Systolic blood pressure time in target range and long-term outcomes in patients with ischemic cardiomyopathy.

BACKGROUND: The relationship between the degree of systolic blood pressure (SBP) control and outcomes remains unclear in patients with ischemic cardiomyopathy (ICM). Current control metrics may not take into account the potential effects of SBP fluctuations over time on patients. METHODS: This study was a post-hoc analysis of the surgical treatment of ischemic heart failure trial which enrolled 2,136 participants with ICM. Our SBP target range was defined as 110 to 130 mm Hg and the time in target range (TTR) was calculated by linear interpolation. RESULTS: A total of 1,194 patients were included. Compared with the quartile 4 group (TTR 77.87%-100%), the adjusted hazard ratios and 95% confidence intervals of all-cause mortality were 1.32 (0.98-1.78) for quartile 3 group (TTR 54.81%-77.63%), 1.40 (1.03-1.90) for quartile 2 group (TTR 32.59%-54.67%), and 1.53 (1.14-2.04) for quartile 1 group (TTR 0%-32.56%). Per 29.28% (1-SD) decrement in TTR significantly increased the risk of all-cause mortality (1.15 [1.04-1.26]). Similar results were observed in the cardiovascular (CV) mortality and the composite outcome of all-cause mortality plus CV rehospitalization, and in the subgroup analyses of either coronary artery bypass grafting or medical therapy, and different baseline SBP. CONCLUSIONS: In patients with ICM, the higher TTR was significantly associated with decreased risk of all-cause mortality, CV mortality and the composite outcome of all-cause mortality plus CV rehospitalization, regardless of whether the patient received coronary artery bypass grafting or medical therapy, and the level of baseline SBP. TTR may be a surrogate metric of long-term SBP control in patients with ICM.

Risk factors for mortality in surgical patients on combined continuous renal replacement therapy and extracorporeal membrane oxygenation: single-center retrospective study.

OBJECTIVE: In patients receiving extracorporeal membrane oxygenation (ECMO), continuous renal replacement therapy (CRRT) is increasingly being used for renal replacement and fluid management. However, critically ill surgical patients receiving combined ECMO and CRRT tend to have a high mortality rate, and there are limited studies on this population. Therefore, we aimed to investigate the risk factors for mortality in surgical patients receiving combined ECMO and CRRT. METHODS: Data of surgical patients who underwent ECMO between December 2013 and April 2023 were retrospectively reviewed. Univariate and multivariate logistic regression analysis were used to identify the risk variables. Receiver operating characteristic (ROC) curve analysis was used to determine the cutoff value of albumin and age to predict death. RESULTS: A total of 199 patients on ECMO support were screened, of which 105 patients were included in the final analysis. Of 105 patients, 77 (73.33%) were treated with CRRT. Veno-arterial ECMO was performed in 97 cases (92.38%), and the rest were veno-venous ECMO (n = 8, 7.62%). Cardiovascular-related surgery was performed in the main patients (n = 86, 81.90%) and other types of surgery in 19 patients. In surgical patients on ECMO support, the logistic regression analysis showed that CRRT implantation, male sex, and age were the independent risks factors for mortality. Furthermore, the ROC curve analysis showed that age 48.5 years had the highest Youden index. In surgical patients on combined CRRT and ECMO, age, valvular heart disease, and albumin were the independent risk factors for prognosis. Albumin had the highest Youden index at a cutoff value of 39.95 g/L for predicting mortality, though the overall predictive value was modest (area under ROC 0.704). Age had the highest Youden index at a cutoff value of 48.5 years for predicting mortality. CONCLUSIONS: In our cohort of surgical patients requiring ECMO, which consisted mostly of patients undergoing cardiovascular surgery requiring VA-ECMO, the need for CRRT was an independent risk factor for mortality. In the subset of patients on combined CRRT and ECMO, independent risk factors for mortality included higher age, lack of valvular heart disease, and lower serum albumin.

Novel physiologic nomogram discriminates symptom outcome in patients with erosive esophagitis.

