Ischemic Cardiomyopathy Research Articles

Achieving theorical cardiorespiratory fitness is associated with high-volumen training in a phase II cardiac rehabilitation program

Abstract Background and Puropose Cardiac Rehabilitation (CR) is an interdisciplinary therapeutic program with demonstrated success rates in reducing cardiovascular outcomes. To obtain these benefits, it is important to achieve a level of cardiorespiratory fitness (CRFIt) that should be close to the ideal according to age and gender (theorical). The best way to measure it, is through VO2p, or with its surrogate value in METs-load. In our Phase II CR program, both aerobic and strength training is supervised 3 times per week, but emphasis is placed on weekly aerobic training volume (TVol) for a sufficient dose, in order to guarantee outcomes. Our hypothesis is that with adequate TVol, CRFit will be achieved at ideal levels (theorical). The aim of the study is to evaluate the safety and achievement in CRFit measured by METs-load in patients with heart disease during a high-volume Phase II CR program. Methods Quasi-experimental study of a comprehensive Phase II CR program in which patients were evaluated by initial and final exercise testing. Depending on the result, they were assigned for 4-6 weeks (4 to those patients with >5METs and 6 to those with <5METs) to 3 weekly concurrent training sessions (30 mins of aerobic at 70-85% of their heart rate reserve plus strength training), in addition to the corresponding educational, nutritional and psychological intervention. TVol was calculated by METs/week (METs-minute obtained by ergo or treadmill multiplied by 90 minutes). Progressions were made to achieve a weekly program average TVol>500 METs/week according to guidelines recomendations. An adverse event was defined as malignant ventricular arrhythmias, cardiorespiratory arrest, or death. Results A population of 522 patients was analyzed, 72% men, average age of 58.8 years (+-0.59), with coronary ischemic disease, heart failure and cardiomyopathies as the most common heart diseases. Regarding the average theorical METs (8.23, +-0.6), our patients achieved final average METs of 10.2 (+-0.26) and 90.02% (+-0.53) of attendace (Figure 1). The average of TVol were 637.4 (+-37.35) METs/week. The differential between the initial and final METs (Delta1) was correlated by Spearman with the differential between the final METs and its theorical (Delta2) and a significant moderate correlation was found (r=0.32 Spearman, p <0.001). TVol and Delta2 shows a strong and significant correlation (r=0.72 Spearman, p<0.001) (Figure 2). No adverse events were reported in any of the training sessions. Conclusion The Phase II CR program with concurrent training only 3 times per week but with TVol>600 METs/week is safe and guarantees a CRFit above the ideal level (theorical). We recommend to measure and fullfill training volume as a strategy to achieve promising results in exercise tolerance and functional capacity in patients with heart disease.

Impact of dapagliflozin on supraventricular and ventricular arrhythmias, assessed by Holter ECG, in patients with heart failure with reduced ejection fraction

Abstract Background & Introduction Dapagliflozin has significantly reduced morbidity & mortality in patients with heart failure with reduced ejection fraction (HFrEF) (1). Some studies reported supraventricular & ventricular arrhythmia suppression, but Holter ECG was underused, hindering precise assessment of arrhythmia burden. Purpose We aim to assess the impact of dapagliflozin on reduction of arrhythmia in HFrEF at 1 year follow-up (FU) by Holter ECG. Methods This is a single center, prospective study. We have screened 219 HFrEF patients, but only 156 patients were enrolled with LVEF <40% in sinus rhythm from December 2021 to July 2023. All patients had dapagliflozin 10 mg once/day tablet with the standard HF therapy. Clinical evaluation, NYHA evaluation, 6-minute walking test (6MWT), echocardiogram, 24-hours Holter ECG and laboratory work-up were done at baseline, and FU at 6 months and 12 months. Results Males constituted 61.5% of study population; mean± SD participants’ age was 56.8 ± 8.6 years. The most common comorbidities were: ischemic etiology (63.3%), dilated cardiomyopathy (28.1%), hypertension (27.3%), smokers (14.7%), and type II diabetes (31.4%). LVEF was ≤ 35% in 85.9% of patients. We have reported (7.69%) deaths during 1-year FU, and 4 patients (2.56%) didn't complete 1-year FU. Main clinical and echocardiographic findings (baseline vs. 1-year FU): NYHA FC III& ambulant IV dropped from (42.9 to 32.9%), P value<0.05. Distance walked in 6MWT improved from 191.52 ± 75.37 to 219.35 ± 71.51 mean± SD meters, P value<0.05. E/e improved (9.4 to 8.3 cm/s, P value <0.01), LVEF improved (31.3 to 36.4%, P value<0.05). HF emergency: [HF visits dropped (23.7 to 19.2%) and HF hospitalization dropped (11.1 to 7.8%)], P value<0.05. Holter ECG (baseline vs. 1-year FU): Supraventricular Arrhythmia: [Paroxysmal AF reduced (56.2 to 47.6%), frequent PACs (≥ 10%) dropped (3.8 to 1.4%) & Intermittent 1st degree heart block dropped (12.5 to 7.3%)] P value <0.01. Ventricular Arrhythmia: [PVCs >5%-<10% dropped (16% to 9.3%), Frequent PVCs >10% dropped (3.2 to 1.4%), and NSVT dropped (7.8 to 3.1%)], P value <0.01. Stepwise logistic regression multivariable model aiming to predict the occurrence of ventricular and supraventricular arrhythmias has indicated a direct linear correlation with male gender, smoking, body mass index, left atrial volume, and a history of myocardial infarction. Conversely, there is an inverse relationship with systolic blood pressure, 6MWT distance, LVEF, and the administration of dapagliflozin (OR 0.72 [0.61 - 1.07], P value <0.01) concerning the likelihood of supraventricular and ventricular arrhythmias. Conclusions Dapagliflozin has demonstrated significant improvement in functional and echocardiographic parameters in HFrEF patients. Furthermore, it has effectively decreased the incidence of supraventricular and ventricular arrhythmias, identified through 24-hour Holter ECG monitoring during 1-year follow-up.

