Validity of Charlson Comorbidity Index in patients hospitalised with acute coronary syndrome. Insights from the nationwide AMIS Plus registry 2002-2012

OBJECTIVE This study aimed to assess the impact of individual comorbid conditions as well as the weight assignment, predictive properties and discriminating power of the Charlson Comorbidity Index (CCI) on outcome in patients with acute coronary syndrome (ACS). METHODS A prospective multicentre observational study (AMIS Plus Registry) from 69 Swiss hospitals with 29 620 ACS patients enrolled from 2002 to 2012. The main outcome measures were in-hospital and 1-year follow-up mortality. RESULTS Of the patients, 27% were female (age 72.1±12.6 years) and 73% were male (64.2±12.9 years). 46.8% had comorbidities and they were less likely to receive guideline-recommended drug therapy and reperfusion. Heart failure (adjusted OR 1.88; 95% CI 1.57 to 2.25), metastatic tumours (OR 2.25; 95% CI 1.60 to 3.19), renal diseases (OR 1.84; 95% CI 1.60 to 2.11) and diabetes (OR 1.35; 95% CI 1.19 to 1.54) were strong predictors of in-hospital mortality. In this population, CCI weighted the history of prior myocardial infarction higher (1 instead of -0.4, 95% CI -1.2 to 0.3 points) but heart failure (1 instead of 3.7, 95% CI 2.6 to 4.7) and renal disease (2 instead of 3.5, 95% CI 2.7 to 4.4) lower than the benchmark, where all comorbidities, age and gender were used as predictors. However, the model with CCI and age has an identical discrimination to this benchmark (areas under the receiver operating characteristic curves were both 0.76). CONCLUSIONS Comorbidities greatly influenced clinical presentation, therapies received and the outcome of patients admitted with ACS. Heart failure, diabetes, renal disease or metastatic tumours had a major impact on mortality. CCI seems to be an appropriate prognostic indicator for in-hospital and 1-year outcomes in ACS patients. CLINICALTRIALSGOV IDENTIFIER NCT01305785.

The 2011-12 pilot European Sentinel Registry of Transcatheter Aortic Valve Implantation: in-hospital results in 4,571 patients

AIMS The aim of this prospective multinational registry is to assess and identify predictors of in-hospital outcome and complications of contemporary TAVI practice. METHODS AND RESULTS The Transcatheter Valve Treatment Sentinel Pilot Registry is a prospective independent consecutive collection of individual patient data entered into a web-based case record form (CRF) or transferred from compatible national registries. A total of 4,571 patients underwent TAVI between January 2011 and May 2012 in 137 centres of 10 European countries. Average age was 81.4±7.1 years with equal representation of the two sexes. Logistic EuroSCORE (20.2±13.3), access site (femoral approach: 74.2%), type of anaesthesia and duration of hospital stay (9.3±8.1 days) showed wide variations among the participating countries. In-hospital mortality (7.4%), stroke (1.8%), myocardial infarction (0.9%), major vascular complications (3.1%) were similar in the SAPIEN XT and CoreValve (p=0.15). Mortality was lower in transfemoral (5.9%) than in transapical (12.8%) and other access routes (9.7%; p<0.01). Advanced age, high logistic EuroSCORE, pre-procedural ≥grade 2 mitral regurgitation and deployment failure predicted higher mortality at multivariate analysis. CONCLUSIONS Increased operator experience and the refinement of valve types and delivery catheters may explain the lower rate of mortality, stroke and vascular complications than in historical studies and registries.

Percutaneous left-ventricular support with the Impella-2.5-assist device in acute cardiogenic shock: results of the Impella-EUROSHOCK-registry