BACKGROUND AND AIM: Most of patients with erosive esophagitis (EE) are of LA grade A&B with low reflux burden, therefore require further esophageal function tests (EFTs). One-third of them respond poorly to pump proton inhibitor (PPI) treatment. The aim was to establish and validate a physiologic nomogram to discriminate symptom outcome to PPI treatment in patients with EE. METHODS: A total of 79 EE patients with heartburn who underwent EFTs and received PPI therapy were randomly assigned into a training set (n = 55) and a validation set (n = 24). Clinical data including physiologic parameters from EFTs were collected. Significant factors for the positive symptomatic outcome were identified using logistic regression analysis. Physiologic signature was developed using the least absolute shrinkage and selection operator algorithm. The nomogram was established by combining significant factors and physiologic signature, and its performance was evaluated and validated in the training and validation set. The clinical value of the nomogram was measured by decision curve analysis. RESULTS: Significant factors for positive symptomatic response to PPI treatment were identified as follows: acid exposure time, total number of reflux episodes, and two novel metrics including mean nocturnal baseline impedance and post-reflux swallow-induced peristaltic wave index. The nomogram which incorporated both significant factors and physiologic signature demonstrated good performance in the training and validation sets [C-index: 0.938 (95% CI 0.882-0.995); 0.839 (95% CI 0.678-0.995), respectively]. Decision curves showed significant clinical usefulness. CONCLUSION: The first physiologic nomogram was developed to discriminate the individualized response to PPI therapy among EE patients.

M2b Macrophages Regulate Cardiac Fibroblast Activation and Alleviate Cardiac Fibrosis After Reperfusion Injury.

BACKGROUND: Macrophages play an important role in the development of cardiac fibrosis. However, the roles of different macrophage subtypes in cardiac fibroblast (CF) activation and cardiac fibrosis are unknown.Methods and Results:Bone marrow-derived macrophages (BMDMs) were treated with different stimuli to induce differentiation into M1, M2a, M2b, and M2c macrophage subtypes. CFs were co-cultured with different subtypes of macrophages or cultured with macrophage supernatants. Results revealed that M2b macrophages significantly suppressed the proliferation and migration of CFs, the expression of fibrosis-related proteins (collagen I [COL-1] and α-smooth muscle actin [α-SMA]), and differentiation into cardiac myofibroblasts (MFs). The opposite effects were observed with M2a macrophages. A rat model of cardiac ischemia/reperfusion (I/R) injury was used to determine the effect of M2b macrophages transplantation. After cardiac I/R injury, transplantation of M2b macrophages improved cardiac function and reduced cardiac fibrosis. The effect of macrophage subtypes on p-ERK, ERK, p-p38, and p38 phosphorylation was examined by Western blotting. The results showed that M2b macrophages significantly inhibited the mitogen-activated protein kinase (MAPK) signaling pathway. CONCLUSIONS: These study results demonstrate for the first time that different subtypes of macrophages have different roles in regulating CF activation. M2b macrophages inhibit CF activation, and thus can be considered anti-fibrotic macrophages. M2a macrophages promote CF activation, and thus are pro-fibrotic macrophages.

A study of proximal esophageal baseline impedance in identifying and predicting laryngopharyngeal reflux.

BACKGROUND AND AIM: Laryngopharyngeal reflux (LPR) is caused by the reflux of gastric contents beyond the esophagus into the larynx and pharynx. However, upper esophageal sphincter (UES) motility and proximal esophagus reflux parameters are poorly studied. This study aims to explore the characteristics of UES motility and reflux parameter among LPR patients. METHODS: Patients with laryngopharyngeal symptoms only (L), patients with laryngopharyngeal symptoms and typical esophageal symptoms (L + E), patients with typical esophageal symptoms only (E), and healthy controls (H) were retrospectively included. Physiological profiles were studied and compared among groups using both high-resolution manometry and pH-impedance monitoring, including UES basal pressure, residual pressure, relaxation duration time, recovery time, the time to nadir pressure, UES length, proximal contractile integral, and proximal mean nocturnal baseline impedance (MNBI). Patients' symptom outcomes were also analyzed. RESULTS: A total of 242 patients were included. Proximal MNBI was significantly lower in patients with both laryngopharyngeal and esophageal symptoms (17 cm above low esophageal sphincter [LES]: L vs L + E vs E vs H = 3689.7 vs 2500.0 vs 3073.0 vs 3996.0; 15 cm above LES: L vs L + E vs E vs H = 3155.9 vs 2553.4 vs 3198.9 vs 2985.2; P < 0.001). Patients responded to proton pump inhibitor treatment also had lower proximal MNBI than those who did not (17 cm above LES: 1834.0 vs 3500.0; 15 cm above LES: 1946.5 vs 3432.6; P < 0.001). CONCLUSION: Decreased proximal MNBI can not only identify LPR patients but also predict patients' symptom outcomes.