Secretoneurin plasma levels are decreased after catheter ablation for atrial fibrillation, patients with AF produce lower SN levels than healthy individuals

Abstract Background Secretoneurin (SN) is a novel biomarker with potential use in cardiovascular medicine. The main effect of SN is mediated through its inhibition of calmodulin-dependent kinase II (CaMKII), which influences calcium handling[1], plasma SN levels differ in ischemic vs. dilated cardiomyopathy [2]. We aim to associate the levels of SN pre- and postprocedurally and according to the type of atrial fibrillation (AF). Methods We prospectively enrolled patients indicated for catheter ablation (CA) for AF, sequentially sampled patients for SN before, during and after CA for AF. We also sampled healthy individuals as controls. SN was analysed from venous, left atrial and coronary sinus (CS) blood by the use of the ELISA method. Values are expressed as means±SD, variables are compared by standard statistical methods. Results A total of 104 patients (59.4% male) with AF aged 64±10.4, with BMI 30.1±5 and 34 healthy individuals (38% male) were included in the analysis. SN plasma levels were significantly lower 32.3±15.1 after the procedure (SN2) as compared to levels before (SN1) 38.4±17.5 pmol/L (P=0.02, Fig.1). SN was not associated with any marker of cardiac injury or overload, echocardiographic parameters, or ablation characteristics (P=NS), even though Troponin I was significantly increased after the procedure (P<0.0001, Fig.2). Left atrial SN was numerically higher 40.9±19.1 than SN sampled from CS 32.9±13 (P=NS).The SN levels in our patients with AF were generally lower than in healthy individuals (50.7±15.3 pmol/L) before (P=0.0004) as well as after the procedure (P=0.0001). Conclusion Catheter ablation of AF leads to a decrease in SN plasma levels even though markers of cardiac injury are increased. Patients with AF irrespective of actual rhythm produce lower levels of SN than healthy individuals.

MicroRNA-145-5p restricts cardiac scar resolution during cardiac regeneration

Abstract Background Human hearts have a very limited capacity to renew cardiomyocytes following injury. The lost myocardium is permanently replaced with noncontractile fibrotic tissue, consequently leading to heart failure. In contrast, zebrafish retain cardiac regenerative capacity during their lifetime. After injury, zebrafish hearts undergo transient fibrotic scarring that subsequently resolves and is replaced with new cardiomyocytes over time. Thus, understanding the molecular mechanisms governing cardiac scar resolution in zebrafish could offer insights into enhancing the regenerative capacities of human hearts. Objective We aimed to decipher the molecular pathways associated with zebrafish cardiac scar resolution. Methods We investigated the mRNA and miRNA responses to injury at 14 days post-injury by high-throughput transcriptome profiling of RNAs isolated from healthy or cryoinjured hearts. The prediction of miRNA-mRNA interactions was performed to identify the most differentially expressed miRNAs and their target genes. These miRNAs and genes were validated in zebrafish regenerating hearts and in the left ventricles of ischemic cardiomyopathy or dilated cardiomyopathy patients. The potential role of identified miRNAs in cardiac scar resolution was investigated in human cardiac fibroblasts. Results Principal component analyses identify two distinct clusters in both the mRNAome and miRNAome corresponding to healthy and injured hearts, indicating significant changes in transcriptome profiles during zebrafish cardiac regeneration. Gene set enrichment analyses indicate that molecular pathways involved in extracellular matrix organization and inflammatory response are markedly activated whereas genes associated with mitochondrial organization and oxidative phosphorylation are downregulated in injured hearts. We observed the downregulation of miR-145-5p and the upregulation of procollagen V in the injured hearts. In contrast to zebrafish, in the left ventricles of ischemic cardiomyopathy patients, miR-145-5p is significantly upregulated and procollagen V α1 is downregulated. Theoretical prediction of miRNA-mRNA interactions indicates procollagen V α1 is negatively correlated with miR-145-5p. Overexpression of miR-145-5p in human cardiac fibroblasts downregulates collagen V α1 and alpha smooth muscle actin, upregulates procollagen I and matrix metalloproteinase 9, and inhibits cell proliferation and migration. In contrast, inhibition of miR-145-5p upregulates collagen V α1 and alpha smooth muscle actin, downregulates procollagen I and matrix metalloproteinase 9, and stimulates cell proliferation and migration. Conclusion Our study suggests that miR-145-5p may play a role in the suppression of myofibroblast transdifferentiation via collagen V α1, which restricts scar resolution and cardiac repair.

Efficacy and safety of ultrasound guided stellate ganglion block: developing new clinical indications beyond electrical storm

