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 × 108 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 108 (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.

Putting the humanities back into medicine: some suggestions.

The practice of medicine is an art as well as a science. As doctors diagnose illness and treat patients day after day, they constantly interweave the social, psychological, ethical and scientific aspects of clinical practice. However, the humanistic values necessary for this approach are generally perceived to be lacking in today’s medical practice.

Congestive heart failure in Indians: How do we improve diagnosis & management.

Heart failure is a common cardiovascular disease with high morbidity and mortality. Unlike western countries where heart failure is predominantly a disease of the elderly, in India it affects younger age group. Important risk factors include coronary artery disease, hypertension, diabetes mellitus, valvular heart disease and cardiomyopathies. Plasma brain natriuretic peptide levels are helpful in the diagnosis of heart failure. Echocardiography is the primary imaging modality of choice, through recently cardiac magnetic resonance imaging (MRI) has been found to play an increasing role. Aim of management is to improve symptoms & enhance survival. Diuretics are important in relieving symptoms. Beta-blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers and adosterone antagonists improve survival in patients with impaired systolic function. Device therapy including cardiac resynchronization therapy and implantable cardiac defibrillators, though expensive are useful in selected patients. Unlike in patients with systolic heart failure where several therapies have been shown to improve survival, clinical trial results in diastolic heart failure have been disappointing and therapy in these patients is restricted to symptom improvement and risk factor control. Therapies like stem cell therapy are being evaluated in clinical trials and appear promising. Early diagnosis and appropriate therapy helps in reversing the process of remodelling and clinical improvement in most of the patients.

Association between subclinical inflammation & fasting insulin in urban young adult north Indian males.

BACKGROUND & OBJECTIVES: Elevated levels of c-reactive protein (CRP) are known to be associated with insulin resistance and metabolic syndrome in adults. A substantial prevalence of hyperinsulinaemia and elevated CRP levels have been shown in Indian young adults. We therefore studied the association of serum high-sensitivity C-reactive protein (hs-CRP) with fasting insulin and insulin resistance in urban adolescent and young adult males in north India. METHODS: In this cross-sectional study 324 healthy males, 14-25 yr of age were selected randomly and their clinical and anthropometric profile [body mass index (BMI), waist and hip circumferences, waist-to-hip circumference ratio (W-HR), and skinfold thickness at four sites], percentage of body fat (%BF) and biochemical (fasting blood glucose, lipoprotein profile, fasting insulin and hs-CRP) parameters were recorded. Insulin resistance was assessed by the homeostasis model of assessment (HOMA-IR). RESULTS: Fasting insulin and hs-CRP levels correlated significantly with BMI, waist circumference, and triceps and subscapular skinfold thickness. Fasting insulin also correlated with %BF, and hs- CRP correlated with W-HR. No correlation was observed between hs-CRP and fasting insulin levels or insulin resistance. In multiple logistic regression analysis different independent risk factors for hyperinsulinaemia and elevated hs-CRP levels were observed; hypercholesterolaemia, overweight and high subscapular skinfold thickness for the former, and high triceps skinfold thickness for the latter. INTERPRETATION & CONCLUSION: Lack of correlation between hs-CRP and surrogate markers of insulin resistance and different risk factors for each, in young Indian males are unique observations of our study. Further studies on a larger sample of both genders need to be done to confirm these findings.

Screening for pre-clinical hypertrophic cardiomyopathy by tissue Doppler imaging.

BACKGROUND: Hypertrophic cardiomyopathy is an autosomal dominant inherited disorder. On a routine clinical basis, genetic analysis is both time consuming and impractical at present. Thus, use of tissue Doppler imaging as a surrogate for genetic screening is an attractive option. METHODS AND RESULTS: Fifty-five first-degree relatives of 15 patients with hypertrophic cardiomyopathy were screened. Of them, two were found to have hypertrophic cardiomyopathy and were included in Group 1, which hence had 17 patients with overt hypertrophic cardiomyopathy. Group 2 had 53 family members who did not manifest any overt echocardiographic abnormality. Twenty healthy volunteers comprised Group 3. Doppler tissue myocardial longitudinal velocities were measured in systole and early diastole and with atrial contraction at the medial mitral annulus, lateral mitral annulus, mid lateral wall and mid interventricular septum. The tissue Doppler characteristics were analyzed for the presence of abnormalities suggestive of subclinical myocardial involvement. Myocardial velocities were highest in the normal control group and lowest in the hypertrophic cardiomyopathy group. The velocities of the relatives without overt hypertrophy were intermediate in range. Of the 53 relatives screened, nine (17%) subjects showed tissue Doppler abnormality in the systolic and early diastolic velocities at the medial and lateral mitral annulus suggestive of a possibility of pre-clinical hypertrophic cardiomyopathy and a carrier state for a hypertrophic cardiomyopathy. Twenty-two of the 53 screened members had a mean early diastolic velocity less than 13.5 cm/s, among this group 9 had an ejection fraction more than 68%. These findings suggest that at least 16.7% of the screened population may carry beta-myosin heavy chain mutation. CONCLUSIONS: Screening for hypertrophic cardiomyopathy is feasible and tissue Doppler imaging is a sensitive and easy means to detect subclinical myocardial involvement in apparently normal family members without overt hypertrophy.

