Correlation between circulating fibrosis biomarkers with left atrial function and left atrial volume index in rheumatic mitral stenosis.

Mitral stenosis is the most common rheumatic heart disease (RHD) disorder worldwide, including in Indonesia. This pathological condition causes left atrial pressure, leading to left atrial fibrosis that affects the structure and function of the left atrial as well as the clinical condition. The aim of this study was to assess the correlation between circulating fibrosis biomarkers with net atrioventricular compliance (Cn) as a parameter of left atrial function, and left atrial volume index (LAVI) as a parameter left atrium structure of changes. A cross-sectional study was conducted at Panti Rahayu Hospital and Permata Bunda Hospital, Purwodadi, Central Java, with a total of 40 RHD patients with severe mitral stenosis. The ELISA was used to measure the levels of carboxy-terminal propeptide of type I procollagen (PICP), matrix metalloproteinase I (MMP-1), tissue inhibitor matrix metalloproteinase 1 (TIMP-1), and transforming growth factor-ß1 (TGF-ß1). The left atrial function was assessed by measuring Cn, and the LAVI parameters were measured to assess left atrium structure/size. The mean levels of circulating fibrosis biomarkers were as follows: PICP 153.96±89.12 ng/mL; MMP-1 1.44±2.12 ng/mL; MMP-1/TIMP-1 ratio 0.38±0.54 and TGF-ß1 2.66±1.96 pg/mL. From the echocardiographic evaluation, the mean Cn was 5.24±1.93 mL/mmHg and the mean LAVI was 152.55±79.36 mL/m2. There were significant correlation between MMP-1 and MMP-1/TIMP-1 ratio with Cn (r=0.345 and r=0.333, respectively; both had p<0.05). PICP and TGF-ß1 biomarkers did not significantly correlate with Cn (p>0.05). Meanwhile, none of the biomarkers had a significant correlation with LAVI (p>0.05). This study highlights that MMP-1 and MMP-1/TIMP-1 ratio are potentially to be used as markers to determine the Cn in RHD patients with severe mitral stenosis. However, further studies with a higher sample size are needed to confirm this finding.

Hemolysis and cardiopulmonary bypass: meta-analysis and systematic review of contributing factors.

BACKGROUND: The use of cardiopulmonary bypass (CPB) is almost inevitable in cardiac surgery. However, it can cause complications, including hemolysis. Until now, there have not been any standards for reducing hemolysis from CPB. Therefore, this systematic review was conducted to determine the factors that increase or reduce hemolysis in the use of CPB. METHODS: Keywords Earches (cardiac surgery AND cardiopulmonary bypass AND hemolysis) were done on PubMed databases and Cochrane CENTRAL from 1990-2021 for published randomized controlled trials (RCTs) that studied interventions on CPB, in cardiac surgery patients, and measured hemolysis as one of the outcomes. Studies involving patients with preoperative hematological disorders, prosthetic valves, preoperative use of intra-aortic balloon pumps and extracorporeal circulation, emergency and minimally invasive surgery are excluded RESULTS: The search yielded 64 studies that met the inclusion criteria, which involved a total of 3,434 patients. The most common surgery was coronary revascularization (75%). Out of 64 studies, 33 divided into 7 analyses. Remaining 31 studies were synthesized qualitatively. Significant decreases were found in centrifugal vs roller pumps for PFHb (p = 0.0006) and Hp (p < 0.0001) outcomes, separated vs combined suctioned blood (p = 0.003), CPB alternatives vs conventional CPB (p < 0.0001), and mini extracorporeal circulation (MiniECC) vs conventional CPB for LDH (p = 0.0008). Significant increases were found in pulsatility (p = 0.03) and vacuum-assisted venous drainage (VAVD) vs gravity-assisted venous drainage (GAVD) (p = 0.002). CONCLUSION: The review shows that hemolysis could be caused by several factors and efforts have been made to reduce it, combining significant efforts could be beneficial. However, this review has limitations, such as heterogeneity due to no standards available for conducting CPB. Therefore, further research with standardized guidelines for CPB is needed to yield more comparable studies. Meta-analyses with more specific parameters should be done to minimize heterogeneity.

Low Plasma Atherogenic Index Associated with Poor Prognosis in Hospitalized Patients with Acute Myocardial Infarction.

