Medical Care as Flea Market Bargaining? An International Interdisciplinary Study of Varieties of Shared Decision Making in Physician-Patient Interactions.

Phenomenon: Shared decision making (SDM) is a core ideal in the interaction between healthcare providers and patients, but the implementation of the SDM ideal in clinical routines has been a relatively slow process. Approach: In a sociological study, 71 interactions between physicians and simulated patients enacting chronic heart failure were video-recorded in China, Germany, the Netherlands, and Turkey as part of a quasi-experimental research design. Participating physicians varied in specialty and level of experience. The secondary analysis presented in this article used content analysis to study core components of SDM in all of the 71 interactions and a grounded theory approach to observe how physicians responded actively to patients even though they did not actively employ the SDM ideal. Findings: Full realization of the SDM ideal remains an exception, but various aspects of SDM in physician-patient interaction were observed in all four locations. Analyses of longer interactions show dynamic processes of interaction that sometimes surprised both patient and physician. We observed varieties of SDM that differ from the SDM ideal but arguably achieve what the SDM ideal is intended to achieve. Our analysis suggests a need to revisit the SDM ideal-to consider whether varieties of SDM may be acceptable, even valuable, in their own right. Insights: The gap between the SDM ideal and SDM as implemented in clinical practice may in part be explained by the tendency of medicine to define and teach SDM through a narrow lens of checklist evaluations. The authors support the argument that SDM defies a checklist approach. SDM is not uniform, but nuanced, dependent on circumstances and setting. As SDM is co-produced by patients and physicians in a dynamic process of interaction, medical researchers should consider and medical learners should be exposed to varieties of SDM-related practice rather than a single idealized model. Observing and discussing worked examples contributes to the physician's development of realistic expectations and personal professional growth.

Predictors of adverse diastolic remodeling in non-diabetic patients presenting with ST-elevation myocardial infarction.

BACKGROUND: Adverse systolic remodeling after ST-elevation myocardial infarction (STEMI) is associated with poor clinical outcomes. However, little is known about diastolic remodeling. The purpose of this study was to identify the factors leading to diastolic remodeling. METHODS: Echocardiography was performed during hospitalization and at 4 months follow-up in 267 non-diabetic STEMI patients from the GIPS-III trial. As parameters of diastolic remodeling we used (1.) the E/e' at 4 months adjusted for the E/e' at hospitalization and (2.) the change in E/e' between hospitalization and 4 months. Multivariable regression models correcting for age and sex were constructed to identify possible association of clinical and angiographic variables as well as biomarkers with diastolic remodeling. RESULTS: Older age, female gender, hypertension, multi vessel disease, higher glucose and higher peak CK were independent predictors of higher E/e' at 4 months in a multivariable model (R2:0.20). After adjustment for E/e' during hospitalization only female gender, multivessel disease and higher glucose remained predictors of E/e' at four months (R2:0.40). Lower myocardial blush grade, AST and NT-proBNP were independent predictors of a higher increase of E/e' between hospitalization and at 4 months in a multivariable model (R2:0.08). CONCLUSIONS: Our data supports the hypothesis that female gender, multivessel coronary artery disease, and microvascular damage are important predictors of adverse diastolic remodeling after STEMI. In addition, our data suggests that older age and hypertension prior to STEMI may have contributed to worse pre-existing diastolic function. TRIAL REGISTRATION: NIH, NCT01217307. Prospectively registered on October 8th 2010, https://clinicaltrials.gov/ct2/show/NCT01217307 .

Hearts in their hands-Physicians' gestures embodying shared professional knowledge around the world.

