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Hitesh C Patel,1 Carl Hayward,1 Vassilis Vassiliou,1 Ketna Patel,2 James P Howard,3 Carlo Di Mario11NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, UK; 2Department of Cardiology, Royal Free Hospital, London, UK; 3National Heart and Lung Institute, Imperial College, London, UKAbstract: Renal sympathetic denervation (RSD) as a therapy for patients with resistant hypertension has attracted great interest. The majority of studies in this field have demonstrated impressive reductions in blood pressure (BP). However, these trials were not randomized or sham-controlled and hence, the findings may have been overinflated due to trial biases. SYMPLICITY HTN-3 was the first randomized controlled trial to use a blinded sham-control and ambulatory BP monitoring. A surprise to many was that this study was neutral. Possible reasons for this neutrality include the fact that RSD may not be effective at lowering BP in man, RSD was not performed adequately due to limited operator experience, patients’ adherence with their antihypertensive drugs may have changed during the trial period, and perhaps the intervention only works in certain subgroups that are yet to be identified. Future studies seeking to demonstrate efficacy of RSD should be designed as randomized blinded sham-controlled trials. The efficacy of RSD is in doubt, but many feel that its safety has been established through the thousands of patients in whom the procedure has been performed. Over 90% of these data, however, are for the Symplicity™ system and rarely extend beyond 12 months of follow-up. Long-term safety cannot be assumed with RSD and nor should it be assumed that if one catheter system is safe then all are. We hope that in the near future, with the benefit of well-designed clinical trials, the role of renal denervation in the management of hypertension will be established.Keywords: resistant hypertension, renal denervation, sympathetic nervous system, symplicity

We described a case of IPEX syndrome successfully controlled with dupilumab, an anti-IL4 receptor alpha subunit inhibitor. IPEX syndrome is a rare and generally fatal genetic disorder characterized by immune dysregulation, polyendocrinopathy and enteropathy, mostly diagnosed in early childhood. Nonetheless, cases reported in the last 20 years demonstrated that IPEX clinical spectrum encompasses more than the classical triad of early-onset intractable diarrhea, type 1 diabetes and eczema. Atypical cases of IPEX include patients with late-onset of symptoms, single-organ involvement, mild disease phenotypes or rare clinical features. A 21-year-old caucasian man presented with immune dysregulation (hypereosinophilia and elevated IgE), proteinlosing enteropathy, polyendocrinopathy (thyroiditis, osteoporosis, delayed puberty), weight loss, eczema manifestations and celiac disease. IPEX syndrome was diagnosed because of the presence of a hemizygous mutation in FOXP3 gene (c.543C>T (p.S181S) in the exon 5). During the course of the disease, the patient developed erosive proctitis, pyoderma gangrenosum, and erythema nodosum. Symptoms improved only after enteral and parenteral corticosteroid therapy and the patient soon developed steroid-dependence. Notwithstanding various therapies including azathioprine, sirolimus, tacrolimus, adalimumab, vedolizumab, the patient failed to achieve a good control of symptoms without steroids. Almost exclusive enteral nutrition with a hypoallergenic, milk-protein free, amino acid-based food for special medical purposes. He continued to lose weight (BMI 14.5 kg/m2) with a consequent high limitation of physical activity and a progressive worsening of the quality of life. In consideration of the poor response to conventional immunosuppressants and the presence of type 2 inflammatory manifestations, treatment with dupilumab at an initial dose of 600 mg, followed by a maintenance dose of 300 mg every other week, according to atopic dermatitis labeled dose, was started and combined to oral budesonide 6 mg/day and 6-mercaptopurine 75 mg/day. The patient experienced a rapid improvement in bowel and skin symptoms, leading to a progressive tapering of steroids. By our knowledge, this is the first report of IPEX syndrome successfully treated by antiIL-4/IL-13 therapy. In this case dupilumab demonstrated to be an effective, safe and steroid-sparing option. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that carpal tunnel syndrome (CTS) and brachial biceps tendon rupture (BBTR) represent red flags for ATTR cardiac amyloidosis (ATTR‐CA). The prevalence of upper limb tenosynovial complications in conditions entering differential diagnosis with CA, such as HCM or Anderson–Fabry disease (AFD), and hence their predictive accuracy in this setting, still remains unresolved. Objective: To investigate the prevalence of CTS and BBTR in a consecutive cohort of ATTR‐CA patients, compared with patients with HCM or AFD and with individuals without cardiac disease history. Participants: Consecutive patients with a diagnosis of ATTR‐CA, HCM and AFD were evaluated. A control group of consecutive patients was recruited among subjects hospitalized for noncardiac reasons and no cardiac disease history. The presence of BBTR, CTS or prior surgery related to these conditions was ascertained. Results: 342 patients were prospectively enrolled, including 168 ATTR‐CA (141 ATTRwt, 27 ATTRm), 81 with HCM/AFD (N = 72 and 9, respectively) and 93 controls. CTS was present in 75% ATTR‐CA patients, compared with 13% and 10% of HCM/AFD and controls (P = 0.0001 for both comparisons). Bilateral CTS was present in 60% of ATTR‐CA patients, while it was rare (2%) in the other groups. BBTR was present in 44% of ATTR‐CA patients, 8% of controls and 1% in HCM/AFD. Conclusions: CTS and BBTR are fivefold more prevalent in ATTR‐CA patients compared with cardiac patients with other hypertrophic phenotypes. Positive predictive accuracy for ATTR‐CA is highest when involvement is bilateral. Upper limb assessment of patients with HCM phenotypes is a simple and effective way to raise suspicion of ATTR‐CA. [ABSTRACT FROM AUTHOR]

