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BACKGROUND & AIMS The use of oral nutritional supplements (ONS) in the hospital setting is important to reach individual protein and energy goals in patients at risk for malnutrition. Compliance with ONS can be challenging but may be improved by prescribing ONS in smaller portions with medication rounds (MEDPass). We compared the likelihood of meeting energy and protein requirements in patients receiving ONS with MEDPass versus conventional ONS administration. METHODS The MEDPass Trial is a randomized, controlled, open-label superiority trial conducted on medical and geriatric wards in a University Hospital in Switzerland. The MEDPass group was allocated to receive 50 ml of ONS four times per day with the medication rounds. The control group received ONS per conventional care between the meals. The primary outcome was the percentage of energy in relation to the individual requirement. Secondary outcomes included the coverage of protein intake in relation to the individual requirement, the amount of daily consumed ONS, the course of handgrip strength (HGS), body weight appetite and nausea. Furthermore, we compared 30-day mortality and hospital length of stay (LOS) was studied in medical patients. RESULTS From November 22nd, 2018 until November 30th, 2021, 204 patients were included in the trial (MEDPass group n = 100, control group n = 104). A total of 203 patients at nutritional risk were analyzed in the intention-to-treat analysis (ITT). Regarding the primary endpoint, there was no difference in the coverage of energy requirement between the MEDPass and control group (82 vs. 85% (Δ -3%, 95%CI -11 to 4%), p = 0.38). Similarly, no differences were found for the secondary outcomes including coverage of protein requirement (101 vs. 104% (Δ -3%, 95% CI -12 -7%), p = 0.57, average daily intake of ONS (170 vs 173 ml (Δ - 3 ml, 95% CI -14 to 8 ml), p = 0.58) and 30-day mortality (3 vs. 8 patients, OR 0.4 (95% CI 0.1-1.4), p = 0.15). The course of HGS, body weight, appetite and nausea did not differ between the groups (p = 0.29, p = 0.14, p = 0.65 and p = 0.94, respectively). The per protocol analysis including 178 patients showed similar results. CONCLUSION Within this controlled trial setting, we found a high compliance for ONS intake and high coverage of protein requirements but no further improvement when ONS was administered using MEDPass compared to conventional care. MEDPass administration may provide an alternative that is easy to integrate into nursing routines, which may lead to lower workload with cost benefits and reduction of food waste. TRIAL REGISTRATION ClinicalTrials.gov: NCT03761680.

BACKGROUND/OBJECTIVES To assess the course and prediction of basic activities of daily living (ADL) function in patients after transcatheter aortic valve implantation (TAVI). DESIGN This was a prospective cohort study. SETTING The setting was a single academic center in Switzerland. PARTICIPANTS Participants included individuals aged ≥70 years (n = 330) undergoing TAVI. MEASUREMENTS A frailty index (based on geriatric assessment) and cardiac risk scores (EuroSCORE, Society of Thoracic Surgeons [STS] score) were determined in patients before TAVI. Basic ADL function was measured with patient or proxy interviews at baseline and 1-year follow up. We used logistic regression models to investigate the association between baseline factors and functional decline. RESULTS At 1-year follow up, 229 (69.4%) of the 330 patients had stable or improved basic ADL function, 49 (14.8%) experienced a decline in basic ADL function, and 52 (15.8%) died. The frailty index, but not cardiac risk scores, significantly predicted decline in basic ADL function. Among the 34 surviving very frail patients, 12 (35.3%) experienced a functional status decline, and the remaining 22 (64.7%) had stable or improved functional status at 1-year follow up. CONCLUSION This study confirms that a frailty index, and not cardiac risk scores, identifies patients at an increased risk of functional status decline after TAVI. Identifying patients with a high frailty index before TAVI is clinically relevant as these patients might benefit from targeted geriatric management and rehabilitation after TAVI. However, based on current data, it is not justified to use information on frailty status as the criterion for identifying patients in whom TAVI might be futile. Although the probability of poor outcome is high, very frail patients also have a high probability of favorable long-term functional outcome.

In older patients, sarcopenia is a prevalent disease associated with negative outcomes. Sarcopenia has been investigated in patients undergoing transcatheter aortic valve implantation (TAVI), but the criteria for diagnosis of the disease are heterogeneous. This systematic review of the current literature aims to evaluate the prevalence of sarcopenia in patients undergoing TAVI and to analyse the impact of sarcopenia on clinical outcomes. A comprehensive search of the literature has been performed in electronic databases from the date of initiation until March 2020. Using a pre-defined search strategy, we identified studies assessing skeletal muscle mass, muscle quality and muscle function as measures for sarcopenia in patients undergoing TAVI. We evaluated how sarcopenia affects the outcomes mortality at ≥1 year, prolonged length of hospital stay, and functional decline. We identified 18 observational studies, enrolling a total number of 9’513 patients. For assessment of skeletal muscle mass, all included studies used data from computed tomography. Cutoff points for definition of low muscle mass were heterogeneous, and prevalence of sarcopenia varied between 21.0% and 70.2%. In uni- or multivariate regression analysis of different studies, low muscle mass was found to be a significant predictor of mortality, prolonged length of hospital stay, and functional decline. No interventional study was identified measuring the effect of nutritional or physiotherapy interventions on sarcopenia in TAVI patients. Sarcopenia is highly prevalent among patients undergoing TAVI, and negatively affects important outcomes. Early diagnosis of this condition might allow a timely start of nutritional and physiotherapy interventions to prevent negative outcomes in TAVI patients.

