Hypertrophic cardiomyopathy (HCM) often requires repeated enhanced cardiac magnetic resonance (CMR) imaging to detect fibrosis. We aimed to develop a practical model based on cine imaging to help identify patients with high risk of fibrosis and screen out patients without fibrosis to avoid unnecessary injection of contrast.A total of 273 patients with HCM were divided into training and test sets at a ratio of 7:3. Logistic regression analysis was used to find predictive image features to construct CMR model. Radiomic features were derived from the maximal wall thickness (MWT) slice and entire left ventricular (LV) myocardium. Extreme gradient boosting was used to build radiomic models. Integrated models were established by fusing image features and radiomic models. The model performance was validated in the test set and assessed by ROC and calibration curve and decision curve analysis (DCA).CMR+R1 and ICMR+R2). In the test set, ICMR+R2 model had an excellent AUC value (0.898), diagnostic accuracy (89.02%), sensitivity (92.54%), and F1 score (93.23%) in identifying patients with positive late gadolinium enhancement. The calibration plots and DCA indicated that ICMR+R2 model was well-calibrated and presented a better net benefit than other models.We established five prediction models, including CMR, R1 (based on the MWT slice), R2 (based on the entire LV myocardium), and two integrated models (IA predictive model that fused image and radiomic features from the entire LV myocardium had good diagnostic performance, robustness, and clinical utility.• Hypertrophic cardiomyopathy is prone to fibrosis, requiring patients to undergo repeated enhanced cardiac magnetic resonance imaging to detect fibrosis over their lifetime follow-up.• A predictive model based on the entire left ventricular myocardium outperformed a model based on a slice of the maximal wall thickness.• A predictive model that fused image and radiomic features from the entire left ventricular myocardium had excellent diagnostic performance, robustness, and clinical utility.The online version contains supplementary material available at 10.1007/s00330-022-09217-0. Myocardial fibrosis is a characteristic pathological manifestation of hypertrophic cardiomyopathy (HCM). Myocardial fibrosis in patients with HCM is a predictor of poor prognosis, including sudden cardiac death, heart failure, and ventricular arrhythmia , 2. CardThe application and exploration of extensive data mining in clinical medicine have vastly grown in recent years. Radiomics has become increasingly widespread in heart diseases as it can characterize the myocardial tissue –11. NeisThe study aimed to establish models that fuse image features and texture characteristics based on cine imaging to detect fibrosis in patients with HCM and compare the performance of models constructed using a single slice and the entire LV myocardium.The ethics committee of our hospital approved this study and waived the requirement for informed consent due to its retrospective nature. The study included patients with HCM who underwent CMR scans between January 2013 and December 2020  was used in the GE scanner, while the generalized auto-calibrating partially parallel acquisition (acceleration factor = 2) in the Siemens scanner. LGE images were obtained 8–10 min after intravenous injection of 0.15–0.2 mmol/kg of gadopentetate dimeglumine (Beilu) with the following parameters: slice thickness/gap, 8 mm/2 mm; TR, 6.6 and 2.5 ms; TE, 3.1 and 1.09 ms; flip angle, 20° and 40°; FOV, 360 × 324 and 340 × 255 mm2 (Supplementary Table CMR scans were performed on 1.5-T magnetic resonance scanners (GE Signa Excite HD or Siemens MAGNETOM Avanto) with a phased-array body coil. Short-axis cine images covering the entire LV and long-axis cine images (two/ three/ four-chamber) were acquired using a retrospective electrocardiogram-gated and balanced steady-state free precession sequence. The respective parameters were as follows: slice thickness/gap, 8 mm/2 mm; repetition time (TR), 3.5 and 2.64 ms; echo time (TE), 1.5 and 1.11 ms; flip angle, 45° and 56°; field of view (FOV), 360 × 360 and 340 × 276 mmCardiac function and strain analysis were performed using CVI42, Version 5.13.5 (Circle Cardiovascular Imaging Inc.). LV function, including LV ejection fraction (LVEF), LV end-diastolic volume index (LVEDVI), LV end-systolic volume index (LVESVI), systolic volume index, and LV mass index (LVMI), was calculated automatically by loading short-axis images into the short-3D module. A stack of long- (two-/three-/four-chamber) and short-axis images were loaded into the tissue tracking module for two-dimensional strain analysis. Endocardial and epicardial borders at end-diastolic LV were automatically drawn to track the myocardium throughout the heart cycle and manually adjusted when necessary for optimal tracking. Then, peak values of myocardial strains and strain rates were derived: global radial, circumferential, and longitudinal strains ; global radial, circumferential, and longitudinal strain rates ; early global radial, circumferential, and longitudinal strain of diastolic rates . The end-diastolic maximum wall thickness (MWT) was measured in the short-axis images. Left atrial anteroposterior diameter was measured on a three-chamber view.LGE analysis was obtained in the tissue characteristic module. Radiologist A, with 4 years of CMR experience, visually estimated LGE in short- and long-axis views. Patients were classified as LGE(+) if they had myocardial enhancement in at least one segment. If uncertain, a senior radiologist was consulted, reaching a consensus through discussion. LGE extent was quantified as the percentage of total LV mass (%LGE) using a grayscale threshold of > 5 SDs from remote normal myocardium. The HCM cohort was divided into LGE (+) and LGE (−) groups.http://www.itksnap.org/). Before feature extraction, cine images were interpolated to voxel sizes of 1 × 1 × 4 mm3 using a SimpleITK nearest-neighbor resampling filter to reduce within-image variability. A min-max normalization was performed for all images to map the pixel intensity to 0–255. The Pyradiomics package, version 3.0.1 (https://github.com/Radiomics/pyradiomics), extracted 1130 and 1688 features from the MWT slice and the entire LV myocardium, respectively, including four categories: 18 first-order, 14 shape (2D/3D), and 75 texture features for both, and 1023 and 1581 high-order features, respectively.Radiologist A manually delineated the entire LV myocardium at the end of diastole in short-axis cine views as the region of interest using ITK-SNAP, version 3.8.0  > 0.85 were considered reproducible and retained for further analysis. Subsequently, the Boruta algorithm reduced the dimensionality of the total radiomic features . The impCMR+R1 and ICMR+R2 models were built by integrating CMR model and R1 or R2 model through logistic regression. Receiver operating characteristic (ROC) curves evaluated the models’ diagnostic performance. Calibration curve and Hosmer-Lemeshow test evaluated the calibration performance and goodness of fit. Decision curve analysis (DCA) assessed the net benefits of models. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) evaluated the incremental value of ICMR+R2 for identifying fibrosis. Figure CMR imaging parameters with significant differences were selected in the training set using logistic regression and collinearity analysis. These were used to build the CMR model. R1 and R2 models were constructed based on the MWT slice and entire LV myocardium, respectively, using radiomic features selected by XGBoost. Ihttp://www.r-project.org/). Continuous variables were expressed as mean ± SD or median (interquartile range). Shapiro Wilk test evaluated the normality of data distributions. Student’s t-test or Mann–Whitney test was used appropriately to assess differences between groups. Categorical data were expressed as frequencies (percentages), and the chi-square test or Fisher’s exact test compared differences between groups. Statistical significance was set at p < 0.05.Data analysis was performed using IBM SPSS Statistics for Windows, version 23.0 (IBM Corp.) and R studio . Patients and CMR characteristics are summarized in Table The radiomics workflow is illustrated in Fig. CMR+R1 and ICMR+R2). In the training set, R2, ICMR+R1, and ICMR+R2 models could better distinguish between LGE(+) and LGE(–) groups  than CMR and R1 models  patients  from LGE(–) patients in the training set  and test set . The R2 model achieved a specificity of 93.33% in the test cohort. Supplementary Figure Univariate and multivariate logistic regression and collinearity analyses revealed that MWT, LVMI, and GLS were independent predictors of LGE(+) Fig. . Therefoels Fig. . In the CMR+R2 model was well calibrated, with a mean predicted probability for each group close to the observed probability  probability in each group. The DCA results comparing the performance of five models are shown in Fig. CMR+R2 models had better net benefits than other models for threshold probabilities ranging from 40 to 90%. Furthermore, ICMR+R2 model yielded significantly positive NRI and IDI compared to the CMR model in the training  and test set , indicating that the ICMR+R2 model could improve the discrimination and reclassification for fibrosis in HCM. Moreover, we performed a subgroup analysis of R2 and ICMR+R2 models. AUC values in the GE and Siemens scanners were similar to the mixed data in both datasets  of the LGE(+) patients, while R2 model screened out 14 (93.33%) of LGE(–) patients. A model including radiomic features derived from the entire LV myocardium may provide a reliable and stable tool to identify patients with HCM at high risk of fibrosis and screen out those at low risk, avoiding unnecessary contrast-enhanced CMR scanning.In this study, we constructed CMR, radiomics, and integrated models based on cine imaging to identify fibrosis in patients with HCM. The results in the independent test set showed that IThe apparent manifestation of HCM is myocardial thickening , 2. LV wCMR+R1 models had similar AUC values for identifying LGE(+) patients, suggesting that radiomic models based on a single myocardial slice have no advantage over imaging features in diagnosing fibrosis in HCM. In comparison, R2 and ICMR+R2 models had better discrimination power with AUC values of 0.906 and 0.898 in the test cohort. ICMR+R2 model correctly identified most LGE(+) patients (92.54%) who would benefit from LGE scanning. At least 93.33% of patients without fibrosis could avoid repeated enhanced CMR based on the R2 model. Therefore, after a comprehensive evaluation of the ROC curves, confusion matrix, decision curves, and reclassification indices, we believe that the ICMR+R2 model is the optimal tool to identify LGE(+) patients, while the R2 model is more suitable for screening out LGE(–) patients. In clinical practice, enhanced CMR is used most frequently to evaluate fibrosis. LGE scanning is recommended for patients with HCM without contraindications, regardless of the probability of fibrosis. This study proposed a personalized strategy, namely, performing gadolinium-free CMR in patients with HCM at low risk of fibrosis and LGE scanning in those at high risk of fibrosis. A multi-center study on 1099 patients with HCM established a deep learning model that combined morphology (MWT and radiomic features) and function  [CMR+R2 model could only identify 68.75% of patients without fibrosis, it still exhibited satisfactory discriminability and stability and excellent sensitivity (92.54%) and F1 score (93.23%), even with limited data.Radiomics can conduct an in-depth analysis of medical images and extract a large number of features that the naked eyes cannot observe . Baessleckening) . Among tckening) , 26. AltCMR+R2 model was constructed by radiomics based on routine cine images, presenting great discriminative performance and considerable clinical benefit, which would help promote its application in clinical practice.Previous studies have shown that radiomics or deep learning based on CT and other MR sequences can identify patients with HCM at high risk of fibrosis. Qin et al  demonstrThis study had some limitations. First, it was a single-center study with a small sample size. A multi-center study with a larger sample is required to confirm the model effectiveness. Second, the results were based on two MR scanners. Future studies should test models for generality across diverse populations and scanners. Third, our study lacked a quantitative scar analysis. We are trying to collect multi-center data for further quantitative and prognostic studies, hoping to soon implement gadolinium-free scans in selected patients with HCM. Fourth, we assessed end-diastolic but not end-systolic cine images. This was because MWT data available for HCM diagnosis and CMR model training were acquired at the end of diastole. Finally, our study included slightly more patients with LGE(+) than in other studies, possibly because the patients referred to our center were screened by lower-level hospitals, resulting in a selection bias.A predictive model that fused radiomics from the entire LV myocardium had good diagnostic performance, robustness, and clinical utility. This model may represent an economical and feasible alternative follow-up plan for patients who do not have to undergo repeated enhanced CMR, avoiding unnecessary contrast injection.ESM 1(DOCX 656 kb)


