Transcatheter aortic valve replacement: The year in review 2016

Transcatheter aortic valve replacement (TAVR) continued to make major strides in 2016, simultaneously expanding its application to lower risk patients as well as more technically challenging subsets of patients with aortic stenosis (AS). The two major accomplishments this year were the establishment of TAVR as the preferred treatment strategy over surgical aortic valve replacement (SAVR) in intermediate risk patients, and initial signals that TAVR and SAVR may be clinically equivalent in low‐risk populations. Meanwhile, there is continued expansion of TAVR to challenging clinical subsets (bicuspid aortic valve [BAV], patients with concomitant advanced coronary artery disease [CAD], and failed surgical bioprostheses), and encouraging initial experiences with newer transcatheter heart valve systems. This paper summarizes the major research studies published on TAVR in 2016.

     

Complete versus incomplete revascularization with drug‐eluting stents for multi‐vessel disease in stable,unstable angina or non‐ST‐segment elevation myocardial infarction: A meta‐analysis

Objectives

To determine whether drug‐eluting stent (DES) coronary complete revascularization (CR) confers clinical benefit over incomplete revascularization (IR) in patients with multivessel coronary artery disease (MVD).

Background

Clinical benefit of CR over IR in patients with MVD with angina (both stable and unstable) and non‐ST‐segment elevation myocardial infarction (NSTEMI) in DES has not been well studied.

Methods

We conducted a systematic online literature search of PUBMED and EMBASE. Literatures that compared the clinical outcomes between CR and IR with exclusively or majority (>80%) using DES in patients without or included only small portion (<20%) of ST‐segment elevation myocardial infarction or single‐vessel coronary artery disease were included. Hazards ratio (HR) with 95% confidence interval (CI) was calculated with random‐effects model.

Results

No randomized clinical trials were identified. A total of 14 observational studies with total of 41 687 patients (CR 39.6% and IR 60.4%) were included in this meta‐analysis. CR was associated with lower incident of all‐cause mortality (HR 0.71, P = 0.001), major adverse events (HR 0.75, P < 0.001), cardiovascular mortality (HR 0.39, P < 0.001). Meta‐regression analysis showed that CR significantly reduced the risk of all‐cause mortality in advanced age, triple vessel disease and male sub‐groups.

Conclusions

CR with DES conferred favorable outcomes compared to IR in MVD patients with stable, unstable angina or NTEMI. Further research to achieve higher CR in MVD patients may lead to improvement in prognosis in these cohorts.

     

Treating comorbid anxiety and depression: Psychosocial and pharmacological approaches

Comorbid anxiety with depression predicts poor outcomes with a higher percentage of treatment resistance than either disorder occurring alone. Overlap of anxiety and depression complicates diagnosis and renders treatment challenging. A vital step in treatment of such comorbidity is careful and comprehensive diagnostic assessment. We attempt to explain various psychosocial and pharmacological approaches for treatment of comorbid anxiety and depression. For the psychosocial component, we focus only on generalized anxiety disorder based on the following theoretical models: (1) “the avoidance model”; (2) “the intolerance of uncertainty model”; (3) “the meta-cognitive model”; (4) “the emotion dysregulation model”; and (5) “the acceptance based model”. For depression, the following theoretical models are explicated: (1) “the cognitive model”; (2) “the behavioral activation model”; and (3) “the interpersonal model”. Integration of these approaches is suggested. The treatment of comorbid anxiety and depression necessitates specific psychopharmacological adjustments as compared to treating either condition alone. Serotonin reuptake inhibitors are considered first-line treatment in uncomplicated depression comorbid with a spectrum of anxiety disorders. Short-acting benzodiazepines (BZDs) are an important “bridging strategy” to address an acute anxiety component. In patients with comorbid substance abuse, avoidance of BZDs is recommended and we advise using an atypical antipsychotic in lieu of BZDs. For mixed anxiety and depression comorbid with bipolar disorder, we recommend augmentation of an antidepressant with either lamotrigine or an atypical agent. Combination and augmentation therapies in the treatment of comorbid conditions vis-à-vis monotherapy may be necessary for positive outcomes. Combination therapy with tricyclic antidepressants, gabapentin and selective serotonin/norepinephrine reuptake inhibitors (e.g., duloxetine) are specifically useful for comorbid chronic pain syndromes. Aripiprazole, quetiapine, risperidone and other novel atypical agents may be effective as augmentations. For treatment-resistant patients, we recommend a “stacking approach” not dissimilar from treatment of hypertension In conclusion, we delineate a comprehensive approach comprising integration of various psychosocial approaches and incremental pharmacological interventions entailing bridging strategies, augmentation therapies and ultimately stacking approaches towards effectively treating comorbid anxiety and depression.     

Deficiency in the 15 kDa selenoprotein inhibits human colon cancer cell growth

Selenium is an essential micronutrient for humans and animals, and is thought to provide protection against some forms of cancer. These protective effects appear to be mediated, at least in part, through selenium-containing proteins (selenoproteins). Recent studies in a mouse colon cancer cell line have shown that the 15 kDa selenoprotein (Sep15) may also play a role in promoting colon cancer. The current study investigated whether the effects of reversing the cancer phenotype observed when Sep15 was removed in mouse colon cancer cells, were recapitulated in HCT116 and HT29 human colorectal carcinoma cells. Targeted down-regulation of Sep15 using RNAi technology in these human colon cancer cell lines resulted in similarly decreased growth under anchorage-dependent and anchorage-independent conditions. However, the magnitude of reduction in cell growth was much less than in the mouse colon cancer cell line investigated previously. Furthermore, changes in cell cycle distribution were observed, indicating a delayed release of Sep15 deficient cells from the G(0)/G(1) phase after synchronization. The potential mechanism by which human colon cancer cells lacking Sep15 revert their cancer phenotype will need to be explored further.