Risk and fate of residual interatrial shunting after transcatheter closure of patent foramen ovale: a long term follow up study

<p>Abstract</p> <p>Background</p> <p>Percutaneous transcatheter closure of patent foramen ovale (PFO) in cryptogenic stroke is an alternative to medical therapy. There is still debate on different outcome for each currently available device. The impact of residual shunting after PFO-clo- sure on recurrent arterial embolism is unknown.</p> <p>Aims</p> <p>(i) To evaluate the prevalence of residual interatrial shunting after device- closure of PFO, (ii) to identify risk factors predicting residual interatrial shunting after device implantation, and (iii) to investigate the outcome of patients after PFO-closure during long- term follow- up (FU).</p> <p>Methods and results</p> <p>Between 2000- 2005 PFO-closure was performed in 124 patients using four different devices: Amplatzer PFO-(n = 52), CardioSeal (n = 33), Helex (n = 23) and Premere (n = 16) occluder. All patients underwent serial contrast-enhanced transesophageal echocardiography (TEE) for 24 months after PFO- closure; clinical FU was at minimum 5 years up to 9.75 years (mean 6.67 ± 1.31 years). Overall-closure rate was 87% at 2 years, device-specific closure time curves differed significantly (p-logrank = 0.003). Independent risk factors for residual-shunting were implantation of a Helex occluder (hazard ratio [HR] 12.6, 95% confidence interval [CI] 2.6- 57.4, p = 0.002), PFO- canal- lengths (HR 1.2, 95%CI 1.1- 1.3, p = 0.004) and extend of atrial-septal-aneurysm (HR 1.1, 95%CI 0.9- 1.3; p = 0.05). 4 (3.2%) arterial embolic events occurred during a FU-period of 817.2 patient-years, actuarial annual thromboembolic-risk was 0.49%. All ischemic events were not related to residual PFO-shunting or device-related thrombus- formation.</p> <p>Conclusion</p> <p>Success rates of PFO- closure are mainly dependent on occluder-type, extend of concomitant atrial-septum-aneurysm and PFO-canal- length. Importantly, residual shunting after PFO-closure was not associated with recurrence of arterial embolism during long-term follow-up.</p

Significant reduction in heart rate variability is a feature of acute decompensation of cirrhosis and predicts 90-day mortality

Background: Heart rate variability (HRV) is reduced in cirrhosis and in conditions of systemic inflammation. Whether HRV is associated with cirrhosis decompensation and development of acute‐on‐chronic liver failure (ACLF) is unknown. // Aims: To (a) validate wireless remote HRV monitoring in cirrhosis decompensation; (b) determine if severely reduced HRV is a surrogate for inflammation and progression of cirrhosis decompensation; (c) assess if measuring HRV determines prognosis in cirrhosis decompensation. // Methods: One hundred and eleven patients at risk of cirrhosis decompensation at two clinical sites were monitored for HRV. Standard deviation of all normal beat‐beat intervals (SDNN) reflecting HRV was assessed using remote monitoring (Isansys Lifetouch) and/or Holter ECG recording. Clinical outcomes and major prognostic scores were recorded during 90‐day follow‐up. // Results: Reduced HRV denoted by lower baseline SDNN, correlated with severity of decompensation (median 14 (IQR 11‐23) vs 33 (25‐42); P < 0.001, decompensated patients vs stable outpatient cirrhosis). Furthermore, SDNN was significantly lower in patients developing ACLF compared to those with only decompensation (median 10 (IQR9‐12) vs 16 (11‐24); P = 0.02), and correlated inversely with MELD and Child‐Pugh scores, and C‐reactive protein (all P < 0.0001) and white cell count (P < 0.001). SDNN predicted disease progression on repeat measures and appeared an independent predictor of 90‐day mortality (12 patients). An SDNN cut‐off of 13.25 ms had a 98% negative predictive value. // Conclusions: This study demonstrates that remote wireless HRV monitoring identifies cirrhosis patients at high risk of developing ACLF and death, and suggests such monitoring might guide the need for early intervention in such patients. Clinical Trial number: NIHR clinical research network CPMS ID 4949