AIM: the impact of atherogenic index of plasma (AIP), calculated as logarithmic of triglyceride:HDL ratio (log10.[TG:HDL]), on major adverse cardiovascular events (MACE) during acute myocardial infarction (AMI) has not been fully accepted. This study aims to investigate the role of AIP in predicting major adverse cardiovascular events following AMI during intensive care in the hospital. METHODS: this was a prospective cohort study. We enrolled subjects with AMI hospitalized in intensive coronary care unit at Dr. Sardjito General Hospital, Yogyakarta. The AIP was measured in fasting blood within 24 hours of hospital admission. The total cholesterol, LDL, HDL, and triglyceride (TG), were measured and AIP value was determined as log10.[TG:HDL]). Based on AIP value, subjects were allocated into low AIP (<0.24) and high AIP (0.24). The outcome of the study was major adverse cardiovascular events during hospitalization, i.e. multipart of all cause mortality, acute heart failure, cardiogenic shock, reinfarction, and rescucitated VT/VF. RESULTS: among 277 subjects, the high AIP group comprised 213 subjects (77%) and low AIP group comprised 64 subjects (33%). During intensive hospitalisation, 66 subjects (24%) developed MACE and 20 subjects (7%) developed fatal outcome (all cause mortality). The incidence of MACE tended to be higher in low AIP group, however its difference was not significant. The incidence of all cause mortality was significantly higher in low AIP group (14%) than in high AIP group (5%). Multivariable analysis showed that low AIP predicted all cause mortality independently with a risk ratio 3.71 (95% CI 1.26-10.97, p=0.02). CONCLUSION: low AIP value (<0.24) is an independent predictor for all cause mortality in patients with acute myocardial infarction undergoing intensive hospitalisation.

On-admission High Neutrophil to Lymphocyte Ratio as Predictor of In-hospital Adverse Cardiac Event in ST-elevation Myocardial Infarction.

AIM: to investigate the role of neutrophil-to-lymphocyte ratio (NLratio) in predicting in-hospital adverse cardiac events in patients with STEMI. METHODS: this was a cohort study on patients with STEMI onset 24 hour hospitalised in ICCU. NLratio was calculated as absolute neutrophil count divided with lymphocyte count measured by automated blood cell counter on admission.The outcome was in-hospital adverse cardiac events, which were recorded during follow-up. The cut-off value of NLratio to predict outcome was determined by ROC curve analysis. Univariate and multivariable analysis to assess whether high NLratio was independent predictor for in-hospital adverse events were performed. RESULTS: among 165 subjects, in-hospital adverse cardiac events occurred in 49 subjects (29%). The cut-off value of NLratio was 6.2. The univariate analysis showed that NLratio >6.2 had an odd ratio of 3.19 (95% CI 1.55-6.55, p=0.002) to develop in-hospital adverse cardiac events. The multivariate analysis showed that NLratio was an independent predictor of in-hospital adverse cardiac events with an odd ratio of 4.10 (95% CI 1.59-10.54, p=0.003). CONCLUSION: high on-admission NLratio is an independent predictor for in-hospital adverse cardiac events in patients hospitalised for STEMI.

Serum matrix metalloproteinase-9 levels in acute coronary syndrome patients with and without hyperglycemia.

AIM: to determine the difference in serum matrix metalloproteinase-9 (MMP-9) levels among acute coronary syndrome patients with and without hyperglycemia. METHODS: this study was a cross-sectional study on patients with acute coronary syndrome admitted to ICCU of Dr.Sardjito Hospital Yogyakarta Indonesia. Measurements of blood glucose level were performed on hospital admission, while measurement of MMP-9 level was performed upon arrival at the ICCU. Hyperglycemia was defined as a random blood glucose level of >140 mg/dL. Student's t test was performed to analyze the difference of MMP-9 level between subjects with and without hyperglycemia. RESULTS: of 72 enrolled subjects, there were 34 subjects with hyperglycemia and 38 subjects without hyperglycemia. The mean blood glucose level was significantly different in subjects with hyperglycemia as compared to those without hyperglycemia (204.4±92.16 vs. 108.93±19.1 mg/dL, p=0.0001). The mean MMP-9 level in subjects with hyperglycemia was significantly higher than those without hyperglycemia (1574±573.61 vs. 1370±573.66 ng/mL, p=0.025). The prevalence ratio of high MMP-9 level among subjects with hyperglycemia was 2.88 (95% CI: 1.16-7.14), p=0.004. CONCLUSION: serum MMP-9 level in patients suffering from acute coronary syndrome with hyperglycemia was significantly higher than those without hyperglycemia.