Mitral regurgitation (MR) induces left ventricular failure and pulmonary hypertension (PH) and can lead to right ventricular (RV) failure. Inhaled nitric oxide (iNO) decreases pulmonary vessel resistance. iNO has been used in patients with PH and RV failure.We present a case with cardiogenic shock due to severe degenerative MR. The patient underwent emergent transcatheter mitral valve edge-to-edge repair (TEER). Despite TEER had been successfully performed, hemodynamics did not improve due to RV failure. Administration of iNO improved hemodynamics. This case suggests administration of iNO could be an effective option for RV failure after TEER. Mitral regurgitation (MR) elevates left atrial and pulmonary venous pressures. Those elevated pressures might cause disruption of the alveolar-capillary complex and elevation of pulmonary vascular resistance (PVR), resulting in pulmonary hypertension (PH) and right ventricular (RV) failure . InhaledTranscatheter mitral valve edge-to-edge repair (TEER) is a minimally invasive option for the treatment of patients with MR who are judged to be inoperable or at high surgical risk . PatientIn this case report, we present a case in which iNO was an effective option for residual RV failure after the emergent TEER in a patient with cardiogenic shock due to severe degenerative MR.A 68-year-old male  had chronic heart failure with severe MR, moderate tricuspid regurgitation, and paroxysmal atrial fibrillation.The patient had been scheduled for surgical mitral valve repair three years ago for severe MR but refused the intervention and dropped out of the follow-up. The patient was rushed to our hospital due to dyspnea followed by anuria and leg edema caused by exacerbation of heart failure. The patient had no history of kidney disease. When examined in the emergency department, the patient’s blood pressure was 106/75 mmHg, pulse rate was 126/min irregular, and respiratory rate was 22/min with percutaneous oxygen saturation (SpO2) of 99% with 3 L/min of oxygen insufflation. A chest X-ray revealed an enlarged heart and bilateral pleural effusion. A transthoracic echocardiogram showed an LV ejection fraction of 55% (modified Simpson method) and an LV end-diastolic diameter of 56.1 mm without LV wall asynergy. The pathology of MR was prolapse of the mid-posterior mitral leaflet (P2) . We assumed that successful TEER reduced left atrial pressure, making the right-to-left shunt continuous. We decided to occlude the iatrogenic atrial septal defect (iASD). Occlusion of the iASD was performed with a 6-mm-diameter Amplatzer cribriform occluder . When the occlusion of the iASD successful, SpO2 increased 94 % to 100% (FIO2: 0.5). The patient remained in cardiogenic shock (SvO2 was 55%) despite inotropic and IABP support.After the introduction of general anesthesia, arterial blood pressure (ABP) dropped from 122/64 to 60/32 mmHg despite the administration of dobutamine (5 mcg/kg/min), milrinone (0.25 mcg/kg/min), and noradrenaline (0.05 mcg/kg/min) and IABP support. PAP was 51/28/40 mmHg and central venous pressure (CVP) was 17 mmHg at that time. The procedure began with the right femoral vein puncture. A slight right-to-left shunt appeared on transesophageal echocardiography after atrial trans-septal puncture. Subsequently, a 24-Fr steerable guiding catheter was inserted into the left atrium. Finally, a clip was implanted in the A2/P2 segment. Transesophageal echocardiography showed that residual MR was mild without mitral stenosis. Although MitraClip was successful, hemodynamics did not improve. Immediately after removing the steerable guiding catheter, a right-to-left shunt developed continuously  of 1.5 to complement echocardiographic findings. Despite unloading pulmonary circulation by TEER, the patient still suffered from PH and RV failure. When iNO was administered at 20 ppm through an INOflo DS  without any other additional anesthetic interventions, hemodynamics improved dramatically in a few minutes. ABP increased from 59/27 to 93/44 mmHg, PAP decreased from 43/25/33 to 36/18/27 mmHg, CVP decreased from 12 to 8mmHg, SvO2 increased from 55% to 75%, and cardiac output increased from 2.1 to 3.1 L/min (Table Transesophageal echocardiography revealed that RV fractional area change was 28%. PAP was 43/25/33 mmHg and CVP was 12 mmHg. PVR was high at 876 dynes・sec・cmThe patient was transferred from the operating room to the intensive care unit. The patient was withdrawn from IABP support on postoperative day 2. Administration of iNO was stopped, and the patient was extubated on postoperative day 3. The patient was discharged from the intensive care unit on postoperative day 7 without major complications.PH was redefined in 2022 as a mean PAP higher than 20 mmHg at rest as assessed by right heart catheterization . PH is aPatients with perioperative RV failure in TEER have high rates of mortality and hospitalization due to heart failure . It takeEchocardiographic predictors of RV dysfunction include TAPSE <17 mm, pulsed Doppler S wave <9.5 cm/s, RV fractional area change <35%, RV three-dimensional ejection fraction <45%, and pulsed Doppler RV index of myocardial performance >0.43 .A relatively novel hemodynamic parameter of RV function, PAPi, is defined as the ratio of pulmonary artery pulse pressure to the right atrium pressure. The importance of PAPi in predicting severe RV failure requiring additional hemodynamic support has been reported. However, the normal range of PAPi has not been reported. According to previous reports, receiver operating characteristic curves have demonstrated an optimal PAPi cut-off of <1.85 for RV failure after left ventricular assist device implantation  and <1.9The right ventricle has a unique crescent shape so each echocardiographic parameter has its own limitations . PAPi isiNO relaxes pulmonary artery smooth muscle to decrease PVR, which leads to increased cardiac output in patients with RV failure . Other bSome studies have reported that iNO is associated with improved RV function, decreased PVR, and optimized ventilation-perfusion matching ,4. On thPatients undergoing urgent/emergent TEER are often complicated by cardiogenic shock or RV failure. Some patients do not improve their hemodynamics due to residual RV failure after urgent/emergent TEER. This is the first report that indicates that the administration of iNO could be an effective option in such cases. Further studies are warranted to validate the safety and efficacy of this strategy.


Propofol is a widely used general anesthetic agent with a generally familiar and predictable adverse effect profile. Severe left ventricular dysfunction to an ejection fraction of < 35% is a rare adverse effect of propofol, with a scarcity of data in the literature. In this case, we report a 36-year-old female at 36 weeks gestation with a prior remote history of peripartum cardiomyopathy, who, while receiving propofol for general anesthesia during a C-section, developed severe left ventricular dysfunction with an ejection fraction of 20-25%, flash pulmonary edema, and cardiogenic shock. She required initiation of inotropic support and, following weaning of propofol, gradually recovered her ejection fraction over the next 24 hours to 40-45% and to 50-55% at follow-up two weeks after discharge. This case highlights a unique adverse effect of propofol with scarce pre-existing literature and no guidelines on appropriate management. It is essential for clinicians to be familiar with this uncommon complication, particularly as propofol use continues to rise worldwide. Propofol is a general anesthetic widely used for adults, including peripartum patients. While its multifaceted mechanism is believed to increase the GABA-mediated inhibitory tone within the central nervous system. While the adverse effects of hypotension and bradycardia are well-recognized in clinical practice, these are usually transient and rapidly improve without any need for intervention . Left veA 36-year-old G5P4004 female at 36 weeks gestation presented for pre-delivery optimization before a scheduled cesarean section. She had a history of peripartum cardiomyopathy in her last cesarean delivery 6 years prior, with a reduced ejection fraction (EF) of 25-30%, which had recovered to 50-55% after goal-directed medical therapy with lisinopril, that had since been discontinued for the past 5 years. She was asymptomatic in the intervening years, had an excellent functional status with a Duke Activity Status Index of 58.2, and was pre-emptively admitted for pre-delivery risk stratification, given her prior history of peripartum cardiomyopathy and advanced maternal age. On presentation, she denied shortness of breath, orthopnea, bendopnea, paroxysmal nocturnal dyspnea, palpitations, or chest pain. She was euvolemic on physical examination with no evidence of pulmonary edema, jugular venous distension, or lower extremity edema. Her baseline NT-pro-BNP was 192pg/ml [reference range 0 - 125pg/ml]. A transthoracic echocardiogram revealed an ejection fraction of 50-55%, with no abnormalities. She was deemed low-risk from a cardiac standpoint and was scheduled for a C-section with epidural anesthesia.While the patient was in her regular state of health before the C-section, immediately following the administration of epidural anesthesia with bupivacaine, she became acutely agitated and disruptive. At the time, delivery was considered urgent, and the decision was made to sedate and intubate the patient for an emergent C-section. She was given a bolus of 150 mg of propofol, followed by an infusion at 35 mcg/kg/min. However, 20 minutes following the initiation of propofol, the patient became hypotensive with an acute reduction in mean arterial pressure to 56 and hypoxic, requiring up-titration of FiO2 to 100% and initiation of an epinephrine infusion. An immediate bedside transthoracic echocardiogram (TTE) revealed an ejection fraction of 10-15% with global hypokinesis. She was transferred to the cardiac care unit after delivery for further management. Her exam revealed bilateral diffuse rales and an S3 gallop. A chest x-ray revealed diffuse pulmonary edema. A TTE demonstrated severe left ventricular systolic dysfunction with EF of 20-25% and global hypokinesis (Video The patient rapidly improved and was extubated to bilevel positive pressure ventilation shortly after. She continued a short course of bolus diuresis leading to a resolution of pulmonary edema and improvement in EF to 40-45% within 24 hours of admission to the cardiac care unit. She was discharged successfully on day 2 following admission on losartan 25 mg once daily and metoprolol succinate 50 mg once daily. On outpatient follow-up, two weeks after discharge, her EF on TTE was improved to 50-55%, and she was well-compensated, with no further complaints. The differential diagnoses of stress-induced cardiomyopathy and recurrence of peripartum cardiomyopathy were considered; however, the diagnosis of propofol-induced LV dysfunction was made based on the rapid acuity of LV systolic dysfunction with the initiation of intra-operative propofol, alongside the rapid improvement of LV systolic function with cessation of propofol.Our case represents a case of acute decompensated heart failure with reduced ejection fraction in a young female undergoing Cesarean section shortly after the initiation of propofol. The acute onset of LV systolic dysfunction and the rapid recovery of her ejection fraction after discontinuation supported a diagnosis of propofol-induced LV dysfunction. While recurrence of peripartum cardiomyopathy and stress-induced cardiomyopathy remained on the differential diagnoses, they were considered less likely due to a lack of recurrent postpartum cardiomyopathy in interim pregnancies and the onset of LV systolic dysfunction acutely following propofol infusion. Furthermore, while the meantime for recurrence of peripartum cardiomyopathy is within 2.2 years, our patient presents 6 years following her last occurrence of peripartum cardiomyopathy . Our casIt is prudent for clinicians to be aware of adverse outcomes from propofol use. Propofol can result in hypotension and bradycardia due to a sympatholytic effect at clinical doses, which typically is transient and requires vasoactive support in less than 0.2% of all cases . One stuIn higher doses, propofol has been shown to directly impair myocardial contractility . PropofoLV dysfunction from propofol is an extremely important consideration in peri-operative management. Given the ability of propofol to depress left ventricular systolic dysfunction, it is possible that it may result in clinical presentations of peripartum cardiomyopathy or as an agent that can exacerbate stress cardiomyopathy. It is reasonable, particularly those patients with a prior cardiac history of LV dysfunction, to use propofol judiciously to avoid this notable adverse outcome on patient care due to the paucity of data available on propofol's effect on myocardial contractility, further prospective studies and necessary to elaborate clinical recommendations from these findings.Left ventricular dysfunction from propofol use is an uncommon complication requiring increased awareness in peri-operative management. While propofol is a widely used anesthetic agent with a generally predictable adverse effect profile, we propose that in patients with pre-existing left ventricular dysfunction, propofol be used judiciously with a standardized management protocol should LV dysfunction arise. Due to the paucity of existing literature on propofol's effect on myocardial contractility, further randomized controlled trials are necessary to elucidate more data on this uncommon effect.


