A 20-year journey in transcatheter aortic valve implantation: Evolution to current eminence.

Since the first groundbreaking procedure in 2002, transcatheter aortic valve implantation (TAVI) has revolutionized the management of aortic stenosis (AS). Through striking developments in pertinent equipment and techniques, TAVI has now become the leading therapeutic strategy for aortic valve replacement in patients with severe symptomatic AS. The procedure streamlining from routine use of conscious sedation to a single arterial access approach, the newly adapted implantation techniques, and the introduction of novel technologies such as intravascular lithotripsy and the refinement of valve-bioprosthesis devices along with the accumulating experience have resulted in a dramatic reduction of complications and have improved associated outcomes that are now considered comparable or even superior to surgical aortic valve replacement (SAVR). These advances have opened the road to the use of TAVI in younger and lower-risk patients and up-to-date data from landmark studies have now established the outstanding efficacy and safety of TAVI in patients with low-surgical risk impelling the most recent ESC guidelines to propose TAVI, as the main therapeutic strategy for patients with AS aged 75 years or older. In this article, we aim to summarize the most recent advances and the current clinical aspects involving the use of TAVI, and we also attempt to highlight impending concerns that need to be further addressed.

Clinical outcomes following single access transfemoral transcatheter aortic valve implantation.

OBJECTIVES: We describe the first experience using calcification of anatomical landmarks to obviate the need for transcatheter aortic valve implantation (TAVI) alignment aortography and secondary TAVI access. BACKGROUND: TAVI alignment conventionally involves secondary femoral access for contrast aortography using a second catheter. Secondary femoral access accounts for up to 25% of all vascular complications. Heavily calcified aortic leaflets are often visible fluoroscopically and can act as markers for TAVI alignment. METHODS: We considered 100 consecutive patients for transfemoral TAVI. The first group was considered for a conventional dual access technique and the subsequent group was considered for a single access technique. Relevant baseline, and procedural and outcome measures were recorded. RESULTS: Baseline characteristics were comparable between groups. Balloon-expandable transcatheter heart valves (THV) were used in all cases. THV implantation was successful in 100% of cases with no procedural or in-hospital mortality. Procedural time and contrast use were lower in the single access group. There were no Valve Academic Research Consortium (VARC)-2 major vascular complications with the single access technique. CONCLUSIONS: This is the first study describing the use of calcification of anatomical landmarks to obviate the need for secondary TAVI access. Notable observations included successful device implantation in all cases, no VARC-2 major vascular complications, comparable rates of paravalvular leak and permanent pacemaker requirement, shorter procedural times, and lower contrast use. Single access TAVI is a viable alternative technique to minimize vascular access, contrast use, and procedural duration in experienced centers and with selected patients, allowing successful device implantation and low complication rates while further streamlining TAVI workflow.

"Gazing Into the Abyss": Transcatheter Mitral Valve-in-Valve Implantation Through a Cavernous Left Atrium.

We describe the case of a 73-year-old woman presenting with heart failure, a degenerating bioprosthetic mitral valve, and severely dilated left atrium, and highlight the role of multimodality imaging in planning transseptal transcatheter mitral valve-in-valve implantation. (Level of Difficulty: Advanced.).

Benralizumab for Prednisone-Dependent Eosinophilic Asthma Associated With Novel STAT3 Loss of Function Mutation.

Some severe asthmatic patients experience frequent bacterial respiratory tract infections, which contribute significantly to their disease burden, and often are attributed to their use of systemic corticosteroids and comorbid bronchiectasis. We report a case of a 58-year-old woman who had prednisone-dependent asthma and exacerbations with intense mixed eosinophilic and neutrophilic bronchitis. Autosomal dominant hyper-IgE syndrome, which is a primary immunodeficiency characterized by elevated IgE, eosinophilia, and recurrent infections, caused by a novel pathogenic mutation in STAT3 was identified as the cause of her airway disease. We believe that this is the first report of the demonstration of an IL-5 driven eosinophilia that is associated with a STAT3 mutation that was treated successfully with an anti-IL5 biological.

Baseline NT-proBNP Accurately Predicts Symptom Response to Transcatheter Aortic Valve Implantation.

