Implementing the new European Regulations on medical devices-clinical responsibilities for evidence-based practice: a report from the Regulatory Affairs Committee of the European Society of Cardiology.

The new European Union (EU) law governing the regulatory approval of medical devices that entered into force in May 2017 will now take effect from 26 May 2021. Here, we consider how it will change daily practice for cardiologists, cardiac surgeons, and healthcare professionals. Clinical evidence for any high-risk device must be reported by the manufacturer in a Summary of Safety and Clinical Performance (SSCP) that will be publicly available in the European Union Database on Medical Devices (Eudamed) maintained by the European Commission; this will facilitate evidence-based choices of which devices to recommend. Hospitals must record all device implantations, and each high-risk device will be trackable by Unique Device Identification (UDI). Important new roles are envisaged for clinicians, scientists, and engineers in EU Expert Panels-in particular to scrutinize clinical data submitted by manufacturers for certain high-risk devices and the evaluations of that data made by notified bodies. They will advise manufacturers on the design of their clinical studies and recommend to regulators when new technical specifications or guidance are needed. Physicians should support post-market surveillance by reporting adverse events and by contributing to comprehensive medical device registries. A second law on In Vitro Diagnostic Medical Devices will take effect from 2022. We encourage all healthcare professionals to contribute proactively to these new systems, in order to enhance the efficacy and safety of high-risk devices and to promote equitable access to effective innovations. The European Society of Cardiology will continue to advise EU regulators on appropriate clinical evaluation of high-risk devices.

Long-Term Durability of Transcatheter Valves: The Importance of Accurate Data.

As transcatheter valves are offered to progressively lower-risk patients, it is increasingly important to have accurate data about durability. Structural valve deterioration (SVD) implies an adverse change in the morphology of the leaflets and function of the valve compared with the state at implantation. However, a recent European statement allows SVD to be defined solely by a threshold mean gradient ≥20 mm Hg. Absolute mean gradients above this threshold may be observed immediately after implantation and represent patient-prosthesis mismatch and not SVD. This paper describes a definition of SVD more in keeping with routine clinical practice, incorporating a change in leaflet morphology and an increase in the grade of transvalvar regurgitation or an increase in gradient from the post-implantation study.

The need for transparency of clinical evidence for medical devices in Europe.

To use medical devices rationally, health-care professionals must base their choices of which devices to recommend for individual patients on an objective appraisal of their safety and clinical efficacy. The evidence submitted by manufacturers when seeking approval of their high-risk devices must be publicly available, including technical performance and premarket clinical studies. Giving physicians access to this information supplements the peer-reviewed scientific literature and might be essential for comparing alternative devices within any class. Interested patients should be encouraged to review the evidence for any device that has been recommended for them. The new EU law on medical devices states that the manufacturer is to prepare a summary of the evidence for any implantable or high-risk device. Defining its content, however, has been delegated to implementing legislation, which is now being considered. From a clinical perspective, it is imperative that all evidence reviewed by notified bodies and regulatory authorities is disclosed-with the exception, if justified, only of technical specifications that are considered confidential or manufacturing details that are protected as intellectual property-and public access to this evidence must be guaranteed by EU law. From ethical and other perspectives, there are no grounds for less clinical evidence being available to health-care professionals about the medical devices that they use than is already available for new pharmaceutical products. Full transparency is needed; without it, informed decisions relating to the use of new medical devices will remain impossible.

Clinical evaluation of new heart valve prostheses: update of objective performance criteria.

This article summarizes the long-term clinical results of the Food and Drug Administration-approved heart valves, provides current updates to the objective performance criteria (OPC) used to evaluate new heart valve prostheses, and documents the steps that the International Organization for Standardization Committee used to arrive at the updated OPC. Data were extracted from 19 Food and Drug Administration summaries of safety and effectiveness data reports (31 series) and 56 literature articles (85 series) published from 1999 to 2012. The OPC were calculated for five valve-related complications by valve type (mechanical and bioprosthetic) and valve position (aortic and mitral).

Three decades of experience in the surgical multi-modality management of pleural mesothelioma.

