Decrease In Left Ventricular Ejection Fraction Research Articles

Prognostic value of high-sensitivity cardiac troponin I early after coronary artery bypass graft surgery

BackgroundThe diagnosis of periprocedural myocardial infarction (PMI) after coronary artery bypass graft (CABG) is based on biochemical markers along with clinical and instrumental findings. However, there is not a clear cutoff value of high-sensitivity cardiac troponin (hs-cTn) to identify PMI. We hypothesized that isolated hs-cTn concentrations in the first 24 h following CABG could predict cardiac adverse events (in-hospital death and PMI) and/or left ventricular ejection fraction (LVEF) decrease.MethodsWe retrospectively enrolled all consecutive adult patients undergoing CABG, alone or in association with other cardiac surgery procedures, over 1 year. Hs-cTn I concentrations (Access, Beckman Coulter) were serially measured in the post-operative period and analyzed according to post-operative outcomes.Results300 patients were enrolled; 71.3% underwent CABG alone, 33.7% for acute coronary syndrome. Most patients showed hs-cTn I values superior to the limit required by the latest guidelines for the diagnosis of PMI. Five patients (1.7%) died, 8% developed a PMI, 10.6% showed a LVEF decrease ≥ 10%. Hs-cTn I concentrations did not significantly differ with respect to death and/or PMI whereas they were associated with LVEF decrease ≥ 10% (p value < 0.005 at any time interval), in particular hs-cTn I values at 9–12 h post-operatively. A hs-cTn I cutoff of 5556 ng/L, a value 281 (for males) and 479 (for females) times higher than the URL, at 9–12 h post-operatively was identified, representing the best balance between sensitivity (55%) and specificity (79%) in predicting LVEF decrease ≥ 10%.ConclusionsHs-cTn I at 9–12 h post-CABG may be useful to early identify patients at risk for LVEF decrease and to guide early investigation and management of possible post-operative complications.

Association of Soluble IL-1 Receptor Type 2 with Recovery of Left Ventricular Function and Clinical Outcomes in Acute Myocardial Infarction.

The role of soluble interleukin-1 receptor type 2 (sIL-1R2) in acute myocardial infarction (AMI) remains undocumented. In the present study, we aimed to evaluate the possible associations of sIL-1R2 with left ventricular (LV) function, remodeling and future clinical events in the setting of AMI. Circulating sIL-1R2 levels were quantified after percutaneous coronary intervention (PCI) on day 1 of hospital admission for 204 AMI patients, and upon enrollment of 204 healthy controls. Echocardiography was conducted in the acute phase and at 12-month follow-up. Adverse clinical events were registered after 12 months. Circulating sIL-1R2 levels were significantly higher in AMI patients than in healthy controls (medians respectively 6652.81 pg/mL, 3799.13 pg/mL, p 0.0001). AMI patients with sIL-1R2 levels less than the median had a larger proportion of worsened LV ejection fraction [a decrease in LV ejection fraction (LVEF) of more than 10% units] and reduced LVEF (a final LVEF 50%). After multivariate adjustment, sIL-1R2 levels less than the median were associated with an increased risk of worsened LVEF [odds ratio (OR): 3.7, 95% confidence interval (CI): 1.6-8.5, p = 0.002] and reduced LVEF at 12 months (OR: 2.1, 95% CI: 1.1-4.3, p = 0.035). Moreover, low sIL-1R2 levels were associated with an increased risk of having an adverse clinical event during the first 12 months after AMI [hazard ratio (HR): 2.5, 95% CI: 1.0-6.1, p = 0.039]. Low levels of circulating sIL-1R2 were associated with impaired recovery of LV function and adverse clinical outcomes in AMI patients. These findings might contribute to understanding the important role of sIL-1R2 in postinfarction inflammation.

Molecular Imaging of Fibroblast Activity in Radiation-Induced Acute Myocardial Damage Using a [18F]AlF-Labeled Fibroblast Activation Protein Inhibitor, FAPI-04

<h3>Purpose/Objective(s)</h3> A previous retrospective analysis revealed increased [¹⁸F]AlF-NOTA-FAPI uptake in myocardial tissue of patients with esophageal squamous cell cancer (ESCC) treated with concurrent chemoradiotherapy (CCRT). The present study investigated and verified the feasibility of [¹⁸F]AlF-NOTA-FAPI positron emission tomography (PET)/computed tomography (CT) imaging for detecting radiation-induced myocardial damage (RIMD). <h3>Materials/Methods</h3> Myocardial FAPI uptake was analyzed before radiotherapy and during radiotherapy (36–50 Gy) in 13 ESCC patients treated with CCRT. In an animal study, a single dose of 50 Gy was delivered to the cardiac apex of female Wistar rats using conformal radiotherapy. RIMD model rats were scanned with [¹⁸F]AlF-NOTA-FAPI PET/CT weekly for 12 weeks, and then MRI was conducted. Dynamic, competition, and [¹⁸F]FDG PET/CT studies were performed on RIMD rats at 5 weeks post-radiation, and histopathological analyses were conducted. <h3>Results</h3> Three patients showed potentially increased FAPI uptake in myocardial tissue after radiotherapy. In the RIMD rat model, a significant increase in FAPI uptake in the damaged myocardium was observed from the 2nd week post-radiation exposure, with peak values observed in the 5th week. Significantly more intense tracer accumulation was observed in the damaged myocardial region than in remote myocardial tissue, as identified by decreased [¹⁸F]FDG uptake and confirmed by autoradiography, Masson's trichrome staining and immunohistochemical staining. The left ventricular ejection fraction (LVEF) remained unchanged from baseline at the 3rd week post-radiation exposure but was remarkably decreased compared with that in the control group at the 8th week. <h3>Conclusion</h3> An increase in myocardial uptake of [¹⁸F]AlF-NOTA-FAPI occurred in patients with ESCC after radiotherapy. These results indicated that FAPI PET/CT imaging can detect RIMD noninvasively and before a decrease in LVEF is detected, indicating the clinical potential of FAPI as a radiotracer for in vivo imaging of RIMD.

