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Background Given the shortage of cardiac rehabilitation (CR) programs in India and poor uptake worldwide, there is an urgent need to find alternative models of CR that are inexpensive and may offer choice to subgroups with poor uptake (e.g., women and elderly). Objectives This study sought to evaluate the effects of yoga-based CR (Yoga-CaRe) on major cardiovascular events and self-rated health in a multicenter randomized controlled trial. Methods The trial was conducted in 24 medical centers across India. This study recruited 3,959 patients with acute myocardial infarction with a median and minimum follow-up of 22 and 6 months. Patients were individually randomized to receive either a Yoga-CaRe program (n = 1,970) or enhanced standard care involving educational advice (n = 1,989). The co-primary outcomes were: 1) first occurrence of major adverse cardiovascular events (MACE) (composite of all-cause mortality, myocardial infarction, stroke, or emergency cardiovascular hospitalization); and 2) self-rated health on the European Quality of Life–5 Dimensions–5 Level visual analogue scale at 12 weeks. Results MACE occurred in 131 (6.7%) patients in the Yoga-CaRe group and 146 (7.4%) patients in the enhanced standard care group (hazard ratio with Yoga-CaRe: 0.90; 95% confidence interval [CI]: 0.71 to 1.15; p = 0.41). Self-rated health was 77 in Yoga-CaRe and 75.7 in the enhanced standard care group (baseline-adjusted mean difference in favor of Yoga-CaRe: 1.5; 95% CI: 0.5 to 2.5; p = 0.002). The Yoga-CaRe group had greater return to pre-infarct activities, but there was no difference in tobacco cessation or medication adherence between the treatment groups (secondary outcomes). Conclusions Yoga-CaRe improved self-rated health and return to pre-infarct activities after acute myocardial infarction, but the trial lacked statistical power to show a difference in MACE. Yoga-CaRe may be an option when conventional CR is unavailable or unacceptable to individuals. (A study on effectiveness of YOGA based cardiac rehabilitation programme in India and United Kingdom; CTRI/2012/02/002408)., Central Illustration

Aims: The prevalence of premature coronary artery disease (CAD) in India is two to three times more than other ethnic groups. Untreated heterozygous familial hypercholesterolemia (FH) is one of the important causes for premature CAD. As the age advances, these patients without treatment have 100 times increased risk of cardiovascular (CV) mortality resulting from myocardial infarction (MI). Recent evidence suggests that one in 250 individuals may be affected by FH (nearly 40 million people globally). It is indicated that the true global prevalence of FH is underestimated. The true prevalence of FH in India remains unknown. Methods: A total of 635 patients with premature CAD were assessed for FH using the Dutch Lipid Clinical Network (DLCN) criteria. Based on scores, patients were diagnosed as definite, probable, possible, or no FH. Other CV risk factors known to cause CAD such as smoking, diabetes mellitus, and hypertension were also recorded. Results: Of total 635 patients, 25 (4%) were diagnosed as definite, 70 (11%) as probable, 238 (37%) as possible, and 302 (48%) without FH, suggesting the prevalence of potential (definite + probable) FH of about 15% in the North Indian population. FH is more common in younger patients, and they have lesser incidence of common CV risk factors such as diabetes, hypertension, and smoking than the younger MI patients without FH (26.32% vs.42.59%; 17.89% vs.29.44%; 22.11% vs.40.74%). Conclusion: FH prevalence is high among patients with premature CAD admitted to a cardiac unit. To detect patients with FH, routine screening with simple criteria such as family history of premature CAD combined with hypercholesterolemia, and a DLCN criteria score >5 may be effectively used. Keywords: Familial hypercholesterolemia, Premature coronary artery disease, Dutch Lipid Clinic Network Criteria, Correction factor, Arcus cornealis

