Acellular Human Amniotic Membrane Scaffold with 15d-PGJ2 Nanoparticles in Postinfarct Rat Model.

AimsTo evaluate echocardiographic and biomarker changes during chemotherapy, assess their ability to early detect and predict cardiotoxicity and to define the best time for their evaluation.Methods and resultsSeventy‐two women with breast cancer (52 ± 9.8 years) treated with anthracyclines (26 also with trastuzumab), were evaluated for 14 months (6 echocardiograms/12 laboratory tests). We analysed: high‐sensitivity cardiac troponin T, NT‐proBNP, global longitudinal strain (GLS), left ventricle end‐systolic volume (LVESV), left ventricle end‐diastolic volume (LVEDV), and left ventricular ejection fraction (LVEF). Cardiotoxicity was defined as a reduction in LVEF>10% compared with baseline with LVEF<53%. High‐sensitivity troponin T levels rose gradually reaching a maximum peak at 96 ± 13 days after starting chemotherapy (P < 0.001) and 62.5% of patients presented increased values during treatment. NT‐proBNP augmented after each anthracycline cycle (mean pre‐cycle levels of 72 ± 68 pg/mL and post‐cycle levels of 260 ± 187 pg/mL; P < 0.0001). Cardiotoxicity was detected in 9.7% of patients (mean onset at 5.2 months). In the group with cardiotoxicity, the LVESV was higher compared with those without cardiotoxicity (40 mL vs. 29.5 mL; P = 0.045) at 1 month post‐anthracycline treatment and the decline in GLS was more pronounced (−17.6% vs. −21.4%; P = 0.03). Trastuzumab did not alter serum biomarkers, but it was associated with an increase in LVESV and LVEDV (P < 0.05). While baseline LVEF was an independent predictor of later cardiotoxicity (P = 0.039), LVESV and GLS resulted to be early detectors of cardiotoxicity [odds ratio = 1.12 (1.02–1.24), odds ratio = 0.66 (0.44–0.92), P < 0.05] at 1 month post‐anthracycline treatment. Neither high‐sensitivity troponin T nor NT‐proBNP was capable of predicting subsequent cardiotoxicity.ConclusionsOne month after completion of anthracycline treatment is the optimal time to detect cardiotoxicity by means of imaging parameters (LVESV and GSL) and to determine maximal troponin rise. Baseline LVEF was a predictor of later cardiotoxicity. Trastuzumab therapy does not affect troponin values hence imaging techniques are recommended to detect trastuzumab‐induced cardiotoxicity.

PurposeVentricular function is a powerful predictor of survival in patients with heart failure (HF). However, studies characterizing gated F-18 FDG PET for the assessment of the cardiac function are rare. The aim of this study was to prospectively compare gated F-18 FDG PET and cardiac MRI for the assessment of ventricular volume and ejection fraction (EF) in patients with HF.MethodsEighty-nine patients with diagnosed HF who underwent both gated F-18 FDG PET/CT and cardiac MRI within 3 days were included in the analysis. Left ventricular (LV) end-diastolic volume (EDV), end-systolic volume (ESV), and EF were obtained from gated F-18 FDG PET/CT using the Quantitative Gated SPECT (QGS) and 4D-MSPECT software.ResultsLV EDV and LV ESV measured by QGS were significantly lower than those measured by cardiac MRI (both P<0.0001). In contrast, the corresponding values for LV EDV for 4D-MSPECT were comparable, and LV ESV was underestimated with borderline significance compared with cardiac MRI (P = 0.047). LV EF measured by QGS and cardiac MRI showed no significant differences, whereas the corresponding values for 4D-MSPECT were lower than for cardiac MRI (P<0.0001). The correlations of LV EDV, LV ESV, and LV EF between gated F-18 FDG PET/CT and cardiac MRI were excellent for both QGS (r = 0.92, 0.92, and 0.76, respectively) and 4D-MSPECT (r = 0.93, 0.94, and 0.75, respectively). However, Bland-Altman analysis revealed a significant systemic error, where LV EDV (−27.9±37.0 mL) and ESV (−18.6±33.8 mL) were underestimated by QGS.ConclusionDespite the observation that gated F-18 FDG PET/CT were well correlated with cardiac MRI for assessing LV function, variation was observed between the two imaging modalities, and so these imaging techniques should not be used interchangeably.