Objectives: To define baseline clinical and immunological characteristics [anti-citrullinated peptide antibodies (ACPAs), immunoglobulin M (IgM)- and IgA-rheumatoid factor (RF), and interleukin-6 (IL-6) levels] involved in determining baseline erosiveness, outcome, and radiographic progression among seropositive and seronegative early rheumatoid arthritis (ERA) patients.Method: The 408 ERA patients enrolled in the study were monitored every 3 months according to the treat-to-target strategy. At baseline and after 12 months, hand and foot radiographs were evaluated using the Sharp/van der Heijde erosion score.Results: At diagnosis, seronegative patients were older and had higher Disease Activity Scores (DASs) than seropositive patients. A higher risk of erosiveness at baseline was conferred by IgA-RF positivity and IL-6 plasma levels ≥7.6 pg/mL, particularly when simultaneously present. In multivariate analysis, disease duration and IL-6 plasma levels ≥7.6 pg/mL arose as independent variables associated with presence of erosions at onset. Radiographic progression at 1 year follow-up, which occurred in 11.1% of ERA patients, was predicted by ACPA positivity, together with higher age at diagnosis. Despite similar percentages of good European League Against Rheumatism response, DAS and Boolean remission being observed over time among seropositive and seronegative patients and between erosive and non-erosive subjects, ERA patients who were erosive at onset, IgA-RF seropositive, and simultaneously having high baseline IL-6 plasma levels (≥7.6 pg/mL) were treated to a greater extent with tumour necrosis factor blockers after 12 months.Conclusion: IgA-RF positivity and IL-6 plasma levels are crucial for baseline erosiveness, while ACPA positivity represents the strongest risk factor for developing radiographic progression in ERA. [ABSTRACT FROM AUTHOR]

Background: Lesions located at the ostium of the left anterior descending coronary artery (LAD) are considered an ideal target for directional atherectomy (DCA), but few data are available about the value of using this strategy before stenting in comparison with stenting alone.Objectives: To investigate the immediate and mid term clinical and angiographic results of DCA followed by stent implantation for ostial LAD lesions.Design: Retrospective comparison of the immediate and mid term angiographic and clinical results of a series of 117 consecutive patients with de novo lesions located at the ostium of the LAD. Of these, 46 underwent DCA before stenting and 71 were treated with stenting alone.Results: Technical success in the two groups was similar at around 98%. DCA plus stenting provided a larger minimum lumen diameter at the end of the procedure than stenting alone (3.57 (0.59) mm v 3.33 (0.49) mm, p = 0.022). There were no differences for in-hospital major adverse events (MACE) (7.5% for atherectomy plus stenting, and 5.3% for stenting alone; p = 0.41). All patients had clinical follow up at a mean of 7.9 (2.7) months. Angiographic follow up was done in 89 patients (76%) at a mean of 5.9 (2.2) months. The atherectomy plus stenting group had a larger minimum lumen diameter than the stenting group (2.79 (0.64) mm v 2.26 (0.85) mm, p = 0.004) and a lower binary restenosis rate (13.8% v 33.3%, p = 0.031). Six month MACE were reduced in the atherectomy plus stenting group (8.7% v 23.9%, p = 0.048).Conclusions: Debulking before stenting in de novo lesions located at the ostium of the LAD is safe and is associated with a high rate of technical success. Follow up data show that DCA plus stenting results in a significantly larger minimum lumen diameter and a lower incidence of restenosis than stenting alone. [ABSTRACT FROM AUTHOR]

