Search

The aging process involves numerous biological mechanisms that have been characterized and proposed as the "hallmarks of aging." Targeting the processes and pathways related to these hallmarks of aging that cause and promote skin aging could provide anti-aging benefits. A novel topical growth factor-based skin care serum (A+) was developed using human fibroblast conditioned media. This study aimed to assess the effects of A+ on four hallmarks of aging and its clinical efficacy in skin rejuvenation in subjects with moderate to severe overall facial photodamage.Preclinical studies included immunohistochemistry in human ex vivo skin, and gene expression analysis in human 3D skin models. A 24-week, vehicle placebo-controlled study, including FaceQ patient-reported outcomes and skin biopsy analysis, was performed to assess clinical efficacy and tolerability.Treatment with A+ resulted in reduced expression of cell senescence biomarker H2A.J and upregulation of genes associated with proteasome, autophagy, stemness, and intercellular communication. Clinical assessments showed A+ provided significantly greater reductions in sagging, coarse lines/wrinkles, fine lines/wrinkles, overall photodamage, and overall hyperpigmentation compared with placebo. Subjects felt they appeared younger-looking, reporting a median decrease in self-perceived age of 6 years after 12 weeks of use. Decreased levels of H2A.J and increased expression of key dermal extracellular matrix and epidermal barrier components, including collagen and elastin, were observed in skin biopsy samples.The present study shows for the first time the potential effects of a topical growth factor-based cosmeceutical on cellular processes related to four hallmarks of aging (cellular senescence, loss of proteostasis, stem cell exhaustion, and altered intercellular communication) to help delay the aging process and restore aged skin. A+ targets the biological mechanisms underlying the aging process itself and stimulates skin regeneration, resulting in rapid and significant clinical improvements.

The neck plays a telling role as an age indicator. Due to its anatomy and function, neck skin ages differently than facial skin and special considerations need to be taken when providing treatment. A randomized, double-blind, regimen-controlled study was conducted to assess the efficacy and tolerability of a novel topical cosmetic cream (NCC) specifically tailored to address the signs of skin aging of the neck and deacute;colletage. Twice daily application of NCC significantly improved skin sagging/laxity of the neck as well as the appearance of fine and coarse lines/wrinkles, crepiness, tactile roughness, overall skin texture, hyperpigmentation, skin tone evenness, and radiance. NCC also significantly improved the appearance of fine and coarse lines/wrinkles, tactile roughness, hyperpigmentation, skin tone evenness, and radiance of the deacute;colletage. Investigator assessments were corroborated by objective cutometer measurements that demonstrated improved skin firmness and elasticity. In vitro analysis in human 3D skin models show that stimulation of neocollagenesis and neoelastogenesis as well as support of cellular proteostasis through proteasome and autophagy activation are potential mechanisms of action for the observed clinical outcomes. J Drugs Dermatol. 2021;20(2):184-191. doi:10.36849/JDD.5819 THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

Introduction Positron Emission Tomography/Computed Tomography (PET/CT) has many advantages over Single Photon Emission Computed Tomography in Myocardial Perfusion Imaging (MPI). However, UK availability, has been limited. We describe a new Rubidium (Rb) PET MPI service; the third in the National Health Service in England. Methods Audit of the first 100 patients from November 2019 to January 2020. 66 men, 34 women, mean age 65 ±11, mean Body Mass Index 28.3 ±6.8. Imaging comprised CT for attenuation correction, CT for Agatston scoring if no known Coronary Artery Disease (CAD) or prior intervention, and PET with and without adenosine vasodilation. Results The commonest indication was symptoms post-revascularization (36%). 31% had had previous percutaneous intervention, 15% had had previous coronary surgery. 21% had had prior cardiac CT. The mean wait from request to scan was 30 days. 98% were reported the same or next working day. 96% received 140 mcg/kg/min adenosine, 4% received 210 mcg/kg/min. Two patients did not show adequate vasodilation. All PET MPI scans were diagnostic quality. 43% had Agatston scoring. The mean total Agatston score was 511. The normalcy rate for PET MPS was 60%. The prevalence of infarction was 20%. The mean Myocardial Flow Reserve was 2.3 ±0.8. Conclusion Rb PET MPI is feasible and high quality in a new service. It provides detailed coronary assessment, with plaque burden, relative perfusion and absolute myocardial blood flow quantification. It will be an essential contributor to patient diagnosis, treatment response and risk stratification.

Anthracycline chemotherapy maintains a prominent role in treating many forms of cancer. Cardiotoxic side effects limit their dosing and improved cancer outcomes expose the cancer survivor to increased cardiovascular morbidity and mortality. The basic mechanisms of cardiotoxicity may involve direct pathways for reactive oxygen species generation and topoisomerase 2 as well as other indirect pathways. Cardioprotective treatments are few and those that have been examined include renin angiotensin system blockade, beta blockers, or the iron chelator dexrazoxane. New treatments exploiting the ErbB or other novel pro-survival pathways, such as conditioning, are on the cardioprotection horizon. Even in the forthcoming era of targeted cancer therapies, the substantial proportion of today’s anthracycline-treated cancer patients may become tomorrow’s cardiac patient.

