Beyond conduction impairment: Unveiling the profound myocardial injury in left bundle branch block.

BACKGROUND: Left bundle branch block (LBBB) represents a frequently encountered conduction system disorder. Despite its widespread occurrence, a continual dilemma persists regarding its intricate association with underlying cardiomyopathy and its pivotal role in the initiation of dilated cardiomyopathy. The pathologic alterations linked to LBBB-induced cardiomyopathy (LBBB-CM) have remained elusive. OBJECTIVE: This study sought to investigate the chronologic dynamics of LBBB to left ventricular dysfunction and the pathologic mechanism of LBBB-CM. METHODS: LBBB model was established through main left bundle branch trunk ablation in 14 canines. All LBBB dogs underwent transesophageal echocardiography and electrocardiography before ablation and at 1 month, 3 months, 6 months, and 12 months after LBBB induction. Single-photon emission computed tomography imaging was performed at 12 months. We then harvested the heart from all LBBB dogs and 14 healthy adult dogs as normal controls for anatomic observation, Purkinje fiber staining, histologic staining, and connexin43 protein expression quantitation. RESULTS: LBBB induction caused significant fibrotic changes in the endocardium and mid-myocardium. Purkinje fibers exhibited fatty degeneration, vacuolization, and fibrosis along with downregulated connexin43 protein expression. During a 12-month follow-up, left ventricular dysfunction progressively worsened, peaking at the end of the observation period. The association between myocardial dysfunction, hypoperfusion, and fibrosis was observed in the LBBB-afflicted canines. CONCLUSION: LBBB may lead to profound myocardial injury beyond its conduction impairment effects. The temporal progression of left ventricular dysfunction and the pathologic alterations observed shed light on the complex relationship between LBBB and cardiomyopathy. These findings offer insights into potential mechanisms and clinical implications of LBBB-CM.

Epigallocatechin-3-gallate protects sepsis-induced myocardial dysfunction by inhibiting the nuclear factor-κB signaling pathway.

Sepsis-induced myocardial dysfunction (SIMD) has become one of the most lethal complications of sepsis, while the treatment was limited by a shortage of pertinent drugs. Epigallocatechin-3-gallate (EGCG) is the highest content of active substances in green tea, and its application in cardiovascular diseases has broad prospects. This study was conducted to test the hypothesis that EGCG was able to inhibit lipopolysaccharide (LPS) induced myocardial dysfunction and investigate the underlying molecular mechanisms. The cardiac systolic function was assessed by echocardiography. The cardiomyocyte apoptosis was determined by TUNEL staining. The expression of inflammatory factors and apoptosis-related protein, cardiac markers were examined by Western Blot and qRT-PCR. EGCG effectively improve LPS-induced cardiac function damage, enhance left ventricular systolic function, and restore myocardial cell vitality. It can effectively inhibit the upregulation of TLR4 expression induced by LPS and inhibit IκB α/NF- κB/p65 signaling pathway, thereby inhibiting cardiomyocyte apoptosis and improving myocarditis. In conclusion, EGCG protects against SIMD through anti-inflammatory and anti-apoptosis effects; it was mediated by the inhibition of the TLR4/NF-κB signal pathway. Our results demonstrated that EGCG might be a possible medicine for SIMD prevention and treatment.

Causal relationship between aspirin consumption and heart failure: a Mendelian randomization study.