BACKGROUND Acute cardiogenic shock after myocardial infarction is associated with high in-hospital mortality attributable to persisting low-cardiac output. The Impella-EUROSHOCK-registry evaluates the safety and efficacy of the Impella-2.5-percutaneous left-ventricular assist device in patients with cardiogenic shock after acute myocardial infarction. METHODS AND RESULTS This multicenter registry retrospectively included 120 patients (63.6±12.2 years; 81.7% male) with cardiogenic shock from acute myocardial infarction receiving temporary circulatory support with the Impella-2.5-percutaneous left-ventricular assist device. The primary end point evaluated mortality at 30 days. The secondary end point analyzed the change of plasma lactate after the institution of hemodynamic support, and the rate of early major adverse cardiac and cerebrovascular events as well as long-term survival. Thirty-day mortality was 64.2% in the study population. After Impella-2.5-percutaneous left-ventricular assist device implantation, lactate levels decreased from 5.8±5.0 mmol/L to 4.7±5.4 mmol/L (P=0.28) and 2.5±2.6 mmol/L (P=0.023) at 24 and 48 hours, respectively. Early major adverse cardiac and cerebrovascular events were reported in 18 (15%) patients. Major bleeding at the vascular access site, hemolysis, and pericardial tamponade occurred in 34 (28.6%), 9 (7.5%), and 2 (1.7%) patients, respectively. The parameters of age >65 and lactate level >3.8 mmol/L at admission were identified as predictors of 30-day mortality. After 317±526 days of follow-up, survival was 28.3%. CONCLUSIONS In patients with acute cardiogenic shock from acute myocardial infarction, Impella 2.5-treatment is feasible and results in a reduction of lactate levels, suggesting improved organ perfusion. However, 30-day mortality remains high in these patients. This likely reflects the last-resort character of Impella-2.5-application in selected patients with a poor hemodynamic profile and a greater imminent risk of death. Carefully conducted randomized controlled trials are necessary to evaluate the efficacy of Impella-2.5-support in this high-risk patient group.

Testing an alternative search algorithm for compound identification with the 'Wiley Registry of Tandem Mass Spectral Data. MSforID'

A tandem mass spectral database system consists of a library of reference spectra and a search program. State-of-the-art search programs show a high tolerance for variability in compound-specific fragmentation patterns produced by collision-induced decomposition and enable sensitive and specific 'identity search'. In this communication, performance characteristics of two search algorithms combined with the 'Wiley Registry of Tandem Mass Spectral Data, MSforID' (Wiley Registry MSMS, John Wiley and Sons, Hoboken, NJ, USA) were evaluated. The search algorithms tested were the MSMS search algorithm implemented in the NIST MS Search program 2.0g (NIST, Gaithersburg, MD, USA) and the MSforID algorithm (John Wiley and Sons, Hoboken, NJ, USA). Sample spectra were acquired on different instruments and, thus, covered a broad range of possible experimental conditions or were generated in silico. For each algorithm, more than 30,000 matches were performed. Statistical evaluation of the library search results revealed that principally both search algorithms can be combined with the Wiley Registry MSMS to create a reliable identification tool. It appears, however, that a higher degree of spectral similarity is necessary to obtain a correct match with the NIST MS Search program. This characteristic of the NIST MS Search program has a positive effect on specificity as it helps to avoid false positive matches (type I errors), but reduces sensitivity. Thus, particularly with sample spectra acquired on instruments differing in their Setup from tandem-in-space type fragmentation, a comparably higher number of false negative matches (type II errors) were observed by searching the Wiley Registry MSMS.

Hereditary thrombotic thrombocytopenic purpura and the hereditary TTP registry

Hereditary thrombotic thrombocytopenic purpura, Upshaw-Schulman syndrome, ADAMTS13 Hereditary thrombotic thrombocytopenic purpura (TTP), also known as Upshaw-Schulman syndrome, is a rare recessively inherited disease. Underlying is a severe constitutional deficiency of the von Willebrand factor-cleaving protease, ADAMTS13, due to compound heterozygous or homozygous mutations in the ADAMTS13 gene. The clinical picture is variable and more and more patients with an adult-onset are diagnosed. In the majority of countries the only available treatment is plasma, which when administered regularly can efficiently prevent acute disease bouts. The decision to initiate regular prophylaxis is often not easy, as evidence based guidelines and long term outcome data are lacking. Through the hereditary TTP registry (www.ttpregistry.net, ClinicalTrials.gov identifier: NCT01257269), which was initiated in 2006 and is open to all patients diagnosed with Upshaw-Schulman syndrome and their family members, we aim to gain further information and insights into this rare disease, which eventually will help to improve clinical management of affected patients.