In-hospital major cardiovascular events between STEMI receiving thrombolysis therapy and primary PCI.

AIM: to compare the in-hospital major cardiovascular events between thrombolysis therapy and primary percutaneous coronary intervention (PCI) in patients with ST-elevation acute myocardial infarction (STEMI. METHODS: the study design is retrospective cohort. Medical record of patients with STEMI onset<12 hour receiving thrombolysis treatment or primary PCI in Dr. Sardjito Hospital Yogyakarta between January 2008 and March 2010 are evaluated. The primary outcome is major cardiovascular events which comprise cardiovascular death, reinfarction and stroke during hospitalisation. The secondary outcomes are post infarction angina pectoris, heart failure, cardiogenic shock and bleeding. RESULTS: among 78 patients with thrombolysis and 53 patients with primary PCI, in-hospital major cardiovascular events do not differ significantly (10.3% versus 9.4%; RR 1.09, 95%CI 0.33-3.55; p=0.87). Post infarction angina pectoris is 7% versus 3.8% (RR 2.51, 95%CI 0.50-12.60; p=0.24). The incidence of heart failure is significantly higher in thrombolysis (17.9% versus 5.7%; RR 3.64, 95%CI 0.99-13.38; p=0.04), primary PCI reduces 68.1% relative risk to develop acute heart failure in STEMI. The incidence of cardiogenic shock is not different. Major and minor bleeding do not differ significantly either. CONCLUSION: the in-hospital major cardiovascular events between STEMI receiving thrombolysis therapy and primary PCI is not significantly different. Heart failure is significantly higher in thrombolysis therapy and the primary PCI reduces the risk.

Predictive value of different estimated glomerular filtration rates on hospital adverse events following acute myocardial infarction.

AIM: to assess whether different glomerular filtration rate (GFR) equations render different predictive value on hospital adverse events in patients hospitalised due to acute myocardial infarction. METHODS: the study design is cross-sectional. Data from consecutive patients with acute myocardial infarction were analyzed. Three different estimated GFR equations, i.e. Cockroft-Gault (eGFRC-G), MDRD (eGFRMDRD) and CKD-EPI (eGFRCKD-EPI) were calculated. Hospital adverse events in these study patients were recorded. The predictive values of these eGFRs on hospital adverse events were compared with ROC curve. Univariate and multivariable analysis to assess which GFR equation as independent predictor for hospital adverse events were performed. RESULTS: among 103 study patients, 49 patients (47.6%) experienced hospital adverse events. Proportion of hospital adverse events were significantly associated with eGFRMDRD (p<0.01) and eGFRCKD-EPI (p=0.02), but not with eGFRC-G (p=0.10). Hospital adverse events were better predicted by eGFRMDRD than by eGFRCKD-EPI (AUC, 0.698; 95%CI: 0.596-0.800, p<0.01 versus AUC, 0.693; 95%CI: 0.591-0.796, p<0.01). Multivariable analysis showed moderate (adjusted OR 3.50; 95%CI: 1.38-8.85, p<0.01) and severe (adjusted OR 8.13, 95%CI: 1.38-47.91, p=0.02) kidney dysfunctions based on eGFRMDRD were independent predictors for hospital adverse events. CONCLUSION: an eGFR based on MDRD gave better predictive value than eGFR based on CKD-EPI on hospital adverse events among acute myocardial infarction. Moderate and severe kidney dysfunctions based on eGFRMDRD were independent predictors for hospital adverse events following acute myocardial infarction.

Transcatheter coil embolization in coronary artery fistulae.

