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Objectives: This study aims to estimate the association of the often, in daily clinical practice, used biological age-related biomarkers high-sensitivity troponin-T (hs-TnT), C reactive protein (CRP) and haemoglobin (Hb) with all-cause mortality for the purpose of older patient's risk stratification in the emergency department (ED)., Design: Exploratory, prospective cohort study with a follow-up at 2.5 years after recruitment started. For the predictors, data from the hospital files including the routinely applied biological age-related biomarkers hs-TnT, CRP and Hb were supplemented by a questionnaire., Setting: A cardiological ED, Chest Pain Unit, University Hospital Heidelberg, Germany., Participants: N=256 cardiological ED patients with a minimum age of 70 years and the capability to informed consent., Primary Outcome Measures: The primary outcome of this study was all-cause mortality which was assessed by requesting registry office information., Results: Among N=256 patients 63 died over the follow-up period. Positive results in each of the three biomarkers alone as well as the combination were associated with increased all-cause mortality at follow-up. The number of positive age-related biomarkers appeared to be strongly indicative of the risk of mortality, even when controlled for major confounders (age, sex, body mass index, creatinine clearance and comorbidity)., Conclusions: In older ED patients, biomarkers explicitly related to biological ageing processes such as hs-TnT, CRP and Hb were to a certain degree independently of each other as well as combined associated with an increased risk of all-cause mortality. Thus, they may have the potential to be used to supplement the general risk stratification of older patients in the ED. Validation of the results in a large dataset is needed., Competing Interests: Competing interests: ALK: no funds, grants or other support to report. AS, MSc: has received research grants from the Robert Bosch Foundation. PB, MD, MHBA: has received no funds, grants or other support for this manuscript. EG, MD: has received research grants and honoraria from Roche Diagnostics, Bayer and Mitsubishi Chemicals. H-WW, PhD: no funds, grants or other support to report. HAK, MD: has received honoraria from AstraZeneca, Daiichi Sankyo, Boehringer Ingelheim, Berlin-Chemie, Bayer Vital and Novo Nordisk. He developed the cTnT assay, but the troponin patent has expired. NF, MD: has received no funds, grants or other support to report. AB, MD: has received research support for her other project the Trade Study (Transport and Delirium in Elderly Study) from the Innovation Committee by the Joint Federal Committee (G-BA), but not for this study. AB has received speaking engagements from Bayer, Pfizer, Lilly, Novartis, Boehringer Ingelheim, Daiichi Sankyo, Novo Nordisk and Sanofi Aventis., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To evaluate the diagnostic performance of N-terminal pro-B-type natriuretic peptide (NT-proBNP) thresholds for acute heart failure and to develop and validate a decision support tool that combines NT-proBNP concentrations with clinical characteristics., Design: Individual patient level data meta-analysis and modelling study., Setting: Fourteen studies from 13 countries, including randomised controlled trials and prospective observational studies., Participants: Individual patient level data for 10 369 patients with suspected acute heart failure were pooled for the meta-analysis to evaluate NT-proBNP thresholds. A decision support tool (Collaboration for the Diagnosis and Evaluation of Heart Failure (CoDE-HF)) that combines NT-proBNP with clinical variables to report the probability of acute heart failure for an individual patient was developed and validated., Main Outcome Measure: Adjudicated diagnosis of acute heart failure., Results: Overall, 43.9% (4549/10 369) of patients had an adjudicated diagnosis of acute heart failure (73.3% (2286/3119) and 29.0% (1802/6208) in those with and without previous heart failure, respectively). The negative predictive value of the guideline recommended rule-out threshold of 300 pg/mL was 94.6% (95% confidence interval 91.9% to 96.4%); despite use of age specific rule-in thresholds, the positive predictive value varied at 61.0% (55.3% to 66.4%), 73.5% (62.3% to 82.3%), and 80.2% (70.9% to 87.1%), in patients aged <50 years, 50-75 years, and >75 years, respectively. Performance varied in most subgroups, particularly patients with obesity, renal impairment, or previous heart failure. CoDE-HF was well calibrated, with excellent discrimination in patients with and without previous heart failure (area under the receiver operator curve 0.846 (0.830 to 0.862) and 0.925 (0.919 to 0.932) and Brier scores of 0.130 and 0.099, respectively). In patients without previous heart failure, the diagnostic performance was consistent across all subgroups, with 40.3% (2502/6208) identified at low probability (negative predictive value of 98.6%, 97.8% to 99.1%) and 28.0% (1737/6208) at high probability (positive predictive value of 75.0%, 65.7% to 82.5%) of having acute heart failure., Conclusions: In an international, collaborative evaluation of the diagnostic performance of NT-proBNP, guideline recommended thresholds to diagnose acute heart failure varied substantially in important patient subgroups. The CoDE-HF decision support tool incorporating NT-proBNP as a continuous measure and other clinical variables provides a more consistent, accurate, and individualised approach., Study Registration: PROSPERO CRD42019159407., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the British Heart Foundation, Medical Research Council, and Chief Scientist Office; Y-EC has received honorariums for lectures and presentations from Biomérieux, Roche Diagnostics, and Thermo Fisher; CdF has received consulting fees from Fuji Rebio, Ortho Diagnostics, Quidel, and Roche Diagnostics and a patent entitled “Methods for assessing differential risk for developing heart failure” (patent number: PCT/US2015/029838); SS has received a grant from Roche Diagnostics and a patent entitled “Methods for assessing differential risk for developing heart failure” (patent number: PCT/US2015/029838); ABG has received personal fees and non-financial support from Roche Diagnostics during the conduct of the study and personal fees from Abbott and AstraZeneca, grants, personal fees, and non-financial support from Boehringer-Ingelheim, and personal fees and non-financial support from Novartis and Vifor outside the submitted work. YP has received consulting fees from Roche Diagnostics, Pfizer, and Forbion and honorariums from CVOI and Daiichi Sankyo; HKG has received grants from Roche Diagnostics, Jana Care, Ortho Clinical, Novartis, Pfizer, Alnylam, and Akcea (IONIS), consulting fees from Amgen, Eko, Merck, and Pfizer, and stock in Eko; JCW works as a biostatistician at the biotech company BRAHMS GmbH, part of Thermo Fisher Scientific; MM has received grants from Health Care Research Projects and Biomarker Research and personal fees from Consulting outside the submitted work; ASVS has received speaker fees from Abbott Diagnostics outside the submitted work; AMR has received grants, personal fees, and non-financial support from Roche Diagnostics outside the submitted work; JJVM has received consulting fees from Alnylam, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Cardurion, Dal-Cor, GSK, Ionis, KBP Biosciences, Novartis, Pfizer, and Theracos, payments for advisory boards, symposiums, or lectures from Abbott, Alkem Metabolics, Canadian Medical and Surgical Knowledge Translation Research Group, Eris Lifesciences, Hikma, Lupin, Sun Pharmaceuticals, Medscape/Heart.Org, ProAdWise Communications, Radcliffe Cardiology, Servier, and the Corpus, has participated on a data safety monitoring board or advisory board for Cardialysis (MONITOR study) and Merck (VICTORIA trial), and works as company director for Global Clinical Trial Partners Ltd (GCTP) outside the submitted work; CM has received grants and non-financial support from several diagnostic companies during the conduct of the study and grants, personal fees, and non-financial support from several diagnostic companies outside the submitted work; JJ has received grants from Abbott Diagnostics, Innolife, and Novartis and consulting fees from Abbott, Jana Care, Novartis, Roche Diagnostics, Bristol-Myers Squibb, Janssen, and Prevencio; NLM has received grants from Siemens Healthineers, consulting fees from Roche Diagnostics and LumiraDx, and speaker fees from Abbott Diagnostics and Siemens Healthineers outside the submitted work; KKL, DD, and NLM are employed by the University of Edinburgh, which has filed a patent on the CoDE-HF score (patent reference: PCT/GB2021/051470); no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The 2020 European Society of Cardiology (ESC) guidelines recommend using the 0/1-hour and 0/2-hour algorithms over the 0/3-hour algorithm as the first and second choices of high-sensitivity cardiac troponin (hs-cTn)-based strategies for triage of patients with suspected acute myocardial infarction (AMI)., Purpose: To evaluate the diagnostic accuracies of the ESC 0/1-hour, 0/2-hour, and 0/3-hour algorithms., Data Sources: PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus from 1 January 2011 to 31 December 2020. (PROSPERO: CRD42020216479)., Study Selection: Prospective studies that evaluated the ESC 0/1-hour, 0/2-hour, or 0/3-hour algorithms in adult patients presenting with suspected AMI., Data Extraction: The primary outcome was index AMI. Twenty unique cohorts were identified. Primary data were obtained from investigators of 16 cohorts and aggregate data were extracted from 4 cohorts. Two independent authors assessed each study for methodological quality., Data Synthesis: A total of 32 studies (20 cohorts) with 30 066 patients were analyzed. The 0/1-hour algorithm had a pooled sensitivity of 99.1% (95% CI, 98.5% to 99.5%) and negative predictive value (NPV) of 99.8% (CI, 99.6% to 99.9%) for ruling out AMI. The 0/2-hour algorithm had a pooled sensitivity of 98.6% (CI, 97.2% to 99.3%) and NPV of 99.6% (CI, 99.4% to 99.8%). The 0/3-hour algorithm had a pooled sensitivity of 93.7% (CI, 87.4% to 97.0%) and NPV of 98.7% (CI, 97.7% to 99.3%). Sensitivity of the 0/3-hour algorithm was attenuated in studies that did not use clinical criteria (GRACE score <140 and pain-free) compared with studies that used clinical criteria (90.2% [CI, 82.9 to 94.6] vs. 98.4% [CI, 88.6 to 99.8]). All 3 algorithms had similar specificities and positive predictive values for ruling in AMI, but heterogeneity across studies was substantial. Diagnostic performance was similar across the hs-cTnT (Elecsys; Roche), hs-cTnI (Architect; Abbott), and hs-cTnI (Centaur/Atellica; Siemens) assays., Limitation: Diagnostic accuracy, inclusion and exclusion criteria, and cardiac troponin sampling time varied among studies., Conclusion: The ESC 0/1-hour and 0/2-hour algorithms have higher sensitivities and NPVs than the 0/3-hour algorithm for index AMI., Primary Funding Source: National Taiwan University Hospital.

