart. We refer to the transport and subsequent carboxylation of pyruvate in the mitochondrial matrix as an example and a proposed target for metabolic support to reverse impaired contractile function.

Anthropometric measures and long-term mortality in non-ischaemic heart failure with reduced ejection fraction: Questioning the obesity paradox.

Although body mass index (BMI) is the most commonly used anthropometric measure to assess adiposity, alternative indices such as the waist-to-height ratio may better reflect the location and amount of ectopic fat as well as the weight of the skeleton. The prognostic value of several alternative anthropometric measures was compared with that of BMI in 1116 patients with non-ischaemic heart failure with reduced ejection fraction (HFrEF) enrolled in DANISH. The association between anthropometric measures and all-cause death was adjusted for prognostic variables, including natriuretic peptides. Median follow-up was 9.5 years (25th-75th percentile, 7.9-10.9). Compared to patients with a BMI 18.5-24.9 kg/m2 (n = 363), those with a BMI ≥25 kg/m2 had a higher risk of all-cause and cardiovascular death, although this association was only statistically significant for a BMI ≥35 kg/m2 (n = 91) (all-cause death: hazard ratio [HR] 1.78, 95% confidence interval [CI] 1.28-2.48; cardiovascular death: HR 2.46, 95% CI 1.69-3.58). Compared to a BMI 18.5-24.9 kg/m2, a BMI <18.5 kg/m2 (n = 24) was associated with a numerically, but not a significantly, higher risk of all-cause and cardiovascular death. Greater waist-to-height ratio (as an exemplar of indices not incorporating weight) was also associated with a higher risk of all-cause and cardiovascular death (HR for the highest vs. the lowest quintile: all-cause death: HR 2.11, 95% CI 1.53-2.92; cardiovascular death: HR 2.17, 95% CI 1.49-3.15). In patients with non-ischaemic HFrEF, there was a clear association between greater adiposity and higher long-term mortality. ClinicalTrials.gov NCT00542945.

Targeting Cyclophilin A in the Cardiac Microenvironment Preserves Heart Function and Structure in Failing Hearts.

Cardiac hypertrophy is characterized by remodeling of the myocardium, which involves alterations in the ECM (extracellular matrix) and cardiomyocyte structure. These alterations critically contribute to impaired contractility and relaxation, ultimately leading to heart failure. Emerging evidence implicates that extracellular signaling molecules are critically involved in the pathogenesis of cardiac hypertrophy and remodeling. The immunophilin CyPA (cyclophilin A) has been identified as a potential culprit. In this study, we aimed to unravel the interplay between eCyPA (extracellular CyPA) and myocardial dysfunction and evaluate the therapeutic potential of inhibiting its extracellular accumulation to improve heart function. Employing a multidisciplinary approach encompassing in silico, in vitro, in vivo, and ex vivo experiments we studied a mouse model of cardiac hypertrophy and human heart specimen to decipher the interaction of CyPA and the cardiac microenvironment in highly relevant pre-/clinical settings. Myocardial expression of CyPA (immunohistology) and the inflammatory transcriptome (NanoString) was analyzed in human cardiac tissue derived from patients with nonischemic, noninflammatory congestive heart failure (n=187). These analyses were paralleled by a mouse model of Ang (angiotensin) II-induced heart failure, which was assessed by functional (echocardiography), structural (immunohistology, atomic force microscopy), and biomolecular (Raman spectroscopy) analyses. The effect of inhibiting eCyPA in the cardiac microenvironment was evaluated using a newly developed neutralizing anti-eCyPA monoclonal antibody. We observed a significant accumulation of eCyPA in both human and murine-failing hearts. Importantly, higher eCyPA expression was associated with poor clinical outcomes in patients (P=0.043) and contractile dysfunction in mice (Pearson correlation coefficient, -0.73). Further, myocardial expression of eCyPA was critically associated with an increase in myocardial hypertrophy, inflammation, fibrosis, stiffness, and cardiac dysfunction in vivo. Antibody-based inhibition of eCyPA prevented (Ang II)-induced myocardial remodeling and dysfunction in mice. Our study provides strong evidence of the pathogenic role of eCyPA in remodeling, myocardial stiffening, and dysfunction in heart failure. The findings suggest that antibody-based inhibition of eCyPA may offer a novel therapeutic strategy for nonischemic heart failure. Further research is needed to evaluate the translational potential of these interventions in human patients with cardiac hypertrophy.