Complete heart block (CHB) as a first presentation of acute viral myocarditis is a rare occurrence associated with increased morbidity and mortality. In such cases, an endomyocardial biopsy is recommended to make a clear histological diagnosis aiding to differentiate from other possible conditions such as sarcoiditic myocarditis, giant cell myocarditis, and eosinophilic myocarditis. Insertion of a permanent pacemaker may be considered on a case-to-case basis.A previously healthy 21-year-old female presented to the emergency department after having suffered two episodes of syncope on a background of a few days’ history of myalgias, chills, and rigors. Electrocardiogram showed high-grade Mobitz II block with intermittent periods of CHB. A bedside echocardiogram upon admission demonstrated normal biventricular systolic function. Given the patient’s unstable haemodynamic status and lack of obvious reversible causes for the CHB, a permanent dual-chamber pacemaker was inserted urgently. Initial blood investigations indicated an ongoing inflammatory process highlighting the possibility of myocarditis as a cause of the CHB. Therefore, a troponin level was taken and was noted to be elevated confirming the suspicion of myocarditis. The left ventricular ejection fraction (LVEF) decreased over the following days to approximately 20%, clinically resulting in pulmonary oedema and acute shortness of breath. The patient required aggressive intravenous diuresis and anti-heart failure medication. An endomyocardial biopsy (EMB) confirmed the diagnosis of lymphocytic myocarditis. The patient’s condition improved secondary to an improvement in LVEF and resolution of the heart block. A cardiac magnetic resonance (CMR) imaging performed 6 weeks from admission reported an improved LVEF of 51% with no late gadolinium enhancement (LGE). Based on the reassuring CMR findings and the resolution of CHB on follow-up pacemaker checks, it was deemed safe to explant the pacemaker.Acute myocarditis may be complicated with high-degree AV block and cardiogenic shock necessitating close observation in a critical care unit. A permanent pacemaker may provide atrio-ventricular synchrony which helps stabilise the patient’s condition and protect from a prolonged period of heart block. Early myocardial fibrosis on EMB and degree of LGE on CMR are indicators of persistent atrioventricular block. Guideline-directed treatment of heart failure is essential.The online version contains supplementary material available at 10.1186/s43044-023-00406-w. Complete heart block (CHB) as a first presentation of acute myocarditis is a rare occurrence and is associated with an increased morbidity and mortality , 2. We rA previously healthy 21-year-old female presented to the emergency department after experiencing two episodes of syncope (the first while climbing stairs and the second while at rest). Prior to her presentation, she had been feeling unwell for several days with myalgias, chills, and rigors, but had no documented fevers. She gave no history of chest pain, breathlessness, or palpitations. Her only regular medication was a combined oral contraceptive pill, and she denied any recreational drug use.At the time of the first clinical assessment, she was apyrexial, clammy, and lethargic and kept experiencing recurrent pre-syncopal episodes. The patient was euvolaemic with normal vesicular breath sounds, no lower limb oedema, and normal heart sounds. She was bradycardic with a heart rate of 40 bpm and hypotensive with a non-invasive blood pressure measurement of 95/45 mmHg.Her electrocardiogram (ECG) showed Mobitz II second-degree AV block and intermittent episodes of CHB with a marginally wide ventricular escape rhythm QRS 120 ms) at 40 bpm . A high-sensitivity troponin was taken due to the viral prodrome with an elevated CRP, indicating the possibility of myocarditis as a cause of the CHB. It was noted to be elevated at 976 ng/L . An autoimmune and a serological viral screen were negative. Computed tomography (CT) coronary angiography excluded coronary artery disease as a cause for the myocardial injury.Full blood results that became available later showed an ongoing inflammatory process with a C-reactive protein (CRP) level of 75 mg/l. Other blood counts revealed a microcytic anaemia with a haemoglobin of 10.7 g/dL and a normal white blood cell count  resolved; however, her condition worsened due to a deterioration in LV systolic function with an ejection fraction of approximately 20–25%  was performed. Three biopsies were taken from the right ventricular septum under fluoroscopic guidance with no complications. The biopsies revealed extensive severe inflammatory infiltrate consisting exclusively of lymphocytes surrounding myocytes with myocyte destruction, but no identifiable inflammatory giant cells, consistent with viral myocarditis Fig. . Viral pThe clinical presentation was indicative of myopericarditis ; however, it is uncommon for CHB to be associated with myocarditis. Given the rarity, other conditions were considered, including giant cell myocarditis, eosinophilic myocarditis, cardiac sarcoidosis, myocarditis exacerbating a pre-existing congenital AVB, and acute myocardial infarction.Giant cell myocarditis is characterised by cytotoxic T cell-mediated destruction of cardiomyocytes, and it often follows a fulminant course which may be fatal unless the patient undergoes cardiac transplantation. Complete AVB is a well-known presenting feature of giant cell myocarditis and tends to affect young-to-middle-aged individuals, highlighting the importance of excluding this diagnosis on cardiac biopsy.Eosinophilic myocarditis is also a potentially lethal condition caused by eosinophilic infiltration of the heart. However, this condition was unlikely given no prior history of other features of hypereosinophilia syndromes such as dermatological involvement. Cardiac sarcoidosis is a rare inflammatory granulomatous disorder which can infiltrate several organs including the heart and may subsequently cause arrhythmias and various degrees of AVB. A cardiac biopsy was performed in this case which excluded the above differential diagnoses.The patient’s CHB recovered after a few days of admission making congenital AVB unlikely. Myocardial infarction was unlikely in this clinical case in view of the patient’s young age, absence of ischaemic risk factors, and atypical presentation. A CT coronary angiogram was performed which adequately excluded this diagnosis.The patient’s clinical condition stabilised gradually without the need for inotropic support and her LV ejection fraction increased to approximately 40% during admission  following the patient’s discharge reported an LV ejection fraction of 51% with no signs of late gadolinium enhancement indicating the absence of ongoing myocardial inflammation , myocarditis is defined on the basis of histological, immunological, and immunohistochemical criteria . DespiteThe EMB reported a diagnosis of lymphocytic myocarditis which is characterised by CD3+ T lymphocyte and CD68+ macrophage infiltrates leading to myocyte inflammation and necrosis of varying degrees , 8. The High-grade AVB is an uncommon finding in patients with acute lymphocytic myocarditis . VaryingHeart failure in acute myocarditis may lead to cardiogenic shock, hence the importance of guideline-directed heart failure treatment to assist in the myocardium recovery . InotropThis case highlights the importance of prompt intervention in patients with acute myocarditis complicated with high degree AVB. It also highlights the possibility of rapid deterioration in LV systolic function necessitating close observation and monitoring in a critical care unit. It is reasonable to insert a permanent pacemaker as the duration and re-emergence of the block is difficult to predict while it also provides atrio-ventricular synchrony which helps stabilise patients' condition. Factors which may indicate a persistent block may include early myocardial fibrosis by EMB and degree of late gadolinium enhancement on CMR. Effective guideline-directed heart failure treatment is essential, aiming for a recovery in LV systolic function.Additional file 1: Video 1. Transthoracic echocardiogram with severely impaired LV systolic function. Transthoracic echocardiogram in parasternal long-axis, parasternal short-axis, and apical 4-chamber views demonstrating severely impaired left ventricular systolic function with particular hypokinesia of the septal wall. Small circumferential pericardial effusion may be seen. Pacemaker lead in-situ.Additional file 2: Video 2. Transthoracic echocardiogram with improved LV systolic function. Transthoracic echocardiogram in parasternal long-axis, parasternal short-axis, and apical 4-chamber views demonstrating an improved left ventricular systolic function. A persistent small circumferential pericardial effusion is present. Pacemaker lead in-situ.Additional file 3: Video 3. Cardiac magnetic resonance imaging in 2-chamber, 4-chamber, and short-axis views, demonstrating low-normal LV systolic function with an estimated ejection fraction of 51%. Artefact present due to the presence of the pacemaker and motion.


