Gurushankar Govindarajan

The Cardiometabolic Syndrome as a Cardiovascular Risk Factor

The cardiometabolic syndrome (CMS) is associated with cardiovascular disease (CVD) and includes a constellation of risk factors such as central obesity, hypertension, insulin resistance, dyslipidemia, microalbuminuria, and hypercoagulability. Collectively, these risk factors increase CVD endpoints such as stroke, congestive heart failure, chronic kidney disease (CKD), and overall mortality. The CMS is associated with endothelial dysfunction, inflammation, abnormal thrombolysis, and increased oxidative stress that accentuate progression of CVD. We will review how the varying components of the CMS relate to an increased CVD and renal disease risk.

Effect of Weight Loss After Bariatric Surgery on Left Ventricular Mass and Ventricular Repolarization in Normotensive Morbidly Obese Patients

To assess the effect of weight loss on ventricular repolarization in morbidly obese patients, 39 normotensive subjects whose baseline body mass indexes were ≥40 kg/m(2) before weight loss from bariatric surgery were studied. All patients were free of underlying organic heart disease, heart failure, and conditions that might affect ventricular repolarization. Twelve-lead electrocardiography and transthoracic echocardiography were performed just before surgery and at the nadir of postoperative weight loss. The corrected QT interval (QTc) was derived using Bazetts formula. QTc dispersion was calculated by subtracting the minimum from the maximum QTc on the 12-lead electrocardiogram. Echocardiographic left ventricular (LV) mass was indexed to height(2.7). The mean body mass index decreased from 42.8 ± 2.1 to 31.9 ± 2.2 kg/m(2) (p <0.0005). For the entire group, weight loss was associated with significant reductions in mean QTc (from 428.7 ± 18.5 to 410.5 ± 11.9 ms, p <0.0001) and mean QTc dispersion (from 44.1 ± 11.2 to 33.2 ± 3.3 ms, p <0.0005). Mean QTc and QTc dispersion decreased significantly with weight loss in patients with LV hypertrophy but not in subjects without LV hypertrophy. Multivariate analysis identified pre-weight loss LV mass/height(2.7) as the most important predictor of pre-weight loss QTc and QTc dispersion and also identified weight loss-induced change in LV mass/height(2.7) as the most important predictor of weight loss-induced changes in QTc and QTc dispersion. In conclusion, LV hypertrophy is a key determinant of QTc and QTc dispersion in normotensive morbidly obese patients. Regression of LV hypertrophy associated with weight loss decreases QTc and QTc dispersion.

Stroke prevention in diabetes and obesity

Stroke is an important cause of morbidity and mortality, and is an economic burden. Diabetes and obesity are two important modifiable risk factors for stroke. Patients with diabetes have a higher incidence of stroke and a poorer prognosis after stroke. Risk-factor modification is the most important aspect of prevention of stroke in diabetes and obesity. This includes lifestyle modifications and different therapeutic modalities to control conditions, such as diabetes, hypertension, dyslipidemia and arrhythmia. Recent landmark studies have shown the beneficial effects of statins in diabetic patients even with close to normal or normal low-density lipoprotein cholesterol. Obesity, which is a risk factor for diabetes, hypertension and hyperlipidemia has been shown to be an independent risk factor for stroke. Increased leptin, dysregulation of adipocyte proteins, increased insulin resistance and C-reactive protein may be factors involved in the increased incidence of cardiovascular morbidity and mortality directly related to obesity. Visceral fat is a much bigger health risk than subcutaneous fat. Lifestyle interventions and pharmacotherapeutic agents have been used to manage obesity. In morbidly obese patients, surgical intervention seems to be the best method of treatment with a long-lasting favorable metabolic outcome. In the 21st Century, with the advanced medical knowledge and the therapeutic modalities available, it should be possible to reduce the incidence of stroke associated with diabetes and obesity.

Endocrine and metabolic effects of fat: cardiovascular implications.