Real-life results of balloon kyphoplasty for vertebral compression fractures from the SWISSspine registry

BACKGROUND CONTEXT The Swiss Federal Office of Public Health mandated a nationwide health technology assessment-registry for balloon kyphoplasty (BKP) for decision making on reimbursement of these interventions. The early results of the registry led to a permanent coverage of BKP by basic health insurance. The documentation was continued for further evidence generation. PURPOSE This analysis reports on the 1 year results of patients after BKP treatment. STUDY DESIGN Prospective multicenter observational case series. PATIENT SAMPLE The data on 625 cases with 819 treated vertebrae were documented from March 2005 to May 2012. OUTCOME MEASURES Surgeon-administered outcome instruments were primary intervention form for BKP and the follow-up form; patient self-reported measures were EuroQol-5D questionnaire, North American Spine Society outcome instrument /Core Outcome Measures Index (including visual analog scale), and a comorbidity questionnaire. Outcome measures were back pain, medication, quality of life (QoL), cement extrusions, and new fractures within the first postoperative year. METHODS Data were recorded preoperatively and at 3 to 6-month and 1-year follow-ups. Wilcoxon signed-rank test was used for comparison of pre- with postoperative measurements. Multivariate logistic regression was used to identify factors with a significant influence on the outcome. RESULTS Seventy percent of patients were women with mean age of 71 years (range, 18-91 years); mean age of men was 65 years (range, 15-93 years). Significant and clinically relevant reduction of back pain, improvement of QoL, and reduction of pain killer consumption was seen within the first postoperative year. Preoperative back pain decreased from 69.3 to 29.0 at 3 to 6-month and remained unchanged at 1-year follow-ups. Consequently, QoL improved from 0.23 to 0.71 and 0.75 at the same follow-up intervals. The overall vertebra-based cement extrusion rates with and without extrusions into intervertebral discs were 22.1% and 15.3%, respectively. Symptomatic cement extrusions with radiculopathy were five (0.8%). A new vertebral fracture within a year from the BKP surgery was observed in 18.4% of the patients. CONCLUSIONS The results of the largest observational study for BKP so far are consistent with published randomized trials and systematic reviews. In this routine health care setting, BKP is safe and effective in reducing pain, improving QoL, and lowering pain_killer consumption and has an acceptable rate of cement extrusions. Postoperative outcome results show clear and significant clinical improvement at early follow-up that remain stable during the first postoperative year.

Cement volume is the most important modifiable predictor for pain relief in BKP: results from SWISSspine, a nationwide registry

Purpose The effectiveness of vertebral augmentation techniques is a currently highly debated issue. The biomechanical literature suggests that cement filling volumes may play an important role in the ‘‘dosage’’ of vertebral augmentation and its pain alleviating effect. Good clinical data about filling volumes are scarce and most patient series are small. Therefore, we investigated the predictors of pain alleviation after balloon kyphoplasty in the nationwide SWISSspine registry where cement volumes are also recorded. Methods All single-level vertebral fractures with no additional fracture stabilization and availability of at least one follow-up within 6 months after surgery were included. The following potential predictors were assessed in a multivariate logistic regression model with the group’s average pain alleviation of 41 points on VAS as the desired outcome: patient age, patient sex, diagnosis, preoperative pain, level of fracture, type of fracture, age of fracture, segmental kyphotic deformity, cement volume, vertebral body filling volume, and cement extrusions. Results There were 194 female and 82 males with an average age of 70.4 and 65.3 years, respectively. Female patients were about twice as likely for achieving the average pain relief compared to males (p = 0.04). The preoperative pain level was the strongest predictor in that the likelihood for achieving an at least 41-point pain relief increased by about 8 % with each additional point of preoperative pain (p\0.001). A thoraco-lumbar fracture had a three times higher odds for the average pain relief compared with a lumbar fracture (p = 0.03). An A.3.1 fracture only had about a third of the probability for average pain relief compared with an A.1.1 fracture (p = 0.004). Cement volumes up to 4.5 ml only had an approximately 40 % chance for a minimum 41-point pain alleviation as compared with cement volumes of at least 4.5 ml (p = 0.007). In addition, the relationship between cement volume and pain alleviation followed a dose-dependent pattern. Conclusions Cement volume was revealed as a significant predictor for pain relief in BKP. Cement volume was the third most important influential covariate and the most important modifiable and operator dependent one. The clear dose-outcome relationship between cement filling volumes and pain relief additionally supports these findings. Cement volumes of [4.5 ml seem to be recommendable for achieving relevant pain alleviation. Patient sex and fracture type and location were further significant predictors and all these covariates should be recorded and reported in future studies about the pain alleviating effectiveness of vertebral augmentation procedures.