ObjectiveLonger QRS duration on the ECG is associated with increased cardiovascular (CV) mortality. To evaluate potential mechanisms, we examined in this study the relationship between QRS duration and left ventricular...

Cardiac magnetic resonance (CMR) has been recognized as the gold standard for the evaluation of left ventricular (LV) function. Cardiac gated PET allows the simultaneous assessment of LV function with the evaluation of myocardial perfusion and metabolism. But the correlations between PET and CMR remain controversial. We conducted a systematic electronic search of PubMed, Embase and the Cochrane Library . Forest plot, spearman correlation analysis and Bland-Altman analysis were used to evaluate the correlations between PET and CMR. Pooled analysis of 13 studies showed that PET underestimated left ventricular end-diastolic volumes (LVEDV) [mean difference (MD), -15.30; 95% confidence interval (CI), -23.10 to -7.50; P < 0.001] and left ventricular end-systolic volumes (LVESV) (MD, -6.20; 95% CI, -12.58 to 0.17; P = 0.06) but not left ventricular ejection fraction (LVEF) (MD, -0.35; 95% CI, -1.75 to 1.06; P = 0.63). Overall, there were very good correlations between PET and CMR measurements for LVEDV ( r , 0.897), LVESV ( r , 0.924) and LVEF ( r , 0.898). Subgroup analysis indicated that LVEDV ≥180 ml and LVEF <40% reduced the accuracy of PET, especially the measurement of LVEF ( r , LVEDV ≥180 vs . r , LVEDV < 180 : 0.821 vs. 0.944; r , LVEF < 40% vs . r , LVEF ≥40% : 0.784 vs. 0.901). Correlations between PET and CMR measurements of LVEDV, LVESV and LVEF were excellent, but these two methods could not be used interchangeably for accurate measurements of LV volume and LVEF in patients with significantly increased LV volume and decreased LVEF.

To evaluate early and dynamic changes of the left ventricular systolic function of patients with septic shock by two-dimensional speckle tracking imaging (2D-STI), and to provide guidance for treatment and prognosis. Fifty-eight septic shock patients admitted to intensive care unit (ICU) of Subei People's Hospital from January 2016 to April 2017 were enrolled. The septic shock patients were given early fluid resuscitation. The left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), early diastolic mitral flow velocity/early diastolic mitral annular peak velocity (E/Em) were obtained by conventional echocardiography, and the left ventricular global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS) were obtained by 2D-STI before fluid resuscitation and 1, 3, 7, 14 days after fluid resuscitation. According to the 28-day survival, the septic shock patients were divided into survival group (38 cases) and death group (20 cases). Thirty normal subjects with age and sex matched were selected as control group. (1) Compared with control group, heart rate (HR) and LVESV were increased [HR (bpm): 92.71±12.51 vs. 73.07±5.52, LVESV (mL): 42.50±7.89 vs. 38.73±4.23, both P < 0.05], while LVEF, GLS, GCS were decreased [LVEF: 0.57±0.06 vs. 0.61±0.03, GLS: (-17.72±1.35)% vs. (-22.07±1.95)%, GCS: (-17.08±1.49)% vs. (-22.98±1.97)%] in septic shock group (all P < 0.01). (2) Compared with the data before fluid resuscitation, heart rate was declined (bpm: 87.83±11.50 vs. 92.71±12.51, P < 0.01), while LVEDV and LVEF were increased [LVEDV (mL): 102.32±9.23 vs. 99.24±8.86, LVEF: 0.59±0.05 vs. 0.56±0.06] in patients of the septic shock after fluid resuscitation (all P < 0.01). (3) With the extension of treatment time, HR, LVEDV, LVESV, E/Em were increased gradually, and LVEF, GLS, GCS, GRS were decreased gradually in dead patients. In septic shock patients, compared with survival group, GCS was significantly different on day 1 [(-15.98±1.41)% vs. (-17.66±1.22)%, P < 0.05], HR, LVEDV, LVESV, GLS were significantly different on the 3rd day [HR (bpm): 104.60±10.94 vs. 88.71±5.06, LVEDV (mL): 109.69±10.00 vs. 103.99±5.74, LVESV (mL): 47.78±7.21 vs. 42.29±5.13, GLS: (-14.44±0.92)% vs. (-16.36±1.00)%, all P < 0.05], LVEF, GRS were significantly different on the 7th day [LVEF: 0.47±0.07 vs. 0.58±0.04, GRS: (28.27±3.23)% vs. (31.48±3.12)%, both P < 0.05], and E/Em was significantly different on the 14th day (12.81±1.56 vs. 10.61±1.27) in dead group (P < 0.05). Our study demonstrates myocardial dysfunction at the early phase in septic shock patients, and 2D-STI GCS can be more sensitive than the conventional echocardiography to determine prognosis. 2D-STI GCS, GLS, GRS were not volume-load dependent parameter. Low levels of GLS, GCS might suggest a poor prognosis.