Expanded adaptation of an artificial intelligence model for predicting chemotherapy-induced cardiotoxicity using baseline electrocardiograms

Abstract Introduction While effective as chemotherapeutics, anthracyclines can cause cancer therapy-related cardiac dysfunction (CTRCD), which adversely affects the prognosis of patients with malignancies1–5. Despite guideline recommendations6–9, repeated echocardiograms are rarely performed10 with delayed diagnosis of CTRCD leading to unrecoverable cardiac dysfunction11. Recently, artificial intelligence (AI) was shown to be capable of detecting reduced left ventricular ejection fraction (LVEF) solely from electrocardiogram (ECG)12. Furthermore, this model was predictive of a future decrease in LVEF. Therefore, we hypothesized that an AI model detecting reduced LVEF (AI-EF model) could predict CTRCD from ECGs. Purpose To assess whether the AI-EF model could detect patients at a high risk of CTRCD by analyzing ECGs taken immediately prior to the initiation of cardiotoxic chemotherapy. Methods Among patients who received chemotherapy with a regimen including anthracyclines in two institutions between June 1st, 2015 and October 1st, 2020, those who underwent both an ECG and echocardiogram ≤90 days prior to initial treatment were selected. The ECGs were analyzed by the AI-EF model and patients were divided into two groups according to the scores from the model. CTRCD was defined as LVEF &amp;lt;53% and ≥10% decrease in LVEF from the baseline at any time after the start of chemotherapy13. The cumulative incidence of CTRCD was compared for the two groups using Kaplan-Meier curves, log-rank test, a univariate Cox proportional hazard model, and a multivariable Cox proportional hazard model adjusting for known risk factors for CTRCD. Finally, a prediction model for CTRCD using readily available clinical variables with the AI-EF score was compared with the model using the same variables without the AI-EF score. Results 1,158 patients were included in this study. 99 of them developed CTRCD during follow-up. The AI-EF model displayed excellent risk stratification of developing CTRCD: while 7.1% in the low AI-EF score group developed CTRCD, 12.9% of the patients in the high AI-EF score group developed CTRCD (hazard ratio (HR), 2.14; 95% confidence interval (CI), 1.43–3.19; log-rank p&amp;lt;0.001; Figure 1). This finding was robust across subgroups such as cancer types, the initial dose of anthracycline and baseline LVEF, and consistent after adjusting for multiple risk factors (adjusted HR, 2.10; 95% CI, 1.37–3.22; p&amp;lt;0.001; Figure 2). Furthermore, the addition of the AI-EF score significantly improved the accuracy of predicting CTRCD compared to clinical features alone (time-dependent area under the received operating curve (AUROC) for 2 years, 77.1; 95% CI, 71.8–82.3 for the model with AI-EF score and AUROC 73.9; 95% CI, 69.0–80.1 for the model without AI-EF score; p=0.02). Conclusion The AI-EF model, by utilizing baseline ECG, could stratify patients according to the risk of CTRCD and robustly augmented CTRCD prediction. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): American Heart AssociationVerily

CRT-D non-responders have worse cardiovascular outcome than patients after primary ICD implantation with similar baseline left ventricular ejection fraction

Abstract Background Cardiac resynchronisation therapy (CRT) fails to improve echocardiographic parameters and outcome in 20–40% of heart failure (HF) patients with reduced ejection fraction (EF) referred to as CRT non-responders (CRT-NR). The aim of this study was to compare the outcomes of CRT-NR patients who received a CRT defibrillator (CRT-D) device with patients after primary implantable cardioverter-defibrillator (ICD) implantation for impaired left ventricular (LV) function. Methods CRT-NR status was defined as no or less than 10% improvement in LV EF 12 months post implantation. CRT-NR patients and those after primary ICD implantation for LV EF&amp;lt;35% were identified in our database between 2010 and 2019. CRT-NR patients were further categorized as progressors (decrease in LV EF ≥5%) or non-progressors (LV EF change between +9 to −5%). Primary endpoint was all-cause mortality or the need for heart transplantation during follow-up. Statistical significance was assessed by Log-rank test of Kaplan-Meier survival analysis. Results 151 CRT-NR patients and 219 patients after primary ICD implantation were identified with a mean ± SEM follow-up of 43.7±2.5 and 47.3±2.2 months, respectively. Baseline (preoperative) LV EFs were higher (p&amp;lt;0.05) for the overall CRT-NR group (EF = 27.4±0.4%) than for the ICD group (EF = 25.2±0.3%) Further, both CRT-NR subgroups of progressors (n=49; EF = 28.6±0.7%) and non-progressors (n=102; EF = 26.9±0.5%) had also significantly higher baseline LV EF as compared to ICD patients (p&amp;lt;0.05). No statistical significance was found between the two CRT-NR subgroups. Event free median survival for the overall CRT-NR group (55.6 months) was significantly worse than for the ICD group (79.6; p&amp;lt;0.05). This difference was driven by progressor patients who had a significantly worse event free survival (37.8 months, p&amp;lt;0.05) than ICD patients, while vent free survival in non-progressors (60.8 months) was comparable to ICD patients (p=0.18). Conclusion Progressor subgroup of CRT-NR have worse outcome as compared to non-progressors and also to those after primary prevention ICD implantation. The poor prognosis of these patients should have implications for timely decision regarding all therapeutic measures currently available for the management of heart failure. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Project no. TKP2021-EGA-18 has been implemented with the support provided from the National Research, Developement and Innovation Fund of Hungary, financed under the TKP2021-EGA funding scheme