Objective: Primary objective was to compare the effects of atorvastatin 40 mg vs 80 mg on LDL-C in Indian patients with atherosclerotic dyslipidemia. Secondary objectives were to compare the effects of atorvastatin 40 mg vs 80 mg on HDL-C and triglycerides and also comparing of side effects (myopathy, hepatotoxicity and new onset diabetes mellitus) of both doses. Method: This Study is A Prospective, randomized, open-label, comparative study. This study was conducted on 240 patients of dyslipidemia (as per ACC/AHA 2013 lipid guidelines) attending the OPD/wards/CCU of department of cardiology, Sir Ganga Ram Hospital. They were randomly divided into 2 groups of 120 each. Group A consisted patients who received Atorvastatin 40 mg daily and Group B Atorvastatin 80 mg daily. The follow up period was 6 months. Results: At 3 and 6 month follow up, Atorvastatin 40 mg leads to mean LDL cholesterol reduction of 47.18 ± 20.81 & 50.03 ± 18.06 respectively. While Atorvastatin 80 mg results in LDL reduction as 50.11 ± 15.85 & 52.30 ± 13.72. The comparison between two doses revealed a non-significant difference (p = .118 & p = .149 respectively).At 6 months of follow up, few patients reported myalgia (2 in group A and 7 in Group B). The difference between groups was significant (p = .045). Although none of our patient had significant elevation of CPK. Conclusion: This study concluded that both doses of atorvastatin (40 & 80 mg) are equally efficacious in improving dyslipidemia but higher dose leads to more incidence of myalgia. Keywords: Atherosclerosis, Atorvastatin, Dyslipidemia, Myalgia

Background Cardiac rehabilitation (CR) is a standard treatment for secondary prevention of acute myocardial infarction (AMI) in high income countries (HICs), but it is inaccessible to most patients in India due to high costs and skills required for multidisciplinary CR teams. We developed a low-cost and scalable CR program based on culturally-acceptable practice of yoga (Yoga-CaRe). In this paper, we report the rationale and design for evaluation of its effectiveness and cost-effectiveness. Methods This is a multi-center, single-blind, two-arm parallel-group randomized controlled trial across 22 cardiac care hospitals in India. Four thousand patients aged 18–80 years with AMI will be recruited and randomized 1:1 to receive Yoga-CaRe program (13 sessions supervised by an instructor and encouragement to self-practice daily) or enhanced standard care (3 sessions of health education) delivered over a period of three months. Participants will be followed 3-monthly till the end of the trial. The co-primary outcomes are a) time to occurrence of first cardiovascular event (composite of all-cause mortality, non-fatal myocardial infarction, non-fatal stroke and emergency cardiovascular hospitalization), and b) quality of life (Euro-QoL-5L) at 12 weeks. Secondary outcomes include need for revascularization procedures, return to pre-infarct activities, tobacco cessation, medication adherence, and cost-effectiveness of the intervention. Conclusion This trial will alone contribute >20% participants to existing meta-analyses of randomized trials of CR worldwide. If Yoga-CaRe is found to be effective, it has the potential to save millions of lives and transform care of AMI patients in India and other low and middle income country settings.

Yoga is a holistic mind–body intervention aimed at physical, mental, emotional and spiritual well being. Several studies have shown that yoga and/or meditation can control risk factors for cardiovascular disease like hypertension, type II diabetes and insulin resistance, obesity, lipid profile, psychosocial stress and smoking. Some randomized studies suggest that yoga/meditation could retard or even regress early and advanced coronary atherosclerosis. A recent study suggests that transcendental meditation may be extremely useful in secondary prevention of coronary heart disease and may reduce cardiovascular events by 48 % over a 5-year period. Another small study suggests that yoga may be helpful in prevention of atrial fibrillation. However, most studies have several limitations like lack of adequate controls, small sample size, inconsistencies in baseline and different methodologies, etc. and therefore large trials with improved methodologies are required to confirm these findings. However, in view of the existing knowledge and yoga being a cost-effective technique without side effects, it appears appropriate to incorporate yoga/meditation for primary and secondary prevention of cardiovascular disease.