AIMS: This study aimed to investigate the causal association of aspirin consumption with the risk of heart failure. METHODS: Our study included a total of 218 208 individuals, with 23 397 cases of heart failure. Genetic summary data on the association between single-nucleotide polymorphisms (SNPs) and aspirin consumption were obtained from a large-scale genome-wide association study involving 462 933 individuals, of which 61 702 people were taking aspirin. After the exclusion of critical confounding factors, we assessed the final and independent association between the aspirin consumption and the risk of heart failure using 3 two-sample Mendelian randomization (MR) methods-inverse variance weighted (IVW), weighted-median, and MR-Egger regression. Sensitivity analyses and directionality test were employed to further validate the stability of the results. RESULTS: After excluding the SNPs that exhibited associations with potential confounders and harmonizing the data, a total of 32 SNPs were finally selected for MR analysis from the initially identified 60 SNPs that displayed strong associations with the exposure. The results of the main method (IVW) showed a significant positive association between aspirin use and the occurrence of heart failure (OR [odds ratio]: 1.085; 95% CI [confidence interval]: 1.015-1.161; P = 0.017), although other methods did not showed statistically significant results (MR-Egger, OR: 1.211, 95% CI: 0.842-1.21, P = 0.896; weighted-median, OR: 1.087, 95% CI: 0.983-1.202, P = 0.105). Heterogeneity test, the MR-Egger intercept, and the funnel plot did not reveal any evidence of heterogeneity (Cochran's Q statistic = 29.263; P = 0.556) or horizontal pleiotropy (intercept = 0.007; P = 0.319). The 'leave-one-out' analysis indicated that no individual SNP exerted a dominant influence on the main estimate. Directionality test confirmed the accuracy of the causal relationship between exposure and outcome direction in our data. CONCLUSIONS: Our results support a potential positive causal relationship between aspirin consumption and the occurrence of heart failure.

Severe thrombocytopenia induced by tirofiban after percutaneous coronary intervention: a case report.

BACKGROUND: Tirofiban is a nonpeptide glycoprotein IIb/IIIa receptor antagonist used widely in patients subjected to percutaneous coronary intervention. While the usage of tirofiban sets an important clinical benefit, severe thrombocytopenia can occur with use of this agent. CASE PRESENTATION: A 76-year-old Chinese man was admitted with 1-month history of sudden onset of chest tightness. He was diagnosed as having subacute inferior myocardial infarction, and percutaneous coronary intervention was performed. After the procedure, patient received tirofiban at 0.15 µg/kg/minute for 4 h. A blood sample was obtained for a complete blood count; severe thrombocytopenia was reported according to routine orders at our hospital. All antiplatelet drugs including tirofiban, aspirin, and clopidogrel were immediately discontinued. The patient received platelet transfusions and was treated with immunoglobulin G. Two days later, the patient's platelet count had increased to 75 × 109/L. There was a significant improvement after day 5, and the platelet count was 112 × 109/L. Seven days after the acute thrombocytopenia, he was discharged with normal platelet count. CONCLUSIONS: Clinicians should be particularly aware of tirofiban-induced thrombocytopenia in routine practice.

The influence of arm positions on mechanical dyssynchrony measured by gated myocardial perfusion imaging.

Background: In routine procedures, patient's arms are positioned above their heads to avoid potential attenuation artifacts and reduced image quality during gated myocardial perfusion imaging (G-MPI). However, it is difficult to achieve this action in the acute period following pacemaker implantation. This study aimed to explore the influence of arm positioning on myocardial perfusion imaging (MPI) in different types of heart disease. Methods: This study was conducted retrospectively. A total of 123 patients were enrolled and underwent resting G-MPI using a standard protocol with arms positioned above their heads and again with their arms at their sides. All individuals were divided into 3 groups: the normal group, the obstructive coronary artery disease (O-CAD) group, and the dilated cardiomyopathy (DCM) group. The G-MPI data were measured by QGS software and Emory Reconstruction Toolbox, including left ventricular ejection fraction (LVEF), end-diastolic volume (EDV), end-systolic volume (ESV), extent, total perfusion deficit (TPD), summed rest score (SRS), scar burden, phase standard deviation (SD), and phase histogram bandwidth (BW). Results: In total, extent, TPD, EDV, ESV, LVEF, systolic SD, systolic BW, diastolic SD, and diastolic BW were all significantly different between the 2 arm positions (all P<0.01). On the Bland-Altman analysis, both EDV and ESV with the arm-down position were significantly underestimated (P<0.001). Meanwhile, TPD, extent, and LVEF with the arm-down position were significantly overestimated (P<0.05). Systolic SD, systolic BW, diastolic SD, and diastolic BW were systematically overestimated (P<0.001). In the DCM group (n=52), EDV, ESV, systolic SD, systolic BW, diastolic SD, and diastolic BW were identified as significantly different by the paired t-test between the 2 arm positions (P<0.05). In the O-CAD group (n=32), scar burden, ESV, LVEF, and diastolic BW were significantly different between the 2 arm positions (P<0.05). Conclusions: Systolic and diastolic dyssynchrony parameters and most left ventricular (LV) functional parameters were significantly influenced by arm position in both normal individuals and patients with heart failure (HF) with different pathophysiologies. More attention should be given to LV dyssynchrony data during clinical evaluation of cardiac resynchronization therapy (CRT) implantation procedure.