The biomedical approach to medical knowledge is widely accepted around the world. This article considers whether the incorporated aspects of physician-patient interaction have become similarly common across the globe by comparing the gestures that physicians use in their interactions with patients. Up to this point, there has been little research on physicians' use of gestures in health-care settings. We explore how-in four university hospitals in Turkey, the People's Republic of China, The Netherlands and Germany-physicians use gesture in their discussions with simulated patients about the condition of heart failure. Our analysis confirms the importance of gestures for organising both the personal interaction and the knowledge transfer between physician and patient. From the perspective of global comparison, it is notable that physicians in all four hospitals used similar gestures. This demonstrates the globality of biomedical knowledge in an embodied mode. Physicians used gestures for a range of purposes, including to convey the idea of an 'anatomical map' and for constructing visual models of (patho-)physiological processes. Since biomedical language is rife with metaphor, it was not surprising that we also identified an accompanying metaphorical gesture which has a similar form in the various locations that were part of the study.

Rationale and Design of the Groningen Intervention Study for the Preservation of Cardiac Function with Sodium Thiosulfate after St-segment Elevation Myocardial Infarction (GIPS-IV) trial.

BACKGROUND: Ischemia and subsequent reperfusion cause myocardial injury in patients presenting with ST-segment elevation myocardial infarction (STEMI). Hydrogen sulfide (H2S) reduces "ischemia-reperfusion injury" in various experimental animal models, but has not been evaluated in humans. This trial will examine the efficacy and safety of the H2S-donor sodium thiosulfate (STS) in patients presenting with a STEMI. STUDY DESIGN: The Groningen Intervention study for the Preservation of cardiac function with STS after STEMI (GIPS-IV) trial (NCT02899364) is a double-blind, randomized, placebo-controlled, multicenter trial, which will enroll 380 patients with a first STEMI. Patients receive STS 12.5 grams intravenously or matching placebo in addition to standard care immediately at arrival at the catheterization laboratory after providing consent. A second dose is administered 6 hours later at the coronary care unit. The primary endpoint is myocardial infarct size as quantified by cardiac magnetic resonance imaging 4 months after randomization. Secondary endpoints include the effect of STS on peak CK-MB during admission and left ventricular ejection fraction and NT-proBNP levels at 4 months follow-up. Patients will be followed-up for 2 years to assess clinical endpoints. CONCLUSIONS: The GIPS-IV trial is the first study to determine the effect of a H2S-donor on myocardial infarct size in patients presenting with STEMI.

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.

Plasma syndecan-1 in hemodialysis patients associates with survival and lower markers of volume status.

Syndecan-1, a transmembrane heparan sulfate proteoglycan, associates with renal and cardiovascular functioning. We earlier reported syndecan-1 to be involved in renal tubular regeneration. We now examined plasma values of syndecan-1 in a hemodialysis cohort and its association with volume and inflammatory and endothelial markers in addition to outcome. Eighty-four prevalent hemodialysis patients were evaluated for their plasma syndecan-1 levels by ELISA before the start of hemodialysis, as well as 60, 180, and 240 min after start of dialysis. Patients were divided into sex-stratified tertiles based on predialysis plasma syndecan-1 levels. We studied the association between plasma levels of syndecan-1 and volume, inflammation, and endothelial markers and its association with cardiovascular events and all-cause mortality using Kaplan-Meier curves and Cox regression analyses with adjustments for gender, age, diabetes, and dialysis vintage. Predialysis syndecan-1 levels were twofold higher in men compared with women ( P = 0.0003). Patients in the highest predialysis plasma syndecan-1 tertile had a significantly higher ultrafiltration rate ( P = 0.034) and lower plasma values of BNP ( P = 0.019), pro-ANP ( P = 0.024), and endothelin ( P < 0.0001) compared with the two lower predialysis syndecan-1 tertiles. No significant associations with inflammatory markers were found. Cox regression analysis showed that patients in the highest syndecan-1 tertile had significantly less cardiovascular events and better survival compared with the lowest syndecan-1 tertile ( P = 0.02 and P = 0.005, respectively). In hemodialysis patients, higher plasma syndecan-1 levels were associated with lower concentrations of BNP, pro-ANP, and endothelin and with better patient survival. This may suggest that control of volume status in hemodialysis patients allows an adaptive tissue regenerative response as reflected by higher plasma syndecan-1 levels.

Effect of isolated ultrafiltration and isovolemic dialysis on myocardial perfusion and left ventricular function assessed with 13N-NH3 positron emission tomography and echocardiography.