Circulating oxidized phospholipids are increasingly recognized as biomarkers of atherosclerosis. Clinical association studies have been mainly performed using an immune assay based on monoclonal antibody E06, which recognizes a variety of molecular species of oxidized phosphatidylcholine (OxPC) in lipoproteins, cell membranes or covalently bound to plasma proteins. Accumulating evidence shows that individual molecular species of OxPC demonstrate different biological activities and have different half-life times. Therefore, it is likely that certain molecular species can be associated with pathology more strongly than others. This hypothesis can only be tested using LC-MS/MS allowing quantification of individual molecular species of OxPCs. In order to ensure that laborious LC-MS/MS methods do not simply replicate the results of a technically simpler E06-OxPCs assay, we have performed relative quantification of 8 truncated molecular species of OxPCs in plasma of 132 probands and compared the data with the results of the E06-OxPCs and OxLDL assays. We have found a strong correlation between individual molecular species of OxPCs but only a weak correlation of LC-MS/MS-OxPCs data with the E06-OxPCs assay and no correlation with the OxLDL assay. Furthermore, in contrast to the results of E06-OxPCs or OxLDL assays, 7 out of 8 OxPC species were associated with hypertension. The data suggest that the results of the LC-MS/MS-OxPCs assay do not replicate the results of two ELISA-based lipid oxidation tests and therefore may produce additional diagnostic information. These findings necessitate development of simplified mass spectrometric procedures for high-throughput and affordable analysis of selected molecular species of OxPCs.

Aims The objective of this study was to examine baseline frailty status (including cognitive deficits) and important clinical outcomes, to inform shared decision-making in older adults receiving transcatheter aortic valve implantation (TAVI). Methods and results We conducted a prospective, observational study of 82 TAVI patients, recruited 2013 to 2015, with 2-year follow-up. Mean age was 83 years (standard deviation (SD) 4.7). Eighteen percent of the patients were frail, as assessed with an 8-item frailty scale. Fifteen patients (18%) had a Mini-Mental Status Examination (MMSE) score below 24 points at baseline, indicating cognitive impairment or dementia and five patients had an MMSE below 20 points. Mean New York Heart Association (NYHA) class at baseline and 6 months was 2.5 (SD 0.6) and 1.4 (SD 0.6), (p p = 0.7). At 2 years, six patients (7%) had died, four (5%, n = 79) lived in a nursing home, four (5%) suffered from disabling stroke, and six (7%) contracted infective endocarditis. Conclusions TAVI patients had improvement in symptoms and maintenance of activity of daily living at 6 months. They had low mortality and most patients lived in their own home 2 years after TAVI. Complications like death, stroke, and endocarditis occurred. Some patients had cognitive impairment before the procedure which might influence decision-making. Our findings may be used to develop pre-TAVI decision aids.

Abstract. We investigated the effect of age on cardiometabolic risk and protective factors in females living in a countryside area of Switzerland. For this cross-sectional analysis, data from 268 female adults, who live in two neighboring countryside villages in Italian-speaking Switzerland were retained. 89 study participants were premenopausal, 82 climacteric and 97 postmenopausal. Television viewing time, short duration of sleep, overweight, blood pressure, levels of atherogenic lipids and glycated hemoglobin significantly increased with age. Walking time also significantly increased with age. Tobacco smoking was more common among premenopausal women. It is concluded that in these countryside villages climacteric and postmenopausal women generally have an unfavorable cardiometabolic risk profile. On the other side, low physical activity and smoking are, compared to premenopausal and climacteric women, less prevalent in postmenopausal women.

Background In a three-month report from the CGA-TAVI registry, we found the Multidimensional Prognostic Index (MPI) and Short Physical Performance Battery (SPPB) to be of value for predicting short-term outcomes in elderly patients undergoing transcatheter aortic valve implantation (TAVI). In the present analysis, we examined the association of these tools with outcomes up to one year post-TAVI. Methods CGA-TAVI is an international, observational registry of geriatric patients undergoing TAVI. Patients were assessed using the MPI and SPPB. Efficacy of baseline values and any postoperative change for predicting outcome were established using logistic regression. Kap-lan-Meier analysis was carried out for each comprehensive geriatric assessment tool, with survival stratified by risk category. Results One year after TAVI, 14.1% of patients deceased, while 17.4% met the combined endpoint of death and/or non-fatal stroke, and 37.7% the combined endpoint of death and/or hospitalisation and/or non-fatal stroke. A high-risk MPI score was associated with an increased risk of all-cause mortality (aOR = 36.13, 95% CI: 2.77-470.78, P = 0.006) and death and/or non-fatal stroke (aOR = 10.10, 95% CI: 1.48-68.75, P = 0.018). No significant associations were found between a high-risk SPPB score and mortality or two main combined endpoints. In contrast to a worsening SPPB, an aggravating MPI score at three months post-TAVI was associated with an increased risk of death and/or non-fatal stoke at one year (aOR = 95.16, 95% CI: 3.41-2657.01). Conclusions The MPI showed value for predicting the likelihood of death and a combination of death and/or non-fatal stroke by one year after TAVI in elderly patients.

Objectives This study sought to evaluate whether frailty improves mortality prediction in combination with the conventional scores. Background European System for Cardiac Operative Risk Evaluation (EuroSCORE) or Society of Thoracic Surgeons (STS) score have not been evaluated in combined models with frailty for mortality prediction after transcatheter aortic valve replacement (TAVR). Methods This prospective cohort comprised 330 consecutive TAVR patients ≥70 years of age. Conventional scores and a frailty index (based on assessment of cognition, mobility, nutrition, and activities of daily living) were evaluated to predict 1-year all-cause mortality using Cox proportional hazards regression (providing hazard ratios [HRs] with confidence intervals [CIs]) and measures of test performance (providing likelihood ratio [LR] chi-square test statistic and C-statistic [CS]). Results All risk scores were predictive of the outcome (EuroSCORE, HR: 1.90 [95% CI: 1.45 to 2.48], LR chi-square test statistic 19.29, C-statistic 0.67; STS score, HR: 1.51 [95% CI: 1.21 to 1.88], LR chi-square test statistic 11.05, C-statistic 0.64; frailty index, HR: 3.29 [95% CI: 1.98 to 5.47], LR chi-square test statistic 22.28, C-statistic 0.66). A combination of the frailty index with either EuroSCORE (LR chi-square test statistic 38.27, C-statistic 0.72) or STS score (LR chi-square test statistic 28.71, C-statistic 0.68) improved mortality prediction. The frailty index accounted for 58.2% and 77.6% of the predictive information in the combined model with EuroSCORE and STS score, respectively. Net reclassification improvement and integrated discrimination improvement confirmed that the added frailty index improved risk prediction. Conclusions This is the first study showing that the assessment of frailty significantly enhances prediction of 1-year mortality after TAVR in combined risk models with conventional risk scores and relevantly contributes to this improvement.

