Evaluation of terlipressin-related patient outcomes in hepatorenal syndrome-acute kidney injury using point-of-care echocardiography.

BACKGROUND AND AIMS: Treatment of hepatorenal syndrome-acute kidney injury (HRS-AKI), with terlipressin and albumin, provides survival benefits, but may be associated with cardiopulmonary complications. We analyzed the predictors of terlipressin response and mortality using point-of-care echocardiography (POC-Echo) and cardiac and renal biomarkers. APPROACH: Between December 2021 and January 2023, patients with HRS-AKI were assessed with POC-Echo and lung ultrasound within 6 hours of admission, at the time of starting terlipressin (48 h), and at 72 hours. Volume expansion was done with 20% albumin, followed by terlipressin infusion. Clinical data, POC-Echo data, and serum biomarkers were prospectively collected. Cirrhotic cardiomyopathy (CCM) was defined per 2020 criteria. RESULTS: One hundred and forty patients were enrolled (84% men, 59% alcohol-associated disease, mean MELD-Na 25±SD 5.6). A median daily dose of infused terlipressin was 4.3 (interquartile range: 3.9-4.6) mg/day; mean duration 6.4 ± SD 1.9 days; the complete response was in 62% and partial response in 11%. Overall mortality was 14% and 16% at 30 and 90 days, respectively. Cutoffs for prediction of terlipressin nonresponse were cardiac variables [ratio of early mitral inflow velocity and mitral annular early diastolic tissue doppler velocity > 12.5 (indicating increased left filling pressures, C-statistic: 0.774), tissue doppler mitral velocity < 7 cm/s (indicating impaired relaxation; C-statistic: 0.791), > 20.5% reduction in cardiac index at 72 hours (C-statistic: 0.885); p < 0.001] and pretreatment biomarkers (CysC > 2.2 mg/l, C-statistic: 0.640 and N-terminal proBNP > 350 pg/mL, C-statistic: 0.655; p <0.050). About 6% of all patients with HRS-AKI and 26% of patients with CCM had pulmonary edema. The presence of CCM (adjusted HR 1.9; CI: 1.8-4.5, p = 0.009) and terlipressin nonresponse (adjusted HR 5.2; CI: 2.2-12.2, p <0.001) were predictors of mortality independent of age, sex, obesity, DM-2, etiology, and baseline creatinine. CONCLUSIONS: CCM and reduction in cardiac index, reliably predict terlipressin nonresponse. CCM is independently associated with poor survival in HRS-AKI.

Incidence of Interstitial Alveolar Syndrome on Point-of-Care Lung Ultrasonography in Pre-eclamptic Women With Severe Features: A Prospective Observational Study.

BACKGROUND: Lung interstitial edema is a clinically silent pathology that develops before overt pulmonary edema among pre-eclamptic women with severe features. Point-of-care lung ultrasonography (LUS) has been suggested as an accessible bedside tool that may identify lung interstitial edema before developing clinical signs and symptoms. Thus, we planned to use bedside LUS as a diagnostic tool in admitted pre-eclamptic women with severe features, with the aim of identifying alveolar-interstitial fluid, seen as B-lines. Our primary objective was to assess the incidence of interstitial alveolar syndrome on lung ultrasonography. METHODS: We conducted a prospective, single-center, observational study on parturients with pre-eclampsia with severe features over a period of 15 months. LUS in 4 intercostal spaces (ICS) was performed on all eligible patients. The number of single or confluent B-lines in each space was recorded by an independent observer. A scoring system was used to grade the lung fluid content based on the number of single and confluent B-lines per ICS, with scores ranging from 0 to 32 (low, 0-10; moderate, 11-20; and high, 21+). The incidence of B-lines at admission and before and after delivery was calculated. In addition, bedside 2D echocardiography was performed to assess left ventricular systolic and diastolic function. Any correlation between presence of B-lines on LUS and blood pressure, clinical symptoms, or echocardiography findings was assessed. RESULTS: Seventy patients were enrolled in the study. On LUS, B-lines were seen in 64.3% patients at admission (45/70 vs 25/70 without B-lines; P = .02), 65.7% patients before delivery (46/70 vs 24/70 without B-lines; P = .01), and 58.6% patients 24 hours postpartum (41/70 versus 29/70 without B-lines; P = .15). Nearly all patients (94.3%) exhibited low to moderate severity of pulmonary fluid burden at admission. Echocardiography revealed diastolic dysfunction in 47.1% (n = 33/70) patients with associated B-lines in the majority (n = 32/33). The total B-line score and E/e' ratio among patients with diastolic dysfunction was found to be strongly correlated (r = 0.848; P < .001). All pre-eclamptic women with presence of breathlessness (11/11; 100%) and facial puffiness (16/16; 100%) on admission had B-lines on LUS. CONCLUSIONS: We conclude that ultrasonographic pulmonary interstitial syndrome is present in more than half of the women with pre-eclampsia with severe features and correlates with diastolic dysfunction, high blood pressure records, and acute-onset breathlessness.