Outcome analysis for prediction of intraaortic balloon pump support failure and long-term survival in high-risk patients undergoing mitral valve surgery.

The outcome predictors of intra-aortic balloon pump (IABP) in patients who undergo mitral valve surgery remain unknown. This study aimed to retrospectively review valvular surgery in patients who received an IABP to identify the predictors of failure of IABP support and anticipate the necessary therapy. This retrospective observational study recruited a total of 157 consecutive patients who underwent open-heart mitral valve surgery with IABP implantation intraoperatively or postoperatively. Univariate and multivariate logistic regression analyses were performed to identify the risk factors attributed to 30-day mortality. Follow-up data of survivors were collected to investigate the effect of IABP support to evaluate long-term outcomes. The overall 30-day mortality was 35.7% (56 patients). The following factors that contributed to 30-day mortality included sepsis (P < .001, OR: 5.627, 95%CI: 2.422-11.683); IABP implantation postoperatively rather than intraoperatively (P = .001, OR: 6.395, 95%CI: 2.085-19.511); right heart failure (P = .042, OR: 3.419, 95%CI: 1.225-12.257); and lack of subvalvular apparatus preservation (P = .033, OR: 3.710, 95%CI: 1.094-13.167). Furthermore, follow-up data of these patients showed an estimation of 5-year and 10-year survival rates of 58.9% and 35.7%, respectively. Patients with intraoperative IABP demonstrated better long-term survival outcomes when compared to those with postoperative IABP (χ2  = 4.291, P = .038). In summary, this study distinguished the preoperative predictors of 30-day mortality of IABP-support in mitral valve surgery patients. These results indicated that early intervention with IABP should be taken into consideration in case of hemodynamic instability in critically ill patients undergoing mitral valve surgery.

Long-Term Results of Surgical Atrial Fibrillation Radiofrequency Ablation: Comparison of Two Methods.

BACKGROUND: This retrospective study aimed to evaluate the long-term results of two kinds of surgical atrial fibrillation radiofrequency ablations in concomitant cardiac operations. METHODS: We enrolled 129 patients from January 2006 to December 2015 and performed cardiac operations concomitantly with surgical atrial fibrillation. The patients were divided into a biatrial MAZE group (94 patients) and a left atrial MAZE group (35 patients). A preoperative baseline was compared with intraoperative and postoperative data. Similarly, complications and follow-up results were compared. A matching process based on propensity-score was performed to equalise the potential prognostic factors in both groups and to formulate a balanced 2:1 matched cohort study. RESULTS: There were four deaths (4.3%) in the biatrial MAZE group and one death in left atrial MAZE group due to multiple organ failures followed by low cardiac output. No permanent pacemaker implantations were used in either group. The sinus rhythm maintenance rates at the 6-month, 1-year, 6-year and 8-year follow-ups between the biatrial MAZE group and the left atrial MAZE group were not significantly different (84.7%, 83.3%, 67.3%, and 58.8% vs. 84.9%, 77.4%, 61.1%, and 50%, p>0.05). Similarly, between the propensity-score matched groups, there were no significant differences. CONCLUSION: The left atrial MAZE ablation for the patients with mitral valve diseases who needed open cardiac operation was safe and effective when compared with the biatrial MAZE ablation group.

Platelet Derived Growth Factor Alpha (PDGFRα) Induces the Activation of Cardiac Fibroblasts by Activating c-Kit.

BACKGROUND Enhanced platelet-derived growth factor receptor a (PDGFRα) signaling pathway activity leads to cardiac fibrosis. However, because of the pleiotropic effects of PDGFR signaling, its role in mediating the cardiac fibrotic response remains poorly understood. This study aimed to investigate the regulatory effect of c-Kit in cardiac fibroblasts activated by PDGFRa signaling. MATERIAL AND METHODS A cardiac fibrosis mice model was induced using isoproterenol, and the heart tissues of mice were tested through western blotting and real-time quantitative PCR (RT-qPCR). The cardiac fibroblasts of neonatal mice were treated with PDGF-AA or transfected with small interfering RNAs (siRNAs) specific for the mouse c-Kit gene. The levels of collagen I, collagen III, and alpha-smooth muscle actin (α-SMA) were analyzed using western blotting and RT-qPCR. RESULTS In the heart of the cardiac fibrosis mice model, the activity of c-Kit was enhanced. PDGF-AA treatment accelerated the activity of c-Kit in cardiac fibroblasts. In addition, imatinib inhibited the activity of c-Kit in vivo and in vitro. Moreover, inhibition of c-Kit by siRNAs reduced the expression of α-SMA and collagens in the activated cardiac fibroblasts. Furthermore, PDGFRa directly bound c-Kit in cardiac fibroblasts and stimulated the expression of stem cell factor (SCF). CONCLUSIONS Our data demonstrated that PDGF/PDGFRa induced the activation of cardiac fibroblasts by activating c-Kit. This study indicated that c-Kit could be used as a potential therapeutic target for treatment of cardiac fibrosis.

