Anand Chockalingam

Dynamic Left Ventricular Outflow Tract Obstruction in Acute Myocardial Infarction With Shock Cause, Effect, and Coincidence

Case presentation: A 70-year-old white woman with a prior history of tobacco abuse, emphysema, and recent pneumonia presented to an outside emergency room with brief episodes of dull chest pressure recurring over 5 days. Because the current episode was not relieved after 4 hours, and because her ECG showed ST elevation up to 3 mm in V2 through V6, she was given heparin and nitroglycerin infusions and was transferred to the University of Missouri. On admission to our hospital, she was pain-free with stable vital signs. Her examination was remarkable for a grade 2/6 systolic ejection murmur in the left third intercostal space. An ECG showed Q waves in V1 through V3. Echocardiography revealed significant left ventricular (LV) dysfunction, ejection fraction of 35% with systolic anterior motion (SAM) of the anterior mitral leaflet, and moderate mitral regurgitation (MR; Figure 1). LV outflow tract (LVOT) gradients were not quantified owing to MR Doppler contamination. Her maximum troponin was 5 ng/mL, and brain natriuretic peptide was 190 pg/mL. Catheterization showed normal coronaries with anteroapical akinesia and LV dysfunction with an ejection fraction of 30%. Figure 1. Apical 4-chamber view showing SAM of anterior mitral leaflet. LA indicates left atrium. The patient became hypotensive after catheterization, with systolic pressures between 70 and 85 mm Hg. Dopamine infusion did not improve blood pressure, and the murmur increased to grade 3/6 intensity. Atrial fibrillation developed with a ventricular rate of 150 bpm. Dopamine was discontinued, and intravenous amiodarone converted the …

Acute left ventricular dysfunction in the critically ill.

Acute left ventricular (LV) dysfunction is common in the critical care setting and more frequently affects the elderly and patients with comorbidities. Because of increased mortality and the potential for significant improvement with early revascularization, the practitioner must first consider acute coronary syndrome. However, variants of stress (takotsubo) cardiomyopathy may be more prevalent in ICU settings than previously recognized. Early diagnosis is important to direct treatment of complications of stress cardiomyopathy, such as dynamic LV outflow tract obstruction, heart failure, and arrhythmias. Global LV dysfunction occurs in the critically ill because of the cardio-depressant effect of inflammatory mediators and endotoxins in septic shock as well as direct catecholamine toxicity. Tachycardia, hypertension, and severe metabolic abnormalities can independently cause global LV dysfunction, which typically improves with addressing the precipitating factor. Routine troponin testing may help early detection of cardiac injury and biomarkers could have prognostic value independent of prior cardiac disease. Echocardiography is ideally suited to quantify LV dysfunction and determine its most likely cause. LV dysfunction suggests a worse prognosis, but with appropriate therapy outcomes can be optimized.

Exercise and the metabolic syndrome with weight regain

Weight loss improves metabolic syndrome (MetS) factors, but risk may return with weight regain. This study was designed to determine if exercise training can maintain improvements in MetS risk factors during weight regain. In a randomized control trial,102 overweight or obese (body mass index 25.0-39.9 kg/m(2)) men and women (age 21-52 yr), with characteristics of the MetS, lost 10% of body weight with supervised walking/jogging at 60% of maximal oxygen consumption (Vo(2 max)) (-400 kcal/session), 5 days/wk, and caloric restriction (-600 kcal/day) over a 4- to 6-mo period. After weight loss, 77 remaining subjects underwent programmed weight regain (+50% of lost weight) for 4-6 mo with random assignment to two groups: no exercise (NoEX) or continued supervised exercise (EX). Blood pressure, regional fat, glucose homeostasis, lipids, and inflammatory markers were assessed at baseline, post-weight loss, and post-weight regain. Groups were compared by two-way repeated-measures ANOVA on the 67 subjects. After weight loss (9.7 +/- 0.2% of body weight), significant (P < 0.05) improvements were observed in almost all parameters assessed. Following weight regain (54.4 +/- 1.6% of lost weight), the NoEX group exhibited deterioration in most metabolic markers, while the EX group maintained improvements in Vo(2 max), blood pressures, glucose homeostasis, high- and low-density lipoprotein cholesterol (HDL-C and LDL-C), oxidized LDL, and other markers of inflammation, but did not maintain improvements in triglyceride and cholesterol concentrations or abdominal fat. Results of this design of controlled human weight regain suggest that aerobic exercise can counter the detrimental effects of partial weight regain on many markers of disease risk.