Risk of pacing-induced cardiomyopathy in patients with high-degree atrioventricular block – comparison between right ventricular pacing sites using computed tomography

Abstract Background Right ventricular (RV) pacing may induce significant left ventricular (LV) dyssynchrony resulting in pacing-induced cardiomyopathy (PICM). LV activation sequence is affected by RV pacing site and previous studies suggest that RV septal pacing may be superior compared to traditional RV apical pacing. However, results are conflicting and randomized controlled trials have failed to show clear benefits from RV septal pacing. Traditionally, studies have applied fluoroscopy to determine RV lead implantation site. However, locating pacing site using this method is known to be inaccurate and poorly reproducible compared with cardiac computed tomography (CT). The purpose of our study was to evaluate the association between RV pacing site determined by cardiac CT and risk of PICM. Methods We retrospectively included 153 patients with pre-implant LV ejection fraction (LVEF) ≥50% who underwent fluoroscopy-guided dual chamber pacemaker implantation due to high-degree atrioventricular block between March 2012 and May 2020. All patients attended a follow-up visit including cardiac CT and transthoracic echocardiography. RV lead position was evaluated from CT dividing the RV into three segments: apical, septum or free wall (Figure 1). Furthermore, RV lead position estimated by the implanting physician, using fluoroscopy during pacemaker implantation, was retrieved from medical records. The primary endpoint was PICM defined as ≥10% decrease in LVEF from time of pacemaker implantation to follow-up, resulting in LVEF &amp;lt;50%. Results Mean duration of follow-up was 3.7 years (range 2.1–8.7). The implanting physician estimated 131 (85.6%) leads to be located septal, 5 (3.3%) located non-septal and 17 (11.1%) were unknown. Based on CT, 48 (31.4%) leads were located septal and 105 (68.6%) were located non-septal of which 31 were located on the free wall (20.4%). With CT as the golden standard, 47 (35%) leads were estimated correctly during fluoroscopy-guided implantation. No significant differences between patient characteristics in the CT-estimated septal and non-septal groups were observed except for ischemic heart disease (P=0.05) (Table 1). There were 16 (33.3%) patients in the septal group who developed PICM compared to 31 (29.5%) in the non-septal group (P=0.6). Adjusting for ischemic heart disease did not change this result. In the septal group, the change in LVEF from baseline to follow-up was −9.0±10.4% compared to −7.5±9.1% in the non-septal group (P=0.4). Conclusion In total 31% developed PICM despite having a normal pre-implant LVEF with no observed difference between RV septal and non-septal pacing. With CT as the golden standard, RV leads were inaccurately located during fluoroscopy-guided pacemaker implantation with only 35% being located correctly. Misclassification of pacing sites in previous studies may have contributed to the inconsistent results. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Svend Andersens FondKarl G Andersens Fond

Sepsis-Induced Cardiomyopathy Detected With Focused Cardiac Ultrasound in the Emergency Department

BackgroundSepsis is a high mortality condition characterized by multi-organ dysfunction. Sepsis-induced cardiomyopathy (SIC) refers to cardiac dysfunction in sepsis. ObjectivesOur goal was to determine whether SIC can be detected in the emergency department (ED) using focused cardiac ultrasound (FCU). MethodsA retrospective analysis of adults presenting to a single ED with sepsis over a 21-month period was performed. Patients were included if they met clinical sepsis criteria, received an FCU by an emergency physician in the ED, and a baseline echocardiogram performed in the previous 12 months. SIC was defined as a significant decrease in estimated left ventricular ejection fraction (LVEF) by FCU relative to baseline. Demographic and outcome characteristics were compared between three cohorts: patients with normal baseline LVEF and no decrease on presentation, patients with decreased LVEF and no significant change, and those with a significant decrease in LVEF from their normal baseline (SIC). ResultsThere were 110 patients that met inclusion criteria: 89 patients (81%) in the normal LVEF group, 12 (11%) in the prior decreased LVEF group, and 9 (8%) in the SIC group. Unadjusted mortality at 90 days for patients with SIC (67%) and prior decreased LVEF (58%) was significantly higher than those with normal EF (29%) (p = 0.019). When adjusted for age, gender, Charlson Index score, and lactate > 4.0 mmol/L, SIC was associated with mortality at 90 days (odds ratio 6.1, 95% confidence interval 1.37–32.92). ConclusionSIC can be detected using FCU by emergency physicians in the ED and is associated with increased 90-day mortality.