Prevalence of antiphospholipid antibodies in patients with overt myocardial dysfunction in systemic lupus erythematosus. A case-control study.

BACKGROUND: Small case-series have reported overt myocardial dysfunction to be associated with positive antiphospholipid antibodies in patients of systemic lupus erythematosus (SLE). However, there is no case-control study that has examined this association. METHODS: This case-control study recruited patients of SLE (fulfilling SLICC criteria) with overt myocardial dysfunction as cases and those without this as controls. Overt myocardial dysfunction was defined by echocardiography as global left ventricular dysfunction and reduced ejection fraction (<50%). Those patients with a prior diagnosis of anti-phospholipid antibody syndrome, coronary artery disease, rheumatic heart disease or severe pulmonary artery hypertension were excluded. Antibodies tested included lupus anticoagulant, anticardiolipin antibodies (IgM and IgG) and anti-beta 2 glycoprotein 1 antibodies (IgM and IgG). Patients with positive tests underwent repeat testing for persistent positivity after 12 weeks. RESULTS: This study included 51 patients (21 cases and 30 controls) having a mean (SD) age of 33 (13.3) years, and disease duration (median, IQR) of 28 months (12-38 months). The mean ejection fraction of cases was 31.7 (9.3)% while that of controls was 55.7 (1.7)% (p = 0.03). The frequency (percentage) of positive antiphospholipid antibodies was not significantly different between cases and controls (43%, 40%, p = 0.8). The frequency (percentage) of anti-cardiolipin antibody was also not significant between the groups (38%, 37%, p = 0.57). Serositis and leucopenia were more prevalent in SLE patients with myocardial dysfunction (p = 0.005). CONCLUSION: This study did not find any significant association of anti-phospholipid antibodies with overt myocardial dysfunction in patients of SLE.

Prognostic value of left ventricular mechanical dyssynchrony indices in long-standing type II diabetes mellitus with normal perfusion and left ventricular systolic functions on SPECT-MPI.

OBJECTIVE: To test whether phase analysis indices from SPECT-MPI for left ventricular mechanical dyssynchrony (LVMD) are predictors of major adverse cardiac events (MACEs) in long-standing diabetes mellitus (DM). METHODS: A total of 136 DM patients with normal perfusion and left ventricular systolic functions were followed up for about two years and divided into two groups according to the presence and the absence of MACEs. RESULT: Thirteen (9.5%) patients experienced MACEs during follow-up. Patients experiencing MACEs showed significantly higher phase standard deviation (PSD) and wider phase bandwidth (PBW) than those who did not. Moreover, both PSD and PBW showed significant correlations (r = 0.25 and 0.27; P < 0.05) with duration of DM. Logistic regression analysis revealed significant associations of DM duration, microvascular complications, and LVMD indices for predicting MACEs. Kaplan-Meier event-free survival analysis revealed significantly higher rate of MACEs (Logrank = 10.02; P = 0.001) in patients with high PSD and wide PBW. An overall fit model consisting of high-PSD and wide-PBW group was improved with the addition of microvascular complications (χ2 = 15.9; P = 0.03) and further by addition of DM duration of ≥ 15 years (χ2 = 24.3; P = 0.007) as variables. CONCLUSION: LVMD indices are novel prognostic markers in diabetic patients with normal perfusion and left ventricular systolic functions and their increases in magnitudes with DM-duration and in the presence of microvascular complications.