Abstract Background Percutaneous stellate ganglion block (PSGB) is recommended by the latest European guidelines for patients with drug and ventricular tachycardia (VT) ablation refractory electrical storm (ES). Yet, due to the strong antiarrhythmic potential, combined with the good safety profile, we’ve recently used it for to the prophylaxis of ventricular arrhythmias (VAs) in high-risk patients and the prophylaxis/treatment of atrial arrhythmias in patients with acute heart failure (HF). Purpose To describe our single-center experience with PSGB usage outside the conventional indication of ES. Methods We hereby describe our single center experience with PSGB from 2/2021 to 2/2024. Results 56 patients (87% male, mean age 64 ± 12 years) received a total of 91 PSGB performed with the lateral, ultrasound (US) guided technique. Most of the procedures consisted of a single bolus anesthetic injection of lidocaine plus ropivacaine, 27% in an additional continuous infusion, mainly with ropivacaine. All procedures except for 3 in a single patient who had previously received left cardiac sympathetic denervation, were performed on the left side. Most of the patients (61%) suffered ischemic cardiomyopathy (CMP), including 11 with an acute coronary syndrome; the rest had non-ischemic CMP. 63 PSGB (69%) were performed in patients with impending or manifested cardiogenic shock (SCAI classification B or more). Mean LVEF was 24 ± 12%. Most of the procedures (n=80, 88%) were performed due to ongoing refractory VAs, yet 6 (6%) aimed to prevent major VAs in high-risk patients, mostly in the setting of recent ES (within 1 month) and need for Levosimendan to support cardiac output, in one case due to recent stereotactic VT ablation, to prevent early VAs in the phase of acute radiation induced microvascular damage. All 6 were effective in preventing clinically significant VAs. Additionally, 5 single bolus PSGBs (5%) were performed due to atrial arrhythmias with high ventricular rate despite intravenous drugs in the setting of acute HF. Specifically, 3 patients had atrial fibrillation (AF), 1 patient runs of ectopic atrial tachycardia (AT) and 1 patient 2:1 atrial flutter. Left-sided PSGB significantly reduced (≥25% reduction) ventricular rate during AF and AT but not during the single case of 2:1 atrial flutter, in 2/3 AF cases a cardioversion into sinus rhythm occurred within 40 minutes from PSGB. Only 1 (1%) major complication occurred (respiratory arrest), that was quickly and effectively treated with lipid emulsion, while minor complications were observed in 11% of PSGBs (mostly transient left arm weakness). Conclusions Our data suggest that US-guided PSGB usage, thanks to its feasibility at bed-side and good safety profile, may expand, beyond ES, to not only VAs prevention in high-risk settings, but also to prophylaxis/treatment of atrial arrhythmias in critically ill patients with acute heart failure requiring concomitant inotropic support.

Subendocardial ischemic-like state in patients with severe aortic stenosis: insights from myocardial histopathology and ultrastructure

Abstract Background myocardial adaptation to severe aortic stenosis (AS) is a complex process that involves myocardial fibrosis (MF) beyond cardiomyocyte hypertrophy. Perfusion impairment is believed to be involved in myocardial remodeling in chronic pressure overload. Aim to describe morphological and ultrastructural myocardial changes at EMB, possibly reflecting subendocardial ischemia, in a group of patients with severe AS referred to surgical aortic valve replacement (AVR), with no previous history of ischemic cardiomyopathy. Methods one-hundred-fifty-eight patients (73 [68-77] years, 50% women) referred for surgical AVR because of severe symptomatic AS with pre-operative clinical and imaging study and no previous history of ischemic cardiomyopathy. Intra-operative septal EMB was obtained in 129 patients. Tissue sections were stained with Masson ́s Trichrome for MF quantification and periodic acid-Schiff (PAS) staining was performed to assess the presence of intracellular glycogen. Ultrastructure was analyzed through Transmission electron microscopy (TEM). Results MF totalized a median fraction of 11.90% [6.54-19.97%] of EMB, with highly prevalent perivascular involvement (95.3%). None of the samples had histological evidence of myocardial infarction. In 58 patients (45%) we found subendocardial groups of cardiomyocytes with cytoplasmatic enlargement, vacuolization and myofiber derangement, surrounded by extensive interstitial fibrosis. These cardiomyocytes were PAS positive, PAS-diastase resistant and Alcian Blue/PAS indicative of the presence of neutral intracellular glyco-saccharides. At TEM there were signs of cardiomyocyte degeneration with sarcomere disorganization and reduction, organelle rarefaction but no signs of intracellular specific accumulation. Conclusion almost half of the patients with severe AS referred for surgical AVR have histological and ultrastructural signs of subendocardial cardiomyocyte ischemic insult. It might be inferred that local perfusion imbalance contributes to myocardial remodeling and fibrosis in chronic pressure overload.

Vascular complications in patients with peripheral veno-arterial extracorporeal membrane oxygenation: clinical-echocardiographic characteristics and predictors

Abstract Introduction Veno-arterial Extracorporeal membrane oxygenation (VA ECMO) is a salvage intervention in patients with cardiogenic shock (CS), and cardiac arrest (CA) refractory to standard therapies. Lower limb ischemia associated with peripheral VA ECMO is frequent, and is considered a serious complication with a significant impact on the morbidity and mortality. Purpose The aim of this study was to describe the clinical-echographic parameters and analyze predictors related to vascular complications in patients with peripheral VA ECMO. Methods The study was a single-center cohort analysis. It included all consecutive adult patients with peripheral femoro-femoral VA ECMO due to refractory cardiogenic shock (CS) or cardiac arrest (CA) between March 2014 and December 2022. Patients with central cannulation were excluded. The primary endpoint was evidence of vascular complications resulting in surgical intervention. A multivariate logistic regression model was used to adjust for variables of interest. Results The study included 83 patients (65± 12 years, 54% male). The main previous diagnosis was necrotic ischemic cardiomyopathy (33%), and the most frequent indication was postcardiotomy (40.9%), mainly in SCAI D (85.5%). Cardiopulmonary resuscitation was performed in 18.1%. Femoro-femoral cannulation was percutaneuos in 95.2%. Most patients had intra-aortic balloon pump (87.1%) and distal percutaneous cannula (88.8%). A total of 18 patients presented vascular complications (21.7%): 2 patients (11.1%) amputation, 5 patients (27.7%) compartment syndrome requiring fasciotomy, 9 patients (50.0%) thrombectomy, and 2 patients (11.1%) a surgical resolution post decannulation due to AV fistula. The median duration of VA ECMO was 5 days (IQR 2-8). Among the ultrasound variables, the systolic peak velocity (SPV) in the distal territory (tibioperoneal segment) had a median of 22 cm/sec (IQR 10-30). Pulsatile spectral Doppler flow in the cannulated limb was evidenced in 42 patients (50.6%) of total population, and only in 3 patients (16.6%) with vascular complications. The survival rate from VA ECMO was 57.8%, and the survival rate to discharge 42.1%. In-hospital mortality of patients with or without vascular complications did not show statistically significant differences (54.2 % vs 58.2 %, p= 0.26). After multivariate analysis, distal territory SPV less than 20 cm/sec (OR: 2.1, 95%CI: 1.3 – 12.1, p: 0.03), as well as history of previous vascular disease, were associated with a higher number of vascular complications (OR: 2.5, 95% CI: 1.5 – 10.1, P; 0.02). Conclusions Vascular complications in patients with femoro-femoral VA ECMO remain frequent and constitute an important cause of morbidity. Decreased peak systolic velocities in the cannulated tibio-peroneal territory, as well as a history of previous vascular disease were significantly associated with a higher rate of vascular complications.