Is the measurement of left ventricular ejection fraction the proper end point for cell therapy trials? An analysis of the effect of bone marrow mononuclear stem cell administration on left ventricular ejection fraction after ST-segment elevation myocardial infarction when evaluated by cardiac magnetic resonance imaging

BackgroundSodium-glucose co-transporter 2 inhibitors (SGLT2i) have been suggested to exert cardioprotective effects in patients with heart failure, possibly by improving the metabolism of ketone bodies in the myocardium.MethodsThis post hoc analysis of the EMMY trial investigated the changes in serum β-hydroxybutyrate (3-βOHB) levels after acute myocardial infarction (AMI) in response to 26-week of Empagliflozin therapy compared to the usual post-MI treatment. In addition, the association of baseline and repeated measurements of 3-βOHB with cardiac parameters and the interaction effects of Empagliflozin were investigated. Cardiac parameters included N-terminal pro-B-type natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), left ventricle end-systolic volume (LVESV), left ventricle end-diastolic volume (LVEDV), and left ventricular filling pressure (E/é ratio).ResultsThe mean 3-βOHB levels increased from baseline (46.2 ± 3.0 vs. 51.7 ± 2.7) to 6 weeks (48.8 ± 2.2 vs. 42.0 ± 2.3) and 26 weeks (49.3 ± 2.2 vs. 35.8 ± 1.9) in the Empagliflozin group compared to a consistent decline in placebo over 26 weeks (pinteraction < 0.001). Baseline and longitudinal measurements of 3-βOHB were not significantly associated with NT-proBNP and E/é ratio. Baseline 3-βOHB value was negatively associated with LVEF (coefficient: − 0.464, 95%CI − 0.863;− 0.065, p = 0.023), while an increase in its levels over time was positively associated with LVEF (0.595, 0.156;1.035, 0.008). The baseline 3-βOHB was positively associated with LVESV (1.409, 0.186;2.632, 0.024) and LVEDV (0.640, − 1.170;− 2.449, 0.488), while an increase in its levels over time was negatively associated with these cardiac parameters (LVESV: − 2.099, − 3.443;− 0.755, 0.002; LVEDV: − 2.406, − 4.341;− 0.472, 0.015). Empagliflozin therapy appears to modify the association between 3-βOHB, LVEF (pinteraction = 0.090), LVESV (pinteraction = 0.134), and LVEDV (pinteraction = 0.168), particularly at 26 weeks; however, the results were not statistically significant.ConclusionThis post hoc analysis showed that SGLT2i increased 3-βOHB levels after AMI compared to placebo. Higher baseline 3-βOHB levels were inversely associated with cardiac function at follow-up, whereas a sustained increase in 3-βOHB levels over time improved these markers. This highlights the importance of investigating ketone body metabolism in different post-MI phases. Although more pronounced effect of 3-βOHB on cardiac markers was observed in the SGLT2i group, further research is required to explore this interaction effect.

