Characteristics and outcomes of patients with spontaneous coronary artery dissection who suffered sudden cardiac arrest.

PURPOSE: Spontaneous coronary artery dissection (SCAD) can cause life-threatening ventricular arrhythmias, but the characteristics and outcomes of this population are not well characterized. We sought to determine the characteristics and outcomes of patients with SCAD who suffered sudden cardiac arrest, whether treated with or without an implantable cardioverter-defibrillator (ICD). METHODS: Retrospective cohort study of patients diagnosed with SCAD between 2006 and 2016. RESULTS: Eleven of 208 SCAD patients suffered sudden cardiac arrest (5.3%). Those who suffered cardiac arrest were more likely to have pregnancy-associated SCAD (27.3% vs 7.1%, p = 0.018). They were more likely to have left main (18.2% vs 1.0%, p = 0.01) or proximal coronary vessel involvement (36.4% vs 8.1%, p = 0.002), and with left ventricular ejection fraction of < 50% (45.5% vs 13.2%, p = 0.013). Percutaneous coronary intervention was more commonly performed in patients who suffered cardiac arrest (54.6% vs 8.6%, p < 0.001). Left main or proximal LAD involvement increased the odds of cardiac arrest by over 6-fold (OR 6.2, 95% CI 1.2-32.9, p = 0.03). Eight of the 11 patients suffered VT/VF arrest, of which one was treated with an ICD and one with a wearable cardioverter-defibrillator. Of these, no shocks were reported at follow-up and no ventricular arrhythmic events were reported in those not receiving defibrillator treatment. CONCLUSION: Sudden cardiac arrest in SCAD patients is associated with left main or proximal coronary lesions. Secondary prevention ICD did not show benefit in this cohort. Future larger studies are needed to determine the role of ICD therapy in SCAD patients who suffer cardiac arrest.

Characteristics and Clinical Outcomes of Patients With Spontaneous Coronary Artery Dissection.

Background The goal of this study is to report the characteristics and long-term clinical outcomes of patients with spontaneous coronary artery dissection (SCAD) and to identify factors associated with recurrent SCAD . Methods and Results This is a retrospective cohort study that included patients who underwent coronary angiography for evaluation of acute myocardial infarction between 2006 and 2016. Among 26 598 patients hospitalized with a principal diagnosis of acute myocardial infarction, 208 (0.78%) were diagnosed with SCAD . Patients with SCAD were younger (49.0±11.6 versus 65.6±12.2 years) and more likely to be women (88.9% versus 31.6%). Atherosclerotic risk factors, such as hypertension, hyperlipidemia, obesity, and diabetes mellitus, were less prevalent. Median follow-up was 4.7 years. Mortality was lower in patients with SCAD (1-year mortality: 2.4% versus 8.8%; P<0.001). After using propensity score matching to control for differences in age, sex, and comorbidities, the difference in mortality was no longer present, suggesting that lower mortality in patients with SCAD is attributed primarily to their baseline characteristics. Recurrent SCAD occurred in 22 patients (10.6%). Multivariate Cox regression modeling showed concomitant fibromuscular dysplasia (hazard ratio, 5.1; 95% CI , 1.6-15.8; P=0.005) and migraine headaches (hazard ratio, 3.4; 95% CI , 1.4-8.4; P=0.008) to be associated with increased risk of recurrent SCAD . Conclusions Among patients with acute myocardial infarction, patients with SCAD have a lower risk of mortality, which is attributed primarily to their younger age, female sex, and low prevalence of atherosclerotic risk factors. Risk of recurrent SCAD persists years after the initial presentation. Patients with fibromuscular dysplasia and migraine are at higher risk for recurrent SCAD .

Comparison of Effects of Statin Use on Mortality in Patients With Heart Failure and Preserved Versus Reduced Left Ventricular Ejection Fraction.

Randomized trials showed no survival benefit with statin therapy in heart failure (HF) patients with reduced ejection fraction (HFrEF). Whether these results are generalizable to HF patients with preserved ejection fraction (HFpEF) or with mid-range ejection fraction is unclear. In a cohort of 13,440 patients with HF, 9,903 (73.7%) were treated with statins. The association between statin use and all-cause mortality was assessed with Cox proportional hazard regression models and survival time inverse probability weighting propensity scores analyses. Multivariable Poisson regression models with robust error variance were applied to estimate the rate ratios (RR) for hospitalization. The association between statin treatment and clinical outcomes differed by ejection fraction group. In patients with HFpEF, statin use was associated with reduced mortality (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.66 to 0.81, p <0.001; average treatment effect [ATE] 0.48, 95% CI 0.13 to 0.84, p = 0.007) and reduced all-cause hospitalization (RR 0.82, 95% CI 0.76 to 0.89, p <0.001). In contrast, in patients with HFrEF, no significant association was observed between statin use and mortality (HR 0.86, 95% CI 0.74 to 1.0, p = 0.054; ATE 0.41, 95% CI -0.09 to 0.93, p = 0.11) or hospitalization (RR 0.92, 95% CI 0.82 to 1.04, p = 0.17). Similarly, in patients with mid-range ejection fraction, there was no significant association with reduced mortality (HR 0.76, 95% CI 0.60 to 0.95, p = 0.02, ATE 0.3, 95% CI -0.84 to 1.43, p = 0.61) or hospitalization (RR 1.07, 95% CI 0.9 to 1.27, p = 0.44). In conclusion, statin use was associated with improved clinical outcomes in patients with HFpEF but not in patients with HFrEF or mid-range ejection fraction.

