Measurement Of Ejection Fraction Research Articles

Simplification of a registry-based algorithm for ejection fraction prediction in heart failure patients: Applicability in cardiology centres of the Netherlands.

Left ventricular ejection fraction (EF) is used to categorize heart failure (HF) into phenotypes but this information is often missing in electronic health records or non-HF registries. We tested the applicability of a simplified version of a multivariable algorithm, that was developed on data of the Swedish Heart Failure Registry to predict EF in patients with HF. We used data from 4,868 patients with HF from the Cardiology Centers of the Netherlands database, an organization of 13 cardiac outpatient clinics that operate between the general practitioner and the hospital cardiologist. The algorithm included 17 demographical and clinical variables. We tested model discrimination, model performance and calculated model sensitivity, specificity, positive and negative predictive values for EF ≥ vs. <50% and EF ≥ vs. <40%. We additionally performed a multivariable multinomial analysis for all three separate HF phenotypes (with reduced, mildly reduced and preserved EF) HFrEF vs. HFmrEF vs. HFpEF. Finally, we internally validated the model by using temporal validation. Mean age was 66 ±12 years, 44% of patients were women, 68% had HFpEF, 17% had HFrEF, and 15% had HFmrEF. The C-statistic was of 0.71 for EF ≥/< 50% (95% CI: 0.69-0.72) and of 0.74 (95% CI: 0.73-0.75) for EF ≥/< 40%. The model had the highest sensitivities for EF ≥50% (0.72, 95% CI: 0.63-0.75) and for EF ≥40% (0.70, 95% CI: 0.65-0.71). Similar results were achieved by the multinomial model, but the C-statistics for predicting HFpEF vs HFrEF was lower (0.61, 95% CI 0.58-0.63). The internal validation confirmed good discriminative ability. A simple algorithm based on routine clinical characteristics can help discern HF phenotypes in non-cardiology datasets and research settings such as research on primary care data, where measurements of EF is often not available.

Evaluation of early cardiotoxicity in HER2-positive breast cancer patients receiving radiotherapy and concurrent trastuzumab.

Overexpression of human epidermal growth factor receptor 2 (HER-2) is associated with aggressive disease in breast cancer. Trastuzumab and radiotherapy are standard treatments for patients with HER-2 + breast cancer, but they may increase the risk of cardiotoxicity. This study aimed to assess early cardiotoxicity in patients receiving radiotherapy (RT) and concurrent trastuzumab. The study included 116 patients with HER-2 + breast cancer who received concurrent treatment with trastuzumab and RT (52 right-side; 64 left-side). Five left ventricular ejection fraction (LVEF) measurements were performed: one before treatment and four subsequent measurements taken at three-month intervals. LVEF was also assessed before (preRT-EF) and after (postRT-EF) radiotherapy. The baseline LVEF was 62.27 ± 5.5%, while the 12-month LVEF was 59.8 ± 5.8% (p < 0.05). In subgroups, post-RT LVEF values ​​were significantly lower than pre-RT LVEF values (p < 0.05). No significant difference was found between the reduction in LVEF for patients receiving 50Gy and 60Gy doses. Moreover, the contribution of regional lymph node irradiation to the decrease in LVEF could not be demonstrated. A positive correlation was found between the total trastuzumab dose and the decrease in LVEF from preRT to postRT. Additionally, a positive correlation was observed between the total taxane dose and the reduction in LVEF from baseline to 9months, both in the overall group and in the left breast cancer group. In our study,it was found that not only trastuzumab but also taxane-based agents could be cardiotoxic. However, no connection was found between RT doses and the decrease in LVEF.

Mitigation of pacing-induced cardiomyopathy with superficial right ventricular mid-septal pacing: A long-term retrospective comparison with apical pacing.

It remains unclear if pacing induced cardiomyopathy (PICM) may be minimized by standard pacing of the right ventricle (RV) at sites other than the RV apex. The purpose of this study is to compare the relative frequency of PICM in a population of patients paced at either the superficial RV mid septum (RVMS) or RV apex (RVA), and other outcomes that may differ between these sites. A retrospective evaluation was performed on all patients undergoing pacemaker implantation between 2011 and 2022. Potential study patients were those with Medtronic 3830 superficial RVMS leads placed with septal specific guidance catheters, and any with RVA leads. Patients were included if they had ≥20% RV pacing, available baseline and follow-up measurements of left ventricular ejection fraction (LVEF) at least 6 months postimplantation, and a baseline LVEF ≥50%. PICM was defined as a decline in the LVEF of at least 10%, resulting in LVEF <50%. Patients were excluded for Biventricular devices, and for alternative causes of cardiomyopathy. The study criteria were met in 324 patients, with 220 RVMS and 104 RVA paced patients. PICM occurred in 4.5% of RVMS patients, and 22.1% of RVA patients (p < .001). Additional differences were demonstrated in paced QRS duration (144 ± 15.5 ms in RVMS, 166 ± 19.4 ms in RVA; p < .001); QRS axis (2.3 ± 64.9 in RVMS, -65.2 ± 49.5 in RVA; p < .001), and various qualitative QRS morphologic characteristics. Patients with normal LVEF experienced significantly less PICM with superficial RVMS pacing performed via septal specific guidance catheters than similar counterparts with RVA pacing. Narrower paced QRS duration and less left axis deviation was also demonstrated.