Tailored therapy for the refractory GERD patients by combined multichannel intraluminal impedance-pH monitoring.

BACKGROUND AND AIMS: About 30% of patients with gastroesophageal reflux disease (GERD) are refractory to proton pump inhibitor (PPI). The reason for the PPI failure in Asian GERD patients has rarely been studied, and the therapy remained unclear. The aims were to explore the possible reasons for PPI failure and to treat these patients with the guidance of 24-h multichannel intraluminal impedance-pH (MII-pH) monitoring. METHODS: Thirty-nine consecutive patients with refractory GERD were enrolled; 24-h MII-pH monitoring was performed on PPI. The refractory GERD patients were grouped into acid overexposure, non-acid reflux, and functional heartburn after the MII-pH monitoring. Double dose of either PPI or paroxetine was administered to refractory GERD patients within different groups. RESULTS: The number of patients in groups of acid overexposure, non-acid reflux, and functional heartburn was 6, 12, and 21, respectively. The acid overexposure group had the most acid reflux events. Among the acid overexposure group, five (5/6) patients accomplish symptom relief with double dose of esomeprazole. For the patients in non-acid reflux group, double dose of esomeprazole made half (6/12) of the patients obtain symptom relief. For the patients in functional heartburn group, the paroxetine had relieved the symptoms in 14 patients among all the 21 patients. In total, with the guidance of MII-pH monitoring, 64.1% (25/39) of refractory GERD patients accomplished symptom relief. CONCLUSIONS: Acid overexposure, non-acid reflux, and functional heartburn were the common reasons for persistent reflux symptoms despite PPI. With the guidance of MII-pH, a tailored therapy could resolve the persistent reflux symptoms among two-third of patients.

Retrograde Cerebral Perfusion Results in Better Perfusion to the Striatum Than the Cerebral Cortex During Deep Hypothermic Circulatory Arrest: A Microdialysis Study.

It remains controversial whether contemporary cerebral perfusion techniques, utilized during deep hypothermic circulatory arrest (DHCA), establish adequate perfusion to deep structures in the brain. This study aimed to investigate whether selective antegrade cerebral perfusion (SACP) or retrograde cerebral perfusion (RCP) can provide perfusion equally to various anatomical positions in the brain using metabolic evidence obtained from microdialysis. Eighteen piglets were randomly assigned to 40 min of circulatory arrest (CA) at 18°C without cerebral perfusion (DHCA group, n = 6) or with SACP (SACP group, n = 6) or RCP (RCP group, n = 6). Microdialysis parameters (glucose, lactate, pyruvate, and glutamate) were measured every 30 min in cortex and striatum. After 3 h of reperfusion, brain tissue was harvested for Western blot measurement of α-spectrin. After 40 min of CA, the DHCA group showed marked elevations of lactate and glycerol and a reduction in glucose in the microdialysis perfusate (all P < 0.05). The changes in glucose, lactate, and glycerol in the perfusate and α-spectrin expression in brain tissue were similar between cortex and striatum in the SACP group (all P > 0.05). In the RCP group, the cortex exhibited lower glucose, higher lactate, and higher glycerol in the perfusate and higher α-spectrin expression in brain tissue compared with the striatum (all P < 0.05). Glutamate showed no difference between cortex and striatum in all groups (all P > 0.05). In summary, SACP provided uniform and continuous cerebral perfusion to most anatomical sites in the brain, whereas RCP resulted in less sufficient perfusion to the cortex but better perfusion to the striatum.

Is selective antegrade cerebral perfusion superior to retrograde cerebral perfusion for brain protection during deep hypothermic circulatory arrest? Metabolic evidence from microdialysis.