Epidemiology of Trauma Patients Admitted to a Trauma Center in New Delhi, India.

INTRODUCTION: The rapid economic and automobile growth in India leads to a rapid increase in road traffic accidents (RTAs) and factors affecting it. This study evaluates the epidemiology of trauma patients' reports to the major trauma center in New Delhi, India. MATERIALS AND METHODS: The 1,583 patients over 6 months reporting to the casualty of the trauma center attached to Lok Nayak Hospital, New Delhi were included in the study. The patients reporting to the outpatient department as follow-up visits were not included in the study. The data were collected with the help of a structured pro forma. RESULTS: The data depicted the RTAs as the most common cause affecting adults between 20 years and 40 years. The study reports other risk factors like alcohol intoxication and motorcycle riders. Mostly, the patients present in a semiconscious and disoriented state requiring fluid resuscitation. Abrasions and bruises in the extremities stand out as the most common injury pattern. The fractures suffered were the most common injury suffered by the patients. CONCLUSION: Our study shows that RTAs and workplace injuries are the predominant causes of trauma affecting mostly the adults. This study defines the correlation of various parameters with causation and distribution of the trauma in the sample population. This study was performed to improve the understanding of the mode of trauma, severity of injuries, and outcome in our hospital, so that effective prevention and comprehensive management strategies could be made. CLINICAL SIGNIFICANCE: This study signifies the fundamental study for the occurrence, distribution, and prevention of trauma in the society. The acquisition of knowledge of different patterns of trauma patients along with other descriptive factors helps to understand the causation of this disease as well as development of preventive measures. This can form the basis of hospital and regional trauma management strategies. HOW TO CITE THIS ARTICLE: Harna B, Arya S, Bahl A. Epidemiology of Trauma Patients Admitted to a Trauma Center in New Delhi, India. Indian J Crit Care Med 2020;24(12):1193-1197.

Correction to: ACE2, CALM3 and TNNI3K polymorphisms as potential disease modifiers in hypertrophic and dilated cardiomyopathies.

In the original publication of the article, the location and rs number of TNNI3K mouse SNP (3784 C>T) (rs49812611) has been mentioned inadvertently in place of its human homologue. The correct information for human SNP is rs760769780 located at position 74436534, resulting in (G>A) change in human TNNI3K gene.

Left ventricular mechanical dyssynchrony assessment in long-standing type II diabetes mellitus patients with normal gated SPECT-MPI.

BACKGROUND: Assessment of left ventricular mechanical dyssynchrony (LVMD) using phase analysis of gated SPECT-MPI is well established. However, there is little information about the influence of diabetes mellitus on phase analysis. The present work was to evaluate the LVMD in longstanding type II diabetes mellitus (DM) patients with normal gated SPECT-MPI. METHODS: Retrospective analysis of 146 (86 type II diabetics for > 5 years' duration and 60 nondiabetics) consecutive patients with normal gated SPECT-MPI and adequate LVEF was done. Sixty age- and sex-matched nondiabetic served as control. LVMD was determined from the cutoff values (> mean + 2 SD) observed for phase standard deviation (PSD) and phase bandwidth (PBW) from the control subjects. Multivariate logistic regression analysis was applied to assess the correlation between various confounding factors. RESULTS: LVMD was detected in 24 (28%) diabetic patients with the pre-defined cut-off values for PSD (> 10.8) and PBW (> 35.6) derived from the controls. Hyperlipidemia, overweight/obesity, duration of DM and its long-term complications were independently associated with LVMD, with long-term complications being the highest risk factor (OR 28.00; P < .001). CONCLUSION: The evolution time of the patients with type II diabetes mellitus affects the left ventricular mechanical synchrony.

ACE2, CALM3 and TNNI3K polymorphisms as potential disease modifiers in hypertrophic and dilated cardiomyopathies.