Automated selection of echocardiographic views using a novel artificial intelligence software

Abstract Background/Introduction Evaluation of a single echocardiographic study involves sorting, selecting, measuring and interpreting a large number of images. As these steps are currently performed manually, this can turn into a repetitive, time-consuming and tedious task. Although the use of artificial intelligence (AI) software could potentially improve this entire workflow, most of the efforts have been focused on measurement automatization. Incorporation of automated selection of echocardiographic views could further optimize this process. Purpose We investigated whether an AI-derived measurements software can be supplemented by automated view selection using an AI model. We hypothesized that automated selection of echocardiographic views yields similar results compared to manually selected views when using the same tool for automated measurements in both groups (Figure 1, top). Methods We trained an AI model (convolutional neural network) to recognize the main standard 2D echocardiographic views. This model was trained on individual frames from 20,000 DICOM clips to predict a specific cardiac view, based on the view annotation provided by an echocardiography expert (ground-truth). We then selected a test set of 5,000 DICOMs where we applied the AI model to all images in the study. We selected the highest-ranking apical 2 chamber (A2C) and apical 4 chamber (A4C) images, based on the model’s output probability (Figure 1, bottom). For the same 21 studies, an expert selected the best A2C and A4C image for left ventricular volumes and ejection fraction measurements. Then, we ran Philips AutoMeasure both on manually and automatically selected images. We then compared the measurement values for statistical significance using a pair-wise t-test, see Figure 2. Results The AI model achieved an accuracy of 96% and AUC of 0.99 on the test set. The results obtained when comparing the automatic and manually selected images in the 21 studies are shown in Figure 2. For all the measured parameters, there was no statistically significant difference in mean values between both selection methods. Conclusions Manual and AI-derived selection of standard echocardiographic images do not lead to a statistically significant difference in automated measurements, suggesting that incorporation of automated view selection may contribute to improve daily echocardiographic workflow. Future research could aim in extending these findings to more cardiac views, parameters, and populations.Comparison of the approachesResults

Real-world experience with mavacamten in obstructive hypertrophic cardiomyopathy: observations from a tertiary care center

Abstract Background In symptomatic obstructive hypertrophic cardiomyopathy (oHCM) patients, mavacamten is commercially approved to help improve left ventricular (LV) outflow tract (LVOT) gradients, symptoms, and reduce eligibility for septal reduction therapy (SRT) under the risk evaluation and mitigation strategy (REMS) program. We sought to prospectively report the initial real-world clinical experience with the use of commercially available mavacamten in a multi-hospital tertiary healthcare system. Methods We studied the first 150 consecutive oHCM patients (mean age 65 years, 53% women, 83% on betablockers and 61% in New York Heart Association [NYHA] class III) who were initiated on 5 mg of mavacamten with dose titrations using symptom assessment and echocardiographic measurements of LVOT gradient and LV ejection fraction (LVEF) measurements. We measured changes in NYHA class, LVEF, LVOT gradients (resting and Valsalva) at baseline, 4, 8 and 12 weeks. Results At 261±143 days (range of 31-571 days), 69 (46%) patients had ≥1 NYHA class, 27 (18%) additional patients had ≥2 NYHA class improvement and 40 (27%) reported a no change in symptoms. The mean LVOT gradient at rest decreased from 41±33 mmHg at baseline to 16±17 mmHg at 4 weeks, 16±16 mmHg at 8 weeks and 15±16 mmHg at 12 weeks. The mean drop in resting LVOT gradient from baseline to last follow-up was 26±3 mmHg (p&amp;lt;0.0001). The mean Valsalva LVOT gradient decreased from 72±43 mmHg at baseline to 29±31 mmHg at 4 weeks, 29±28 mmHg at 8 weeks and 30±29 mmHg at 12 weeks (p&amp;lt;0.001). The mean reduction in post Valsalva LVOT gradient from baseline to last follow-up was 43±4 mmHg (p&amp;lt;0.0001). At baseline, 100% patients had Valsalva LVOT gradients ≥ 30 mm Hg and 142 (95%) had ≥ 50 mm Hg. After initiation of mavacamten therapy, Valsalva LVOT gradient ≥ 30 mm Hg was observed in 44/150 (29%) at 4 weeks, 40/141 (28%) at 8 weeks and 41/136 (30%) at 12 weeks. In 40 patients who reported no symptomatic improvement, the mean Valsalva LVOT gradient decreased from 73±39 mmHg at baseline to 34± 27 mmHg at 4 weeks, 35±28 mmHg at 8 weeks and 30±24 mmHg at 12 weeks (P&amp;lt;0.001). The mean LVEF at baseline was 66±6% and changed to 64±5% at 4 weeks, 63±5% at 8 weeks and 62±7% at 12 weeks (p&amp;lt;0.0001). No patient underwent SRT, developed LVEF ≤30% or developed heart failure requiring admission. Three (2%) patients needed temporary interruption of mavacamten due to LVEF&amp;lt;50. During follow up, dose reduction or discontinuation of background HCM therapy (betablockers, calcium channel blockers and disopyramide) occurred in 33 (22%) patients. The breakdown of various drug doses of mavacamten, at last follow-up, is as follows: 2.5 mg (n=29, 19%), 5 mg (n=80, 53%), 10 mg (n=37, 25%) and 15 mg (n=3, 2%). Conclusions In a real-world study in symptomatic oHCM patients at a multi-hospital tertiary care referral center, we demonstrate the efficacy and safety of prescribing mavacamten under the REMS program.