Background Up to 30% of patients undergoing transcatheter aortic valve implantation (TAVI) experience minimal symptomatic benefit or die within 1 year, indicating an urgent need for enhanced patient selection. Previous analyses of baseline NT-proBNP (N-terminal pro-brain natriuretic peptide) and TAVI outcomes have assumed a linear relationship, yielding conflicting results. We reexamined the relationship between baseline NT-proBNP and symptomatic improvement after TAVI. Methods and Results Symptom status, clinical and echocardiographic data, and baseline NT-proBNP were reviewed from 144 consecutive patients undergoing TAVI for severe symptomatic aortic stenosis. The primary end point was change in New York Heart Association functional class at 1 year. There was a nonlinear, inverted-U relationship between log-baseline NT-proBNP and post-TAVI change in NYHA class (R2=0.4559). NT-proBNP thresholds of <800 and >10 000 ng/L accurately predicted no symptomatic improvement at 1 year (sensitivity 88%, specificity 83%, positive predictive value 72%, negative predictive value 93%). In adjusted analyses, baseline NT-proBNP outside this "sweet-spot" range was the only factor independently associated with poor functional outcome (high: NT-proBNP >10 000 ng/L, odds ratio [OR], 65; 95% CI, 6-664; low: NT-proBNP <800 ng/L, OR, 73; 95% CI, 7-738). Conclusions Baseline NT-proBNP is a useful prognostic marker to predict poor symptom relief after TAVI and may indicate when intervention is likely to be futile. Both low (<800 ng/L) and very high (>10 000 ng/L) levels are strongly associated with poor functional outcome, suggesting an alternative cause for symptoms in the former scenario and an irrevocably diseased left ventricle in the latter. Further evaluation of this relationship is warranted.

Incidence and outcomes of infective endocarditis following transcatheter aortic valve implantation.

INTRODUCTION: Prosthetic valve infective endocarditis is a feared and potentially catastrophic complication of valvular intervention. Transcatheter aortic valve implantation has transformed the modern management of aortic stenosis and vastly altered the demographics of those patients undergoing valve replacement. AREAS COVERED: As a relatively nascent development, what TAVI means for the epidemiology of infective endocarditis, how to identify those patients undergoing the procedure at greatest risk, and how best to prevent and manage the condition remains the subject of fervent research activity. In this review, we appraise relevant contemporary data discussing the incidence, microbiological profiles, associated risk factors and clinical outcomes of infective endocarditis after TAVI. EXPERT OPINION: Present outcomes are poor, with exceedingly high in-hospital and long-term mortality. Evidence to support surgical management in this patient group is lacking. Prevention is therefore paramount and a logical focus for future research attention.

Simultaneous Transcatheter Double Valve Treatment of Mediastinal Radiation-Induced Severe Calcific Aortic and Mitral Stenosis.

Mediastinal radiation-induced severe calcific valve disease carries increased operative mortality. Transcatheter therapies are also challenging and potentially hazardous. We used a unique constellation of imaging and planning technologies to successfully plan, simulate, and perform novel combined transcatheter aortic valve replacement and valve in mitral annular calcification in a high-risk patient. (Level of Difficulty: Advanced.).

Measurement of the liver iron concentration in transfusional iron overload by MRI R2* and by high-transition-temperature superconducting magnetic susceptometry.

PURPOSE: To compare measurement of the liver iron concentration in patients with transfusional iron overload by magnetic resonance imaging (MRI), using R2*, and by magnetic susceptometry, using a new high-transitiontemperature (high-Tc; operating at 77 K, cooled by liquid nitrogen) superconducting magnetic susceptometer. METHODS: In 28 patients with transfusional iron overload, 43 measurements of the liver iron concentration were made by both R2* and high-Tc magnetic susceptometry. RESULTS: Measurements of the liver iron concentration by R2* and high-Tc magnetic susceptometry were significantly correlated when comparing all patients (Pearson's r = 0.91, p < 0.0001) and those with results by susceptometry >7 mg Fe/g liver, dry weight (r = 0.93, p = 0.006). In lower ranges of liver iron, no significant correlations between the two methods were found (0 to <3.2 mg Fe/g liver, dry weight: r = 0.2, p = 0.37; 3.2 to 7 mg Fe/g liver, dry weight: r = 0.41; p = 0.14). CONCLUSION: The lack of linear correlation between R2* and magnetic susceptibility measurements of the liver iron concentration with minimal or modest iron overload may be due to the effects of fibrosis and other cellular pathology that interfere with R2* but do not appreciably alter magnetic susceptibility.

Audit of a tertiary heart failure outpatient service to assess compliance with NICE guidelines.