The marked clinical and genetic heterogeneity seen in hypertrophic (HCM) and dilated cardiomyopathies (DCM) suggests involvement of disease modifiers and environmental factors in the pathophysiology of these diseases. In the current study, we examined association of single nucleotide polymorphisms (SNPs) of three candidate genes, ACE2 (rs6632677), TNNI3K (rs49812611) and CALM3 (rs13477425) with clinical phenotypes of HCM and DCM patients of North Indian ethnicity. Prevalence of ACE2 (7160726 C>G) variant genotypes (CG and GG) was significantly higher in DCM subjects as compared to controls. Prevalence of TNNI3K (3784 C>T) and CALM3 (-34T>A) variant homozygous genotype were significantly higher in HCM and DCM subjects as compared to controls. DCM patients with CT genotype showed significant decrease in LVEF as compared to CC genotype (p < 0.03). There was significant gene-gene interaction between these SNPs and three-way SNP combination of ACE2 C>G, TNN13K C>T, CALM3 A>T gene variants and was associated with high risk of HCM and DCM. Presence of ACE2 (7160726 C>G) and CALM3 (-34T>A) variant genotypes in HCM Patients with mutations (sarcomeric or non sarcomeric genes) was associated with increased mean septal thickness, further suggesting a role of these gene variants in modifying disease phenotype. Our results suggest that ACE2, TNNI3K and CALM3 polymorphisms are associated with increased risk of HCM and DCM and may act as disease modifiers of these diseases.

Evaluation of Endothelial Dysfunction in Idiopathic Dilated Cardiomyopathy Patients.

Background: Endothelial dysfunction has early been characterized in ischemic cardiomyopathy patients. The study was aimed to study evaluation of endothelial dysfunction in idiopathic cardiomyopathy patients (DCM). Methods: Thirty newly diagnosed patients (age >18 years) of DCM were enrolled in the study from cardiology OPD, PGIMER, Chandigarh from January 2011 to June 2012. Age-and sex-matched 30 healthy controls were also enrolled. Idiopathic DCM was diagnosed by presence of left ventricular dilatation and systolic dysfunction (LVEF <40%) on echocardiography in the absence of coronary artery disease, hypertension or valvular disease. All patients underwent echocardiography and coronary arteriography. Flow mediated dilation (FMD) and carotid intima media thickness (IMT) were compared between patients and controls. Results: There was no significant difference in mean IMT between patients (0.73±0.04 mm) and controls (0.747±0.03 mm) (P=0.18). There was significant difference in left IMT in NHYA class (P=0.010). There was significant difference in mean percentage of FMD (patients vs. controls; 4.37% vs. 8.35%; P=0.001) while baseline FMD was different (patients vs. controls; 3.6 mm±0.26 mm vs. 3.72±0.32 mm; P=0.13). There was no significant difference in percentage NMD (P=0.057) and mean NMD (P=0.26) between patients and controls. There was no correlation between FMD and IMT. Conclusion: Endothelial dysfunction occurs in IDC patients. Also, there is a positive correlation with NHYA class; however, IMT is not affected in dilated cardiomyopathy.

Renin-angiotensin system gene polymorphisms as potential modifiers of hypertrophic and dilated cardiomyopathy phenotypes.

The renin-angiotensin (RAS) pathway has an important role in the etiology of heart failure and given the importance of RAS as a therapeutic target in various cardiomyopathies, genetic polymorphisms in the RAS genes may modulate the risk and severity of disease in cardiomyopathy patients. In the present study, we examined the association of RAS pathway gene polymorphisms, angiotensin converting enzyme (ACE), angiotensinogen (AGT), and angiotensin receptor type 1 (AGTR1) with risk and disease severity in Asian Indian idiopathic cardiomyopathy patients. The case-control study was conducted in 400 cardiomyopathy patients diagnosed with HCM, DCM, or restrictive cardiomyopathy (RCM) and 235 healthy controls. Genotyping of patients and controls was done by PCR-RFLP assays. Left ventricular wall thickness and left ventricular ejection fraction were measured by means of M-mode echocardiography. We observed significantly higher prevalence of ACE DD and AGTR1 1166CC genotypes in hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) patients. Also, 235TT genotype of AGT (M235T) was significantly associated with enhanced risk of the disease phenotype in HCM, DCM, and RCM.

Inhibition of coxsackievirus infection in cardiomyocytes by small dsRNA targeting its cognate coxsackievirus adenovirus receptor.