Relationships between 18-month kinetics and functional capacity and left ventricular remodeling and cardiac fibrosis in dilated cardiomyopathy

Abstract Introduction Myocardial fibrosis is a primary pathogenetic process in dilated cardiomyopathy (DCM) that is responsible for progressive cardiac remodeling and functional capacity impairment. We sought to verify whether there were differences between 18-month kinetics of functional capacity and left ventricular remodeling in DCM patients with different types and advancement of fibrosis who were up-titrated with guideline directed pharmacotherapy (GDMT). Methods Between May 2019 and September 2020, 99 DCM patients (88 male, mean age 45.2 ± 11.8 years, mean EF 29.7 ± 10%) underwent cardiac magnetic resonance with assessment of replacement fibrosis via late gadolinium enhancement (LGE) and interstitial fibrosis via extracellular volume (ECV). Each patient had serial (baseline, 6-, 12-, 18 month) functional assessment: NYHA class and 6- minute walking test (6-MWT) and follow-up echocardiography, including measurement of left ventricular end-diastolic volume (LVEDvol) and ejection fraction (EF). Patients were divided into LGE-negative and LGE-positive groups, whereas based on median ECV – they were divided into those with ECV below and above median values. Results Overall, LGE was identified in 44 (44%) of patients, whereas median ECV was 27.7%. NYHA class was significantly worse in patients with LGE (1.5±0.5 vs. 1.9±0.6) and with higher ECV (1.93±0.6 vs. 1.6±0.5) in comparison to those without LGE and lower ECV. However, NYHA class improved during observational period in all groups. There were no differences in 6-MWT distance in LGE positive and negative groups at all time points. Baseline 6-MWT distance in LGE positive group was 494.2±88.2 vs. 453.9±98.8 meters in LGE negative group. Baseline 6-MWT distance in upper median ECV group was (408.8±103.5 vs. 492.4±92.9 meter) was significantly lower ECV group (p=0.03). During 18 months 6-MWT distance increased only in LGE negative group but in both ECV groups (Figure 1 A-D). There were no differences in EF between patients with and without LGE and also with higher and lower ECV. Baseline EF in LGE positive group was 27.4±11.2% and 31.7±10.6% in LGE negative. Baseline indexed LVEDvol in LGE positive group was 107.7±40.7 vs. 91.8±37.8 ml/m2 (p=0.09) in LGE negative group. EF increased significantly in both groups, whereas indexed LVEDvol decreased only in LGE negative group (Figure 2 A-D). Conclusions Regardless of the presence of replacement and to some extent of interstitial fibrosis, functional and cardiac morphological improvement was observed during 18 months observation in DCM patients on GDMT. The greatest improvement occurred during the first 3 (occasionally 6) months which was associated with the greatest escalation of GDMT. Further dose escalation was not associated with a significant improvement in both functional and morphological parameters.

Impact of global longitudinal strain and anemia for predicting cardiovascular mortality in patients hospitalized for acute heart failure with atrial fibrillation

Abstract Background Iron deficiency is a prognostic factor in heart failure (HF) with reduced ejection fraction (EF). In patients with atrial fibrillation (AF) and HF, left ventricular EF (LVEF) measurements are imprecise due to irregular tachycardia, but it is unclear whether global longitudinal strain (GLS) and anemia assessment are prognostic. Purpose We examined whether GLS and anemia predict cardiovascular death (CD) in patients with acute HF complicated by AF. Methods We retrospectively enrolled patients aged 18 years or older with acute HF complicated by AF who were consecutively admitted to our hospital from January 2014 to December 2018. Exclusion criteria were acute coronary syndromes, no transthoracic echocardiogram performed within 30 days before or after admission, and missing data. All patients were followed up from admission to CD (due to myocardial infarction, HF, stroke or sudden death), or were censored at the date of last contact or 3 years. Anemia was defined as hemoglobin &amp;lt; 12 g/dL in females and hemoglobin &amp;lt; 13 g/dL in males. Patients were divided into four groups according to median GLS and anemia status. Results A total of 320 patients (mean age 79 ± 12 years, 163 females) were included in the analysis. The median duration of AF was 1.2 years; 11% (36/320) had paroxysmal AF. The median brain natriuretic peptide value was 623 pg/ml, and 52% of the patients (165/320) were in New York Heart Association functional class 4. During a median follow-up of 528 days, 24% (77/320) patients were observed with CDs: 2 myocardial infarctions, 51 HF-related deaths, 6 strokes, and 18 sudden cardiac deaths. At the 3-year follow-up, the survival rate by the Kaplan-Meier curve was 89% (95% confidence interval (CI) 76%-95%) in the no anemia group with high GLS (&amp;lt; -10%) and 40% (95% CI 25%-54%) in the anemia group with low GLS (≥ -10%) (p &amp;lt; 0.001, log-rank test). In multivariate Cox regression analysis, GLS (adjusted hazard ratio (aHR) 1.06, 95% CI 1.01-1.14, p = 0.017) and hemoglobin (aHR 0.85, 95% CI 0.76-0.96, p = 0.009) were independent factors for CD, with a significantly increased risk in the anemia group with low GLS compared to the no anemia group with high GLS (aHR 4.11, 95% CI 1.59-10.6, p = 0.004). The results were consistent with no interaction by gender or LVEF 50%. Conclusions Anemic patients with low GLS with AF and HF may have poor prognosis. Prospective studies are needed to determine whether iron supplementation improves prognosis in such patients.