We innovatively devised a cardio-oncology echocardiogram report pro forma to promote evidence-based reporting, achieve standardisation and incorporate checklist practices. The report pro forma was based on the case report form for the ERIC-ONC cardio-oncology cancer cardioprotection trial. It

Skin care products may use various active ingredients to support skin rejuvenation including growth factors and other molecules that help to regenerate extracellular matrix (ECM) and promote skin repair. The biological effect of skin care products with a strong anti-aging claim was assessed in gene expression analyses using an in vitro human skin model. Application of products containing human fibroblast-derived growth factors resulted in signifcant upregulation of genes encoding ECM components including collagens and elastin. Human fibroblasts cultured under hypoxic conditions show increased gene expression of stem cell markers, and their conditioned media could possibly further support skin rejuvenation. Furthermore, a double-blind, randomized, placebo-controlled study was con-ducted in subjects with moderate to severe facial photodamage to assess the cosmetic clinical efficacy of a product containing human fibroblast-derived growth factors. The test product group demonstrated significantly greater reductions in the appearance of fne lines/wrinkles, coarse line/wrinkles, and overall photodamage, compared to the placebo group. Altogether, the results suggest that human fibroblast-derived growth factors support skin rejuvenation by stimulating dermal fibroblasts to generate ECM.

Introduction Remote Ischaemic Conditioning (RIC) using transient limb ischemia/reperfusion has been reported to reduce peri-operative myocardial injury (PMI) in patients undergoing coronary artery bypass grafting (CABG) and/or valve surgery. The role of intravenous Glyceryl Trinitrate (GTN) therapy administered during cardiac surgery as a cardioprotective agent and whether it interferes with RIC cardioprotection is not clear and is investigated in the ERIC-GTN trial (Clinicaltrial.govidentifier:NCT01864252). Aims The ERIC-GTN trial has been designed to determine whether intraoperatively administered IV GTN is cardioprotective during cardiac surgery and to investigate the interaction between RIC and IV GTN in their cardioprotective effects. Hypothesis 1: Intra-operative intravenous GTN will reduce PMI in patients undergoing CABG and/or valve surgery. Hypothesis 2: RIC will reduce PMI in the absence of GTN in patients undergoing CABG and/or valve surgery. Hypothesis 3: RIC will not reduce PMI in the presence of GTN in patients undergoing CABG and/or valve surgery. Design The ERIC-GTN trial is a single site, double-blind, randomised placebo-controlled study. Consenting adult patients (>18 years) undergoing elective CABG ±valve surgery with blood cardioplegia will be eligible for inclusion. 260 patients will be randomised to one of four treatment groups following aesthetic induction: (1) RIC alone : RIC protocol comprising three 5-minutes cycles of simultaneous upper arm and thigh cuff inflation/deflation followed by an intravenous (IV) placebo infusion; (2) GTN alone : A simulated sham RIC protocol will be applied followed by an IV GTN infusion; (3) RIC+GTN : RIC protocol followed by IV GTN infusion; and (4) Neither RIC or GTN : Sham RIC protocol followed by IV placebo infusion. The primary endpoint will be peri-operative myocardial injury as quantified by the 72 hour area-under-the-curve (AUC) serum high sensitive Troponin-T. Implication The ERIC-GTN trial will determine whether intra-operative GTN therapy is cardioprotective during cardiac surgery, and whether it affects RIC cardioprotection. We recruited 180 out of 260 patients so far and are currently undertaking a pre-specified interim analysis.

OBJECTIVE: This study sought to explore the diagnostic insight of cardiovascular magnetic resonance (CMR)-derived wave intensity analysis to better study systolic dysfunction in young patients with chronic diastolic dysfunction and preserved ejection fraction (EF), comparing it against other echocardiographic and CMR parameters.BACKGROUND: Evaluating systolic and diastolic dysfunctions in children is challenging, and a gold standard method is currently lacking.METHODS: Patients with presumed diastolic dysfunction [n = 18; nine aortic stenosis (AS), five hypertrophic, and four restrictive cardiomyopathies] were compared with age-matched control subjects (n = 18). All patients had no mitral or aortic incompetence, significant AS, or reduced systolic EF. E/A ratio, E/E' ratio, deceleration time, and isovolumetric contraction time were assessed on echocardiography, and indexed left atrial volume (LAVi), acceleration time (AT), ejection time (ET), and wave intensity analyses were calculated from CMR. The latter was performed on CMR phase-contrast flow sequences, defining a ratio of the peaks of the early systolic forward compression wave (FCW) and the end-systolic forward expansion wave (FEW).RESULTS: Significant differences between patients and controls were seen in the E/E' ratio (8.7 ± 4.0 vs. 5.1 ± 1.3, p = 0.001) and FCW/FEW ratio (2.5 ± 1.6 vs. 7.2 ± 4.2 × 10-5 m/s, p CONCLUSION: This study shows that the wave intensity-derived ratio summarizing systolic and diastolic function could provide insight into ventricular function in children, on top of CMR and echocardiography, and it was here able to identify an element of ventricular dysfunction with preserved EF in a small group of young patients.