Background and Aims: The Charlson Comorbidity Index (CCI) is the most widely used assessment tool to report the presence of comorbid conditions. The Barthel index (BI) is used to measure performance in activities of daily living. We prospectively investigated the performance of CCI or BI to predict length of hospital stay (LOS), mortality, cardiovascular (CV) mortality and rehospitalization in unselected older patients on admission to the emergency department (ED). We also studied the association of CCI or BI with costs., Methods: We consecutively enrolled 307 non-surgical patients ≥ 68 years presenting to the ED with a wide range of comorbid conditions. Baseline characteristic, clinical presentation, laboratory data, echocardiographic parameters and hospital costs were compared among patients. All patients were followed up for mortality, CV mortality and rehospitalization within the following 12 months. A multivariate analysis was performed., Results: Mortality was increased for patients having a higher CCI or BI with a hazard ratio around 1.17-1.26 or 0.75-0.81 (obtained for different models) for one or ten point increase in CCI or BI, respectively. The prognostic impact of a high CCI or BI on CV mortality and rehospitalization was also significant. In a multiple linear regression using the same independent variables, CCI and BI were identified as a predictor of LOS in days. Multiple linear regression analysis did not confirm an association between CCI and costs, but for BI after adjusting for multiple factors., Conclusion: CCI and BI independently predict LOS, mortality, CV mortality, and rehospitalization in unselected older patients admitted to ED.

Based on established risk scores, such as the CHA 2 DS 2 -VASc score, the indications for oral anticoagulation are given for patients over 65 years old with atrial fibrillation and even more so for patients over 75 years old. Before beginning anticoagulation a geriatric assessment for evaluation of the cognitive ability, the activities of daily living and the risk of falling should be made because of the known complications of anticoagulation. Geriatric patients with non-valvular atrial fibrillation (AF) are increasingly being treated with non-vitamin K antagonist oral anticoagulants (NOAC) to prevent ischemic stroke. The European Society for Cardiology (ESC) guidelines for the management of AF recommended NOACs as the preferred treatment and vitamin K antagonists (VKA) only as an alternative option. Meanwhile, apixaban, rivaroxaban, and edoxaban as factor Xa inhibitors and dabigatran as a thrombin inhibitor, are more commonly used in clinical practice in patients with AF. Although, these drugs have pharmacodynamics and pharmacokinetic similarities and are often grouped together, it is important to recognize that the pharmacology and dose regimens differ between compounds. Especially in elderly patients the new drugs have interesting advantages compared to VKA, i. e., less drug-drug interactions with concomitant medication and a more favorable risk-benefit ratio mostly driven by the reduction of bleeding. Treatment of anticoagulation in elderly patients requires weighing the serious risk of stroke with an equally high risk of major bleeding and pharmacoeconomic considerations. The easier practicality of NOACs in routine practice must be emphasized as no international normalized ratio (INR) monitoring is necessary and the interruption of treatment for planned interventions is uncomplicated. A regular monitoring of the indications for NOACs is indispensable (as for all other medications). Especially elderly patients have the greatest benefit from NOAC along with a low renal elimination rate and they should certainly not be withheld from elderly patients who have a clear need for oral anticoagulation.

The incidence and prevalence of chronic heart failure (CHF) increase with age. In the second edition of the National Disease Management Guidelines (NVL) on CHF, published in August 2017, geriatric aspects are specifically addressed. The paper provides an overview of the recommendations by the guidelines on drug therapy, device therapy and operative therapy as well on the coordination of care focusing on older and multimorbid patients.

Background: Increases in the novel serum marker cystatin C are detectable much earlier in the course of chronic kidney disease (CKD) even when levels of serum creatinine are still in the normal range. A major factor causing a decrease in serum creatinine is increasing age. Patients with CKD are more likely to develop cardiovascular disease (CVD) than a healthy population and to suffer premature deaths from CVD related to CKD. The aim of this study was to investigate whether cystatin C, serum creatinine, and estimated glomerular filtration rate (eGFR) predict cardiovascular mortality in patients admitted to the emergency department (ED) with suspected acute coronary syndromes (ACS)., Methods: In 1,282 patients (mean age 62 ± 15 years, 477 women, 805 men) with suspected ACS, baseline cystatin C concentrations, serum creatinine, and estimated glomerular filtration rate (eGFR) were measured at the ED. Clinical assessment and serial high sensitivity cardiac troponin T (hs-cTnT) measurements were used for the diagnosis of ACS. Seventeen cardiovascular deaths were registered during a median follow-up of 365 days., Results: HRs from univariate Cox regression models for each of the potential biomarkers were 12.02 (95% CI 5.10 - 28.34) for cystatin C, 4.53 (1.75 - 11.70) for serum creatinine, and 0.97 (0.96 - 0.99) for eGFR. All three biomarkers showed a significant association with cardiovascular mortality in univariate analyses. The HRs from a model with all three potential biomarkers were 59.21 (95% CI 9.69 - 361.76) for cystatin C, 0.08 (0.01 - 0.58) for serum creatinine, and 0.98 (0.96 - 1.01) for eGFR. The risk association was significant for ln (cystatin C) and ln (serum creatinine)., Conclusions: Results of this prospective study show that the quantification of renal function using cystatin C is useful for predicting cardiovascular mortality in patients with suspected ACS at the ED.