Various population studies have reported the association of rare S2 allele of apolipoprotein C3 (APOC3) SstI polymorphism with hypertriglyceridemia (HTG) and coronary artery disease (CAD). We were the first to report an association of S2 allele with high triglyceride (TG) levels in healthy volunteers from Northern India. Since HTG is suggested to be a predominant risk factor for CAD among Indians, we have elucidated the relationship of APOC3 SstI polymorphism with the lipid profile and CAD. A total of 158 patients with ≥ 70% stenosis in one or more coronary artery (angiographically proven CAD patients), 35 subjects with < 70% stenosis (NCAD) and 151 normal controls (free of heart disease) from Northern plains of India were recruited in the study. DNA samples were analyzed by polymerase chain reaction (PCR) followed by SstI digestion. Lipid profile was estimated by enzymatic kit. We found a strong association of S2 allele with high TG levels, which was more significant in patients. Prevalence of S2 allele in normal controls and CAD patients were comparable, despite the fact that mean TG level was significantly higher in patients. A greater insight into this observation revealed that the prevalence of high TG, if not coupled with other risk factors (like high total cholesterol, low HDL), was comparable in patients and controls. Thus, our study reveals that rare S2 allele may be employed as a susceptibility marker for high TG. However, high TG or S2 allele alone may not contribute to the etiology of CAD.

The risk/benefit of moderate to high doses of calcium antagonists in stable angina is uncertain. This study investigates the efficacy and acceptability of low dose diltiazem in combination with trimetazidine for the treatment of stable angina.In a 28-day, randomized, double blind study, treatment with 90 mg diltiazem in combination with 60 mg trimetazidine or placebo per day was compared in 50 patients with stable angina. The primary outcomes were time to 1-mm ST segment depression and the Duke treadmill score.Of the 25 patients in each treatment group, the number (%) of patients responding to trimetazidine compared to placebo was, in time to 1-mm ST segment depression, 13 (52) versus 5 (20), P0.05; in the Duke treadmill score, 18 (72) versus 8 (32), P0.01; and in angina 17 (68) versus 3 (12), P0.01. Compared to placebo there was an improvement with trimetazidine in mean exercise time to 1-mm ST segment depression of 128 s (95% confidence interval 45.0-208.5; P0.01); in the mean Duke treadmill score of 57.4% (95% confidence interval 9.9-100; P0.02); and in mean anginal attacks of 5.1 per week (95% confidence interval, 3.1-7.3, P0.01).The combination of low dose diltiazem with trimetazidine is effective with few side-effects in the symptomatic control of patients with stable angina.

The objective of this study was to prospectively investigate various clinical and echocardiographic variables to predict the left atrial and left atrial appendage clot and spontaneous echo contrast in patients with severe rheumatic mitral stenosis. We studied 200 consecutive patients (112 males and 88 females; mean age 29.6+/-9.6 years). Left atrial clot and spontaneous echo contrast were present in 26 and 53.5% of cases, respectively. There were no significant differences in the mitral valve area, mean transmitral diastolic gradient and left ventricular ejection fraction between patients with and without clot. Patients with clot were older (34.4+/-11.4 vs. 28.2+/-8.5 years, P0.001), had longer duration of symptoms (41. 4+/-36.0 vs. 28.8+/-22.9 months, P0.001), more frequent atrial fibrillation and spontaneous echo contrast (69.2 vs. 16.9%, P0. 00001 and 76.9 vs. 45.3%, P0.00001, respectively) and larger left atrial area and diameter (41.0+/-12.7 vs. 29.9+/-7.4 cm(2), P0.00001 and 53.9+/-8.3 vs. 47.6+/-7.4 mm, P0.0001, respectively) as compared to patients without clot. Similarly patients with spontaneous echo contrast were older (31+/-10.4 vs. 27.8+/-8.3 years, P0.01), had more frequent atrial fibrillation (48.6 vs. 9.7%, P0.0001), left atrial clot (37.4 vs. 12.9%, P0.0001), larger left atrial area and diameter (37.6+/-11.2 vs. 28.1+/-6.7 cm(2), P0.00001 and 52.2+/-8.3 vs. 45.9+/-6.5 mm, P0.00001, respectively) and smaller mitral valve area (0.77+/-0.14 vs. 0.84+/-0.13 cm(2), P0.01) as compared to patients without spontaneous echo contrast. There were no significant differences in the mean transmitral diastolic gradient and left ventricular ejection fraction. On multiple regression and discriminant function analysis, atrial fibrillation and left atrial area were independent predictors of left atrial clot formation. In a subgroup of patients with sinus rhythm, larger left atrial area and presence of spontaneous echo contrast were significantly associated with the presence of clot in left atrium and appendage. We conclude that in patients with severe mitral stenosis, the presence of atrial fibrillation and in the subgroup of the patients with sinus rhythm the presence of large left atrium (or =40 cm(2)) and spontaneous echo contrast were associated with higher risk of clot formation in the left atrium and might be benefited by prophylactic anticoagulation.