Cardiac involvement drives the prognosis and treatment in systemic amyloid. Echocardiography, the mainstay of current cardiac imaging, defines cardiac structure and function. Echocardiography, in conjunction with clinical phenotype, electrocardiogram and biomarkers (brain natriuretic peptide and troponin), provides an assessment of the likelihood and extent of cardiac involvement. Two tests are transforming our understanding of cardiac amyloidosis, bone tracer scanning and cardiovascular magnetic resonance (CMR). CMR provides a "second opinion" on the heart's structure and systolic function with better accuracy and more precision than echocardiography but is unable to assess diastolic function and is not as widely available. Where CMR adds unique advantages is in evaluating myocardial tissue characterisation. With administration of contrast, the latest type of late gadolinium enhancement imaging (phase-sensitive inversion recovery sequence) is highly sensitive and specific with images virtually pathognomonic for amyloidosis. CMR is also demonstrating that the range of structural and functional changes in cardiac amyloid is broader than traditionally thought. CMR with T1 mapping, a relatively new CMR technique, can measure the amyloid burden and the myocyte response to infiltration (hypertrophy/cell loss) with advantages for tracking change (e.g. the wall thickness can stay the same but the composition can change) over time or during therapy. Such techniques hold great promise for advancing drug development in this arena and providing new prognostic insights. CMR with tissue characterisation is rewriting our understanding of cardiac amyloidosis and may lead to the development of new classification, therapies and prognostic systems.

Functional mitral regurgitation (MR) is a common findingoccurring in 20% of the general population1 and nearly 40% ofheart failure patients exhibiting at least moderate regurgitation.2Severity of MR predicts mortality3 and increased morbidityin ischaemic and non-ischaemic aetiologies4, regardless ofrevascularisation techniqueas well as in asymptomatic patients.5Mitral valve repair, by surgical or interventional techniques, aimsto restore valve competence and electromechanical synchronyto improve symptoms and survival.

The commonest cause of breathlessness in hypertrophic cardiomyopathy (HCM) is left ventricular outflow tract (LVOT) obstruction which improves with its removal. However, in the absence of outflow tract obstruction, as in dilated cardiomyopathy, patients may be limited by similar symptoms, thus suggesting a potential common mechanism for the two conditions. We aimed to assess cardiac function at the time of symptoms in a group of unselected patients with HCM to identify other patterns of cardiac dysfunction which coincide with their breathlessness.We studied 37 HCM patients (aged 55 ± 15 years, 13 female) with septal thickness15 mm and 17 controls (aged 58 ± 12 years, 12 female) using Doppler echocardiography, at rest and at peak dobutamine stress. Stress end points were symptoms,20 mmHg drop in systolic blood pressure, arrhythmia, or maximum dobutamine dosage of 40 μg/kg/min.At rest: LV systolic function was maintained (EF 68 ± 7 v 76 ± 12%, respectively), LVOT velocity raised (p0.005), lateral and septal long axis amplitude reduced (p0.05 and p0.005, respectively) and dyssynchronous and QRS duration was also broader (p0.005) in patients compared to controls. At peak stress: Overall LVOT velocities were higher in patients than controls (4.3 ± 1.7 v 1.7 ± 1.0m/s, p0.005, respectively) due to systolic anterior movement of the mitral valve and mitral regurgitation developing. In the 15 patients who did not develop significant LVOT obstruction (velocity4m/s), LV ejection time increased and peak systolic amplitude did not increase. In the 10 patients with neither LVOT obstruction nor restrictive filling, QRS duration prolonged by 12 ms (p0.05), post-ejection shortening worsened and peak systolic amplitude fell (p0.005). Also, LV ejection time prolonged by 5s/min (p0.05), filling time failed to increase as it did in controls (p0.005) and Tei index was higher than controls (p0.01).Exertional breathlessness in HCM is associated with LV outflow tract obstruction and functional mitral regurgitation in almost two thirds of patients. The remaining one third have either resistant restrictive physiology or dyssynchronous cavity at fast heart rate. Despite similar exercise limiting breathlessness in the three groups, means of management should be quite different.