Background & objectives: Coxsackievirus B (CVB), a member of human Enterovirus group, is the most common cause of viral myocarditis. Coxsackievirus adenovirus receptor (CAR) is identified as a key determinant for the entry of CVB in the target cells. Thus, blockade of receptor by RNA interference (RNAi) may inhibit the entry and pathogenesis of CVB in cardiac cells. The present study was aimed to determine the effect of CAR small dsRNA (siRNA) on coxsackieviral load and CAR expression in coxsackievirus-infected cardiomyocytes. Methods: Transfection efficiency in rat cardiomyocytes (H9c2) was determined by the fluorescent microscopy and flow cytometry. CAR siRNA dose was optimized based on cell viability and relative CAR messenger RNA (mRNA) expression. Cardiomyocytes were transfected with CAR siRNA followed by infection with 100 multiplicity of infection of CVB, which were harvested after 24, 48 and 72 h post-infection (p.i.). RNA was extracted for relative CAR mRNA expression. Cells were freeze-thawed thrice for estimating coxsackieviral load. Results: The efficiency of transfection was optimized to be >80 per cent and CAR siRNA dose of 60 pmol was standardized. The knockdown of CAR by siRNA decreased its expression twice the expression in normal cardiomyocytes after 24 h p.i. of CVB. The treatment with CAR siRNA resulted in significant two log reduction of CVB load in cardiomyocytes infected with CVB at 24 h p.i. and retained till 72 h p.i. Interpretation & conclusions: The inhibition of CAR by siRNA was found to be effective against CVB in cardiomyocytes. However, this treatment strategy has to be evaluated in vivo to develop a new treatment strategy for patients suffering with viral myocarditis.

Transesophageal Echocardiography, 3-Dimensional and Speckle Tracking Together as Sensitive Markers for Early Outcome in Patients With Left Ventricular Dysfunction Undergoing Cardiac Surgery.

OBJECTIVE: Speckle tracking, when combined with 3-dimensional (3D) left ventricular ejection fraction, might prove to be a more sensitive marker for postoperative ventricular dysfunction. This study investigated early outcomes in a cohort of patients with left ventricular dysfunction undergoing cardiac surgery. DESIGN: Prospective, blinded, observational study. SETTING: University hospital; single institution. PARTICIPANTS: The study comprised 73 adult patients with left ventricular ejection fraction <50% undergoing cardiac surgery using cardiopulmonary bypass. INTERVENTIONS: Routine transesophageal echocardiography before and after bypass. MEASUREMENTS AND MAIN RESULTS: Global longitudinal strain using speckle tracking and 3D left ventricular ejection fraction were computed using transesophageal echocardiography. Mean prebypass global longitudinal strain and 3D left ventricle ejection fraction were significantly lower in patients with postoperative low-cardiac-output syndrome compared with patients who did not develop low cardiac output (global longitudinal strain -7.5% v -10.7% and 3D left ventricular ejection fraction 29% v 39%, respectively; p < 0.0001). The cut-off value of global longitudinal strain predicting postoperative low-cardiac-output syndrome was -6%, with 95% sensitivity and 68% specificity; and 3D left ventricular ejection fraction was 19% with 98% sensitivity and 81% specificity. CONCLUSIONS: Preoperative left ventricular global longitudinal strain (-6%) and 3D left ventricular ejection fraction (19%) together could act as predictor of postoperative low-cardiac-output states with high sensitivity (99.9%) in patients undergoing cardiac surgery.

Impact of transsphenoidal surgery on asymptomatic cardiomyopathy in patients with acromegaly. A single-blinded study.