To determine whether the mitral valve morphology influences the results of percutaneous balloon mitral valvuloplasty for mitral stenosis, two-dimensional echocardiography was performed before valvuloplasty in 126 patients (mean age 25.5+/-9.4 years) and in 30 normal controls. The 2D echocardiographic features of mitral valve leaflets: thickness, length and motion; diastolic mitral valvular excursion; chordal length; mitral annular diameter; subvalvular distance ratio; distance between mid mitral annulus to left ventricular apex, base and tip of papillary muscle and effective balloon dilating area, effective balloon dilating area/body surface area and effective balloon dilating diameter/mitral annular diameter were then correlated to the immediate post-valvuloplasty mitral valve area. For the total patients population, post-valvuloplasty valve area increased from 0.67+/-0.17 to 2.1+/-0.86 cm2 (P0.0001), mean transmitral diastolic gradient decreased from 24.5+/-9.0 to 6.0+/-3.0 mm Hg (P0.0001), mean left atrial pressure decreased from 29.7+/-6.2 to 12.7+/-4.8 mm Hg (P0.0001), mean pulmonary artery pressure decreased from 44.8+/-14.2 to 25.4+/-9.5 mm Hg (P0.0001) and cardiac index increased from 2.7+/-0.38 to 3.1+/-0.55 l/min/m2 (P0.0001). The patients were divided into three groups on the basis of post-valvuloplasty mitral valve area. Group I had valve area1.5 cm2, group II had valve area from 1.5 to 1.9 cm2 and group III had valve areaor =2.0 cm2. On comparison, no statistically significant difference was found in any of the echocardiographic variables in the three groups. On univariate, multivariate, multiple regression and discriminate function analysis, none of the variables were found to have significant influence on immediate result of valvuloplasty. There was no significant difference in the incidence of mitral regurgitation in any of the three groups. We conclude that the extent of mitral valvular and subvalvular deformity do not have a significant effect on the immediate outcome of mitral valvuloplasty using the Inoue balloon and it can be successfully performed in patients with severe subvalvular fibrosis. Unique balloon geometry and stepwise balloon sizing may explain these acceptable immediate results in severely deformed valves.

We reviewed our clinical and echocardiographic experience in 70 consecutive patients with 73 cardiac myxomas, diagnosed over an 11 year period. There were 21 males and 49 females, ages ranged from 18 to 80 years. Only in 5.7% cases was the diagnosis of myxomas made clinically. 88.6% cases were initially diagnosed as having: mitral valve disease (70%), tricuspid valve disease (10%), ischemic heart disease (5.7%), cardiomyopathy (2.9%), and the remaining 5.7% were detected during family screening and follow-up. The mean duration of symptoms was 10.6 months. The commonest symptom was dyspnoea (80%), followed by constitutional symptoms (45.7%), embolization (30%), palpitation (25.7%), syncope (15.7%), pedal oedema (15.7%) and pain chest (12.9%). The sites of myxomas were as follows: left atrium, 58; right atrium, 9; and, biatrium, 3. All myxomas except 3 were attached to the interatrial septum. The site, size, shape, attachment, mobility, prolapse into ventricle, and surface characteristic of myxomas were accurately assessed by 2D-echocardiography and confirmed in all (65 of 70) who underwent surgery. When the morphological characteristic of myxomas were studied and correlated with clinical features large left atrial myxoma size was closely related with constitutional symptoms, congestive heart failure, with syncope and auscultatory findings suggestive of mitral valve disease, whereas smaller myxoma size and irregular surface were associated with embolization. Constitutional symptoms were only present in left atrial myxoma. Post-operative mean echocardiographic follow-up of 60 months showed no recurrence except in 2 with familial myxoma. We conclude that the majority of myxomas mimic many cardiovascular diseases and were detected in symptomatic patients, so a high index of clinical suspicion is important for its early and correct diagnosis. The size and appearance of the myxomas correlated with the presenting symptoms.