The effect of Trimetazidine on the left ventricular global longitudinal strain assessed by cardiac magnetic resonance in stable angina patients with previous myocardial infarction and left ventricular

Abstract Introduction Trimetazidine (TMZ) is an anti-ischemic metabolic agent that is indicated in adults as add-on therapy for the symptomatic treatment of patients with stable angina pectoris (SA). Global left ventricular (LV) systolic function is an important predictor of outcomes in patients after myocardial infarction (MI). Cardiac magnetic resonance (CMR) imaging has now evolved into a major tool for the evaluation of patients with LV dysfunction, providing precise measurements of ejection fraction (EF) and viability assessment but also now allowing assessment of global longitudinal strain (GLS) from standard cine CMR images. We hypothesized that the use of TMZ 80 mg as an anti-ischemic agent in patients with SA, history of MI, reduced EF and in the presence of viable myocardium may produce an early modification of GLS. Methods TRIM-AZ - was a non-interventional, prospective Azerbaijan study to analyze the capacity of short-term therapy with TMZ 80 mg on LV GLS evaluated by CMR in patients with previous MI. Patients with a confirmed diagnosis of heart failure (HF) with impaired LV systolic function and SA in the presence of viable myocardium were included. The treatment of all patients was optimized according to the latest ESC guidelines before entry in the study. Patients were randomized into two groups, one received TMZ 80 mg on top of guidelines directed medical therapies, and the other was the control group. A CMR as well as a transthoracic echography were performed for all patients at the inclusion visit and 8 weeks later. Results 52 patients were included in the study, 30 patients in the TMZ group and 22 in the control group,. At baseline, the mean age was 62±7 years , 63% were smokers, 60% hypertensive, 60% diabetics, 48% had a family history of MI, 12% had typical symptoms of SA while 88% had atypical form (e.g. like shortness of breath). All patients received baseline therapy with ARNI/ACE-i, SGLT2 inhibitors, beta-blockers, MRA, ASA, and statin. 8 weeks after the initiation of TMZ, there were no significant changes in LVEF assessed both by Echo and CMR (29,8%±3,2% vs 30,1%±3,5% by echo in TMZ group; 31,3%±2,7% vs 31,6%±2,7% by echo in the control group; 25,9%±3,1% vs 26,9±4,1% by CMR in TMZ group; 26,9%±2,1% vs 30,1%±2,3% by CMR in the control group), however GLS was significantly improved in TMZ group (-9,9%±1,1% to -12,7%±1,2%, p=0,00), but not in control group (-9,3%±1,3% vs -10,3%±1,4% p=0,3). No adverse event related to TMZ use was reported during the study. Conclusion These findings suggest that the use of trimetazidine in patients with stable angina , previous MI and heart failure in the presence of viable myocardium could improve the left ventricular global longitudinal strain assessed by CMR.

Assessment of Biventricular Systolic and Diastolic Function Using Conventional and Strain Echocardiography in Children with Sickle Cell Disease Surviving 1-year After Hematopoietic Stem Cell Transplant.

Hematopoietic stem cell transplant (HSCT) is a potentially curative therapy for children with sickle cell disease (SCD). The effects of HSCT on ventricular function are not well characterized in children with SCD. Echocardiograms from children with SCD who underwent HSCT between 2007 and 2017 were retrospectively analyzed before and 1-year after HSCT. Left ventricular (LV) volumes, mass, and ejection fraction were calculated by the 5/6 area*length method. LV end-diastolic and systolic dimensions, septal, and posterior wall thickness, and fractional shortening were measured by M-mode. Mitral and tricuspid inflow Dopplers (E and A waves) as well as mitral, tricuspid, and septal tissue Dopplers (E', A') were assessed. E/A, E'/A' and E/E' ratios were calculated. Biventricular strain imaging was performed using speckle-tracking echocardiography. Peak global systolic longitudinal and circumferential LV strain, and global longitudinal right ventricular strain, as well as early and late diastolic strain rate, were measured on LV apical 4-chamber, LV short-axis mid-papillary, and RV apical views, respectively. Forty-seven children (9.7 ± 5.5years, 60% male) met inclusion criteria. Pre-HSCT, subjects had mild LV dilation with normal LV systolic function by conventional measure of ejection fraction and fractional shortening. There was a significant reduction in LV volume, mass, and ejection fraction after HSCT, but measurements remained within normal range. LV longitudinal and circumferential strain were normal pre-HSCT and showed no significant change post-HSCT. RV strain decreased after HSCT, but the absolute change was small, and mean values were normal both pre- and post-HSCT. Conventional measures of diastolic function were all normal pre-HSCT. Post-HSCT there was a reduction in select parameters, but all parameters remained within normal range. Early and late diastolic strain rate parameters showed no significant change from pre- to post-HSCT. At one-year after HSCT in children with SCD conventional measures of systolic and diastolic function are within normal limits. Except for a small decrease in RV systolic strain with values remaining within normal limits, systolic strain and diastolic strain rate values did not significantly change 1-year after HSCT.

