Myocardial ischemia-reperfusion injury released cellular fibronectin containing domain A (CFN-EDA): A destructive positive loop amplifying arterial thrombosis formation and exacerbating myocardial reperfusion injury.

Previous research has identified intravascular platelet thrombi in regions affected by myocardial ischemia-reperfusion (MI/R) injury and neighbouring areas. However, the occurrence of arterial thrombosis in the context of MI/R injury remains unexplored. This study utilizes intravital microscopy to investigate carotid artery thrombosis during MI/R injury in rats, establishing a connection with the presence of prothrombotic cellular fibronectin containing extra domain A (CFN-EDA) protein. Additionally, the study examines samples from patients with coronary artery disease (CAD) both before and after coronary artery bypass grafting (CABG). Levels of CFN-EDA significantly increase following MI with further elevation observed following reperfusion of the ischemic myocardium. Thrombotic events, such as thrombus formation and growth, show a significant increase, while the time to complete cessation of blood flow in the carotid artery significantly decreases following MI/R injury induced by ferric chloride. The acute infusion of purified CFN-EDA protein accelerates in-vivo thrombotic events in healthy rats and significantly enhances in-vitro adenosine diphosphate and collagen-induced platelet aggregation. Treatment with anti-CFN-EDA antibodies protected the rat against MI/R injury and significantly improved cardiac function as evidenced by increased end-systolic pressure-volume relationship slope and preload recruitable stroke work compared to control. Similarly, in a human study, plasma CFN-EDA levels were notably elevated in CAD patients undergoing CABG. Post-surgery, these levels continued to rise over time, alongside cardiac injury biomarkers such as cardiac troponin and B-type natriuretic peptide. The study highlights that increased CFN-EDA due to CAD or MI initiates a destructive positive feedback loop by amplifying arterial thrombus formation, potentially exacerbating MI/R injury.

Does high dose statin pretreatment affect global strains in patients undergoing valve replacement.

Purpose: To study the effect of rosuvastatin 40 mg (initiated 7 days prior to surgery) in patients undergoing valve replacement (VR) for rheumatic mitral valve disease on left ventricular (LV) strain and biomarker release kinetics. Methods: In this randomized study, cardiac biomarkers viz. troponin I (TnI), Creatine kinase MB (CK-MB), N-terminal pro B-type natriuretic peptide (NTPBNP) were measured before surgery; and 8, 24 and 48 h postoperatively. Global LV (circumferential, global circumferential strain (GCS); longitudinal, GLS; radial, global radial strain (GRS)) strains were measured preoperatively; and 48 h and 30 days postoperatively. Results: Following VR, Global Longitudinal Strain (GLS), Global Circumferential Strain (GCS) and Global Radial Strain (GRS) declined at 48 h in both statin loaded (SL) and non loaded (NL) groups. The %decline in strain was significantly lower in SL group (% change in GLS 35.8% vs 38.8%, GCS 34% vs 44.1%, GRS 45.7% vs 52.6%; p < 0.001).All strain values improved at 30 days with higher improvement in SL group (GLS -15.92 ± 2.00% vs -12.6 ± 1.66%, GCS -15.12 ± 2.93% vs -13.04 ± 2.44%; GRS 22.12 ± 6.85% vs 19.32 ± 6.48%). While TnI, CKMB, NTPBNP increased following surgery, values at 8, 24 and 48 h were lower in the SL vs. NL group. Mean change (baseline to peak biomarker value) was also significantly lower in SL group.The SL group had shorter hospital and Intensive Care Unit (ICU) stay. On Receiver Operating Characteristic Curve (ROC) analysis, baseline GCS ≤ 14% best predicted postoperative 30 day Left Ventricular Ejection Fraction (LVEF) ≤ 50%. Conclusion: Pre-operative high dose rosuvastatin was "cardioprotective" with favorable effect on LV global strain and release kinetics of biomarkers. These cut-offs (described for the first time for rheumatic VR) can be used as prognostic predictors.

Differences in the serum metabolic profile to identify potential biomarkers for cyanotic versus acyanotic heart disease.