This study attempts a systematic evaluation of the clinical evidence for the use of odourless garlic prepared by ageing or fermentation. By PubMed, CENTRAL, and handsearching, 59 clinical studies were identified for potential extraction, of which 24 fulfilled the inclusion criteria. The quality of the studies and evidence of effectiveness were assessed by an established set of conventional criteria. Even the 12 best clinical trials (50%) had fundamental flaws that prevented to grade them as confirmatory. On the basis of a subsample of 19 exploratory studies (79%), an impressive reduction of cardiovascular risk was found for odourless garlic (evidence of effectiveness, “moderate” and for other indications, “poor”). Evidence of effectiveness is further limited by the fact that most studies used aged garlic produced by one pharmaceutical company and that products differed in composition and dose of the marker substance S-allyl-cysteine. In case odourless garlic is potentially an effective remedy in particular for cardiovascular diseases, we discern an urgent need for long-term confirmatory studies. The ultimate cardiovascular endpoint for definitive studies would be mortality, but reductions in blood pressure or demonstrable decreases in atherosclerotic plaques or blood markers of cardiovascular risk would be useful surrogates. Sample sizes for various assumptions are provided.

Objective To evaluate cognitive trajectories after radical cystectomy and their impact on surgical outcomes, including urinary continence. Materials and Methods Ninety patients received cognitive testing using the Mini Mental State Examination before open radical cystectomy as well as 3 days and 2 weeks after surgery. Based on the Mini Mental State Examination changes ≥3 points between the three time points, five cognitive trajectories emerged (stable cognition, persistent or transient deterioration, or persistent or transient improvement). Surgical outcomes were assessed 90 days, 6 months, and 1 year postoperatively. Results Mean age was 67.9 ± 9.3 years (range 40-88 years). Sixty-six patients (73.3%) had stable cognition, 9 patients (10.0%) had persistent deterioration and 7 patients (7.8%) had transient deterioration, 5 patients (5.6%) had persistent improvement and 3 patients (3.3%) had transient improvement. An impaired preoperative cognition was the only significant risk factor of short-term cognitive deterioration (odds ratio adjusted for age and sex 9.4, 95% confidence interval 1.6-56.5, P = .014). Cognition showed no associations with 1-year mortality, 90-day complication rate, cancer progression, or duration of in-hospital stay. Patients with transient or persistent cognitive deterioration had an increased risk for nighttime incontinence (odds ratio adjusted for age and sex 5.1, 95% confidence interval 1.1-22.4, P = .032). Conclusion In this study, the majority of patients showed stable cognition after major abdominopelvic surgery. Cognitive deterioration occurred in a small subgroup of patients, and an impaired preoperative cognition was the only significant risk factor. Postoperative cognitive deterioration was associated with nighttime incontinence.

Comprehensive geriatric assessment (CGA) is an efficient and effective way for evaluating complex elderly patients and for planning improved care based on CGA findings. Based on these findings, a plan for geriatric management is developed, usually involving a multidisciplinary team. CGA has been shown to improve functional status as well as survival, while reducing healthcare utilization and costs. Therefore, CGA should be systematically performed in the growing population of older patients with cardiovascular diseases.

Aims Established surgical scores have limitations in delineating risk among candidates for transcatheter aortic valve implantation (TAVI). Assessment of frailty might help to estimate the mortality risk and identify patients likely to benefit from treatment. The aim of the study was to develop a frailty score to guide the decision for TAVI. Methods and results We conducted a prospective observational study in patients ≥70 years referred for TAVI during 2011–15. A Heart Team had declined the patients for open heart surgery due to high risk but accepted them for TAVI. Prior to the procedure, a geriatric assessment (GA) was performed. Based on this, an 8-element frailty score with a 0–9 (least frail–most frail) scale was developed. A total of 142 patients, 54% women, mean age 83 (standard deviation 4) years, with severe and symptomatic aortic stenosis were assessed. All-cause 2 year mortality was 11%. The novel GA frailty score predicted 2-year mortality in Cox analyses, also when adjusted for age, gender, and logistic EuroSCORE [hazard ratio (HR) 1.75, 95% confidence interval (CI): 1.28–2.42, P < 0.001]. A receiver operating characteristic (ROC) curve analysis indicated that a GA frailty score cut-off at ≥4 predicted 2-year mortality with a specificity of 80% (95% CI: 73–86%) and a sensitivity of 60% (95% CI: 36–80%). The area under the curve was 0.81 (95% CI 0.71–0.90). Conclusion A novel 8-element GA frailty score identified gradations in survival in patients declined for open heart surgery. Patients with higher GA frailty scores had significantly higher 2-year mortality after TAVI.