Intra- and postoperative complications of navigated and conventional techniques in percutaneous iliosacral screw fixation after pelvic fractures: Results from the German Pelvic Trauma Registry

Background: Percutaneous iliosacral screw placement following pelvic trauma is a very demanding technique involving a high rate of screw malpositions possibly associated with the risk of neurological damage or inadequate stability. In the conventional technique, the screw’s correct entry point and the small target corridor for the iliosacral screw may be difficult to visualise using an image intensifier. 2D and 3D navigation techniques may therefore be helpful tools. The aim of this multicentre study was to evaluate the intra- and postoperative complications after percutaneous screw implantation by classifying the fractures using data from a prospective pelvic trauma registry. The a priori hypothesis was that the navigation techniques have lower rates of intraoperative and postoperative complications. Methods: This study is based on data from the prospective pelvic trauma registry introduced by the German Society of Traumatology and the German Section of the AO/ASIF International in 1991. The registry provides data on all patients with pelvic fractures treated between July 2008 and June 2011 at any one of the 23 Level I trauma centres contributing to the registry. Results: A total of 2615 patients were identified. Out of these a further analysis was performed in 597 patients suffering injuries of the SI joint (187 � with surgical interventions) and 597 patients with sacral fractures (334 � with surgical interventions). The rate of intraoperative complications was not significantly different, with 10/114 patients undergoing navigated techniques (8.8%) and 14/239 patients in the conventional group (5.9%) for percutaneous screw implantation (p = 0.4242). Postoperative complications were analysed in 30/114 patients in the navigated group (26.3%) and in 70/239 patients (29.3%) in the conventional group (p = 0.6542). Patients who underwent no surgery had with 66/197 cases (33.5%) a relatively high rate of complications during their hospital stay. The rate of surgically-treated fractures was higher in the group with more unstable Type-C fractures, but the fracture classification had no significant influence on the rate of complications. Discussion: In this prospective multicentre study, the 2D/3D navigation techniques revealed similar results for the rate of intraoperative and postoperative complications compared to the conventional technique. The rate of neurological complications was significantly higher in the navigated group.

The FReedom from Ischemic Events-New Dimensions for Survival (FRIENDS) registry: design of a prospective cohort study of patients with advanced peripheral artery disease.

BACKGROUND Advanced lower extremity peripheral artery disease (PAD), whether presenting as acute limb ischemia (ALI) or chronic critical limb ischemia (CLI), is associated with high rates of cardiovascular ischemic events, amputation, and death. Past research has focused on strategies of revascularization, but few data are available that prospectively evaluate the impact of key process of care factors (spanning pre-admission, acute hospitalization, and post-discharge) that might contribute to improving short and long-term health outcomes. METHODS/DESIGN The FRIENDS registry is designed to prospectively evaluate a range of patient and health system care delivery factors that might serve as future targets for efforts to improve limb and systemic outcomes for patients with ALI or CLI. This hypothesis-driven registry was designed to evaluate the contributions of: (i) pre-hospital limb ischemia symptom duration, (ii) use of leg revascularization strategies, and (iii) use of risk-reduction pharmacotherapies, as pre-specified factors that may affect amputation-free survival. Sequential patients would be included at an index "vascular specialist-defined" ALI or CLI episode, and patients excluded only for non-vascular etiologies of limb threat. Data including baseline demographics, functional status, co-morbidities, pre-hospital time segments, and use of medical therapies; hospital-based use of revascularization strategies, time segments, and pharmacotherapies; and rates of systemic ischemic events (e.g., myocardial infarction, stroke, hospitalization, and death) and limb ischemic events (e.g., hospitalization for revascularization or amputation) will be recorded during a minimum of one year follow-up. DISCUSSION The FRIENDS registry is designed to evaluate the potential impact of key factors that may contribute to adverse outcomes for patients with ALI or CLI. Definition of new "health system-based" therapeutic targets could then become the focus of future interventional clinical trials for individuals with advanced PAD.