Owing to the persistent and worsening shortage of donor hearts, this case illustrates that expanding the donor acceptance criteria to include more distant donor locations and enrolling recipients with extended criteria  is feasible.A 55-year-old man with end-stage heart failure, who had an orthotopic heart transplant 21 years prior, underwent heart retransplantation using a heart from a donor with circulatory death in a distant location and an extended transport period with normothermic  Improvements in preservation and transportation conditions can improve organ quality at the time of transplantation, shorten the acceptable maximum allograft ischemic time, and optimize patient outcomes.Orthotopic heart transplantation remains the gold standard of treatment for end-stage heart failure. Recently, heart transplantation from donors after circulatory death (DCD) has expanded, which was enabled by the usage of the FDA-approved transportable Organ Care System™ (OCS)  . This inex vivo perfusion system, using a heart from a DCD, for an extended transport period >7 h using our modified strategy. To our knowledge, this is the first report of heart retransplantation using a normothermic ex vivo perfusion system in DCDs.We describe our successful experience with a normothermic A 55-year-old man with heart failure and reduced ejection fraction (EF 30%) following a heart transplant in 2001 was listed for heart retransplantation .The donor heart was attached to the Organ Care System (OCS™) after cannulation of the aorta and pulmonary arteries. according to the manufacturer's instructions , the OrgWe began the transplantation when the perfusion and lactate profiles met the OCS parameters. Once stable OCS pump flow, several initial downward trends in serum lactate concentrations, and biventricular motion were confirmed, we administered general anesthesia and placed arterial and venous monitoring lines. The difference in arteriovenous lactate levels improved and remained stable at less than 5 mmol/L. While the heart was being transported, the recipient underwent a repeat median sternotomy. Following successful sternal reentry, extensive dissection was performed, confirming hemostasis.ex vivo perfusion was turned off, supplemented cold del Nido cardioplegia solution was delivered to the donor heart with prompt electromechanical arrest, and the heart was removed from the OCS for implantation. This reduced the total ex vivo heart perfusion time.As soon as the OCS arrived in the operating room, the transportable Cardiopulmonary bypass was initiated at 34°C with aortic and bicaval cannulations, and cardiectomy was performed. During this process, the heart was cooled on ice for 30 min, which was expected to reduce oxygen demand and afford adequate cellular protection .2.Donor heart implantation was performed with left atrial anastomosis, followed by ascending aortic anastomosis. During heart reperfusion, the remaining cardiac anastomoses, such as the pulmonary artery, inferior vena cava, and superior vena cava, were performed using an end-to-end anastomosis technique. This modified implantation technique  shorteneex vivo heart perfusion time was 423 min. The allograft ischemic time was 107 min, including the first and second warm ischemic times of 9 min and 15 min, respectively. The recipient cardiopulmonary bypass and aortic cross-clamp times were 233 min and 50 min, respectively. The patient recovered well and was discharged on postoperative day 17. Six months after transplantation, the patient continued to have excellent graft function without any evidence of rejection.The total ex vivo cardiac perfusion device.This report describes a successful clinical heart retransplantation using a heart from a DCD with an extended transport period and an The use of organs from DCDs has been successful for heart transplantation, which has helped reduce the discrepancy between the number of patients awaiting transplantation and the number of suitable donors. Strong endorsements for such transplants by national and international regulatory bodies have led to the wider adoption of this strategy, with organs from DCDs contributing to an increasing percentage of the total number of donors worldwide. Donor selection in DCD donations is the same as donation after brain death (DBD) scenarios, avoiding size mismatch based on predicted heart mass ratio. According to OCS heart EXPAND trial, marginal donors with an anticipated total ischemic time more than 4 h or age >50 years are now included. Further cardiac evaluations, echocardiography and cardiac catheterization, are required prior to withdrawal of life support .Our retrospective outcomes after 50 years of experience of heart retransplantation demonstrated inferior short-term survival compared to primary transplantation. The decision of heart retransplantation listing is made by our multidisciplinary team based on case-by-case basis and we do not reluctant to offer heart retransplantation for candidates with severe graft dysfunction and have no other options. Given the inferior outcomes, careful candidate selection is recommended to optimize donor heart utilization .Following DCD transplant, the incident of severe primary graft dysfunction (PGD) is found to be higher compared to similar DBD recipients. The pathophysiology of PGD is not well addressed in DCD hearts but thought to be due to functional warm ischemia occurring during and post withdrawal of life support. The study showed DCD recipients with severe PGD required shorter duration of mechanical circulatory supports (MCS) and spent fewer days in ICU and hospital compared to similar DBD recipients suggests DCD heart procurement process may contribute to a period of delayed graft function with subsequent rapid recovery which may differ from what we observed in DBD recipients with severe PGD . Therefoex vivo heart preservation systems have made it possible to maintain physiological perfusion of a donor organ coming from a distance. The device has been used for both the resuscitation and assessment of marginal hearts from DCDs for transplantation. Approximately 20% more transplantations could be done if hearts were donated after circulatory deaths . The OCS Heart system is FDA approved for commercial use and patients will be followed per transplant center's standard of care protocols. A waiver of consent has been granted for the data collection by WCG IRB.


P = 0.014). In conclusion, in acute myocardial infarction, elevated blood acetoacetate levels reduce the risk of MACCE.Although elevated blood ketone body levels reduce major adverse cardiac and cerebrovascular events (MACCEs) risk in chronic heart failure, their relationship with acute myocardial infarction remains unknown. We investigated this relationship in patients with acute myocardial infarction. This single-institution retrospective observational study analyzed data from 114 patients with acute myocardial infarction at Nihon University Hospital from May 1, 2018, to November 1, 2022. The cut-off value of acetoacetate for the incidence of in-hospital MACCE was determined by drawing a receiver operating characteristic curve (ROC) and defining patients with acetoacetate above and below the optimal cut-off point value as ROC and low-acetoacetate (LA) groups, respectively. Propensity score matching was performed between the LA and high-acetoacetate (HA) groups. Sex, peak creatine kinase, lactate, and blood glucose were defined as confounding factors between in-hospital MACCEs and acetoacetate, and 1:1 propensity score matching between the LA and HA groups was used, resulting in 40 patients from both groups enrolled in the analysis. There was a significantly lower incidence of in-hospital MACCEs in the HA group (LA group: 9 [22%] vs HA group: 1 [3%],  The healthy adult heart obtains 60–80% of its energy from fatty acids and 20–40% from glucose . Additio22.1This study was designed as a single-institution, retrospective observational investigation of data from 169 patients treated for acute myocardial infarction at Nihon University Hospital from May 1, 2018, to November 1, 2022. A flow diagram of the study participants’ selection process is shown in Although early and effective treatment of acute myocardial infarction with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) can reduce mortality, adverse events, such as stroke or recurrent myocardial infarction, can hamper a patient’s activities of daily living. Therefore, MACCEs during hospitalization were analyzed as an endpoint. In-hospital MACCEs included all-cause mortality, non-fatal myocardial infarction, and non-fatal stroke. The cut-off value of acetoacetate to predict the incidence of in-hospital MACCE was determined by plotting a receiver operating characteristic curve (ROC) and defining patients with acetoacetate above the optimal cut-off point value as the high-acetoacetate group and those below it as the low-acetoacetate group. Propensity score matching was performed between the low-acetoacetate (LA) and high-acetoacetate (HA) groups.Myocardial infarction was defined based on the Fourth Universal Definition of Myocardial Infarction published in 2018 . The fol2.2U test. Categorical variables are expressed as numbers (%). Categorical variables were evaluated using Fisher’s exact test or the chi-square test. The Spearman rank test (ρ) was used to evaluate the relationship among the variables. Statistical significance was defined as a P value of <0.05.Propensity score matching analysis was performed using EZR, and other analyses were performed using IBM SPSS Statistics . Skewed data are presented as median (interquartile range [IQR]) and were evaluated using the Mann–Whitney 2 + (1 − specificity)2], which represents the minimum distance from the top left corner to a point on the ROC curve.The optimal cut-off value was determined based on the minimum value of the square root of : 0.584–0.825)  . There wρ = −0.013, P = 0.891). Peak CK-MB and peak TnI were significantly correlated with peak CK  and were excluded from the confounding factors because of multicollinearity. We added sex to the confounding factors, as it is an important factor. As a result, sex, peak CK, lactate, and blood glucose were defined as confounding factors between in-hospital MACCEs and acetoacetate, and 1:1 propensity score matching between the LA and HA groups was used, resulting in 40 patients from both groups enrolled in the analysis.We then determined the confounding factors between in-hospital MACCEs and acetoacetate. The relationship between the incidence of in-hospital MACCEs and each factor analyzed using logistic regression analysis in the original cohort is presented in P = 0.912). There were no significant differences in the confounding factors used for propensity