Effects of single low dose of dexamethasone before noncardiac and nonneurologic surgery and general anesthesia on postoperative cognitive dysfunction : a phase III double blind, randomized clinical trial

Postoperative cognitive dysfunction (POCD) is a multifactorial adverse event most frequently in elderly patients. This study evaluated the effect of dexamethasone on POCD incidence after noncardiac and nonneurologic surgery. METHODS: One hundred and forty patients (ASA I-II; age 60–87 years) took part in a prospective phase III, double blind, randomized study involving the administration or not of 8 mg of IV dexamethasone before general anesthesia under bispectral index (BIS) between 35–45 or 46–55. Neuropsychological tests were applied preoperatively and on the 3rd, 7th, 21st, 90th and 180th days after surgery and compared with normative data. S100β was evaluated before and 12 hours after induction of anesthesia. The generalized estimating equations (GEE) method was applied, followed by the posthoc Bonferroni test considering P<0.05 as significant. RESULTS: On the 3rd postoperative day, POCD was diagnosed in 25.2% and 15.3% of patients receiving dexamethasone, BIS 35–45, and BIS 46–55 groups, respectively. Meanwhile, POCD was present in 68.2% and 27.2% of patients without dexamethasone, BIS 35–45 and BIS 46–55 groups (p<0.0001). Neuropsychological tests showed that dexamethasone associated to BIS 46–55 decreased the incidence of POCD, especially memory and executive function. The administration of dexamethasone might have prevented the postoperative increase in S100β serum levels. CONCLUSION: Dexamethasone can reduce the incidence of POCD in elderly patients undergoing surgery, especially when associated with BIS 46–55. The effect of dexamethasone on S100β might be related with some degree of neuroprotection

Percutaneous mitral valve edge-to-edge Repair: In-hospital results and 1-year follow-up of 628 patients of the 2011-2012 pilot European Sentinel Registry

The use of transcatheter mitral valve repair (TMVR) has gained widespread acceptance in Europe, but data on immediate success, safety, and long-term echocardiographic follow-up in real-world patients are still limited

Inhibition of Renin-Angiotensin System Reverses Endothelial Dysfunction and Oxidative Stress in Estrogen Deficient Rats

BACKGROUND: Estrogen deficiency increases the cardiovascular risks in postmenopausal women. Inhibition of the renin-angiotensin system (RAS) and associated oxidative stress confers a cardiovascular protection, but the role of RAS in estrogen deficiency-related vascular dysfunction is unclear. The present study investigates whether the up-regulation of RAS and associated oxidative stress contributes to the development of endothelial dysfunction during estrogen deficiency in ovariectomized (OVX) rats. METHODOLOGY/PRINCIPAL FINDINGS: Adult female rats were ovariectomized with and without chronic treatment with valsartan and enalapril. Isometric force measurement was performed in isolated aortae. The expression of RAS components was determined by immunohistochemistry and Western blotting method while ROS accumulation in the vascular wall was evaluated by dihydroethidium fluorescence. Ovariectomy increased the expression of angiotensin-converting enzyme (ACE), angiotensin II type 1 receptor (AT(1)R), NAD(P)H oxidase, and nitrotyrosine in the rat aorta. An over-production of angiotensin II and ROS was accompanied by decreased phosphorylation of eNOS at Ser(1177) in OVX rat aortae. These pathophysiological changes were closely coupled with increased oxidative stress and decreased nitric oxide bioavailability, culminating in markedly impaired endothelium-dependent relaxations. Furthermore, endothelial dysfunction and increased oxidative stress in aortae of OVX rats were inhibited or reversed by chronic RAS inhibition with enalapril or valsartan. CONCLUSIONS/SIGNIFICANCE: The novel findings highlight a significant therapeutic benefit of RAS blockade in the treatment of endothelial dysfunction-related vascular complications in postmenopausal states

Gene Expression, Function and Ischemia Tolerance in Male and Female Rat Hearts After Sub-Toxic Levels of Angiotensin II