Cardiac resynchronization therapy (CRT) improves LV structure, function, and clinical outcomes in New York Heart Association class III/IV heart failure with prolonged QRS. It is not known whether patients with New York Heart Association class I/II systolic heart failure exhibit left ventricular (LV) reverse remodeling with CRT or whether reverse remodeling is modified by the cause of heart failure. Six hundred ten patients with New York Heart Association class I/II heart failure, QRS duration > or =120 ms, LV end-diastolic dimension > or =55 mm, and LV ejection fraction < or =40% were randomized to active therapy (CRT on; n=419) or control (CRT off; n=191) for 12 months. Doppler echocardiograms were recorded at baseline, before hospital discharge, and at 6 and 12 months. When CRT was turned on initially, immediate changes occurred in LV volumes and ejection fraction; however, these changes did not correlate with the long-term changes (12 months) in LV end-systolic (r=0.11, P=0.31) or end-diastolic (r=0.10, P=0.38) volume indexes or LV ejection fraction (r=0.07, P=0.72). LV end-diastolic and end-systolic volume indexes decreased in patients with CRT turned on (both P<0.001 compared with CRT off), whereas LV ejection fraction in CRT-on patients increased (P<0.0001 compared with CRT off) from baseline through 12 months. LV mass, mitral regurgitation, and LV diastolic function did not change in either group by 12 months; however, there was a 3-fold greater reduction in LV end-diastolic and end-systolic volume indexes and a 3-fold greater increase in LV ejection fraction in patients with nonischemic causes of heart failure. CRT in patients with New York Heart Association I/II resulted in major structural and functional reverse remodeling at 1 year, with the greatest changes occurring in patients with a nonischemic cause of heart failure. CRT may interrupt the natural disease progression in these patients. Clinical Trial Registration- Clinicaltrials.gov Identifier: NCT00271154.

Cardiac Resynchronization Therapy

Background: Galectin-3, is a biomarker believed to reflect cardiac remodeling and fibrosis in patients with heart failure. Spironolactone, has been reported to reduce fibrosis, improve cardiac function and survival in heart failure patients. Whether spironolactone improves remodeling process by altering galectin-3 is unknown. Methods: 14 patients (ejection fraction ≤35, NYHA class II) being treated with guideline base treatments were enrolled to the study. Baseline echocardiographic measurements were noted and serum samples were obtained for galectin-3 levels. After excluding renal failure and hyperkalemia they were prescribed spironolactone, 25 mg daily. Patients were followed during 3 months for side effects. After the third month of follow up, echocardiographic measurements were repeated and serum samples were recollected for galectin-3 levels. Results: The mean age of the patients was 67±11, 64% of the patients were male. Most of the patients (93%) had ischemic cardiomyopathy. Of all, 14% had diabetes, 71% had hypertension. There was no significant change in left atrial diameter, left atrial volume, left ventricular end systolic diameters and myocardial performance indexes. Comparing to baseline measurements, there were significant improvements in left ventricular ejection fraction (30.3±4.6 vs. 31.3±4.5, p=0.04), left ventricular end diastolic diameter (58.9±0.5 vs. 58.2±0.6, p=0.03), left ventricular end diastolic volume (137.2±16.4 vs. 127.8±20.4, p=0.002), left ventricular end systolic volume (95.4±15.3 vs. 88±16.9, p=0.002). Galectin-3 levels decreased significantly after commencing spironolactone treatment (1.49±0.58 vs. 0.98±0.29 p=0.01). Decrease in galectin-3 levels were significantly correlated with the improvements in the left ventricular end diastolic and end systolic volumes (p=0.01 and p=0.02 respectively). Conclusions: Administration of spironolactone to patients with mildly symptomatic heart failure has beneficial effects on left ventricular remodeling and has a correlation with a significant decrease in serum galectin-3 levels. Spironolactone may improve remodeling by altering galectin-3 levels. Larger studies are necessary to evaluate whether these findings have clinical implications.