BACKGROUND: Optimal management of diffuse malignant pleural mesothelioma (DMPM) remains unclear. We report our 30-year surgical experience with DMPM with emphasis on surgical procedure and post-operative adjuvant therapy. METHODS: During the period of the study, 217 patients with DMPM were referred for surgical opinion. Patients who only had pleural biopsies were excluded (n=78). Consecutive patients who underwent surgical treatment were included (n=139). Surgical options were extra-pleural pneumonectomy (EPP) for Butchart stage I disease in clinically fit patients (n=49) or pleurectomy/decortication in patients who were either not fit for EPP or had advanced disease (Butchart stage II and III) or both (n=90). Post-operative adjuvant therapy included either chemotherapy, radiotherapy, both or none. RESULTS: The median follow-up was 10.0 months. The longest survival (median 26.0 months, IQR: 11.14-40.9 months) occurred in the pleurectomy/decortication group who received both post-operative chemotherapy and radiotherapy (n=24) (p<0.001). EPP whether or not combined with adjuvant therapy provided no significant survival advantage in comparison to pleurectomy/decortication (overall median survival 10.3 months vs 10.1 months, p=0.09). On univariate analysis, pleurectomy/decortication combined with chemotherapy and radiotherapy was the strongest predictor of prolonged survival (Hazard Ratio=3.6). Multivariate analysis with the inclusion of histological type, surgical procedure and type of adjuvant therapy, EPP without adjuvant therapy was an independent risk-factor for decreased survival (Hazard Ratio=9.2). CONCLUSIONS: In this series, cytoreductive surgery combined with post-operative adjuvant therapy provided better survival despite either advanced disease or surgically less fit patients. Thus, pleurectomy/decortication may be the procedure of choice, given that neither surgical procedure (EPP or PD) is not curative.

SV40 large T antigen-specific human T cell memory responses.

The continued presence of simian virus 40 (SV40), a monkey polyomavirus, in man is confirmed by the regular detection of SV40-specific antibodies in 5-10% of children who are unlikely to have received contaminated polio-vaccines. The aim of our experiments was to find cellular immunological evidence of SV40 infection in humans by testing memory T cell responses to SV40 large T antigen (Tag). As there is some indication that the virus may be present in malignant pleural mesothelioma (MPM) cells, we analyzed T cell responses in MPM patients and in healthy donors. The frequencies of responding T cells to overlapping Tag peptides were tested by cytokine flow cytometry. CD8+ T cells from 4 of 32 MPM patients responded (above twofold of control) to SV40 Tag peptides, while no positive responses were detected in 12 healthy donors. Within SV40 Tag we identified three 15 amino acid-long immunogenic sequences and one 9 amino acid-long T cell epitope (p138) (138FPSELLSFL146), the latter including a HLA-B7-restriction motif. T cell responses to p138 were SV40-specific as T cells stimulated with p138 did not cross-react with the corresponding sequences of Tag of human polyomaviruses BKV and JCV. Similarly, the relevant BKV and JCV Tag peptides did not generate T cell responses against SV40 TAg p138. Peptide-stimulated T cells also killed SV40 Tag-transfected target cells. This article demonstrates the presence, and provides a detailed analysis, of SV40-specific T cell memory in man.

Valvular heart disease in the community: a European experience.

The Euro Heart Survey on valvular heart disease included 5001 patients from 92 centers in 25 European countries in 2001: 71.9% had native valve disease and 28.1% had previously undergone valve surgery. Aortic stenosis (AS) and mitral regurgitation (MR) accounted for 43.1 and 33.6%, respectively, of single-valve diseases and were mostly caused by degenerative diseases. Mean age was 69 and 65 years, respectively, and at least one comorbidity was present in 36.3% of patients with AS and 41.7% with MR. Analysis of the therapeutic decision in patients with severe valve diseases showed that symptomatic patients were frequently denied surgery (32.3% in AS after the age of 75 and 51.3% in MR), more on the basis of age and left ventricular function than comorbidities. There was a better concordance between practice and guidelines concerning interventions in asymptomatic patients. These findings underline the need for better implementation of guidelines.

What are the characteristics of patients with severe, symptomatic, mitral regurgitation who are denied surgery?