BACKGROUND: Patients with acromegaly have 2-3 times the expected mortality rates primarily due to cardiovascular risks. Echocardiographic studies showing improvement of cardiac function following transsphenoidal surgery (TSS) are limited. MATERIALS AND METHODS: All patients with acromegaly underwent preoperative echocardiography and tissue Doppler (Philips i33, 3D ECHO) for assessment of cardiac indices. In the prospective group of patients, echocardiography was repeated after 6 months of surgery. In the retrospective group of patients, echocardiography was performed for left ventricular diastolic dysfunction and ejection fraction. Biochemical cure was confirmed at least after 6 months by glucose-suppressed plasma growth hormone (GH) concentrations (GH-OGTT) of less than 0.4 ng/ml, random GH of less than 1 ng/ml, and normal age-corrected insulin-like growth factor (IGF-1) values. RESULTS: In the prospective group (38 patients), there was a significant decrease in the left ventricular mass (LVM) and LVM index (LVMI) in patients who were cured as well as in patients with postoperative growth hormone (GH) 1-5 ng/ml. In the prospective group, LVMI completely normalized in 2 and a new-onset deterioration was detected in 1 patient (who was not cured) and improved in 8 others. Left ventricular systolic function was abnormal at baseline in 18 (47.3%) patients, which normalized in 11 (61.1%) patients postoperatively, and in 7 patients, it improved significantly although it did not normalize completely. There was also a significant improvement in the left ventricular ejection fraction (P = 0.01). Post TSS, in patients with GH-OGTT >5 ng/ml, there was no significant decrease in the LVM, LVMI and ejection fraction (EF). In the retrospective group, 62 patients were analyzed for a change in the EF with a mean follow-up of 20.3 months. There was a significant improvement in the left ventricular EF in patients who were cured (P < 0.001). CONCLUSION: Reduction in growth hormone levels and insulin-like growth factor type 1 can decrease the LVM and LVMI, which directly or indirectly contributes to the improvement in diastolic as well as systolic function and probably mortality.

Role of cardiac TBX20 in dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is an important cause of heart failure and sudden cardiac death worldwide. Transcription factor TBX20 has been shown to play a crucial role in cardiac development and maintenance of adult mouse heart. Recent studies suggest that TBX20 may have a role in pathophysiology of DCM. In the present study, we examined TBX20 expression in idiopathic DCM patients and in an animal model of cardiomyopathy, and studied its correlation with echocardiographic indices of LV function. Endomyocardial biopsies (EMBs) from intraventricular septal from the right ventricle region were obtained from idiopathic DCM patients (IDCM, n = 30) and from patients with ventricular septal defect (VSD, n = 14) with normal LVEF who served as controls. An animal model of DCM was developed by right renal artery ligation in Wistar rats. Cardiac TBX20 mRNA levels were measured by real-time PCR in IDCM, controls, and in rats. The role of DNA promoter methylation and copy number variation (CNVs) in regulating TBX20 gene expression was also investigated. Cardiac TBX20 mRNA levels were significantly increased (8.9 fold, p < 0.001) in IDCM patients and in RAL rats as compared to the control group. Cardiac TBX20 expression showed a negative correlation with LVEF (r = -0.71, p < 0.001) and a positive correlation with left ventricular end-systolic volume (r = 0.39, p = 0.038). No significant difference in TBX20 CNVs and promoter methylation was observed between IDCM patients and control group. Our results suggest a potential role of TBX20 in pathophysiology of DCM.

Role of coxsackievirus and adenovirus receptor (CAR) expression and viral load of adenovirus and enterovirus in patients with dilated cardiomyopathy.

Enteroviruses (EVs) and adenoviruses (AdVs) are two important etiological agents of viral myocarditis and dilated cardiomyopathy (DCM). Both these viruses share a common receptor, the coxsackievirus and adenovirus receptor (CAR), for their infection. However, the role of viral load and CAR expression in disease severity has not yet been completely elucidated. The present study aimed to determine viral load of EV and AdV in DCM patients and correlate them with the level of CAR expression in these patients. Sixty-three DCM cases and 30 controls, each of whom died of heart disease other than DCM and non-cardiac disease respectively, were included. Viral load was determined by TaqMan real-time PCR using primers and probes specific for the AdV hexon gene and the 5'UTR region of EV. The CAR mRNA level was semi-quantitated by RT-PCR, and antigen expression was studied by immunohistochemistry. A significantly high AdV load (p < 0.05) and CAR expression (p < 0.05) were observed in DCM cases versus controls, whereas the EV load showed no significant difference. The data suggests a clinical threshold of 128 AdV copies/500 ng of DNA for DCM, with 66.7 % sensitivity and 65 % specificity. A positive correlation between AdV load and CAR expression (p < 0.001) was also observed in DCM cases. The high adenoviral load and increased CAR expression in DCM and their association with adverse disease outcome indicates role of both virus and receptor in disease pathogenesis. Thus, the need for targeting both the virus and the receptor for treatment of viral myocarditis and early DCM requires further confirmation with larger studies.