Reducing Emissions from Deforestation and forest Degradation (REDD+) aims to avoid forest conversion to alternative land-uses through financial incentives. Oil-palm has high opportunity costs, which according to current literature questions the financial competitiveness of REDD+ in tropical lowlands. To understand this more, we undertook regional finescale and coarse-scale analyses (through carbon mapping and economic modelling) to assess the financial viability of REDD+ in safeguarding unprotected forest (30,173 ha) in the Lower Kinabatangan floodplain in Malaysian Borneo. Results estimate 4.7 million metric tons of carbon (MgC) in unprotected forest, with 64% allocated for oil-palm cultivations. Through fine-scale mapping and carbon accounting, we demonstrated that REDD+ can outcompete oil-palm in regions with low suitability, with low carbon prices and low carbon stock. In areas with medium oil-palm suitability, REDD+ could outcompete oil palm in areas\ud with: very high carbon and lower carbon price; medium carbon price and average carbon stock; or, low carbon stock and high carbon price. Areas with high oil palm suitability, REDD + could only outcompete with higher carbon price and higher carbon stock. In the coarse-scale model, oil-palm outcompeted REDD+ in all cases. For the fine-scale models at the landscape level, low carbon offset prices (US $3 MgCO2e) would enable REDD+ to outcompete oil-palm in 55% of the unprotected forests requiring US $27 million to secure these areas for 25 years. Higher carbon offset price (US $30 MgCO2e) would increase the competitiveness of REDD+ within the landscape but would still only capture between 69%-74% of the unprotected forest, requiring US $380–416 million in carbon financing. REDD+ has been identified as a strategy to mitigate climate change by many countries (including Malaysia). Although REDD+ in certain scenarios cannot outcompete oil palm, this research contributes to the global REDD+ debate by: highlighting REDD+ competitiveness in tropical floodplain landscapes; and, providing a robust approach for identifying and targeting limited REDD+ funds.

To evaluate the predictors for mortality following aortic valve replacement (AVR) in elderly patients with aortic stenosis (AS).112 consecutive elderly AS patients (aged 77+/-2 years) with AVR between 1998 and 2003 were studied. Clinical and echocardiographic data of LV function were recorded before and 46 months after AVR. Results were compared with 72 younger patients (aged 60+/-1 years). Outcome measures were 30-day and long-term all cause mortalities.Elderly patients had higher NYHA class, more frequent atrial fibrillation, coronary artery disease, emergency operation and use of bioprosthetic valves. They also had shorter E-wave deceleration time (DT) and larger left atria (p0.05 for all). 30-day mortality was 12% vs 4% (Log Rank x(2)=3.02, p=0.08) and long term mortality was 18% vs 7% (Log Rank x(2)=4.38, p=0.04) in two groups respectively. Age was not related to mortality after adjustment for other variables. Among all variables, anemia (OR 4.20, CI: 1.02-6.86, p=0.04), cardiopulmonary bypass (CPB) time (OR 1.02, CI 1.01-1.04, p0.01), significant prosthesis patient mismatch (PPM) (OR 5.43, CI 1.04-18.40, p0.05) were associated with 30-day mortality in elderly patients. Their long-term mortality was related to CBP time (OR 1.02, CI 1.00-1.05, p=0.04), PPM (OR 4.64, CI 1.33-16.11, p=0.02) and raised left atrial pressure: DT (OR 0.94, CI 0.84-0.99, p=0.03) and pulmonary arterial systolic pressure (OR 1.12, CI 1.03-1.19, p0.001).Peri-operative AVR survival is encouraging. While pre-operative anemia and a longer CBP time determine early mortality, long term mortality is related to PPM, LV diastolic dysfunction and secondary pulmonary hypertension.

Cancer survival continues to improve, and thus cardiovascular consequences of chemotherapy are increasingly important determinants of long‐term morbidity and mortality. Conventional strategies to protect the heart from chemotherapy have important hemodynamic or myelosuppressive side effects. Remote ischemic conditioning (RIC) using intermittent limb ischemia‐reperfusion reduces myocardial injury in the setting of percutaneous coronary intervention. Anthracycline cardiotoxicity and ischemia‐reperfusion injury share common biochemical pathways in cardiomyocytes. The potential for RIC as a novel treatment to reduce subclinical myocyte injury in chemotherapy has never been explored and will be investigated in the Effect of Remote Ischaemic Conditioning in Oncology (ERIC‐ONC) trial (clinicaltrials.gov NCT 02471885). The ERIC‐ONC trial is a single‐center, blinded, randomized, sham‐controlled study. We aim to recruit 128 adult oncology patients undergoing anthracycline‐based chemotherapy treatment, randomized in a 1:1 ratio into 2 groups: (1) sham procedure or (2) RIC, comprising 4, 5‐minute cycles of upper arm blood pressure cuff inflations and deflations, immediately before each cycle of chemotherapy. The primary outcome measure, defining cardiac injury, will be high‐sensitivity troponin‐T over 6 cycles of chemotherapy and 12 months follow‐up. Secondary outcome measures will include clinical, electrical, structural, and biochemical endpoints comprising major adverse cardiovascular clinical events, incidence of cardiac arrhythmia over 14 days at cycle 5/6, echocardiographic ventricular function, N‐terminal pro‐brain natriuretic peptide levels at 3 months follow‐up, and changes in mitochondrial DNA, micro‐RNA, and proteomics after chemotherapy. The ERIC‐ONC trial will determine the efficacy of RIC as a novel, noninvasive, nonpharmacological, low‐cost cardioprotectant in cancer patients undergoing anthracycline‐based chemotherapy.