Contemporary outcome of subsequent pregnancies in patients with previous peripartum cardiomyopathy.

To describe the effect of subsequent pregnancies (SSP) on left ventricular (LV) function and outcomes in patients with peripartum cardiomyopathy (PPCM). Among146 women with PPCM who were prospectively followed at two medical centres in Israel (2007-2019), 75 SSPs (in 50 women) were identified: 8 miscarriages, 8 terminations, and 59 life birth. Forty-five patients with 59 full-term SSPs [mean age was 32.9±4.1years, LV ejection fraction (LVEF) 57.7±5.1%] were analysed. Data on LVEF at 1-month post-delivery were available in 46 and at 6months in 36 SSPs. There was a small decrease in the mean LVEF, mostly at third trimester (57.2±5.6 vs. 54.4.±7.3, P<0.001); and at 1-mont (57.9±5.7% vs. 55.4±6.1%, P=0.001) and at 6-month post-delivery (57.4±6.1 vs. 55.3±7.9%, P=0.03). In patients with pre-SSP LV LVEF ≥55%, a mild reduction in the mean group LVEF was seen at 1-month post-delivery (P=0.009). One patient with pre-SSP LVEF ≥55% developed severe relapse. In patients with pre-SSP LVEF <55%, a mild reduction in LVEF was obtained mostly at third trimester (51.1±5.6 vs 47.0±7.4%, P<0.001), which persisted at 6months (P=0.03). A relapse was observed in three (25%) women with LVEF <55%. There was no maternal mortality, 32 patients delivered by caesarean section, and there were no foetal complications. Our study indicates a favourable outcome and low likelihood of maternal mortality associated with SSP in women with a history of PPCM and recovered LV systolic function. SSP was associated with a slight reduction in LVEF mostly during the third trimester, which persisted up to 6months after delivery.

Early detection of radiation-induced myocardial damage by [18F]AlF-NOTA-FAPI-04 PET/CT imaging.

Retrospective analysis revealed increased [18F]AlF-NOTA-FAPI-04 uptake in the myocardium of patients with esophageal squamous cell cancer (ESCC) treated with concurrent chemoradiotherapy (CCRT). This study investigated and verified the feasibility of [18F]AlF-NOTA-FAPI-04 PET/CT for detecting radiation-induced myocardial damage (RIMD). Myocardial FAPI uptake was analyzed before and during radiotherapy in thirteen ESCC patients treated with CCRT. In the animal study, a single dose of 50Gy was delivered to the cardiac apex of Wistar rats (24 rats, including 16 RIMD model rats and 8 control model rats). RIMD model rats were scanned with [18F]AlF-NOTA-FAPI-04 PET/CT weekly for 12weeks, and left ventricular ejection fraction (LVEF) was measured by magnetic resonance imaging. Dynamic, blocking, and [18F]FDG PET/CT studies (4 rats/group) were performed on RIMD rats at 5weeks post-radiation, and histopathological analyses were conducted. Increased FAPI uptake in the myocardium was found after CCRT (1.53 ± 0.53 vs 1.88 ± 0.70, P = 0.015). In RIMD rats, significantly increased FAPI uptake in the damaged myocardium was observed from the 2nd week post-radiation exposure and peaked in the 5th week. Significantly more intense tracer accumulation was observed in the damaged myocardium than in the remote myocardium, as identified by decreased [18F]FDG uptake and confirmed by autoradiography, hematoxylin-eosin, Masson's trichrome, and immunohistochemical staining. The LVEF remained unchanged at the 3rd week post-radiation exposure but was remarkably decreased compared with that in the control group at the 8th week. Through clinical phenomena and animal experimental studies, this study indicated that [18F]AlF-NOTA-FAPI-04 PET/CT imaging can detect RIMD noninvasively and before a decrease in LVEF, indicating the clinical potential of [18F]AlF-NOTA-FAPI-04 as a PET/CT tracer for early monitoring of RIMD.

Long-term follow-up results of patients with left bundle branch pacing and exploration for potential factors affecting cardiac function.

Background: Left bundle branch pacing (LBBP) is an alternative strategy for His bundle pacing (HBP). This study aimed to analyze the long-term performance of LBBP and the potential factors affecting long-term cardiac function. Methods: Patients with LBBP were continuously enrolled from January 2018 to August 2020. Pacing parameters, electrocardiogram (ECG), and echocardiography were collected. The anatomic position of LBBP leads was described by echocardiographic and fluoroscopic parameters. Results: A total of 91 patients with a median follow-up of 18 months were enrolled. Most patients maintained stable pacing parameters during follow-up. The intra-septal position of the 3830 lead also remained stable as the distance from the lead tip to the left surface of the ventricular septum was 0.4 (0, 1.4) mm. The overall level of left ventricular ejection fraction (LVEF) slightly increased. 59 patients had improved LVEF (∆LVEF > 0), while 28 patients had unchanged or reduced LVEF (∆LVEF ≤ 0). The declines of baseline LVEF, ∆ Paced QRSd, and corrected longitudinal distance (longit-dist) of lead-implanted site correlated with LVEF improvement, and these three factors had negative linear correlations with ∆LVEF. Patients with tricuspid valve regurgitation (TVR) deterioration had longer follow-up duration (20.5 vs. 15.0 months, p = 0.01) and shorter Lead-TVA-dist (18.6 vs. 21.6 mm, p = 0.04) than those without TVR deterioration. Conclusion: Patients with LBBP generally remained stable in pacing performance, anatomic lead positions, and cardiac function in long-term follow-up. Baseline LVEF, ∆ Paced QRSd, and corrected longit-dist might be associated with potential LVEF decrease, which required further confirmation.