The aim of this study was to assess the use of ambulatory acoustic cardiography during the initial data collection of the longitudinal study of a rural population in Switzerland (n=297, mean age 48.9 ±16.5 years, 57% female). Ambulatory acoustic cardiography non-invasively can assess sleep disordered breathing (SDB) and provides markers of left ventricular systolic and diastolic dysfunction. The percentage of the third heart sound detected during sleep decreased significantly across age groups (age < 40 years, 40-60 years, > 60 years) for both genders (males, p=0.04; females, p=0.02). The percentage of a fourth heart sound detected exhibited an increasing trend for both genders with age suggesting increased diastolic dysfunction with aging. Mean electromechanical activation time (EMAT) during sleep was within the normal range across age groups and both genders (male 93.7 ± 11.6 ms, female 94.6 ± 13.0 ms), and did not vary significantly with age. A large proportion of subjects had a high likelihood of sleep disordered breathing (17.6%). Baseline characteristics categorized by SDB severity indicate increasing age, male gender and being overweight (BMI ≥ 25) to be associated with greater SDB severity. Acoustic cardiography findings categorized by SDB severity reveal increased nocturnal non-dipping heart rate, presence of atrial fibrillation, prolonged QRS duration and QTc interval, increased percentage of fourth heart sound detected, and longer EMAT to be significantly associated with greater SDB severity. Overall, acoustic cardiography detected a very low prevalence of systolic dysfunction, age-related increases in diastolic dysfunction and a moderate prevalence of sleep disordered breathing.

BACKGROUND The early diagnosis of acute myocardial infarction (AMI) very soon after symptom onset remains a major clinical challenge, even when using high-sensitivity cardiac troponin (hs-cTnT). METHODS AND RESULTS We investigated the incremental value of heart-type fatty acid-binding protein (hFABP) in a pre-specified subgroup analysis of patients presenting with suspected AMI within 1 h of symptom onset to the emergency department (ED) in a multicentre study. HFABP was measured in a blinded fashion. Two independent cardiologists using all available clinical information, including hs-cTnT, adjudicated the final diagnosis. Overall, 1411 patients were enrolled, of whom 105 patients presented within 1 h of symptom onset. Of these, 34 patients (32.4%) had AMI. The diagnostic accuracy as quantified by the area under the receiver-operating characteristics curve (AUC) of hFABP was high (0.84 (95% CI 0.74-0.94)). However, the additional use of hFABP only marginally increased the diagnostic accuracy of hs-cTnT (AUC 0.88 (95% CI 0.81-0.94) for hs-cTnT alone to 0.90 (95% CI 0.83-0.98) for the combination; p=ns). After the exclusion of 18 AMI patients with ST-segment elevation, similar results were obtained. Among the 16 AMI patients without ST-segment elevation, six had normal hs-cTnT at presentation. Of these, hFABP was elevated in two (33.3%) patients. CONCLUSIONS hFABP does not seem to significantly improve the early diagnostic accuracy of hs-cTnT in the important subgroup of patients with suspected AMI presenting to the ED very early after symptom onset.

This study attempts a critical evaluation of the clinical evidence behind the use of dietary pomegranate preparations in the prevention and treatment of cardiovascular diseases. A search of PubMed on August 10, 2014 identified 228 references, which yielded extractable data from 24 clinical studies of pomegranate preparations. Hand searching identified two further studies. The quality of the studies and evidence of effectiveness of pomegranate were assessed by an established set of conventional criteria. Overall, the study quality was poor. Even in the best studies, indications of benefit did not reach the conventional levels of statistical significance. The only study with a definitive design had a biochemical rather than a clinical endpoint: it showed the expected difference in blood concentrations of myeloperoxidase after a single dose of either pomegranate or placebo. Only 10 of the 26 studies provided HPLC data on the amounts of co-active ingredients in the preparations that were consumed by the subjects. If pomegranate has a role in the prevention and treatment of cardiovascular diseases, there is a pressing need for dose-finding and long-term confirmatory studies. The ultimate endpoint for definitive studies would be mortality, but reductions in blood pressure or demonstrable decreases in atherosclerotic plaques would be useful surrogates. Sample sizes for various assumptions are provided. Future studies need to prove the clinical benefit.

AIMS: To determine the effect of anti-ischaemic drug therapy on long-term outcomes of asymptomatic patients without coronary artery disease (CAD) history but silent exercise ST-depression. METHODS AND RESULTS: In a randomized multicentre trial, 263 of 522 asymptomatic subjects without CAD but at least one CAD risk factor in whom silent ischaemia by exercise ECG was confirmed by stress imaging were asked to participate. The 54 (21%) consenting patients were randomized to anti-anginal drug therapy in addition to risk factor control (MED, n = 26) or risk factor control-only (RFC, n = 28). They were followed yearly for 11.2 +/- 2.2 years. During 483 patient-years, cardiac death, non-fatal myocardial infarction, or acute coronary syndrome requiring hospitalization or revascularization occurred in 3 (12%) of MED vs. 17 (61%) of RFC patients (P < 0.001). In addition, MED patients had consistently lower rates of exercise-induced ischaemia during follow-up, and left ventricular ejection fraction remained unchanged (-0.7%, P = 0.597) in contrast to RFC patients in whom it decreased over time (-6.0%, P = 0.006). CONCLUSION: Anti-ischaemic drug therapy and aspirin seem to reduce cardiac events in subjects with asymptomatic ischaemia type I. In such patients, exercise-induced ST-segment depression should be verified by stress imaging; if silent ischaemia is documented, anti-ischaemic drug therapy and aspirin should be considered.