Short-term clinical outcomes among patients undergoing transcatheter aortic valve implantation in Switzerland: the Swiss TAVI registry

Aims: To evaluate short-term clinical outcomes following transcatheter aortic valve implantation (TAVI) using CE-mark approved devices in Switzerland. Methods and results: The Swiss TAVI registry is a national, prospective, multicentre, monitored cohort study evaluating clinical outcomes in consecutive patients undergoing TAVI at cardiovascular centres in Switzerland. From February 2011 to March 2013, a total of 697 patients underwent TAVI for native aortic valve stenosis (98.1%), degenerative aortic bioprosthesis (1.6%) or severe aortic regurgitation (0.3%). Patients were elderly (82.4±6 years), 52% were females, and the majority highly symptomatic (73.1% NYHA III/IV). Patients with severe aortic stenosis (mean gradient 44.8±17 mmHg, aortic valve area 0.7±0.3 cm2) were either deemed inoperable or at high risk for conventional surgery (STS 8.2%±7). The transfemoral access was the most frequently used (79.1%), followed by transapical (18.1%), direct aortic (1.7%) and subclavian access (1.1%). At 30 days, rates of all-cause mortality, cerebrovascular events and myocardial infarction were 4.8%, 3.3% and 0.4%, respectively. The most frequently observed adverse events were access-related complications (11.8%), permanent pacemaker implantation (20.5%) and bleeding complications (16.6%). The Swiss TAVI registry is registered at ClinicalTrials.gov (NCT01368250). Conclusions: The Swiss TAVI registry is a national cohort study evaluating consecutive TAVI procedures in Switzerland. This first outcome report provides favourable short-term clinical outcomes in unselected TAVI patients.

Trends and outcomes in the use of surgery and radiation for the treatment of locally advanced esophageal cancer: a propensity score adjusted analysis of the surveillance, epidemiology, and end results registry from 1998 to 2008

We examined outcomes and trends in surgery and radiation use for patients with locally advanced esophageal cancer, for whom optimal treatment isn't clear. Trends in surgery and radiation for patients with T1-T3N1M0 squamous cell or adenocarcinoma of the mid or distal esophagus in the Surveillance, Epidemiology, and End Results database from 1998 to 2008 were analyzed using generalized linear models including year as predictor; Surveillance, Epidemiology, and End Results doesn't record chemotherapy data. Local treatment was unimodal if patients had only surgery or radiation and bimodal if they had both. Five-year cancer-specific survival (CSS) and overall survival (OS) were analyzed using propensity-score adjusted Cox proportional-hazard models. Overall 5-year survival for the 3295 patients identified (mean age 65.1 years, standard deviation 11.0) was 18.9% (95% confidence interval: 17.3-20.7). Local treatment was bimodal for 1274 (38.7%) and unimodal for 2021 (61.3%) patients; 1325 (40.2%) had radiation alone and 696 (21.1%) underwent only surgery. The use of bimodal therapy (32.8-42.5%, P = 0.01) and radiation alone (29.3-44.5%, P < 0.001) increased significantly from 1998 to 2008. Bimodal therapy predicted improved CSS (hazard ratios [HR]: 0.68, P < 0.001) and OS (HR: 0.58, P < 0.001) compared with unimodal therapy. For the first 7 months (before survival curve crossing), CSS after radiation therapy alone was similar to surgery alone (HR: 0.86, P = 0.12) while OS was worse for surgery only (HR: 0.70, P = 0.001). However, worse CSS (HR: 1.43, P < 0.001) and OS (HR: 1.46, P < 0.001) after that initial timeframe were found for radiation therapy only. The use of radiation to treat locally advanced mid and distal esophageal cancers increased from 1998 to 2008. Survival was best when both surgery and radiation were used.

Statin therapy and long-term adverse limb outcomes in patients with peripheral artery disease: insights from the REACH registry