The aim of this single-center observational study was to determine the outcome of patients with 'paradoxical' low-flow, low-gradient aortic valve stenosis (PLF-LG-AS) after transcatheter aortic valve implantation (TAVI).Based on pre-procedural echocardiographic data, a total of 150 patients with severe aortic valve stenosis (AS) (indexed aortic valve area (AVA) ≤ 0.6 cm2/m2) who underwent TAVI at the authors' institution were allocated retrospectively to three groups: Group 1: PLF-LG-AS (ejection fraction (EF) ≥ 50%, indexed stroke volume (SV) ≤ 35 ml/m2, mean AV gradient40 mmHg; n = 30); Group 2: Classical low-flow, low-gradient AS (CLF-LG-AS: EF50%, SV ≤ 35 ml/m2, mean AV gradient40 mmHg; n = 21); and Group 3: High-gradient AS (HG-AS: EFor ≥ 50%, mean AV gradient ≥ 40 mmHg; n = 99).PLF-LG-AS was associated with an increased relative wall thickness (RWT) and a higher post-procedural systolic blood pressure (sBP) and pulse pressure (PP) (RWT 60.6 ± 15.3%, sBP 144 ± 14 mmHg, PP 79 ± 15 mmHg) compared to patients with HG-AS or CLF-LG-AS: (RWT 52 ± 13% and 40 ± 9%, p0.001; sBP 138 ± 15 mmHg and 125 ± 25 mmHg, p = 0.006; PP 68 ± 16 mmHg and 60 ± 21 mmHg, p = 0.01). These patients experienced less improvement in a 6-min walk test (improvement for PLF-LG-AS 14 ± 84 m, for CLF-LG-AS 86 ± 83 m, for HG-AS 87 ± 66 m; intergroup p0.007). PLF-LG-AS and CLF-LG-AS were also associated with significantly increased one-year overall mortality (PLF-LG-AS 31%, CLF-LG-AS 19%, HG-AS 6%; p = 0.001) and cardiovascular mortality (PLF-LG-AS 20%, CLF-LG-AS 19%, HG-AS 3%; p = 0.002).Patients with PLF-LG-AS may represent a subgroup with a worse clinical outcome after TAVI.

Lowland tropical forests are increasingly threatened with conversion to oil palm as global demand and high profit drives crop expansion throughout the world’s tropical regions. Yet, landscapes are not homogeneous and regional constraints dictate land suitability for this crop. We conducted a regional study to investigate spatial and economic components of forest conversion to oil palm within a tropical floodplain in the Lower Kinabatangan, Sabah, Malaysian Borneo. The Kinabatangan ecosystem harbours significant biodiversity with globally threatened species but has suffered forest loss and fragmentation. We mapped the oil palm and forested landscapes (using object-based-image analysis, classification and regression tree analysis and on-screen digitising of high-resolution imagery) and undertook economic modelling. Within the study region (520,269 ha), 250,617 ha is cultivated with oil palm with 77% having high Net-Present-Value (NPV) estimates ($413/ha− yr–$637/ha− yr); but 20.5% is under-producing. In fact 6.3% (15,810 ha) of oil palm is commercially redundant (with negative NPV of $-299/ha− yr-$-65/ha− yr) due to palm mortality from flood inundation. These areas would have been important riparian or flooded forest types. Moreover, 30,173 ha of unprotected forest remain and despite its value for connectivity and biodiversity 64% is allocated for future oil palm. However, we estimate that at minimum 54% of these forests are unsuitable for this crop due to inundation events. If conversion to oil palm occurs, we predict a further 16,207 ha will become commercially redundant. This means that over 32,000 ha of forest within the floodplain would have been converted for little or no financial gain yet with significant cost to the ecosystem. Our findings have globally relevant implications for similar floodplain landscapes undergoing forest transformation to agriculture such as oil palm. Understanding landscape level constraints to this crop, and transferring these into policy and practice, may provide conservation and economic opportunities within these seemingly high opportunity cost landscapes.

For many congenital heart defects treated in infancy (eg, tetralogy of Fallot, transposition of the great arteries, double outlet right ventricle), long-term right ventricular outflow tract (RVOT) dysfunction, in the form of pulmonary stenosis and regurgitation, is a common finding as patients become older (older children, adolescents, and adults). This dysfunction can lead to right ventricular (RV) dilatation, progressive dyspnea, arrhythmia, and sudden cardiac death.1,2 Patients are often treated with RV to pulmonary artery (PA) conduits or homograft, which have a finite lifespan and may require replacement every decade or sooner, with pulmonary valve replacement at open-heart surgery.3,4 Medical management has a limited role,5 and although conduit/homograft stenosis can be managed percutaneously with balloon dilatation and bare metal stent insertion6 to prolong conduit/homograft life, this has the inevitable consequence of inducing free pulmonary regurgitation. During the last decade, however, percutaneous pulmonary valve implantation (PPVI) has been developed to provide a minimally invasive, transcatheter-based approach to prolong conduit/homograft life by treating stenosis and regurgitation without the need for open-heart surgery, thereby reducing procedural risks, hospital stay, and the time it takes to return to normal daily activities. Since the first, pioneering human PPVI in 2000 by Bonhoeffer et al,7 the technique has gained acceptance, with >4000 procedures performed to date. Several studies have now demonstrated the short-term efficacy of PPVI8–13 and defined the potential complications of the procedure, including device migration and fractures,14 coronary compression,15 and infective endocarditis. Sustained relief from stenosis and regurgitation has also been demonstrated in the medium term, with freedom from reoperation of 93%, 86%, 84%, and 70% at 10, 30, 50, and 70 months, respectively, with similar freedom from redo interventions 95%, 87%, 73%, and 73% at the same intervals. Survival at …

