Influence of Hemoglobin Strasbourg, a Rare High Oxygen Affinity Hemoglobin Variant, on Different Methods of HbA1c Measurement.

Hemoglobin Strasbourg is a rare high oxygen affinity hemoglobin variant which leads to secondary erythrocytosis. This variant is caused by a HBB gene mutation c.71T > A resulting in an amino acid exchange on position 23 of the ß globin chain (p.Val23Asp.). The influence of Hb Strasbourg on HbA1c measurement has not been studied to date. For patients with hemoglobin variants it is important to know whether possible interferences exist with the measurement of HbA1c. We therefore investigated the influence of Hb Strasbourg on HbA1c measurement with two different HPLC (high-performance liquid chromatography) systems and one turbidimetric immunoassay in two non-diabetic brothers who are heterozygous carriers of Hb Strasbourg. The examined tests are all used in routine diagnostics. In the case of Hb Strasbourg, the HbA1c measured by HPLC showed lower results than those obtained by the immunoassay. We conclude that HbA1c is underestimated when measured with these methods as glycated Hb Strasbourg is most likely not co-eluting with HbA1c in HPLC.

Blood markers of cardiac stress after generalized convulsive seizures.

OBJECTIVE: Generalized convulsive seizures (GCS) are associated with high demands on the cardiovascular system, thereby facilitating cardiac complications. To investigate occurrence, influencing factors, and extent of cardiac stress or injury, the alterations and time course of the latest generation of cardiac blood markers were investigated after documented GCS. METHODS: Adult patients with refractory epilepsy who underwent video-electroencephalography (EEG) monitoring along with simultaneous one-lead electrocardiography (ECG) recordings were included. Cardiac biomarkers (cardiac troponin I [cTNI]; high-sensitive troponin T [hsTNT]; N-terminal prohormone of brain natriuretic peptide [NT-proBNP]; copeptin; suppression of tumorigenicity-2 [SST-2]; growth differentiation factor 15, [GDF-15]; soluble urokinase plasminogen activator receptor [suPAR]; and heart-type fatty acid binding protein [HFABP]) and catecholamines were measured at inclusion and at different time points after GCS. Periictal cardiac properties were assessed by analyzing heart rate (HR), HR variability (HRV), and corrected QT intervals(QTc). RESULTS: Thirty-six GCS (6 generalized-onset tonic-clonic seizures and 30 focal to bilateral tonic-clonic seizures) were recorded in 30 patients without a history of cardiac or renal disease. Postictal catecholamine levels were elevated more than twofold. A concomitant increase in HR and QTc, as well as a decrease in HRV, was observed. Elevations of cTNI and hsTNT were found in 3 of 30 patients (10%) and 6 of 23 patients (26%), respectively, which were associated with higher dopamine levels. Copeptin was increased considerably after most GCS, whereas SST-2, HFABP, and GDF-15 displayed only subtle variations, and suPAR was unaltered in the postictal period. Cardiac symptoms did not occur in any patient. SIGNIFICANCE: The use of more sensitive biomarkers such as hsTNT suggests that signs of cardiac stress occur in about 25% of the patients with GCS without apparent clinical symptoms. SuPAR may indicate clinically relevant troponin elevations. Copeptin could help to diagnose GCS, but specificity needs to be tested.

Effects of the flavonol quercetin and α-linolenic acid on n-3 PUFA status in metabolically healthy men and women: a randomised, double-blinded, placebo-controlled, crossover trial.

