Myocardial dysfunction after out-of-hospital cardiac arrest: predictors and prognostic implications.

We aim to determine the incidence of early myocardial dysfunction after out-of-hospital cardiac arrest, risk factors associated with its development, and association with outcome. A retrospective chart review was performed among consecutive out-of-hospital cardiac arrest (OHCA) patients who underwent echocardiography within 24 h of return of spontaneous circulation at three urban teaching hospitals. Our primary outcome is early myocardial dysfunction, defined as a left ventricular ejection fraction < 40% on initial echocardiogram. We also determine risk factors associated with myocardial dysfunction using multivariate analysis, and examine its association with survival and neurologic outcome. A total of 190 patients achieved ROSC and underwent echocardiography within 24 h. Of these, 83 (44%) patients had myocardial dysfunction. A total of 37 (45%) patients with myocardial dysfunction survived to discharge, 39% with intact neurologic status. History of congestive heart failure (OR 6.21; 95% CI 2.54-15.19), male gender (OR 2.27; 95% CI 1.08-4.78), witnessed arrest (OR 4.20; 95% CI 1.78-9.93), more than three doses of epinephrine (OR 6.10; 95% CI 1.12-33.14), more than four defibrillations (OR 4.7; 95% CI 1.35-16.43), longer duration of resuscitation (OR 1.06; 95% CI 1.01-1.10), and therapeutic hypothermia (OR 3.93; 95% CI 1.32-11.75) were associated with myocardial dysfunction. Cardiopulmonary resuscitation immediately initiated by healthcare personnel was associated with lower odds of myocardial dysfunction (OR 0.40; 95% CI 0.17-0.97). There was no association between early myocardial dysfunction and mortality or neurological outcome. Nearly half of OHCA patients have myocardial dysfunction. A number of clinical factors are associated with myocardial dysfunction, and may aid providers in anticipating which patients need early diagnostic evaluation and specific treatments. Early myocardial dysfunction is not associated with neurologically intact survival.

Epicardial YAP/TAZ orchestrate an immunosuppressive response following myocardial infarction.

Ischemic heart disease resulting from myocardial infarction (MI) is the most prevalent form of heart disease in the United States. Post-MI cardiac remodeling is a multifaceted process that includes activation of fibroblasts and a complex immune response. T-regulatory cells (Tregs), a subset of CD4+ T cells, have been shown to suppress the innate and adaptive immune response and limit deleterious remodeling following myocardial injury. However, the mechanisms by which injured myocardium recruits suppressive immune cells remain largely unknown. Here, we have shown a role for Hippo signaling in the epicardium in suppressing the post-infarct inflammatory response through recruitment of Tregs. Mice deficient in epicardial YAP and TAZ, two core Hippo pathway effectors, developed profound post-MI pericardial inflammation and myocardial fibrosis, resulting in cardiomyopathy and death. Mutant mice exhibited fewer suppressive Tregs in the injured myocardium and decreased expression of the gene encoding IFN-γ, a known Treg inducer. Furthermore, controlled local delivery of IFN-γ following MI rescued Treg infiltration into the injured myocardium of YAP/TAZ mutants and decreased fibrosis. Collectively, these results suggest that epicardial Hippo signaling plays a key role in adaptive immune regulation during the post-MI recovery phase.

Right ventricular dysfunction after resuscitation predicts poor outcomes in cardiac arrest patients independent of left ventricular function.

OBJECTIVE: Determination of clinical outcomes following resuscitation from cardiac arrest remains elusive in the immediate post-arrest period. Echocardiographic assessment shortly after resuscitation has largely focused on left ventricular (LV) function. We aimed to determine whether post-arrest right ventricular (RV) dysfunction predicts worse survival and poor neurologic outcome in cardiac arrest patients, independent of LV dysfunction. METHODS: A single-center, retrospective cohort study at a tertiary care university hospital participating in the Penn Alliance for Therapeutic Hypothermia (PATH) Registry between 2000 and 2012. PATIENTS: 291 in- and out-of-hospital adult cardiac arrest patients at the University of Pennsylvania who had return of spontaneous circulation (ROSC) and post-arrest echocardiograms. MEASUREMENTS AND MAIN RESULTS: Of the 291 patients, 57% were male, with a mean age of 59 ± 16 years. 179 (63%) patients had LV dysfunction, 173 (59%) had RV dysfunction, and 124 (44%) had biventricular dysfunction on the initial post-arrest echocardiogram. Independent of LV function, RV dysfunction was predictive of worse survival (mild or moderate: OR 0.51, CI 0.26-0.99, p<0.05; severe: OR 0.19, CI 0.06-0.65, p=0.008) and neurologic outcome (mild or moderate: OR 0.33, CI 0.17-0.65, p=0.001; severe: OR 0.11, CI 0.02-0.50, p=0.005) compared to patients with normal RV function after cardiac arrest. CONCLUSIONS: Echocardiographic findings of post-arrest RV dysfunction were equally prevalent as LV dysfunction. RV dysfunction was significantly predictive of worse outcomes in post-arrest patients after accounting for LV dysfunction. Post-arrest RV dysfunction may be useful for risk stratification and management in this high-mortality population.