441: Do elevated NT-proBNP levels of hypertensive pregnant women reflect cardiac dysfunction?

Introduction: New permanent pacemaker (PPM) requirement has been linked with left ventricular dysfunction after TAVR. Objective: We sought to study the impact of new PPM on echocardiographic outcomes after TAVR with SAPIEN-3 (S3) valve. Methods: We included consecutive patients who underwent TAVR with S3 valve at the Cleveland Clinic between April 2015 and December 2018. Patients with prior PPM were excluded. Echocardiograms were reviewed to determine left ventricular ejection fraction (LVEF), left ventricular end diastolic volume index (LVEDVi), left ventricular end systolic volume index (LVESVi), left ventricular dimension during diastole (LVDd), posterior wall thickness during diastole (PWTd), interventricular septum during diastole (IVSd), right ventricular systolic pressure (RVSP), inferior vena cava (IVC) diameter and tricuspid regurgitation (TR) grade. Results: Among 886 patients, the rate of 30-day PPM was 10.2%. Baseline LVEF was similar between new PPM and no PPM (55.4 ± 12.7% vs. 57.2 ± 11.2%; p = 0.188). There were no differences in the other studied echocardiographic parameters at baseline. Among patients with new PPM, LVEF was lower at both 30 days (54.4 ± 11.3% vs. 58.4 ± 10.1%; p = 0.001) and 1 year (54.2 ± 12% vs. 59.1 ± 11.3%; p = 0.009) compared to no PPM with Δ LVEF -0.9% vs. +1.4%; p = 0.023. There were no differences in LVEDVi (52 ± 20.8 vs. 48.3 ± 17.6; p = 0.186) at 1 year. LVESVi was higher with new PPM (24.8 ± 16.1 vs. 20.2 ± 10.9; p = 0.038). However, Δ LVESVi was similar between the 2 groups (-1.6 vs. -2.6; p = 0.517). There were no differences in RVSP (38.9 ± 14.1 vs. 40 ± 14; p = 0.58). LVIDd, PWTd, IVSd and IVC diameter also did not show variations whether patients were paced or not. Moderate to severe TR rates were similar as well (17.7% vs. 21.5%; p = 0.407). Conclusion: Among S3 TAVR recipients, new pacing requirement had a detrimental impact on LVEF at both 30 days and 1 year. However, it did not seem to affect the other studied echocardiographic outcomes after TAVR.

Gated positron emission testing with computed tomography (PET-CT) yields left ventricular (LV) volume analysis along with perfusion analysis. The correlation between PET-CT volumes and cardiac magnetic resonance imaging (CMR) volumes remains unknown. Understanding of the accuracy of these volumes and ejection fractions (EF) by PET is clinically relevant, particularly in the sarcoid population where patients receive initial diagnostic CMR and then are followed by PET for inflammation. 89 patients undergoing cardiac sarcoidosis evaluation with both rest PET-CT and CMR within approximately 1 year were identified at Cleveland Clinic from 2011 to 2021. LV volumes and EF were collected. Linear regression and Bland-Altman analyses were performed. Mean PET-CT derived left ventricular ejection fraction (LVEF) was 46 ± 16% with mean LV end diastolic volume (LVEDV) of 127 ± 60 mL and mean LV end systolic volume (LVESV) of 75 ± 54 mL. Mean CMR-derived LVEF was 47 ± 15% with mean LVEDV of 189 ± 61 mL and mean LVESV of 106 ± 60 mL. Pearson correlation coefficient with standard measurements was 0.85 for EF, 0.80 for LVEDV, and 0.86 for LVESV. In our cohort, there is an excellent correlation of LVEF between PET-CT and CMR with a mean difference of 1.1% and a good correlation of volumes between these two imaging modalities. This has potential clinical implications when judging LVEF qualifications for medical and device therapies although future larger validation cohorts are warranted.