The prevalence of obesity is increasing rapidly in both industrialized and developing nations. Obesity causes complex metabolic, endocrine, and hemodynamic changes that may lead to adverse cardiovascular outcomes such as coronary heart disease and congestive heart failure. Adipose tissue is no longer considered to be an inert organ of energy storage, but in fact possesses important endocrine and metabolic functions that are closely involved in energy homeostasis. During the past decade, our understanding of the unique pathophysiologic changes that occur with obesity has rapidly grown. This review discusses our current understanding of the endocrine and metabolic effects of fat and their potential relation to cardiovascular disease.

Insights into the emerging cardiometabolic prevention and management of diabetes mellitus.

Cardiovascular disease (CVD) and Type 2 diabetes mellitus (DM2), once conceived as different entities, share common origins and pathways. Increased activity of the renin-angiotensin-aldosterone-system, insulin resistance, chronic low-grade inflammation and oxidative stress collectively contribute to endothelial dysfunction and atherosclerosis, which manifest clinically as CVD. Nowadays, it is possible to identify and intervene in high-risk populations even before the clinical diagnosis of DM2. The control of dietary patterns and increased physical activity is completely feasible, as well as the management of hypertension and dyslipidaemia. Pharmacological interventions targeted at blocking renin-angiotensin-aldosterone-system and sensitising to insulin have a role in the prevention of DM2 and CVD, and are avidly explored worldwide. In the near future, ongoing trials should provide data that will allow us to better treat patients with the cardiometabolic syndrome and diabetes in order to reduce CVD morbidity and mortality.

Sweet syndrome associated with furosemide

This case report describes a case of Sweet syndrome (SS) related to use of furosemide in a 46-year-old female who was admitted for treatment of congestive heart failure. Three days after administration of furosemide, the patient had a fever and a skin eruption appeared on her wrists, forearms, and legs. Biopsy of the skin lesion was consistent with SS. Infection was thought to be unlikely because of negative blood cultures, echocardiography, and other imaging studies. Careful review of her medications revealed that the patient received furosemide before the appearance of the skin eruption and fever. After discontinuation of furosemide, the patients skin lesion and fever resolved. A MEDLINE search from June 1966 to May 2004 revealed only one reference documenting the association of SS with furosemide administration. Patients who have development of SS without an obvious cause should have their medication list closely reviewed.

Relation of Left Ventricular Mass to QTc in Normotensive Severely Obese Patients

Prolongation of the corrected QT interval (QTc) has been described in obese subjects. This study assesses the relation of left ventricular (LV) mass to QTc in normotensive severely obese subjects. Fifty normotensive patients whose BMI was ≥40 kg/m2 (mean age: 38 ± 7 years) were studied. QTc was derived using Bazetts formula. LV mass was calculated using the formula of Devereux et al. and was indexed to height2.7. Mean QTc was 428.8 ± 19.0 ms and was significantly longer in those with than in those without LV hypertrophy (P < 0.01) QTc correlated positively and significantly with BMI (r = 0.392, P < 0.025), LV mass/height2.7 (r = 0.793, P < 0.0005), systolic blood pressure (r = 0.742, P < 0.001), LV end — systolic wall stress (r = 0.746, P < 0.001) and LV internal dimension in diastole (r = 0.788, P < 0.0005). Among five variables tested, LV mass/height2.7 was identified as the sole predictor of QTc by multivariate analysis. In conclusion, LV mass and loading conditions that may affect LV mass are important determinants of QTc in normotensive severely obese subjects.

Cardiac safety of conducted electrical devices in pigs and their effect on pacemaker function.