An experimental design for induction of non-specific aortoarteritis.

BACKGROUND: An attempt was made to induce aortoarteritis in mice by using various antigens. METHODS AND RESULTS: The Swiss mice were immunized with eight different antigens and were grouped A to G. Group H served as control. The mice were then bled at 1st, 2nd, 4th, 6th and 8th month interval post-immunization for estimating antibody titer. Then the mice were sacrificed and the heart, aorta and kidney were taken out and processed for hematoxylin-eosin staining. There was gradual increase in the antibody titer from 1st month till 4th month within all the experimental groups (A-G), when compared with control group H. The titer started falling sharply from 6th month post-immunization. However, the control group H did not show much variation. When each individual group was compared separately with control group H, the significant statistical value was obtained. Histopathological examination revealed mild inflammation (+) in kidney by 2nd month, moderate inflammation (++) by 6th month, extensive inflammation (+++) by 8th month and alteration in the normal parenchyma of kidney by 8th month. CONCLUSIONS: The histopathological changes brought out through antigens were more pronounced by 8th month following injection of tunica media, tunica adventitia, tunica intima and aorta collagen as compared to that of standard collagen and mouse aorta injections.

Transcatheter closure of aortopulmonary window.

Aortopulmonary window is an uncommon congenital cardiac defect. Most infants presenting with aortopulmonary window will require conventional surgical repair. Experience with transcatheter closure of aortopulmonary window is limited. We report the case of a 9-year-old girl with aortopulmonary window, in whom transcatheter closure was performed successfully using Amplatzer ductal occluder device.

Identification and management of ventricular tachycardia.

Recognising ventricular origin of a broad QRS tachycardia helps to appropriately identify and manage patients with ventricular tachycardia (VT) in the emergency. Relatively simple clinical and ECG clues help in reaching the correct diagnosis in the majority of patients. Management strategies vary with the clinical diagnosis and an implantable cardioverter defibrillator (ICD) is indicated for chronic prophylactic therapy in patients with coronary artery disease and serious ventricular arrhythmias, especially in those with ventricular dysfunction. The role of this device in patients with stable VT and ejection fractions > 0.35 deserves closer scrutiny. Radiofrequency ablation mostly plays an adjunctive role. Anti-arrhythmic drugs (amiodarone/sotalol and beta-blockers) are required to prevent frequent recurrences. A hybrid approach combining all these therapeutic modalities is often needed. Prognosis in patients with specific VT syndromes such as right ventricular outflow VT, left ventricular fascicular VT and left ventricular outflow VT is excellent with drugs. Radiofrequency ablation is curative in such syndromes.

Management of cardiomyopathy resulting from incessant supraventricular tachycardia in infants and children.

BACKGROUND: Radiofrequency ablation is considered to be the treatment of choice in patients with ventricular dysfunction related to incessant supraventricular tachycardia. However, reservations regarding its use in infants and children prompted us to try alternative strategies for this group. METHODS AND RESULTS: Eight children (age range: 1 day to 10 years) were diagnosed to have tachycardia-related ventricular dysfunction in the past 6 years. They presented with symptoms of palpitation, dyspnea and/or generalized swelling over the body of 3 months to 2 years'duration. The cardiothoracic ratio at presentation was 64% (52%-70%) and ejection fraction was 22.2% (15%-45%). In 7 patients tachycardia was diagnosed to be ectopic atrial and in 1 it was permanent junctional reciprocating tachycardia. Six of these children were managed with intravenous/oral amiodarone in combination with digoxin (3) and/or propranolol (2). In one child addition of amiodarone to digoxin and propranolol led to polymorphic ventricular tachycardia, and amiodarone was withdrawn. Only one child underwent radiofrequency ablation as the first choice because regular follow-up was not possible due to logistic reasons. Sinus rhythm with normalization of ventricular function was achieved in 6 of the 7 children treated medically. One child continued to have frequent episodes of tachycardia and underwent successful radiofrequency ablation of a high right atrial ectopic focus. Two out of the 6 patients on amiodarone could be managed with only digoxin and propranolol after their ventricular function had returned to normal. A third patient relapsed on stopping amiodarone and underwent successful radiofrequency ablation of a left atrial ectopic tachycardia. CONCLUSIONS: Short-term amiodarone in combination with digoxin/propranolol is a safe and effective treatment strategy for infants/children with tachycardiomyopathy. Control of tachycardia is achieved in the majority, leading to recovery of ventricular function. This approach may avoid unnecessary ablations in children or at least postpone it till the procedure would be safer.