Statin therapy lowers muscle sympathetic nerve activity and oxidative stress in patients with heart failure

Despite standard drug therapy, sympathetic nerve activity (SNA) remains high in heart failure (HF) patients making the sympathetic nervous system a primary drug target in the treatment of HF. Studies in rabbits with pacing-induced HF have demonstrated that statins reduce resting SNA, in part, due to reductions in reactive oxygen species (ROS). Whether these findings can be extended to the clinical setting of human HF remains unclear. We first performed a study in seven statin-naïve HF patients (56 ± 2 yr; ejection fraction: 31 ± 4%) to determine if 1 mo of simvastatin (40 mg/day) reduces muscle SNA (MSNA). Next, to control for possible placebo effects and determine the effect of simvastatin on ROS, a double-blinded, placebo-controlled crossover design study was performed in six additional HF patients (51 ± 3 yr; ejection fraction: 22 ± 4%), and MSNA, ROS, and superoxide were measured. We tested the hypothesis that statin therapy decreases resting MSNA in HF patients and this would be associated with reductions in ROS. In study 1, simvastatin reduced resting MSNA (75 ± 5 baseline vs. 65 ± 5 statin bursts/100 heartbeats; P < 0.05). Likewise, in study 2, simvastatin also decreased resting MSNA (59 ± 5 placebo vs. 45 ± 6 statin bursts/100 heartbeats; P < 0.05). In addition, statin therapy significantly reduced total ROS and superoxide. As expected, cholesterol was reduced after simvastatin. Collectively, these findings indicate that short-term statin therapy concomitantly reduces resting MSNA and total ROS and superoxide in HF patients. Thus, in addition to lowering cholesterol, statins may also be beneficial in reducing sympathetic overactivity and oxidative stress in HF patients.

Adaptive mechanisms to compensate for overnutrition-induced cardiovascular abnormalities.

In conditions of overnutrition, cardiac cells must cope with a multitude of extracellular signals generated by changes in nutrient load (glucose, amino acids, and lipids) and the hormonal milieu [increased insulin (INS), ANG II, and adverse cytokine/adipokine profile]. Herein, we review the diverse compensatory/adaptive mechanisms that counter the deleterious effects of excess nutrients and growth factors. We largely focus the discussion on evidence obtained from Zucker obese (ZO) and Zucker diabetic fatty (ZDF) rats, which are useful models to evaluate adaptive and maladaptive metabolic, structural, and functional cardiac remodeling. One adaptive mechanism present in the INS-resistant ZO, but absent in the diabetic ZDF heart, involves an interaction between the nutrient sensor kinase mammalian target of rapamycin complex 1 (mTORC1) and ANG II-type 2 receptor (AT2R). Recent evidence supports a cardioprotective role for the AT2R; for example, suppression of AT2R activation interferes with antihypertrophic/antifibrotic effects of AT1R blockade, and AT2R agonism improves cardiac structure and function. We propose a scenario, whereby mTORC1-signaling-mediated increase in AT2R expression in the INS-resistant ZO heart is a cardioprotective adaptation to overnutrition. In contrast to the ZO rat, heart tissues of ZDF rats do not show activation of mTORC1. We posit that such a lack of activation of the mTOR↔AT2R integrative pathway in cardiac tissue under conditions of obesity-induced diabetes may be a metabolic switch associated with INS deficiency and clinical diabetes.

Unexplained hypotension: the spectrum of dynamic left ventricular outflow tract obstruction in critical care settings.