score matching  between the two groups. AKBR was significantly lower in the HA group . There was a significantly lower incidence of in-hospital MACCEs in the HA group . In the matched cohort, we plotted ROC curves for acetoacetate to predict the incidence of in-hospital MACCEs .The baseline characteristics, laboratory data, procedural characteristics, and outcomes for the matched and original cohorts are presented in l MACCEs . The cut4Blood ketone bodies are elevated in acute myocardial infarction and chronic heart failure ,10. HoweAcetoacetate and β-hydroxybutyrate are the two main types of ketone bodies. The third type is acetone, which is spontaneously metabolized from acetoacetate and exhaled; therefore, it has not been discussed in this study. Ketone bodies are produced in the liver and used in peripheral tissues under conditions of limited carbohydrate availability, such as fasting and starvation, exercise, and insulin failure . The metSeveral studies have shown that blood ketone levels benefit myocardial energy production. SGLT2 inhibitors reduce the risk of MACCEs in patients with chronic heart failure with or without diabetes ,13. The This study had a significant relationship between acetoacetate levels and in-hospital MACCEs, which was not observed for β-hydroxybutyrate before propensity score matching. This may be because of the balance between acetoacetate and β-hydroxybutyrate production in the liver, which is influenced by endogenous catecholamine stimulation. AKBR, which reflects the redox potential (nicotinamide adenine dinucleotide [NAD]+/NADH) of hepatic mitochondria, is decreased by shock liver and catecholamine stimulation ,20. ThisA key limitation of this study is that arterial blood ketone body levels were measured at admission without considering meal timing; arterial blood ketone body levels might have been elevated if the patient had fasted.5In patients with acute myocardial infarction, elevated blood acetoacetate levels are associated with a reduced risk of MACCEs. These results indicate that acetoacetate may serve as a potential protective factor in mitigating severe cardiovascular complications following myocardial infarction, possibly because acetoacetate is an important energy source during myocardial ischemia. Further research and investigations are warranted to elucidate the underlying mechanisms and explore the clinical implications of these findings.CABGcoronary artery bypass graftingCAGcoronary angiographyCKcreatine kinaseCK-MBcreatine kinase myocardial bandLVEFleft ventricular ejection fractionMACCEsmajor adverse cardiac and cerebrovascular eventsMCTsmonocarboxylate transportersPCIpercutaneous coronary interventionSCOTsuccinyl-CoA:3-ketoacid CoA transferaseSGLT2sodium-glucose cotransporter-2TnItroponin IβDH1β-hydroxybutyrate dehydrogenase


Cardiac electrical stimulation in children usually is needed in the setting of complete congenital atrioventricular block, atrioventricular block after heart surgery, and bradycardia associated with some specific channelopathies. In cases of atrioventricular block, the high percentage of ventricular stimulation raises concern on the deleterious effects of chronic stimulation of the right ventricle. In recent years, physiologic stimulation has developed as a valid approach for adult patients and a great interest has risen in offering conduction system pacing also to the pediatric population. We present three pediatric cases of stimulation of the conduction system (His bundle or left bundle branch), in order to show the intrinsic particularities and challenges implied in these new techniques. Since the first pacemaker (PM) implant performed in 1958 by Senning and Elmqvist , researcIn the case of implantable cardioverter defibrillators (ICDs), the pediatric recommendations have been limited by the lack of randomized controlled trials and small patient numbers, and the implant indications are extrapolated from adult data, which is based on specific diagnosis as the defined cause or presumed risk factor for sudden cardiac arrest (SCA), such as ischemia, cardiomyopathy, or genetic cardiovascular disease. Almost half of the cases of SCA in the pediatric population remain undefined, and, in the case of channelopathies, SCA is often the initial symptom of the disease. Recently, the 2021 PACES Expert consensus statement published guidelines for implantable electronic device in pediatrics, including ICDs, where they make the observation that are still extensive “gaps” in current ICD recommendations, irrespective of age, for many of the diseases associated with SCA in pediatrics, and the recommendations are based on limited clinical data or expert opinion and consensus .n = 1) and left bundle branch (n = 2), in Mexican children with different clinical conditions, to show the intrinsic particularities and challenges implied in these techniques.We report three cases of physiological stimulation, Hisian (A 5-year-old girl weighing 16.5 kg presented with a 3-month history of syncope. Electrocardiogram (ECG) documented sinus arrest, with pauses of up to 2.3 s and junctional0 rhythm at 37 bpm with hemodynamic compromise requiring temporary PM placement . There wElectrophysiology study showed the absence of electrical activity in both atria, with inability to capture in various locations at maximum voltage ; with veA 12-year-old boy weighing 39.5 kg with Holt–Oram syndrome and a persistent left superior vena cava was sent to our service due to complete atrioventricular (AV) block, significant decrease in functional capacity, and chronotropic incompetence during the stress test.The initial ECG showed a complete AV block with normal axes, QRS of 80 ms, and a mean ventricular rate of 40 bpm .Dual-chamber endocardial PM with stimulation of the His bundle was attempted. Before starting the procedure, a venography was performed, demonstrating the absence of the brachiocephalic vein and a direct connection of the left venous system to the coronary sinus . TherefoUltrasound-guided puncture of the right axillary vein was performed on two occasions and two 7 Fr introducers were placed; through the first, the atrial electrode was advanced to the appendage of the right atrium, and adequate capture was evidenced. Through the SelectSite C304-His deflectable sheath , the SelectSecure MRI SureScan 3830 electrode was advanced to the anatomical region of His, documenting a supra-Hisian block with an HV interval of 33 ms . The eleZ-score +3.59) and left ventricular systolic and diastolic dysfunction [left ventricular eyection fraction (LVEF) 15%]; there was also a significant tricuspid regurgitation. The thickness of the interventricular septum was measured at 5.4 mm. After ruling out residual defects, PM-induced cardiomyopathy was concluded as etiology of the heart failure.A 5-year-old girl weighing 13.5 kg with Down syndrome and a history of congenital heart disease-type perimembranous ventricular septal defect and surgical closure with bovine pericardial patch developed postsurgical complete AV block; therefore, a permanent dual-chamber epicardial PM was implanted in 2017. She was referred to our institute due to functional class deterioration. Intraventricular and interventricular dyssynchrony were evidenced by echocardiography, with significant dilation of the left ventricle (The admission ECG showed PM rhythm with single-chamber stimulation and atrioventricular dissociation . The cheZ-Score +2.19), and a significant improvement of left ventricular systolic function as LVEF increased to 31.8%.It was decided to implant a permanent dual-chamber endocardial pacemaker with selective stimulation of the left bundle branch, considering the congenital heart disease, the anatomy of the conduction system, and the surgical correction. Through the left axillary vein, an atrial electrode was placed in the right atrial appendage, where adequate capture was evidenced. Using the C315 sheath, the SelectSecure MRI SureScan 3830 electrode was implanted guided by electrograms. After three turns, it was possible to show left bundle branch potential and a notch in the descending limb of the S wave in V1 . Two morThe technique and criteria for stimulation of the His bundle and the left bundle branch have been recently described by Vijayaraman and Ponnusamy , 11. PhyAnatomical differences in the pediatric population early in life have encouraged the preferential use of epicardial pacing in very young patients. In our institute, endocardial pacemakers have been placed in patients from 6 months of age and weighing 4.4 kg; however, these cases are the exception and not the rule . The epiIn congenital heart disease, it is important to know the cardiovascular anatomical variants, particularly in the case of isomerism, and the conduction system of each type of congenital heart disease to which we are facing , 12, 22,Ventricular septal defects can occur in isolation or in association with complex congenital heart disease. The closure of perimembranous interventricular defects is associated with a complete AV block because the conduction system runs in close relation to the posterior edge of the defect , and wheFor such situation, stimulation of the left bundle branch is a feasible alternative, where we must not forget the differences in the interventricular septum between children  and adulvia the epicardial route. In addition, CRT-P has been associated with complications such as phrenic stimulation, venous congestion, mitral valve dysfunction, sepsis, and cerebral vascular events  , have shown less benefit in patients with normal QRS, as well as the fact that left ventricular pacing is performed ectrode) , 24. In ectrode) , 12, 22.Theoretically, His pacing is the ideal resynchronization method. However, the His bundle is only 1–2 mm in diameter, so Hisian pacing remains a challenge . In addiPhysiological stimulation of the conduction system is still in very early stages with some disadvantages already mentioned, such as the Hisian stimulation thresholds, the location of the His potential, as well as the chronic increase and stability of the electrodes. From our point of view, more studies are still required to assess the long-term safety and effectiveness of left septal/left branch stimulation since it does not have the drawbacks of His pacing (see below) and may be much more accessible to the common implanter.As it has been described by Vijayaraman et al. , His bunPhysiological stimulation could be performed in pediatric patients, with or without structural heart disease. It should be the priority to avoid PM-induced left ventricular dysfunction. The knowledge of anatomical variants of the cardiovascular system and the conduction system in children is essential to decide the ideal approach for this age group.