Abstract P3114: Intermittent Fasting Potentiates Anthracycline Cardiotoxicity

Background: Anthracyclines such as doxorubicin (Dox) cause cardiotoxicity and associated autophagic impairment, though controversy exists increasing autophagy ameliorates or exacerbates Dox cardiotoxicity. Because intermittent fasting (IF), a potent stimulus of autophagy, is presently under clinical investigation in multiple human clinical trials of cancer patients receiving chemotherapy, we tested whether IF would ameliorate or exacerbate Dox cardiotoxicity in multiple murine models. Methods: Chow-fed C57BL/6 mice (n=150) were randomized to ad libitum feeding ( adlib ) or IF (every other day) and treated with vehicle or Dox (5 mg/kg IP x 4 doses). Alternatively, to stimulate autophagy and lysosomal biogenesis transcriptionally, we employed adeno-associated virus 9 (AAV9)-driven overexpression of transcription factor EB (TFEB) vs null, followed by vehicle or Dox (n=40). We further analyzed TFEB nuclear content in myocardial tissue from patients with anthracycline cardiomyopathy vs non-failing donors and patients with other non-ischemic cardiomyopathies (n=17). Results: In Dox-treated mice (but not in vehicle controls), IF significantly reduced survival (18% absolute reduction or AR) ( figure A ), left ventricular ejection fraction (LVEF) (8% AR) ( figure B ) and heart weight index (12% relative reduction) ( figure C ) compared to adlib group. Mechanistically, in Dox-treated mice, IF significantly decreased phosphorylation of mammalian target of rapamycin, increased active, nuclear TFEB content, and increased levels of the atrophy factor muscle RING-finger protein-1. In myocardial tissue from patients with anthracycline cardiomyopathy, we observed a 3.5-fold increase (p&lt;0.01) in nuclear TFEB content compared to both tissues from donors without heart failure and tissues from patients with other non-ischemic cardiomyopathies. Overexpression of TFEB exacerbated Dox-induced cardiotoxicity, including significant decreases in LVEF, left ventricular mass index, and survival. Conclusions: IF exacerbates Dox-related mortality and cardiomyopathy, likely by stimulating the autophagy-lysosomal transcriptional regulator TFEB. Our data raise concerns about the safety of IF and augmentation of TFEB activity in the context of anthracycline chemotherapy.

Cardiac Safety in Breast Cancer Patients Receiving Pegylated Liposome Doxorubicin Sequential Anti-HER2 Monoclonal Antibody Therapy.

Background: Cardiotoxicity associated with the sequential use of anthracyclines followed by trastuzumab is common in adjuvant therapy of patients with HER2-positive early breast cancer (eBC). However, the cardiac safety of trastuzumab concurrent with pegylated liposomal doxorubicin (PLD) is relatively less studied. Method: Clinical data of patients with HER2-positive eBC treated with PLD and cyclophosphamide (PLD-C) followed by taxanes plus trastuzumab ± pertuzumab (TH or TPH) who then completed standard anti-HER2 treatment for 12 months from June 2012 to August 2021 were retrospectively collected. The primary endpoints were clinical and subclinical cardiotoxicity. Result: In total, 70 eligible patients were enrolled. Among them, 55 patients (78.6%) received PLD-C → TH and 15 patients (21.4%) received PLD-C → TPH. The median follow-up time was 41.8 months. Until August 2021, only two patients had recurrent or metastatic diseases, with 2-year and 5-year disease-free survivals of 98.6% and 96.8%, respectively. Clinical cardiotoxicity occurred in six patients (8.6%), and all of them had an absolute decline of ≥16% from baseline left ventricular ejection fraction (LVEF) but not below the lower limit of normal (LLN = 50%). Subclinical cardiotoxicity events occurred in 17 patients (24.3%), and all of them had absolute declines of ≥10% and <16% from baseline LVEF but not below the LLN. No patients were interrupted from treatment, and all patients completed anti-HER2 treatment for 12 months. The sharpest decrease in LVEF was observed at 18 months after the start of PLD treatment. The cumulative incidences of clinical and subclinical cardiotoxicity were 9.8% and 28.3%, respectively. In the univariate analysis, body mass index, age, left chest wall radiotherapy, and ongoing cardiovascular risk factors were not significantly associated with clinical or subclinical cardiotoxicity (p > 0.05). No patients had congestive heart failure or death caused by PLD or anti-HER2 treatment. Conclusion: The sequential use of PLD and trastuzumab showed a lower incidence of clinical cardiotoxicity, presented as asymptomatic decreased LVEF, compared with the results obtained in previous clinical studies using conventional anthracycline, taxanes and trastuzumab. The study regimen demonstrated good cardiac tolerance and is an alternative strategy for cardioprotection in patients with HER2-positive eBC.