Objective To investigate the clinical value and safety of low molecular weight heparin calcium therapy before interventional therapy in patients with acute myocardial infarction. Methods A total of 110 patients with acute myocardial infarction treated in the Second People’s Hospital of Nanyang from March 2018 to May 2019 were selected. The patients were divided into reference group and observation group by digital random table, 55 cases in each group. Anticoagulant therapy was given to all the patients before coronary intervention, reference group was treated with heparin sodium and observation group was treated with low molecular weight heparin calcium. The number markedly effective, effective, ineffective, and total effective rate during treatment between the two groups were compared. The occurrence of cardiovascular risk events, such as cardiogenic death, reinfarction, malignant heart failure, target vessel revascularization, severe arrhythmia, the occurrence of adverse reactions (mild hemorrhage, thrombocytopenia, severe bleeding), changes of cardiac function associated index, including left ventricular end diastolic volume (LVEDV), left ventricular end systolic volume (LVESV) and left ventricular ejection fraction (LVEF), were observed and compared between the two groups. Results After treatment, the total effective rate of observation group was significantly higher than that of reference group (P 0.05); the incidence of cardiovascular risk events in observation group had fallen (P<0.05); the incidence of adverse reactions in observation group decreased significantly (P<0.05); the levels of cardiac function indexes such as LVEF, LVEDV, LVESV in the two groups improred obviously, the improvement of the observation group was more significant (P<0.05). Conclusions Low molecular weight heparin calcium in treatment of patients with acute myocardial infarction has better outcome, and has great significance in improvement of patients’ heart function, and safety is high, so the clinical application value is very satisfactory. Key words: Acute myocardial infarction; Interventional therapy; Low molecular weight heparin calcium

Regenerative medicine, including cell therapy, is a promising strategy for recovery of the damaged myocardium. C-kit-positive cardiac stem cells (CSCs) have been shown to improve myocardial function after ischemic injury in animal models and in early clinical experience. We used a chronic large animal model of myocardial infarction with substantial reductions in left-ventricular (LV) ejection fraction and adverse remodeling to examine the effect of late autologous CSC intramyocardial injection on long-term cardiac structure and function. Thoracotomy and ligation of the proximal left anterior descending artery, additional diagonal branches, and atrial biopsy for CSC culture were performed in canines. Baseline cardiac MRI was performed at 6 weeks postinfarct followed by repeat thoracotomy for randomization to intramyocardial injection of CSCs (n=13) or vehicle alone (n=6). At 30 weeks postmyocardial infarction, repeat MRI was performed. Data were analyzed using nonparametric tests (Wilcoxon signed-rank and rank-sum tests). In control animals, LV end-systolic volume and end-diastolic volume increased from 6 to 30 weeks (median and interquartile range, 51.3 mL [43.3-57.4] to 76.1 mL [72.0-82.4]; P=0.03 and 78.5 mL [69.7-86.1] to 99.2 mL [97.1-100.4]; P=0.03). Left-ventricular ejection fraction declined further (35.2% [27.9-38.7] to 26.4% [22.0-31.0]; P=0.12). In the cell-treated animals, this late adverse LV remodeling was attenuated (LV end-systolic volume, 42.6 mL [38.5-50.5] to 56.1 mL [50.3-63.0]; P=0.01 versus control). There was a nonsignificant attenuation in the increase in LV end-diastolic volume (64.8 mL [60.7-71.3] to 83.5 mL [74.7-90.8]; P=0.14 versus control) and LV ejection fraction change over time differed (30.5% [28.4-33.4] to 32.9% [28.6-36.9]; P=0.04 versus control). Intramyocardial injection of autologous CSCs in a late phase model of chronic infarction resulted in less increase in LV end-systolic volume and preservation of LV ejection fraction.