Cardiac magnetic resonance (CMR) global longitudinal strain and circumferential strain abnormalities have been associated with left ventricular ejection fraction (LVEF) reduction and cardiotoxicity from oncologic therapy. However, few studies have evaluated the associations of strain and cardiovascular outcomes.To assess CMR circumferential and global longitudinal strain (GLS) correlations with cardiovascular outcomes including myocardial infarction, systolic dysfunction, diastolic dysfunction, arrhythmias and valvular disease in breast cancer patients treated with and without anthracyclines and/or trastuzumab therapy.Breast cancer patients with a CMR from 2013–2017 at Yale New Haven Hospital were included. Patient co-morbidities, medications, and cardiovascular outcomes were obtained from chart review. Biostatistical analyses, including Pearson correlations, competing risk regression model, and competing risk survival curves comparing the two groups were analyzed.116 breast cancer with CMRs were included in our analysis to assess differences between Anthracycline/Trastuzumab (AT) (62) treated versus non anthracycline/trastuzumab (NAT) (54) treated patients in terms of imaging characteristics and outcomes. More AT patients 17 (27.4%) developed systolic heart failure compared to the NAT group 6 (10.9%), p = 0.025. Statin use was associated with a significant reduction in future arrhythmias . In a sub-group of 13 patients that underwent stress CMR, we did not find evidence of microvascular dysfunction by sub-endocardial/sub-epicardial myocardial perfusion index ratio after adjusting for ischemic heart disease.In our study, CMR detected signs of subclinical cardiotoxicity such as strain abnormalities despite normal LV function and abnormal circumferential strain was associated with adverse cardiovascular outcomes such as valvular disease and systolic heart failure. Thus, CMR is an important tool during and after cancer treatment to identity and prognosticate cancer treatment-related cardiotoxicity. In the United States, breast cancer is the most common cancer diagnosed among women  and, aftCancer treatment-related cardiac dysfunction (CTRCD) has been well documented in the literature . In a reMonitoring for adverse cardiovascular outcomes associated with oncologic therapies is crucial in improving long term outcomes of breast cancer patients. Cardiac imaging plays a critical role during and after cancer treatment in identifying CTRCD. Recent European Society of Cardiology (ESC) guidelines recommend baseline echo using 3D analysis of left ventricular ejection fraction (LVEF) for those undergoing anthracycline therapy, regardless of cardiovascular risk, and use of CMR imaging as second line if echo is of suboptimal quality –15. IschThe objective of our study is to assess CMR parameters and cardiovascular risk factors for prediction of cardiovascular outcomes in breast cancer patients, comparing those treated with anthracyclines and/or trastuzumab (AT) vs those who were not treated with anthracyclines nor trastuzumab (NAT).depicts how the sample of patients was selected. A small subset (n = 13) had stress CMR performed during chemotherapy treatment. Information on patient comorbidities, demographics, cancer treatments, cardiac medications, and cardiovascular outcomes were obtained by chart review from the electronic health record system at Yale New Haven Hospital. The institutional review board of Yale University School of Medicine reviewed and approved this research.Patients in the sample included all breast cancer patients who underwent a CMR at Yale New Haven Hospital from 2013 to 2017, and chart review was conducted as far back as 1990 to assess for patient co-morbidities. The sample consisted of 116 patients with a history of breast cancer. Of these 116 patients, 62 were in the AT group, while 54 were in the NAT group. Patients were excluded if they had poor quality/nondiagnostic CMRs (n = 3). CMR imaging was performed on 1.5 and 3T scanners  with standard image acquisitions. Steady state free precession (SSFP) cine imaging . T2W mapping used T2W-prepared balanced steady-state free precession (bSSFP) single shot images acquired in 9 heart beats  with FOV = 360 mm x 270 mm, slice thickness = 8 mm, FA = 30°, parallel imaging = generalized autocalibrating partially parallel acquisition (GRAPPA 2), bandwidth = 1395Hz/pixel). The T2W maps were generated using an exponential fit (image resolution 1.5mm×1.5mm x 8mm). Late gadolinium enhancement (LGE) evaluation was performed 8–10 min after administration of 0.2 mmol/kg gadolinium contrast agent. After performing an inversion scout sequence, LGE imaging was obtained using inversion recovery gradient echo . Normal MRI reference ranges are featured in S1 Table in S1 File [Quantitative analysis for volumes, function, and feature tracking strain for 3D LV global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) was performed using SSFP cine in short axis, 2-chamber, 3-chamber, and 4-chamber views with CMR42 . This tissue tracking module recognizes patterns of features in the image that can be tracked in successive images . All six segments were averaged to obtain a global sub-endocardial/sub-epicardial myocardial perfusion index ratio .Stress CMR protocol included first-pass vasodilatory stress-only perfusion (ssGRE) with regadenoson 0.4 mg and injection of 0.05 mmol/kg contrast agent, injected 90 seconds and 8 minutes after stress agent. The perfusion scan protocol was: field of view (FOV) = 360mm×270mm, TR/TE = 6/2 ms, slice thickness = 8 mm, FA = 20°, bandwidth = 781 Hz/pixel, spatial resolution 3x3mm, 3 slices per heart-beat. Quantitative parameters were processed  for LV volume and function, feature tracking GLS , diastolic HF, coronary artery disease, myocardial infarction, peripheral arterial disease, thromboembolism, arrhythmia , and valvular disease  starting from time of oncologic therapy initiation. Systolic dysfunction was defined as LVEF <50%, and diastolic dysfunction included grades 1–3 of diastolic dysfunction by echo. Myocardial infarction (MI) was defined by having non-ST elevation MI or ST elevation MI. Peripheral arterial disease is defined as having clinically significant peripheral artery disease where the patient had symptoms. Arrhythmia included bradycardia that was symptomatic or required intervention, heart block, atrial fibrillation, atrial flutter, supraventricular tachycardia, and ventricular arrhythmias). Valvular disease included greater than mild mitral regurgitation, aortic regurgitation, aortic stenosis, mitral stenosis, or tricuspid regurgitation. Thromboembolism is defined as having imaging confirmed deep venous thrombosis or pulmonary embolism. All diagnoses were clinically determined and documented in clinical notes. Results are expressed in hazard ratios (HRs) for each predictor, its 95% confidence interval (CI), and corresponding p-value.p-value of less than 0.05. The selected predictors then were used to build the multivariate competing risk regression model. In survival analyses, an outcome of interest may prevent the observation of or affect the chance of another outcome of interest from occurring. Such an outcome is known as a competing risk and must be properly addressed to avoid incorrect conclusions. To avoid the bias in the Kaplan Meier method when there are multiple events or failures, a competing risk regression model was used [The cardiotoxicity analysis first involved a univariate analysis on nineteen different predictors and across six different outcomes. The predictors include age, diabetes (DM), peripheral artery disease (PAD), hyperlipidemia (HLD), hypertension (HTN), pulmonary embolus/deep vein thrombosis (PE/DVT), preexisting arrhythmia, pulmonary hypertension (pHTN), obesity, smoking, preexisting valvular disease, preexisting systolic HF, preexisting diastolic HF, beta-blocker use, ACE-inhibitor/ARB use, statin use, hydralazine/nitrate use, LGE and CMR circumferential and longitudinal strain. The six outcomes include MI, systolic HF, valvular disease, arrhythmia, and diastolic HF. With univariate regression analysis, each predictor is examined. Predictors were selected based on a was used .Our study was approved by the Yale IRB committee. The IRB waived the requirement for informed consent as this was a retrospective review and no identifiers are used in reporting results.Of the 116 female breast cancer patients who had received CMR for evaluation of either cardiomyopathy or cardiac symptoms included in this study, the median age was 66 years old. Majority of the patients were Caucasian (83%). In our sample, 62 were in the AT group and 54 were in the NAT group.Table 1. The AT group had a mean age of 62 years old, and the NAT group was older with a mean age of 68 years old (p = 0.001). The incidence of diastolic dysfunction by echo was higher in the NAT group compared to AT group (37 vs 16%) (p = 0.019).Patient demographic and clinical characteristics at the time of CMR are listed in Table 2. Cancer stage, estrogen, progesterone receptor, Her2 positivity are featured in S2 Table in S1 File. A greater number of AT patients had CMR performed for an indication of cardiomyopathy as compared with the NAT group  S3 Table in p = 0.399). The majority of patients also received anti estrogens . Immune checkpoint inhibitors and tyrosine kinase inhibitors were not commonly used treatments in this patient cohort.Patients’ cardiac and cancer medications are included in p = 0.004). Right ventricular ejection fraction (RVEF) was lower in the AT group compared to the NAT group . Furthermore, reduced RVEF was found significantly more in the AT cohort compared to the NAT cohort . The right ventricular end diastolic volume indexed (RVEDVI) was also higher in the AT group (85.2 = /-37) compared to the NAT group (69.8 +/-26.2), p = 0.004. The CMR LA volume was smaller in the AT vs the NAT group  CMR imaging was performed during cancer treatment in 30 patients (48%) in the AT group and in 20 patients (37%) in the NAT group, with no significant difference between the two groups (p = 0.218). The remainder of the studies were completed after chemotherapy. There was no significant difference in LVEF  nor LV mass index  between the two groups. The AT group had higher left ventricular end systolic volume indexed (LVESVI) compared to the NAT group . In a sub-analysis of the AT group, GLS was similar in those who received anthracycline alone compared to those who received HER-2 inhibitors alone . However, GLS in those who received anthracycline alone was more abnormal compared to those who received both anthracycline and a HER2i agent (-13.1 vs -15.6 p = 0.02). However, GLS was not statistically significant between those who received both anthracycline and HER-2 inhibitors versus HER-2i alone (p = 0.803). Circumferential strain was similar amongst the groups in this sub-analysis of the AT cohort, with no statistical significance seen . Anthracycline use was associated with significantly more abnormal GLS (GLS >-18) (74.4%) compared to no anthracycline use (40%) (p = 0.036) (Table 4).Average GLS was reduced for both the AT and NAT cohorts, without a significant difference between the two groups . Values for average GCS were borderline normal and not significantly different between the two groups  (p = 0.0001)). Additionally, GCS significantly correlated with LVEF  and LVESVI . In an AT group sub-analysis, GLS remained significantly correlated with GCS , and GCS was negatively correlated with LVEF  (Table 4A)Among all patients, when compared with other CMR parameters, GLS significantly correlated with GCS .In the overall cohort, 22 had LGE and there was significantly more LGE positivity in the NAT group compared to AT group . In the AT cohort, 8 patients demonstrated LGE (13%), all in a nonischemic pattern, and one had no contrast given. In the NAT cohort, 14 (29%) had LGE, of which 11 (20%) were nonischemic, 3 (5%) were ischemic, and 2 (4%) had nondiagnostic LGE images. LGE positivity was significantly associated with abnormal GLS, GCS, increased LV mass index, and reduced RVEF. Other imaging parameters were not statistically significant and are listed in p < 0.01), when ischemic segments were excluded , and when patients with IHD were excluded . No significant correlation was found between different breast cancer therapies and CMR SS-MPIR or GLS.In this sub-analysis, 13 patients had stress CMR performed for cardiomyopathy evaluation while on chemotherapy . In this cohort, the average LVEF was 59.7% and average GLS was -15.12%. Three patients (23%) had perfusion defects and/or LGE consistent with ischemic heart disease (IHD), and 1 patient had a non-ischemic pattern of LGE, whom had prior anthracycline exposure. The average sub-endocardial/sub-epicardial myocardial perfusion index ratio (SS-MPIR) at stress was 0.98 for all patients, which was normal based on published references . When alTable 5). There is a significant difference in regards to systolic heart failure, with the AT group having a higher incidence of systolic heart failure over time, p = 0.006, Fig 5C. No significant differences in outcomes were seen between the two groups for CAD/myocardial infarction (p = 0.530) , valvular disease (p = 0.630) , arrhythmia (p = 0.42)  or diastolic heart failure (p = 0.16) .Cardiovascular outcomes between the AT and NAT cohorts were evaluated. The AT cohort had an increase in systolic heart failure outcome compared with the NAT cohort   . Competing risk regression showed that HTN was significantly associated with a 9.8-fold increase in developing CAD/myocardial infarction , PE/DVT , pre-existing valvular disease  and abnormal CMR GCS  were significantly associated with increased risk of developing systolic heart failure. However, HLD  and HTN  were associated with reduced incidence of systolic heart failure Fig 5A. Competing risk regression found that use of anthracycline and/or Her2i, PE/DVT and pre-existing valvular disease were independently associated with the systolic heart failure outcome, whereas HLD was negatively associated Fig 5B.In univariate analysis, use of anthracycline and/or Her2i , preexisting systolic HF  and CMR GCS  were significantly associated with increased risk Fig 6A. However, in the competing risk model, only obesity remained significantly correlated  Fig 6B. Cumulative incidence of valvular disease over time is featured in Fig 6C.In the univariate analysis for the valvular disease outcome, obesity  Fig 7A and in the competing risk regression model for arrhythmia  Fig 7B. Cumulative incidence of arrhythmia over time is featured in Fig 7C.Statin use was significantly associated with reduced risk in the univariate model Click here for additional data file.S1 Data(XLSX)Click here for additional data file.


