Takotsubo syndrome (TTS) is caused by catecholamine surge, which is also observed in COVID-19 disease due to the cytokine storm. We performed a systematic literature search using PubMed/Medline, SCOPUS, Web of Science, and Google Scholar databases to identify COVID-19-associated TTS case reports and evaluated patient-level demographics, clinical attributes, and outcomes. There are 12 cases reported of TTS associated with COVID-19 infection with mean age of 70.8 ± 15.2 years (range 43–87 years) with elderly (66.6% > 60 years) female (66.6%) majority. The time interval from the first symptom to TTS was 8.3 ± 3.6 days (range 3–14 days). Out of 12 cases, 7 reported apical ballooning, 4 reported basal segment hypo/akinesia, and 1 reported median TTS. Out of 12 cases, during hospitalization, data on left ventricular ejection fraction (LVEF) was reported in only 9 of the cases. The mean LVEF was 40.6 ± 9.9% (male, 46.7 ± 5.7%, and female, 37.7 ± 10.6%). Troponin was measured in all 12 cases and was elevated in 11 (91.6%) without stenosis on coronary angiography except one. Out of 11 cases, 6 developed cardiac complications with 1 case each of cardiac tamponade, heart failure, myocarditis, hypertensive crisis, and cardiogenic shock in 2. Five patients required intubation, 1 patient required continuous positive airway pressure, and 1 patient required venovenous extracorporeal membrane oxygenation. The outcome was reported in terms of recovery in 11 (91.6%) out of 12 cases, and a successful recovery was noted in 10 (90.9%) cases. COVID-19-related TTS has a higher prevalence in older women. Despite a lower prevalence of cardiac comorbidities in COVID-19 patients, direct myocardial injury, inflammation, and stress may contribute to TTS with a high complication rate.

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.

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.

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.

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Genome-wide association studies (GWAS) have led to a rapid increase in available data on common genetic variants and phenotypes and numerous discoveries of new loci associated with susceptibility to common complex diseases. Integrating the evidence from GWAS and candidate gene studies depends on concerted efforts in data production, online publication, database development, and continuously updated data synthesis. Here the authors summarize current experience and challenges on these fronts, which were discussed at a 2008 multidisciplinary workshop sponsored by the Human Genome Epidemiology Network. Comprehensive field synopses that integrate many reported gene-disease associations have been systematically developed for several fields, including Alzheimer's disease, schizophrenia, bladder cancer, coronary heart disease, preterm birth, and DNA repair genes in various cancers. The authors summarize insights from these field synopses and discuss remaining unresolved issues—especially in the light of evidence from GWAS, for which they summarize empirical P-value and effect-size data on 223 discovered associations for binary outcomes (142 with P < 10−7). They also present a vision of collaboration that builds reliable cumulative evidence for genetic associations with common complex diseases and a transparent, distributed, authoritative knowledge base on genetic variation and human health. As a next step in the evolution of Human Genome Epidemiology reviews, the authors invite investigators to submit field synopses for possible publication in the American Journal of Epidemiology.

Case presentation: A 70-yearold 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 V 2 through V 6 , she was given heparin and nitroglycerin infusions and was transferred to the University of Missouri. On admission to our hospital, she was painfree 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 V 1 through V 3 . 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%.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 atrial fibrillation to sinus tachycardia at 115 bpm, but the hypotension and murmur persisted. Under close supervision, intravenous metoprolol was initiated. With reduction of heart rate to below 70 bpm, the murmur disappeared, and her blood pressure improved. Several hours later, a repeat echocardiogram showed no SAM or LVOT obstruction (LVOTO) and only mild MR.Numerous reports have highlighted the occurrence of dynamic LVOTO as a complication of ST-elevation myocardial infarction (STEMI). 1,2 LVOTO has also been detected in Ϸ20% of transient LV apical ballooning syndrome, also called Takatsubo cardiomyopathy. 3 The actual incidence of dynamic LVOTO is unclear, but it may be significantly underdiagnosed and can indeed mimic cardiogenic shock in an acute-care setting. 4 Mechanism of LVOTOStructural and functional factors contribute to the midsystolic development of gradients referred to as dynamic LVOTO. The asymmetrically hypertrophied septum, progressive narrowing of the LVOT during systole, and direction of the bloodstream cause drag forces and a Venturi effect on the anterior mitral leaflet, which results in SAM of the anterior mitral leaflet. This movement results in the anterior mitral leaflet contacting the septum for a period of systole, effectively obstructing the path of ventricular outflow. Failure of the anterior mitral leaflet to coapt with the posterior leaflet in systole results in MR. The degree and duration of mitral SAM determine the severity of the dynamic LVOTO gradients and MR. Although classically descr...

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.