Background: Risk stratification of elderly patients presenting with heart failure (HF) to an emergency department (ED) is an unmet challenge. We prospectively investigated the prognostic performance of different biomarkers in unselected older patients in the ED., Methods: We consecutively enrolled 302 non-surgical patients ⩾70 years presenting to the ED with a wide range of cardiovascular and non-cardiovascular comorbid conditions. N-terminal pro-B-type natriuretic peptide (NT-proBNP), mid-regional pro-adrenomedullin (MR-proADM), mid-regional pro-atrial natriuretic peptide (MR-proANP), C-terminal pro-endothelin-1 (CT-proET-1), ultrasensitive C-terminal pro-arginine-vasopressin (Copeptin-us) and high-sensitivity cardiac troponin T (hs-cTnT) were measured at admission. Two cardiologists independently adjudicated the final diagnosis of HF after reviewing all available baseline data using circulating NT-proBNP levels. A final diagnosis of HF was found in 120 (40%) of the 302 patients. All patients were followed up for cardiovascular death within the following 12 months. In order to test the prognostic performance of the investigated biomarkers we used boosting models with age and sex as mandatory covariates. Boosting is a statistical learning technique with built-in variable selection developed to obtain sparse and interpretable prediction models., Results: Follow-up was 100% complete. During a median follow-up time of 225 days (interquartile range (IQR) 156-319 days), 30 (9.9%) of 302 patients (aged 81±6 years) had cardiovascular deaths. Of these 30 patients, 21 had HF and nine had no HF diagnosed prior to admission. The boosting model selected MR-proADM and hs-cTNT as predictors of cardiovascular deaths. The median values of MR-proADM and hs-cTnT at presentation were significantly higher in patients with cardiovascular deaths compared to surviving patients during follow-up (2.56 nmol/L (IQR 1.62-4.48) vs. 1.11 nmol/L (IQR 0.83-1.80), P<0.001 and 81 ng/L (IQR 38-340) vs. 17 ng/L (IQR 0.9-38), P=0.004). One unit increase in the log-transformed MR-proADM levels was associated with a 1.99-fold risk of death (95% confidence interval (CI) 1.61-2.45, P<0.001). The second marker, hs-cTnT, showed an increased predicted risk but was not significantly correlated to event-free survival (hazard ratio 3.22, 95% CI 0.97-10.68, P=0.056)., Conclusion: Within different biomarkers, MR-proADM was the only predictor of cardiovascular deaths in unselected older patients presenting to the ED., (© The European Society of Cardiology 2015.)

Geriatric patients with non-valvular atrial fibrillation (AF) are increasingly being treated with novel oral anticoagulants (NOAC) to prevent ischemic stroke. This article highlights the outcome of an expert meeting on the practical use of NOAC in elderly patients. An interdisciplinary group of experts discussed the current situation of stroke prevention in geriatric patients and its practical management in daily clinical practice. The topic was examined through focused impulse presentations and critical analyses as the basis for the expert consensus. The key issues are summarized in this paper. The European Society of Cardiology (ESC) guidelines from 2012 for the management of patients with non-valvular AF recommend NOAC as the preferred treatment and vitamin K antagonists (VKA) only as an alternative option. Currently, the NOAC factor Xa inhibitors apixaban and rivaroxaban and the thrombin inhibitor dabigatran are more commonly used in clinical practice for patients with AF. Although these drugs have many similarities and are often grouped together it is important to recognize that the pharmacology and dose regimes differ between compounds. Especially n elderly patients NOAC drugs have some advantages compared to VKA, e.g. less drug-drug interactions with concomitant medication and a more favorable risk-benefit ratio mostly driven by the reduction of bleeding. Treatment of anticoagulation in geriatric patients requires weighing the serious risk of stroke against an equally high risk of major bleeding and pharmacoeconomic considerations. Geriatric patients in particular have the greatest benefit from NOAC, which can also be administered in cases of reduced renal function. Regular control of the indications is indispensable, as also for all other medications of the patient. The use of NOAC should certainly not be withheld from geriatric patients who have a clear need for oral anticoagulation.

The present position paper summarises the outcomes of an expert panel discussion held by hospital-based and office-based physicians with ample experience in the treatment of geriatric patients. The optimal approach to stroke prevention in geriatric patients with atrial fibrillation (AF) has not been adequately clarified. Despite their high risk of stroke and clear indication for anticoagulation according to established risk scores, in practice geriatric AF patients often are withheld treatment because of comorbidities and comedications, concerns about low treatment adherence or fear of bleeding events, in particular due to falls. The panel agreed that geriatric patients should receive oral anticoagulation as a rule, unless a comprehensive neurological and geriatric assessment (including clinical examination, gait tests and validated instruments such as Modified Rankin Scale, Mini-mental state examination or Timed Test of Money Counting) provides sound reasons for refraining from treatment. All patients with a history of falls should be thoroughly evaluated for further evaluation of the causes. Patients with CHADS2 score ≥ 2 should receive anticoagulation even if at high risk for falls. The novel oral anticoagulants (NOAC) facilitate management in the geriatric population with AF (no INR monitoring needed, easier bridging during interventions) and have, based on available data, an improved benefit-risk ratio compared to vitamin K antagonists. Drugs with predominantly non-renal elimination are safer in geriatric patients and should be preferred., (© Georg Thieme Verlag KG Stuttgart · New York.)

Aim: The goal of this study was to perform a structured analysis of the treatment quality and acute complications of geriatric patients with diabetes mellitus (DM) cared for by nursing services and nursing home facilities. Secondly, structural problems and potentials for improvement in the care of multimorbid older people with DM treated by nursing homes and nursing services were analysed from the viewpoint of geriatric nurses, managers of nursing homes and general practitioners., Methods: In all, 77 older persons with DM from 13 nursing homes and 3 nursing services were included in the analysis (76.6% female, HbA1c 6.9 ± 1.4%, age 81.6 ± 9.9 years). Structural problems and potentials for improvement were collected from 95 geriatric nurses, 9 managers of nursing homes and 6 general practitioners using semistandardized questionnaires., Results: Metabolic control was too strict in care-dependent older people with DM (mean HbA1c value: 6.9 ± 1.4 %; recommended by guidelines: 7-8%). The measurement of HbA1c was performed in 16 of 77 people (20.8%) within the last year despite a high visitation frequency of the general practitioners (12.7 ± 7.7 within the last 6 months). The incidence of severe hypoglycemia was 7.8%/patient/year. Regarding the management in case of diabetes-related acute complications 33 geriatric nurses (34.7%) stated not having any written standard (nursing home 39%, geriatric services 16.7%)., Conclusion: Complex insulin therapies are still used in older people with DM with the consequence of a high incidence of severe hypoglycemia. Concrete management standards in the case of diabetes-related acute complications for geriatric nurses are lacking for more than one third of the nursing services.

Aim: Biomarkers can help to identity acute heart failure (AHF) as the cause of symptoms in patients presenting to the emergency department (ED). Older patients may prove a diagnostic challenge due to co-morbidities. Therefore we prospectively investigated the diagnostic performance of N-terminal pro-B-type natriuretic peptide (NT-proBNP) alone or in combination with other biomarkers for AHF upon admission at the ED., Methods: 302 non-surgical patients aged ≥ 70 years were consecutively enrolled upon admission to the ED. In addition to NT-proBNP, mid-regional pro-adrenomedullin (MR-proADM), mid-regional pro-atrial natriuretic peptide (MR-proANP), C-terminal pro-endothelin-1 (CT-proET-1) and ultra-sensitive C-terminal pro-vasopressin (Copeptin-us) were measured at admission. Two cardiologists independently adjudicated the final diagnosis of AHF after reviewing all available baseline data excluding the biomarkers. We assessed changes in C-index, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) for the multimarker approach., Results: AHF was diagnosed in 120 (40%) patients (age 81±6 years, 64 men, 56 women). Adding MR-ADM to NT-proBNP levels improved C-index (0.84 versus 0.81; p=0.045), and yielded IDI (3.3%; p=0.002), NRI (17%, p<0.001) and continuous NRI (33.3%; p=0.002). Adding CT-proET-1 to NT-proBNP levels improved C index (0.86 versus 0.81, p=0.031), and yielded robust IDI (12.4%; p<0.001), NRI (31.3%, p<0.001) and continuous NRI (69.9%; p<0.001). No other dual or triple biomarker combination showed a significant improvement of both C-index and IDI., Conclusion: In older patients presenting to the ED, the addition of CT-proET-1 or MR-proADM to NT-proBNP improves diagnostic accuracy of AHF. Both dual biomarker approaches offer significant risk reclassification improvement over NT-proBNP., (© The European Society of Cardiology 2014.)

