Hemodialysis-induced left ventricular dysfunction:Identification of prevalence, triggers, and prognostic impact

Hemodynamische instabiliteit is één van de meest voorkomende complicaties van hemodialyse. De onderzoeken, die beschreven staan in dit proefschrift, laten zien dat de huidige conventionele hemodialyse procedure acute schadelijke effecten heeft op de linker kamer functie. Ongeveer een kwart van de onderzochte dialysepatienten ontwikkelde tijdens hemodialyse regionale wandbewegingsstoornissen van de linker hartkamer. De ontwikkeling van deze hemodialyse-geïnduceerde regionale linker kamer disfunctie was geassocieerd met een hogere mortaliteit en het vaker voorkomen van cardiale problemen. Patienten, die tijdens hemodialyse regionale linker kamer disfunctie ontwikkelden, hadden een hogere concentratie van diverse ontstekingsmarkers in het bloed. Vervolgonderzoek zal duidelijk moeten maken wat de exacte rol is van de verhoogde ontstekingmarkers en of het mogelijk is om het optreden van linker kamerdisfunctie te voorkomen

Sex differences in leukocyte profile in ST-elevation myocardial infarction patients

BACKGROUND: Whether sex differences exist in the inflammatory response after ST-elevation myocardial infarction (STEMI) remains to be elucidated. We studied leukocyte profiles and their prognostic value in men and women presenting with STEMI. METHODS: From a total of 552 consecutive STEMI patients, blood samples were collected at hospital admission. Linear regression was used to assess the relationship between leukocyte profiles and enzymatic infarct size. Cox regression was used to assess the association between leukocyte profiles and one-year mortality. RESULTS: Women presented with higher lymphocyte counts (2.3·109 cells/L (IQR 1.6-3.1) vs. 1.8·109 cells/L (IQR 1.4-2.5), p = 3.00 ∙ 10-4) and percentages (21.1% (IQR 14.4-28.1) vs. 17.1% (IQR 12.3-24.3), p = 0.004). Lymphocyte to monocyte ratio (LMR) was also higher in women (3.25 (IQR 2.56-4.5) vs. 2.68 (IQR 2.08-3.59), p = 7.28 ∙ 10-7). Higher LMR was associated with lower peak CK-MB (β = -0.27 (95% CI: -0.50, -0.03), p = 0.026), lower peak troponin T (β = -0.45 (95% CI: -0.77, -0.13), p = 0.006) and lower one-year mortality risk (HR 0.35 (95% CI: 0.13, 0.96), p = 0.042). CONCLUSION: At admission for STEMI, women present with higher lymphocyte count and LMR. Higher LMR is associated with smaller infarct size and decreased one-year mortality risk and could be used as a biomarker to predict outcome

Associations of systemic oxidative stress with functional outcomes after ST-segment elevation myocardial infarction

BackgroundIschemia-reperfusion is accompanied by oxidative stress. Serum free thiols (FTs; sulfhydryl groups) reliably reflect systemic oxidative stress. This study evaluates longitudinal changes in FTs and their associations with outcomes after ST-segment elevation myocardial infarction (STEMI).MethodsFTs were detected in archived serum samples from 378 participants of a neutral randomized trial on metformin therapy after STEMI. FT levels were determined at presentation with STEMI and at 24 h, 2 weeks, 4 months and 1 year thereafter. Outcomes included infarct size and left ventricular ejection fraction (LVEF), both determined with cardiac magnetic resonance imaging after 4 months, and 5-year major adverse cardiovascular events (MACE).ResultsSerum FT concentrations at presentation and at 24 h were 356 ± 91 and 353 ± 76 μmol/L, respectively. The change in FTs between presentation and 24 h (ΔFTs) was associated with outcomes in age- and sex-adjusted analysis (per 100 μmol/L FT increase, β = −0.87 for infarct size, 95%-confidence interval (CI): −1.75 to −0.001, P = 0.050; β = 1.31, 95%-CI: 0.37 to 2.25 for LVEF, P = 0.007). Associations between ΔFTs and LVEF were markedly stronger in patients with Thrombolysis in Myocardial Infarction flow of 0 or 1 before percutaneous coronary intervention (PCI)(β = 2.73, 95%-CI: 0.68 to 4.77, P = 0.009). Declining FTs during the first 24 h might be associated with higher incidence of 5-year MACE (P = 0.09).ConclusionsChanges in oxidative stress early post-PCI may predict functional outcomes after STEMI. Our findings warrant validation in larger cohorts, and then may be used as rationale for development of thiol-targeted therapy in ischemic heart disease

Safety and Tolerability of Sodium Thiosulfate in Patients with an Acute Coronary Syndrome Undergoing Coronary Angiography:A Dose-Escalation Safety Pilot Study (SAFE-ACS)