"Paradoxical" Low flow, low gradient severe aortic valve stenosis (PLF-LG-AS) is characterized by reduced stroke volume despite preserved EF. If managed conservatively this entity of AS is associated with poor prognosis. Our observational single center study aimed to investigate the outcome of these

In the past decade, Transcatheter Aortic Valve Replacement (TAVI) has been shown to be a feasible, less invasive option to open heart surgery for aortic valve replacement; however, TAVI is indicated only in patients with severe, symptomatic, aortic stenosis and who are considered at high or prohibitive risk for conventional surgery [1]. To date, two different TAVI devices are available on the market — the balloon-expandable Edwards-Sapien® Valve (Edwards Lifesciences, CA, USA) and the self-expandable CoreValve ReValving System® (Medtronic, MN, USA) — with many other devices currently under development and clinical trials. The procedural success rate has been >90% in all studies [1], but vascular complications, electrical conduction abnormalities and paravalvular leak — 65–89% of cases, the majority being trivial to mild, with 0 to 26% moderate and 0 to 10% severe — still remain major safety concerns. In particular, a negative influence of moderate to severe paravalvular leak on survival rates has recently been demonstrated [2].Copyright © 2013 by ASME

The right ventricle is multicompartmental in orientation.To assess the normal differential function of the right ventricular (RV) inflow, apical and outflow compartments, also their inter-relations and the response to pulmonary arterial hypertension (PAH).45 people were studied--16 controls and 29 patients with left-sided heart failure, 15 without (group 1) and 14 with (group 2) secondary PAH, using two-dimensional (2D) and 3D echocardiography in addition to conventional Doppler techniques.There was a strong correlation between RV inlet diameter (2D) and end-diastolic volume (3D) (r=0.69, p0.001) and between tricuspid annular plane systolic excursion and RV ejection fraction (3D) (r=0.71, p0.001). In controls and patients, the apical ejection fraction was less than the inflow and outflow (controls: p0.01 and p0.01, group 1: p0.05 and p0.01 and group 2: p0.05 and p0.01, respectively). Ejection fraction was reduced in patients (inflow: p0.001 for both, apical: p0.01 for both and outflow tract: p0.05 for both). In controls, the inflow compartment reached the minimum volume 20emsp14;ms before the outflow and apex but in group 2 it was simultaneous. Isovolumic contraction and relaxation times were prolonged in patients (Group 1: p=0.02 and p0.01 and Group 2: p=0.01 for both). Peak RV ejection time correlated with the rate of outflow volume fall in controls but with the apex in group 2 (r=0.6, p0.05).The right ventricle has distinct features for the inflow, apical and outflow tract compartments, with different extent of contribution to the overall systolic function. In PAH, the right ventricle becomes one dyssynchronous compartment, which itself may have perpetual effect on overall cardiac dysfunction.

To identify predictors of survival following aortic valve replacement (AVR) in patients with low-flow and high-gradient aortic stenosis (AS).Eighty-six patients (aged 71 +/- 10 years) with severe AS [aortic valve mean pressure gradient40 mmHg or valve area1.0 cm(2)] and left ventricular (LV) dysfunction [ejection fraction (EF)50%] underwent AVR. Cox proportional hazards were used to identify independent clinical and echocardiographic predictors of mortality. Operative (30-day) mortality was 10%. Peri-operative mortality was associated with lower mean LVEF, higher mitral E:A ratio, peak systolic pulmonary artery pressure (PSPAP), and serum creatinine (by 12%, 2.3, 28 mmHg, and 74 mmol/L, respectively, all P0.001), NYHA class III-IV (100 vs. 65%), concomitant CABG (89 vs. 55%), urgent surgery (78 vs. 35%), and longer bypass-time (by 28 min, all P0.05). Mortality at 4 years was 17%. Univariate predictors [hazard ratio (HR)] of 4-year mortality were: lower EF (HR 0.68 per % increase, P0.001), presence of restrictive LV filling (HR: 3.52, P0.001), raised PSPAP (HR: 1.07, P0.001), and CABG (HR: 4.93, P = 0.037). However, only low EF (40%, HR 0.74, P = 0.030), the presence of restrictive filling (HR 1.77, P = 0.033), and raised PSPAP (45 mmHg, HR 2.71, P = 0.010) remained as independent predictors after multivariate analysis.The severity of pre-operative systolic and diastolic LV dysfunction is the major predictor of mortality following AVR for low-flow and high-gradient AS.