Objective:To illustrate the clinical and hemodynamic abnormalities caused by dynamic left ventricular outflow tract obstruction (LVOTO) in critical care setting. Design:We reviewed cases referred to Cardiology with echocardiographic evidence of LVOTO and their clinical presentations. We present those cases where LVOTO can transiently occur without hypertrophic cardiomyopathy when inotropic agents are used for hypotension. Measurements and Main Results:Five women in the 50–70 age range and prior history of hypertension presented with various symptoms like chest discomfort, fatigue, dizziness, atrial fibrillation, and hypotension. An ejection systolic murmur was noted most often in the left third intercostal space and ECG revealed ST-T wave abnormalities. LVOTO caused by mitral systolic anterior motion was detected by echocardiography and catheterization excluded acute coronary disease. In critical care setting, LVOTO can occur due to apical ballooning syndrome, coronary disease, medications, volume depletion, and valvular abnormalities. Because this condition mimics acute coronary syndrome or other etiologies of hypotension in medical and surgical intensive care units, appropriate treatment can be delayed. Nonhypertrophic cardiomyopathy LVOTO usually responds well to fluid replacement, beta blockers, and medication changes. Conclusions:LVOTO should be suspected especially in women presenting with hypotension and systolic murmur in critical care settings. Clinical acumen and timely echocardiography are required to effectively counter this transient but potentially lethal problem.

Tachycardia‐Induced Cardiomyopathy: Evaluation and Therapeutic Options

Tachycardia-induced cardiomyopathy is caused by sustained rapid ventricular rates and is one of the well-known forms of reversible myocardial dysfunction. The diagnosis is usually made retrospectively after marked improvement in systolic function is noted following control of the heart rate. Physicians should be aware that patients with seemingly idiopathic systolic dysfunction may have tachycardia-induced cardiomyopathy and that controlling the heart rate may result in improvement or even complete restoration of systolic function.

Meal frequency differentially alters postprandial triacylglycerol and insulin concentrations in obese women.

The aim of this study was to compare postprandial lipemia, oxidative stress, antioxidant activity, and insulinemia between a three and six isocaloric high‐carbohydrate meal frequency pattern in obese women.

Treatment of 25-OH vitamin D deficiency in older men with chronic kidney disease stages 3 and 4 is associated with reduction in cardiovascular events.

Observational studies in healthy people suggest an inverse relationship between serum 25-hydroxyvitamin D (25OHD) levels and cardiovascular (CV) mortality. Treating vitamin D deficiency in patients with moderate chronic kidney disease (CKD) may reduce CV events in this high-risk population. Study data were abstracted from Harry S. Truman Memorial Veterans Hospital electronic medical record system. The medical records of all veterans who had CKD stages 3 and 4 and had 25OHD levels determined from April 2006 to September 2007 were reviewed. Patients with 25OHD deficiency, serum level <30 ng/mL, were included (N = 126, all men, mean age = 70 years). Successful 25OHD replacement was defined as prescription of ergocalciferol sufficient to increase serum 25OHD level by 25% from baseline within 6 months (treatment group, n = 90). Otherwise patients were considered as untreated controls (n = 36). The date when the 25OHD level was drawn was considered as the date of inclusion. All the patients were followed up from the date of inclusion until July 2009 to capture CV events prospectively. During mean follow-up of 27.2 months, 44% of the controls had CV events, whereas only 21% of the patients in the treatment group had CV events (P = 0.001). In multivariate logistic regression analysis, adjusting for CV disease predictors age, initial parathyroid hormone level, statin use, history of CV disease, and glomerular filtration rate, the estimated odds ratio for 25OHD replacement status was 0.37 (95% confidence interval: 0.14–1.0). Treatment of 25OHD deficiency with ergocalciferol in patients with moderate CKD is associated with significant reduction in CV events.

Echocardiography in stress cardiomyopathy and acute LVOT obstruction

Widespread use of echocardiography has contributed to more frequent recognition of takotsubo stress cardiomyopathy. Initial presentation is similar to acute coronary syndrome and the acute course can be complicated by heart failure, arrhythmias, dynamic left ventricular outflow tract obstruction, hypotension and death. We briefly review the clinical presentation and propose a unified diagnostic algorithm for cardiologists acutely managing this cardiac emergency. We highlight the central role of echocardiography and emphasize the nuances of this peculiar acute cardiomyopathy from an echocardiographers’ perspective.