Increased dietary intake and tissue status of the long-chain n-3 PUFA, EPA and DHA, is associated with cardiovascular benefits. Epidemiological and animal studies suggest that concomitant nutritive intake of flavonoids may increase the conversion of α-linolenic acid (ALA) to longer-chain n-3 fatty acids EPA and DHA. We investigated the effects of increased ALA intake on fatty acid composition of serum phospholipids and erythrocytes in metabolically healthy men and women and whether fatty acid profiles and ALA conversion were affected by regular quercetin intake or sex. Subjects (n 74) were randomised to receive at least 3·3 g/d ALA with either 190 mg/d quercetin (ALA+quercetin) or placebo (ALA+placebo) in a double-blinded, placebo-controlled, crossover trial with 8-week intervention periods separated by an 8-week washout period. A total of seven subjects dropped out for personal reasons. Data from the remaining sixty-seven subjects (thirty-four males and thirty-three females) were included in the analysis. Both interventions significantly increased serum phospholipid ALA (ALA+placebo: +69·3 %; ALA+quercetin: +55·8 %) and EPA (ALA+placebo: +37·3 %; ALA+quercetin: +25·5 %). ALA + quercetin slightly decreased DHA concentration by 9·3 %. Erythrocyte ALA and EPA significantly increased with both interventions, whereas DHA decreased. Fatty acid composition did not differ between sexes. We found no effect of quercetin. Intake of 3·6 g/d ALA over an 8-week period resulted in increased ALA and EPA, but not DHA, in serum phospholipids and erythrocytes. Neither quercetin supplementation nor sex affected the increment of ALA and relative proportions of n-3 PUFA in serum phospholipids and erythrocytes.

Influence of Apnea-induced Hypoxia on Catecholamine Release and Cardiovascular Dynamics.

Prolonged breath-hold causes complex compensatory mechanisms such as increase in blood pressure, redistribution of blood flow, and bradycardia. We tested whether apnea induces an elevation of catecholamine-concentrations in well-trained apneic divers.11 apneic divers performed maximal dry apnea in a horizontal position. Parameters measured during apnea included blood pressure, ECG, and central, in addition to peripheral hemoglobin oxygenation. Peripheral arterial hemoglobin oxygenation was detected by pulse oximetry, whereas peripheral (abdominal) and central (cerebral) tissue oxygenation was measured by Near Infrared Spectroscopy (NIRS). Exhaled O2 and CO2, plasma norepinephrine and epinephrine concentrations were measured before and after apnea.Averaged apnea time was 247±76 s. Systolic blood pressure increased from 135±13 to 185±25 mmHg. End-expiratory CO2 increased from 29±4 mmHg to 49±6 mmHg. Norepinephrine increased from 623±307 to 1 826±984 pg ml-1 and epinephrine from 78±22 to 143±65 pg ml-1 during apnea. Heart rate reduction was inversely correlated with increased norepinephrine (correlation coefficient -0.844, p=0.001). Central (cerebral) O2 desaturation was time-delayed compared to peripheral O2 desaturation as measured by NIRSabdominal and SpO2.Increased norepinephrine caused by apnea may contribute to blood shift from peripheral tissues to the CNS and thus help to preserve cerebral tissue O2 saturation longer than that of peripheral tissue.

Psychosocial assessment of living kidney donors: What implications have temperament and character for decision-making?

OBJECTIVE: We compared the personality of kidney donor candidates to non-donor controls and analyzed the personality profile of candidates psychosocially at risk. METHODS: 49 consecutive living kidney donor candidates underwent an extensive psychosocial evaluation. Psychosocial risk factors concerning knowledge of donation risks (1), donor-recipient-relationship (2), and/or mental health (3) were rated on a 3-point rating scale (0=high risk, 2=no risk). Furthermore, candidates as well as 49 age-and gender-matched non-donor controls filled in questionnaires concerning psychological distress (Symptom Checklist 90-R) and personality (Temperament and Character Inventory). RESULTS: There were no significant differences between candidates and controls concerning psychological distress or personality. Psychosocial assessment identified 13 candidates (26.5%) with increased psychosocial risk. This group displayed compared to candidates without psychosocial risk no difference concerning age, gender, formal education, donor-recipient relationship and psychological distress. However, this group scored significantly higher on reward dependence compared to suitable donors and controls (p<0.05). Reward dependence was associated with a lack of adequate knowledge on donation (r=-0.35, p<0.05). CONCLUSION: Reward dependence has important implications for decision-making, because it is associated with an increased tendency to deny potential risks of donation. Careful identification and assessment of reward dependent donor candidates is needed to ensure a free-willed decision.

Risk scores and biomarkers for the prediction of 1-year outcome after transcatheter aortic valve replacement.