Background. In animal studies, hydrogen sulfide (H2S) has been shown to protect the heart from ischemia-reperfusion injury. This study evaluates the safety and tolerability of the H2S donor sodium thiosulfate (STS) in patients with acute coronary syndrome (ACS). Methods. Eighteen patients, undergoing coronary angiography for ACS, received STS intravenously immediately after arrival at the catheterization laboratory according to a “3 + 3 dose-escalation design” with fixed dosing endpoint (0, 2.5, 5, 10, 12.5, and 15 grams). This first dose STS was combined with verapamil and nitroglycerin required for transradial procedures. A second dose STS was administered 6 hours later. Primary endpoint was dose-limiting toxicity, defined as significant hemodynamic instability or death up to 24 hours or before discharge from the coronary care unit. Secondary outcomes included the occurrence of anaphylaxis, nausea, vomiting, and systolic blood pressure (SBP) course. Results. Sixteen patients received two dosages of STS and two patients one dosage. None of the patients reached the primary endpoint, nor experienced a serious adverse event. We observed a clinically well-tolerated decline in SBP 1 hour after administration of the first STS dose and concomitant verapamil/nitroglycerin. SBP for all patients together reduced 16.8 (8.1–25.5) mmHg (P=0.0008). No significant decline in SBP occurred after the second dose. Mild nausea was observed in one patient. Conclusion. This is the first report on sodium thiosulfate administration in patients with acute coronary syndromes. Our data suggest that sodium thiosulfate was well tolerated in this setting. The potential benefit of this intervention has to be examined in larger studies

Association of Circulating Ketone Bodies With Functional Outcomes After ST-Segment Elevation Myocardial Infarction

Background: Circulating ketone bodies (KBs) are increased in patients with heart failure (HF), corresponding with increased cardiac KB metabolism and HF severity. However, the role of circulating KBs in ischemia/reperfusion remains unknown. Objectives: This study sought to investigate longitudinal changes of KBs and their associations with functional outcomes in patients presenting with ST-segment elevation myocardial infarction (STEMI). Methods: KBs were measured in 369 participants from a randomized trial on early metformin therapy after STEMI. Nonfasting plasma concentrations of KBs (β-hydroxybutyrate, acetoacetate, and acetone) were measured by nuclear magnetic resonance spectroscopy at presentation, at 24 hours, and after 4 months. Myocardial infarct size and left ventricular ejection fraction (LVEF) were determined by cardiac magnetic resonance imaging at 4 months. Associations of circulating KBs with infarct size and LVEF were determined using multivariable linear regression analyses. Results: Circulating KBs were high at presentation with STEMI (median total KBs: 520 μmol/L; interquartile range [IQR]: 315-997 μmol/L). At 24 hours after reperfusion, KBs were still high compared with levels at 4-month follow-up (206 μmol/L [IQR: 174-246] vs 166 μmol/L [IQR: 143-201], respectively; P < 0.001). Increased KB concentrations at 24 hours were independently associated with larger myocardial infarct size (total KBs, per 100 μmol/L: β = 1.56; 95% confidence interval: 0.29-2.83; P = 0.016) and lower LVEF (β = −1.78; 95% CI: (−3.17 to −0.39; P = 0.012). Conclusions: Circulating KBs are increased in patients presenting with STEMI. Higher KBs at 24 hours are associated with functional outcomes after STEMI, which suggests a potential role for ketone metabolism in response to myocardial ischemia. (Metabolic Modulation With Metformin to Reduce Heart Failure After Acute Myocardial Infarction: Glycometabolic Intervention as Adjunct to Primary Coronary Intervention in ST Elevation Myocardial Infarction (GIPS-III): a Randomized Controlled Trial; NCT01217307

Renal Handling of Galectin-3 in the General Population, Chronic Heart Failure, and Hemodialysis

Background-Galectin-3 is a biomarker for prognostication and risk stratification of patients with heart failure (HF). It has been suggested that renal function strongly relates to galectin-3 levels. We aimed to describe galectin-3 renal handling in HF. Methods and Results-In Sprague-Dawley rats, we infused galectin-3 and studied distribution and renal clearance. Furthermore, galectin-3 was measured in urine and plasma of healthy controls, HF patients and hemodialysis patients. To mimic the human situation, we measured galectin-3 before and after the artificial kidney. Infusion in rats resulted in a clear increase in plasma and urine galectin-3. Plasma galectin-3 in HF patients (n=101; mean age 64 years; 93% male) was significantly higher compared to control subjects (n=20; mean age 58 years; 75% male) (16.6 ng/mL versus 9.7 ng/mL, P Conclusions-In this small cross-sectional study, we report that urine levels of galectin-3 are not increased in HF patients, despite substantially increased plasma galectin-3 levels. The impaired renal handling of galectin-3 in patients with HF may explain the described relation between renal function and galectin-3 and may account for the elevated plasma galectin-3 in HF