LV reverse remodeling after SAVR in patients with severe symptomatic aortic stenosis: impact on the clinical outcome

Abstract Introduction Surgical aortic valve replacement (SAVR) is the treatment of choice for young patients with severe aortic stenosis (AS) and low surgical risk. Left ventricular (LV) reverse remodeling (RR) after surgery is expected to occur. However, this is not always the case following afterload relief, and this may impact the prognosis. We aimed to assess the prognostic effect of distinct definitions of LV RR after SAVR in the long-term outcome of patients with severe AS. Methods Single-centre prospective study including patients referred for SAVR due to severe symptomatic AS, with no previous history of ischemic cardiomyopathy. Both pre- and post-operative transthoracic echocardiographic (TTE) and cardiac magnetic resonance (CMR) study (at the 3rd to 6th month after SAVR) were performed. LV RR was defined when in presence of at least one of the imaging criteria: >15% decrease in end-diastolic volume (EDV) by CMR; >15% decrease in LV indexed mass (LVM) by CMR; >10% decrease in geometric remodeling (LV mass/EDV ratio) by CMR; >10% increase in LV ejection fraction (LVEF) by CMR; >50% increase on global longitudinal strain (GLS) by TTE. We assess the prognostic value of RR definitions for the outcome after SAVR using Cox regression and Kaplan-Meier analysis. The primary endpoint was defined as all-cause mortality, heart failure (HF) hospitalization or worsening HF. Results We enrolled 140 patients – mean age 71±9 years-old, 49% male, predominantly high-gradient-normal flow AS (mean gradient 65±18mmHg, aortic valve area 0.7±0.2cm2, index stroke volume 47±11mL/m2) submitted to SAVR. At a mean follow-up (FUP) of 34±12 months, 23 (16%) patients met the primary endpoint: 4% (5 patients) died immediately after surgery; three patients died at the FUP (overall mortality rate of 6%). 12 patients (9%) were admitted for HF and 7 (5%) had at least one episode of worsening HF. 118 patients had complete pre and post-surgery imaging study (mean FUP: 36±10 months): 103 patients (87%) had at least one RR parameter (Table 1). Post-operative RR was not independently associated with the clinical outcome (Figure 1A). LVM was the sole independent predictor of the outcome at univariate analysis (Figure 1B–F). Conclusions LV RR after SAVR is highly prevalent in a cohort of patients with classical severe symptomatic AS. However, only LVM regression independently predicts the clinical outcome after surgery. This may stand the greater importance of structural reverse remodeling, rather than LV functional improvement, after pressure overload relief.

3D modelling-based left atrium geometry analysis to predict atrial fibrillation in patients with cryptogenic stroke

Abstract Introduction Atrial fibrillation (AF) is a high prevalence condition associated with high morbidity and mortality. Its early diagnosis allows to initiate several prophylactic treatments that have proved to improve its prognosis. 3D modeling techniques allow to design accurate representations of cardiac cavities from diverse source images. Purpose We evaluated the association between new geometrical measurements obtained by 3D echocardiographic models of the left atrium (LA) and the presence of underlying paroxysmal AF in patients with cryptogenic stroke (CS). Methods 3D LA volumes from a sample of consecutive patients aged ≥60 years old and admitted to our Stroke Unit with the diagnosis of CS from April 2019 to November 2020 were analyzed. 15 days ECG monitoring was performed after discharge to detect underlying paroxysmal AF. All 3D echo volumes were analyzed by a 3D modeling open-source application. From this analysis several LA geometry parameters were obtained: sphericity, elongation, flatness, major axis length, minor axis length, maximum 2D diameter (max2Ddiam) and surface-volume ratio (S/V). Functional atrial parameters (3D left atrial ejection fraction, LAEF) were also determined. Results 36 patients were analyzed. Mean age was 78 ± 7 years old. 19% were diabetic, 58% had high blood pressure and 14% of patients had history of ischemic cardiomyopathy. Mean body-mass index was 26. These baseline characteristics were equally distributed between groups. Baseline proBNP was significantly higher in patients developing atrial fibrillation (949 vs 275 pg/mL; p= 0,014.). Maximum 2D diameter (max2Ddiam) and Surface-volume ratio (S/V) were the best predictors of AF (AUC of ROC curves: 0.69; 0.49 – 0.88 and 0.63; 0.42 – 0.84, respectively). An optimal cut-off point of 39 mm was selected for max2Ddiam and of 0.20 for S/V. These values were included in a multivariate model adjusted by baseline proBNP. A Max2Ddiam <39 mm and a S/V ≥0.20 were both significantly associated with the presence of paroxysmal AF (OR 6.96; p= 0.048 and OR 12.22; p = 0.043, respectively). Conclusions New geometrical atrial parameters can be obtained from echo 3D models and might be able to predict AF in patients with CS. Further analysis and larger samples are required to better understand these findings.TableFigure