AIMS This study evaluated associations between plasma T cadherin levels and severity of atherosclerotic disease. METHODS AND RESULTS Three hundred and ninety patients undergoing coronary angiography were divided into three groups based on clinical and angiographic presentation: a group (n=40) with normal coronary arteries a group (n=250) with chronic coronary artery disease and a group (n=100) with acute coronary syndrome. Plasma T cadherin levels were measured by double sandwich ELISA. Intravascular ultrasound data of the left anterior descending artery were acquired in a subgroup of 284 patients. T cadherin levels were lower in patients with acute coronary syndrome than in normal patients (p=0.007) and patients with chronic coronary artery disease (p=0.002). Levels were lower in males (p=0.002) in patients with hypertension (p=0.002) and inpatients with diabetes (p=0.008) and negatively correlated with systolic blood pressure (p=0.014) body mass index (p=0.001) and total number of risk factors (p=0.001). T cadherin negatively associated with angiographic severity of disease (p=0.001) and with quantitative intravascular ultrasound measures of lesion severity (p

Severe symptomatic aortic stenosis is a serious condition of elderly, mostly geriatric patients with a poor prognosis if the valve is not replaced. Since geriatricians are able to provide major expertise in the prognostic assessment as well in the clinical management of these patients, they need to be more closely involved in the decision making process. For this reason the European Union Geriatric Medicine Society (EUGMS) represented by the authors phrased three propositions: (1) geriatricians need to be aware of the impact of severe aortic stenosis on patients’ outcomes and should be encouraged to take an active role in aortic stenosis management; (2) they need to be aware of treatment options and are required to support multidisciplinary teams with their expertise in assessing geriatric patients; (3) they should routinely perform a comprehensive geriatric assessment in patients with severe aortic stenosis scheduled to undergo surgical or transcatheter aortic valve replacement and during long-term follow-up. 1.326 JCR (2015) Q4, 40/49 Geriatrics & gerontology UEM

AIMS Device-based pacing-induced diaphragmatic stimulation (PIDS) may have therapeutic potential for chronic heart failure (HF) patients. We studied the effects of PIDS on cardiac function and functional outcomes. METHODS AND RESULTS In 24 chronic HF patients with CRT, an additional electrode was attached to the left diaphragm. Randomized into two groups, patients received the following PIDS modes for 3 weeks in a different sequence: (i) PIDS off (control group); (ii) PIDS 0 ms mode (PIDS simultaneously with ventricular CRT pulse); or (iii) PIDS optimized mode (PIDS with optimized delay to ventricular CRT pulse). For PIDS optimization, acoustic cardiography was used. Effects of each PIDS mode on dyspnoea, power during exercise testing, and LVEF were assessed. Dyspnoea improved with the PIDS 0 ms mode (P = 0.057) and the PIDS optimized mode (P = 0.034) as compared with the control group. Maximal power increased from median 100.5 W in the control group to 104.0 W in the PIDS 0 ms mode (P = 0.092) and 109.5 W in the PIDS optimized mode (P = 0.022). Median LVEF was 33.5% in the control group, 33.0% in the PIDS 0 ms mode, and 37.0% in the PIDS optimized mode (P = 0.763 and P = 0.009 as compared with the control group, respectively). PIDS was asymptomatic in all patients. CONCLUSION PIDS improves dyspnoea, working capacity, and LVEF in chronic HF patients over a 3 week period in addition to CRT. This pilot study demonstrates proof of principle of an innovative technology which should be confirmed in a larger sample. TRIAL REGISTRATION NCT00769678.

There are three principal causes of valvular aortic stenosis (AS): congenital, rheumatic, and degenerative. While congenital AS clinically manifests at younger ages and rheumatic AS dwindled in importance with the decline in rheumatic fever, age-related degenerative calcific AS is now the most common cause of valvular AS in adults [1]. Degenerative calcific AS is the result of a progressive calcification of the aortic valves based on a process of inflammation, lipid accumulation, and calcification. This dynamic process resembles the process of atherosclerosis in many regards. Some clinical risk factors of atherosclerosis have also been identified as risk factors of calcific AS, including hypertension, hyperlipidemia, smoking, and diabetes [2]. Degenerative calcific AS occurs in patients with congenitally normal tricuspid aortic valves, but a congenitally bicuspid aortic valve seems to be an important additional risk factor of degenerative calcific AS development [1, 3].

T-cadherin is gaining recognition as a determinant for the development of incipient invasive squamous cell carcinoma (SCC). However, effects of T-cadherin expression on the metastatic potential of SCC have not been studied. Here, using a murine model of experimental metastasis following tail vein injection of A431 SCC cells we report that loss of T-cadherin increased both the incidence and rate of appearance of lung metastases. T-cadherin-silenced SCC metastases were highly disordered with evidence of single cell dissemination away from main foci whereas SCC metastases overexpressing T-cadherin developed as compact, tightly organised sheets. SCC cell adhesion to vascular endothelial cells (EC) in culture was increased for T-cadherin-silenced SCC and decreased for T-cadherin-overexpressing SCC. Confocal microscopy showed that T-cadherin-silenced SCC adherent on EC display an elongated morphology with long thin extensions and a high degree of intercalation within the EC monolayer, whereas SCC overexpressing T-cadherin formed poorly-spread multicellular aggregates that remain on the outer surface of the EC monolayer. T-cadherin-deficient SCC or human keratinocyte cells exhibited increased transendothelial migration in vitro which could be attenuated in the presence of EGFR inhibitor gefitinib. Our data suggest that loss of T-cadherin can increase metastatic potential and aggressiveness of SCC, possibly due to facilitating arrest and extravasation through the vascular wall and/or more efficient establishment of metastases in the new microenvironment.

Introduction Increased longevity and consequent major changes in demographics and population lifestyles necessitate new approaches to reduce the burden of ageing-related diseases (including cardiovascular disease) and maintain an optimal quality of life. This study aims to examine and longitudinally follow health status and disease risk factors in a Swiss rural cohort, evaluating all health-related research and practice disciplines to assure development of new implementable and successful preventive strategies for healthy ageing. Methods and objectives Small Swiss villages with low migration rates will be selected for this study. 2 villages (Cama/Lostallo) have already been selected as initial study sites. All residents (age ≥6 years, no upper age limit) are eligible. The target enrolment number per village is 300. Examinations and measurements encompass medical history, anthropometry, cardiac and vascular health, pulmonary function, physical performance, nutritional, mental and emotional status, biochemical and molecular analyses. Follow-up examinations (identical to baseline) will be performed after 5 and 10 years, and in 10-year intervals thereafter. The major objective is to assess, and observe change in, health status over time in a prospective manner. Secondary objectives are to: (1) identify ‘hidden’ (asymptomatic and/or unrecognised) health problems which enhance risk for chronic diseases; (2) identify barriers to accessing healthcare and adapting health behaviours; (3) evaluate efficacy of present preventive strategies and recommendations; (4) evaluate knowledge and attitude towards ongoing health programmes and public health recommendations; (5) monitor change and progress towards the national health objectives; (6) formulate new preventive strategies and recommendations based on the findings and knowledge base of the past 10 years; (7) formulate models for successful prevention of chronic diseases and for healthy ageing. Ethics and dissemination The Ethics Committee of Nordwest-und Zentralschweiz approved this study (EKNZ 2014-209). It is registered at ClinicalTrials.gov (NCT02282748). Findings will be disseminated through scientific articles/presentations and public events.