The Interplay between Severe Cirrhosis and Heart: A Focus on Diastolic Dysfunction.

Background/Objectives: Cardiovascular involvement in severe cirrhosis presents diagnostic challenges and carries significant prognostic implications. This study aims to evaluate the relationship between liver disease severity and portal hypertension with the burden of diastolic dysfunction. Methods: We prospectively enrolled patients with hepatic cirrhosis, classified according to the Child-Pugh criteria. Of the 102 patients included, 65 were classified as Group A (non-severe cirrhosis: Child-Pugh Classes A and B) and 37 as Group B (severe cirrhosis: Child-Pugh Class C). Portal vein and spleen diameters were assessed using abdominal ultrasound. All patients underwent echocardiographic evaluation. LV systolic function was assessed by measuring ejection fraction, while diastolic function was evaluated using three parameters: E/Em ratio, E/Vp ratio, and indexed left atrial volume. Results: We observed a significantly greater burden of diastolic dysfunction in Group B compared to Group A. Specifically, the E/Vp ratio was 2.2 ± 0.4 in Group B versus 1.9 ± 0.3 in Group A (p < 0.001); the indexed LA volume was 34.5 ± 3.2 mL/m2 in Group B versus 30.1 ± 2.9 mL/m2 in Group A (p < 0.001); and the E/Em ratio was 17.0 ± 3.0 in Group B versus 11.5 ± 2.8 in Group A (p < 0.001). Additionally, the mean diameters of the portal vein and spleen were larger in Group B, with measurements of 14.3 ± 2.1 mm versus 11.5 ± 1.6 mm for the portal vein and 15.0 ± 1.2 mm versus 11.7 ± 1.5 mm for the spleen (p < 0.001), which correlated with the extent of diastolic dysfunction. Conclusions: Diastolic dysfunction was prevalent in 55% of patients with liver cirrhosis. The burden of diastolic dysfunction was higher in patients with severe hepatic cirrhosis compared to those with milder forms, and it correlated with the severity of portal hypertension, as assessed by measuring portal vein diameter and spleen diameter.

ThP2.16 - A prospective study with meta-analysis of echocardiographic changes of left ventricular function in aortic valve replacement patients

Abstract Aortic valve replacement (AVR) improves cardiac function and it reverses adverse remodeling. Measurements of left ventricular ejection fraction (LVEF) are used to identify the patients for pharmacological therapy or AVR. Systematic review identified the Echocardiographic indices followed by AVR. Second part of this study compares the Echocardiographic indices of the patients, who had followed AVR. Results Overall, 145 citations were identified from the initial search, of which 43 studies were retrieved. Later, 8 studies included in the review and 5 were subjected to meta-analysis. There was a change in peak A-wave (MD = 7.30; 95% CI = 5.51 to 9.09), peak E-wave (MD = 3.70; 95% CI = 1.86 to 5.54) before and after AVR. There was no change in LVEF (MD = 0.74; 95% CI = -0.76 to 2.25), E/A ratio (MD = -0.26; 95% CI = -0.75 to 0.23), diastolic dimension (MD = 1.10; 95% CI = -2.08 to 4.28) and systolic dimension (MD = 0.20; 95% CI = -3.41 to 3.81) among AVR cases. Prospective study includes 30 AVR cases. Of these, 23 (76.7%) males and 7 (23.3%) females with mean age was 63.36 + 8.34. There was a change (p &amp;gt;0.05) in peak E-wave, peak gradient and peak diastolic gradient from preoperative to six months after AVR. According to literature, peak E-wave, peak gradient, and peak diastolic gradient changed after AVR. E/A ratio, peak A-wave, E/E ratio, LVEF, diastolic dimension, and systolic dimension were stable (p &amp;gt;0.05) from preoperative to six months after AVR.

Investigation of the mechanism of poly (ADP-ribose) polymerase (PARP) in elderly mouse myocardial ischemia-reperfusion injury.