OBJECTIVES: This study aimed to investigate whether selective antegrade cerebral perfusion or retrograde cerebral perfusion is a better technique for brain protection in deep hypothermic circulatory arrest by obtaining metabolic evidence from microdialysis. DESIGN: Randomized, animal study. SETTING: Assisted circulation laboratory. SUBJECTS: Eighteen piglets of either sex (9.8 ± 3.1 kg). INTERVENTIONS: Animals were randomly assigned to 40 minutes of circulatory arrest at 18°C without cerebral perfusion (deep hypothermic circulatory arrest group, n = 6) or with selective antegrade cerebral perfusion (selective antegrade cerebral perfusion group, n = 6) or retrograde cerebral perfusion (retrograde cerebral perfusion group, n = 6). Reperfusion was continued for 3 hours. MEASUREMENTS AND MAIN RESULTS: Microdialysis (glucose, lactate, pyruvate, and glycerol) variables in the cortex dialysate were measured every 30 minutes. Intracerebral pressure and serum S-100 levels were also monitored. After 3 hours of reperfusion, cortical tissue was harvested for terminal deoxynucleotidyl transferase dUTP nick-end labeling staining. After 40 minutes of circulatory arrest, the deep hypothermic circulatory arrest group presented marked elevations of intracerebral pressure, and serum S-100 levels were higher in the deep hypothermic circulatory arrest group than in the other two groups (p < 0.001, respectively). The selective antegrade cerebral perfusion group exhibited higher glucose, lower lactate, and lower glycerol levels and a lower lactate-to-pyruvate ratio in comparison to the deep hypothermic circulatory arrest group (p < 0.05, respectively); the retrograde cerebral perfusion group had lower lactate and glycerol levels and a lower lactate-to-pyruvate ratio (p < 0.05, respectively) but similar glucose levels compared to deep hypothermic circulatory arrest alone. Furthermore, selective antegrade cerebral perfusion provided better preservation of energy and cell integrity than retrograde cerebral perfusion with higher glucose and lower glycerol levels (p < 0.05, respectively). After 3 hours of reperfusion, fewer apoptotic neurons were found in selective antegrade cerebral perfusion animals than in the other two groups (p < 0.05, respectively). CONCLUSIONS: Both selective antegrade cerebral perfusion and retrograde cerebral perfusion were superior to deep hypothermic circulatory arrest alone during circulatory arrest. Retrograde cerebral perfusion was a moderate technique that had similar advantages with regard to less cerebral edema, better clearance of metabolic waste, and lower levels of biomarkers of injury than selective antegrade cerebral perfusion, but its capacity for energy preservation, maintenance of cellular integrity, and protection against apoptosis was lower than that of selective antegrade cerebral perfusion.

Comparative expression profiles of microRNA in left and right atrial appendages from patients with rheumatic mitral valve disease exhibiting sinus rhythm or atrial fibrillation.

BACKGROUND: The atrial fibrillation (AF) associated microRNAs (miRNAs) were found in the right atrium (RA) and left atrium (LA) from patients with rheumatic mitral valve disease (RMVD). However, most studies only focus on the RA; and the potential differences of AF-associated miRNAs between the RA and LA are still unknown. The aim of this study was to perform miRNA expression profiles analysis to compare the potential differences of AF-associated miRNAs in the right atrial appendages (RAA) and left atrial appendages (LAA) from RMVD patients. METHODS: Samples tissues from the RAA and LAA were obtained from 18 RMVD patients (10 with AF) during mitral valve replacement surgery. From these tissues, miRNA expression profiles were created and analyzed using a human miRNA microarray. Then, the results were validated using qRT-PCR analysis for 12 selected miRNAs. Finally, potential targets of 10 validated miRNAs were predicted and their functions and potential pathways were analyzed using the miRFocus database. RESULTS: In RAA, 65 AF-associated miRNAs were found and significantly dysregulated (i.e. 28 miRNAs were up-regulated and 37 were down-regulated). In LAA, 42 AF-associated miRNAs were found and significantly dysregulated (i.e. 22 miRNAs were up-regulated and 20 were down-regulated). Among these AF-associated miRNAs, 23 of them were found in both RAA and LAA, 45 of them were found only in RAA, and 19 of them were found only in LAA. Finally, 10 AF-associated miRNAs validated by qRT-PCR were similarly distributed in RAA and LAA; 3 were found in both RAA and LAA, 5 were found only in RAA, and 2 were found only in LAA. Potential miRNA targets and molecular pathways were identified. CONCLUSIONS: We have found the different distributions of AF-associated miRNAs in the RAA and LAA from RMVD patients. This may reflect different miRNA mechanisms in AF between the RA and LA. These findings may provide new insights into the underlying mechanisms of AF in RMVD patients.