Hemodialysis is associated with a fall in myocardial perfusion and may induce regional left ventricular (LV) systolic dysfunction. The pathophysiology of this entity is incompletely understood, and the contribution of ultrafiltration and diffusive dialysis has not been studied. We investigated the effect of isolated ultrafiltration and isovolemic dialysis on myocardial perfusion and LV function. Eight patients (7 male, aged 55 ± 18 yr) underwent 60 min of isolated ultrafiltration and 60 min of isovolemic dialysis in randomized order. Myocardial perfusion was assessed by 13N-NH3 positron emission tomography before and at the end of treatment. LV systolic function was assessed by echocardiography. Regional LV systolic dysfunction was defined as an increase in wall motion score in ≥2 segments. Isolated ultrafiltration (ultrafiltration rate 13.6 ± 3.9 ml·kg-1·h-1) induced hypovolemia, whereas isovolemic dialysis did not (blood volume change -6.4 ± 2.2 vs. +1.3 ± 3.6%). Courses of blood pressure, heart rate, and tympanic temperature were comparable for both treatments. Global and regional myocardial perfusion did not change significantly during either isolated ultrafiltration or isovolemic dialysis and did not differ between treatments. LV ejection fraction and the wall motion score index did not change significantly during either treatment. Regional LV systolic dysfunction developed in one patient during isolated ultrafiltration and in three patients during isovolemic dialysis. In conclusion, global and regional myocardial perfusion was not compromised by 60 min of isolated ultrafiltration or isovolemic dialysis. Regional LV systolic dysfunction developed during isolated ultrafiltration and isovolemic dialysis, suggesting that, besides hypovolemia, dialysis-associated factors may be involved in the pathogenesis of hemodialysis-induced regional LV dysfunction.

Strong predictive value of mannose-binding lectin levels for cardiovascular risk of hemodialysis patients.

BACKGROUND: Hemodialysis patients have higher rates of cardiovascular morbidity and mortality compared to the general population. Mannose-binding lectin (MBL) plays an important role in the development of cardiovascular disease. In addition, hemodialysis alters MBL concentration and functional activity. The present study determines the predictive value of MBL levels for future cardiac events (C-event), cardiovascular events (CV-event) and all-cause mortality in HD patients. METHODS: We conducted a prospective study of 107 patients on maintenance hemodialysis. Plasma MBL, properdin, C3d and sC5b-9 was measured before and after one dialysis session. The association with future C-events, CV-events, and all-cause mortality was evaluated using Cox regression models. RESULTS: During median follow-up of 27 months, 36 participants developed 21 C-events and 36 CV-events, whereas 37 patients died. The incidence of C-events and CV-events was significantly higher in patients with low MBL levels (<319 ng/mL, lower quartile). In fully adjusted models, low MBL level was independently associated with increased CV-events (hazard ratio 3.98; 95 % CI 1.88-8.24; P < 0.001) and C-events (hazard ratio 3.96; 95 % CI 1.49-10.54; P = 0.006). No association was found between low MBL levels and all-cause mortality. Furthermore, MBL substantially improved risk prediction for CV-events beyond currently used clinical markers. CONCLUSIONS: Low MBL levels are associated with a higher risk for future C-events and CV-events. Therefore, MBL levels may help to identify hemodialysis patients who are at risk to develop cardiovascular disease.

Fibroblast growth factor 23 correlates with volume status in haemodialysis patients and is not reduced by haemodialysis.