This study investigated the role of Poly (ADP-ribose) Polymerase (PARP) in myocardial ischemia-reperfusion injury (MIRI) in elderly mice. It involves 30 elderly male KM mice divided into three groups: Sham, MIRI, and DPQ, where the MIRI and DPQ groups undergo myocardial ischemia-reperfusion with the DPQ group also receiving DPQ for PARP-1 inhibition. Over three weeks, assessments include histological analysis of myocardial lesions, left ventricular ejection fraction (LVEF) measurements, and evaluations of serum cardiac enzymes and inflammatory markers. This approach aims to understand the protective effects of DPQ in MIRI, focusing on its impact on cardiac health and inflammation via the JAK2/STAT3 pathway. The findings suggest that PARP activation exacerbates cardiac dysfunction and inflammation in MIRI by possibly modulating the JAK2/STAT3 signaling pathway. Inhibition of PARP-1 with DPQ mitigates these effects, as indicated by reduced myocardial lesions and inflammatory infiltration, improved LVEF, and altered levels of inflammatory markers and signaling molecules. However, the differences in STAT3 and p-STAT3 protein expression between the DPQ and MIRI groups were not statistically significant, suggesting that while PARP inhibition affects many aspects of MIRI pathology, its impact on the JAK2/STAT3 pathway may not fully explain the observed benefits. This study contributes to our understanding of the complex mechanisms underlying myocardial ischemia-reperfusion injury, particularly in the context of aging. It highlights the potential of PARP inhibition as a therapeutic strategy to attenuate cardiac dysfunction and inflammation in MIRI, though further research is necessary to fully elucidate the underlying molecular pathways and to explore the clinical relevance of these findings in humans.

Correlation of greyzone fibrosis compared to troponin T and late gadolinium enhancement with survival and ejection fraction in patients after acute myocardial infarction.

To quantify greyzone fibrosis (GZF) in patients after acute myocardial infarction (MI) and to evaluate its correlation with MI-free survival and improvements in left ventricular ejection fraction (LVEF) compared with the established risk factors high-sensitivity cardiac troponin T (hs-cTnT) and Late Gadolinium Enhancement (LGE). The study involved 176 patients who experienced acute MI and underwent cardiac magnetic resonance (CMR) prior to hospital discharge, followed by a second CMR on average six months later. LGE was quantified in both examinations, a separate analysis of the GZF was conducted only in the follow-up CMR after resolution of the initial infarct edema. LVEF was measured in both CMR. hs-cTnT levels were assessed at hospital admission, as well as 8, 16, 24, 48 and 72h after coronary intervention. Telephone follow-ups were conducted annually for up to 8years. LGE measurements showed better correlation with MI-free survival (Harrell's C of 0.711 of LGE mass) compared to GZF (0.579 of GZF mass). Additionally, hs-cTnT outperformed GZF (Harrell's C of 0.645). As an univariable predictor for MI-free survival, only hs-cTnT reached significance (p < 0.05). With regard to improvements in ejection fraction, both hs-cTnT and LGE measurements showed acceptable correlation with improvement in ejection fraction (p < 0.05), while GZF measurements showed no correlation (p > 0.5). In CMR, the assessment of GZF demonstrated inferior p correlation compared to hs-cTnT and LGE in patients after acute MI with respect to the endpoint of MI-free survival. Furthermore, GZF showed no correlation with the improvement of LVEF.

Mavacamten for Obstructive Hypertrophic Cardiomyopathy: Rationale for Clinically Guided Dose Titration to Optimize Individual Response.

Mavacamten is the first and only cardiac myosin inhibitor approved in 5 continents for the treatment of adults with symptomatic New York Heart Association class II and III obstructive hypertrophic cardiomyopathy. An evidence-based rationale was used to develop individualized mavacamten dosing, guided by commonly used clinical parameters. Echocardiography is recommended as part of routine clinical assessment of patients with hypertrophic cardiomyopathy, and left ventricular (LV) outflow tract gradient and LV ejection fraction are parameters that can be readily assessed and monitored by echocardiography. Therefore, an echocardiography-based, clinically guided dose-titration strategy was developed to optimize patient benefit from mavacamten for the treatment of symptomatic obstructive hypertrophic cardiomyopathy while minimizing the risk of LV ejection fraction reduction. Results from clinical trials paired with extensive modeling and simulation analyses support a dose-titration and monitoring strategy based on serial echocardiographic measures of Valsalva LV outflow tract gradient and LV ejection fraction. This dosing approach allows for the identification of the lowest individualized mavacamten dose and exposure required to provide improvements in LV outflow tract obstruction, functional capacity, and symptoms. Mavacamten is primarily metabolized by CYP2C19 (cytochrome P450 2C19), and CYP2C19 metabolizer phenotype has an effect on mavacamten exposure. Therefore, this approach has also been demonstrated to provide a favorable safety profile irrespective of patients' CYP2C19 metabolizer status. The dose-titration strategy includes additional considerations for the potential onset of systolic dysfunction in the context of intercurrent illness, and for the potential of drug-drug interactions with inhibitors and substrates of cytochrome P450 enzymes. This posology is reflected in the mavacamten US prescribing information.