Objective: Hypertrophic cadiomyopathy (HCM) results in exertional symptoms due to limited cardiac output that improve after removal of the left ventricular outflow tract (LVOT) obstruction. We aimed to assess the effect of pharmacological stress on LV asynchrony in a group of patients with HCM limited by exertional breathlessness. Methods: We studied 17 normal controls (aged 58 ± 12 years) and 37 HCM patients (aged 54 ± 15 years, 13 female) with septal thickness >15 mm using Doppler echocardiography, at rest and at peak dobutamine stress. Stress end points were symptoms, >20 mmHg drop in systolic blood pressure, arrhythmia, or maximum dobutamine infusion of 40μcg/kg/min. Ventricular asynchrony was assessed by total isovolumic time and Tei index. Results: At rest: LVOT velocity was raised in HCM patients compared to normals (2.0 ± 0.9 v 1.0 ± 2.4, p Conclusion: Stress results in LV outflow tract obstruction in HCM patients, resulting in known pathophysiological consequences– mitral regurgitation and raised left atrial pressure. In addition, increased ventricular asynchrony compromises filling time. The historical benefit from DDD pacing in this condition may be explained on the basis of LV resynchronisation rather than simply drop in outflow tract gradient.

BACKGROUND: The relationship between left ventricular (LV) long and short axes, aortic pressure (P), flow velocity (U) and wave intensity is not well established. METHODS: Eleven dogs were anaesthetized and mechanically ventilated and LV long and minor axes shortening velocities were calculated using ultrasound crystals. P and U were measured in the ascending aorta using a high fidelity pressure catheter and ultrasonic flow transducer. RESULTS: Pre-ejection: The LV minor axis began to shorten as the long axis lengthened creating LV shape change. Early ejection: The aortic valve opened 83+/-20 ms after the ECG Q-wave. Aortic P and U simultaneously increased; peak aortic velocity and maximum minor axis shortening velocity (M(max)) occurred at 152+24 and 147+24 ms, respectively; p=0.66, intra-class correlation ICC 0.93). M(max) also corresponded to the time when the reflected compression wave arrived back to the heart (ICC 0.75). Late ejection: LV long axis reached its peak shortening velocity 28+21 ms later than the minor axis at 175+/-33 ms, coinciding with peak LV pressure (187+25 ms; p=0.77, ICC 0.65) and onset of the forward expansion wave (177+28 ms, p=0.88, ICC 0.89). Both axes then continued to slow until 210+/-30 ms when an increased rate of decline of shortening velocity corresponded with peak aortic pressure. CONCLUSION: Long axis peak shortening velocity lagged consistently behind the minor axis, representing a degree of normal asynchrony. The arrival of the reflected wave appears to bring about the slowing down of the minor axis.

The search for optimal sedation for transesophageal echocardiography (TEE) continues. We hypothesized that the ultra-short acting opioid remifentanil combined with very low-dose midazolam would provide a better sedation and recovery profile compared to midazolam alone.41 consecutive outpatients scheduled for TEE received either IV midazolam (group M, 2.5 mg bolus plus 1 mg increments repeated as needed, n=18) or a combination of a low-dose IV bolus of midazolam (0.5 mg) plus an infusion of remifentanil (group RM, 0.1 mcg/kg/min, reduced to 0.08 mcg/kg/min after probe insertion, n=23). All patients received topical pharyngeal anesthesia with 2 puffs of lidocaine 4% spray. We recorded BP, SpO(2), HR, time-to-discharge (modified Aldrete score of 13), duration of procedure, resource utilization, complications, ease of probe introduction, ease and quality of the procedure. Patients' satisfaction with sedation was assessed using the Iowa Satisfaction with Anesthesia Scale (ISAS).Mean dose of midazolam in group M was 3.7+/-1.3 mg. Median time-to-discharge was significantly reduced in the RM group compared with the M group (5 (5-10) vs. 30 (5-240) min, p0.0001), with 22 of the 23 group RM patients ready for "street discharge" within 5 min of removal of the TEE probe. Ease of probe insertion (p=0.001), resource utilization (p=0.0001), patient satisfaction (p=0.03) and overall ease and quality of the procedure (p=0.0001) were significantly better in the RM group than in the M group. No episodes of desaturation were observed.This is the first report of the use of an ultra-short acting opioid, remifentanil, combined with a low-dose of midazolam, as a sedative technique for outpatient TEE. In this pilot, non-randomized prospective study, remifentanil plus low-dose midazolam provided better sedation than our current practice of higher bolus doses of midazolam alone. This novel approach is associated with improved procedure tolerance, faster recovery and minimal resource utilization. A randomized, controlled study is under way to verify our preliminary results.