Association between CZT­SPECT myocardial blood flow and coronary stenosis: A cross­sectional study.

The association between the quantitative and semi-quantitative parameters of myocardial blood flow obtained using cadmium-zinc-telluride single photon emission computed tomography (CZT-SPECT) and coronary stenosis remains unclear. Therefore, the objective of the present study was to evaluate the diagnostic value of two parameters obtained using CZT-SPECT in patients with suspected or known coronary artery disease. A total of 24 consecutive patients who underwent CZT-SPECT and coronary angiography within 3 months of each other were included in the study. To evaluate the predictive ability of the regional difference score (DS), coronary flow reserve (CFR), and the combination thereof for positive coronary stenosis at the vascular level, receiver operating characteristic (ROC) curves were plotted and the area under the curves (AUCs) were calculated. Comparisons of the reclassification ability for coronary stenosis between different parameters were assessed by calculating the net reclassification index (NRI) and the integrated discrimination improvement (IDI). The 24 participants (median age: 65 years; range: 46-79 years; 79.2% male) included in this study had a total of 72 major coronary arteries. When stenosis ≥50% was defined as the criteria for positive coronary stenosis, the AUCs and the 95% confidence interval (CI) for regional DS, CFR, and the combination of the two indices were 0.653 (CI, 0.541-0.766), 0.731 (CI, 0.610-0.852) and 0.757 (CI, 0.645-0.869), respectively. Compared with single DS, the combination of DS and CFR increased the predictive ability for positive stenosis, with an NRI of 0.197-1.060 (P<0.01) and an IDI of 0.0150-0.1391 (P<0.05). When stenosis ≥75% was considered as the criteria, the AUCs were 0.760 (CI, 0.614-0.906), 0.703 (CI, 0.550-0.855), and 0.811 (CI, 0.676-0.947), respectively. Compared with DS, CFR had an IDI of -0.3392 to -02860 (P<0.05) and the combination of DS and CFR also enhanced the predictive ability, with an NRI of 0.0313-1.0758 (P<0.01). In conclusion, both regional DS and CFR had diagnostic values for coronary stenosis, but the diagnostic abilities differed in distinguishing between different degrees of stenosis, and the efficiency was improved with a combination of DS and CFR.

Texture analysis of SPECT myocardial perfusion provides prognostic value for dilated cardiomyopathy.

BACKGROUND: Texture analysis (TA) has demonstrated clinical values in extracting information, quantifying inhomogeneity, evaluating treatment outcomes, and predicting long-term prognosis for cardiac diseases. The aim of this study was to explore whether TA of SPECT myocardial perfusion could contribute to improving the prognosis of dilated cardiomyopathy (DCM) patients. METHODS: Eighty-eight patients were recruited in our study between 2009 and 2020 who were diagnosed with DCM and underwent single-photon emission tomography myocardial perfusion imaging (SPECT MPI). Forty TA features were obtained from quantitative analysis of SPECT imaging in subjects with myocardial perfusion at rest. All patients were divided into two groups: the all-cause death group and the survival group. The prognostic value of texture parameters was assessed by Cox regression and Kaplan-Meier analysis. RESULTS: Twenty-five all-cause deaths (28.4%) were observed during the follow-up (39.2±28.7 months). Compared with the survival group, NT-proBNP and total perfusion deficit (TPD) were higher and left ventricular ejection fraction (LVEF) was lower in the all-cause death group. In addition, 26 out of 40 texture parameters were significantly different between the two groups. Univariate Cox regression analysis revealed that NT-proBNP, LVEF, and 25 texture parameters were significantly associated with all-cause death. The multivariate Cox regression analysis showed that low gray-level emphasis (LGLE) (P = 0.010, HR = 4.698, 95% CI 1.457-15.145) and long-run low gray-level emphasis (LRLGE) (P =0.002, HR = 6.085, 95% CI 1.906-19.422) were independent predictors of the survival outcome. When added to clinical parameters, LVEF, TPD, and TA parameters, including LGLE and LRLGE, were incrementally associated with all-cause death (global chi-square statistic of 26.246 vs. 33.521; P = 0.028, global chi-square statistic of 26.246 vs. 34.711; P = 0.004). CONCLUSION: TA based on gated SPECT MPI could discover independent prognostic predictors of all-cause death in medically treated patients with DCM. Moreover, TA parameters, including LGLE and LRLGE, independent of the total perfusion deficit of the cardiac myocardium, appeared to provide incremental prognostic value for DCM patients.