Reliability of Machine Learning in functional assessment in cardiac magnetic resonance imaging

PurposeOur study aims at evaluating Machine Learning’s reliability to calculate ventricular volumes and functions in cardiac magnetic resonance imaging (CMR).Material and methodsEighty-five patients underwent CMR: forty healthy subjects, fifteen affected by myocarditis, seventeen dilated cardiomyopathy patients (DCM), and thirteen hypertrophic cardiomyopathy patients (HCM). Left ventricle (LV) and right ventricle (RV) analyses were performed both manually by operators and using Cvi42 software, which automates the identification of telesystolic and telediastolic phases. Statistical analysis assessed the concordance between measurements obtained manually and through the software, considering the following parameters: end-diastolic volume (EDV-BSA), end-systolic volume (ESV-BSA), stroke volume (SV), ejection fraction (EF), and detection of telesystolic and telediastolic phases.ResultsIntraclass correlation coefficient (ICC) analysis for LV volumes showed high concordance between manual and automatic measurements (ESV-BSA 0.97, EDV-BSA 0.98, SV 0.87, EF 0.93). ICC analysis for RV volumes presented high concordance between ESV-BSA and EDV-BSA measurements as well (ICC 0.90 and 0.91, respectively), whereas SV and EF measurements showed lower values (0.65 and 0.67, respectively). Statistical analysis also exhibited good concordance between manual and automated methods in the detection of telesystolic and telediastolic phases (ICC 0.80 and 0.84, respectively).ConclusionThe LV and RV analyses conducted using the automated tool provide non-inferior performance to manual analyses, in particular for LV volumes.

A Study on Ejection Fraction in Patients with Mitral and Aortic Regurgitation Based on Cardiovascular Models

Background: Whether it is healthy or patients with mitral and aortic regurgitation, clinicians cannot measure the regurgitation of the valve when using two-dimensional echocardiography to measure ejection fraction. Whether the mitral valve and aortic valve are in a healthy state or in a reflux state, there is a reflux volume. The actual stroke output will be less than the stroke output measured by echocardiography, making the calculated ejection fraction higher. Methods: This article proposes for the first time the concept of net ejection fraction (NEF) as the percentage of net stroke output to left ventricular end diastolic volume. The net stroke output is the integral of aortic valve flow during one cardiac cycle at the same time. Using a systemic arterial circulation model, investigate the relationship between ejection fraction and net ejection fraction through numerical simulation methods. Results: The final results showed a strong linear correlation between mitral regurgitation volume (VRmi), aortic regurgitation volume (VRao), and the difference between ejection fraction and net ejection fraction (DEF). The net ejection fraction of the moderate mitral regurgitation group decreased by an average of 26.3% ± 9.95% compared to the ejection fraction measured by echocardiography. The severe mitral regurgitation group showed a decrease of 31.9% ± 9.3%. Moderate descent of aortic valve by 25.8% ± 11.1%. Severe aortic valve descent of 30.9% ± 10.3%. Conclusions: Clinical doctors can evaluate the left ventricular systolic function of patients based on the ejection fraction measured by echocardiography combined with valve regurgitation. The net ejection fraction avoids overestimation of left ventricular systolic function and has high reliability. It can accurately reflect the left ventricular systolic function of patients with mitral and aortic regurgitation, and has certain guiding significance for clinical doctors to grasp the patient's condition.

Connecting intermediate phenotypes to disease using multi-omics in heart failure.

Heart failure (HF) is one of the most common, complex, heterogeneous diseases in the world, with over 1-3% of the global population living with the condition. Progression of HF can be tracked via MRI measures of structural and functional changes to the heart, namely left ventricle (LV), including ejection fraction, mass, end-diastolic volume, and LV end-systolic volume. Moreover, while genome-wide association studies (GWAS) have been a useful tool to identify candidate variants involved in HF risk, they lack crucial tissue-specific and mechanistic information which can be gained from incorporating additional data modalities. This study addresses this gap by incorporating transcriptome-wide and proteome-wide association studies (TWAS and PWAS) to gain insights into genetically-regulated changes in gene expression and protein abundance in precursors to HF measured using MRI-derived cardiac measures as well as full-stage all-cause HF. We identified several gene and protein overlaps between LV ejection fraction and end-systolic volume measures. Many of the overlaps identified in MRI-derived measurements through TWAS and PWAS appear to be shared with all-cause HF. We implicate many putative pathways relevant in HF associated with these genes and proteins via gene-set enrichment and protein-protein interaction network approaches. The results of this study (1) highlight the benefit of using multi-omics to better understand genetics and (2) provide novel insights as to how changes in heart structure and function may relate to HF.

Diagnostic and Prognostic Role of Circulating microRNAs in Patients with Coronary Artery Disease-Impact on Left Ventricle and Arterial Function.