Invasively measured and CMR-assessed LV hemodynamics during BIV pacing were significantly associated. Conclusions: Post-CRT implantation CMR assessing acute LV pump function is feasible and provides important insights into the effects of BIV pacing on cardiac function and contraction patterns. LV assessment during CMR may constitute a future CRT optimization strategy.Objectives: This prospective pilot study assessed the feasibility of cardiovascular magnetic resonance (CMR) imaging during biventricular (BIV) pacing in patients with a CMR conditional cardiac resynchronization therapy defibrillator (CRT-D) and compared the results with invasive volume measurements. Methods: Ten CRT-D patients underwent CMR imaging prior to device implantation (baseline) and six weeks after device implantation, including CRT-on and CRT-off modes. Left ventricular (LV) function, volumes, and strain measurements of LV dyssynchrony and dyscoordination were assessed. Invasive pressure–volume measurements were performed, matching the CRT settings used during CMR. Results: Post-implantation imaging enabled reliable cine assessment, but showed artefacts on late gadolinium enhancement images. After six weeks of CRT, significant reverse remodeling was observed, with a 22.7 ± 11% reduction in LV end-systolic volume during intrinsic rhythm (CRT-off). During CRT-on, the LV ejection fraction significantly improved from 27.4 ± 5.9% to 32.2 ± 8.7% ( Cardiac resynchronization therapy (CRT) is a well-established therapy for patients with drug-refractory heart failure (HF) presenting with systolic left ventricular (LV) dysfunction and a broad QRS complex, typically a left bundle branch block (LBBB) . To dateCardiac magnetic resonance (CMR) imaging has emerged as a highly accurate and reproducible imaging technique which can offer valuable information for CRT screening, including the assessment of the left ventricular (LV) ejection fraction, as well as scar quantification and localization using late gadolinium enhancement (LGE) . On the Recently, CMR conditional CRT devices with approval for use in the magnetic resonance imaging (MRI) environment have been introduced . The devThe objective of this pilot study is to assess the feasibility of CMR imaging after the implantation of a CRT with defibrillator function (CRT-D), and to detect volumetric and functional changes when BIV stimulation is either turned on or off. Moreover, acute changes in LV function are related to invasively assessed acute pump function changes measured using a conductance catheter, which is considered the gold standard for acute pressure–volume analysis.This prospective single-center pilot study was conducted according to the principles outlined in the 1964 Declaration of Helsinki and its subsequent amendments. The collection and management of data was approved by the local medical ethics committee . Written informed consent was obtained from all individual participants included in the study.2, significant rhythm abnormalities , pacemaker dependency, artificial aortic valve, aortic valve stenosis, or the impossibility to undergo a CMR scan with a gadolinium contrast agent.Ten patients referred for CRT-D implantation were enrolled in the study between February 2019 and December 2021. All patients had a class 1 indication for CRT-D therapy, according to the 2013 ESC guidelines: a New York Heart Association (NYHA) chronic heart failure classification of II, III, or ambulant IV, with an intrinsic QRS width ≥ 120 ms with LBBB, and a left ventricular (LV) ejection fraction ≤ 35%, despite optimal medical therapy . ExclusiPatients underwent a CMR scan for LV function and fibrotic tissue assessment prior to device implantation. Subsequently, device implantation was performed by experienced operators in accordance with local and international guidelines. Patients were implanted with a CMR conditional CRT-D system and leads . After device implantation, a six-week waiting period was maintained and subsequently, the follow-up CMR examination was performed. The follow-up CMR examination consisted of a two-stage scanning protocol: during BIV pacing (CRT pacing on), in MRI mode, and during intrinsic rhythm (CRT pacing off). On the same day, patients underwent invasive pressure–volume (PV) loop assessment using a conductance catheter at intrinsic rhythm and during BIV pacing (matching the CRT settings during CMR). Conductance catheter measurements are considered the gold standard invasive reference method for the assessment of acute hemodynamic response during CRT ,10.All scans were performed with a 1.5 Tesla MRI system  using a 32-channel array coil. The pre-device implant CMR protocol included balanced steady-state free precession (SSFP) cine imaging in long axis  and short axis orientations . LGE imaging was performed for the assessment of myocardial scarring/fibrosis.®, Guerbet, Roissy, France) in short axis views copying cine orientations. A detailed CMR protocol is presented in the The post-device implant CMR protocol involved two stages, during which the device was programmed to the MRI-safe mode. First, BIV pacing during the CMR scan was performed with the CRT-D in DOO mode (10 beats per minute above intrinsic rhythm) with the use of a fixed atrioventricular (AV) delay set to 100 ms and simultaneous biventricular pacing. During this first stage, cine long axis and short axis acquisition was performed using a spoiled gradient echo sequence. Thereafter, the patient was moved out of the scanner, and the BIV pacing function was turned off (intrinsic rhythm). The above mentioned imaging sequence was repeated, and finally, LGE imaging was performed after 0.15 mmol/kg contrast administration . An assessment of the cardiac dimensions and function was performed on the short axis cine images. Endo- and epicardial contouring was performed using the automatic contouring algorithm, and manual adjustments were made, if necessary. End systolic and end diastolic volumes , stroke volume (SV), and LV ejection fraction (LVEF) were evaluated.Cine image analysis was performed using Circle CVI42 feature tracking software, excluding the LV outflow tract slice(s). Global LV longitudinal strain (GLS), circumferential strain (GCS), and radial strain (GRS) parameters were quantified. To assess LV dyssynchrony and dyscoordination, circumferential peakseptal - peaklateral delay, as an absolute value, and systolic rebound stretch of the septum  were calculated on the mid-LV slice [A quantitative deformation assessment was performed on cine images using Circle CVILV slice .After CMR imaging, on the same day, invasive hemodynamic measurements were obtained. A conductance catheter  was placed in a stable position in the LV apex to obtain PV loops. PV loops were recorded during intrinsic rhythm and BIV pacing . Approximately 60 representative cardiac cycles were averaged, disregarding all inappropriate beats  with the use of Conduct NT software . CMR-derived LV volumes during intrinsic rhythm were used for the conductance catheter calibration of volumes recorded during intrinsic rhythm. Consequently, the effects of BIV pacing on LV function were quantified by EDV, ESV, SV, and EF.t-tests. Pearson’s correlation was used to quantify associations between continuous variables. Agreement between measurements was assessed by intraclass correlation coefficients (ICCs). ICCs for absolute agreement of single measurements were estimated using a two-way random effect model. Data were considered statistically significant if the p-value was <0.05. Statistical analysis was performed using SPSS Statistics v26 .The results are presented as mean ± standard deviation, for normally distributed data, and median with interquartile range (IQR), for data with a non-normal distribution. Between-group comparison was performed using paired Student’s p = 0.83). This change in QRS duration did not significantly relate to a change in LV ESV, LV EDV, or LVEF between baseline and follow-up during BIV pacing .A total of 10 patients were enrolled in the study . Three patients showed a non-ischemic LGE pattern on CMR, three patients showed ischemic sub-endocardial/transmural LGE, and four patients exhibited no LGE . The basDetailed results regarding assessment of artefact extent on the cine and LGE images are given in p < 0.001, and EDV: 268.1 ± 42.3 mL, p < 0.001), but no significant improvement in LVEF was observed . Moreover, there was no improvement in septal systolic rebound stretch   and the LV systolic function was impaired . At follow-up during intrinsic rhythm (CRT-off), LV ESV and LV EDV were decreased, as compared to baseline measurements  .p < 0.01, and EDV: 268.1 ± 42.3 mL vs. 236.2 ± 31.8 mL, p < 0.01) and an increase in LVEF  (p = 0.02). Regional dyssynchrony and regional dyscoordination significantly improved at BIV pacing compared to intrinsic rhythm . A typical example of regional dyssynchrony and regional dyscoordination assessment is presented in Compared to the intrinsic rhythm during the follow-up scan, BIV pacing showed an additional decrease in LV ESV and EDV  . No diffp = 0.001; EDV: r = 0.79, p = 0.007; SV: r = 0.64, p = 0.047; EF: r = 0.75, p = 0.01) (In  = 0.01) E–H. AgreThis pilot study demonstrated that post-implantation CMR imaging can be used to assess the effects on cardiac pump function during BIV pacing in patients implanted with a CRT-D, despite minor image artefacts originating from the generator. The quality of post-implant images was deemed good for cine acquisitions, allowing for reliable assessment of LV volumes and regional wall strains. However, significant device-related artefacts were observed, predominantly in the anterior wall, during LGE imaging, rendering these segments unanalyzable. A decrease in LV ESV and EDV between baseline and follow-up provides evidence of reverse LV remodeling. Moreover, acute hemodynamic improvement was observed upon turning on BIV pacing at follow-up. Furthermore, The ability to detect improvement and deterioration of cardiac function during different CRT settings was validated using invasive hemodynamic measurements. Proving the feasibility of CMR to measure LV pump function during CRT paves the way for using CMR for CRT optimization in the future.CMR imaging is currently considered the gold standard for the non-invasive assessment of ventricular function, mechanics, and detection of scar tissue ,13. The Recent advances have led to the opportunity to safely perform MRI scans in CRT-implanted patients during BIV pacing, and developments in MR sequences have significantly reduced artefacts arising from the generator and leads. These high-quality cine images are essential for the precise quantification of ventricular hemodynamics, including strain, and evaluation of resynchronization effectiveness and patient monitoring after CRT implantation .In the present study, some CRT generator-related signal loss remained in the LV anterior wall segments on the cine images, even when using a spoiled gradient echo-based sequence . HoweverIn this study, evidence was obtained for reverse LV remodeling as early as six weeks after CRT implantation by observing improvement in LV volumes at follow-up during intrinsic rhythm as compared to the baseline assessments . It has Moreover, an acute deterioration in LV pump function mediated by dyssynchrony and discoordination was observed by turning off BIV pacing during the follow-up scan. This finding underlines that BIV pacing during CMR is crucial for the proper assessment of LV hemodynamics and can be useful in the identification of non-responders who might benefit from CRT optimization.Optimizing cardiac function can be achieved by individualized programming of the pacing configuration and timing delays ,24. AccoIn our study, we sought to explore the potential of CMR as a non-invasive alternative for device optimization. CMR-based optimization can overcome the inherent limitations of invasive hemodynamic testing and may serve as a promising future alternative . MoreoveTo assess the agreement between invasively obtained and CMR-derived LV volumes, we compared both strategies during an identical BIV pacing configuration and intrinsic rhythm. Despite the fact that both techniques measure LV volumes in a significantly different manner, our results demonstrate a modest relationship between the two modalities. The dissimilarity can possibly be explained by the different assessment times during the day and especially by differences in heart rate between the CMR study and the invasive procedure. Moreover, the insuperable limitations of the conductance catheter can also contribute to the differences measured using both techniques, as elucidated by Vernooy et al. . PositioAdditionally, only two device settings were tested in patients implanted with a CRT-D, and the study focus was predominantly on feasibility. The CRT-D device used in the present study is currently the only one allowing BIV pacing in the MRI-safe mode. Unfortunately, this MRI safe mode comprises a restricted BIV pacing option, with non-variable AV delays and pacing configurations. This could hamper the evaluation of the response on CRT by possibly underestimating the patients’ cardiac function. Nevertheless, we have shown a response in LV function and mechanics upon turning off BIV pacing. More research is needed to test whether more subtle changes in BIV pacing settings, such as pacing configurations and AV delay variation, demonstrate a clear response in CMR-derived hemodynamic parameters. Furthermore, research involving other device manufacturers to determine the generalizability of the results would enhance the overall validity and applicability of the study’s results.This pilot study is an initial step in exploring the feasibility of CMR imaging during BIV pacing. Inherent to its setup, the study has a small sample size. Furthermore, as the MRI safe mode did not include AOO pacing as an option, the CRT-off option was used to mimic the AOO mode. As a result, there was a difference in heartrate (>10 bpm) between the BIV pacing mode and the CRT-off mode, potentially affecting diastolic filling time and cardiac function . Lastly,Post-CRT implantation CMR assessing acute pump function changes in regards to different CRT-pacing settings is feasible and provides important insights into the effects of BIV pacing on cardiac function and contraction patterns. Post CRT-implantation assessment using CMR may constitute a future CRT optimization strategy.