Association between energy intake patterns and outcome in US heart failure patients.

Background: The association between dietary energy patterns, calories, and the outcomes of heart failure (HF) is still unclear. Objectives: To evaluate the proper energy intake patterns and daily calorie intake in patients with heart failure among US adults. Methods: The data were derived from the 2001-2014 National Health and Nutrition Examination Survey (NHANES). A calorie intake pattern variable was created using latent class analysis (LCA) based on the calorie ratio of three major nutrients. Cox proportional hazard regression models were used to evaluate the hazard ratios (HR) and 95% confidence intervals (CI) of the association between calorie intake and energy patterns. The primary endpoint was all-cause mortality. Results: Among 991 participants (mean age 67.3 ± 12.9 years; 55.7% men) who suffered from heart failure; the median calorie intake was 1,617 kcal/day [interquartile range (IQR): 1,222-2,154 kcal/day]. In the multivariable-adjusted model, moderate malnutrition was more frequent to death (HR: 2.15; 95% CI: 1.29-3.56). Low-carbohydrate pattern (LCP) and median-carbohydrate pattern (MCP) had lower risks of death compared to high-carbohydrate pattern (HCP) (LCP: HR: 0.76; 95% CI: 0.59-0.97; MCP: HR: 0.77; 95% CI: 0.60-0.98). No association between different amounts of calorie intake and all-cause mortality was found. There was an adjusted significant interaction between calorie intake and energy intake patterns (p = 0.019). There was a linear relationship between energy intake through HCP and all-cause mortality (p for non-linear = 0.557). A non-linear relationship between energy intake through MCP and all-cause mortality (p for non-linear = 0.008) was observed. Conclusion: Both LCP and MCP, compared to HCP, were associated with better outcomes in the HF population. The relationship between energy intake and all-cause death may be influenced by energy intake patterns in HF patients.

Application of medical imaging methods and artificial intelligence in tissue engineering and organ-on-a-chip.

Organ-on-a-chip (OOC) is a new type of biochip technology. Various types of OOC systems have been developed rapidly in the past decade and found important applications in drug screening and precision medicine. However, due to the complexity in the structure of both the chip-body itself and the engineered-tissue inside, the imaging and analysis of OOC have still been a big challenge for biomedical researchers. Considering that medical imaging is moving towards higher spatial and temporal resolution and has more applications in tissue engineering, this paper aims to review medical imaging methods, including CT, micro-CT, MRI, small animal MRI, and OCT, and introduces the application of 3D printing in tissue engineering and OOC in which medical imaging plays an important role. The achievements of medical imaging assisted tissue engineering are reviewed, and the potential applications of medical imaging in organoids and OOC are discussed. Moreover, artificial intelligence - especially deep learning - has demonstrated its excellence in the analysis of medical imaging; we will also present the application of artificial intelligence in the image analysis of 3D tissues, especially for organoids developed in novel OOC systems.

Three-dimensional Fusion of Myocardial Perfusion SPECT and Invasive Coronary Angiography Guides Coronary Revascularization.