The National Institute for Health and Care Excellence (NICE) updated its guidelines for chronic heart failure (HF) in 2010. This re-audit assessed interim improvement as compared with an audit in 2011. Patients with HF (preserved and reduced ejection fraction) attending a tertiary cardiac centre over a 2-year period (January 2013-December 2014) were audited. The data collected included demographics, HF aetiology, medications, clinical parameters and cardiac rehabilitation. In total, 513 patients were audited. Compared with 2011, male preponderance (71%) and age (68±14 years, (Mean ± SD)) were similar. 73% of patients lived outside of London. HF aetiologies included ischaemic heart disease (37% versus 40% in 2011), dilated cardiomyopathy (26% versus 20%) primary valve disease (13% versus 12%). For patients with left ventricular systolic dysfunction (n=434, 85% of patients audited) 89% were taking beta-blockers (compared with 77% in 2011), 91% an angiotensin converting enzyme inhibitor or angiotensin receptor blocker (86% in 2011) and 56% a mineralocorticoid receptor antagonist (44% in 2011); 6% were prescribed ivabradine. All patients were reviewed at least 6-monthly. Although 100% of patients were educated about exercise, only 21 (4%) enrolled in a supervised exercise programme. This audit demonstrated high rates of documentation, follow-up and compliance with guideline-based medical therapies. A consistent finding was poor access to cardiac rehabilitation.

Ivabradine: A Current Overview.

Ivabradine, acting on the funny channel (If) in the sino-atrial node, reduces myocardial oxygen demand without inducing hypotension. It was developed as a specific bradycardic agent in the 1980s, avoiding the adverse effects of more traditional antianginal agents (beta-blockers and calcium channel antagonists). This has seen significant interest in this first-in-class treatment, and is perceived as a promising drug in the management of ischaemic heart disease and heart failure. There has been much clinical research conducted exploring its role in these fields, to try to elucidate potential benefits and target patient group. The side effect profile of ivabradine ensures it is well tolerated, and consistently leads to a reduction in heart rate. This review discusses the drug development and trial data in ischaemic heart disease and chronic left ventricular systolic dysfunction. Key clinical trials and observational studies are discussed in depth to examine potential explanations of unexpected or diverging results. The emerging role of ivabradine in acute decompensated heart failure is explored with recent trial data, providing a potential novel treatment avenue in this difficult to manage patient cohort. The role of intravenous ivabradine, as a beneficial tool in the acute hospital setting, when oral medication is not ideal, or where fast onset of action is required, in cardiac computerised tomography for example, is also discussed. Future directions for research are highlighted, including options for further elucidating unexplained results from previous studies.

How to Improve Time to Diagnosis in Acute Heart Failure - Clinical Signs and Chest X-ray.

Acute heart failure (AHF) is a leading cause of hospitalisation in developed nations with stubbornly poor outcomes in both the short and long term. Furthermore, alongside an ageing population the incidence continues to increase. Contemporary practice guidelines accordingly emphasise the importance of early recognition of heart failure in the acute setting to facilitate the timely instigation of key investigations, appropriate management and access to specialist care; all of which improve outcome. However, the diagnosis of AHF is often challenging, with no gold standard diagnostic test and presenting clinical features that may be non-specific, particularly in the elderly where they may be atypical, or masked by co-morbidity. This short review explores the main clinical signs and radiographic changes in patients with AHF relevant to clinical practice in accordance with the best available evidence.

Lipid and smoker's inclusions in sputum macrophages in patients with airway diseases.

We studied the effect of tobacco smoking on macrophage lipid index and macrophage smokers inclusions in induced sputum in 256 patients (143 non-smokers, 81 ex-smokers and 32 current smokers). Lipid index was, using the Oil red O stain, the sum of the lipid staining droplet score (range 0-4) in 100 macrophages. Smokers inclusions were assessed using Wright's stain and graded as "none", "few", "moderate" or "many". Lipid index was significantly higher in current smokers (112.5, SD 58.5 units) than ex-smokers (29.2, SD 42.8 units) or non-smokers (13.4, SD 121.7). Smokers inclusions were present in all current smokers but only in 2 non-smokers. The mean smoking history of current smokers with few macrophage inclusions was 15.0 (SD 11.2), moderate 21.6 (SD 15.7), and many 30.0 (SD 21.9) pack years. There was a significant difference between the length of time ex-smokers had quit smoking if they had no or few smokers inclusions (mean 17.6 (SD 11.2) years) compared to those with moderate or many smokers inclusions (mean 2.8 (SD 5.8) years) (p = 0.01). Lipid index was significantly correlated with smokers inclusions (r = 0.72, p < 0.01). We conclude that smoker's inclusions within sputum macrophages is a reliable indicator of cigarette smoking and that the sputum lipid index cannot be used as an assessment of oropharyngeal reflux in cigarette smokers.

Sputum neutrophilia can mask eosinophilic bronchitis during exacerbations.