Abstract: Background: Hyperuricemia may be involved in the atherosclerotic process due to endothelial dysfunction and facilitation of smooth muscle cell proliferation. However, debates still exist on the independent role of hyperuricemia, due to its association with several cardiovascular risk factors, such as hypertension, hyperlipidemia, obesity and insulin resistance. Thus, the aim of the current study was to investigate in a consecutive cohort of patients undergoing coronary angiography whether hyperuricemia is associated with the extent of coronary artery disease. Methods and Results: Our population is represented by a total of 1901 consecutive patients undergoing coronary angiography between May 2007 and January 2010 at the Azienda Ospedaliera “Maggiore della Carità”, Novara, Italy. We additionally evaluated platelet aggregation by PFA-100 (Collagen/Epinefrine) and Multiplate. Quantitative coronary angiography and analysis of IMT were performed by experienced cardiologists who had no knowledge of the patients’ clinical information. Higher uric acid was associated with advanced age, larger prevalence of male gender, diabetes, renal insufficiency, hypertension, previous CABG and MI, but with a lower prevalence of family history of CAD. Patients with high uric acid were more often on calcium antagonists, ace-inhibitors, angiotensin receptor antagonists, and, as expected, on diuretics. A significant relationship was observed between uric acid and the prevalence (OR [95% CI] = 1.18 [1.04–1.32], p = 0.01) and severity of CAD (OR [95% CI] = 1.17 [1.03–1.33], p = 0.014). However, the relationship disappeared after correction for baseline confounding factors for both prevalence (OR [95% CI] = 1.06 [0.93–1.21], p = 0.35) and extent of CAD (OR [95% CI] = 1.0 [0.87–1.15], p = 0.96). No relationship was observed between acid uric and IMT (p = 0.73) analyzed in 359 consecutive patients. Finally, there was no relationship between uric acid and platelet aggregation in patients with or without aspirin therapy, as measured by PFA-100 and Multiplate. Conclusions: Our study showed that uric acid is not associated with platelet aggregation, the extent of coronary artery disease and IMT. Thus, waiting for the results of additional large studies, uric acid may not be considered as a risk factor for coronary artery disease, and its reduction by specific therapies may not be recommended to prevent coronary artery disease and atherosclerosis. [Copyright &y& Elsevier]

Background: Biolimus-eluting stents (BESs) with a biodegradable polymer in abluminal coating achieve more complete coverage at 9 months compared with sirolimus-eluting stents (SESs) with a durable polymer, as assessed by optical coherence tomography (OCT). Whether this advantage persists or augments after complete resorption of the polymer (>12 months) is unknown.Methods: The LEADERS trial compared the performance of BES with that of SES. Patients were randomly allocated to a sequential angiographic follow-up, including OCT in selected sites, at 9 and 24 months. Struts coverage was compared using Bayesian hierarchical models as the primary outcome for the OCT substudy.Results: Fifty-six patients (26 BES, 30 SES) were enrolled in the OCT substudy. Twenty-one patients (10 BES, 11 SES) agreed to perform a second OCT follow-up at 24 months. Eleven lesions and 12 stents were analyzed sequentially in the BES group (2,455 struts at 9 months, 2,131 struts at 24 months) and 11 lesions and 18 stents in the SES group (3,421 struts at 9 months, 4,170 struts at 24 months). The previously reported advantage of BES over SES in terms of better strut coverage at 9 months was followed by improvement in coverage of the SES, resulting in identical coverage in both BES and SES at 24 months: 1.5% versus 1.8% uncovered struts, difference -0.2%, 95% credibility interval, -3.2% to 2.6%, P = .84.Conclusions: More complete strut coverage of BES as compared with SES at 9 months was followed by improvement of coverage in SES between 9 and 24 months and a similar long-term coverage in both stent types at 24 months. [ABSTRACT FROM AUTHOR]