Optimal lipid targets for the new era of cardiovascular prevention.

Optimal lipid targets (OLT) should be the goal for all individuals treated in the new era of cardiovascular (CV) disease prevention. Evidence supports that average LDL cholesterol (LDL-C) values in Westernized populations are not optimal. Lessons from nature and science support a physiologic LDL-C target of <70 mg/dL. Clinical trial evidence further supports optimal LDL-C targets, although several critical questions remain unanswered. Using a calculated LDL-C may have limitations in clinical practice. Non-HDL-C cholesterol may be a better predictor of outcomes, and should therefore be provided on all laboratory reports. Specific HDL cholesterol (HDL-C) targets are significantly more complicated. Although a low HDL-C predicts a less favorable outcome independent of LDL-C level, an HDL-C level > 50 mg/dL is associated with lower CV risk. Clinical trials on HDL-C have thus far been disappointing. OLT should be the goal for all individuals as an important part of addressing global CV risk.

Non-high-density lipoprotein cholesterol versus apolipoprotein B in cardiovascular risk stratification: do the math.

With the emergence of new lipid risk markers and a growing cardiometabolic risk burden in the United States, there is a need to better integrate residual risk into cardiovascular disease (CVD) risk stratification. In anticipation of the Adult Treatment Panel IV (ATP IV) guidelines from the National Cholesterol Education Program (NCEP), there exists controversy regarding the comparative performance of the 2 foremost markers, apolipoprotein B (apoB) and non-high-density lipoprotein cholesterol (non-HDL-C), as they relate to the current standard of risk assessment and treatment: low-density lipoprotein cholesterol (LDL-C). Although some emerging markers may demonstrate better performance compared with LDL-C, certain fundamental characteristics intrinsic to a beneficial biomarker must be met prior to routine use. Collectively, studies have found that non-HDL-C and apoB perform better than LDL-C in CVD risk prediction, both on- and off-treatment, as well as in subclinical CVD risk prediction. The performance of non-HDL-C compared with apoB, however, has been a point of ongoing debate. Although both offer the practical benefits of accuracy independent of triglyceride level and prandial state, non-HDL-C proves to be the better marker of choice at this time, given established cutpoints with safe and achievable goals, no additional cost, and quick time to result with an easy mathematical calculation. The purpose of this review is to assess the performance of these parameters in this context and to discuss the considerations of implementation into clinical practice.

High-grade, nonmyogenic pulmonary artery sarcoma: rare findings on coronary angiography.

Pulmonary artery sarcomas are exceptionally rare, and they are often misdiagnosed as chronic pulmonary thromboemboli. Early and accurate diagnosis is crucial to the prognosis of patients who have pulmonary artery sarcomas.Herein, we describe the case of a 74-year-old man who presented with dyspnea and was initially thought to have a pulmonary embolus. Anticoagulation with unfractionated heparin was ineffective. Rare angiographic findings during routine cardiac catheterization led to the diagnosis of a high-grade, nonmyogenic, primary pulmonary artery sarcoma. This case illustrates the usefulness of angiographic findings as an adjunct to conventional diagnostic methods in correctly identifying this rare, aggressive malignancy.

Aortic angiosarcoma masquerading as a thoracic aortic aneurysm.

Aortic angiosarcoma is an exceedingly rare clinical entity. Significant delay in diagnosis can occur due to a low index of suspicion on the part of the clinician. We report a case of aortic angiosarcoma masquerading as a descending thoracic aneurysm arising from a penetrating ulcer. The patient was initially treated with an endovascular stent graft for rapid growth, but the lesion continued to enlarge despite angiographic exclusion. FDG-PET CT scan and biopsy ultimately confirmed the diagnosis of aortic angiosarcoma. This case highlights some of the difficulties of making the early diagnosis of aortic angiosarcoma.

A common neural substrate for perceiving and knowing about color.

Functional neuroimaging research has demonstrated that retrieving information about object-associated colors activates the left fusiform gyrus in posterior temporal cortex. Although regions near the fusiform have previously been implicated in color perception, it remains unclear whether color knowledge retrieval actually activates the color perception system. Evidence to this effect would be particularly strong if color perception cortex was activated by color knowledge retrieval triggered strictly with linguistic stimuli. To address this question, subjects performed two tasks while undergoing fMRI. First, subjects performed a property verification task using only words to assess conceptual knowledge. On each trial, subjects verified whether a named color or motor property was true of a named object (e.g., TAXI-yellow, HAIR-combed). Next, subjects performed a color perception task. A region of the left fusiform gyrus that was highly responsive during color perception also showed greater activity for retrieving color than motor property knowledge. These data provide the first evidence for a direct overlap in the neural bases of color perception and stored information about object-associated color, and they significantly add to accumulating evidence that conceptual knowledge is grounded in the brain's modality-specific systems.