Performance of the European Society of Cardiology 0/1-Hour, 0/2-Hour, and 0/3-Hour Algorithms for Rapid Triage of Acute Myocardial Infarction : An International Collaborative Meta-analysis.

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.

The Charlson Comorbidity and Barthel Index predict length of hospital stay, mortality, cardiovascular mortality and rehospitalization in unselected older patients admitted to the emergency department.

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.

[Chronic heart failure in older patients : Updated national healthcare guidelines on chronic heart failure from a geriatric perspective]. / Chronische Herzinsuffizienz beim älteren Patienten : Aktualisierte Nationale VersorgungsLeitlinie "Chronische Herzinsuffizienz" aus geriatrischer Perspektive.

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.

Quantification of Renal Function and Cardiovascular Mortality in Patients Admitted to the Emergency Department with Suspected Acute Coronary Syndromes.

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.

[New oral anticoagulants for prophylaxis of stroke. Results of an expert conference on practical use in geriatric patients]. / Neue orale Antikoagulanzien zur Prophylaxe von Schlaganfällen. Ergebnis einer Expertenkonferenz zum praktischen Einsatz bei geriatrischen Patienten.

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.

Additional diagnostic and prognostic value of copeptin ultra-sensitive for diagnosis of non-ST-elevation myocardial infarction in older patients presenting to the emergency department.

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.

Early detection of non-ST-elevation myocardial infarction in geriatric patients by a new high-sensitive cardiac troponin T assay.

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.

Exploring biomarkers in routine diagnostics for the risk stratification of older patients in the Chest Pain Unit: a prospective cohort study.

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.

Development and validation of a decision support tool for the diagnosis of acute heart failure: systematic review, meta-analysis, and modelling study.

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.

High-sensitivity troponin assays in the evaluation of patients with acute chest pain in the emergency department.

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.

Pumpless extracorporeal lung assist for the treatment of severe, refractory status asthmaticus.

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.

Detection of coronary microembolization by Doppler ultrasound in patients with stable angina pectoris undergoing elective percutaneous 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.

[Surgical therapy of infective endocarditis. General aspects and case report]. / Indikationen zur herzchirurgischen Therapie bei Endokarditis. Fallbeschreibung und allgemeine Aspekte.

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.

Turbulent flow as a cause for underestimating coronary flow reserve measured by Doppler guide wire.

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.

Prognostic value of different biomarkers for cardiovascular death in unselected older patients in the emergency department.

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.

Regression of collateral function after recanalization of chronic total coronary occlusions: a serial assessment by intracoronary pressure and Doppler recordings.

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.

Determinants of target vessel failure in chronic total coronary occlusions after stent implantation. The influence of collateral function and coronary hemodynamics.

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.

Collaterals and the recovery of left ventricular function after recanalization of a chronic total coronary occlusion.

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.