In 136 consecutive patients who underwent percutaneous transvenous mitral commissurotomy (PTMC) with use of the single rubber-nylon (Inoue) balloon Inoue balloon angiographically analyzed subvalvular fibrosis was assessed retrospectively with regard to results and complications. There were 53 males and 83 females, with a mean age of 22 +/- 11 years (range 10 to 48 years). For the entire group, mitral valve area increased from 0.7 +/- 0.3 to 2.1 +/- 0.6 cm2 (p0.001). Valve area increased from 0.7 +/- 0.12 to 1.8 +/- 0.14 cm2 in patients with severe subvalvular fibrosis (n = 55) and from 0.8 +/- 0.11 to 1.9 +/- 0.12 cm2 in cases with mild to moderate subvalvular fibrosis (n = 80; p = NS). The number of patients with 2+ or greater increase in mitral regurgitation was not different between the two groups (6% vs 5.5%, p = NS). None of the patients required mitral valve replacement immediately after PTMC. We conclude that, with use of the Inoue balloon, PTMC can be successfully performed in patients with severe subvalvular fibrosis.

In practice, chronic heart failure is often not treated with angiotensin-converting enzyme inhibitors. One reason is the fear of first-dose hypotension. In the majority of patients, this condition is asymptomatic and the consequences are unexpected. Presently, little is known of its epidemiology.This was a prospective, 48-hour observational study of 160 patients with chronic heart failure due to systolic dysfunction, previously untreated with angiotensin-converting enzyme inhibitors, randomly drawn from the clinical practice of selected cardiologists across India. The primary outcome was a change in the mean arterial pressure during the first 24-hours after the first dose of an angiotensin-converting enzyme inhibitor. In 131/160 patients (81.9%) with no hypotensive symptoms, the incidence of first-dose hypotension (maximum 24-hour fall in mean arterial pressure greater than 10% from baseline) was 56/131 (42.7%). Pre-treatment diastolic pressure had a negative, independent association with 24-hour change in mean arterial pressure, accounting for 29% (R2=0.29, p0.01) of its variability, and its predictive value was greater with pro-drug angiotensin-converting enzyme inhibitors. The incidence of first-dose hypotension increased from 1 patient (4.8%) at a pre-treatment diastolic pressure of 50-70 mmHg to 35 patients (42.7%) at 71-90 mmHg, p0.01.The incidence of first-dose hypotension with angiotensin-converting enzyme inhibitors in outpatients with chronic heart failure due to systolic dysfunction is high. Pre-treatment diastolic pressure is an independent risk factor, and its predictive value increases with pro-drug angiotensin-converting enzyme inhibitors. This could help physicians to anticipate asymptomatic first-dose hypotension and increase the utilization of these agents in heart failure.

The association between Chlamydia pneumoniae infection and atherosclerosis has gained recognition. However, the nature of this association is controversial. The infective link may not be specific for atherosclerosis and may also exist in other nonatherosclerotic arterial diseases. We investigated patients with nonspecific aortoarteritis for serological evidence of prior Chlamydia pneumoniae infection.Fifty patients each of nonspecific aortoarteritis and coronary artery disease with angiographic evidence of significant (70%) coronary artery lesions were tested for the presence of IgG antibodies against Chlamydia pneumoniae by micro-immunofluorescence assay and compared with 50 age- and sex-matched normal healthy controls. The number of patients with nonspecific aortoarteritis who tested positive for Chlamydia pneumoniae antibodies (IgG) was not significantly different from controls (8 v. 7, p=ns). The mean titer amongst positive subjects in the two groups was also similar (1:40+/-40 v. 1:50+/-25; p=ns). Patients with coronary artery disease were significantly older than patients with nonspecific aortoarteritis and controls (53.2+/-5.8 v. 21.2+/-9.9 years and 24.5+/-5.2 years, p0.01 for both) and showed a higher seroprevalence of prior Chlamydia pneumoniae infection (18 v. 8 and 7, p0.05 for both). The mean IgG titers of patients with coronary artery disease who tested positive were also significantly higher than the other two groups (1:98+/-34 v. 1:40+/-40, p0.001 and 1:98+/-34 v. 1:50+/-25, p0.01, respectively).In patients with nonspecific aortoarteritis, the seroprevalence of prior Chlamydia pneumnoniae infection is not more than that in healthy individuals of the same age group, but is significantly lesser than that in patients with coronary artery disease. Thus Chlamydia pneumoniae infection may not be associated with all forms of chronic inflammatory arterial lesions.