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.

Mesenchymal stromal cells to treat patients with non-ischaemic heart failure: Results from SCIENCE II pilot study.

Allogeneic stem cell therapy is more logistically suitable compared with autologous cell therapy for large-scale patient treatment. We aim to investigate the clinical safety and efficacy profile of the allogeneic adipose tissue derived mesenchymal stromal cell product (CSCC_ASC) as an add-on therapy in patients with chronic non-ischaemic heart failure with reduced left ventricular ejection fraction (HFrEF)<40%. This is a single-centre investigator-initiated randomized phase I/II study with direct intra-myocardial injections of 100 million allogeneic CSCC_ASC. A total of 30 HFrEF patients with New York Heart Association (NYHA) class ≥II despite optimal anticongestive heart failure medication and plasma NT-proBNP>300pg/mL (>35pmol/L) were included and randomized 2:1 to CSCC_ASC or standard care. The primary endpoint left ventricular end systolic volume (LVESV) and other echo related parameters were analysed by an investigator blinded for treatment allocation. No difference in serious adverse events was observed between groups. LVESV decreased significantly from baseline to 6months follow-up in the ASC group (153.7±53.2mL and 128.7±45.6mL, P<0.001) and remained unchanged in the standard care group (180.4±39.4mL and 186.7±48.9mL, P=0.652). There was a significant difference between the groups in LVESV change (31.3±11.0mL, P=0.009). The difference from baseline to follow-up between the two groups in left ventricular end diastolic volume (LVEDV) was 18.7±12.4mL, P=0.146 and in left ventricular ejection fraction (LVEF) -7.8±2.1%, P=0.001. Considering the baseline values of LVESV, LVEDV and LVEF as covariates, the difference between groups for change from baseline to follow-up resulted in a P-value of 0.056, 0.076, and 0.738, respectively. NYHA class and self-reported health did also improve significantly in the ASC group compared with the standard care group (0.7±0.2, P=0.001 and -12.8±5.3, P=0.025; respectively). There was no difference in NT-proBNP (-371±455pmol/L, P=0.422) or in 6min walk test (12±31m, P=0.695) between groups. Intramyocardial injections of allogeneic CSCC_ASC in patients with chronic non-ischaemic HFrEF was safe and improved LVESV, LVEF, NYHA class, and self-reported health compared with standard care group.

Cardiomyocyte PANX1 Controls Glycolysis and Neutrophil Recruitment in Hypertrophy.

PANX1 (pannexin 1), a ubiquitously expressed ATP release membrane channel, has been shown to play a role in inflammation, blood pressure regulation, and myocardial infarction. However, the possible role of PANX1 in cardiomyocytes in the progression of heart failure has not yet been investigated. We generated a novel mouse line with constitutive deletion of PANX1 in cardiomyocytes (Panx1MyHC6). PANX1 deletion in cardiomyocytes had no effect on unstressed heart function but increased the glycolytic metabolism and resulting glycolytic ATP production, with a concurrent decrease in oxidative phosphorylation, both in vivo and in vitro. In vitro, treatment of H9c2 (H9c2 rat myoblast cell line) cardiomyocytes with isoproterenol led to PANX1-dependent release of ATP and Yo-Pro-1 uptake, as assessed by pharmacological blockade with spironolactone and siRNA-mediated knockdown of PANX1. To investigate nonischemic heart failure and the preceding cardiac hypertrophy, we administered isoproterenol, and we demonstrated that Panx1MyHC6 mice were protected from systolic and diastolic left ventricle volume increases as a result of cardiomyocyte hypertrophy. Moreover, we found that Panx1MyHC6 mice showed decreased isoproterenol-induced recruitment of immune cells (CD45+), particularly neutrophils (CD11b+ [integrin subunit alpha M], Ly6g+ [lymphocyte antigen 6 family member G]), to the myocardium. Together, these data demonstrate that PANX1 deficiency in cardiomyocytes increases glycolytic metabolism and protects against cardiac hypertrophy in nonischemic heart failure at least in part by reducing immune cell recruitment. Our study implies PANX1 channel inhibition as a therapeutic approach to ameliorate cardiac dysfunction in patients with heart failure.