Selective antegrade cerebral perfusion attenuating the TLR4/NF-κB pathway during deep hypothermia circulatory arrest in a pig model.

OBJECTIVES: The alteration of the Toll-like receptor/nuclear factor-kappa B (TLR4/NF-κB) signaling pathway during deep hypothermia circulatory arrest (DHCA) has not yet been defined. The aim of this study was to explore the expression of the TLR4/NF-κB pathway cytokine in cerebral injury resulting from DHCA as well as the effect of selective antegrade cerebral perfusion (SACP) on TLR4/NF-κB pathway expression. METHODS: Twelve pigs were randomly assigned to DHCA alone (n = 6) or DHCA with SACP (n = 6) at 18°C for 80 min. Serum interleukin (IL)-6 was assayed by ELISA. Apoptosis and NF-κB proteins were detected by fluorescence TUNEL and Western blot, respectively. The level of TLR4 mRNA and protein were determined through qRT-PCR and Western blot. RESULTS: The serum IL-6 level of the SACP group was significantly lower than that of the DHCA group at the end of circulation arrest and experimentation. Apoptotic index and NF-κB protein were apparently lower in SACP animals (p < 0.05). Compared to the DHCA group, the levels of TLR4 protein and mRNA in the SACP group were lower with significance (p < 0.05). CONCLUSIONS: The TLR4/NF-κB signaling pathway plays a critical role in the pathogenesis of DHCA cerebral injury. Attenuation of the TLR4/NF-κB inflammatory cytokines probably contributes to the neuroprotective effect of SACP. The TLR4/NF-κB inflammatory signaling pathway may be a novel therapeutic target for developing a new strategy for neuroprotection in DHCA.

Atrial fibrillation alters the microRNA expression profiles of the left atria of patients with mitral stenosis.

BACKGROUND: Structural changes of the left and right atria associated with atrial fibrillation (AF) in mitral stenosis (MS) patients are well known, and alterations in microRNA (miRNA) expression profiles of the right atria have also been investigated. However, miRNA changes in the left atria still require delineation. This study evaluated alterations in miRNA expression profiles of left atrial tissues from MS patients with AF relative to those with normal sinus rhythm (NSR). METHODS: Sample tissues from left atrial appendages were obtained from 12 MS patients (6 with AF) during mitral valve replacement surgery. From these tissues, miRNA expression profiles were created and analyzed using a human miRNA microarray. Results were validated via reverse-transcription and quantitative PCR for 5 selected miRNAs. Potential miRNA targets were predicted and their functions and potential pathways analyzed via the miRFocus database. RESULTS: The expression levels of 22 miRNAs differed between the AF and NSR groups. Relative to NSR patients, in those with AF the expression levels of 45% (10/22) of these miRNAs were significantly higher, while those of the balance (55%, 12/22) were significantly lower. Potential miRNA targets and molecular pathways were identified. CONCLUSIONS: AF alters the miRNA expression profiles of the left atria of MS patients. These findings may be useful for the biological understanding of AF in MS patients.

Postoperative Dipping Patterns of Mean Arterial Pressure and Mortality After Coronary Artery Bypass Grafting.

Blood pressure dipping patterns have long been considered to be associated with adverse events. We aimed to investigate whether dipping patterns of postoperative MAP were related to 90-day and hospital mortality in patients undergoing CABG. Four thousand three hundred ninety-one patients were classified into extreme dippers (night-to-day ratio of MAP ≤ 0.8), dippers (0.8 < night-to-day ratio of MAP ≤ 0.9), non-dippers (0.9 < night-to-day ratio of MAP ≤ 1), and reverse dippers (> 1). Compared with non-dippers, reverse dippers were at a higher risk of 90-day mortality (aHR = 1.58; 95% CI, 1.10-2.27) and hospital mortality (aOR = 1.97; 95% CI, 1.12-3.47). A significant interaction was observed between hypertension and dipping patterns (P for interaction = 0.02), with a significant increased risk of 90-day mortality in non-hypertensive reverse dippers (aHR = 1.90; 95% CI, 1.17-3.07) but not in hypertensive reverse dippers (aHR = 1.26; 95% CI, 0.73-2.19).

The altered expression profile of microRNAs in cardiopulmonary bypass canine models and the effects of mir-499 on myocardial ischemic reperfusion injury.