BACKGROUND: Growth retardation, malnutrition, and failure to thrive are some of the consequences associated with congenital heart diseases. Several metabolic factors such as hypoxia, anoxia, and several genetic factors are believed to alter the energetics of the heart. Timely diagnosis and patient management is one of the major challenges faced by the clinicians in understanding the disease and provide better treatment options. Metabolic profiling has shown to be potential diagnostic tool to understand the disease. OBJECTIVE: The present experiment was designed as a single center observational pilot study to classify and create diagnostic metabolic signatures associated with the energetics of congenital heart disease in cyanotic and acyanotic groups. METHODS: Metabolic sera profiles were obtained from 35 patients with cyanotic congenital heart disease (TOF) and 23 patients with acyanotic congenital heart disease (ASD and VSD) using high resolution 1D 1H NMR spectra. Univariate and multivariate statistical analysis were performed to classify particular metabolic disorders associated with cyanotic and acyanotic heart disease. RESULTS: The results show dysregulations in several metabolites in cyanotic CHD patients versus acyanotic CHD patients. The discriminatory metabolites were further analyzed with area under receiver operating characteristic (AUROC) curve and identified four metabolic entities (i.e. mannose, hydroxyacetone, myoinositol, and creatinine) which could differentiate cyanotic CHDs from acyanotic CHDs with higher specificity. CONCLUSION: An untargeted metabolic approach proved to be helpful for the detection and distinction of disease-causing metabolites in cyanotic patients from acyanotic ones and can be useful for designing better and personalized treatment protocol.

Postoperative atrial fibrillation in coronary artery bypass grafting herald poor outcome.

Introduction: Atrial fibrillation in postoperative period is common. Although the event of atrial fibrillation is associated with reduced cardiac output and its consequences and cerebrovascular events, its effect on outcome is not clearly documented. This study is done to evaluate the effect of atrial fibrillation on outcome of the operation. Materials and Methods: This is a retrospective case-control study. A total of 263 patients received coronary artery bypass grafting during this period. The data for demographics, comorbidities, preoperative medications, operative details, and echocardiographic parameters of left ventricular functions were acquired. A total of 24 patients had atrial fibrillation (Group I), while 239 remained in normal sinus rhythm (Group II). The outcome is measured as combined of death and postoperative myocardial infarction (MI). Results: The groups are comparable in demographic, preoperative medications, operative, and left ventricular parameters. Of the 24 (9.12%) patients who had postoperative atrial fibrillation, 11 were discharged on medical management. Nine patients reverted to sinus rhythm at discharge. Atrial fibrillation persisted in 8 patients 1 week after discharge and 3 patients after 1 month. The requirement of intraaortic balloon pump (IABP) was statistically significant in group I (5 in group I vs. 10 in group II, n = 0.001). There were 4 deaths in group 1 and 7 in group 2 (P = 0.002), however, the combined end point was achieved in 4 (16.6%) vs. 22 (9.2%), respectively, P = 0.1. Conclusion: The appearance of atrial fibrillation heralds increased requirement of IABP, MI, and death in patients undergoing coronary artery bypass grafting.

Mechanical prosthetic valve thrombosis in current era: 5-year follow-up.

INTRODUCTION: The incidence of prosthetic valve dysfunction (stuck valve) is variable and is dependent on various factors. There are studies from Indian groups that have emphasized the success of thrombolysis; however, none of them reported a follow-up. This study was designed to emphasize on the follow-up of these patients at midterm. MATERIAL AND METHODS: The patients of prosthetic valve thrombosis between period of January 2013 and December 2017 were included in this retrospective observational study. Sixty-six patients were admitted with stuck valve during this period. Thrombolysis was preferred modality of treatment. Survivors were followed up with serial echocardiography, which included estimation of left ventricular and valve functions. RESULTS: Of a total of 66 patients, 59 were of stuck mitral valve and 7 stuck aortic valve. The event happened at a mean of 48.86 ± 48.80 months after index operation of valve replacement using mechanical valve prosthesis. The median age was 40.27 ± 10.8 years with 39 males and 27 females. Thrombolysis was successful in 61 patients with a mortality of 5 (7.57%). During a mean follow-up of 22.7 ± 20.9 months, 42 patients were alive with 14 (22.95%) patients dead and 5 patients lost to follow-up. The average follow-up was 18.7 ± 22.7 months before death. CONCLUSION: Following good early results after thrombolysis, patients of prosthetic heart valve thrombosis experience high mortality within 2 years of follow-up. These patients require frequent follow-up to avoid early mortality.