BACKGROUND: Recent data suggest a role for fibroblast growth factor 23 (FGF-23) in volume regulation. In haemodialysis patients, a large ultrafiltration volume (UFV) reflects poor volume control, and both FGF-23 and a large UFV are risk factors for mortality in this population. We studied the association between FGF-23 and markers of volume status including UFV, as well as the intradialytic course of FGF-23, in a cohort of haemodialysis patients. METHODS: We carried out observational, post hoc analysis of 109 prevalent haemodialysis patients who underwent a standardized, low-flux, haemodialysis session with constant ultrafiltration rate. We measured UFV, plasma copeptin and echocardiographic parameters including cardiac output, end-diastolic volume and left ventricular mass index at the onset of the haemodialysis session. We measured the intradialytic course of plasma C-terminal FGF-23 (corrected for haemoconcentration) and serum phosphate levels at 0, 1, 3 and 4 h after onset of haemodialysis and analysed changes with linear mixed effect model. RESULTS: Median age was 66 (interquartile range: 51-75) years, 65% were male with a weekly Kt/V 4.3 ± 0.7 and dialysis vintage of 25.4 (8.5-52.5) months. In univariable analysis, pre-dialysis plasma FGF-23 was associated with UFV, end-diastolic volume, cardiac output, early diastolic velocity e' and plasma copeptin. In multivariable regression analysis, UFV correlated with FGF-23 (standardized ß: 0.373, P < 0.001, model R(2): 57%), independent of serum calcium and phosphate. The association between FGF-23 and echocardiographic volume markers was lost for all but cardiac output upon adjustment for UFV. Overall, FGF-23 levels did not change during dialysis [7627 (3300-13 514) to 7503 (3109-14 433) RU/mL; P = 0.98], whereas phosphate decreased (1.71 ± 0.50 to 0.88 ± 0.26 mmol/L; P < 0.001). CONCLUSIONS: FGF-23 was associated with volume status in haemodialysis patients. The strong association with UFV suggests that optimization of volume status, for example by more intensive haemodialysis regimens, may also benefit mineral homeostasis. A single dialysis session did not lower FGF-23 levels.

Hemodialysis-induced regional left ventricular systolic dysfunction and inflammation: a cross-sectional study.

BACKGROUND: Hemodialysis may acutely induce regional left ventricular (LV) systolic dysfunction, which is associated with increased mortality and progressive heart failure. We tested the hypothesis that hemodialysis-induced regional LV systolic dysfunction is associated with inflammation and endothelial injury. Additionally, we studied whether hemodialysis-induced LV systolic dysfunction is associated with an exaggerated bioincompatibility reaction to hemodialysis. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 105 hemodialysis patients on a thrice-weekly dialysis schedule were studied between March 2009 and March 2010. PREDICTORS: Plasma indexes of inflammation (high-sensitivity C-reactive protein, pentraxin 3 [PTX3], interleukin 6 [IL-6], and IL-6:IL-10 ratio), bioincompatibility (leukocytes, neutrophils, complement C3, and myeloperoxidase), and endothelial function (soluble intercellular adhesion molecule 1 [ICAM-1], von Willebrand factor, proendothelin, and endothelin) were measured just before dialysis and at 60, 180, and 240 minutes intradialysis. OUTCOMES: Hemodialysis-induced regional LV systolic function. Wall motion score was measured by echocardiography at 30 minutes predialysis, 60 and 180 minutes intradialysis, and 30 minutes postdialysis. We defined hemodialysis-induced regional LV systolic dysfunction as an increase in wall motion score in 2 or more segments. RESULTS: Patients with hemodialysis-induced regional LV systolic dysfunction (n=29 [27%]) had significantly higher predialysis high-sensitivity C-reactive protein, PTX3, IL-6, and lL-6:IL-10 ratio values. Predialysis levels of bioincompatibility and endothelial markers did not differ between groups. Intradialysis courses of markers of inflammation, bioincompatibility, and endothelial function did not differ in patients with versus without hemodialysis-induced regional LV systolic dysfunction. LIMITATIONS: Coronary angiography or computed tomography for quantification of coronary calcifications in our patients was not performed; therefore, we could not relate markers of inflammation to the extent of atherosclerosis. CONCLUSIONS: Patients with hemodialysis-induced regional LV systolic dysfunction have a proinflammatory cytokine profile. There was no indication of an association with an exaggerated bioincompatibility reaction to hemodialysis.

Changes in left ventricular diastolic function during hemodialysis sessions.