BACKGROUND: Exacerbations of airway disease are eosinophilic, neutrophilic, both or neither. The primary objective of the present study was to identify whether the treatment of a neutrophilic bronchitis can unmask an associated eosinophilia. METHODS: A retrospective survey of 2160 consecutive sputum cell counts from 1343 patients with airway disease was conducted to identify patients with an isolated neutrophilic bronchitis, which was defined as a sputum total cell count of greater than or equal to 12 x 10(6) cells/g of sputum and a proportion of neutrophils of 80% or greater. The characteristics of the patients who subsequently demonstrated sputum eosinophilia (3% or greater) within eight weeks of resolving the neutrophilia were compared with the patients who subsequently did not have sputum eosinophilia. RESULTS: Two hundred thirty-seven patients had 273 neutrophilic exacerbations. The sputum was re-examined within eight weeks in 65 patients (27.4%), of whom 38 (58.5%) had resolution of the neutrophilic bronchitis after treatment with an antibiotic. Of these 38 patients, 13 (34%) showed eosinophilia. CONCLUSIONS: A neutrophilic exacerbation of airway disease was observed to mask sputum eosinophilia in one-third of patients who had sputum cell counts available before and after antibiotic therapy. Hence, the absence of sputum eosinophilia during an infective exacerbation should not be used as an indication to reduce the dose of corticosteroids. To optimize therapy, repeat sputum cell count measurements are recommended after antibiotic treatment before changing corticosteroid treatment.

Changing pattern of sputum cell counts during successive exacerbations of airway disease.

BACKGROUND: Exacerbations of airway disease are eosinophilic, neutrophilic, both or neither, and this determines the treatment needed. We examined changes in the cellular nature of airway inflammation between consecutive exacerbations and their predictors in individual patients. METHODS: In a retrospective survey of 1786 consecutive sputum cell counts from 1139 patients with airway disease, we identified 79 patients with two or more exacerbations at an interval of >or=6 weeks. The patients were divided into those who demonstrated a change in the type of airway inflammation and those who did not. RESULTS: There were 186 exacerbations of airway disease over 22 months. The cellular nature of inflammation was eosinophilic in 43%, neutrophilic in 40%, combined eosinophilic and neutrophilic in 5% and unclassified in 12%. A change in the type of airway inflammation was seen in 38 patients (48%). Patients, whose previous exacerbation was eosinophilic or neutrophilic were twice or nearly three times more likely, respectively, to have a subsequent exacerbation of the same type. There was no significant difference in the time to the second exacerbation or the inflammatory type of the second exacerbation in relation to the first exacerbation, irrespective of the cellular nature of the first exacerbation. CONCLUSIONS: Quantitative sputum cell counts during successive exacerbations identify that they are commonly of different type, reflecting different causes and the need for different treatment. Their use, when available, helps to optimize therapy.

Does laparoscopic Nissen fundoplication prevent the progression of Barrett's oesophagus? Is the length of Barrett's a factor?

INTRODUCTION: Recent studies have suggested that both laparoscopic and open anti-reflux surgery may produce regression of Barrett's mucosa. MATERIAL AND METHODS;: We reviewed 21 patients (13M: 8F, mean age 46.7±3.18 years) with documented Gastroesophageal Reflux Disease (GERD) and Non-dysplastic Barrett's esophagus (15 patients ?3 cm segment, 6 patients < 3 cm segment) on long term proton pump inhibitor therapy who underwent laparoscopic Nissen fundoplication (LNF) between 1993 and 2000. All patients had undergone pre and yearly postoperative upper GI endoscopy with 4 quadrant biopsies every 2 cm. All patients also underwent pre- and 6 months postoperative 24-hr pH study, esophageal manometry, SF36, and GERD symptom score. The mean duration of GERD symptoms was 8.4±1.54 years pre-operative. The mean follow-up after surgery was 39±6.32 months. RESULTS: Postoperatively, there was significant improvement in reflux symptom score (37.5 ± 3.98 points versus 8.7 ± 2.46 points, P = 0.0001), % acid reflux in 24 hr (26.5 ± 3.91% versus 2.1 ± 0.84%, P< 0.0001) and an increase in lower esophageal sphincter pressure (3.71 ± 1.08 mmHg versus 12.29 ± 1.34 mmHg, P = 0.0053). Complete or partial regression of Barrett's mucosa occurred in 9 patients. All patients with complete regression had <4 cm segment of Barrett's. Progression or cancer transformation was not observed in any of the patients. CONCLUSION: LNF in patients with Barrett's oesophagus results in significant control of GERD symptoms. LNF can prevent progression of Barrett's oesophagus and in patients with Barrett's <4 cm may lead to complete regression.