Open Versus Endovascular or Hybrid Thoracic Aortic Aneurysm Repair.

Thoracic aortic aneurysms are associated with significant morbidity and mortality. There are multiple underlying etiologies, including genetic abnormalities, that have important implications in their natural history. The variable histologic, anatomic, and clinical presentations necessitate careful consideration of available treatment options. Surgical repair of these aneurysms has been the mainstay of treatment; however, these approaches can carry a relatively high risk of morbidity and mortality. Endovascular approaches have now become first-line therapy for descending thoracic aneurysms, and with advancements in graft technology, endovascular approaches are being increasingly employed for hybrid repairs of the aortic arch and even the ascending aorta. However, to date, clinical outcomes from randomized trials and long-term follow-up are limited. As technology continues to advance, there is the potential for further integration of surgical and endovascular treatments so that patients have the best opportunity for a favorable outcome.

Synapse loss in dementias.

Synaptic transmission is essential for nervous system function, and its dysfunction is a known major contributing factor to Alzheimer's-type dementia. Antigen-specific immunochemical methods are able to characterize synapse loss in dementia through the quantification of various synaptic proteins involved in the synaptic cycle. These immunochemical methods applied to the study of Alzheimer's disease (AD) brain specimens have correlated synaptic loss with particularly toxic forms of amyloid-beta protein and have also established synapse loss as the best correlate of dementia severity. A significant but comparatively circumscribed amount of literature describes synaptic decline in other forms of dementia. Ischemic vascular dementia (IVD) is quite heterogeneous, and synapse loss in IVD seems to be variable among IVD subtypes, probably reflecting its variable neuropathologic correlates. Loss of synaptic protein has been identified in vascular dementia of the Binswanger type and Spatz-Lindenberg's disease. Here we demonstrate a significant loss of synaptophysin density within the temporal lobe of frontotemporal dementia (FTD) patients.

Cerebral microinfarcts associated with severe cerebral beta-amyloid angiopathy.

Cerebral amyloid angiopathy (CAA) is common in elderly individuals, especially those affected with Alzheimer's disease. Eighteen brains with severe SCAA (SCAA) were compared with 21 brains with mild CAA (MCAA) to investigate whether the presence of SCAA in the brains of demented patients was associated with a higher burden of old microinfarcts than those with MCAA. Immunohistochemistry for CD68 was employed to highlight old microinfarcts in tissue blocks from various brain regions. Old microinfarcts, manually counted by light microscopy, were present in 14 of 18 SCAA brains and in 7 of 21 MCAA brains (P = 0.01, two-tailed Fisher's exact test). The average number of old microinfarcts across geographic regions in each brain ranged from 0 to 1.95 (mean rank 24.94, sum of ranks 449) in the SCAA group, and from 0 to 0.35 (mean rank 15.76, sum of ranks 331) in the MCAA group (P = 0.008, two-tailed Mann-Whitney U-test). Frequent old microinfarcts in demented individuals with severe CAA may contribute a vascular component to the cognitive impairment in these patients.

Increased activation of Iba1+ microglia in pediatric epilepsy patients with Rasmussen's encephalitis compared with cortical dysplasia and tuberous sclerosis complex.

Microgliosis is prominent in Rasmussen's encephalitis (RE), a disease with severe seizure activity. However, it is unclear if microglial activation is similar with different histopathologic substrates. Iba1-immunolabelled microglial activation was assessed in neocortex from pediatric epilepsy surgery patients with RE (n=8), cortical dysplasia (CD; n=6) and tuberous sclerosis complex (TSC; n=6). Microglial reactivity was increased, in severely affected RE areas (29% labeling) compared with minimally affected areas of RE cases (15%) and cases of TSC (14%) and CD (12%). There was no qualitative association of Iba1 immunolabelling with the presence of CD8(+) cytotoxic T-cells and no statistical association with clinical epilepsy variables, such as seizure duration or frequency. Iba1 appears to be an excellent marker for detecting extensive microglial activation in patients with RE. In addition, this study supports the notion that Iba1-labeled microglial activation is increased in patients with active RE, compared with cases of CD and TSC.

Attenuation of neuroinflammation and Alzheimer's disease pathology by liver x receptors.

Alzheimer's disease (AD) is an age-dependent neurodegenerative disease that causes progressive cognitive impairment. The initiation and progression of AD has been linked to cholesterol metabolism and inflammation, processes that can be modulated by liver x receptors (LXRs). We show here that endogenous LXR signaling impacts the development of AD-related pathology. Genetic loss of either Lxralpha or Lxrbeta in APP/PS1 transgenic mice results in increased amyloid plaque load. LXRs regulate basal and inducible expression of key cholesterol homeostatic genes in the brain and act as potent inhibitors of inflammatory gene expression. Ligand activation of LXRs attenuates the inflammatory response of primary mixed glial cultures to fibrillar amyloid beta peptide (fAbeta) in a receptor-dependent manner. Furthermore, LXRs promote the capacity of microglia to maintain fAbeta-stimulated phagocytosis in the setting of inflammation. These results identify endogenous LXR signaling as an important determinant of AD pathogenesis in mice. We propose that LXRs may be tractable targets for the treatment of AD due to their ability to modulate both lipid metabolic and inflammatory gene expression in the brain.