BACKGROUND: SPECT myocardial perfusion imaging (SPECT MPI) and invasive coronary angiography (ICA) provide complementary clinical information in the diagnosis of coronary artery disease (CAD). We have developed an approach for 3D fusion of perfusion data from SPECT MPI and coronary anatomy from ICA. In this study, we aimed to evaluate its clinical value when compared to the traditional side-by-side readings. METHODS: Thirty-six CAD patients who had at least one stenosis ≥ 50% were retrospectively enrolled. Based on the presence of a perfusion defect in a territory subtended by a coronary vessel, all vessels were classified as matched, unmatched, or normal groups via both the fusion and side-by-side analysis. The treatments recommended by the fusion and side-by-side analysis were compared with those that the patients received. Major adverse cardiac events (MACE), defined as all-cause death, myocardial infarction, unstable angina requiring hospitalization, and unplanned revascularization, were assessed. RESULTS: The overall vessel-based concordance was 78.7% between the fusion and side-by-side analysis. Compared with the side-by-side analysis, 23 coronary arteries (29 equivocal segments) of 19 patients were reclassified via fusion of data. In the matched, unmatched, and normal groups, the numbers of vessels with hemodynamically significant stenosis which caused reversible defect were 37 vs 53, 28 vs 14, and 43 vs 41 (P < .01) when comparing the side-by-side analysis with the fusion, and the revascularization ratios per vessel were 69% vs 88%, 29% vs 10%, and 2% vs 2% between them. During the five-year follow-up, 8 patients (22.2%) experienced MACE. Patients who received the same treatment as the guidance of 3D fusion results (n = 22) had superior outcomes when compared with those who did not (n = 14) (P < .01). CONCLUSIONS: Compared with the side-by-side analysis, the 3D fusion of SPECT MPI and ICA provided incremental diagnostic and prognostic value.

Predictive values of left ventricular mechanical dyssynchrony for CRT response in heart failure patients with different pathophysiology.

BACKGROUND: Cardiac resynchronization therapy (CRT) patients with different pathophysiology may influence mechanical dyssynchrony and get different ventricular resynchronization and clinical outcomes. METHODS: Ninety-two dilated cardiomyopathy (DCM) and fifty ischemic cardiomyopathy (ICM) patients with gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) were included in this retrospective study. Patients were classified based on the concordance between the left ventricular (LV) lead and the latest contraction or relaxation position. If the LV lead was located on or adjacent to both the latest contraction and relaxation position, the patient was categorized into the both match group; if the LV lead was located on or adjacent to the latest contraction or relaxation position, the patient was classified into the one match group; if the LV lead was located on or adjacent to neither the latest contraction nor relaxation position, the patient was categorized to the neither group. CRT response was defined as [Formula: see text] improvement of LV ejection fraction at the 6-month follow-up. Variables with P < .05 in the univariate analysis were included in the stepwise multivariate model. RESULTS: During the follow-up period, 58.7% (54 of 92) for DCM patients and 54% (27 of 50) for ICM patients were CRT responders. The univariate analysis and stepwise multivariate analysis showed that QRS duration, systolic phase bandwidth (PBW), diastolic PBW, diastolic phase histogram standard deviation (PSD), and left ventricular mechanical dyssynchrony (LVMD) concordance were independent predictors of CRT response in DCM patients; diabetes mellitus and left ventricular end-systolic volume were significantly associated with CRT response in ICM patients. The intra-group comparison revealed that the CRT response rate was significantly different in the both match group of DCM (N = 18, 94%) and ICM (N = 24, 62%) patients (P = .016). However, there was no significant difference between DCM and ICM in the one match and neither group. For the inter-group comparison, Kruskal-Wallis H-test revealed that CRT response was significantly different in all the groups of DCM patients (P < .001), but not in ICM patients (P = .383). CONCLUSIONS: Compared with ICM patients, systolic PBW, diastolic PBW and PSD have better predictive and prognostic values for the CRT response in DCM patients. Placing the LV lead in or adjacent to the latest contraction and relaxation position can improve the clinical outcomes of DCM patients, but it does not apply to ICM patients.

Comparison of left ventricular mechanical dyssynchrony parameters between exercise and adenosine triphosphate stress tests using gated single-photon emission computed tomography myocardial perfusion imaging.