Recent studies reported that circulating microRNAs (miRNAs) can target different metalloproteases (MMPs) involved in matrix remodeling and plaque vulnerability. Consequently, they might have a role in the diagnosis and prognosis of coronary artery disease. To quantify circulating miRNAs (miRNA126, miRNA146, and miRNA21) suggested to have possible cardiovascular implications, as well as levels of MMP-1 and MMP-9, and to determine their association with left ventricular (LV) function and with arterial function, in patients with either ST-segment elevation acute myocardial infarction (STEMI) or stable ischemic heart disease (SIHD). A total of 90 patients with coronary artery disease (61% men, 58 ± 12 years), including 60 patients with STEMI and 30 patients with SIHD, were assessed within 24 h of admission, by measuring serum microRNAs, and serum MMP-1 and MMP-9. LV function was assessed by measuring ejection fraction (EF) by 2D and 3D echocardiography, and global longitudinal strain (GLS) by speckle tracking. Arterial function was assessed by echo tracking, CAVI, and peripheral Doppler. Circulating levels of miRNA146, miRNA21, and MMP1 were significantly increased in patients with STEMI vs. SIHD (p = 0.0001, p = 0.0001, p = 0.04, respectively). MiRNA126 negatively correlated with LVEF (r = -0.33, p = 0.01) and LV deformation parameters (r = -0.31, p = 0.03) in patients with STEMI and negatively correlated with ABI parameters (r = -0.39, p = 0.03, r = -0.40, p = 0.03, respectively) in patients with SIHD. MiRNA146 did not have any significant correlations, while higher values of miRNA21 were associated with lower values of GLS in STEMI patients and with higher values of GLS in SIHD patients. Both MMP1 and MMP9 correlated negatively with LVEF (r = -0.27, p = 0.04, r = -0.40, p = 0.001, respectively) and GLS in patients with STEMI, and positively with arterial stiffness in patients with SIHD (r = 0.40 and r = 0.32, respectively; both p < 0.05). MiRNA126, miRNA21, and both MMP1 and MMP9 are associated with LV and arterial function parameters in patients with acute coronary syndrome. Meanwhile, they inversely correlate with arterial function in patients with chronic atherosclerotic disease. However, further studies are needed to establish whether these novel biomarkers have diagnosis and prognosis significance.

Abstract Mo112: ARA290, a small peptide non-erythropoietic Erythropoietin derivative, ameliorates heart functional deterioration in a chronic cardiac stress model

Objective: To determine whether ARA290 can prevent or delay age-related declines in cardiac function and structure in the TG AC8 heart failure model. Methods: The study consists of 9 TG AC8 + mice that were randomly assigned to treatment group (n=5) or non-treatment saline group (n=4). Both groups received intraperitoneal injections of ARA290 (100 μg/kg) or saline tri-weekly. Monthly echocardiographic assessment of heart systolic function prior to, and monthly during 7 months of treatment was performed starting at 10 months of age. Two Way ANOVA was used to analyze the data. Results: At baseline, 10 months of age, prospective treatment and non-treatment group did not exhibit any statistically significant difference in their measure of ejection fraction (EF), fractional shortening (FS), and stroke volume (SV) ( P &gt; 0.05). ARA290 treatment preserved EF, FS, and SV, (compared to a progressive, time dependent deterioration of these systolic functions in the saline treated group). Significant interaction terms for EF ( P &lt; 0.04), FS ( P &lt; 0.03), and SV ( P &lt; 0.02), and time indicated that the ARA290 effect depended upon treatment time. Conclusion: The prevention of the decline in heart systolic functional by ARA290 suggests that this small peptide derivative of EPO has therapeutic potential as a novel intervention to retard declines in cardiac function that accompany chronic heart diseases.

Abstract Tu090: P21-activated kinase 1 safeguards cardiac function from impairment during fasting

Excessive calorie intake poses a heightened risk for cardiovascular disease, while caloric restriction and intermittent fasting have demonstrated benefits in enhancing cardiovascular health and improving cardiometabolic risk profiles. Despite this knowledge, the precise mechanisms underlying the cardioprotective effects of these dietary regimens remain inadequately understood. P21-activated kinase 1 (PAK1) is a serine/threonine protein kinase known to play a crucial role in promoting cardiomyocyte survival in response to various stressors. In this study, we aimed to elucidate the role of PAK1 in maintaining cardiac function during fasting, utilizing mice with modified PAK1 activity in the heart. Under normal feeding conditions, heart function exhibited no discernible differences among wild type (WT), transgenic (TG), and knockout (KO) mice, as evidenced by consistent fractional shortening (FS), ejection fraction (EF), E/A ratio, and isovolumic relaxation time (IVRT). After a one-day fast, systolic contractile function remained robust across all groups of mice. However, the E/A ratio decreased in KO mice, and IVRT was prolonged in KO mice, while shortened in TG mice, highlighting the crucial role of PAK1 in maintaining diastolic cardiac function. Upon a two-day fast, systolic function was compromised in both WT and KO mice, whereas TG mice exhibited preserved function, as evidenced by FS and EF measurements, emphasizing PAK1's equal significance in sustaining systolic cardiac function. Furthermore, fasting accelerated mitophagy, a process eliminating dysfunctional mitochondria through lysosomal degradation, as observed by mitochondria-associated LC3-II and a dual fluorescent mitophagy reporter. Additionally, we established PAK1 as a positive regulator of mitophagy, suggesting its potential protective role in the heart during fasting via mitophagy modulation. In summary, PAK1 emerges as a critical mediator of cardiac function during fasting, presenting promising avenues for therapeutic interventions aimed at improving cardiovascular health.