AIMS Due to a high burden of systemic cardiovascular events, current guidelines recommend the use of statins in all patients with peripheral artery disease (PAD). We sought to study the impact of statin use on limb prognosis in patients with symptomatic PAD enrolled in the international REACH registry. METHODS Statin use was assessed at study enrolment, as well as a time-varying covariate. Rates of the primary adverse limb outcome (worsening claudication/new episode of critical limb ischaemia, new percutaneous/surgical revascularization, or amputation) at 4 years and the composite of cardiovascular death/myocardial infarction/stroke were compared among statin users vs. non-users. RESULTS A total of 5861 patients with symptomatic PAD were included. Statin use at baseline was 62.2%. Patients who were on statins had a significantly lower risk of the primary adverse limb outcome at 4 years when compared with those who were not taking statins [22.0 vs. 26.2%; hazard ratio (HR), 0.82; 95% confidence interval (CI), 0.72-0.92; P = 0.0013]. Results were similar when statin use was considered as a time-dependent variable (P = 0.018) and on propensity analysis (P < 0.0001). The composite of cardiovascular death/myocardial infarction/stroke was similarly reduced (HR, 0.83; 95% CI, 0.73-0.96; P = 0.01). CONCLUSION Among patients with PAD in the REACH registry, statin use was associated with an ∼18% lower rate of adverse limb outcomes, including worsening symptoms, peripheral revascularization, and ischaemic amputations. These findings suggest that statin therapy not only reduces the risk of adverse cardiovascular events, but also favourably affects limb prognosis in patients with PAD.

A propensity score-matched comparison between Cardia and Amplatzer PFO closure devices - insights from the SOLUTION registry (Swiss percutaneOus patent foramen ovale cLosUre in recurrent clinical events prevenTION)

Aims: To compare clinical outcome of Amplatzer PFO (APFO) to Cardia PFO (CPFO) occluder. Percutaneous patent foramen ovale (PFO) closure prevents stroke recurrence in stroke due to paradoxical embolism. Methods and results: The primary endpoint was a composite of stroke, TIA, or peripheral embolism at follow-up. The secondary endpoint was residual shunt. Outcome was compared among 934 (APFO: 712; CPFO: 222) patients, and in 297 propensity score-matched patients. The primary endpoint occurred in 29 patients (0.71/100 patient-years): four (2%) with the CPFO (0.31/100 patient-years), and 25 (4%) with the APFO (0.89/100 patient-years) (p=0.20). Residual shunt at six months was more frequent with the CPFO (31% versus 9%, p<0.001). No differences in residual shunts were seen at the last available echocardiographic follow-up (9±18 months): APFO 11%, CPFO 14%, p=0.22. Conclusions: This study suggests that PFO closure with APFO or CPFO is equally effective for the prevention of recurrent events. Residual shunt was more frequent at six months with CPFO, but was similar to APFO at later follow-up.

Percutaneous mitral valve edge-to-edge repair: in-hospital results and 1-year follow-up of 628 patients of the 2011-2012 Pilot European Sentinel Registry.

BACKGROUND The use of transcatheter mitral valve repair (TMVR) has gained widespread acceptance in Europe, but data on immediate success, safety, and long-term echocardiographic follow-up in real-world patients are still limited. OBJECTIVES The aim of this multinational registry is to present a real-world overview of TMVR use in Europe. METHODS The Transcatheter Valve Treatment Sentinel Pilot Registry is a prospective, independent, consecutive collection of individual patient data. RESULTS A total of 628 patients (mean age 74.2 ± 9.7 years, 63.1% men) underwent TMVR between January 2011 and December 2012 in 25 centers in 8 European countries. The prevalent pathogenesis was functional mitral regurgitation (FMR) (n = 452 [72.0%]). The majority of patients (85.5%) were highly symptomatic (New York Heart Association functional class III or higher), with a high logistic EuroSCORE (European System for Cardiac Operative Risk Evaluation) (20.4 ± 16.7%). Acute procedural success was high (95.4%) and similar in FMR and degenerative mitral regurgitation (p = 0.662). One clip was implanted in 61.4% of patients. In-hospital mortality was low (2.9%), without significant differences between groups. The estimated 1-year mortality was 15.3%, which was similar for FMR and degenerative mitral regurgitation. The estimated 1-year rate of rehospitalization because of heart failure was 22.8%, significantly higher in the FMR group (25.8% vs. 12.0%, p[log-rank] = 0.009). Paired echocardiographic data from the 1-year follow-up, available for 368 consecutive patients in 15 centers, showed a persistent reduction in the degree of mitral regurgitation at 1 year (6.0% of patients with severe mitral regurgitation). CONCLUSIONS This independent, contemporary registry shows that TMVR is associated with high immediate success, low complication rates, and sustained 1-year reduction of the severity of mitral regurgitation and improvement of clinical symptoms.