Background Thrombolytic therapy (TT) has evolved as an alternative to surgery for prosthetic valve thrombosis (PVT), but its utility in patient management is still debated and the long-term results are not available. Methods From 1990 through 1999, we treated 110 consecutive patients (52 men, mean age 35.4 ± 10.8 years) of left-sided obstructive PVT (96 mitral, 14 aortic) with TT (streptokinase in 108, urokinase in 2) according to a specified protocol of prolonged infusion. Serial echo Doppler parameters were monitored in all patients to guide the duration of TT and to quantify its efficacy. Ninety of the 102 survivors of the index episode were followed up for a mean period of 31.3 ± 27.8 months (range 1-112 months). Results Complete hemodynamic response (on cinefluoroscopy and echo Doppler criteria) was seen in 90 (81.8%) episodes, partial response in 11 (10%), and failure in 9 (8.2%). The mean duration of TT was 42.8 ± 20.4 hours. Five of the 7 patients who were initially seen in cardiogenic shock/overt pulmonary edema died during therapy. After these patients were excluded, the rate of complete response did not differ among patients with New York Heart Association class I/II (80%), class III (86.3%), or class IV (81.5%). The response rate also did not vary with the type, position of prosthesis, duration of symptoms, or time lag since surgery. There were 21 (19.1%) embolic episodes during therapy, including 6 strokes. These were significantly more frequent in patients with atrial fibrillation (AF) (odds ratio on multivariate analysis 2.3, 95% confidence interval 1.3-3.9, P =.01). On follow-up, there were 25 recurrences of PVT, of which 20 again received TT with a complete response in 14 (70%). At 5 years the actuarial survival was 85.2% and the event-free survival was 61.5%. The presence of chronic AF was a significant predictor of recurrence of PVT (odds ratio 2.2, 95% confidence interval 1.2-3.9, P =.008). Conclusions TT is effective in the majority of patients with PVT but is associated with a high rate of embolism, especially in patients with AF. Excluding patients with cardiogenic shock/overt pulmonary edema (in whom TT is largely ineffective), the success of TT does not vary with the New York Heart Association class, duration of symptoms, or other patient variables. The recurrence rates of PVT are high after even successful TT, especially in patients with AF. (Am Heart J 2000;140:906-16.)

During the last eight years a total of nine cases of isolated congenital coronary arteriovenous fistula (CAVF) have been diagnosed at our centre. Age of these patients ranged from 11 days to 22 years (mean 6.4 +/- 4.2 years). There were seven male and two female patients. Right and left coronary arteries were the sites of origin in seven and three cases respectively. One patient had two fistulae, one each originating from right coronary artery and obtuse marginal artery. The drainage sites were right ventricle in seven cases and right atrium in two. The pulmonary artery pressure was normal in eight cases and elevated in one case. The pulmonary artery to systemic flow ratio ranged from 1.1:1-2.4:1 in all except the 11 day-old-baby in whom it was 4:1. Pulmonary vascular resistance (PVRI) was below 3.5 in all cases (range 1.0-3.5 units). Surgical ligation of fistula was done in four cases and two patients underwent coil embolisation of fistula. Follow-up is available in five out of eight patients including three cases in whom CAVF was closed. Two other young patients are being followed-up conservatively and all the patients are asymptomatic. CAVF can present at any age; majority of the cases have small left to right shunts and more commonly CAVF arise from right coronary artery. Surgical ligation of fistula is safe in older patients, non-surgical embolisation using coils may be an alternative to surgery in selected cases.