Effect of statin on perioperative myocardial injury in isolated valve surgery.

BACKGROUND: Statins have known pleiotropic effects that confer protection from ischemia-reperfusion injury. Because cardiopulmonary bypass is a potentially reversible ischemia-reperfusion sequence, we aimed to assess whether statin loading could help to limit myocardial injury in patients undergoing isolated heart valve replacement under cardiopulmonary bypass. METHODS: One hundred patients with rheumatic valvular heart disease undergoing valve replacement received either a loading dose of rosuvastatin (40 mg initiated 7 days before surgery; loaded group) or no statins (non-loaded group). Cardiac troponin I, creatine kinase MB, and brain natriuretic peptide were measured at 8, 24, and 48 hours postoperatively. The primary endpoint was the extent of perioperative myocardial injury measured by the area under the curve for each biomarker. RESULTS: Despite similar baseline levels, all biomarkers at 8, 24, and 48 h were significantly lower in the loaded group. The area under the curve of each biomarker was significantly lower in the loaded group than in the non-loaded group (troponin I: 31.43 vs. 77.21 ng·h·mL-1, creatine kinase MB 309.31 vs. 429.12 ng·h·mL-1, brain natriuretic peptide 5176.11 vs. 16119.31 pg·h·mL-1, all p < 0.001). The mean changes from baseline to peak levels were also significantly lower in the loaded group. The loaded group had a shorter hospital stay but no significant difference was seen in ventilator time, inotrope time, aortic crossclamp time, cardiopulmonary bypass time, or intensive care unit stay. CONCLUSION: In patients undergoing valve replacement, high-dose statin loading before surgery had a favorable impact on the release kinetics of various cardiac biomarkers.

Optimal timing of renal replacement therapy for favourable outcome in patients of acute renal failure following cardiac surgery.

OBJECTIVES: Acute renal failure is a serious complication following cardiac surgery. This may lead to fatal outcome if not treated timely. Continuous renal replacement therapy (RRT) has shown improvement in outcome. There is no clear consensus on the timing of the initiation of RRT in these patients. This study evaluates the factors predicting favourable outcome in this group of patients. METHODS: Patients undergoing cardiac surgery between January 2015 and December 2018 are included in this retrospective study. RRT is required in 24 patients out of 2254 operated during this period. Patients are divided into groups, survivors (group 1, n = 8) and dead (group 2, n = 16). The preoperative information is accessed from the hospital information system and intensive care unit data. Multivariate analysis of pre continuous renal replacement therapy (CRRT) bicarbonate level, pH, potassium, time of initiating CRRT and central venous pressure is performed. RESULTS: The incidence of acute renal failure requiring RRT is 1.06%. Patients in two groups were similar in demographics and presence of risk factors. There was difference in the pre RRT bicarbonate level (p = 0.007). On multivariate analysis, pre RRT bicarbonate levels predict survival (p = 0.003). ROC curve for pre RRT bicarbonate predicts survival for value above 16.83 mg/dl with 80% sensitivity and 78.6% specificity. CONCLUSION: Bicarbonate level in blood predicts the best evidence for initiating the renal replacement therapy in of acute renal failure following cardiac surgery. When urine output drops to < 0.5 ml/kg and not responding to infusion of furosemide, RRT must be initiated at sodium bicarbonate in blood above 16.9 mg%.

Blood transfusion is unlikely to be a source for hepatitis E virus transmission in India.