BACKGROUND: Left ventricular diastolic dysfunction is common in hemodialysis patients and is associated with worse outcome. Previous studies have shown that diastolic function worsens from pre- to post-dialysis session, but this has not been studied during hemodialysis. We studied the evolution of diastolic function parameters early and late during hemodialysis. STUDY DESIGN: Observational study. SETTING & PARTICIPANTS: 109 hemodialysis patients on a thrice-weekly dialysis schedule with a mean age of 62.5 ± 15.6 (SD) years were studied between March 2009 and March 2010. PREDICTOR: Hemodialysis with constant ultrafiltration rate and dialysate conductivity. OUTCOMES: Changes in diastolic function parameters. MEASUREMENTS: Mitral early inflow (E) and tissue Doppler early diastolic velocity (mean e') were evaluated by echocardiography predialysis, at 60 and 180 minutes intradialysis, and postdialysis. Relative blood volume changes were calculated from changes in hematocrit. RESULTS: Predialysis E and mean e' were 0.93 ± 0.24 m/s and 6.6 ± 2.1 cm/s, respectively. E and mean e' values decreased significantly during hemodialysis (P < 0.001). The steepest change occurred at 60 minutes intradialysis (E, -21.4% ± 17.6% and -30.5% ± 19.2% at 60 and 180 minutes, respectively; mean e', -16.0% ± 18.6% and -19.5% ± 21.8% at 60 and 180 minutes, respectively). At 60 minutes intradialysis, changes in relative blood volume and brain natriuretic peptide level were associated significantly with the change in E but not with the change in mean e'. LIMITATIONS: Changes in relative blood volume may not fully reflect central blood volume changes and do not capture the effect of blood loss to the extracorporal circuit. Left atrial volume was not measured. CONCLUSIONS: Left ventricular diastolic function worsens early during a hemodialysis session. The decrease in mean e' at 60 minutes intradialysis was unrelated to changes in relative blood volume. Although this finding does not exclude a role of hypovolemia because of the limitations of the measurement of relative blood volume, it raises the possibility that non-volume-related mechanisms are involved in the early decrease in mean e' during hemodialysis.

Cardiovascular Implantable Electronic Devices Enabled Remote Heart Failure Monitoring; What We Have Learned and Where to Go Next.

Despite recent developments, heart failure (HF) remains to be a great burden to the individual patient, entailing major morbidity and mortality. Moreover, HF is a great burden to overall healthcare, mainly because of frequent hospitalizations. Timely diagnosis of HF deterioration and implementation of appropriate therapy may prevent hospitalization and eventually improve a patient's prognosis; however, depending on the patient's presentation, the signs and symptoms of HF often offer too little therapeutic window to prevent hospitalizations. Cardiovascular implantable electronic devices (CIEDs) can provide real-time physiologic parameters and remote monitoring of these parameters can potentially help to identify patients at high risk. However, routine implementation of remote monitoring of CIEDs has still not been widely used in daily patient care. This review gives a detailed description of available metrics for remote HF monitoring, the studies that provide evidence of their efficacy, ways to implement them in clinical HF practice, as well as lessons learned on where to go on from where we currently are.

Differences in shuntflow (Qa), cardiac function and mortality between hemodialysis patients with a lower-arm fistula, an upper-arm fistula, and an arteriovenous graft.

BACKGROUND: High-flow vascular accesses may contribute to cardiovascular morbidity and mortality in hemodialysis patients. Since shuntflow (Qa) varies between vascular access types, the current study aims to investigate differences in left ventricular hypertrophy (LVH), systolic and diastolic function parameters, and all-cause mortality between patients with a lower-arm arteriovenous fistula (AVF), an upper-arm AVF, and an arteriovenous graft (AVG). METHODS: A post hoc analysis of 100 patients was performed in a single-center, prospective observational study. Echocardiography examinations were performed prior to the dialysis session. Qa measurements were performed using ultrasound dilution. Patient groups were categorized by vascular access type. Cox proportional hazards models were used to investigate the association of shunt type with all-cause mortality with adjustment for potential confounders including, amongst others, age, sex, diabetes, the duration of hemodialysis treatment, shunt vintage, and Qa. RESULTS: Patients with an upper-arm AVF had significantly (p < 0.001) higher Qa (median 1902, IQR 1223-2508 ml/min) compared to patients with a lower-arm AVF (median 891, IQR 696-1414 ml/min) and patients with an AVG (median 881, IQR 580-1157 ml/min). The proportion of patients with LVH and systolic and diastolic echocardiographic parameters did not differ significantly between groups. Survival analysis showed that an upper-arm AVF was associated with a significantly lower all-cause mortality (p = 0.04) compared to a lower-arm AVF. CONCLUSIONS: Patients with an upper-arm fistula had a higher Qa but similar systolic and diastolic cardiac function. Patients with an upper-arm fistula had a significantly lower risk of all-cause mortality compared with patients with a lower-arm fistula.