BACKGROUND: Up to 50% of the patients still die or have to be rehospitalized during the first year after transcatheter aortic valve replacement (TAVR). This emphasizes the need for more strategic patient selection. The aim of this prospective observational cohort study was to compare the prognostic value of risk scores and circulating biomarkers to predict all-cause mortality and rehospitalization in patients undergoing TAVR. METHODS: We calculated the hazard ratios and C-statistics (area under the curve [AUC]) of 4 risk scores (logistic European System for Cardiac Operative Risk Evaluation [EuroSCORE], EuroSCORE II, Society of Thoracic Surgeons predicted risk of mortality, and German aortic valve score) and 5 biomarkers of inflammation and/or myocardial dysfunction (high-sensitivity C-reactive protein, growth differentiation factor (GDF)-15, interleukin-6, interleukin-8, and N-terminal pro-B-type natriuretic peptide) for the risk of death (n = 80) and the combination of death or rehospitalization (n = 132) during the first year after TAVR in 310 consecutive TAVR patients. RESULTS: The EuroSCORE II and GDF-15 had the strongest predictive value for 1-year mortality (EuroSCORE II, AUC 0.711; GDF-15, AUC 0.686) and for the composite end point (EuroSCORE II, AUC 0.690; GDF-15, AUC 0.682). When added to the logistic EuroSCORE and EuroSCORE II, GDF-15 enhanced the prognostic performance of the score and enabled substantial reclassification of patients. Combinations of increasing tertiles of the logistic EuroSCORE or EuroSCORE II and GDF-15 allowed the stratification of the patients into subgroups with mortality rates ranging from 4.0% to 49.1% and death/rehospitalization rates ranging from 15.3% to 68.4%. CONCLUSIONS: Our study identified GDF-15 in addition to the logistic EuroSCORE and the EuroSCORE II as the most promising predictors of a poor outcome after TAVR.

Temperament and character personality profile and illness-related stress in central serous chorioretinopathy.

Psychological stress is a risk factor as well as a consequence of central serous chorioretinopathy (CSC). Impulsiveness, overachievement, emotional instability, and hard-driving competitiveness have been discussed as personality features in CSC patients. We investigated 57 consecutive CSC patients and 57 age- and gender-matched controls by means of the Symptom Checklist 90-R and the Temperament and Character Inventory. Somatic risk factors, illness characteristics, subjective assessment of severity of illness, and illness-related stress in different areas of life (work, private life) were evaluated. CSC patients showed significantly higher emotional distress as measured by the Global Severity Index. The CSC personality was characterized by lower scoring on the character dimension cooperativeness and the temperament dimension reward dependence. Cooperativeness as well as subjective assessment of severity of CSC has been recognized as significant predictors of illness-related work stress accounting for 30% of variance. Implicating competitiveness, hostility and emotional detachment, lower level of cooperativeness, and reward dependence support the existence of specific aspects of type A behaviour in CSC patients. Low perceived social support and loss of control may explain the significant contribution of this personality dimension to illness-related work stress. Treatment of CSC should thus incorporate psychoeducation about factors contributing to illness-related stress.

Case-control studies of novel hemoglobin anomalies as differential diagnosis in sleep apnea syndrome.

PURPOSE: Pulse oximetry plays an essential role in the diagnosis of sleep apnea syndrome. We discovered two novel hemoglobin anomalies, Hb Bonn and Hb Venusberg, which initially resulted in avoidable sleep disorder examinations and therapeutic consequences due to their low oxygen saturation levels as measured by pulse oximetry. METHODS: Hematological as well as clinical chemical diagnosis was carried out. Hemoglobin anomalies were detected through electrophoresis, chromatography, spectrophotometry, and pulse oximetry as well as hemoglobin gene sequencing. RESULTS: Hb Bonn is a novel hemoglobin mutation of the proximal α1 globin with an additional absorption maximum of the oxyhemoglobin at 668 nm. This results in pulse oximetry measurements of false low oxygen saturation due to incorrect calculations at the pulse oximetry measuring point 660 m. Hb Venusberg is a novel oxygen-affine hemoglobin mutation of the ß-globin which is electrophoretically silent. Clinical symptoms include intermittent low oxygen saturation levels, cyanosis of lips and nail beds, and limited physical resistance to stress. CONCLUSIONS: Hemoglobin anomalies, such as Hb Bonn and Hb Venusberg, should be included in differential diagnosis as potential causes of low oxygen saturation especially in case of nonspecific or conflicting findings.