To examine the response to chronic high-dose angiotensin II (Ang II) and a proposed milder response in female hearts with respect to gene expression and ischemic injury. Female and male litter–matched rats were treated with 400 ng kg−1 min−1 Ang II for 14 days. Hearts were isolated, subjected to 30-min ischemia and 30-min reperfusion in combination with functional monitoring and thereafter harvested for gene expression, WB and histology. Ang II-treated hearts showed signs of non-hypertrophic remodeling and had significantly higher end diastolic pressure after reperfusion, but no significant gender difference was detected. Ang II increased expression of genes related to heart function (ANF, β-MCH, Ankrd-1, PKC-α, PKC-δ TNF-α); fibrosis (Col I-α1, Col III-α1, Fn-1, Timp1) and apoptosis (P53, Casp-3) without changing heart weight but with 68% increase in collagen content. High (sub-toxic) dose of Ang II resulted in marked heart remodeling and diastolic dysfunction after ischemia without significant myocyte hypertrophy or ventricular chamber dilatation. Although there were some gender-dependent differences in gene expression, female gender did not protect against the overall response

Statin Therapy in Metabolic Syndrome and Hypertension Post-JUPITER: What is the Value of CRP?

Much evidence supports a pivotal role for inflammation in atherosclerosis. C-reactive protein (CRP), the prototypic marker of inflammation in humans, is a cardiovascular risk marker and may also promote atherogenesis. CRP levels are increased in metabolic syndrome and hypertension and confer increased risk of cardiovascular events in patients in these subgroups. Statins have been shown to lower low-density lipoproteins and CRP independently, and reduce cardiovascular events in subjects with and without metabolic syndrome and hypertension. In this review, we focus on the results from the primary prevention statin trial, Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER), which showed reductions in LDL, CRP, and cardiovascular events. Post-JUPITER, the new guidelines will now need to consider recommending high-sensitivity CRP testing to intermediate-risk metabolic syndrome patients and those with hypertension and intermediate risk so that we can better identify candidates at greater risk and reduce cardiovascular burden in these subjects with statin therapy

Expression of Kruppel-Like Factor KLF4 in Mouse Hair Follicle Stem Cells Contributes to Cutaneous Wound Healing

Kruppel-like factor KLF4 is a transcription factor critical for the establishment of the barrier function of the skin. Its function in stem cell biology has been recently recognized. Previous studies have revealed that hair follicle stem cells contribute to cutaneous wound healing. However, expression of KLF4 in hair follicle stem cells and the importance of such expression in cutaneous wound healing have not been investigated.Quantitative real time polymerase chain reaction (RT-PCR) analysis showed higher KLF4 expression in hair follicle stem cell-enriched mouse skin keratinocytes than that in control keratinocytes. We generated KLF4 promoter-driven enhanced green fluorescence protein (KLF4/EGFP) transgenic mice and tamoxifen-inducible KLF4 knockout mice by crossing KLF4 promoter-driven Cre recombinase fused with tamoxifen-inducible estrogen receptor (KLF4/CreER™) transgenic mice with KLF4(flox) mice. KLF4/EGFP cells purified from dorsal skin keratinocytes of KLF4/EGFP transgenic mice were co-localized with 5-bromo-2'-deoxyuridine (BrdU)-label retaining cells by flow cytometric analysis and immunohistochemistry. Lineage tracing was performed in the context of cutaneous wound healing, using KLF4/CreER™ and Rosa26RLacZ double transgenic mice, to examine the involvement of KLF4 in wound healing. We found that KLF4 expressing cells were likely derived from bulge stem cells. In addition, KLF4 expressing multipotent cells migrated to the wound and contributed to the wound healing. After knocking out KLF4 by tamoxifen induction of KLF4/CreER™ and KLF4(flox) double transgenic mice, we found that the population of bulge stem cell-enriched population was decreased, which was accompanied by significantly delayed cutaneous wound healing. Consistently, KLF4 knockdown by KLF4-specific small hairpin RNA in human A431 epidermoid carcinoma cells decreased the stem cell population and was accompanied by compromised cell migration.KLF4 expression in mouse hair bulge stem cells plays an important role in cutaneous wound healing. These findings may enable future development of KLF4-based therapeutic strategies aimed at accelerating cutaneous wound closure