Coronary artery fistulae (CAF) is a rare anomaly, mostly with the incidence of congenital CAF 0.1% - 0.2% and the incidence of acquired CAF 0.2% at coronary angiography. Symptomatic or high flow shunting CAF must be treated with surgery or non surgery approach such as transcatheter coil embolization (TCCE). A women 63 years old with chief complain of chest pain since one month ago. The patient had undergone coronary angiography with conclusions as follows 95% narrowing of proximal LAD (left anterior descendens) artery and CAF from LAD into the right atrium. Whereas narrowing of proximal LAD was performed PCI (percutaneous coronary intervention) with the implantation of drug eluting stents, but patients still complained chest pain. CAF decided to do the TCCE. Post TCCE chest pain and ECG evaluation were within normal limits.

Coronary artery sequel of Kawasaki disease in adulthood, a concern for internists and cardiologists.

Young adults suffered from acute cardiac event, such as acute coronary syndrome, ischemic-associated arrhythmia and sudden death, are frequently encountered without known etiology and significant risk factors. Coronary vasculitis due to Kawasaki disease contributes to be a risk factor in young adult population to develop acute coronary event. Afflicted predominantly during childhood, Kawasaki disease gives rise to vasculitis of coronary artery which becomes major concern since it leads to coronary aneurysm and stenosis. Self-limited nature of Kawasaki disease make those suffered in childhood survive into adult life. Accelerated coronary atherosclerosis in the Kawasaki disease-related lesion occurring in young adult and subsequent acute coronary syndrome and sudden death in this population are devastating impacts of the sequel of Kawasaki disease. It is expected that internists and adult cardiologists become familiar with this sequel and provide better care for the patients.

Association Between High Serum Matrix Metalloproteinase-9 and MMP-9 (-1562C>T) Polymorphism in Patients With ST-Elevation Acute Myocardial Infarction.

BACKGROUND: Matrix metalloproteinase (MMP)-9 is excessively expressed in frail region of atherosclerotic plaque and released in circulation following plaque rupture. High MMP-9 level associated with severity of occluded thrombus and subsequent myocardial infarction. MMP-9 (-1562C>T) polymorphism associated with acute myocardial infarction, however conflicting data present regarding impact of MMP-9 (-1562C>T) polymorphism on circulating MMP-9 level in acute myocardial infarction with ST-elevation (STEMI), clinical entity represents totally occluded coronary thrombus. METHODS: We enrolled consecutively subjects with acute coronary syndrome treated in intensive coronary care unit. Acute coronary syndrome diagnosis were classified into STEMI and non-ST-elevation acute coronary syndrome (NSTEACS). Seventy consecutive subjects were enrolled for this study, 31 subjects with STEMI and 39 subjects with NSTEACS. RESULTS: On admission serum MMP-9 level, measured with sandwich enzyme immunoassay, were higher in STEMI as compared with NSTEACS (1,574.2 ± 604.1 ng/mL vs. 1,104.4 ± 591.5 ng/mL, P < 0.01). Proportion of subjects with MMP-9 (-1562C>T) polymorphism, analyzed with PCR-RFLP, were higher in STEMI as compared with NSTEACS (66.7% vs. 33.3%, P = 0.15). T allele frequency was almost twice in STEMI as compared to in NSTEACS. Almost all (83%) subjects with MMP-9 (-1562C>T) polymorphism had high serum MMP-9 level (> 1,334.5 ng/mL) during STEMI, whereas in NSTEACS all subjects had low level. CONCLUSION: MMP-9 (-1562C>T) polymorphism associated with high serum MMP-9 level in patients with STEMI.

Association between levels of circulating soluble CD40 ligand on admission and in-hospital events among acute coronary syndrome patients.