INTRODUCTION: Transmission of hepatitis E virus (HEV) through transfusion has been reported from countries where genotype 3 virus is predominant. Data from countries with predominantly genotype 1 HEV, such as India, are limited. We studied the risk of HEV transmission following transfusion of blood or blood components in India. METHODS: Adult patients undergoing cardiac surgery who received transfusion of blood or blood products in the peri-operative period and who lacked history of any transfusion or surgery in the preceding 1 year were studied. A pre-transfusion blood specimen was collected for IgG anti-HEV antibody test. For the participants who were seronegative for anti-HEV, follow up specimens were collected at every 2-3-month intervals for up to 6 months after surgery and were tested for IgM and IgG anti-HEV antibodies. RESULTS: Of the 335 participants originally enrolled, 191 (57%) could be followed up. Of them, 103 (53.9%) were seropositive for HEV IgG at baseline and were excluded. Of the remaining 88 participants (age 42 ± 14.1 years; 55 [63%] male), none reported hepatitis-like illness during the follow up period of 81 ± 23 days. Also, none of these 88 participants was found to have seroconversion to anti-HEV IgM or IgG positivity in the follow up specimens. CONCLUSION: Transfusion-mediated transmission of HEV was not observed in our cohort and may be infrequent in the Indian population, where genotype 1 is the predominant HEV type.

Obstructing Granuloma in Main Pulmonary Trunk.

A patient with main pulmonary artery mass may have severe symptoms and warrants urgent surgical management, whereas in a stable patient with a diagnosis amenable to medical treatment, medical management should be started while monitoring the size of the lesion. We report a case in which the patient experienced severe right heart dysfunction due to obstruction of the main pulmonary artery, diagnosed as a probable thrombus, and the patient was taken for urgent surgical excision, later diagnosed as tuberculoma on histopathologic examination.

Assessment of untreated fresh autologous pericardium as material for construction of heart valve: Result at 5 years.

Introduction: Tetralogy of Fallot requiring transannular repair of the right ventricular outflow tract (RVOT) are exposed to free pulmonary insufficiency and hence inevitable right ventricular dysfunction. This study analyzes the function and structure of untreated autologous pericardium monocusp used to create a competent pulmonary valve. Materials and Methods: This is a retrospective analysis of 52 cases operated between December 2006 and December 2012. Untreated autologous pericardium was used for creating a competent pulmonary valve following a transannular patch. They are followed for functional and structural assessment of the pulmonary valve by echocardiography. Positron emission tomography (PET) with 18 fluorodeoxyglucose was performed in two cases for profiling the pulmonary valve. Results: Median age was 10.5 years (1-38). The follow-up was complete for 42 (80.76%) patients for 3 years and 25 (48.07%) patients for 5 years. The RVOT gradient was 42 mmHg (16-96) in the year of surgery, which reduced to 26 mmHg (10-58) and pulmonary insufficiency that was present in 8.3% of patients in 1st year was witnessed in 22.7% in the 5th year of follow-up. The monocusp patch was successful in creating a competent valve while maintaining its structure at 3 years; however, it became distorted and retracted at 5 years of follow-up. There was no calcification in any of the patients. PET-computed tomography confirmed the uptake of glucose by monocusp at 1 year of follow-up. Conclusion: The untreated autologous pericardium functioned well when it was used to create a competent pulmonary valve at short term and midterm. Although it changed in its structure; there was no calcification at 5 years of follow-up.

Radio-opaque tricuspid aortic valve seen in X-Ray chest as mercedes-benz sign.

We are presenting a very interesting X-ray image of the calcific aortic valve in a septuagenarian male patient who underwent successful aortic valve replacement.

In response to: Unsolved enigma of atrial myxoma with biventricular dysfunction.

Thanks to Raut et al.[1] for appreciating our efforts in managing the case of biatrial myxomas. A brief discussion is warranted here on the types, size of cardiac myxomas, interleukin 6 (IL-6) levels, left ventricle (LV) dysfunction, and their relation. IL-6 is a pleiotropic cytokine with a variety of biologic activities, including differentiation of B cell, thymocytes, and T cells; activation of macrophages; and stimulation of hepatocyte to produce acute-phase proteins such as C-reactive protein.[2],[3] It is also said to have paracrine, endocrine, and autocrine growth functions.[3].

Atrial myxomas causing severe left and right ventricular dysfunction.

Myxomas are the most common cardiac tumors, accounting for about 50% of benign primary cardiac tumors, with the majority located in the left atrium, and 80% of which originate in the interatrial septum. We report two cases with severe cachexia, neurological sequelae, and severe biventricle dysfunction secondary to atrial myxomas with marked early improvement after tumor excision.