Network Meta-analysis of traditional Chinese medicine injections against anthracycline-induced cardiac injury

This study aimed to systematically evaluate the effect of traditional Chinese medicine(TCM) injections on anthracycline-induced cardiac injury. The Cochrane Library, PubMed, EMbase, CNKI, and other databases were electronically retrieved to gather randomized controlled trials(RCTs) of TCM injections against anthracycline-induced cardiac injury from their inception to September 2021. After two research fellows independently screened the literature and extracted the data, the risk of bias of included RCTs was assessed and network Meta-analysis was performed by R 4.1.0 and Stata 15.1. A total of 50 RCTs were included, involving eight TCM injections. Network Meta-analysis showed that:(1)the combination of anthracyclines with Huachansu Injection might be the optimal treatment to reduce the abnormal electrocardiogram.(2)The combination with Shenfu Injection might be the optimum treatment to ameliorate the left ventricular ejection fraction(LVEF) decrease.(3)The combination with Shenqi Fuzheng Injection might reduce the incidence of cardiotoxicity most satisfactorily.(4)The combination with Xinmailong Injection might improve the elevated cardiac troponin I(cTnI) optimally.(5)The combination with Shenmai Injection might be optimal to control the rise of creatine kinase MB isoenzyme(CK-MB).(6)The combination with Kushen Injection might be the regimen with the lowest gastrointestinal reactions. TCM injections had desirable effect on anthracycline-induced cardiac injury, with low incidence of adverse reactions, and each TCM injection had its own unique advantages. Due to the limitations in quality and methodological conduct of the included studies, more high-level RCTs are needed to validate the conclusions.

Olive oil protects against progression of heart failure by inhibiting remodeling of heart subsequent to myocardial infarction in rats

We examined the beneficial effects of olive oil against heart failure post‐myocardial infarction (PMI), induced by coronary artery ligation in rats. Animals were divided into sham and ligated groups and fed either regular chow, olive oil (10% wt/wt), or corn oil (10% wt/wt) and were followed up to 16 weeks. On the echocardiography at 3 days (PMI), in the ligated regular chow (LRC), ligated olive oil (LOO), and ligated corn oil (LCO) left ventricular ejection fraction (LVEF) decrease was 12.14%, 16.42%, and 17.53% from the baseline, respectively. However, only LOO group improved LVEF significantly at 16 weeks PMI and became comparable with all sham groups. Both scar formation and collagen deposition at 16 weeks PMI were less pronounced in the LOO group. Myocardial TNF‐α level at 4 weeks of PMI increased by 176%, 11%, and 181% in the LRC, LOO, and LCO groups, respectively. Plasma TNF‐α levels in LOO were significantly lower than LRC group after 4 weeks of PMI. Myocardial redox ratio (reduced glutathione/oxidized glutathione) decreased at 4 weeks PMI by 44.4%, 16.4%, and 36.9% in the LRC, LOO, and LCO groups, respectively, compared to the baseline. These changes in the redox ratio at 16 weeks PMI were further exacerbated in the LRC and LCO groups. Lipid hydroperoxides formation increased at 4 weeks PMI by 137.4%, 14.6%, and 97.1% in the LRC, LOO, and LCO groups, respectively. Since coronary artery ligation decreased left ventricular ejection fraction, increased myocardial TNF‐α and oxidative stress, and since olive oil was able to inhibit these effects, it is proposed that dietary olive oil modulates cardiac remodeling and heart failure subsequent to myocardial infarction.

The Evaluation of the Obstetric Outcomes in Re-Pregnancy after Recovery from Peripartum Cardiomyopathy

The exceptional form of pregnancy specific idiopathic congestive heart failure is known as peripartum cardiomyopathy. Its onset is highly observed during the last month of pregnancies. Objective: To evaluate the cardiac outcomes in the subsequent pregnancies of patients having history of the cardiomyopathy. Methods: It is a retrospective cohort study conducted at Gynae unit Timergara Teaching hospital Dir Lower KPK for the duration of one year from March 2021 to March 2022. The seventy six patients that had history of peripartum cardiomyopathy with re-pregnancy were selected for the study. The participants were aware of the study and written consent was signed by them. The echocardiography examination of each patients were reviewed. The demographic data maternal and neonatal outcomes data of index was recorded. The SPSS software was used for the statistical analysis of the data. Results: Data of seventy six patients that had history of peripartum cardiomyopathy with re-pregnancy were evaluated. The average age of mother at the time of delivery was 26 years. There were 30 patients that reported about mood disorders and they were already taking medications during the pregnancy. 15 patients reported about migraine headache. There were only small number of patients that had prior diagnosis of cardiovascular diseases. The chronic hypertension was observed in 3 patients and 4 patients had Wolf-Parkinson-White syndrome. Conclusions: In this study the effect of re-pregnancy on cardiac outcomes were studied among patients who had a history of peripartum cardiomyopathy. Patients having peripartum cardiomyopathy history and recover LV function are at risk for a transient minor decrease in LV ejection fraction during future pregnancies. The promising obstetric and neonatal outcomes were observed.