Background: The optimal approach to stroke prevention in geriatric patients with atrial fibrillation (AF) has not been adequately clarified. Despite their high risk of stroke and clear indication for anticoagulation according to established risk scores, in practice geriatric AF patients often are withheld treatment because of comorbidities and comedications, concerns about low treatment adherence or fear of bleeding events, in particular due to falls., Method: The present position paper summarises the outcomes of an expert panel discussion held by hospital-based and office-based physicians with ample experience in the treatment of geriatric patients., Results and Conclusions: The panel agreed that geriatric patients should receive oral anticoagulation as a rule, unless a comprehensive neurological and geriatric assessment (including clinical examination, gait tests and validated instruments such as Modified Rankin Scale, Mini-mental state examination or Timed Test of Money Counting) provides sound reasons for refraining from treatment AII patients with a history of falls should be thoroughly evaluated for further evaluation of the causes. Patients with CHADS2 score ≥ 2 should receive anticoagulation even if at high risk for falls. The novel oral anticoagulants (NOAC) facilitate management in the geriatric population with AF (no INR monitoring needed, easier bridging during interventions) and have an improved benefit-risk ratio compared to vitamin K antagonists. Drugs with predominantly non-renal elimination are safer in geriatric

Objective: To determine the extent to which geriatric patients with diabetes mellitus experience psychological insulin resistance (PIR)., Methods: A total of 67 unselected geriatric patients with diabetes (mean age 82.8±6.7 years, diabetes duration 12.2 [0.04-47.2] years, 70.1% female) were recruited in a geriatric care center of a university hospital. A comprehensive geriatric assessment (CGA) was performed including WHO-5, Hospital Anxiety and Depression Scale (HADS), Mini Mental State Examination (MMSE) and Barthel-Index. We assessed PIR using the Barriers of Insulin Treatment Questionnaire (BIT) and the Insulin Treatment Appraisal Scale in a face-to-face interview., Results: Insulin-naïve patients (INP) showed higher PIR scores than patients already on insulin therapy (BIT-sum score: 4.3±1.4 vs. 3.2±1.0; p<0.001). INP reported in the BIT increased fear of injection and self-testing (2.4±2.4 vs. 1.3±0.8; p=0.016), expect disadvantages from insulin treatment (2.7±1.6 vs. 1.9±1.4; p=0.04), and fear of stigmatization by insulin injection (5.2±2.3 vs. 3.6±2.6; p=0.008). Fear of hypoglycemia, however, did not differ significantly (6.3±2.8 vs. 5.1±3.1; p=0.11). Depression was not shown to be a barrier to insulin therapy., Conclusion: INP with diabetes have a significantly more negative attitude toward insulin therapy in comparison to patients already on insulin., Practice Implications: Systematic assessment of barriers of insulin therapy, individualized diabetes treatment plans and information of patients may help to overcome such negative attitudes, leading to quicker initiation of therapy, improved adherence to treatment and a better quality of life., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Demographic change has also caused changes in perioperative intensive care because the proportion of geriatric patients who must undergo surgical procedures is increasing. With the current preoperative assessment instruments, it is still not possible to identify high-risk patients of this collective or to make a reliable prognosis concerning postoperative course., Materials and Methods: In addition to pain control, important aspects to minimize complications in postoperative intensive care include adequate oxygenation, adequate fluid management, an adequate supply of energy and nutrients, good control of blood sugar levels, and early mobilization of patients., Results: The perioperative intensive care treatment of geriatric patients requires the readiness to engage in interdisciplinary collaboration because only with this close dialog can the treatment results be sustained.

Infections have plagued humans since the beginning of recorded history. Huge segments of the human population were episodically wiped out by epidemic infectious diseases in past centuries. Infection was and is often the final cause of mortality in the debilitated elderly. Substantial ongoing research has been performed to investigate mechanisms, causes, pathogenesis, and therapy for infectious disease. Much of this work has involved the elderly because that group is uniquely predisposed to morbidity and mortality from infection. It is hoped that continued research will result in a decrease in infection morbidity and mortality in elderly., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Identifying older patients with non-ST- elevation myocardial infarction (NSTEMI) within the very large proportion with elevated high-sensitive cardiac troponin T (hs-cTnT) is a diagnostic challenge because they often present without clear symptoms or electrocardiographic features of acute coronary syndrome to the emergency department (ED). We prospectively investigated the diagnostic and prognostic performance of copeptin ultra-sensitive (copeptin-us) and hs-cTnT compared to hs-cTnT alone for NSTEMI at prespecified cut-offs in unselected older patients., Methods: We consecutively enrolled 306 non-surgical patients ≥70 years presenting to the ED. In addition to clinical examination, copeptin-us and hs-cTnT were measured at admission. Two cardiologists independently adjudicated the final diagnosis of NSTEMI after reviewing all available data. All patients were followed up for cardiovascular-related death within the following 12 months., Results: NSTEMI was diagnosed in 38 (12%) patients (age 81±6 years). The combination of copeptin-us ≥14 pmol/L and hs-cTnT ≥0.014 µg/L compared to hs-cTnT ≥0.014 µg/L alone had a positive predictive value of 21% vs. 19% to rule in NSTEMI. The combination of copeptin-us <14 pmol/L and hs-cTnT <0.014 µg/L compared to hs-cTnT <0.014 µg/L alone had a negative predictive value of 100% vs. 99% to rule out NSTEMI. Hs-cTnT ≥0.014 µg/L alone was significantly associated with outcome. When copeptin-us ≥14 pmol/L was added, the net reclassification improvement for outcome was not significant (p=0.809)., Conclusions: In unselected older patients presenting to the ED, the additional use of copeptin-us at predefined cut-offs may help to reliably rule out NSTEMI but may not help to increase predicted risk for outcome compared to hs-cTnT alone.

Objectives: To determine if an algorithm implementing a serial high-sensitive cardiac troponin T (hs-cTnT) measurement at presentation (0 h) and at 3 hours after presentation (3h) is helpful for early diagnosis of non-ST-elevation myocardial infarction (NSTEMI) in older patients., Design: Prospective observational cohort study., Setting: An emergency department (ED) of a city hospital covering a population of approximately 1 million in Germany., Participants: A total of 332 consecutive unselected patients were recruited, of whom 25 had one or more of the prespecified exclusion criteria and 1 had a missing hs-cTnT at 3h, resulting in a final population of 306 patients., Measurements: In addition to clinical examination, hs-cTnT was measured at 0 h and 3 h. The final diagnosis of NSTEMI was adjudicated by two independent consultants and an algorithm for rule-in and rule-out of NSTEMI was developed using classification and regression tree analysis. All patients were followed-up for cardiovascular outcome within 12 months., Results: Among 306 patients (mean age 81 ± 6 years), 38 (12%) patients had NSTEMI. Accuracy to diagnose NSTEMI was significantly higher for hs-cTnT measurements at 3 h versus 0 h (area under the receiver operating characteristic curve [AUC] 0.88 vs. 0.82, P = .0038) and for absolute versus relative hs-cTnT delta changes (AUC 0.89 versus 0.69, P < .001). A diagnostic algorithm using hs-cTnT values at presentation and absolute delta changes values ruled-in NSTEMI in 23% and ruled-out NSTEMI in 35% of patients. For patients neither fulfilling the rule-in nor the rule-out criteria, an observational zone was established. Cumulative 1-year survival was 79.4%, 88.5%, and 99.1% in patients classified as rule-in, observational zone, and rule-out, respectively., Conclusion: In older patients, serial hs-cTnT measurements and absolute delta-changes at 3h were valuable for early diagnosis of NSTEMI. An algorithm ruled-in NSTEMI in one quarter of patients with high risk and ruled-out NSTEMI in one-third with low risk., (Copyright © 2013 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.)