Aim: Oxidized phospholipids (OxPL) are the major pathogenic component of oxidized low-density lipoproteins (OxLDL). Endogenous anti-OxPL activity, defined as the ability to neutralize adverse effects of oxidized lipids, may have biomarker potential. Methods & results: Using two anti-OxPL monoclonal antibodies (commercial mAB-E06 and custom mAB-509) we developed a novel ELISA that measures the global capacity of plasma to inactivate OxPL. Preincubation of OxLDL with plasma inhibits its binding of anti-OxPL mABs. This phenomenon (‘masking’) reflects anti-OxPL plasma activity. A pilot clinical application of the assay revealed reduced anti-OxPL activity in hypertension, coronary artery disease, acute coronary syndrome and diabetes. Conclusion: Inadequate anti-OxPL protection may contribute to cardiovascular disease and have biomarker potential in conditions associated with abnormal lipid peroxidation.

Although reactive hyperemia index (RHI) predicts future coronary events, associations with intravascular ultrasound (IVUS)-assessed coronary plaque structure have not been reported. This study therefore investigated associations between RHI and IVUS-assessed coronary plaques. In 362 patients RHI was measured by noninvasive peripheral arterial tonometry and coronary plaque components (fibrous, fibrofatty, necrotic core, and dense calcium) were identified by IVUS in 594 vessel segments of the left anterior descending, circumflex, and/or right coronary arteries. RHI values

Vieles bei der Abklärung und Behandlung der arteriellen Hypertonie im Alter ist gleich wie bei jungen Patienten. Einige Unterschiede gibt es dennoch. Wegen der zunehmenden Gefäßsteifigkeit haben ältere Patienten meist eine isolierte systolische Hypertonie und deren Prävalenz in der Bevölkerung ist sehr hoch. Die Blutdruckmessung darf nicht nur im Sitzen erfolgen, sondern sie muss zwingend auch kurz nach dem Aufstehen erfolgen, um eine orthostatische Hypotonie, ein häufiges Problem älterer Patienten, nicht zu verpassen. Bei der Blutdruckmessung zusätzlich zu beachten ist das Phänomen der Pseudohypertonie, ebenfalls bedingt durch die zunehmende Gefäßsteifigkeit. Im Vergleich zu anderen Gesundheitsproblemen ist die wissenschaftliche Evidenz zur Therapie der arteriellen Hypertonie im höheren Alter sehr gut. Weil die Behandlung nicht nur die Mortalität verbessert, sondern in noch stärkerem Ausmaß nicht-tödliche Schlaganfälle und Herzinfarkte verhindert, ist eine antihypertensive Therapie eine wichtige Maßnahme zur Erhaltung der Selbständigkeit und Verhinderung von Pflegebedürftigkeit im Alter.

Objectives This study evaluated Multidimensional Geriatric Assessment (MGA) as predictor of mortality and major adverse cardiovascular and cerebral events (MACCE) after transcatheter aortic valve implantation (TAVI). Background Currently used global risk scores do not reliably estimate mortality and MACCE in these patients. Methods This prospective cohort comprised 100 consecutive patients ≥70 years undergoing TAVI. Global risk scores (Society of Thoracic Surgeons [STS] score, EuroSCORE) and MGA-based scores (cognition, nutrition, mobility, activities of daily living [ADL], and frailty index) were evaluated as predictors of all-cause mortality and MACCE 30 days and 1 year after TAVI in regression models. Results In univariable analyses, all predictors were significantly associated with mortality and MACCE at 30 days and 1 year, except for the EuroSCORE at 30 days and instrumental ADL at 30 days and 1 year. Associations of cognitive impairment (odds ratio [OR]: 2.98, 95% confidence interval [CI]: 1.07 to 8.31), malnutrition (OR: 6.72, 95% CI: 2.04 to 22.17), mobility impairment (OR: 6.65, 95% CI: 2.15 to 20.52), limitations in basic ADL (OR: 3.63, 95% CI: 1.29 to 10.23), and frailty index (OR: 3.68, 95% CI: 1.21 to 11.19) with 1-year mortality were similar compared with STS score (OR: 5.47, 95% CI: 1.48 to 20.22) and EuroSCORE (OR: 4.02, 95% CI: 0.86 to 18.70). Similar results were found for 30-day mortality and MACCE. Bivariable analyses, including STS score or EuroSCORE suggested independent associations of MGA-based scores (e.g., OR of frailty index: 3.29, 95% CI: 1.06 to 10.15, for 1-year mortality in a model including EuroSCORE). Conclusions This study provides evidence that risk prediction can be improved by adding MGA-based information to global risk scores. Larger studies are needed for the development and validation of improved risk prediction models.