AIM: to investigate the association between on admission circulating sCD40L level and in-hospital events among patients admitted with acute coronary syndrome. METHODS: a short prognostic study which recruited consecutively patients with acute coronary syndrome (ACS) admitted in Intensive Coronary Care Unit (ICCU). INCLUSION CRITERIA: between 35-70 years old, onset of chest pain 24 hours and approved informed consent. Patients with acute infection, renal failure, heart failure, liver cirrhosis, chronic inflammation, venous thromboemboli, malignancies and pregnancy were excluded. Blood samples of sCD40L was withdrawn on admission and measured with ELISA. Follow-up was conducted during intensive hospitalization. In-hospital events were re-infarction, acute heart failure, cardiogenic shock and mortality. RESULTS: of 77 study patients, 64 (83%) were male with mean age 55 years old. In-hospital events occurred in 33 (43%) patients, namely mortality 6 (18%), acute heart failure 25 (75%) and cardiogenic shock 2 (6%). The level of circulating sCD40L was significantly higher in patients with in-hospital events compared with those without in-hospital events (8559.6 pg/ml vs. 7393.8 pg/ml respectively, p value <0.05). Using ROC curve, we determined cut-off point 7107.0 pg/ml. On multivariate analysis, high sCD40L (7107.0 pg/ml) had a trend to increase the risk of in-hospital events, although statistically not significant (adjusted OR 1.66, 95% CI : 0.56-4.87; p value 0.36). CONCLUSION: on admission circulating sCD40L level was higher in patients with in-hospital events. Nonetheless, high sCD40L level did not significantly associate with increasing risk to develop in-hospital events among ACS.

On Arrival High Blood Glucose Level is Associated With Detrimental and Fatal Hospitalization Outcomes for Acute Coronary Syndrome.

BACKGROUND: High blood glucose level is frequently encountered in acute coronary syndrome. We investigated the effects of high blood glucose measured on arrival on hospitalization adverse events in acute coronary syndrome. Our study patients were Javanese in ethnicity, which constitute half of population in Indonesia. We hypothesized that elevated blood glucose has detrimental effects on hospitalization for acute coronary syndrome. METHODS: We designed an observasional cohort study and recruited 148 consecutive patients with acute coronary syndrome. Venous blood was collected on hospital arrival. High blood glucose level was determined as plasma glucose > 140 mg/dL. Adverse hospitalization events were recorded, i.e. mortality, acute heart failure, cardiogenic shock and heart rhythm disorders. Echocardiography examination was performed to determine left ventricular function. RESULTS: The prevalence of on arrival high blood glucose among Javanese patients with acute coronary syndrome was considerably high (36%). On arrival high blood glucose was associated with acute heart failure (P < 0.001) and shock cardiogenic (P = 0.02). Heart rhythm disorders were higher in high blood glucose patients (P = 0.004). Left ventricular dysfunction was more prevalent in high blood glucose patients (P = 0.001) and ejection fraction was lower (P = 0.001). On arrival high blood glucose was independently associated with hospitalization adverse events (adjusted odds ratio = 2.3, 95% confidence interval: 1.1-4.9, P = 0.03) and hospital mortality (adjusted odds ratio = 6.9, 95% confidence interval: 1.2-38.6, P = 0.03). CONCLUSIONS: Our study suggests that on arrival high blood glucose among Javanese patients with acute coronary syndrome is considerably high and is associated with detrimental and fatal hospitalization outcomes.

Circulating soluble CD40 ligand mediates the interaction between neutrophils and platelets in acute coronary syndrome.

Following plaque rupture, activated platelet will induce subsequent inflammatory process including neutrophil recruitment. In vitro study demonstrated an interaction between neutrophils and platelets via a mechanism involving CD40-CD40 ligand. However, whether this mechanism exists in the clinical setting remains unknown. Fifty-four patients with acute myocardial infarction (AMI) and 25 with unstable angina of pain onset of < or = 24 h were enrolled consecutively. Acute myocardial infarction was diagnosed from three diagnostic criteria, i.e., anginal pain, electrocardiogram ST-T changes, and cardiac enzyme elevation. Unstable angina was diagnosed in patients without elevated cardiac enzymes. Peripheral venous blood was drawn at admission for routine blood count and soluble CD40 ligand (sCD40L) measurement. Neutrophil count was determined by an automated blood cell counter. Circulating sCD40L was measured using a standard enzyme-linked immunosorbent assay. Neutrophil count was significantly higher in AMI as compared with unstable angina (P < 0.001), whereas circulating sCD40L did not significantly differ. Despite marked elevation, no correlation was observed between neutrophil count and circulating sCD40L in AMI. Interestingly, we observed a strong and positive significant correlation between neutrophil count and circulating sCD40L level (r = 0.607, P = 0.002) in unstable angina. Circulating sCD40L is associated with neutrophil count and may mediate interaction between neutrophils and platelets in acute coronary syndrome, particularly in unstable angina.