OBJECTIVE The aims of this study are to evaluate the cardiac safety of the Stinger S-200 Conducted Energy Weapon Device (CED) (Stinger Systems, Tampa, Fla) on a human-sized pig model and to test the effect of various commercially available CEDs, specifically the Stinger S-200, TASER M26 (Taser International, Scottsdale, Ariz), and TASER X26 on pacemaker function. METHODS Two groups of pigs, divided based on weight as group 1 (n = 3, 67.3 ± 4.7 kg) and group 2 (n = 3, 89.3 ± 1.2 kg), were used. In protocol 1, the Stinger S-200 was applied in multiple different orientations to simulate possible field scenarios across the heart. In protocol 2, a single-chamber bipolar lead connected to a pacemaker was placed in the right ventricle of the pig, and different CEDs were applied to test the pacemaker function during CED application. RESULTS In protocol 1, the S-200 was applied a total of 216 times in the 6 pigs, and neither episodes of ventricular fibrillation nor episodes of sustained ventricular tachycardia were noted. In protocol 2, the CED discharges (1) were recognized by the pulse generator and sensed as either high-rate atrial or ventricular activity, (2) did not affect the native rhythm, (3) did not conduct down the lead systems to cause any extra systoles, and (4) had no effect on paced rhythm. CONCLUSIONS In this model, the application of the S-200 in various orientations across the heart did not result in any sustained abnormal cardiac rhythms. None of the tested CEDs adversely affected the functioning of the tested pacemaker. Stinger Systems has now replaced the S-200 with the S-200T with a different output.

Exercise and Weight Loss Improve Exercise Capacity Independent of Cardiac Function in Metabolic Syndrome

Hypertension, diabetes and obesity cause cardiac diastolic dysfunction (DD) which could reduce exercise capacity. Our aim was to determine if 10% weight loss by exercise at 60% VO2max five days/week (~-375 kcal/session) and caloric restriction (~-600 kcal/d) over 6 months improves exercise capacity and DD in Metabolic syndrome (MetS). Eighteen subjects (40 ± 1y, women = 6, BMI = 33.5 ± 1.0 kg/m2) successfully completed the study. Maximal treadmill stress echocardiography was performed at baseline and post weight loss to determine VO2max, resting and stress DD as the ratio of peak early diastolic mitral inflow velocity (E) to tissue Doppler early diastolic annular decent (E’). After weight loss (mean = 9.5 ± 0.2%), all metabolic parameters improved. Resting and stress E/E’ values remained normal before and after weight loss. Exercise intolerance is likely due to general deconditioning and not cardiac dysfunction in early MetS as VO2max increases significantly with lifestyle while cardiac function remains unchanged.

Dobutamine stress echocardiography Doppler estimation of cardiac diastolic function: a simultaneous catheterization correlation study.

Background: Doppler echocardiography using the ratio of early diastolic transmitral velocity to early diastolic mitral annular tissue velocity (E/E′) is routinely used to evaluate left ventricular (LV) filling pressures at rest. We tested the hypothesis that measurement of E/E′ in patients undergoing dobutamine stress echocardiography (DSE) will detect changes in LV filling pressures. Methods: In this prospective study, 16 patients with normal LV ejection fraction and normal coronary arteries by angiography underwent a standard DSE protocol with simultaneous LV filling pressure monitoring with a fluid filled pigtail catheter. Doppler echocardiographic assessment of LV diastolic function was performed using E/E′ at rest and during DSE. Results: The average age of the study participants was 57 ± 8 years. Average heart rate was 61 ± 11 bpm at baseline and 141 ± 12 bpm at peak stress. LV mean diastolic pressure decreased from 12.3 ± 2.6 mmHg at baseline to 9.0 ± 2.3 mmHg at peak stress (P = 0.0001). Baseline E/E′ at the septum and lateral annulus were 8.7 ± 2.2 and 7.5 ± 1.9 and during peak stress were 8.3 ± 3.1 and 7.9 ± 3.5, respectively. There was no significant change in E/E′ at either the septum or the lateral annulus (P = 0.55, P = 0.66). There was no significant correlation between LV mean diastolic pressure and E/E′ with dobutamine stress. Conclusions: In patients with normal LV ejection fraction and no significant coronary artery disease undergoing DSE, the ratio of early diastolic transmitral velocity to early diastolic tissue velocity (E/E′) at peak stress with dobutamine does not predict changes in LV filling pressures. (Echocardiography 2011;28:442‐447)