BACKGROUND: MicroRNAs were enrolled in various cardiovascular disease especially ischemic heart diseases, but the microRNA changes during myocardial ischemia reperfusion injury underwent cardiopulmonary bypass are still unknown. This study screens the microRNA differences in CPB canines and evaluates the relationship of microRNAs with myocardial ischemia reperfusion injury. METHODS: 13 healthy canines received CPB with 60 minutes of aortic clamping and cardioplegic arrest, followed by 90 minutes reperfusion. Left ventricular myocardial samples, blood samples and hemodynamic data were taken at different time points. We performed microRNAs microarray experiments upon the left ventricle myocardium tissue of canines before CPB and after reperfusion for 90 minutes by pooling 3 tissue samples together and used qRT-PCR for confirmation. RESULTS: Statistically significant difference was found in mir-499 level before CPB and after reperfusion (T1 vs. T4, p=0.041). We further examined the mir-499 levels by using qRT-PCR in all 13 canines at 4 different time points (T1 vs. T4, p=0.029). Mir-499 expression was negatively correlated with cardiac troponin T (cTnT) and creatine kinase- MB (CK-MB) levels of canines in all time points samples (r=0.469, p<0.001 and r=0.273, p=0.050 respectively). Moreover, higher mir-499 expression level was associated with higher dP/dtmax at 25 minutes and 90 minutes after reperfusion. CONCLUSION: Myocardial ischemic reperfusion injury with cardiopulmonary bypass results in declining level of mir-499 expression in left ventricle myocardium of canines, suggesting mir-499 would be a potential therapeutic target in cardiac protection during open heart surgery.

Long-term Outcomes After On-Pump vs Off-Pump Coronary Artery Bypass Grafting for Ischemic Cardiomyopathy.

BACKGROUND: A post-hoc analysis of the Surgical Treatment for Ischemic Heart Failure (STICH) trial was performed to evaluate the perioperative and long-term outcomes after off-pump vs on-pump coronary artery bypass graft surgery in patients with ischemic cardiomyopathy (coronary artery disease with left ventricular ejection fraction 35% or less). METHODS: Patients who underwent isolated coronary artery bypass graft surgery were enrolled from the STICH trial. Operative details, perioperative outcomes, and long-term outcomes were compared in a 1-to-2 propensity score matching cohort. The primary outcome was death from any cause. RESULTS: Among 768 included patients operated on between July 2002 and May 2007, 152 (19.8%) received off-pump and 616 (80.2%) received on-pump coronary artery bypass graft surgery. In the 1-to-2 matched cohort (152 off pump and 304 on pump), off pump was associated with a higher prevalence of multiple arterial grafting (17.1% vs 8.6%, P = .01) and incomplete revascularization (34.2% vs 17.1%, P < .001). The overall 30-day mortality (3.3% vs 5.3%, P = .34) was comparable between the two groups. After a median follow-up of 8.7 years, off-pump surgery was associated with a similar risk of death from any cause (hazard ratio 0.82; 95% confidence interval, 0.61 to 1.09), with comparable estimated all-cause mortality at 1 year (12.5% vs 11.9%), 5 years (32% vs 32.8%), and 10 years (51.4% vs 62.3%). No significant interaction was detected in the subgroup analyses of incomplete revascularization, multiple arterial grafting, and three-vessel disease. CONCLUSIONS: In patients with ischemic cardiomyopathy, off-pump coronary artery bypass graft surgery could be performed with comparable 30-day mortality and similar long-term survival, and appears to have a lower incidence of perioperative morbidities.

Heterogeneous treatment effects of coronary artery bypass grafting in ischemic cardiomyopathy: A machine learning causal forest analysis.