Percutaneous transseptal mitral commissurotomy in pregnant women with critical mitral stenosis.

BACKGROUND: Percutaneous transseptal mitral commissurotomy has been successfully performed in selected pregnant patients with severe symptomatic mitral stenosis. Its safety and efficacy needs to be evaluated in a large number of cases. METHODS AND RESULTS: Percutaneous transseptal mitral commissurotomy was performed in 85 severely symptomatic (New York Heart Association functional class III or IV) pregnant women aged 22.7+/-4.1 years (range 18-39 years) with critical mitral stenosis at 24.8+/-4.7 weeks (range 20-34 weeks) of gestation. Percutaneous valvotomy was performed using a flow-guided Inoue balloon in all the patients. The procedure was considered successful in 80 (94%) patients. The hemodynamic mean end-diastolic gradient decreased from 26.7+/-6.8 mm Hg (range 16-35 mmHg) to 4.5+/-3.8 mmHg (range 0-14 mmHg) (p<0.001). The mean diastolic gradient decreased from 29.1+/-9.1 mmHg (range 18-38 mmHg) to 7.2+/-4.1 mmHg (range 4.1-18 mmHg) (p<0.001). The mean mitral valve area assessed by echocardiography increased from 0.75+/-0.5 cm2 (range 0.4-1.0 cm2) to 2.0+/-0.5 (range 1.0-2.7 cm2) (p<0.001). The mean fluoroscopy time was 3.6+/-3.2 minutes. The results of the mitral valvotomy were considered suboptimal in 4 patients. Mitral regurgitation increased by 1 grade in 16 patients and more than 2 grades in 2 patients. One patient developed pericardial tamponade during the procedure and was managed by catheter drainage. Percutaneous mitral valve dilatation was then successfully performed in this patient. No fetal abortion occurred after the procedure. CONCLUSIONS: The results of this study indicate that percutaneous transseptal mitral commissurotomy is a safe and effective procedure for severe symptomatic mitral stenosis in pregnancy.

Fatal atypical mycobacterial infection in a cardiac transplant recipient.

A 37-year-old female underwent heart transplantation for giant cell myocarditis. The patient died within three-and-a-half months of cardiac transplantation. Postmortem specimens from the heart and lung showed multiple necrotizing granulomas with numerous acid-fast bacilli. Polymerase chain reaction done on both the postmortem samples confirmed the presence of atypical mycobacterial infection. This fatal case of atypical mycobacteriosis in a cardiac transplant patient is reported for its rarity.

Two-catheter approach for ablation of accessory pathways in different locations.

Radiofrequency ablation is the treatment of choice for patients with Wolff-Parkinson-White syndrome and symptomatic tachyarrhythmias. The technique involves localising the pathway with multiple catheters at various sites followed by radiofrequency energy application at that site. Single catheter approach has been described for ablation of manifest left-sided accessory pathways. In this article, we report the ablation of accessory pathways in different locations in patients with Wolff-Parkinson-White syndrome by using a two-catheter approach. Twenty-three consecutive patients with symptomatic Wolff-Parkinson-White syndrome were taken up for radiofrequency ablation with this approach. Pathways could be successfully ablated in 11 out of 13 patients with left free wall, 5 out of 7 with right posteroseptal, one patient of left posteroseptal and each of the 2 patients of right mid septal locations giving an overall success in 19/23 (82.6%) patients. Hence, two-catheter approach can be used safely to ablate accessory pathways in different locations with high success rate, thus minimising the procedure time associated with conventional approach.

Non-myxomatous cardiac tumours: twenty-year experience.