Predictors of LV reverse remodeling after SAVR: insights from a prospective TTE and CMR study in patients with severe aortic stenosis

Abstract Background Left ventricular (LV) remodeling in patients with severe aortic stenosis (AS) is believed to be reversible after pressure overload relieve, as provided by both surgical (SAVR) or transcatheter aortic valve replacement. However, LV reverse remodeling (RR) is far from uniform in patients with AS and the same clinical indication for treatment. Aim To determine the prevalence and imaging predictors of LV RR after SAVR in patients with severe symptomatic AS. Methods single-center, prospective cohort study enrolling 119 patients with severe symptomatic AS (age 71±8y, 49% male; mean transaortic gradient 62±18mmHg, mean indexed aortic valve area (AVAi) 0.40±0.10 cm2/m2, mean LV ejection fraction by TTE 58±9%), with no previous history of ischemic cardiomyopathy, undergoing SAVR between 2019 and 2022. All patients underwent serial imaging assessment beyond clinical characterization (transthoracic echocardiogram – TTE, and 1.5T cardiac magnetic resonance - CMR) prior to surgery and at the 3rd to 6th month post-SAVR. Endomyocardial biopsy (EMB) for myocardial fibrosis quantification (Masson ́s Trichrome histochemistry) was performed during SAVR. LV RR was defined when in presence of at least one of the imaging criteria: > 15% reduction in LV end-diastolic indexed volume (LVEDV) by CMR; > 15% reduction in LV indexed mass (LVM) by CMR; > 15% reduction in LV geometric remodeling by CMR; >10% increase in LV ejection fraction (LVEF) either from TTE or CMR; > 50% increase in global longitudinal strain (GLS) at TTE. Clinical, imaging and histology derived data were compared in patients with post-SAVR LV RR and for each of the defined criteria. Results 107 patients (90%) met at least one criteria of LV RR. Morphological criteria were more prevalent than LV functional improvement after SAVR (Figure 1). In patients who met at least one criteria of LV RR, no differences were found between NT- proBNP, LV tissue characterization (by CMR) or myocardial fibrosis at EMB. Yet, those with LV RR had significantly smaller preoperative AVAi (0.4±0.9 vs 0.5±0.9 cm2/m2, p=0.007) and higher mean valvular gradients (62±18 vs 49±12 mmHg, p=0.017). Considering individual LV RR criteria, patients with higher NT-proBNP levels met LVEF and morphological (LVEDV and LVM) LV RR criteria (p=0.027, p=0.016 and p= 0.003, respectively). Patients with higher % of late gadolinium enhancement on pre-operative CMR [7.8 (IQR 2.5-11.3) vs. 1.6 (IQR 0-5.2)%, p=0.017] had significant GLS improvement after SAVR. Conclusion In a cohort of patients with classical severe, symptomatic AS, LV RR is common after SAVR, occurring in almost 9 out of every 10 patients. Both indexes of worse valve narrowing and pre-operative LV adaptation are associated with favorable RR after surgery. This underlines the benefits of a timely intervention even in patients with more advanced disease.

Impaired strain in diabetic patients with stable coronary artery disease assessed by cardiac magnetic resonance

Abstract Background Type 2 diabetes mellitus (T2DM) can contribute or lead to myocardial structural derangement by multiple mechanisms, including ischemic cardiomyopathy and, more rarely and of difficult evaluation, diabetic cardiomyopathy. Early stages of myocardial dysfunction can be assessed by strain analysis with cardiac magnetic resonance feature tracking (CMR-FT), however, there is no studies that examined deformation parameters in diabetic patients with stablished coronary artery disease (CAD). Purpose We sought to compare the strain parameters of patients with and without T2DM with stable CAD. Methods Patients with stable multivessel CAD and preserved left ventricular ejection fraction (LVEF), included in the MASS V trial, underwent contrast-enhanced cardiac magnetic resonance before revascularization procedures. Patients were stratified according to T2DM diagnosis at baseline. Feature tracking was performed using short-axis cine images and 2- and 4-chamber long-axis images. The left ventricular endocardial and epicardial contours of the end diastole phase were manually delineated in all images. Automatically tracking contours were performed to calculate left ventricular global longitudinal (LVGLS), circumferential (LVGCS) and radial (LVGRS) strain (FIGURE 1). Results Of 202 patients studied, 88 (44%) were diabetic and 114 (56%) non-diabetic. Baseline characteristics were similar between groups (age 70 ± 10 vs 69 ± 11; 69% vs 68% males; LVEF 65 ± 13 vs 67 ± 9). Mean Syntax score was 21.2 ± 8.5 vs 20.4 ± 8.5 (P=0.52) in diabetic and non-diabetic, respectively. There were no differences in left ventricle volumes, mass and LVEF. Mean LGE mass was 2.3 ± 0.9 vs 1.9 ± 0.9 grams (P=0.32) respectively in T2DM and control groups. Strain values were all reduced in T2DM patients, as shown in FIGURE 2 (LVGLS: -15.5% ± 2.3% vs -17.5% ± 2.7%, P=0.02; LVGCS: -15.4% ± 2.6% vs -17.4% ± 3.0%, P=0.03; LVGCS: 25.9% ± 5.9% vs 29.5% ± 7.2%, P=0.01). Multivariable analyses adjusted for age, sex, BMI, hypertension, Syntax score and LGE mass showed no differences in the results. Conclusion In this study, T2DM was associated with impaired deformation parameters (decreased left ventricular global longitudinal, circumferential, and radial strain). These findings suggest myocardial dysfunction in diabetic patients when compared to control subjects in the setting of stable multivessel CAD.FIGURE 1FIGURE 2

Clinical profile of patients undergoing percutaneous stellate ganglion block for electrical storm and association with antiarrhythmic efficacy