Method comparison for determination of the tumor markers AFP, CEA, PSA and free PSA between Immulite 2000 XPI and Dimension Vista 1500.

BACKGROUND: For the Luminescent Oxygen Channeling Immunoassay (LOCI) technology as established for Dimension Vista 1500, assays have been developed for the serum tumor markers AFP, CEA, PSA and free PSA. We performed a method analysis for these parameters using the Immulite 2000 XPI. METHODS: Determination of within-day and total imprecision of the methods was carried out according to CLSI guidelines with three serum pools. In addition, parallel measurements were performed with both systems in 1,871 routine serum samples and correlations were calculated. RESULTS: Calculated total imprecision of the three serum pools for AFP was 3.8 - 4.3%, for CEA 3.3 - 4.3%, for tPSA 3.6 - 4.0% and for fPSA it was 3.5 - 8.2%. Correlations of these markers across the entire value range were very good with the following correlation coefficients: 0.997 for AFP, 0.996 for CEA, 0.971 for tPSA and 0.988 for fPSA. While values for AFP and tPSA from both methods were comparable (slopes 1.02 and 1.01), lower values were measured for CEA and fPSA with the Dimension Vista (slopes 0.83 and 0.91). For AFP, a sample cluster with considerably higher values than with Dimension Vista was observed in the lower measurement range (< 20 ng/mL). CONCLUSIONS: The assays for AFP, CEA, tPSA and fPSA, as developed with the LOCI technology for the Dimension Vista, show good comparability with results obtained from the Immulite 2000 XPI. However, lower measurement ranges for CEA and fPSA as well as individual divergences, especially with AFP, must be taken into consideration in the event of method changeover.

Method comparison for CA 15-3, CA 19-9, and CA 125 determination using the new LOCI technique of Dimension Vista 1500 and Immulite 2000 XPI.

We performed method comparison for the tumor markers CA 15-3, CA 19-9, and CA 125 measured by luminescent oxygen channeling immunoassay technology on the Dimension Vista 1500 and by classic luminescence technology on the Immulite 2000 XPI. Within-day and total imprecision were determined according to Clinical and Laboratory Standards Institute (CLSI) guidelines using three serum pools at different clinically relevant levels. In addition, parallel measurements on both systems were performed in a total of 738 routine serum samples (133 CA 15-3, 395 CA 19-9, and 210 CA 125). Total imprecision of serum pools for CA 15-3 ranged between 4.6% and 5.9%, for CA 19-9 between 4.4% and 7.8%, and for CA 125 between 3.3% and 4.3%. Marker values determined within the measurement range of both systems correlated well with each other (R = 0.88 for CA 15-3, R = 0.93 for CA 19-9, and R = 0.96 for CA 125). Slopes between the Vista and the Immulite method were 0.96 for CA 125, 0.72 for CA 15-3, and 0.87 for CA 19-9, indicating lower values for CA 15-3 and CA 19-9 when measured by the Vista method. This was particularly obvious for CA 19-9 levels in the lower measuring range of <100 U/mL (R = 0.85; slope 0.73).

A first report on Hb Q-Iran in association with alpha-thalassemia in a case of spinal ischemia.

BACKGROUND: Hemoglobin Q-Iran is a rare variant which has not been described in association with alpha-thalassemia to date. We present the case of a Turkish patient who developed spinal ischemia. METHODS: Spinal ischemia was diagnosed clinically, via magnetic resonance imaging and angiographically. Blood samples were analyzed by high performance liquid chromatography, electrophoresis, gene sequencing, hematological and biochemical analysis. RESULTS: We detected hemoglobin Q-Iran in association with alpha-thalassemia. The same hemoglobinopathy was detected in two members of the patient's family. CONCLUSIONS: As various differential diagnosis approaches failed to reveal the cause of spinal ischemia, the combined hemoglobinopathy was eventually postulated.