Aim: Guidelines for the management of sepsis have been published but not validated for elderly patients, though a prompt work-up and initiation of appropriate therapy are crucial. This study assesses the impact of a sepsis protocol on timelines for therapy and mortality in standardized management., Methods: Consecutive patients aged 70 years and older who were diagnosed with sepsis and admitted during the observation periods were included in this before-and-after study at a medical intensive care unit (ICU). Age, sex, and process-of-care variables including timely administration of antibiotics, obtaining blood cultures before the start of antibiotics, documenting central venous pressure, evaluation of central venous blood oxygen saturation, fluid resuscitation, and patient outcome were recorded., Results: A total of 122 patients were included. Sepsis was diagnosed in 22.9 % of patients prior to the introduction of the protocol and 57.4 % after introduction. Volume therapy was conducted in 63.9 % of the patients (11.5 % preprotocol). Blood culture samples were taken prior to the administration of antibiotics in 67.2 % of patients (4.9 % preprotocol), and antibiotics were applied early in 72.1 % of patients (32.8 % preprotocol). Lactate was set in 77.0 % of patients (11.5 % preprotocol). A central venous catheter was inserted in 88.5 % of patients (68.9 % preprotocol), and the target central venous pressure was achieved in 64.3 % of patients (47.2 % preprotocol). ICU mortality was reduced by 5.2 % and hospital mortality by 6.4 %., Conclusions: The use of standardized order sets for the management of sepsis in elderly patients should be strongly recommended for better performance in treatment. Compliance with the protocol was associated with reduced length of stay, reduced mortality, and improved initial appropriate therapy.

Introduction: Polypharmacy is closely associated with multimorbidity in the elderly and can lead to problems and drug interactions., Aim: This study assessed polypharmacy in the elderly, tracking inquiries to the Poison Information Centre Nuremberg (PICN) and patients needing toxicological intensive care therapy., Methods: From 2006-2009, all PICN inquiries involving individuals > 70 years were tracked, as were cases at the Toxicological Intensive Care Unit (T-ICU) regarding adverse drug reactions (ADRs) and drug poisoning., Results: Of 11,683 PICN calls about pharmaceuticals, 175 (1.5%) were from people > 70 years; 156 (4.8%) of 3,272 T-ICU patients were > 70 years. Calls about psychopharmaceuticals (46.9%) and analgesics (25.7%) were most frequent. Among the T-ICU patients, psychopharmaceuticals like sedatives and hypnotics were frequently involved (20.5%), as were tricyclic antidepressants (17.9%) and analgesics (29.5%). Ethanol was co-ingested by 18.3%., Conclusion: Population-specific poison prevention strategies are needed to reduce toxic exposures. Such strategies could include pharmacist intervention, improved prescriber communication and education regarding the geriatric population, and computerized drug databases.

Background and Aims: The new high sensitivity cardiac Troponin T (cTnThs) assay has recently been introduced in our clinic and ensures higher sensitivity than the fourth-generation cardiac troponin T (cTnT) assay from the same manufacturer (Roche Diagnostics). We determined the diagnostic performance of the cTnThs compared with the cTnT assay in geriatric patients, especially those with non-ST elevation myocardial infarction (NSTE- MI)., Methods: We retrospectively analysed 253 patients (age 82 ± 8 years; 82 men, 172 women) with diagnoses of suspected NSTEMI admitted to our Department of Geriatric Medicine. Patients were divided into one group of 113 patients using cTnThs, and another of 140 patients using cTnT for diagnosis. Each group included patients at the same months but different years, in either cTnThs or cTnT assays. NSTEMI was diagnosed according to current guidelines., Results: Baseline characteristics were similar in both groups. The proportions of patients with elevated cardiac troponin (cTn) levels significantly increased from 35% in the cTnT group to 76% in the cTnThs group (p<0.001), although no coronary cause for the elevated cTn levels was shown in about two-thirds of these patients. In patients with NSTE- MI, 58% in the cTnThs group vs 42% in the cTnT group were diagnosed within 4 hours of the onset of symptoms, whereas 42% in the cTnThs group vs 58% in the cTnT group were diagnosed more than 4 hours later (p=0.018)., Conclusions: The prevalence of elevated cTn has more than doubled with the use of cTnThs. However, no coronary cause was found in two-thirds of our geriatric patients, al- though more NSTEMI patients were diagnosed earlier by cTnThs.

Diabetes mellitus is a known risk factor for cognitive dysfunction and dementia. Chronic hyperglycemia, genetic predisposition, arterial hypertension, hyperlipoproteinemia, micro- and macrovascular diseases, and depression play a major role in the development of cognitive dysfunction. Both pathophysiology of diabetes and dementia and the specifics of diabetes therapy in patients with dementia are presented in this review.

Evaluating patients with acute chest pain presenting to the emergency department remains an ongoing challenge. The spectrum of etiologies in acute chest pain ranges from minor disease entities to life-threatening diseases, such as pulmonary embolism, acute aortic dissection or acute myocardial infarction (MI). The diagnosis of acute MI is usually made integrating the triad of patient history and clinical presentation, readings of 12-lead ECG and measurement of cardiac troponins (cTn). Introduction of high-sensitivity cTn assays substantially increases sensitivity to identify patients with acute MI even at the time of presentation to the emergency department at the cost of specificity. However, the proportion of patients presenting with cTn positive, non-vascular cardiac chest pain triples with the implementation of new sensitive cTn assays increasing the difficulty for the emergency physician to identify those patients who are at need for invasive diagnostics. The main objectives of this mini-review are 1) to discuss elements of disposition decision made by the emergency physician for the evaluation of chest pain patients, 2) to summarize recent advances in assay technology and relate these findings into the clinical context, and 3) to discuss possible consequences for the clinical work and suggest an algorithm for the clinical evaluation of chest pain patients in the emergency department.

The early diagnosis of an acute myocardial infarction (MI) is improved by the introduction of novel high-sensitivity troponin assays. These assays can measure low level myocardial injury not detectable by standard troponin assays. Especially in older patients who appear to have a higher basal troponin level, the results must always be judged in the context of the medical history, physical examination, electrocardiogram (ECG) and any further findings. Even small increases in high-sensitivity troponin indicate increased risk for death or MI during follow-up. In the case of MI an invasive strategy results in better survival rates compared with conservative therapy but at the expense of an increased risk of bleeding in elderly patients. This article provides an overview on the diagnosis of MI in elderly patients.

The treatment of cardiovascular diseases in diabetic geriatric patients needs an individual risk-benefit analysis. The overtreatment of hyperglycemia in the sense of metabolic control that is too tight (HbA(1)c level <6%) may lead to increased mortality. As a rule, the target HbA(1)c level in geriatric patients with diabetes mellitus should be between 7 and 8%.