A randomized, double-blind, phase III, non-inferiority clinical trial comparing the efficacy and safety of TA4415V (a proposed Trastuzumab biosimilar) and Herceptin (Trastuzumab reference product) in HER2-positive early-stage breast Cancer patients

BackgroundThis study compared efficacy and safety of TA4415V, a trastuzumab biosimilar, with reference trastuzumab in patients with human epidermal growth factor receptor 2–positive (HER2-positive) early-stage breast cancer treated in the neoadjuvant setting in Iran.MethodsPatients were randomly assigned to receive neoadjuvant TA4415V or reference trastuzumab concurrently with docetaxel (TH phase) for 4 cycles after treatment with 4 cycles of doxorubicin and cyclophosphamide (AC phase). Chemotherapy was followed by surgery. The primary endpoint was the comparison of pathologic complete response (pCR) rate in the per-protocol population. Secondary endpoints included comparisons of overall response rate (ORR), breast-conserving surgery (BCS), safety, and immunogenicity.ResultsNinety-two participants were analyzed in the per-protocol population (TA4415V, n = 48; reference trastuzumab, n = 44). The pCR rates were 37.50% and 34.09% with TA4415V and reference drug, respectively. The 95% CI of the estimated treatment outcome difference (− 0·03 [95% CI − 0.23 to 0.16]) was within the non-inferiority margin. No statistically significant difference was observed between the groups for other efficacy variables in the ITT population: ORR (89.13% vs. 83.33%; p = 0.72) and BCS (20.37% vs. 12.96%; p = 0.42) in the TA4415V and reference drug group, respectively.At least one grade 3 or 4 adverse events occurred in 27 (50%) patients in the TA4415V group versus 29 (53.70%) in the reference trastuzumab group (p = 0.70). The decrease in left ventricular ejection fraction (LVEF), as an adverse event of special interest (AESI) for trastuzumab, was compared between treatment groups in TH phase. Results demonstrated an LVEF decrease in 7 (12.96%) and 9 (16.67%) patients in TA4415V and reference trastuzumab groups, respectively (p = 0.59). Anti-drug antibodies (ADA) were not detected in any samples of groups.ConclusionsNon-inferiority for efficacy was demonstrated between TA4415V and Herceptin based on the ratio of pCR rates in HER2-positive early breast cancer patients. In addition, ORR and BCS, as secondary endpoints, were not significantly different. Safety profile and immunogenicity were also comparable between the two groups.

Peri-event plasma PCSK9 and hsCRP after an acute myocardial infarction correlate with early deterioration of left ventricular ejection fraction: a cohort study

BackgroundIt is important to identify patients at increased risk of worsening of left ventricular ejection fraction (LVEF) after a myocardial infarction (MI). We aimed to identify the association of various potential biomarkers with LVEF impairment after an MI in South American patients.MethodsWe studied adult patients admitted to a University Hospital and diagnosed with an acute MI. Plasma concentrations of high-sensitivity C-reactive protein (hsCRP), proprotein convertase subtilisin/kexin type 9 (PCSK9), N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and heart-type fatty-acid-binding protein (FABP3) were determined in samples drawn shortly after the event. Participants had a follow-up visit at least 45 days after the event. The primary endpoint was defined as any decline in LVEF at follow-up relative to baseline.ResultsThe study included 106 patients (77.4% men, 22.6% women), mean age was 64.1, mean baseline LVEF was 56.6, 19% had a prior MI. We obtained a follow-up evaluation in 100 (94.4%) of participants, mean follow-up time was 163 days. There was a significant correlation between baseline PCSK9 and hsCRP (r = 0.39, p < 0.001). Baseline hsCRP concentrations were higher in patients who developed the endpoint than in those who did not (32.1 versus 21.2 mg/L, p = 0.066). After multivariate adjustment, baseline PCSK9, male sex and age were significantly associated with impairment in LVEF. The absolute change in LVEF was inversely correlated with baseline hsCRP (standardized coefficient = − 0.246, p = 0.004).ConclusionHigh plasma levels of PCSK9 and hsCRP were associated with early decreases in LVEF after an MI in Latin American patients.

Impact of type 2 diabetes mellitus on left ventricular deformation in non-ischemic dilated cardiomyopathy patients assessed by cardiac magnetic resonance imaging

BackgroundType 2 diabetes mellitus (T2DM) increases the risk of worse long-term outcomes in patients with non-ischemic dilated cardiomyopathy (NIDCM). However, the additive effects of T2DM on left ventricular (LV) function in NIDCM remain unclear. Accordingly, we aimed to investigate the impact of comorbid T2DM on LV deformation in NIDCM individuals.Materials and methodsThree hundred forty-two NIDCM patients without T2DM [NIDCM (T2DM−)], 93 with T2DM [NIDCM (T2DM+)] and 80 age- and sex-matched normal controls who underwent cardiac magnetic resonance scanning were included. LV geometry, function, and LV global strains, including peak strain (PS), peak systolic strain rate (PSSR) and peak diastolic strain rate (PDSR) in the radial, circumferential and longitudinal directions, were measured. NIDCM (T2DM+) patients were divided into two subgroups based on the HbA1c level (< 7.0% and ≥ 7.0%). The determinants of reduced LV myocardial strain for all NIDCM individuals and NIDCM (T2DM+) patients were assessed using multivariable linear regression analyses.ResultsCompared with normal controls, both NIDCM (T2DM −) and NIDCM (T2DM+) patients exhibited increased LV end-diastolic and end-systolic volume index and decreased LV ejection fraction. LV global strains progressively declined from the normal controls to the NIDCM (T2DM−) group to the NIDCM (T2DM+) group (all p < 0.017), except for radial PDSR and PSSR. Subgroup analysis showed that LV global radial PS and longitudinal PS, PSSR-L and PDSR-L were worse in NIDCM patients with poor glycemic control than in those with good glycemic control (p < 0.017). T2DM was an independent determinant of reduced LV global circumferential PS and longitudinal PS in patients with NIDCM (both p < 0.05). An increased HbA1c level was independently associated with a decreased global radial PS (β = − 0.285, p < 0.01) and longitudinal PS (β = 0.320, p < 0.01) in NIDCM (T2DM+) patients.ConclusionsT2DM has an additive deleterious effect on LV systolic and diastolic function in NIDCM patients. Among NIDCM patients with T2DM, HbA1c was found to be associated with reduced LV myocardial strain.