A case report of combined radical pericardiectomy and beating heart coronary artery bypass grafting in a patient with tubercular chronic constrictive pericarditis with coronary artery disease.

We here report a successful midterm outcome following combined off-pump radical pericardiectomy and coronary artery bypass surgery (CABG) in a 65-year-old male patient who was suffering from chronic constrictive calcified tubercular pericarditis with coronary artery disease. Simultaneous off-pump CABG and radical pericardiectomy for nonsurgical constrictive pericarditis is reported very rarely in English literature.

Salvage pneumonectomy for pulmonary arteriovenous malformation in a 12-year-old boy with brain abscess and hemiparesis: A fatal outcome.

Large pulmonary arteriovenous malformations (PAVMs) constitute an uncommon cause of central cyanosis with septic embolism and brain abscess. This large right to left shunt can lead to chronic severe hypoxemia and significant morbidity and mortality if untreated. Conservative parenchyma-sparing lung resection was used widely as treatment of choice. However, with the advent of embolotheraphy, it is considered the preferred mode of treatment with less invasiveness. We here report a 12-year-old boy with large aneurysmal pulmonary arteriovenous fistula presented with brain abscess and hemiparesis. He underwent thoracotomy and pneumonectomy for large PAVMs, and it was complicated with bleeding and massive blood transfusion. The patient developed acute renal failure as a postoperative complication and succumbed to it. We suggest proper look out for systemic collateral and their management by embolitheraphy either alone or in combination should be tried first. We also suggest median sternotomy and intrapericardial approach for pneumonectomy in such difficult situation can be helpful.

Role of angiotensin II type I (AT1 A1166C) receptor polymorphism in susceptibility of left ventricular dysfunction.

BACKGROUND: Left ventricular dysfunction (LVD) with subsequent congestive heart failure (CHF) constitutes the final common pathway for a host of cardiac disorders. The impaired LV function develops in response to an ischemic insult followed by a fall in cardiac output that leads to activation of renin-angiotensin-system (RAS). Angiotensin II type I receptor (AT1), which mediate the vasoconstrictive and salt-conserving actions of the RAS, represent interesting candidate genes for cardiovascular diseases. Therefore, we conducted an association study between single nucleotide polymorphism (SNP) in AT1 gene and LVD in CAD patients. METHODS AND RESULTS: The present study recruited a total of 950 subjects including 720 angiography confirmed CAD patients and 230 healthy controls. Among 720 CAD patients, 229 with reduced left ventricle ejection fraction (LVEF≤45%) were categorized as LVD. The AT1 (A1166C, rs5186) polymorphism was determined by ARMS-PCR. Our results showed that the frequency of AT1 1166AC and CC genotypes were significantly higher in LVD patients in comparison to non-LVD (LVEF >45%) patients (p value = 0.003; OR = 1.81 and p value <0.001; OR = 4.33). Further analysis showed that AT1 A1166C polymorphism was significantly associated with LV end diastole (p-value = 0.031), end systole (p-value = 0.038) dimensions, and mean LVEF (p-value = 0.035). Moreover, on comparing the AT1 A1166C polymorphism in CAD patients with healthy controls, we did not find any association both at genotypic and allelic level (p value = 0.927; OR = 1.04 and p value = 0.219; OR = 0.83) respectively. CONCLUSIONS: Our study suggests that AT1 A1166C polymorphism may play significant role in conferring genetic susceptibility of LVD.

Differential release kinetics of cardiac biomarkers in off-pump coronary bypass.