Abstract Background Percutaneous stellate ganglion block (PSGB) usage for patients with refractory ventricular arrhythmias (VAs) in form of electrical storm (ES) is in quickly expanding. The clinical profile of patients and the potential association with the antiarrhythmic efficacy of the procedure are mostly unexplored. Purpose To better characterize clinical profile and potential association with antiarrhythmic efficacy of patients undergoing PSGB for ES. Methods Patients undergoing PSGB for ES in our Center from 2/2021 to 2/2024 were enrolled; all the dynamic variables were evaluated in a per procedure analysis. Results 45 patients (93% male, 64 ± 10 years) received a total of 80 PSGB performed with the lateral, ultrasound (US) guided technique; most PSGB consisted of a single bolus anesthetic injection (lidocaine + ropivacaine), 26% in an additional continuous infusion, mostly with ropivacaine. All procedures except for 3 in a single patient who had previously received left cardiac sympathetic denervation, were performed on the left side. Most of the patients (60%) suffered ischemic cardiomyopathy (CMP), including 10 with an acute coronary syndrome; the rest had non-ischemic CMP; 60% had an ICD. The type of VAs was ventricular tachycardia (VTs) only in 86% of the procedures (cycle length 404 ± 143 msec), VT and VF in 10% and VF only in 3 (4%). Most PSGB (81%) were performed in the setting of impending or manifest cardiogenic shock (SCAI classification B or more), including 20% with sepsis. Cardiac US performed before (within 12 hours) each PSGB showed a severely depressed left ventricular (LV) function (mean LVEF 22 ± 10%, mean LV outflow tract velocity time integral 12 ± 4 cm), calculated at a mean heart rate of 81 ± 16 bpm. Mean LVEDV was 252 ± 104 ml, 79% had mitral regurgitation (MR) ≥2+/4+ (including 39% severe MR), 50% had ≥ moderate diastolic dysfunction, 29% had right ventricular dysfunction (mean fractional areal change 33± 7%). Most cases (75%) experienced a complete VAs suppression (sustained or treated) in the 12 hours after PSGB; only 3/80 cases required additional urgent antiarrhythmic strategies (intra-aortic ballon pump in one case, urgent pacing in another one, urgent revascularization in the last one). None of the assessed clinical or echocardiographic characteristics was significantly associated with VT cycle length or the response to PSGB. Only 1 (1%) major complication occurred (respiratory arrest), that was quickly and effectively treated with lipid emulsion. Conclusions PSGB in our Center was mostly performed in the setting of primary impending or manifest cardiogenic shock with severely impaired cardiac function, with an excellent safety profile. None of the assessed clinical or echocardiographic variables were associated with response to PSGB. Our data, despite preliminary and requiring confirmation, suggests always considering PSGB in the urgent/emergent setting independently from patients’ characteristics.

Impact of neonatal hyperoxia on the development of the coronary vascular bed: an experimental model for the study of cardiomyopathy associated with premature birth

Abstract Introduction Very preterm birth (PT; <32 weeks of gestation), nearly 2% of all births, leads to short-term complications such as bronchopulmonary dysplasia and retinopathy of prematurity that are driven by compromised organ vascular development. Adults born preterm display an increased risk of ischaemic cardiomyopathy and heart failure. Our group has shown that neonatal rats exposed to hyperoxia, simulating the PT neonatal conditions, develop cardiomyocytes hypertrophy, fibrosis and cardiac dysfunction, or Oxygen-Induced Cardiomyopathy (OIC). Whether cardiac changes also associate with alterations in vascular development in the left ventricle (LV) remains unknown. Purpose We hypothesized that neonatal exposure to hyperoxia impact the development of the LV vascular network. Methods Male pups were exposed to 80% O2 (OIC) or room air (CTRL) from day 3 (P3) to P10 of life. Hearts were collected at P10, 4- and 16 weeks. Arteriolar length and capillary density per cardiomyocyte were measured using stereology (elastin) and immunofluorescence (WGA, α-SMA, CD31). High-resolution 3D reconstruction of the vascular network was achieved by combining fluorescent labelling of coronaries (anti-α-SMA) and capillaries (anti-CD31) with a tissue-cleaning protocol (iDisco+), allowing detailed morphometric characterization of the vascular network. The expression of vascular endothelial growth factors and receptors (VEGFA, VEGFB, VEGFR 1 and 2, NRP1, and PIGF) were quantified by RT-qPCR and Western blots. Differences between groups were analyzed with Student's t-test (P < 0.05) (N = 6 per group). Results At P10, we observed a notable rise in the number of capillaries per cardiomyocyte (0.88 ± 0.05 vs. 0.62 ± 0.02 mm2) and a significant increase in VEGFA (+76%) and NRP1 (+38%) expression in the LV from OIC vs. CTRL rats. By 4 weeks, the OIC group showed a significant reduction in arteriolar length vs. CTRL (6.51 ± 0.76 vs. 9.77 ± 1.12 m/cm3), coupled with an increase in the number of capillaries per cardiomyocyte (1.11 ± 0.05 vs. 0.85 ± 0.03 mm2). VEGFA was decreased (-14%) and PLGF increased (+24%) in the LV of OIC rats. At 16 weeks, the OIC condition displayed a significant increase in the number of capillaries per cardiomyocyte (1.37 ± 0.03 vs. 0.98 ± 0.07 mm2) and a decrease in VEGFA (-23%), along with reduction in its receptors VEGFR1 (-27%), VEGFR2 (-20%) and NRP1 (-17%). Conclusion OIC resulting from neonatal hyperoxia exposure associates with vascular changes in the LV that persist to adulthood. These changes are characterized by a reduction in arteriolar length and an increase in the number of capillaries, accompanied by modulation of the expression of pro-angiogenic VEGFA and receptors. The impact of these vascular alterations on the susceptibility of the LV to ischemic or hypertension-related damage is to be explored. These findings suggest a crucial mechanistic pathway for understanding the risk of cardiac pathologies associated with preterm birth.