BACKGROUND: Left ventricular mechanical dyssynchrony (LVMD) can be induced after stress test. However, no studies have compared the influence of different stress­inducing methods on LVMD parameters. AIMS: The aim of the study was to determine whether there is a difference between exercise and adenosine triphosphate (ATP) stress tests in terms of changes in LVMD parameters assessed using gated single­photon emission computed tomography myocardial perfusion imaging (GSPECT MPI). METHODS: A total of190 patients who underwent 99mTc ­sestamibi GSPECT MPI were consecutively enrolled. Treadmill exercise and ATP stress tests were performed in 95 patients each. Normal myocardial perfusion was defined as the summed stress score (SSS) ≤3 and summed rest score (SRS) ≤3, myocardial ischemia as SSS >3 and SRS ≤3, and myocardial infarction as SSS >3 and SRS >3. Parameters of LVMD, including phase standard deviation (PSD), phase bandwidth (PBW), skewness, and kurtosis were compared. Subtraction was made between values during stress and rest phases to acquire ∆PSD, ∆PBW, ∆skewness, and ∆kurtosis Results: There were no differences in LVMD parameters between the exercise and ATP groups. The same results were obtained in the normal perfusion, ischemia, and infarction subgroups. Furthermore, no differences were observed in ∆PSD (median [interquartile range, IQR], 0.25 [-2.3 to 3.1] vs 0.42 (-1.7 to 3.1]; P = 0.73), ∆PBW (median [IQR], 1 [-7 to 11] vs 1 [-6 to 11]; P = 0.95), ∆skewness (mean [SD], -0.06 [0.63] vs 0 [0.81]; P = 0.53), and ∆kurtosis (median [IQR], -0.47 [-4.2 to 4.3] vs -0.42 [-4.8 to 5.2]; P = 0.73) between the exercise and ATP stress­inducing methods. CONCLUSIONS: There are no differences between the exercise and ATP stress tests in terms of changes in LVMD parameters. Thus, the 2 methods can be used alternatively.

Left ventricular systolic and diastolic dyssynchrony to improve cardiac resynchronization therapy response in heart failure patients with dilated cardiomyopathy.

BACKGROUND: The systolic and diastolic dyssynchrony is physiologically related, but measure different left ventricular mechanisms. Left ventricular systolic mechanical dyssynchrony (systolic LVMD) has shown significant clinical values in improving cardiac resynchronization therapy (CRT) response in the heart failure patients with dilated cardiomyopathy (DCM). Our recent study demonstrated that LV diastolic dyssynchrony (diastolic LVMD) parameters have important prognostic values for DCM patients. However, there are a limited number of studies about the clinical value of diastolic LVMD for CRT. This study aims to explore the predictive values of both systolic LVMD and diastolic LVMD for CRT in DCM patients. METHODS: Eighty-four consecutive CRT patients with both DCM and complete left bundle branch block (CLBBB) who received gated resting SPECT MPI at baseline were included in the present study. The phase analysis technique was applied on resting gated short-axis SPECT MPI images to measure systolic LVMD and diastolic LVMD, characterized by phase standard deviation (PSD) and phase histogram bandwidth (PBW). CRT response was defined as ≥ 5% improvement of LVEF at 6-month follow-up. Variables with P < 0.10 in the univariate analysis were included in the multivariate cox analysis. RESULTS: During the follow-up period, 59.5% (50 of 84) patients were CRT responders. The univariate cox regression analysis showed that at baseline QRS duration, non-sustained ventricular tachycardia (NS-VT), systolic PSD, systolic PBW, diastolic PSD, diastolic PBW, scar burden and LV lead in the scarred myocardium were statistically significantly associated with CRT response. The multivariate cox regression analysis showed that QRS duration, NS-VT, systolic PSD, systolic PBW, diastolic PSD, and diastolic PBW were independent predictive factors for CRT response. Furthermore, the rate of CRT response was 94.4% (17 of 18) in patients whose LV lead was in the segments with both the first three late contraction and the first three late relaxation; by contrast, the rate of CRT response was only 6.7% (1 of 15, P < 0.000) in patients whose LV lead was in the segments with neither the first three late contraction nor the first three late relaxation. CONCLUSION: Both systolic LVMD and diastolic LVMD from gated SPECT MPI have important predictive values for CRT response in DCM patients. Pacing at LV segments with both late contraction and late relaxation has potential to increase the CRT response.

Exercise electrocardiography combined with stress echocardiography for predicting myocardial ischemia in adults.