Pulmonary transit time is a predictor of outcomes in heart failure: a cardiovascular magnetic resonance first-pass perfusion study

BackgroundPulmonary transit time (PTT) can be measured automatically from arterial input function (AIF) images of dual sequence first-pass perfusion imaging. PTT has been validated against invasive cardiac catheterisation correlating with both cardiac output and left ventricular filling pressure (both important prognostic markers in heart failure). We hypothesized that prolonged PTT is associated with clinical outcomes in patients with heart failure.MethodsWe recruited outpatients with a recent diagnosis of non-ischaemic heart failure with left ventricular ejection fraction (LVEF) < 50% on referral echocardiogram. Patients were followed up by a review of medical records for major adverse cardiovascular events (MACE) defined as all-cause mortality, heart failure hospitalization, ventricular arrhythmia, stroke or myocardial infarction. PTT was measured automatically from low-resolution AIF dynamic series of both the LV and RV during rest perfusion imaging, and the PTT was measured as the time (in seconds) between the centroid of the left (LV) and right ventricle (RV) indicator dilution curves.ResultsPatients (N = 294) were followed-up for median 2.0 years during which 37 patients (12.6%) had at least one MACE event. On univariate Cox regression analysis there was a significant association between PTT and MACE (Hazard ratio (HR) 1.16, 95% confidence interval (CI) 1.08–1.25, P = 0.0001). There was also significant association between PTT and heart failure hospitalisation (HR 1.15, 95% CI 1.02–1.29, P = 0.02) and moderate correlation between PTT and N-terminal pro B-type natriuretic peptide (NT-proBNP, r = 0.51, P < 0.001). PTT remained predictive of MACE after adjustment for clinical and imaging factors but was no longer significant once adjusted for NT-proBNP.ConclusionsPTT measured automatically during CMR perfusion imaging in patients with recent onset non-ischaemic heart failure is predictive of MACE and in particular heart failure hospitalisation. PTT derived in this way may be a non-invasive marker of haemodynamic congestion in heart failure and future studies are required to establish if prolonged PTT identifies those who may warrant closer follow-up or medicine optimisation to reduce the risk of future adverse events.

Multimodal explainable artificial intelligence identifies patients with non-ischaemic cardiomyopathy at risk of lethal ventricular arrhythmias

The efficacy of an implantable cardioverter-defibrillator (ICD) in patients with a non-ischaemic cardiomyopathy for primary prevention of sudden cardiac death is increasingly debated. We developed a multimodal deep learning model for arrhythmic risk prediction that integrated late gadolinium enhanced (LGE) cardiac magnetic resonance imaging (MRI), electrocardiography (ECG) and clinical data. Short-axis LGE-MRI scans and 12-lead ECGs were retrospectively collected from a cohort of 289 patients prior to ICD implantation, across two tertiary hospitals. A residual variational autoencoder was developed to extract physiological features from LGE-MRI and ECG, and used as inputs for a machine learning model (DEEP RISK) to predict malignant ventricular arrhythmia onset. In the validation cohort, the multimodal DEEP RISK model predicted malignant ventricular arrhythmias with an area under the receiver operating characteristic curve (AUROC) of 0.84 (95% confidence interval (CI) 0.71–0.96), a sensitivity of 0.98 (95% CI 0.75–1.00) and a specificity of 0.73 (95% CI 0.58–0.97). The models trained on individual modalities exhibited lower AUROC values compared to DEEP RISK [MRI branch: 0.80 (95% CI 0.65–0.94), ECG branch: 0.54 (95% CI 0.26–0.82), Clinical branch: 0.64 (95% CI 0.39–0.87)]. These results suggest that a multimodal model achieves high prognostic accuracy in predicting ventricular arrhythmias in a cohort of patients with non-ischaemic systolic heart failure, using data collected prior to ICD implantation.

A predictive model of super response to cardiac resynchronization therapy in short-term period.