Regadenoson stress echocardiography: a road ahead

Abstract Introduction Drugs used in stress echocardiography (SE) have important limitations due to side effects and contraindications. Since its approval in 2008, Regadenoson has seen a significant increase in usage. This is largely attributed to its good safety profile and diagnostic accuracy, making it the preferred drug for stress tests in many European centers. However, despite its expanding use and major advantages, current guidelines don't place it as the first choice for SE, probably because the reported experience with this drug remains limited. The aim of the present study was to assess the safety and short-medium term prognosis of patients who underwent Regadenoson SE. Methods Retrospective observational study. Patients who underwent Regadenoson SE between 2017 and 2023 were included. Safety was assessed by monitoring immediate adverse effects following Regadenoson infusion and the need for using an antidote (Aminophylline). A positive test result was defined by the occurrence of any of the following: wall motion abnormalities, left ventricle dilatation, electrocardiographic changes or symptoms of ischemia. During the follow up, we registered the incidence of ischaemic events (admission for unstable angina, acute myocardial infarction (AMI) or cardiovascular (CV) death) and other CV events such as admission for heart failure (HF) and stroke. Additionally, we evaluated patients in both groups who underwent coronary angiography (by computerized tomography or coronary catheterization) during the follow up period. The groups with negative SE (NSE) and positive SE (PSE) were compared. Results The total number of patients was 344, with a median follow up of 29 months. Basal population characteristics and events by group (NSE and PSE) are shown in Figure 1. We needed to use the antidote in only one case, because of ventricular bigeminism, with no other major adverse effects reported. SE was positive in 37 (11%) patients. In this group, patients were more likely to present ischaemic events (16% vs. 3%, p<0.01) and admissions for HF (24% vs. 5%, p <0.01), compared to the NSE one. In those who underwent coronary angiography, revascularization was needed in 14 patients of the PSE group, and only in 7 of the NSE group (38% vs 2%, p < 0.05). The indications for these last cases were persistent angina in 5 patients (2 of them with history of coronary artery disease) and revascularization following an AMI in 2 patients. (Figure 2). Conclusions The probability of an ischaemic event after a negative Regadenoson SE remains very low, unlike positive studies. Regadenoson SE showed to be both safe in assessing ischemic cardiomyopathy and very useful for its prognostic value. These findings encourage its expanding use in the stress echo lab.

Frailty, age, and treatment effect of surgical coronary revascularization in ischemic cardiomyopathy: a post hoc analysis of the STICHES trial.

Frailty is common among older patients with heart failure (HF). The efficacy of coronary artery bypass grafting (CABG) on the risk of mortality amongfrailpatients with ischemic cardiomyopathy and HF is uncertain, and whether frailty burden modifies the treatment benefits of CABG among these patients is unknown. We performed a post hoc analysis of the STICHES trial, a randomized trial of CABG with medical therapy vs medical therapy alone among participants with ischemic cardiomyopathy with ejection fraction ≤ 35%. Baseline frailty was assessed through a Rockwood Frailty Index (FI), and based on FI cut-offs from prior HF studies, participants with FI ≥ 0.311 were classified as more frail, and those with FI < 0.311 were classified as less frail. A multivariable Cox proportional hazard model with multiplicative interaction terms was constructed to evaluate whether frailty status modified the treatment effect of CABG on mortalityin the overall trial cohort and among those < 60 vs ≥ 60 years of age. Of 1187 participants (12.4% female, 2.6% Black, median FI = 0.33 [IQR 0.27-0.39]), 678 were characterized as more frail. Frailty burden did not modify the efficacy of CABG on the risk of all-cause death in the overall cohort (Pint CABG × frailty = 0.2). In age stratified analysis,Baseline frailty status did not modify the treatment effect of CABG on the risk of all-cause mortality among younger (< 60years, Pint CABG × frailty = 0.2) as well as older participants (≥60years, Pint CABG × frailty = 0.6). In this post hoc analysis of the STICHES trial, baseline frailty status did not modify the efficacy of CABG in the overall cohort as well asamong younger or older participants. Frailty alone should not be used as a criterion to determine the utilization of CABG among patients with ischemic cardiomyopathy.

Uncovering underlying cause for heart failure in a 51-year-old woman with fibromuscular dysplasia

Abstract Introduction/Objective Arrhythmogenic cardiomyopathy is a rare disorder characterized by the replacement of the myocardium with fibroadipose tissue, usually affecting the right ventricle and rarely affecting the left. Methods/Case Report We present the case of a 51-year-old woman with past medical history including fibromuscular dysplasia of the internal carotid arteries and suspected ischemic cardiomyopathy with reduced ejection fraction awaiting heart transplant. The patient suffered a spontaneous coronary artery dissection eight years prior, which was the inciting factor that led to the decline in her cardiac function. After transplant, gross examination of the explanted heart showed a moderate amount of epicardial fat and visible intramural ventricular adipose tissue deposits in the myocardium. On histology, both the right and left ventricle walls showed extensive microscopic fatty infiltration along with focal involvement of the interventricular septum. These findings supported the final diagnosis of arrhythmogenic cardiomyopathy of the right and left ventricle, as well as involvement of the interventricular septum making this case especially rare. There were no signs of infarct or ischemic damage, contrary to what was expected given her diagnosis of ischemic cardiomyopathy. Results (if a Case Study enter NA) NA Conclusion The pathological work-up of this case shed light on the true nature of the patient’s cardiomyopathy and has prompted further genetic testing, as arrhythmogenic cardiomyopathy can be caused by several different genetic mutations. In addition to this work-up, a thorough literature review was performed looking for connections between arrhythmogenic cardiomyopathy and fibromuscular dysplasia, as arrhythmogenic cardiomyopathy is not often seen in this setting. Although no direct connection between the two was uncovered, it was found in the literature that a polymorphism in the Phosphatase and Actin Regulator 1 (PHACTR1) gene has been identified as a genetic component of fibromuscular dysplasia. This variant has been linked to spontaneous coronary artery dissection, which our patient experienced at the young age of 43. This could prompt further genetic investigation into her fibromuscular dysplasia in addition to the genetic work up already being done for her arrhythmogenic cardiomyopathy. This case highlights how rare etiologies can be uncovered through diligent histological analysis, and how further analysis using laboratory techniques such as genetic testing can help patients understand the full breadth of their conditions.