Myocardial ischemia (MI) has the highest mortality rate in the world. Traditional noninvasive MI examinations include exercise electrocardiography tests (EETs) and stress echocardiography (SE). Treadmill and dobutamine tests are commonly used as stress protocols. In the present study, 278 patients with suspected MI were examined, 66 of whom were diagnosed with MI and 212 did not show evidence of MI by coronary angiography (CAG)/coronary CT angiography (CCTA). All patients underwent clinical EET and SE evaluations prior to CAG/CCTA. All groups were compared based on specific clinical parameters including age, sex, blood pressure, heart rate, blood oxygen saturation, underlying conditions and ejection fraction/fraction shortening. The data indicated superior diagnostic efficiency of the combined EET+SE method for the diagnosis of suspected MI compared with either EET or SE alone. The sensitivity/specificity/positive predictive value and negative predictive value for detecting MI were excellent compared with those of traditional examinations. The diagnostic efficiency of the combination analysis may reduce the prevalence of MI and medical costs. The present study provided novel insight for the development of methods that may be used for MI detection and prediction.

Treatment with 24 hour istaroxime infusion in patients hospitalised for acute heart failure: a randomised, placebo-controlled trial.

AIM: Istaroxime is a first-in-class agent which acts through inhibition of the sarcolemmal Na+ /K+ pump and activation of the SERCA2a pump. This study assessed the effects of a 24 h infusion of istaroxime in patients hospitalised for acute heart failure (AHF). METHODS AND RESULTS: We included patients hospitalised for AHF with left ventricular ejection fraction ≤40% and E/e' > 10. Patients were randomised to a 24 h intravenous infusion of placebo or istaroxime at doses of 0.5 µg/kg/min (cohort 1: placebo n = 19; istaroxime n = 41) or 1.0 µg/kg/min (cohort 2: placebo n = 20, istaroxime n = 40). The primary endpoint of change in E/e' ratio from baseline to 24 h decreased with istaroxime vs. placebo (cohort 1: -4.55 ± 4.75 istaroxime 0.5 µg/kg/min vs. -1.55 ± 4.11 placebo, P = 0.029; cohort 2: -3.16 ± 2.59 istaroxime 1.0 µg/kg/min vs. -1.08 ± 2.72 placebo, P = 0.009). Both istaroxime doses significantly increased stroke volume index and decreased heart rate. Systolic blood pressure increased with istaroxime, achieving significance with the high dose. Self-reported dyspnoea and N-terminal pro-brain natriuretic peptide improved in all groups without significant differences between istaroxime and placebo. No significant differences in cardiac troponin absolute values or clinically relevant arrhythmias were observed during or after istaroxime infusion. Serious cardiac adverse events (including arrhythmias and hypotension) did not differ between placebo and istaroxime groups. The most common adverse events were injection site reactions and gastrointestinal events, the latter primarily with istaroxime 1.0 µg/kg/min. CONCLUSIONS: In patients hospitalised for AHF with reduced ejection fraction, a 24 h infusion of istaroxime improved parameters of diastolic and systolic cardiac function without major cardiac adverse effects.

A learning-based automatic segmentation and quantification method on left ventricle in gated myocardial perfusion SPECT imaging: A feasibility study.

BACKGROUND: The performance of left ventricular (LV) functional assessment using gated myocardial perfusion SPECT (MPS) relies on the accuracy of segmentation. Current methods require manual adjustments that are tedious and subjective. We propose a novel machine-learning-based method to automatically segment LV myocardium and measure its volume in gated MPS imaging without human intervention. METHODS: We used an end-to-end fully convolutional neural network to segment LV myocardium by delineating its endocardial and epicardial surface. A novel compound loss function, which encourages similarity and penalizes discrepancy between prediction and training dataset, is utilized in training stage to achieve excellent performance. We retrospectively investigated 32 normal patients and 24 abnormal patients, whose LV myocardial contours automatically segmented by our method were compared with those delineated by physicians as the ground truth. RESULTS: The results of our method demonstrated very good agreement with the ground truth. The average DSC metrics and Hausdorff distance of the contours delineated by our method are larger than 0.900 and less than 1 cm, respectively, among all 32 + 24 patients of all phases. The correlation coefficient of the LV myocardium volume between ground truth and our results is 0.910 ± 0.061 (P < 0.001), and the mean relative error of LV myocardium volume is - 1.09 ± 3.66%. CONCLUSION: These results strongly indicate the feasibility of our method in accurately quantifying LV myocardium volume change over the cardiac cycle. The learning-based segmentation method in gated MPS imaging has great promise for clinical use.