Efficacy of stem cell in improvement of left ventricular function in acute myocardial infarction--MI3 Trial.

BACKGROUND & OBJECTIVES: Acute myocardial infarction (AMI) is characterized by irreparable and irreversible loss of cardiac myocytes. Despite major advances in the management of AMI, a large number of patients are left with reduced left ventricular ejection fraction (LVEF), which is a major determinant of short and long term morbidity and mortality. A review of 33 randomized control trials has shown varying improvement in left ventricular (LV) function in patients receiving stem cells compared to standard medical therapy. Most trials had small sample size and were underpowered. This phase III prospective, open labelled, randomized multicenteric trial was undertaken to evaluate the efficacy in improving the LVEF over a period of six months, after injecting a predefined dose of 5-10 × 10 [8] autologous mononuclear cells (MNC) by intra-coronary route, in patients, one to three weeks post ST elevation AMI, in addition to the standard medical therapy. METHODS: In this phase III prospective, multicentric trial 250 patients with AMI were included and randomized into stem cell therapy (SCT) and non SCT groups. All patients were followed up for six months. Patients with AMI having left ventricular ejection fraction (LVEF) of 20-50 per cent were included and were randomized to receive intracoronary stem cell infusion after successfully completing percutaneous coronary intervention (PCI). RESULTS: On intention-to-treat analysis the infusion of MNCs had no positive impact on LVEF improvement of ≥ 5 per cent. The improvement in LVEF after six months was 5.17 ± 8.90 per cent in non SCT group and 4.82 ± 10.32 per cent in SCT group. The adverse effects were comparable in both the groups. On post hoc analysis it was noted that the cell dose had a positive impact when infused in the dose of ≥ 5 X 10 [8] (n=71). This benefit was noted upto three weeks post AMI. There were 38 trial deviates in the SCT group which was a limitation of the study. INTERPRETATION & CONCLUSIONS: Infusion of stem cells was found to have no benefit in ST elevation AMI. However, the procedure was safe. A possible benefit was seen when the predefined cell dose was administered which was noted upto three weeks post AMI, but this was not significant and needs confirmation by larger trials.

Implantable cardioverter defibrillators for primary prevention in cardiomyopathies.

BACKGROUND: Implantable cardioverter defibrillators (ICD) are often used as primary prevention strategy for sudden cardiac death (SCD) in young individuals. This study analyzed appropriate therapies, complications and inappropriate shocks in the real-world Indian population. METHODS: All patients in the cardiomyopathy cohort under follow up who had ICD implanted as a primary prevention strategy were studied. The objective was to assess the incidence of appropriate ICD therapies, inappropriate therapies and complications. ICD was interrogated and stored electrograms analyzed. Underlying arrhythmia or conditions resulting in appropriate or inappropriate ICD therapy were studied. Correlation and regression studies was done to assess for the predictors of appropriate therapy. RESULTS: Fifty patients were followed up for a mean follow-up duration of 4.4 ± 3.1 years with total follow up of 220.2 patient years. Appropriate ICD therapy was delivered in 16 out of 50 (32%) patients, with 65 appropriate therapies (median 2 per patient, range: 0-20). Inappropriate therapy delivered in 7 of the 50 (14%) patients, with 44 inappropriate therapies (median 5 per patient, range: 0-20). Complications occurred in 8 of the 50 (16%) patients. Overall, the rate of appropriate therapy was 29.5 per 100 patient years, that of inappropriate therapy was 19.9 per 100 patient years and the rate of complications was 3.6 per 100 patient years. CONCLUSIONS: When implanted for primary prevention in patients with cardiomyopathies over a mean period of 4.4 ± 3.1 years, appropriate ICD therapy was delivered in 32% patients. However, inappropriate therapy (14% patients) and complications (16% patients) were also common.