Comprehensive Profiling of Blood Coagulation and Fibrinolysis Marker Reveals Elevated Plasmin-Antiplasmin Complexes in Parkinson's Disease.

Parkinson's disease (PD) is the second most common age-related neurodegenerative disease. Accumulating evidence demonstrates that alpha-synuclein (α-Syn), an apparently predominant neuronal protein, is a major contributor to PD pathology. As α-Syn is also highly abundant in blood, particularly in red blood cells (RBCs) and platelets, this in turn raises the question on the function of presumably dysfunctional α-Syn in "peripheral" cells and its putative effect on the other enclosed constituents. Herein, we detected the internal variance in erythrocytes of PD patients by Raman spectroscopy, but no measurable amount of erythrocytic behavioural change (eryptosis) or any haemoglobin variation was noticed. An elevated level of plasmin-antiplasmin complexes (PAP) was observed in the plasma of PD patients, indicating activation of the fibrinolytic system, but platelet activation after thrombin stimulation was not altered. Sex-specific patterns were noticed for blood coagulation factor XIII and factor XII activity in PD patients. Additionally, the alterations in homocysteine levels which have often been observed in PD patients were found to be independent from L-DOPA usage and PAP levels. Furthermore, a selective gene expression analysis identified subsets of genes related to different blood-associated compartments (RBCs, platelets, coagulation-fibrinolysis) also involved in PD-related pathways.

Acute metabolic effects of tonic-clonic seizures.

OBJECTIVE: Tonic-clonic seizures (TCS) lead to metabolic stress and changes in related blood markers. Such markers may indicate harmful conditions but can also help to identify TCS as a cause of transient loss of consciousness. In this study, we hypothesized that the alterations of circulating markers of metabolic stress depend on the clinical features of TCS. METHODS: Ninety-one adults undergoing video-EEG monitoring participated in this prospective study. Electrolytes, renal parameters, creatine kinase (CK), prolactin (PRL), lactate, ammonia, glucose, and other parameters were measured at inclusion and different time points after TCS. RESULTS: A total of 39 TCS were recorded in 32 patients (six generalized onset tonic-clonic seizures in 6 and 33 focal to bilateral tonic-clonic seizures in 26 patients). Shortly after TCS, mean lactate, ammonia, and PRL levels were significantly increased 8.7-fold, 2.6-fold, and 5.1-fold, respectively, with levels of more than twofold above the upper limits of the normal (ULN) in 90%, 71%, and 70% of the TCS and returned to baseline levels within 2 hours. Only postictal lactate levels were significantly correlated with the total duration of the tonic-clonic phase. In contrast, CK elevations above the ULN were found in three TCS (~10%) only with a peak after 48 hours. Immediately after the TCS, hyperphosphatemia occurred in one third of the patients, whereas hypophosphatemia was observed in one third 2 hours later. TCS led to subtle but significant alterations of other electrolytes, creatinine, and uric acid, whereas glucose levels were moderately increased. SIGNIFICANCE: Lactate is a robust metabolic marker of TCS with elevations found in ~90% of cases within 30 minutes after seizure termination, whereas ammonia rises in ~ 70%, similarly to PRL. Phosphate levels show an early increase and a decrease 2 hours after TCS in a third of patients. CK elevations are rare after video-EEG-documented TCS, challenging its value as a diagnostic marker.

Effect of alpha-linolenic acid in combination with the flavonol quercetin on markers of cardiovascular disease risk in healthy, non-obese adults: A randomized, double-blinded placebo-controlled crossover trial.