Prevention of Adjuvant Treatment Induced Cardiotoxicity in Egyptian Breast Cancer (BC) Patients: A Randomized Prospective Study

Background: Adjuvant Anthracyclines Chemotherapy (ANTC) and trastuzumab have been documented to prolong survival in patients with breast cancer (BC). However, these drugs are also well known to induce left ventricular systolic dysfunction (LVSD). Multiple studies have shown that angiotensin converting enzyme inhibitors (ACEIs) and beta blockers (BBs) can prevent LVSD among women with BC.&#x0D; Objectives: We aimed to prospectively evaluate the efficacy of enalapril (ACEI) and carvedilol (BB) in preventing the ANTC ± trastuzumab induced LVSD, in patients with non-metastatic BC.&#x0D; Patients and Methods: We randomized 126 patients with non-metastatic (M0) BC, who were scheduled to be treated with ANTC ± trastuzumab into the intervention group (group 1; n = 63), which received enalapril and carvedilol or the control group (group 2; n = 63), which did not receive enalapril or carvedilol. To evaluate left ventricular (LV) systolic and diastolic functions the conventional echocardiography (ECHO) and cardiac magnetic resonance imaging (CMR) were performed at baseline, after 3 therapy cycles, and at 1-year follow-up. The secondary endpoint was designed to detect the incidence of a decrease in left ventricular ejection fraction (LVEF) ≥ 10%, heart failure (HF), LVSD (defined as LVEF&lt;45%) or deterioration in LV diastolic function.&#x0D; Results: In the intervention group, 58 patients had 3 cycles ANTC, 6 patients received 6 cycles ANTC, and 12 patients received trastuzumab. In the control group, 47 patients had 3 cycles ANTC, 16 patients were given 6 cycles ANTC and 18 patients received trastuzumab (as per the guidelines issued by breast clinic in the department of clinical oncology, faculty of medicine, Ain Shams University) for adjuvant and neoadjuvant chemotherapy in early breast cancer).&#x0D; After 3 ANTC cycles, LVEF did not change in the intervention group, but decreased by M-mode in the control group (p-value: 0.03), which was associated with statistically significant deterioration of LV diastolic function. At 1 year follow-up, while no change was observed in LVEF in group 1, there was a decrease in LVEF by CMR in group 2 (65.78% at baseline, 61.48% at 1 year; p-value: 0.04 8).&#x0D; Conclusion: Combined prophylaxis with enalapril and carvedilol may prevent LVSD in patients with non-metastatic BC treated with anthracycline-containing chemotherapy ± trastuzumab. However, the clinical relevance of this strategy should be confirmed in the future, large-scale randomized studies.

LGG-02. Cardiac toxicity in patients receiving single-agent MEK inhibition

BACKGROUND: MEK inhibitor therapy is increasingly being utilized for the treatment of pediatric tumors, including low-grade glioma, plexiform neurofibroma and Langerhans cell histiocytosis. These drugs are well-tolerated but do have risk of toxicity, including cardiac toxicity. The purpose of this study is to better characterize MEK inhibitor-induced cardiac toxicity in pediatric patients. METHODS: Retrospective review of all patients who underwent MEK inhibitor mono-therapy for at least 3 months, 2015- 2021, age 25 years or less, at St. Louis Children’s hospital and Cardinal Glennon Children's hospital. RESULTS: We evaluated 31 patients, 19 (61%) with brain tumors and 12 (39%) without. Of the thirty-one, fifteen (48%) had NF1, 1 had Tuberous sclerosis. Cardiac toxicity consisted of asymptomatic sinus tachycardia, bradycardia, or decreased ejection fraction (EF). Thirteen patients (42%) experienced an asymptomatic decrease in left-ventricular ejection fraction (EF), Grade I-III. Time on therapy before decreased EF was 5 days to 21 months, median 2.8 months. Decreased EF developed in 5 of 13 patients receiving selumetinib and 8 of 18 receiving trametinib. Of the patients who developed decreased EF, 11 (85%) had brain tumors, 6 (46%) had NF1, and 89% had received prior systemic therapy. Out of the patients who had received no prior systemic therapy (6), 2 (33%) had decreased EF, while 11/25 (44%) of those who had received prior systemic therapy did. Drug was held temporarily for 6 patients, with dose limiting toxicity for 5 patients. Drug was discontinued for 1 patient after EF continued to decline despite dose reduction. Patients showed improvement in EF as early as 2 weeks after holding therapy. CONCLUSIONS: Cardiac toxicity in our patients was limited to asymptomatic reduction in ejection fraction, sinus bradycardia and tachycardia, reinforcing the need for appropriate monitoring via echocardiography. Prior systemic therapy was associated with decreased EF.