Background: It is assumed that patients with non-ST-elevation myocardial infarctions (NSTEMI) showing an infero- or posterolateral occluded culprit artery (OCA) during diagnostic angiography frequently elude standard 12-lead electrocardiogram diagnosis. In addition, coronary collaterals may have beneficial effects in patients with OCA., Methods: We examined 448 consecutive NSTEMI patients within 72 h of symptom onset. All patients underwent early invasive angiography plus optimal medical therapy. We compared clinical characteristics and 30-days/6-month major adverse cardiovascular events (MACE) between patients with OCA and non-OCA. The secondary objective was to investigate the effect of angiographically visible coronary collaterals on 6-month MACE in patients with OCA., Results: The angiograms revealed OCA in 130 (29%) of 448 patients. Patients with OCA showed more often infero- or posterolateral lesions (75 vs. 53%, p < 0.001) and more collaterals (57 vs. 8%, p < 0.001) compared with those with non-OCA. Patients with OCA had larger infarcts (peak CK-MB 2.1 ± 2.3 vs. 1.2 ± 1.1 μmol/L/s, p < 0.001), lower left ventricular ejection fraction (42 ± 21 vs. 48 ± 20%, p = 0.01), were more often revascularized (89 vs. 78%, p = 0.005), and had higher risk-adjusted 6-month MACE largely driven by its association with non-fatal reinfarctions (HR 2.16, 95% CI 1.04-4.50, p = 0.04). Patients with OCA and angiographically absent collaterals had significantly higher risk-adjusted 6-month MACE than those with OCA and angiographically visible collaterals (HR 1.96, 95% CI 1.02-3.76, p = 0.04)., Conclusions: Approximately one-fourth of patients with NSTEMI revealed OCA that was more frequently found in coronary arteries supplying the infero- or posterolateral myocardium. Patients with OCA had larger infarcts and more non-fatal reinfarctions than patients with non-OCA. Well-developed collaterals may limit the myocardial damage in these patients.

Background: Until recently, the only available lung-protective treatment option for carbon dioxide removal due to severe, refractory status asthmaticus has been extracorporeal pump-driven membrane oxygenation (ECMO). Pumpless extracorporeal lung assist (pECLA) may serve as an alternative therapy for these patients., Case Report: A 42-year-old woman presented with an acute exacerbation of asthma to our Emergency Department. Despite optimal pharmacological therapy, the patient developed respiratory failure requiring mechanical ventilation with elevated airway pressures. For severe ventilation-refractory hypercapnia and respiratory acidosis, ECMO was used initially and was later replaced by a pECLA device. The clinical condition continuously improved with sufficient pulmonary gas exchange. The pECLA was removed after 8 days, and the patient was successfully weaned from mechanical ventilation., Conclusions: This report suggests that pECLA is an alternative extracorporeal lung assist in patients with ventilation-refractory hypercapnia and respiratory acidosis due to severe, refractory status asthmaticus.

Background: Infective endocarditis due to viridans streptococci is associated with a mortality of 5-10%. Even today, it remains difficult to diagnose it at an early stage, to select a sufficient antibiotic therapy and to choose the right time for surgical intervention., Case Report: A 37-year-old male patient presented with anemia, fever, adynamia and a loud systolic murmur over the base of the heart. Blood culture data were positive for Streptococcus mitis. Transthoracic echocardiography revealed an endocarditis of the aortic and mitral valve with regurgitations as well as a hypertrophic obstructive cardiomyopathy. The hemodynamically stable patient was treated with penicillin G, gentamicin and verapamil. Because of an extension of valve vegetations and a decline in the hemodynamic situation with an incipient sepsis, the patient was surgically treated urgently by replacement of the aortic and mitral valve as well as a Morrow septal myectomy. A postoperative sepsis required the application of high catecholamine doses. Because of a respiratory insufficiency, a prolonged mechanical ventilation was required. Finally, the patient could be discharged for in-hospital rehabilitation., Conclusion: The indication for surgical therapy in patients with endocarditis of the aortic and mitral valve as well as hypertrophic obstructive cardiomyopathy should be critically discussed with regard to the patient's age, the aims of conservative therapy, and the consequences of a surgical intervention. If there are any indices of a disease progress in spite of antibiotic therapy, patients should be subjected to cardiac surgery immediately.

The objective of this study was to develop an analysis method for the automatic detection of intracoronary microemboli triggered high intensity signals (HITS) during percutaneous coronary interventions (PCI). The recorded ultrasonic Doppler velocity spectra from an intracoronary ultrasonic guide-wire were decomposed into 13 wavelet scales applying the continuous wavelet transform. From 7 wavelet scales which were most suitable for a differentiation between HITS and pulsatile flow, envelopes were calculated and combined to improve the HITS-to-background noise ratio. For different intensity thresholds the resulting number of HITS was automatically counted and compared with the number estimated by experienced observers. In a first validation trial HITS were detected within a simplified in vitro model with a sensitivity of 89.2% and a positive predictive value of 87.6%. In a following clinical study 211 HITS from 18 patients during PCI were counted manually by the observers. With the developed wavelet-based method 189 HITS were correctly detected (sensitivity of 89.6%, positive predictive value of 85.5%). The introduced new method automatically detects intracoronary HITS for the first time with a reliable accuracy. This may support further studies evaluating the incidence and consequences of coronary microembolization during coronary interventions.

Background: Intracoronary Doppler guidewires can be used for real-time detection and quantification of microembolism during percutaneous coronary interventions (PCIs). We investigated whether the frequency of Doppler-detected microembolism is related to the incidence of myonecrosis during elective PCI., Methods and Results: The study population included 52 consecutive patients (aged 64+/-10 years; 36 men, 16 women) with coronary artery disease who underwent elective PCI of a single-vessel stenosis. Using intracoronary Doppler ultrasound, we compared the frequency of microembolism during PCI in 22 patients with periprocedural non-ST-segment elevation myocardial infarctions (pNSTEMI) and 30 patients without pNSTEMI. The 2 groups were comparable with regard to their clinical and procedural characteristics. In the group with pNSTEMI, the total number of coronary microemboli after PCI (27+/-10 versus 16+/-8, P<0.001) was higher than in the group without pNSTEMI. Although high-sensitivity C-reactive protein plasma levels were similar before PCI (2.9+/-2.2 versus 3.4+/-1.7 mg/L, P=NS), they were higher in the group with pNSTEMI after PCI (12.6+/-10.4 versus 6.1+/-5.1 mg/L, P<0.05). Microembolic count independently correlated to postprocedural cardiac troponin I elevation (r=0.565, P<0.001), coronary flow velocity reserve (r=-0.506, P<0.001), and baseline average peak velocity (r=0.499, P<0.001)., Conclusions: Patients with pNSTEMI had a significantly higher frequency of coronary microembolization during PCI, and their systemic inflammatory response and microvascular impairment after PCI were more pronounced. Intracoronary Doppler ultrasound provides evidence that pNSTEMI in patients undergoing elective PCI is caused by microembolization during the procedure.

Background and Objectives: After a percutaneous coronary intervention (PCI) creatine kinase-MB fraction (CK-MB) elevation is observed in 5 to 30% of the cases. The often long and diffuse lesions of chronic total coronary occlusions (CTO) could represent a high risk group. However, there is no systematic data available on the incidence of elevation of cardiac troponin I (cTNI) after recanalisation of CTOs., Methods: In 201 patients a CTO was successfully recanalised with stenting of all lesions and the regional wall motion (WMSI) was assessed at baseline and follow-up. For comparison we analysed 111 stable angina patients with stenting of single non-occlusive lesions. Over a period of 24 hours after PCI, CK-MB and cTNI were measured., Results: CK-MB elevation after recanalisation of CTOs was observed in only 6% of patients with CTOs. The incidence of cardiac biomarker elevation was similar in patients with normal and severely impaired regional function, indicating that the low incidence was not due to a high prevalence of non-vital myocardium. In comparison CK-MB elevation after stenting of single non-occlusive lesions was observed in 13% of patients. In 14% of patients with CTOs and in 20% of patients with a single non-occlusive lesions cTNI increased after PCI., Conclusions: Despite the high plaque load of organised thrombotic material in CTOs, the incidence of cardiac biomarker elevation after recanalisation of CTOs was similar to that after stenting of single non-occlusive lesions. A specific adjunctive medical or interventional therapy may not be warranted during recanalisation of CTOs.