The study reports the results of directional atherectomy with an 8Fr guiding catheter-compatible atherectomy catheter in a series of 31 in-stent restenotic lesions. This preliminary experience indicates a favorable safety profile, with events limited to non-Q-wave myocardial infarction occurring in 3.6% of patients. The secondary end point regarding the incidence of angiographic restenosis at 6 months showed a high restenosis rate (65%). [ABSTRACT FROM AUTHOR]

The European Society of Cardiology has convened a Task Force on Sudden Cardiac Death in order to provide a comprehensive, educational document on this important topic. The main document has been published in the European Heart Journal in August 2001[1].The Task Force has now summarized the most important clinical issues on sudden cardiac death and provided tables with recommendations for risk stratification and for prophylaxis of sudden cardiac death.The present recommendations are specifically intended to encourage the development and revision of national guidelines on prevention of sudden cardiac death.The common challenge for cardiologists, physicians of other medical specialties and health professionals throughout Europe is to realize the potential for sudden cardiac death prevention and to contribute to public health efforts to reduce its burden. [ABSTRACT FROM PUBLISHER]

Introduction Quantitative angiographic assessment after balloon angioplasty is a poor predictor of immediate and long-term outcome. However, the measurement of blood flow velocity during angioplasty has been proved clinically useful.Aims To analyse the value of the maximal stenotic flow velocity and the presence of stenotic flow velocity acceleration (aSV) for the long-term outcome after balloon angioplasty.Methods and Results Patients undergoing single lesion angioplasty within the DEBATE trial were included. aSV was defined as acceleration in the stenotic coronary flow velocity >50% baseline velocity assessed at a reference site of the target vessel. After balloon angioplasty diameter stenosis, minimal lumen diameter (MLD) and coronary flow velocity reserve were similar between the aSV (n=54) and non-aSV group (n=125). At follow-up, the aSV group had a higher restenosis rate (52% vs 30%, P=0·006) The presence of aSV was the strongest independent predictor of restenosis (OR 3·08, 95% CI 1·35 to 7·05, P=0·008). The best predictive cut-off value of SV was 101cm.s−1 (sensitivity of 46%, specificity of 81%, positive predictive value of 85% and a negative predictive value of 58%).Conclusion Following angioplasty, SV appears to be exquisitely sensitive to the changes experienced at the treated area without depending on the status of the microcirculation. Copyright 2002 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved. [ABSTRACT FROM PUBLISHER]

Aims To assess whether coronary flow velocity reserve following stent implantation is predictive of the subsequent need of target lesion revascularization.Methods and Results The outcome was examined of 417 patients enrolled in a multicentre prospective randomized study (DESTINI), who received a successful single vessel stent implantation in native coronary arteries and in whom coronary flow velocity reserve was measured. Logistic regression analysis and the receiver operator characteristic curve were used. When compared with 358 patients not requiring target lesion revascularization, 59 patients (14%) who underwent target lesion revascularization had a lower final coronary flow velocity reserve (2·33±0·87 vs 2·48± 0·80, P=0·20) and smaller final minimal lumen diameter (2·62±0·66mm vs 2·73±0·60,P =0·19); however, those differences were not statistically significant. Patients with a coronary flow velocity reserve of <2·0 (n=109, 26%) exhibited a significantly higher target lesion revascularization rate than patients with a coronary flow velocity reserve of ≥2·0 (22% vs 11%, P=0·010). This difference remained significant (odds ratio=2·01, 95% CI=1·11 to 3·66) after adjustment for other variables that were also correlated with the incidence of target lesion revascularization.Conclusion The presence of a final coronary flow velocity reserve of <2·0 is an independent predictor of the need for target lesion revascularization after stent implantation in native coronary artery lesions. [ABSTRACT FROM PUBLISHER]