Aortic stenosis remains the commonest form of valve disease inmodern cardiology. With fifty years’ experience, surgical valvereplacement remains the gold standard treatment for survivalbenefit, durability and symptomatic relief. Percutaneoustranscatheter aortic valve replacement has recently gained acredible momentum for inoperable and very high risk patientswith severe aortic stenosis. Early and medium term resultshave demonstrated a proven survival benefit over conservativemanagement, with documented complication rates for stroke,vascular complications and pacemaker implantation. Theevidence base for cost effectiveness and long-term results areeagerly anticipated.

We aimed to identify the most sensitive echocardiographic measurements that predict recovery of left ventricular function following valve replacement surgery in patients with severe aortic stenosis (AS) and LV dysfunction.We studied 66 patients (mean age 70+/-2 years, 53 male) who underwent AVR for severe AS with concurrent LV dysfunction between 1998 and 2003 at the Royal Brompton Hospital. Clinical symptoms, co-morbidities and echocardiographic measurements of LV function were recorded before and at a median follow-up of 46 months after AVR. Pre-operative LV systolic dysfunction was defined as LV ejection fraction (EF)50% and the post-op LV recovery as an increase of EF10%.Following AVR peak aortic pressure gradient decreased and aortic valve area index increased (64+/-3 to 19+/-1 mm Hg and 0.30+/-0.01 to 0.89+/-0.03 cm(2)/m(2), p0.001 for both). LV EF increased (from 45+/-1 to 54+/-2%; p0.001) and the LV dimensions fell (LVEDD index: from 33+/-1 to 30+/-1 mm/m(2); and LVESD index: from 27+/-1 to 20+/-1 mm/m(2); p0.01 for both). LV diastolic dysfunction improved as evidenced by the fall in E/A ratio (from 2.6+/-0.2 to 1.9+/-0.4) and prolongation of total filling time; (from 29.2+/-0.6 to 31.4+/-0.5 s/min, p=0.01 for both). Among all echocardiographic variables, LV dimensions (LVEDD index, OR 0.70, CI 0.52-0.97, p0.05; LVESD index, OR 0.57, CI 0.40-0.85, p=0.005) were the two independent predictors of post-operative LV functional recovery on multivariate analysis. A cut off value of pre-operative LVESD index=or27.5 mm/m(2) was 85% sensitive and 72% specific in predicting intermediate-term recovery of LV function after AVR (AUC, 0.72, p=0.002).LV functional recovery was evident in majority of aortic stenotic patients with LV dysfunction after aortic valve replacement. A lower prevalence of LV functional recovery in patients with large pre-operative LV end systolic dimension index might signify the loss of contractile reserve and thus predict post-operative functional recovery.

Conventional two dimensional (2D) echocardiography and colour flow imaging have been widely used for assessment of patients before and after mitral valve surgery, where the residual severity or elimination of mitral regurgitation (MR) remains the primary outcome measure. We present a 62 year old female patient who complained of increasing shortness of breath in the last year, seven years after previous mitral …

Remote ischaemic preconditioning (RIPC) using transient limb ischaemia failed to improve clinical outcomes following cardiac surgery and the reasons for this remain unclear. In the ERIC-GTN study, we evaluated whether concomitant nitrate therapy abrogated RIPC cardioprotection. We also undertook a post-hoc analysis of the ERICCA study, to investigate a potential negative interaction between RIPC and nitrates on clinical outcomes following cardiac surgery. In ERIC-GTN, 185 patients undergoing cardiac surgery were randomized to: (1) Control (no RIPC or nitrates); (2) RIPC alone; (3); Nitrates alone; and (4) RIPC + Nitrates. An intravenous infusion of nitrates (glyceryl trinitrate 1 mg/mL solution) was commenced on arrival at the operating theatre at a rate of 2–5 mL/h to maintain a mean arterial pressure between 60 and 70 mmHg and was stopped when the patient was taken off cardiopulmonary bypass. The primary endpoint was peri-operative myocardial injury (PMI) quantified by a 48-h area-under-the-curve high-sensitivity Troponin-T (48 h-AUC-hs-cTnT). In ERICCA, we analysed data for 1502 patients undergoing cardiac surgery to investigate for a potential negative interaction between RIPC and nitrates on clinical outcomes at 12-months. In ERIC-GTN, RIPC alone reduced 48 h-AUC-hs-cTnT by 37.1%, when compared to control (ratio of AUC 0.629 [95% CI 0.413–0.957], p = 0.031), and this cardioprotective effect was abrogated in the presence of nitrates. Treatment with nitrates alone did not reduce 48 h-AUC-hs-cTnT, when compared to control. In ERICCA there was a negative interaction between nitrate use and RIPC for all-cause and cardiovascular mortality at 12-months, and for risk of peri-operative myocardial infarction. RIPC alone reduced the risk of peri-operative myocardial infarction, compared to control, but no significant effect of RIPC was demonstrated for the other outcomes. When RIPC and nitrates were used together they had an adverse impact in patients undergoing cardiac surgery with the presence of nitrates abrogating RIPC-induced cardioprotection and increasing the risk of mortality at 12-months post-cardiac surgery in patients receiving RIPC.