Background: Doppler-tipped coronary guide-wires (FW) are well-established tools in interventional cardiology to quantitatively analyze coronary blood flow. Doppler wires are used to measure the coronary flow velocity reserve (CFVR). The CFVR remains reduced in some patients despite anatomically successful coronary angioplasty. It was the aim of our study to test the influence of changes in flow profile on the validity of intra-coronary Doppler flow velocity measurements in vitro. It is still unclear whether turbulent flow in coronary arteries is of importance for physiologic studies in vivo., Methods: We perfused glass pipes of defined inner diameters (1.5-5.5 mm) with heparinized blood in a pulsatile flow model. Laminar and turbulent flow profiles were achieved by varying the flow velocity. The average peak velocity (APV) was recorded using 0.014 inch FW. Flow velocity measurements were also performed in 75 patients during coronary angiography. Coronary hyperemia was induced by intra-coronary injection of adenosine. The APV maximum was taken for further analysis. The mean luminal diameter of the coronary artery at the region of flow velocity measurement was calculated by quantitative angiography in two orthogonal planes., Results: In vitro, the measured APV multiplied with the luminal area revealed a significant correlation to the given perfusion volumes in all diameters under laminar flow conditions (r2 > 0.85). Above a critical Reynolds number of 500--indicating turbulent flow--the volume calculation derived by FW velocity measurement underestimated the actual rate of perfusion by up to 22.5 % (13 +/- 4.6 %). In vivo, the hyperemic APV was measured irrespectively of the inherent deviation towards lower velocities. In 15 of 75 patients (20%) the maximum APV exceeded the velocity of the critical Reynolds number determined by the in vitro experiments., Conclusion: Doppler guide wires are a valid tool for exact measurement of coronary flow velocity below a critical Reynolds number of 500. Reaching a coronary flow velocity above the velocity of the critical Reynolds number may result in an underestimation of the CFVR caused by turbulent flow. This underestimation of the flow velocity may reach up to 22.5 % compared to the actual volumetric flow. Cardiologists should consider this phenomena in at least 20 % of patients when measuring CFVR for clinical decision making.

Objective: To validate an intracoronary Doppler ultrasound device for high intensity transient signals (HITS) detection and to assess the incidence of HITS during percutaneous coronary intervention (PCI)., Methods and Results: In an in vitro model, particle count and number of HITS detected by an intracoronary 0.014 inch Doppler wire were closely correlated (r = 0.97, p < 0.001). In the clinical study, 32 patients (mean (SD) age 61 (11) years; 23 men, nine women) with coronary artery disease were treated with balloon dilatation and stent implantation for a single vessel stenosis. In these patients HITS were detected during PCI in 84% (27 of 32). Reproducibility (r = 0.99, p < 0.001) and interobserver agreement (r = 0.84, p < 0.001) of HITS counts were significant. The number of HITS after stent implantation was significantly higher than after balloon dilatation (11 (7) v 2 (4), p < 0.001). Postprocedural coronary flow velocity reserve (CFVR) was < 2.0 in 55% (16 of 29) of all patients after balloon dilatation and < 2.0 in 23% (six of 26) after stent implantation. The number of HITS after stent implantation did not differ significantly between patients with CFVR < 2.0 and patients with CFVR > or = 2.0 (12 (8) v 10 (7), not significant)., Conclusions: Embolic particles can be detected as HITS by an intracoronary Doppler ultrasound device. Coronary microembolism is often observed during PCI, especially after stent implantation. However, the incidence of HITS alone does not explain a reduced CFVR after PCI.

Background: A good collateral function in patients with regional myocardial dysfunction may indicate viability with the potential for left ventricular (LV) recovery after revascularization of a chronic total coronary occlusion (CTO)., Methods: A CTO (duration > 2 weeks) was successfully recanalized in 126 patients. During this procedure, the collateral function was assessed before the first balloon inflation by intracoronary Doppler and pressure wires. Collateral function indexes were calculated. Left ventricular function was assessed by the LV ejection fraction (LVEF) and the wall motion severity index (WMSI [SD/chords]). A repeat angiography was available in 119 patients after 4.9 +/- 1.4 m. An improvement of WMSI > or =1 SD/chord was considered significant., Results: Left ventricular function was normal in 42%, regional dysfunction with LVEF > or = 0.60 was observed in 16%, and regional dysfunction with LVEF < 0.60 in 42%. The former had a better collateral function than patients with LV dysfunction. In 39% of patients with LV dysfunction, a significant myocardial recovery was observed at follow-up. The collateral function was similar in patients with and without recovery. However, patients with recovery had a lower peripheral resistance as an indicator of a better preserved microvascular integrity., Conclusions: Recovery of impaired LV function after revascularization of a CTO is not directly related to the quality of collateral function, as collateral development does not appear to require the presence of viable myocardium. However, a preserved microvascular integrity may be of relevance for myocardial recovery.

Objective: To assess the potential for recovery of impaired microvascular function in collateral dependent myocardium after recanalisation of a chronic total coronary occlusion and the determinants of this recovery., Patients and Design: 120 patients underwent a successful recanalisation of a chronic total coronary occlusion (duration > 2 weeks) and a follow up angiography after a mean (SD) of 5.0 (1.2) months. The coronary flow velocity reserve (CFVR) and the fractional flow reserve were measured after recanalisation and at follow up. Global and regional left ventricular (LV) function were analysed by quantitative angiography., Results: Microvascular dysfunction, defined by a CFVR < 2.0 and a fractional flow reserve > or = 0.75, was observed in 55 (46%) patients after recanalisation. Microvascular function improved during follow up in 24 (20%). The CFVR increased during follow up from 2.01 (0.58) to 2.50 (0.79) (p < 0.001), due to a decrease in basal average peak velocity from 30.7 (14.9) cm/s to 25.5 (13.3) cm/s (p = 0.001). Improved microvascular function was associated with an improved regional LV function, shown by a correlation between increased wall motion severity index and increased CFVR (r = 0.38, p = 0.003). The major determinant of microvascular dysfunction at baseline was the presence of diabetes mellitus (odds ratio 4.3, 95% confidence interval 1.8 to 10.2), which remained so at follow up (odds ratio 4.1, 95% confidence interval 1.3 to 13.4). Improvement of LV function was not impaired by the presence of microvascular dysfunction after recanalisation., Conclusions: The frequently observed microvascular dysfunction after recanalisation of a chronic total coronary occlusion is a transient phenomenon in most patients and is influenced by the presence of diabetes mellitus. It does not impede the recovery of LV function. Improved regional LV function is associated with improved microvascular function.

Introduction: Tumor necrosis factor (TNF)-alpha and interleukin-6 (IL-6) are significantly elevated in patients with congestive heart failure (CHF). Pentoxifylline, a xanthin-derived agent, is known to inhibit the production of TNF-alpha and IL-6. Recent studies have shown that pentoxifylline produces an increase in ejection fraction, a decrease in left-ventricular chamber size and an improvement in clinical status in patients with idiopathic-dilated cardiomyopathy. Therefore, we studied the effects of pentoxifylline in ischemic, hypertensive and idiopathic-dilated cardiomyopathy., Methods: Primary endpoint was left-ventricular ejection fraction (LVEF) assessed by contrast 2D echocardiography. Secondary endpoints were concentrations of TNF-alpha, IL-6, brain natriuretic peptide, maximal oxygen uptake (VO(2 max)) assessed by cardiopulmonary exercise testing and Minnesota Living with Heart Failure Questionnaire score or New York Heart Association scale., Results: Forty-seven patients (31.9% ischemic, 21.3% hypertensive, 10.6% ischemic and hypertensive, 36.2% idiopathic-dilated cardiomyopathy) were randomly assigned to pentoxifylline 600 mg BID (n=23) or placebo (n=24) if they had a compensated CHF with a LVEF less than or equal to 40% and had taken their standard treatment consisting of angiotensin-converting enzyme inhibitors, diuretics and beta-blockers for at least 3 months. Baseline demographic and clinical characteristics of each group were similar. Forty-one patients completed the study protocol and were analysed for primary and secondary endpoints. After 6 months of treatment, LVEF was unchanged in the pentoxifylline group compared with placebo (29+/-7 to 33+/-10% vs. 27+/-9 to 34+/-9%, respectively, P=NS). Also the secondary endpoints did not significantly change during follow-up., Conclusion: Additional treatment with pentoxifylline is neutral with regard to left-ventricular function, inflammatory cytokines and symptoms in patients with ischemic, hypertensive and idiopathic-dilated cardiomyopathy.