Diuretic treatment for heart failure may lead to an increased urinary thiamine excretion and in long-term thiamine deficiency, which may further compromise cardiac function. This study evaluated the effect of high dose thiamine supplementation in heart failure patients. Nine patients with diuretic treatment for symptomatic chronic heart failure and a left ventricular ejection fraction (LVEF)

Acute coronary syndromes (ACS) in very young patients have been poorly described. We therefore evaluate ACS in patients aged 35 years and younger.In this prospective cohort study, 76 hospitals treating ACS in Switzerland enrolled 28,778 patients with ACS between January 1, 1997, and October 1, 2008. ACS definition included ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI), and unstable angina (UA).195 patients (0.7%) were 35 years old or younger. Compared to patients35 years, these patients were more likely to present with chest pain (91.6% vs. 83.7%; P=0.003) and less likely to have heart failure (Killip class II to IV in 5.2% vs. 23.0%; P0.001). STEMI was more prevalent in younger than in older patients (73.1% vs. 58.3%; P0.001). Smoking, family history of CAD, and/or dyslipidemia were important cardiovascular risk factors in young patients (prevalence 77.2%, 55.0%, and 44.0%). The prevalence of overweight among young patients with ACS was high (57.8%). Cocaine abuse was associated with ACS in some young patients. Compared to older patients, young patients were more likely to receive early percutaneous coronary interventions and had better outcome with fewer major adverse cardiac events.Young patients with ACS differed from older patients in that the younger often presented with STEMI, received early aggressive treatment, and had favourable outcomes. Primary prevention of smoking, dyslipidemia and overweight should be more aggressively promoted in adolescence.

Endothelial dysfunction (ED) is frequently present in patients presenting with acute or stable coronary artery disease (CAD), but it is also found in patients presenting with chest pain without angiographic coronary lesions.

Background Patients with left ventricular noncompaction (LVNC) have an increased risk for life-threatening ventricular arrhythmias. The benefit from implantable cardioverter-defibrillators (ICD) in these patients has been investigated only in small series. Therefore, the aim of the present study was to analyze the clinical outcome of a larger population of patients with LVNC who were treated with an ICD. Methods Thirty patients (mean age 48 ± 14) with LVNC who underwent ICD implantation for secondary (n = 12) or primary (n = 18) prevention were included in the study. The mean follow-up period was 40 ± 34 months. Results During follow-up, 11 patients (37%) presented with appropriate ICD therapies: three with antitachycardia pacing, four with ICD shocks, and four with both antitachycardia pacing and ICD shocks. Of these 11 patients, five received the ICD for secondary prevention and six for primary prevention. In six patients, in whom a biventricular ICD was implanted, functional New York Heart Association (NYHA) class improved from 2.5 ± 0.5 to 1.6 ± 0.8. Conclusions In the present study, with the largest cohort of LVNC patients with ICD to date, we demonstrate that such therapy is effective in these patients with an indication for secondary or primary prevention of sudden cardiac death. However, no clinical predictors for appropriate ICD therapy could have been elaborated in these patients. Cardiac resynchronization therapy improves functional NYHA class in patients with LVNC and may hence be considered in patients with a left ventricular ejection fraction ≤35% and signs of ventricular dyssynchrony.

We thank Dr. Afilalo and colleagues and Dr. Lantelme and colleagues for their interest in our paper [(1)][1]. Dr. Afilalo and colleagues refer to the results from the multicentric FRAILTY-AVR (Frailty Assessment Before Cardiac Surgery & Transcatheter Interventions) study [(2)][2], which they

Background Current knowledge about risk factors promoting hypertensive crisis originates from retrospective data. Therefore, potential risk factors of hypertensive crisis were assessed in a prospective longitudinal study. Methods Eighty-nine patients of the medical outpatient unit at the University Hospital of Bern (Bern, Switzerland) with previously diagnosed hypertension participated in this study. At baseline, 33 potential risk factors were assessed. All patients were followed-up for the outcome of hypertensive crisis. Cox regression models were used to detect relationships between risk factors and hypertensive crisis (defined as acute rise of systolic blood pressure (BP) ≥200mmHg and/or diastolic BP ≥120mmHg). Results The mean duration of follow-up was 1.6 ± 0.3 years (range 1.0–2.4 years). Four patients (4.5%) were lost to follow-up. Thirteen patients (15.3%) experienced hypertensive crisis during follow-up. Several potential risk factors were significantly associated with hypertensive crisis: female sex, higher grades of obesity, the presence of a hypertensive or coronary heart disease, the presence of a somatoform disorder, a higher number of antihypertensive drugs, and nonadherence to medication. As measured by the hazard ratio, nonadherence was the most important factor associated with hypertensive crisis (hazard ratio 5.88, 95% confidence interval 1.59–21.77, P < 0.01). Conclusions This study identified several potential risk factors of hypertensive crisis. Results of this study are consistent with the hypothesis that improvement of medical adherence in antihypertensive therapy would help to prevent hypertensive crises. However, larger studies are needed to assess potential confounding, other risk factors and the possibility of interaction between predictors.

In diesem Artikel werden die entscheidenden Schritte zur Diagnose des akuten Koronarsyndroms besprochen. Die mit der Diagnosestellung einhergehende Risikostratifizierung wird erklärt, und die sich aus der Risikostratifizierung ergebenden therapeutischen Schritte werden dargelegt. Aspekte der Qualitätskontrolle werden anhand des AMIS Plus Registers erläutert. Mögliche zukünftige Entwicklungen werden kurz erörtert.

Over the past two centuries, coronary artery disease has emerged as an important cause of morbidity and death in industrialized nations. Increased life expectancy and changed habits (regarding nutrition, physical activity, and smoking) have contributed to this dramatic epidemiologic shift. During the last 50 years, a decline in the coronary artery disease mortality rate was observed due to therapeutic advances and prevention measures targeted at people with coronary artery disease and those potentially at risk for it. This article highlights important epidemiologic data and some definitions in the context of coronary artery disease are presented.