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

BACKGROUND: Ischemia-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). METHODS: FTs 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). RESULTS: Serum 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, ß = -0.87 for infarct size, 95% confidence interval (CI): -1.75 to -0.001, P = 0.050; ß = 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)(ß = 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). CONCLUSIONS: Changes 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.

Sodium Thiosulfate in Acute Myocardial Infarction: A Randomized Clinical Trial.

In this proof-of-principle trial, the hypothesis was investigated that sodium thiosulfate (STS), a potent antioxidant and hydrogen sulfide donor, reduces reperfusion injury. A total of 373 patients presenting with a first ST-segment elevation myocardial infarction received either 12.5 g STS intravenously or matching placebo at arrival at the hospital and 6 hours later. The primary outcome, infarct size, measured by cardiac magnetic resonance at 4 months after randomization, did not differ between the treatment arms. Secondary outcomes were comparable as well, suggesting no clinical benefit of STS in this population at relatively low risk for large infarction.

Systemic oxidative stress associates with disease severity and outcome in patients with new-onset or worsening heart failure.

BACKGROUND: Oxidative stress may be a key pathophysiological mediator in the development and progression of heart failure (HF). The role of serum-free thiol concentrations, as a marker of systemic oxidative stress, in HF remains largely unknown. OBJECTIVE: The purpose of this study was to investigate associations between serum-free thiol concentrations and disease severity and clinical outcome in patients with new-onset or worsening HF. METHODS: Serum-free thiol concentrations were determined by colorimetric detection in 3802 patients from the BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF). Associations between free thiol concentrations and clinical characteristics and outcomes, including all-cause mortality, cardiovascular mortality, and a composite of HF hospitalization and all-cause mortality during a 2-years follow-up, were reported. RESULTS: Lower serum-free thiol concentrations were associated with more advanced HF, as indicated by worse NYHA class, higher plasma NT-proBNP (P < 0.001 for both) and with higher rates of all-cause mortality (hazard ratio (HR) per standard deviation (SD) decrease in free thiols: 1.253, 95% confidence interval (CI): 1.171-1.341, P < 0.001), cardiovascular mortality (HR per SD: 1.182, 95% CI: 1.086-1.288, P < 0.001), and the composite outcome (HR per SD: 1.058, 95% CI: 1.001-1.118, P = 0.046). CONCLUSIONS: In patients with new-onset or worsening HF, a lower serum-free thiol concentration, indicative of higher oxidative stress, is associated with increased HF severity and poorer prognosis. Our results do not prove causality, but our findings may be used as rationale for future (mechanistic) studies on serum-free thiol modulation in heart failure. Associations of serum-free thiol concentrations with heart failure severity and outcomes.

Comparison of cardiac positron emission tomography perfusion defects during stress induced by hemodialysis versus adenosine.

The cardiac stress imposed by hemodialysis may differ from that induced by pharmacologic agents used for myocardial perfusion imaging-based stress testing. With repetitive intradialytic [(13)N]ammonia positron emission tomography, we showed that standard hemodialysis had an acute adverse effect on cardiac perfusion and left ventricular function that was not detected by standard diagnostic adenosine stress testing.

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 (ß-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: ß = 1.56; 95% confidence interval: 0.29-2.83; P = 0.016) and lower LVEF (ß = -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).