OBJECTIVES: We aim to evaluate the heterogeneous treatment effects of coronary artery bypass grafting in patients with ischemic cardiomyopathy and to identify a group of patients to have greater benefits from coronary artery bypass grafting compared with medical therapy alone. METHODS: Machine learning causal forest modeling was performed to identify the heterogeneous treatment effects of coronary artery bypass grafting in patients with ischemic cardiomyopathy from the Surgical Treatment for Ischemic Heart Failure trial. The risks of death from any cause and death from cardiovascular causes between coronary artery bypass grafting and medical therapy alone were assessed in the identified subgroups. RESULTS: Among 1212 patients enrolled in the Surgical Treatment for Ischemic Heart Failure trial, left ventricular end-systolic volume index, serum creatinine, and age were identified by the machine learning algorithm to distinguish patients with heterogeneous treatment effects. Among patients with left ventricular end-systolic volume index greater than 84 mL/m2 and age 60.27 years or less, coronary artery bypass grafting was associated with a significantly lower risk of death from any cause (adjusted hazard ratio, 0.61; 95% CI, 0.45-0.84) and death from cardiovascular causes (adjusted hazard ratio, 0.63; 95% CI, 0.45-0.89). By contrast, the survival benefits of coronary artery bypass grafting no longer exist in patients with left ventricular end-systolic volume index 84 mL/m2 or less and serum creatinine 1.04 mg/dL or less, or patients with left ventricular end-systolic volume index greater than 84 mL/m2 and age more than 60.27 years. CONCLUSIONS: The current post hoc analysis of the Surgical Treatment for Ischemic Heart Failure trial identified heterogeneous treatment effects of coronary artery bypass grafting in patients with ischemic cardiomyopathy. Younger patients with severe left ventricular enlargement were more likely to derive greater survival benefits from coronary artery bypass grafting.

Evolution, coronary artery bypass surgery and outcomes of right ventricular dysfunction in ischaemic cardiomyopathy.

OBJECTIVES: Whether the presence or evolution of right ventricular dysfunction (RVD) affects the prognosis and the therapeutic choice between coronary artery bypass grafting (CABG) or medical therapy alone in patients with ischaemic cardiomyopathy (ICM) remains unclear. We investigate the prognostic and therapeutic implications of RVD in patients with ICM. METHODS: Patients with baseline echocardiographic right ventricular (RV) assessment were included from the Surgical Treatment of Ischaemic Heart Failure trial. The primary outcome was all-cause mortality. RESULTS: Of 1212 patients enrolled in the Surgical Treatment of Ischaemic Heart Failure trial, 1042 patients were included, with 143 (13.7%) mild RVD and 142 (13.6%) moderate-to-severe RVD. After a median follow-up of 9.8 years, compared with patients with normal RV function, patients with RVD had a higher risk of mortality [mild RVD: adjusted hazard ratio (aHR) 1.32; 95% confidence interval (CI) 1.06-1.65; moderate-to-severe RVD: aHR, 1.75; 95% CI 1.40-2.19]. Among patients with moderate-to-severe RVD, CABG provided no additional survival benefits compared to medical therapy alone (aHR: 0.98; 95% CI: 0.67-1.43). Among 746 patients with pre- and post-therapeutic RV assessment, a gradient risk for death increased from patients with consistent normal RV function, to patients with recovery from RVD, new-onset RVD and persistent RVD. CONCLUSIONS: RVD was associated with a worse prognosis in patients with ICM, and CABG provided no additional survival benefits to patients with moderate-to-severe RVD. The evolution of RV function had important prognostic implications, which emphasized the importance of both pre- and post-therapeutic RV assessment.

Controlled oxygen reperfusion protects the lung against early ischemia-reperfusion injury in cardiopulmonary bypasses by downregulating high mobility group box 1.

Restricting oxygen delivery during the reperfusion phase of cardiopulmonary bypass (CPB) protects the heart, but effects on lung ischemia reperfusion (IR) in CPB are unknown. We examined whether extracellular high mobility group box 1 (HMGB1) mediated inflammation during early lung IR injury in CPB. Fourteen healthy canines received CPB with 60 minutes of aortic clamping and cardioplegic arrest, followed by 90 minutes reperfusion. Following surgery, the animals were randomized into control (n = 7) or test (n = 7) groups. Control animals received a constant level of 80% FiO(2) during the entire procedure, and the test group received a gradual increase in FiO(2) during the first 25 minutes of reperfusion. In the test group, the FiO(2) was initiated at 40% and increased by 10% every 5 minutes, to 80%. Histology, lung injury variables, HMGB1 expression, and inflammatory responses were assessed at baseline (T1) and at 25 minutes (T2) and 90 minutes (T3) after starting reperfusion. Treatment with controlled oxygen significantly suppressed lung pathologies, lung injury variables, and inflammatory responses (all P < .001). After lung IR injury, HMGB1 mRNA and protein expressions were significantly decreased in the controlled oxygen group (all P < .001). Controlled oxygen reperfusion is protective in the early stages of lung IR injury in a canine CPB model, and this protection is linked to HMGB1 downregulation.