Background: Collaterals can maintain myocardial function or preserve viability in chronic total coronary occlusions (CTOs). It is unknown whether and to what extent collaterals regress after successful recanalization of a CTO., Methods and Results: In 103 patients with successful recanalization of a CTO collateral function was assessed by intracoronary Doppler and pressure recordings before and after recanalization, and again after 5.0+/-1.3 months. Doppler (CFI) and pressure-derived collateral function indexes (CPI) and collateral (RColl) and peripheral resistance indexes (RP) were calculated. In 10 patients with reocclusion, all without myocardial infarction during follow-up, collateral function had reached a similar level as before the first recanalization. In the other 93 patients with or without restenosis, collateral function was attenuated during follow-up. CPI had decreased by 23% immediately after recanalization (P<0.001) and decreased further by another 23% at follow-up (P<0.001). The RColl increased immediately after recanalization by 82% (P<0.001) and by a further 273% at follow-up (P<0.001). In contrast, RP increased only by 22% after recanalization (P<0.001) and by an additional 12% at follow-up (P<0.05). The initial size of the collaterals but not the incidence of a restenosis influenced the collateral regression. Only 18% of patients at follow-up had collaterals with a CPI >0.30, presumably sufficient to prevent ischemia during acute occlusion., Conclusions: Collateral function regresses during long-term follow-up, especially in collaterals with a small diameter. In the majority of patients, collaterals are not readily recruitable in the case of acute occlusion. However, collaterals have the potential to recover in the case of chronic reocclusion.

Objectives: The goal of this study was to assess the influence of collateral function, coronary hemodynamics, and the angiographic result on the risk of target vessel failure (TVF) after recanalization of a chronic total coronary occlusion (CTO)., Background: Collaterals may have an adverse effect on TVF., Methods: In 111 consecutive patients, a CTO (duration >2 weeks) was successfully recanalized with stent implantation. Collateral function was assessed by intracoronary Doppler flow velocity and pressure recordings distal to the occlusion. Baseline collateral function was determined before the first balloon inflation, and recruitable collateral function after stenting during a balloon reocclusion. Finally, the coronary flow velocity reserve (CFVR) and the fractional flow reserve (FFR) were measured., Results: Angiographic follow-up after 5 +/- 4 months in 106 patients showed a reocclusion in 17% and a restenosis in 36%. The major determinants of TVF were the stent length (p < 0.01) and number of implanted stents (p < 0.01). No difference was observed in baseline or recruitable collateral function between patients with and without TVF; 52% of patients had a CFVR >or= 2.0, and only 18% a CFVR >or=2.5 after percutaneous transluminal coronary angioplasty, but neither cutoff-value predicted TVF. A low FFR discriminated patients with reocclusion (0.81 +/- 07 vs. 0.86 +/- 08, p < 0.05) but not with restenosis (0.87 +/- 0.06)., Conclusions: This study showed that there is no relation between a well-developed collateral supply and the risk of TVF in recanalized CTOs. This was rather determined by the stented segment length. There was also no adverse effect of the frequently observed impaired CFVR on TVF, whereas a low FFR was associated with a higher risk of reocclusion.

After recanalization and stenting of chronic total coronary occlusions (TCO), a reduced coronary flow velocity reserve (CFVR) and rise in collateral resistance (R(Coll)) is frequently observed. Coronary microembolization may account for these observations. In 86 patients (age 64+/-10 years; 77 men, 9 women) with TCO (duration >4 weeks), PTCA was performed with successful stent implantation in all lesions. Before PTCA, viable myocardium was detected by stress echocardiography or nuclear imaging techniques. By simultaneously measuring coronary Doppler flow velocity and pressure before and after PTCA, CFVR and R(Coll) were calculated. Over a period of 24 hours after intervention, creatine kinase (CK; upper limit of normal [ULN] for women 1.17 micromol/L/s, for men 1.33 micromol/L/s) and cardiac troponin I (cTNI; threshold 0.1 ng/mL) were studied. CFVR was <2 in 48% of all patients. A rise in R(Coll) was observed in 83% of all patients. The incidence of CK and/or cTNI elevation was only observed in 10% of all patients. These patients with CK and/or cTNI elevation did not show a significant difference of CFVR and rise in R(Coll) as compared with patients without CK and cTNI elevation. CFVR or rise in R(Coll) did not correlate with CK elevation. Coronary microembolization is not a likely cause of reduced CFVR and increased R(Coll) after PTCA of TCO. Other factors such as microvascular dysfunction and autoregulatory changes in collateral function may account for these observations.

Objective: Angiotensin II (Ang II) increases insulin sensitivity in healthy volunteers. This effect is thought to be mediated, at least in part, by an increase in skeletal muscle blood flow. In the past it had been documented that some biological actions of Ang II are altered in diabetes. We addressed the issue of whether this is also true for its action on insulin sensitivity., Design and Methods: Twelve healthy volunteers (aged 43+/-9 years) and 15 patients with type 2 diabetes mellitus (NIDDM) of recent onset (aged 45+/-9 years) were allocated in random order in a double-blind placebo-controlled design to be administered a sham infusion or an infusion of 2 ng Ang II/kg per min. Insulin-stimulated glucose uptake (the M value) was measured with the euglycaemic clamp technique, leg muscle blood flow (MBF) with plethysmography, blood pressure with a Dinamap device, and glomerular filtration rate and effective renal plasma flow with the steady-state inulin (Cin) and p-aminohippurate (CPAH) clearance methods, respectively., Results: In volunteers the mean M-value after Ang II infusion (10.1+/-1.5 mg/kg per min) was significantly higher (P < 0.01) than that after sham infusion (8.2+/-0.9 mg/kg per min). In contrast, in diabetic patients it was not significantly different with Ang II (6.1+/-1.3 mg/kg per min) and sham infusion (5.5+/-1.2 mg/kg per min). The difference in the mean absolute increase in the M value (deltaM) between groups was significant (P< 0.02). The Ang II-induced increase in MBF under euglycaemic conditions was attenuated in diabetic patients (from 15.0+/-3.5 to 15.5+/-3.9 ml/100 ml per min, NS) compared with volunteers (from 16.8+/-3.3 to 19.1+/-3.7 ml/100 ml per min, P< 0.01). Again, the difference between the mean absolute increases in MBF (deltaMBF) in the groups was significant (P < 0.01). A significant correlation was found between deltaMBF and deltaM (r= 0.62, P<0.01). The absolute acute increase in mean arterial blood pressure with Ang II was similar in diabetic patients and volunteers. Mean Cin, CPAH and fractional sodium excretion values were significantly lower and renal vascular resistances and filtration fractions higher during the Ang II than they were during the placebo clamp period. This was observed in patients as well as in healthy subjects, but the effects of Ang II on renal haemodynamics and sodium handling were more pronounced in diabetic patients., Conclusions: In patients with NIDDM of recent onset the stimulatory effect of Ang II on insulin sensitivity and on skeletal muscle blood flow is attenuated. In contrast, the effects of Ang II on renal perfusion and sodium handling are more pronounced in patients with NIDDM than they are in healthy subjects.