BACKGROUND: Differential release kinetics of the cardiac biomarkers (B-type natriuretic peptide, troponin I, and creatine kinase-MB) following off-pump coronary artery bypass are not well characterized. METHODS: Biomarker levels were assessed at 6, 24, 48 h, and 1 month preoperatively, in 80 patients who underwent off-pump coronary artery bypass. RESULTS: All biomarkers increased within 6 h of surgery. Peak B-type natriuretic peptide levels occurred at 24-48 h in 96% of patients, but only two-thirds had peak troponin I and creatine kinase-MB levels at this time, reflecting different release patterns. Levels of all biomarkers declined within 48 h, but 42% of patients still had B-type natriuretic peptide >100 pg·mL(-1) at 1 month. Those with baseline B-type natriuretic peptide > 100 pg·mL(-1) had a lower left ventricular ejection fraction (43.6% vs. 55.6%, p < 0.01) and longer inotropic (43.8 vs. 31.4 h, p = 0.03) and ventilator support (34 vs. 25.5 h, p = 0.04) than those with lower levels. B-type natriuretic peptide levels correlated positively with angiographic Syntax score (p = 0.02) and negatively with left ventricular ejection fraction (p < 0.001). Only baseline B-type natriuretic peptide predicted the durations of inotropic support (p = 0.01) and ventilation (p = 0.02). Postoperative B-type natriuretic peptide at 6, 24, and 48 h and delta B-type natriuretic peptide were significant predictors of mean ventilation time. CONCLUSION: Even in patients undergoing off-pump surgery, there is significant natriuretic peptide and myocardial enzyme release. Only B-type natriuretic peptide levels had an association with postoperative variables.

CYP4F2 1347 G > A & GGCX 12970 C > G polymorphisms: frequency in north Indians & their effect on dosing of acenocoumarol oral anticoagulant.

BACKGROUND & OBJECTIVES: CYP4F2 and γ-glutamyl carboxylase (GGCX) have small but significant roles in the maintenance dose of coumarinic oral anticoagulants (COAs). CYP4F2 1347 G > A and GGCX 12970 C > G polymorphisms have been used in the pharmacogenetic dosing algorithms of warfarin for Caucasians and Chinese populations. India has a large population with multiple ethnic groups but there are no reports about the frequencies of these polymorphisms in north Indians. In the present study, we aimed to find out the allelic frequencies of CYP4F2 1347 G > A and GGCX 12970 C > G polymorphisms in a north Indian population and relate these to daily maintenance drug dose requirements of COA. METHODS: CYP4F2 1347 G > A and GGCX 12970 C > G polymorphisms were genotyped by polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) protocols and Taqman SNP discrimination assays in healthy volunteers (n=102) and patients (n=225) receiving acenocoumarol, an oral anticoagulant, after cardiac valve replacement surgery. RESULTS: In healthy volunteers, the allele frequencies for CYP4F2 1347 G > A and GGCX 12970 C > G were 43.14 and 1.43 per cent, respectively. No significant differences in mean weight normalized doses of acenocoumarol were found for these CYP4F2 and GGCX genotypes. Binary logistic regression analysis revealed no significant association of any of the genotypes or alleles with the dosing phenotypes for both the SNPs. INTERPRETATION & CONCLUSIONS: We report distinct frequencies of CYP4F2 1347 G > A and GGCX 12970 C > G polymorphisms in north Indians but these polymorphisms did not have significant bearing on maintenance dose of acenocoumarol oral anticoagulant in cardiac valve replacement patients.

Therapeutic dosing of acenocoumarol: proposal of a population specific pharmacogenetic dosing algorithm and its validation in north Indians.

OBJECTIVES: To develop a population specific pharmacogenetic acenocoumarol dosing algorithm for north Indian patients and show its efficiency in dosage prediction. METHODS: Multiple and linear stepwise regression analyses were used to include age, sex, height, weight, body surface area, smoking status, VKORC1 -1639 G>A, CYP4F2 1347 G>A, CYP2C9*2,*3 and GGCX 12970 C>G polymorphisms as variables to generate dosing algorithms. The new dosing models were compared with already reported algorithms and also with the clinical data for various performance measures. Odds ratios for association of genotypes with drug sensitive and resistant groups were calculated. RESULTS: The pharmacogenetic dosing algorithm generated by multiple regression analysis explains 41.4% (p-value <0.001) of dosage variation. Validation of the new algorithm showed its predictive ability to be better than the already established algorithms based on similar variables. Its validity in our population is reflected by increased sensitivity, specificity, accuracy and decreased rates of over- and under-estimation in comparison to clinical data. The VKORC1-1639 G>A polymorphism was found to be strongly associated with acenocoumarol sensitivity according to recessive model. CONCLUSIONS: We have proposed an efficient north India specific pharmacogenetic acenocoumarol dosing algorithm which might become a baseline for personalised medicine approach for treatment of patients in future.