Objectives Our purpose was to perform a systematic review and meta-analysis of randomized trials comparing percutaneous coronary intervention (PCI) of the infarct-related artery (IRA) with medical therapy in patients randomized >12 h after acute myocardial infarction (AMI). Background There is ongoing uncertainty about the risk–benefit ratio of late PCI in stable patients with AMI. Methods PubMed, CENTRAL, and other databases were searched (July 2007). Studies were included if they compared PCI with medical management and randomized patients >12 h and up to 60 days after AMI, and were excluded if patients were hemodynamically unstable. Odds ratios (ORs) were pooled for dichotomous outcomes, with all-cause mortality as the primary end point. Left cardiac remodeling parameters were also pooled with generic inverse-variance weighting. Results We retrieved 10 studies that enrolled 3,560 patients, with median time from AMI to randomization of 12 days (range 1 to 26 days), and follow-up of 2.8 years (42 days to 10 years). Randomization allocated 1,779 subjects to PCI and 1,781 to medical treatment. There were 112 (6.3%) and 149 (8.4%) deaths in the 2 groups, respectively, yielding significantly improved survival in the PCI group (OR 0.49 [95% confidence interval (CI) 0.26 to 0.94], p = 0.030). These benefits were associated with similarly favorable effects on cardiac remodeling, such as improved left ventricular ejection fraction in the PCI group (+4.4% change [95% CI 1.1 to 7.6], p = 0.009). Conclusions Percutaneous coronary intervention of the IRA performed late (12 h to 60 days) after AMI is associated with significant improvements in cardiac function and survival.

To compare the use of guideline-recommended medical and interventional therapies in older and younger patients with acute coronary syndromes (ACSs). DESIGN: Prospective cohort study. SETTING: Fifty-five hospitals in Switzerland. PARTICIPANTS: Eleven thousand nine hundred thirty-two patients with ACS enrolled between March 1, 2001, and June 30, 2006. ACS definition included ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI), and unstable angina pectoris (UA). MEASUREMENTS: Use of medical and interventional therapies was determined after exclusion of patients with contraindications and after adjustment for comorbidities. Multivariate logistic regression models were used to calculate odds ratios (ORs) per year increase in age. RESULTS: Elderly patients were less likely to receive acetylsalicylic acid (OR=0.976, 95% confidence interval (CI)=0.969-0.980) or beta-blockers (OR=0.985, 95% CI=0.981-0.989). No age-dependent difference was found for heparin use. Elderly patients with STEMI were less likely to receive percutaneous coronary intervention (PCI) or thrombolysis (OR=0.955, 95% CI=0.949-0.961). Elderly patients with NSTEMI or UA less often underwent PCI (OR=0.943, 95% CI=0.937-0.949). CONCLUSION: Elderly patients across the whole spectrum of ACS were less likely to receive guideline-recommended therapies, even after adequate adjustment for comorbidities. Prognosis of elderly patients with ACS may be improved by increasing adherence to guideline-recommended medical and interventional therapies.

Background— This study aimed to assess the evolution of cognitive function after transcatheter aortic valve implantation (TAVI). Previous smaller studies reported conflicting results on the evolution of cognitive function after TAVI. Methods and Results— In this prospective cohort, cognitive function was measured in 229 patients ≥70 years using the Mini Mental State Examination before and 6 months after TAVI. Cognitive deterioration or improvement was defined as change of ≥3 points decrease or increase in the Mini Mental State Examination score between baseline and follow-up. Cognitive deterioration was found in 29 patients (12.7%). Predictive analysis using logistic regression did not identify any statistically significant predictor of cognitive deterioration. A review of individual medical records in 8 patients with a major Mini Mental State Examination score decrease of ≥5 points revealed specific causes in 6 cases (postinterventional delirium in 2; postinterventional stroke, progressive renal failure, progressive heart failure, or combination of preexisting cerebrovascular disease and mild cognitive impairment in 1 each). Among 48 patients with impaired baseline cognition (Mini Mental State Examination score 2 ) as compared with patients who did not improve (median aortic valve area 0.70 cm 2 ; P =0.01). Conclusions— This is the first study providing evidence that TAVI results in cognitive improvement among patients who had impaired preprocedural cognitive function, possibly related to hemodynamic improvement in patients with severe aortic stenosis. Our results confirm that some patients experience cognitive deterioration after TAVI.

Aims To determine whether treatment and outcomes of older acute coronary syndrome (ACS) patients changed over time. Methods and results We analysed the use of guideline-recommended therapies and in-hospital outcomes of 13 662 ACS patients ≥70 years enrolled in the prospective Acute Myocardial Infarction in Switzerland (AMIS) cohort between 2001 and 2012 according to 4-year periods (2001–2004, 2005–2008, and 2009–2012). Between first and last 4-year period, percutaneous coronary intervention (PCI) use increased from 43.8 to 69.6% of older ACS patients ( P < 0.001). Use of guideline-recommended drugs as well increased. At the same time, in-hospital mortality of the overall population decreased from 11.6% in the first to 10.0% in the last 4-year period ( P = 0.020), and in-hospital major adverse cardiac and cerebrovascular events from 14.4 to 11.3% ( P < 0.001). Percutaneous coronary intervention was used in increasingly older and co-morbid patients over time (mean age of patients treated with PCI 76.2 years in 2001–2004 and 78.1 years in 2009–2012, P < 0.001; Charlson score ≥2 was found for 27.6% of patients treated with PCI in 2001–2004 and for 32.1% in 2009–2012, P = 0.003). Percutaneous coronary intervention use was associated with similar odds ratios (ORs) of in-hospital mortality over time (adjusted OR 0.29, 95% confidence interval, CI, 0.22–0.40, in 2001–2004; and, adjusted OR 0.26, 95% CI 0.20–0.35, in 2009–2012). Conclusion Use of guideline-recommended therapies for ACS increased and in-hospital outcomes improved over the observed 12-year period. Though PCI was used in increasingly older and co-morbid patients, PCI use was associated with similar ORs of in-hospital mortality over time. This study suggests that increasing use of guideline-recommended therapies was appropriate. Trial registration ClinicalTrials.gov Identifier: [NCT01305785][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01305785&atom=%2Fehj%2F37%2F16%2F1304.atom