Prognostic value of left-ventricular systolic and diastolic dyssynchrony measured from gated SPECT MPI in patients with dilated cardiomyopathy.

BACKGROUND: Left-ventricular systolic dyssynchrony (LVSD) has been an important prognostic factor in the patients with dilated cardiomyopathy (DCM). However, the association between the LV diastolic dyssynchrony (LVDD) and clinical outcome is not well established. This study aims to evaluate the prognostic values of both systolic and diastolic dyssynchrony in patients with DCM. METHODS: Fifty-two patients with DCM were enrolled and divided into two groups according to cardiac deaths from the follow-up data. The phase-analysis technique was applied on resting gated short-axis SPECT MPI images to measure LV systolic and diastolic dyssynchrony, including phase standard deviation (PSD), phase histogram bandwidth (PBW), and phase entropy (PE). Variables with P < 0.10 in the univariate analysis were included in the multivariate cox analysis. RESULTS: During the follow-up period (2.9 ± 1.7 years), 18 (34.6%) cardiac deaths were observed. Compared with survivors, patients with cardiac death had lower LVEF (P = 0.011), and more severe LV systolic and diastolic dyssynchrony. The univariate cox regression analysis showed that hypertension, NT-proBNP, LVEF, systolic PSD, systolic PE, and diastolic PBW were statistically significantly associated with cardiac death. The multivariate cox regression analysis showed that systolic PE and diastolic PE were independent predictive factors for cardiac death. Furthermore, the receiver operating characteristic (ROC) analysis, when applied into the combination of systolic PE and diastolic PE for predicting cardiac death, had an area under curve (AUC) of 0.766, a sensitivity of 0.765, and a specificity of 0.722. CONCLUSIONS: Both the LVSD and LVDD parameters from SPECT MPI have important prognostic values for DCM patients. Both systolic PE and diastolic PE are independent prognostic factors for cardiac death.

p27kip1 haploinsufficiency preserves myocardial function in the early stages of myocardial infarction via Atg5­mediated autophagy flux restoration.

Myocardial infarction (MI) is a leading cause of mortality in adults worldwide. Over the last two decades, gene therapy has been a hot topic in cardiology, and there has been a focus on cell cycle inhibitors and their protective effects on the myocardium post­MI. In our previous study, the haploinsufficiency of p27kip1 (p27) was demonstrated to improve cardiac function in mice post­MI by promoting angiogenesis and myocardium protection through the secretion of growth factors. Autophagy is an adaptive response of cells to environmental changes, such as nutrient deprivation, ischemia and hypoxia. The appropriate regulation of autophagy may improve myocardial function by preventing apoptosis of cardiomyocytes. In this study, we used immunoassays, transmission electron microscopy and cardiac ultrasound to confirm that p27 haploinsufficiency prevents myocardial apoptosis by restoring autophagy protein 5­mediated autophagy flux in the early stages of MI. The present study provides a novel method for studying MI or ischemic heart disease therapy.

Comparative proteomic analysis of plasma of children with congenital heart disease.

Congenital heart disease is one of the largest class of birth defects. Eight subjects with ventricular septal defect (VSD, a kind of congenital heart disease) and 11 health children were enrolled in tandem mass tags label-based quantitative proteomic analysis to compare plasma proteins differentially abundance. A total of 66 proteins were significantly upregulated or downregulated in VSD patients compared with healthy children. These proteins were involved in pathways linked to platelet activation, fructose and mannose metabolism, complement and coagulation cascades, glycolysis/gluconeogenesis, regulation of actin cytoskeleton, and carbon metabolism. The amount of ten proteins changed significantly (p < 0.05) in newly recruited 30 VSD compared with 15 control children, which were validated by ELISA. The areas under the receiver operating characteristic curve values of fructose-bisphosphate aldolase B (ALDOB) and thymosin beta-4 (Tß4) were higher than those of other candidate proteins. ALDOB and Tß4 might be potential biomarkers applied for identifying VSD in the further works.