ECG strain was the only predictor of increased LV mass index on multivariate regression analysis . Patients with persistent ECG strain at 1 year following AVR had more advanced LV remodeling and more histological fibrosis  at baseline assessment. Therefore, ECG strain is a marker of adverse LV remodeling and interstitial myocardial fibrosis. Lack of improvement in ECG strain following AVR indicates more advanced baseline LV injury and higher levels of myocardial fibrosis.The optimal timing for aortic valve replacement (AVR) in aortic stenosis (AS) is still controversial and may be guided by markers of adverse left ventricular (LV) remodeling. We aim to assess electrocardiographic (ECG) strain in relation to LV remodeling and myocardial fibrosis. 83 severe AS patients underwent surgical AVR, with preoperative 12-lead ECG, cardiovascular magnetic resonance with T1 mapping and echocardiography with global longitudinal strain analysis. Collagen volume fraction (CVF) was measured in myocardial biopsies sampled during AVR. Patients with ECG strain had more severe AS, more advanced LV remodeling and evidence of heart failure. Patients with ECG strain had more diffuse fibrosis, as evident by higher mean native T1 values (974.8 ± 34 ms vs. 946.5 ± 28 ms,  Aortic stenosis (AS) is characterized by progressive valve narrowing that eventually leads to aortic valve (AV) intervention in developed countries ,2. ChronMyocardial biopsy, followed by histological analysis, is considered the gold standard for the assessment of myocardial fibrosis ; howeverST segment down-sloping and T-wave inversions on the ECG are attributed to myocardial ischemia 18). However, these ECG abnormalities may be present in the absence of coronary artery disease (CAD). The increase in LV mass also prolongs and distorts electrical impulse propagation within the myocardium, creating depolarization abnormalities. LV strain pattern of lateral ST depression and T-wave inversion (or ECG strain) and increased QRS voltage are the most acknowledged ECG markers of LV hypertrophy in AS . However,18,19,20Our prospective study aims to (i) assess associations between ECG strain and LV remodeling by integrating echocardiographic and CMR data, (ii) analyze the link between ECG strain and invasively and non-invasively measured myocardial fibrosis, and (iii) investigate whether ECG evidence of LV remodeling will resolve following AVR.This is a prospective observational study carried out at Vilnius University Hospital between November 2018 and December 2020. The study included patients with severe symptomatic AS who were scheduled for surgical AVR according to the current treatment recommendations . The stu2 or AVA index ≤ 0.6 cm2/m2, as determined by echocardiography], age > 18 years, and ability to undergo a CMR scan and to sign consent to the study protocol. The exclusion criteria were severe valve disease other than AS, significant CAD , history of myocardial infarction, estimated glomerular filtration rate <30 mL/min/1.73 m2, CMR-incompatible devices, persistent atrial tachyarrhythmias, and previous cardiac surgery. The main reasons for non-eligibility were significant CAD, renal dysfunction, and other valvular abnormalities. Of the 83 participants, 79 underwent surgical AVR and 4 postponed surgeries due to the COVID-19 epidemiologic situation.  ≤ 1 cmtuation. .A standard 12-lead ECG was obtained from all patients preoperatively, 3 and 12 months after surgical AVR. The following automatically provided ECG parameters were collected: heart rate, PQ and QRS duration. The QRS voltage and Sokolow-Lyon index (S-L) were calculated manually. S-L index is calculated as the sum of amplitudes of the S wave in lead V1 and the R wave in lead V5 or V6 based on the highest R wave amplitude . LV straTransthoracic two-dimensional echocardiography was performed using a commercially available Vivid ultrasound system  , and the data were stored on a dedicated workstation for subsequent offline analysis. LV systolic and diastolic function were evaluated according to echocardiographic guidelines, and AVA was calculated using the continuity equation ,27. From®, Version 5.0.1) from a stack of sequential 8-mm short-axis slices (0–2-mm gap) from the atrioventricular ring to the apex. Measurements were indexed to body surface area in m² (using the DuBois formula). To detect delayed hyperenhancement, images were acquired 10–15 min after intravenous administration of gadobutrol (0.2 mmol/kg)  using a breath-hold segmented inversion recovery fast-gradient echo sequence in the short-axis and long-axis planes of the LV, with an 8-mm slice thickness and 20% distance factor. The region of myocardial fibrosis was defined as the sum of pixels with signal intensity above 5 standard deviations of the normal remote myocardium in each short-axis slice. The presence of LGE was determined qualitatively by two independent readers who were blinded to the clinical data. T1 mapping images were acquired in 4-chamber long-axis and short-axis images (at the midventricular levels) before and 15 min after contrast administration. All T1 mapping images were acquired using the modified Look-Locker inversion-recovery sequence . Furthermore, the prevalence of ECG strain gradually decreased from 43% to 17% in 1 year (p = 0.001). We also observed a significant increase in QRS duration at 3 months following AVR (p < 0.05); the result was likely related to newly developed intraventricular conduction abnormalities soon after the surgery (left and right bundle branch blocks).The data of 76 and 59 patients were available at 3- and 12-month follow-up visits, respectively. ECG parameters before and after surgical AVR are shown in p = 0.017 and p = 0.040, respectively), greater QRS duration , and more advanced heart failure, as evident by higher levels of BNP (p = 0.005) at baseline. These patients also had more advanced baseline LV remodeling, as they had greater LV mass (p = 0.023) and larger indexed LV end-systolic (p = 0.003) and LV end-diastolic (p = 0.010) volumes (p < 0.001), lower LVEF (p < 0.001), and lower right ventricle ejection fraction (p < 0.002). In regard to histological analysis, patients with persistent ECG strain had significantly more fibrosis in the midmyocardial layer on histological analysis   .This is a prospective study integrating data of multimodality cardiac imaging and ECG changes in conjunction with a histological analysis in patients with severe AS undergoing surgical AVR. The main study findings are as follows: (i) the presence of LV strain pattern on ECG is associated with adverse LV remodeling and higher native T1 values representing interstitial expansion due to fibrosis, (ii) the presence of LV strain pattern on ECG is an independent predictor of increased LV mass, and (iii) persistence of LV strain pattern on ECG at 1 year following AVR represents more advanced LV remodeling with higher degree of histological fibrosis at baseline.It is of great importance to accurately assess cardiac damage in AS, as it is the main determinant of postoperative clinical outcomes. Structural LV myocardial changes and myocardial fibrosis in AS are associated with electrical alterations and may affect both myocardial depolarization and repolarization . LV straECG strain has been identified as an explicit electrocardiographic marker of midwall LV myocardial fibrosis as a result of subendocardial ischemia. In a study of 102 patients with mild to severe AS, ECG strain was predictive of diffuse and focal myocardial fibrosis assessed by CMR . Our stuLong-standing pressure overload and changes in LV myocardium and collagen accumulation have negative effects on myocardial deformation. GLS is an early and sensitive marker of LV dysfunction and correlates with histological fibrosis ,40. We fp = 0.009). These findings suggest that surgery might have been performed too late for this group of patients and that LV structural and functional changes are only partially reversible or require more time to recover. Interestingly, a difference in the baseline histological fibrosis was detected in the midmyocardial but not the subendocardial layer. We have previously shown that various degrees of subendocardial fibrosis can be detected in biopsy samples of most AS patients and that the subendocardial region is affected by fibrosis the most [The reduction of LV mass within the first years after the AV surgery has been previously reported ,42,43, athe most , but thethe most . In thatthe most . These dThe clinical impact of pre-operative ECG markers of LV myocardial damage was explored in several recent studies. Coisne et al., in a large cohort of 1122 severe AS patients undergoing surgical AVR, showed that both ECG strain and conduction abnormalities were associated with major adverse cardiac events and all-cause and cardiovascular deaths . Heger eECG strain is a marker of advanced structural and functional LV remodeling and interstitial myocardial fibrosis. ECG strain in a pre-operative assessment may help to identify patients at risk who may benefit from further advanced cardiac imaging and earlier intervention. Lack of improvement in ECG strain following AVR indicates a subgroup of patients with more advanced LV damage and higher levels of myocardial fibrosis who may require closer follow-up and additional medical management.This is a single-center study with a limited sample size, which reduces our statistical power. However, the size of our cohort is comparable to other studies on the same topic and includes a significant number of myocardial biopsies. Due to the COVID-19 pandemic, delays in patient examinations and surgeries were experienced, causing uneven time frames between the preoperative patient assessment  and surgery with myocardial sampling, potentially affecting the final result. Furthermore, the proportion of histologically measured myocardial fibrosis could have been affected by the size and depth of biopsy samples, as more superficially sampled and smaller biopsies may contain a higher proportion of fibrotic tissue in comparison to larger biopsy samples. Extracellular volume fraction changes in AS patients are relatively small, and the detection of small deviations from normal ranges warrants a higher sample size. Lastly, we included only isolated AS patients undergoing surgical AVR; therefore, the results cannot be generalized to patients with concomitant CAD, mixed valvular lesions, or TAVI cohorts.