AIM: To identify the proportion and characteristics of patients with severe symptomatic mitral regurgitation (MR) who are denied surgery. METHODS AND RESULTS: In the Euro Heart Survey on valvular heart disease, 396 patients had severe symptomatic MR as assessed by Doppler-echocardiography (grade > or =3/4) and New York Heart Association class II or greater. Patient characteristics were analysed according to the decision to operate or not. A decision not to operate was taken in 193 patients (49%). In multivariable analysis, decreased left ventricular ejection fraction (LVEF) [OR = 1.39 per 10% decrease, 95% CI (1.17-1.66), P = 0.0002], non-ischaemic aetiology [OR = 4.44, 95% CI (1.96-10.76), P = 0.0006], older age [OR = 1.40 per 10-year increase, 95% CI (1.15-1.72), P = 0.001], increased Charlson comorbidity index [OR = 1.38 per 1 point increase, 95% CI (1.12-1.72), P = 0.004], and grade 3 MR [OR = 2.23, 95% CI (1.28-3.29), P = 0.005] were associated with the decision not to operate. One-year survival was 96.0 +/- 1.4% in patients with a positive decision for intervention vs. 89.5 +/- 2.3% in those with a negative decision (P = 0.02). CONCLUSION: Surgery was denied in 49% of patients with severe symptomatic MR. Impaired LVEF, older age, and comorbidity were the most striking characteristics of patients who were denied surgery. The weight of age and LVEF in the decision do not seem justified according to current knowledge.

Long-term outcome of bronchoscopically resected endobronchial typical carcinoid tumors.

BACKGROUND: Typical pulmonary carcinoid tumors represent less than 1% of lung tumors. In a subgroup of patients with this abnormality, the tumor is entirely endobronchial. We assessed the long-term outcome of such cases in which the patient was managed with endobronchial resection only. METHODS: Patients who underwent bronchoscopic resection for a typical carcinoid tumor were identified through case records and histology reports. Data were collected retrospectively, but follow-up was on a prospective basis through the outpatient clinic. RESULTS: Between 1978 and 2004, 28 patients underwent bronchoscopic resection of endobronchial carcinoid tumors. The mean age was 49 years (standard deviation, 19 years; age range, 11-82 years), with 46% (13/28) of the patients being male. The tumor arose from the left bronchial tree in 61% (17/28), with the most common site being the left lower lobe bronchus (8/28). On average, patients required 5 bronchoscopic resections to achieve complete resection. The median follow-up was 8.8 years (interquartile range, 4.5-13.7 years). At 1 and 10 years, 100% and 94% of patients were disease free, respectively. The 1- and 10-year survivals were 89% (interquartile range, 84%-93%) and 84% (interquartile range, 77%-91%), respectively. CONCLUSION: In a selected group of patients, proximal polypoid typical bronchial carcinoid tumors can be treated endobronchially with good outcome.

Increased sensitivity to warfarin after heart valve replacement.

BACKGROUND: The dosage requirement of warfarin to achieve a given international normalized ratio (INR) often varies considerably between the immediate postoperative period and long-term follow-up in patients with prosthetic heart valves, leading to INR instability. OBJECTIVE: To document the extent of warfarin sensitivity in a prospective study of patients receiving heart valve replacements. METHODS: Clinical and laboratory data regarding anticoagulation for 111 patients who received warfarin following heart valve replacement were collected during their hospital stay (induction period) and between 1 and 3 months after surgery (follow-up period). RESULTS: Mean patient age was 65.39 +/- 10.55 years (range 29-85), with 66 men. The mean INR value during the follow-up period was, on average, 0.21 higher than the induction period (2.81 +/- 0.5 vs 2.6 +/- 0.6; p = 0.007). The mean follow-up warfarin dose was 1.54 mg higher than the mean induction warfarin dose (5.09 +/- 2.03 vs 3.55 +/- 1.94 mg; p < 0.001). The warfarin dose index, which indicates relative sensitivity of warfarin, decreased from 1.16 to 0.65 (p < 0.001). Although the INR values during the induction and follow-up periods were similar, the dose requirement in the follow-up period was, on average, 43% higher than that of the induction period. CONCLUSIONS: Immediately after heart valve replacement, patients are more sensitive to warfarin and should receive a lower warfarin dose during the initial phase of oral anticoagulation treatment. This enhanced sensitivity decreases with time. Patients require frequent monitoring and are likely to need an increase in the warfarin dose to avoid insufficient anticoagulation during the early follow-up period.

Bilateral cervical lung hernia with T1 nerve compression.

Lung hernia is a rare condition. Approximately one third of cases occur in the cervical position. We report a case of bilateral cervical lung hernia associated with neuralgic pain that was repaired using bovine pericardium and biological glue.