The left bundle branch block, nonischemic heart failure (HF) and female gender are the most powerful predictors of a super response to cardiac resynchronization therapy (CRT). It is important to identify super responders who can derive most benefits from CRT. We aimed to establish a predicting model that could be used for prognosis of a super response to CRT in short-term period. Patients with QRS ≥ 130ms, New York Heart Association (NYHA) II-III class of HF, left ventricle ejection fraction (LVEF) ≤ 35% and indications for CRT were included in the study. Before and 6month after CRT the electrocardiography, echocardiography and cardiac scintigraphy were performed. The study's primary endpoint was the NYHA class improvement ≥ 1 and left ventricle end systolic volume decrease > 30% or LVEF improvement > 15% after 6month CRT. Based on collected data, we developed a predictive model regarding a super response to CRT. Of 49 (100.0%) patients, 32 (65.3%) had a super response to CRT. Patients with a super response were likelier to have a lower cardiac index (p = 0.007), higher rates of interventricular delay (IVD) (p = 0.003), phase standard deviation of left ventricle anterior wall (PSD LVAW) (p = 0.009) and ∆QRS (p = 0.02). Only IVD and PSD LVAW were independently associated with a super response to CRT in univariate and multivariate logistic regression. We created a logistic equation and calculated a cut-off value. The resulting ROC curve revealed a discriminative ability with AUC of 0.812 (sensitivity 90.62%; specificity 70.59%). Our predictive model is able to distinguish patients with a super response to CRT.

Differences in characteristics and risk factors for acute kidney injury between elderly and very elderly patients: a retrospective review.

Few epidemiologic studies on acute kidney injury (AKI) have focused on the older adult population. This study aimed to clarify the characteristics and risk factors for AKI in this population. This retrospective observational study was performed with the clinical data of all outpatients and inpatients aged ≥ 65years at the time of enrolment at Kochi Medical School Hospital between 1 January 1981 and 31 December 2021. The primary cohort was divided into those aged 65-74 and ≥ 75years. The primary outcome was the occurrence of AKI. Of 83,822 patients, 38,333 were included in the 65-74-year-old group, whereas 45,489 were included in the ≥ 75-year-old group. Prevalences of the first AKI event in the 65-74-year-old and ≥ 75-year-old groups were 11.9% and 12.4%, respectively. Overall, lower estimated glomerular filtration rate, lower albumin level, lower or higher level of serum uric acid, and histories of diabetes mellitus, chronic heart failure, ischaemic heart disease, non-ischaemic heart disease, cerebrovascular disease, cancer, and liver disease were independent risk factors for an AKI event. The risk factors for AKI unique to each cohort were using non-steroidal anti-inflammatory drugs (NSAIDs) and loop diuretics (L-DI), and histories of hypertension (HT) and vascular diseases (VD) in men aged 65-74years; using NSAIDs, angiotensin-converting enzyme inhibitors (ACEIs), L-DI and other diuretics (O-DI), and histories of HT and VD in men aged ≥ 75years; using NSAIDs and O-DI and not using angiotensin-receptor blockers (ARBs), and a history of HT in women aged 65-74years; and use of L-DI and a history of VD in women aged ≥ 75years. Presence of proteinuria was a risk factor for developing AKI. Many AKI risk factors reported thus far are associated with AKI development. However, there are differences in the effects of the renin-angiotensin system inhibitors, ACEIs, and ARBs (ARBs may be protective). Additionally, the U-shaped relationship between AKI onset and uric acid levels differs between sexes in the elderly population, similar to other age groups, but this sex difference disappears in the very elderly population. Pre-existing chronic kidney disease is a risk factor for the development of AKI.