OBJECTIVES: Alpha-linolenic acid (ALA) and quercetin are characteristic compounds in plant-based diets. Cardioprotective effects have been described for both substances, although a possible benefit of combining ALA and quercetin has not, to our knowledge, been evaluated yet. The aim of this study was to investigate the potential independent and additive effects of ALA and quercetin on blood pressure (BP) and lipid and glucose metabolism, as well as on biomarkers of inflammation, oxidative stress, and antioxidant status in healthy, non-obese men and women. Another aim was to examine whether chronic supplementation of supranutritional doses of quercetin would result in an accumulation of plasma quercetin concentration over time. METHODS: In a double-blinded, placebo-controlled crossover trial, healthy volunteers were randomized to receive 3.6 g/d ALA plus 190 mg/d quercetin or placebo for 8 wk. Data from 67 individuals (34 men, 33 women, mean age: 24.6 y) were assessed. RESULTS: Plasma quercetin, tamarixetin, isorhamnetin, and kaempferol increased significantly from baseline to study end with ALA + quercetin but not with ALA + placebo. No significant effect on office systolic BP, mean 24 h ambulatory BP (ABP), or mean daytime ABP was seen in either study group. Both interventions significantly decreased total cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B to a similar extent. No effect on high-density lipoprotein cholesterol, apolipoprotein A1, glucose, uric acid, oxidized low-density lipoprotein, C-reactive protein, or lipid-adjusted retinol, α-tocopherol, or ß-carotene was seen in either group. CONCLUSION: Although dietary supplements of 3.6 g/d ALA over an 8-wk period improved lipid profiles in healthy adults, antioxidative and oxidative status, inflammation, and BP remained unchanged. No evidence was seen for an additive or synergistic effect of ALA plus quercetin on markers of cardiovascular disease risk.

Combination of high-sensitivity C-reactive protein with logistic EuroSCORE improves risk stratification in patients undergoing TAVI.

AIMS: The aim of this study was to assess the clinical value of biomarkers to identify TAVI patients at high risk for adverse outcome, to assess whether these biomarkers provide prognostic information beyond that of established clinical risk scores, and to assess whether a combined multi-marker strategy can improve clinical decision making. METHODS AND RESULTS: In 683 TAVI patients, biomarkers reflecting various pathophysiologic systems were measured before TAVI. The primary endpoint was one-year all-cause mortality. Other outcomes were recorded according to the VARC-2 criteria. Thirty-day and one-year mortality was 2.9% and 12.0%, respectively. Non-survivors at one year had higher risk scores and increased median biomarker levels. Logistic EuroSCORE in combination with hs-CRP had the highest predictive value for 30-day (AUC 0.740 [95% CI: 0.667-0.812], p=0.1117) and one-year mortality (AUC 0.631 [95% CI: 0.569-0.693], p=0.0403). In multivariate regression analysis, logistic EuroSCORE in combination with hs-CRP showed the strongest association with one-year mortality. Combinations of increasing medians of logistic EuroSCORE results and hs-CRP levels allowed the stratification of the TAVI patients into subgroups with one-year mortality rates ranging from 6.6% up to 18.2%. CONCLUSIONS: hs-CRP alongside the logistic EuroSCORE was an independent predictor of one-year all-cause mortality in TAVI patients. A combination of both might help to predict procedural risk and outcome better.

Evaluation of two commercially available ELISA kits for the determination of melatonin concentrations in amniotic fluid throughout pregnancy.

Background The aim of the present study is to evaluate the utility of extraction versus non-extraction-based commercial melatonin ELISA kits for determining the melatonin concentration in amniotic fluid obtained in early and late pregnancy. Methods Pregnancy duration less than 28 weeks was defined as early and from 28 weeks until delivery as late gestation. Nine samples were obtained in early and 18 in late pregnancy. Two commercially available melatonin ELISA kits (melatonin ELISA RE54021, including methanol-based extraction and direct saliva melatonin ELISA RE 54041, not including an extraction step, both from IBL-International, Germany) were used to determine melatonin concentrations in amniotic fluid. Results The mean melatonin concentration in ELISAs assayed by the non-extraction was significantly lower than those assayed after extraction. Subgroup analysis showed that there was no significant difference between melatonin concentration measured by non-extraction versus extraction ELISA in early pregnancy (11.2 ± 7.4 vs. 12.2 ± 7.7, respectively, P = 0.463) but that the mean melatonin concentration in late pregnancy was significantly lower when assayed by non-extraction ELISA than when assayed by extraction ELISA (14.8 ± 9.3 vs. 145.1 ± 179.3, respectively; P < 0.001). Agreement between both measurements in late pregnancy was rather poor (r2 = 0.271, P = 0.022), as opposed to the good correlation found in early pregnancy (r2 = 0.929, P < 0.001). Conclusions The present study revealed that a melatonin assay without an extraction step, such as direct saliva ELISA, does not seem to be a valid method to determine the melatonin concentration of amniotic fluid, especially in late gestation.