Eighty-eight patients underwent surgery for various cardiac tumours from January 1978 to June 1998 at our Institute. Seventy-seven tumours were myxomas, 10 were non-myxomatous and one was secondary cardiac tumour. Case records of the patients with non-myxomatous primary cardiac tumours and one secondary tumour were reviewed. Six of these primary tumours were benign and four, malignant. Age of the patients ranged from 26 days to 47 years. Among patients (3 children, 8 adults) with non-myxomatous primary cardiac tumours, dyspnoea on exertion was the commonest symptom and was the cause of presentation in seven out of 11 patients. Of the eight adults, six were in New York Heart Association functional class II/III and two in class IV. Echocardiographic diagnosis was possible in all the patients. Complete excision of the tumour was possible in all benign and two of the four malignant tumours. Incomplete resection was done in the secondary tumour. Of the six benign tumours, three were rhabdomyomas and one each of fibroma, haemangioma and lipoma. The malignant tumours were one each of fibrosarcoma, angiosarcoma, unclassified sarcoma and malignant mesothelioma. The secondary tumour was a malignant thymoma. Follow-up ranged from 1 to 10 years (mean 7.2 years). Of the patients with benign tumours, four out of six are alive; one patient died on the first post-operative day and one lost to follow-up. Two of the four patients with malignant cardiac tumours died, one was lost to follow-up and one is alive two years after surgery. The patient with secondary malignant thymoma to the superior vena cava was lost to follow-up three months after an uneventful recovery from surgery.

Appraisal of histogenesis of cardiac myxoma: our experience of 78 cases and review of literature.

Cardiac tumours are uncommon. Of these, myxomas have generated significant interest, not only because it is the commonest cardiac neoplasm but also because of controversial theories regarding its histogenesis. We encountered 78 cases of cardiac myxoma in our centre between 1976 and 1997. These included 73 sporadic cases and five cases from a single family of mother, daughter and son. The familial cases had recurrent, biatrial cardiac myxomas. Histopathologic analysis, immunohistochemical study, electron microscopic evaluation and DNA ploidy analysis done in some of these cases revealed evidence in support of the neoplastic nature of this entity. This communication sums up our observations and literature related to the histogenesis of cardiac myxoma.

Enzyme-linked immunosorbent assay and immunoblot study in Takayasu's arteritis patients.

Takayasu's arteritis or non-specific aortoarteritis is an inflammatory and stenotic disease of the aorta of questionable aetiology. Immunopathogenic mechanism, the precise nature of which is uncertain, is often suspected to be one of the basic causes of this disease. The present study was designed to estimate the antiaorta antibody titre in Takayasu's arteritis patients and to further locate the antigen in the vessel wall. Thirty clinically and angiographically proven cases of Takayasu's arteritis patients with appropriate controls were studied. Antiaorta antibody titres were estimated using Enzyme-Linked Immunosorbent Assay method. The controls included patients of vascular diseases other than Takayasu's arteritis, autoimmune diseases like rheumatoid arthritis and systemic lupus erythematosis and normal healthy individuals. Absorbance value at 492 nm at a dilution of 1:500 of the patients' sera was expressed as the antiaorta, antibody titre. There was significant difference (p < 0.005) between the mean value of the antibody titre in patients (0.471 +/- 0.073) and patients of other vascular diseases (0.209 +/- .056); autoimmune diseases (0.143 +/- .024); and, controls (0.108 +/- 0.012). Collagenase treatment of the aorta resulted in the fall of the antibody titre of aortitis patients (0.162 +/- 0.036) suggesting that the collagen might be one of the components responsible for autoantigenecity of aorta resulting in aortitis. The aortic extract was further subjected to 10 percent sodium dodecyle sulphate-polyacrylamide gel electrophoresis and immunoblot was done with Takayasu's arteritis patients' sera as well as controls' sera. The sera in 80 percent of Takayasu's arteritis patients immunoprecipitated a protein of molecular weight 45,000 (45 kilodalton) whereas only 15 percent patients of autoimmune disease group showed precipitation band though of lower molecular weight. Normal human sera gave no immunoprecipitation band. The precise nature of the antigen still needs to be identified.

Effect of endothelial cells on the lymphoproliferative response in Takayasu's arteritis.

Takayasu's arteritis, also known as 'non-specific aortoarteritis' is an inflammatory disease of the aorta and its major branches. It also involves the pulmonary artery. The aetiology of the disease is not known so far. Abnormalities of the endothelial cells in terms of their structure and function are seen in the pathology of a number of diseases affecting the blood vessel wall. However, involvement of the endothelial cells in non-specific aortoarteritis is not known. In an effort to identify the role of endothelial cells in the pathogenesis of Takayasu's arteritis, peripheral blood lymphocytes isolated from the blood of patients suffering from Takayasu's arteritis were cultured in the presence of endothelial cells alone and in the presence of mitogens concanavalin-A and phytohaemagglutinin-P. The peripheral blood lymphocytes of patients with Takayasu's arteritis showed a significantly decreased blastogenic response to the mitogen concanavalin-A when cultured in the presence of endothelial cells. Our result thus suggests that endothelial cells may probably induce an inhibitory effect on the lymphocytes in patients with Takayasu's arteritis.