We performed transcatheter alcohol ablation of the septum in a case of hypertrophic obstructive cardiomyopathy. The patient showed marked reduction in LVOT gradient; however, he developed complete atrioventricular (AV) dissociation following the procedure, requiring AV sequential pacing. This important complication of this novel technique is highlighted. Cathet. Cardiovasc. Diagn. 41:56–58, 1997. © 1997 Wiley-Liss, Inc.

Effects of high altitude hypoxia on systolic time intervals were examined in 34 healthy men: 20 sea level residents studied at rest and at the end of 3 minutes steady isometric (handgrip) exercise at sea level and then serially for the first 5 days and on the tenth day, at an altitude of 3658 m, and I4 permanent residents at high altitude studied at high altitude. In the sea level residents there was a significant increase in the pre-ejection period (PEP), abbreviation of the left ventricular ejection time (LVET), both corrected for heart rate, and prolongation of the PEP/LVET ratio at high altitude. The maximum changes were seen on days 2 and 3; these parameters tended to approach sea level control values by the tenth day. The systolic time interval values of high altitude residents were similar to the control values of the sea level residents obtained at sea level but significantly different from the changes in the sea level values seen in the first 4 days at high altitude. It thus appears that while the high altitude residents do not show any left ventricular dysfunction as determined by systolic time intervals, healthy sea level residents when exposed to high altitude hypoxia show a significant depression of the left ventricular function for at least the first 4 days. This might be a contributing factor in the genesis of high altitude pulmonary oedema.

Changes in transthoracic electrical impedance (T.E.I.) due to high-altitude hypoxia (3,658 m) have been measured in 20 young, healthy Indian soldiers. They were first studied at sea level (198 m) and then rapidly transported by air to 3,658 m, where they were studied daily from day 1 to day 5 and then on days 8 and 10. The mean (+/-S.D.) T.E.I. at sea level (34.6+/-0.6Omega) fell sharply to 29.6+/-0.8Omega, 30.3+/-0.9Omega, and 30.5+/-1.1Omega on days 1, 2, and 3 (P0.001) and levelled off at 31.5+/-0.7Omega on day 10, which was comparable to the mean value obtained in 13 persons permanently resident at high altitude (32.2+/-0.7Omega). Five sea-level residents who had acute mountain sickness (A.M.S.) or high-altitude pulmonary oedema (H.A.P.O.) had a still lower mean value (22.5+/-1.1Omega). One normal healthy subject who at sea level had a T.E.I. of 34.7Omega developed H.A.P.O. when the T.E.I. fell to 21.1Omega. Ninety minutes after the administration of 80 mg of intravenous frusemide the value increased to 35.5Omega. In another subject with A.M.S. who received 40 mg of frusemide intravenously the T.E.I. rose from 21.9 to 33.2Omega.Since the study was non-invasive the changes in impedance could not be correlated objectively with alterations in either pulmonary blood volume or pulmonary extravascular water space. In the subject, however, with x-ray evidence of H.A.P.O. and a low T.E.I. intravenous frusemide produced a marked rise in T.E.I. together with clearing of the chest x-ray picture within 24 hours, indicating an inverse relationship between impedance and thoracic fluid volume. It is suggested that with further objective verification in man the measurement of T.E.I. may be a potentially promising technique for the early detection of increased pulmonary fluid volume.