Soluble ST2 for Risk Stratification and the Prediction of Mortality in Patients Undergoing Transcatheter Aortic Valve Implantation.

This study aimed to assess the prognostic value of soluble ST2 (sST2) for risk stratification in patients undergoing transcatheter aortic valve implantation (TAVI). In 461 patients undergoing TAVI, sST2 was determined at baseline and categorized into quartiles. An optimum cutoff of 29 ng/ml was calculated. Primary end point was 1-year all-cause mortality. Results were validated in an independent cohort. Patients with sST2 >29 ng/ml had an increased 30-day (9.7% vs 4.6%, p = 0.043) and 1-year mortality (38.1% vs 21.8%, p = 0.001). In accordance, patients with N-terminal pro-brain natriuretic peptide (NT-proBNP) >8145 pg/ml revealed a comparable 30-day mortality (7.9% vs 4.7%, p = 0.189) and 1-year mortality (39.5% vs 21.0%, p <0.001). In univariate regression analysis, sST2 and NT-proBNP were associated with increased mortality risk. In multivariate regression analysis, independent predictors of mortality were logistic EuroSCORE, chronic renal failure, left ventricular ejection fraction, and sST2. In receiver operating characteristic curve analysis, sST2 did not provide incremental prognostic information beyond that obtained from surgical risk scores such as the STS-PROM or NT-proBNP. Similar findings could be achieved in an independent validation cohort. In conclusion, sST2 is independently associated with adverse outcome after TAVI but was not superior to NT-proBNP or surgical risk scores for the prediction of postprocedural outcomes.

Periprocedural Myocardial Injury Depends on Transcatheter Heart Valve Type But Does Not Predict Mortality in Patients After Transcatheter Aortic Valve Replacement.

OBJECTIVES: The aims of this study were to determine plasma elevations of biomarkers of myocardial injury associated with transfemoral (TF) transcatheter aortic valve replacement (TAVR) and to evaluate their prognostic value. BACKGROUND: Increases in biomarkers of myocardial injury are a common finding after TAVR, but their clinical significance is unclear. METHODS: In 756 consecutive TF TAVR patients, cardiac high-sensitivity troponin I (hsTnI) and creatine kinase MB (CK-MB) levels were measured at pre-defined time points to assess the occurrence of myocardial injury (defined as 15 times the upper reference limit for hsTnI [≥1.5 ng/ml] or 5 times the upper reference limit for CK-MB [≥18 µg/l]) during the first 72 h. The primary endpoint was all-cause mortality at 1 year. RESULTS: After uneventful TF TAVR, hsTnI was elevated in 51.6% and CK-MB in 7.4% of patients, respectively. Myocardial injury was associated with transcatheter heart valve (THV) type: patients who received the LOTUS THV more frequently had myocardial injury compared with those who received other THVs (LOTUS, 81.6%; Direct Flow Medical, 56.4%; CoreValve, 51.2%; Evolut R, 42.7%; SAPIEN XT, 40.4%; SAPIEN 3, 36.6%; p < 0.001). Myocardial injury defined by hsTnI was not associated with adverse outcomes at 30 days (3.1% vs. 2.7%; p = 0.778) or 1 year (16.7% vs. 17.2%; p = 0.841). Likewise, a CK-MB increase was not associated with 30-day mortality (5.5% vs. 2.8%; p = 0.258) or 1-year mortality (16.4% vs. 17.3%; p = 0.856). CONCLUSIONS: Myocardial injury is common following TF TAVR. The extent of cardiac biomarker elevation depends on THV type but is not associated with adverse short- and long-term outcomes after uneventful TAVR.