Impact of left bundle branch block morphology in predicting response to left bundle branch area pacing for cardiac resynchronization therapy

Abstract Background Left bundle branch area pacing (LBBAP) is a novel pacing technique with an emerging role in resynchronization therapy [1-4]. QRS morphology has shown to significantly influence cardiac resynchronization therapy (CRT) response [5-6]. Purpose The aim of this study was to assess whether different left bundle branch block (LBBB) definitions are associated with response to LBBAP resynchronization therapy. Methods 40 consecutive CRT candidates with previously unsuccessful biventricular (BiV) pacing or in which effective CRT could not be achieved with BiV pacing based on anatomical or functional criteria were selected for this study. Both ischemic and non-ischemic heart failure (HF) patients were included. Patients were divided into two groups according to LBBB morphology. Group 1 included 20 patients (45% ischemic HF) with strict LBBB definition according to Strauss criteria [7], while 20 patients in Group 2 (55% ischemic HF) had conventional LBBB morphology. Response to CRT was defined for (1) reduction in QRS duration; (2) increase in left ventricular ejection fraction (LVEF) ≥ 5% and (3) decrease in left ventricular end systolic volume (LVESV) ≥ 15%. Results LBBAP was successfully achieved in all patients (mean age: 72.0 years; male: 29). The mean baseline QRS duration before implantation was 178.6±13.8 in the Group 1 and 170.8±29.4 in the Group 2, without a statistically significant difference. Over a mean follow-up of 5.6 months, LBBAP resulted in QRS narrowing in both groups, with a greater reduction in Group 1 (-40.6 ms) compared to Group 2 (-15.1 ms), (p 0.002). Pre-implantation ventricular systolic function did not show significant differences between the two groups, with a mean of 30.1±3.5% in the Strauss LBBB group and 31.0±6.0% in the conventional LBBB group. After implantation LVEF was 42.1±8.5 % in the true LBBB patients and 33.2±7.5 in the conventional LBBB group. Echocardiographic response was observed in 65% of patients with a statistically significant difference between Group 1 (90% of responders) and Group 2 (40% of responders), (p 0,001). HF etiology did not impact the response to LBBAP CRT. Conclusions Strict LBBB definition is associated to a greater electrocardiographic and echocardiographic response in patients receiving LBBAP CRT compared to conventional LBBB criteria.\

Relationship between fortilin levels and coronary ischemia in heart failure

Objective: Fortilin is a multifunctional protein that protects cells against apoptosis. We aimed to investigate the levels of fortilin in patients with heart failure. Methods: Patients with ejection fraction (EF) below 40% were divided into two groups according to coronary angiography results: those with ischemic heart failure (Group 1) and those with non-ischemic heart failure (Group 2). Patients with normal anatomy and EF over 50% were included in the control group (Group 3). Results: A total of 119 patients were prospectively included in the study. A total of 81 patients (41 patients with ischemic heart failure and 40 patients with non-ischemic heart failure) were included in the heart failure group. 38 patients with EF &amp;gt;50 and normal coronary anatomy were included in the control group. There was no significant difference in serum fortilin levels between the study groups (Group 1: 5.5±2.6 ng/mL, Group 2: 6.1±3.8 ng/mL, and Group 3: 5.6±3.6 ng/mL; P=0.693). Fortilin did not show a correlation with any other variables. Conclusion: In our study, there was no significant difference in fortilin levels between the groups, and no relationship was found between coronary ischemia and fortilin levels in heart failure.

Delayed Enhancement in Cardiac CT: A Potential Alternative to Cardiac MRI? Technical Updates and Clinical Considerations

Despite cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) being the current gold standard for non-invasive myocardial characterization and fibrosis quantification, its accessibility is limited, particularly in acute settings and in certain patient populations with contraindications to magnetic resonance imaging. Late iodine enhancement (LIE) in computed tomography (CT) imaging has emerged as a potential alternative, capitalizing on the similarities in the contrast kinetics between gadolinium and iodinated contrast agents. Studies have investigated LIE-CT’s effectiveness in myocardial infarction (MI) detection, revealing promising outcomes alongside some disparities compared to LGE-CMR. LIE-CT also proves beneficial in diagnosing non-ischemic heart diseases such as myocarditis, hypertrophic cardiomyopathy, and sarcoidosis. While LIE-CT demonstrates good accuracy in detecting certain myocardial pathologies, including acute MI and chronic fibrotic changes, it has limitations, such as the inability to detect diffuse myocardial enhancement. Nonetheless, thanks to the availability of optimized protocols with minimal radiation doses and contrast medium administration, integrating LIE-CT into cardiac CT protocols could enhance its clinical utility, particularly in acute settings, providing valuable prognostic and management insights across a spectrum of cardiac ischemic and non-ischemic conditions.