Comparison of Electrocardiogram between Dilated Cardiomyopathy and Ischemic Cardiomyopathy Based on Empirical Mode Decomposition and Variational Mode Decomposition.

The clinical manifestations of ischemic cardiomyopathy (ICM) bear resemblance to dilated cardiomyopathy (DCM), yet their treatments and prognoses are quite different. Early differentiation between these conditions yields positive outcomes, but the gold standard (coronary angiography) is invasive. The potential use of ECG signals based on variational mode decomposition (VMD) as an alternative remains underexplored. An ECG dataset containing 87 subjects (44 DCM, 43 ICM) is pre-processed for denoising and heartbeat division. Firstly, the ECG signal is processed by empirical mode decomposition (EMD) and VMD. And then, five modes are determined by correlation analysis. Secondly, bispectral analysis is conducted on these modes, extracting corresponding bispectral and nonlinear features. Finally, the features are processed using five machine learning classification models, and a comparative assessment of their classification efficacy is facilitated. The results show that the technique proposed provides a better categorization for DCM and ICM using ECG signals compared to previous approaches, with a highest classification accuracy of 98.30%. Moreover, VMD consistently outperforms EMD under diverse conditions such as different modes, leads, and classifiers. The superiority of VMD on ECG analysis is verified.

Ablation options for sub-epicardially located ventricular substrates responsible for ventricular tachycardia: where is it all headed?

Patients with nonischemic and ischemic cardiomyopathy (NICM and ICM) exhibit re-entrant tachycardias related to scar tissue in subepicardial, in addition to typical subendocardial locations. Control of ventricular arrhythmias related to these targets has remained elusive despite advances in mapping and ablation technology. Percutaneous epicardial ablation is the standard after failed endocardial ventricular ablation, but recurrence rates are disappointing. Pulsed-field energy has been associated with coronary artery spasm and therefore may be less suitable for epicardial ablation. Commercially available energy sources, including pulsed-field, have limited depths of myocardial penetration when applied epicardially. Lateral volumetric thermal spreading of ablation injury is associated with decreasing depth of ablation and is difficult to control. A new cryoablation technology based on liquid helium and developed specifically for epicardial work may be able to overcome these limitations. Ablation strategies that can improve lesion formation in subepicardial ventricular myocardium may improve outcomes of ablation in nonsubendocardial NICM and ICM targets.

Injury-induced myosin-specific tissue-resident memory T cells drive immune checkpoint inhibitor myocarditis

Cardiac myosin-specific (MyHC) T cells drive the disease pathogenesis of immune checkpoint inhibitor-associated myocarditis (ICI-myocarditis). To determine whether MyHC T cells are tissue-resident memory T (TRM) cells, we characterized cardiac TRM cells in naive mice and established that they have a distinct phenotypic and transcriptional profile that can be defined by their upregulation of CD69, PD-1, and CXCR6. We then investigated the effects of cardiac injury through a modified experimental autoimmune myocarditis mouse model and an ischemia-reperfusion injury mouse model and determined that cardiac inflammation induces the recruitment of autoreactive MyHC TRM cells, which coexpress PD-1 and CD69. To investigate whether the recruited MyHC TRM cells could increase susceptibility to ICI-myocarditis, we developed a two-hit ICI-myocarditis mouse model where cardiac injury was induced, mice were allowed to recover, and then were treated with anti-PD-1 antibodies. We determined that mice who recover from cardiac injury are more susceptible to ICI-myocarditis development. We found that murine and human TRM cells share a similar location in the heart and aggregate along the perimyocardium. We phenotyped cells obtained from pericardial fluid from patients diagnosed with dilated cardiomyopathy and ischemic cardiomyopathy and established that pericardial T cells are predominantly CD69+ TRM cells that up-regulate PD-1. Finally, we determined that human pericardial macrophages produce IL-15, which supports and maintains pericardial TRM cells.

Gene expression profiles, potential targets and treatments of cardiac remodeling.

Hypertensive and ischemic heart diseases have high morbidity all over the world, and they primarily contribute to heart failure associated with high mortality. Cardiac remodeling, as a basic pathological process in heart diseases, is mainly comprised of cardiac hypertrophy and fibrosis, as well as cell death which occurs especially in the ischemic cardiomyopathy. Myocardial remodeling has been widely investigated by a variety of animal models, including pressure overload, angiotensin II stimulation, and myocardial infarction. Pressure overload can cause compensatory cardiac hypertrophy at the early stage, followed by decompensatory hypertrophy and heart failure at the end. Recently, RNA sequencing and differentially expressed gene (DEG) analyses have been extensively employed to elucidate the molecular mechanisms of cardiac remodeling and related heart failure, which also provide potential targets for high-throughput drug screenings. In this review, we summarize recent advancements in gene expression profiling, related gene functions, and signaling pathways pertinent to myocardial remodeling induced by pressure overload at distinct stages, ischemia-reperfusion, myocardial infarction, and diabetes. We also discuss the effects of sex differences and inflammation on DEGs and their transcriptional regulatory mechanisms in cardiac remodeling. Additionally, we summarize emerging therapeutic agents and strategies aimed at modulating gene expression profiles during myocardial remodeling.