Physical work capacity is reduced in sea level residents--lowlanders (LL) as compared to high altitude residents--highlanders (HL). To determine possible etiologies, cardiac performance was studied in two groups of healthy male volunteers (13 LL and 11 HL) utilizing systolic time intervals during rest, submaximal and maximal exercise. The LL were studied at sea level and subsequently during 10 days of residence at an altitude of 3658 m. The HL were studied at high altitude alone. The LL were restudied 30-45 min after administration of intravenous furosemide at high altitude. Mean maximal oxygen uptake (VO2max) was reduced by 26% in the LL group at high altitude in comparison to sea level values and by 20% in relation to the HL group. Cardiac performance was estimated by the pre-ejection period/left ventricular ejection time ratio. This index was significantly increased in the LL group at high altitude in comparison to sea level values during submaximal and maximal exercise (P less than 0.01). Intravenous furosemide in the LL group increased the heart rate (P less than 0.05) at rest and during exercise but VO2max and cardiac performance were unchanged. It is hypothesized that reduced physical work capacity at high altitude in the LL group may be related to depression of cardiac performance in these subjects. Administration of intravenous furosemide did not influence cardiac performance in the LL group at high altitude.

Haemodynamic studies in 8 tribal patients from central India with veno-occlusive disease of the liver are reported. The disease was caused by eating cereals contaminated with seeds of a crotalaria species rich in toxic pyrrolizidine alkaloids similar to monocrotaline and fulvine. All patients showed raised hepatic venous wedge pressures and pressure gradients between hepatic venous wedge and free hepatic vein. Significant pressure gradients were also observed in the inferior vena cava. Right and left heart pressures were normal. Cardiac and stroke indices and ventricular work were significantly increased while systemic and pulmonary resistances were reduced. Hepatic blood flow was also reduced. Hepatic venograms were abnormal and the changes correlated well with the pressure gradients between hepatic venous wedge and free hepatic vein and with the histological changes in the liver.

One hundred four patients (101 men, three women), under 40 years of age, with myocardial infarction (MI), underwent coronary arteriography. Eighty patients had significant obstructive coronary artery disease (CAD) (group 1), 23 had normal coronary arteries (group 2), and one patient had coronary ostial stenosis as a result of nonspecific aortoarteritis (group 3). Coronary risk factors in group 1 included smoking (76.2%), hypercholesterolemia (36.3%), hypertension (32.5%), positive family history (28.7%), and diabetes mellitus (5%). Multiple risk factors were frequent (56.2%). Smoking was common (p less than 0.01) and diabetes mellitus less frequent (p less than 0.05) as compared to older (greater than 40 years) patients with MI and arteriographically proved CAD. The frequency of one-, two-, and three-vessel disease was 33.7%, 26.2%, and 40%, respectively, in group 1. Group 2 patients were almost devoid of coronary risk factors. The only group 3 patient had left coronary ostial stenosis with no risk factors. Similar to their counterparts in developed countries, young Indian patients with MI and obstructive CAD have a high frequency of coronary risk factors, especially smoking and severe multiple-vessel disease. Since normal coronary arteriograms are also frequent in this setting, a detailed evaluation is recommended for purposes of prognosis and management.

Intracardiac frusemide given to seven patients recovering from high-altitude pulmonary oedema caused a significant reduction in the pulmonary blood volume before the onset of diuresis. This supports the suggestion that the mobilization of fluid from the pulmonary circuit is responsible for the relief of symptoms in some patients with pulmonary oedema even when a diuresis does not occur.

ACUTE mountain sickness and high altitude pulmonary oedema are two acute medical problems for troops in the Himalayan terrain who frequently shuttle between sea level and high altitudes (10,000–16,000 ft.). These two acute illnesses have some features in common: time lag (they rarely occur within 12 h of arrival at the altitude or 96 h after arrival), throbbing headache, muscular cramps and pulmonary congestion. We have studied the acute circulatory response to high altitude hypoxia and investigated the extent to which shifts in the circulating blood volumes, if any, could be related to the time lag and clinical features of these acute illnesses.

The immediate haemodynamic effects of peruvoside, a cardiac glycoside obtained from the Indian plant Thevetia neriifolia Juss, were studied in six patients with congestive heart failure. The drug was found to have an immediate and powerful positive inotropic and negative chronotropic effect, like ouabain, on the failing human heart. Oral peruvoside was also effective in the treatment of congestive heart failure when used on a short-term as well as a long-term basis. It therefore seems that peruvoside is a useful cardiac glycoside in the management of congestive heart failure in man as a quick-acting intravenous preparation. It is equally effective when used orally.