Stroke Risk Following Takotsubo Cardiomyopathy.

BACKGROUND AND PURPOSE: Takotsubo cardiomyopathy, also known as stress cardiomyopathy, is an increasingly recognized cause of left ventricular dysfunction. Previously considered a benign disease, Takotsubo cardiomyopathy may be a risk factor of ischemic stroke based on recent small, single-center case series. The strength and temporal profile of this association remains uncertain. METHODS: We performed a cohort-crossover study using administrative claims data on all emergency department visits and acute care hospitalizations from 2005 to 2015 in California, New York, and Florida. We identified patients with Takotsubo cardiomyopathy, excluding those with a prior or concomitant stroke diagnosis. We compared the risk of ischemic stroke in the first year after Takotsubo cardiomyopathy to the risk of ischemic stroke in the second year after Takotsubo cardiomyopathy. Takotsubo cardiomyopathy and ischemic stroke were ascertained using previously validated ICD-9-CM codes. Absolute risks and odds ratios (OR) were calculated using McNemar test for matched data. RESULTS: Among 5283 patients with Takotsubo cardiomyopathy (mean age, 67 years; 92% female), we identified 49 ischemic strokes during the first year after Takotsubo cardiomyopathy versus 19 ischemic strokes during the second year after. The risk of stroke was significantly higher in the year after Takotsubo cardiomyopathy (absolute increase, 0.6%; 95% CI: 0.2-0.9; OR: 2.6; 95% CI: 1.5-4.6) as compared to the control period. CONCLUSION: We found a heightened risk of ischemic stroke in the year after a diagnosis of Takotsubo cardiomyopathy, although the absolute risk increase was small.

Tricuspid Stenosis in Pregnancy: A Valve-in-Valve Conundrum.

Redo tricuspid valve replacement has high surgical operative mortality. Transcatheter valve-in-valve provides a viable option for valve replacement. We discuss the decision-making process involved in performing transcatheter tricuspid valve-in-valve replacement in a 23-week pregnant woman with multiple comorbidities and symptomatic severe bioprosthetic stenosis. (Level of Difficulty: Intermediate.).

Survivin in Insulin-Like Growth Factor-Induced Resistance to Lapatinib in Head and Neck Squamous Carcinoma Cells.

Epidermal growth factor receptor (EGFR) inhibitors have limited efficacy in head and neck squamous cell carcinoma (HNSCC) due to various resistance mechanisms, such as activation of the insulin-like growth factor-1 receptor (IGF1R), which initiates pro-survival signaling. Survivin, a member of the inhibitor of apoptosis proteins family, is expressed at relatively high levels in malignant tissues and plays a role in cell division. Expression of survivin in tumors has been shown to correlate with poor prognosis due to chemotherapy resistance and anti-apoptotic behavior. We previously demonstrated that activation of the IGF1R reduces sensitivity to EGFR-tyrosine kinase inhibitors (TKIs) via reduced apoptosis suggesting a role of survivin in this process. This study evaluates the role of survivin in IGF1R-mediated lapatinib resistance. Using HNSCC cell lines FaDu and SCC25, survivin expression increased and lapatinib sensitivity decreased with IGF1R activation. Further, these effects were reversed by the survivin inhibitor YM-155. Conversely, survivin expression and lapatinib sensitivity were unchanged with IGF1R activation in UNC10 cells. YM-155 enhanced the inhibitory effect of lapatinib on UNC10 cells, regardless of activation of the IGF1R. These results demonstrate that enhanced survivin expression correlates with IGF1R-mediated lapatinib resistance in HNSCC cells and suggest that regulation of survivin expression may be a key mechanistic element in IGF1R-based therapeutic resistance. Combinatorial treatment with survivin antagonists and EGFR-TKIs warrants further investigation.

The Risk of Takotsubo Cardiomyopathy in Acute Neurological Disease.

BACKGROUND: Case series have reported reversible left ventricular dysfunction, also known as stress cardiomyopathy or Takotsubo cardiomyopathy (TCM), in the setting of acute neurological diseases such as subarachnoid hemorrhage. The relative associations between various neurological diseases and Takotsubo remain incompletely understood. METHODS: We performed a cross-sectional study of all adults in the National Inpatient Sample, a nationally representative sample of US hospitalizations, from 2006 to 2014. Our exposures of interest were primary diagnoses of acute neurological disease, defined by ICD-9-CM diagnosis codes. Our outcome was a diagnosis of TCM. Binary logistic regression models were used to examine the associations between our pre-specified neurological diagnoses and TCM after adjustment for demographics. RESULTS: Among acute neurological diagnoses, the strongest associations were seen with subarachnoid hemorrhage (odds ratio [OR] 11.7; 95% confidence interval [CI] 10.2-13.4), status epilepticus (OR 4.9; 95% CI 3.7-6.3), and seizures (OR 1.3; 95% CI 1.1-1.5). In a sensitivity analysis including secondary diagnoses of acute neurological diagnoses, associations were also seen with transient global amnesia (OR 2.3; 95% CI 1.5-3.6), meningoencephalitis (OR 2.1; 95% CI 1.7-2.5), migraine (OR 1.7; 95% CI 1.5-1.8), intracerebral hemorrhage (OR 1.3; 95% CI 1.1-1.5), and ischemic stroke (OR 1.2; 95% CI 1.1-1.3). In addition, female sex was strongly associated with Takotsubo (OR 5.1; 95% CI 4.9-5.4). CONCLUSION: TCM appears to be associated with varying degrees with several acute neurological diseases besides subarachnoid hemorrhage.

Nutritional Risk Index predicts mortality in hospitalized advanced heart failure patients.

BACKGROUND: Hospitalized advanced heart failure (HF) patients are at high risk for malnutrition and death. The Nutritional Risk Index (NRI) is a simple, well-validated tool for identifying patients at risk for nutrition-related complications. We hypothesized that, in advanced HF patients from the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) trial, the NRI would improve risk discrimination for 6-month all-cause mortality. METHODS: We analyzed the 160 ESCAPE index admission survivors with complete follow-up and NRI data, calculated as follows: NRI = (1.519 × discharge serum albumin [in g/dl]) + (41.7 × discharge weight [in kg] / ideal body weight [in kg]); as in previous studies, if discharge weight is greater than ideal body weight (IBW), this ratio was set to 1. The previously developed ESCAPE mortality model includes: age; 6-minute walk distance; cardiopulmonary resuscitation/mechanical ventilation; discharge ß-blocker prescription and diuretic dose; and discharge serum sodium, blood urea nitrogen and brain natriuretic peptide levels. We used Cox proportional hazards modeling for the outcome of 6-month all-cause mortality. RESULTS: Thirty of 160 patients died within 6 months of hospital discharge. The median NRI was 96 (IQR 91 to 102), reflecting mild-to-moderate nutritional risk. The NRI independently predicted 6-month mortality, with adjusted HR 0.60 (95% CI 0.39 to 0.93, p = 0.02) per 10 units, and increased Harrell's c-index from 0.74 to 0.76 when added to the ESCAPE model. Body mass index and NRI at hospital admission did not predict 6-month mortality. The discharge NRI was most helpful in patients with high (≥ 20%) predicted mortality by the ESCAPE model, where observed 6-month mortality was 38% in patients with NRI < 100 and 14% in those with NRI > 100 (p = 0.04). CONCLUSIONS: The NRI is a simple tool that can improve mortality risk stratification at hospital discharge in hospitalized patients with advanced HF.