Effect of severity and etiology of chronic kidney disease in patients with heart failure with mildly reduced ejection fraction.

OBJECTIVE: The study investigates the prognostic impact of the severity and etiology of chronic kidney disease (CKD) in patients with heart failure with mildly reduced ejection fraction (HFmrEF). BACKGROUND: Data regarding the outcomes in patients with CKD in HFmrEF is scarce. METHODS: Consecutive patients with HFmrEF were retrospectively included at one institution from 2016 to 2022. Prognosis of patients with different stages and etiologies of CKD was investigated with regard to the primary endpoint of all-cause mortality at 30 months. RESULTS: A total of 2155 consecutive patients with HFmrEF were included with an overall prevalence of CKD of 31%. Even milder stages of CKD (i.e., KDIGO stage 3a) were associated with an increased risk of 30-months all-cause mortality (HR = 1.242; 95% CI 1.147-1.346; p = 0.001). However, long-term prognosis did not differ in patients with KDIGO stage 5 compared to patients with stage 4 (HR = 0.886; 95% CI 0.616-1.275; p = 0.515). Furthermore, the highest risk of HF-related rehospitalization was observed in patients with KDIGO stages 3b and 4 (log rank p ≤ 0.015), whereas patients with KDIGO stage 5 had a lower risk of HF-related rehospitalization compared to patients with KDIGO stage 4 (HR = 0.440; 95% CI 0.228-0.849; p = 0.014). In contrast, the etiology of CKD was not associated with the risk of 30-month all-cause mortality (log rank p ≥ 0.347) and HF-related rehospitalization (log rank p ≥ 0.149). CONCLUSION: In patients with HFmrEF, even milder stages of CKD were independently associated with increased risk of 30-months all-cause mortality.

Immunometric and functional measurement of endogenous vasoinhibin in human sera.

Introduction: Circulating levels of the antiangiogenic protein vasoinhibin, a fragment of prolactin, are of interest in vasoproliferative retinopathies, preeclampsia, and peripartum cardiomyopathy; however, it is difficult to determine the circulating levels of vasoinhibin due to the lack of quantitative assays. Methods: This study used human serum samples to assess the concentration and bioactivity of vasoinhibin using a novel enzyme-linked immunosorbent assay (ELISA) for human vasoinhibin, which employs an anti-vasoinhibin monoclonal antibody, a human umbilical vein endothelial cell (HUVEC) proliferation assay, and a chick chorioallantoic membrane (CAM) angiogenesis assay. Results: Serum samples from 17 pregnant women without (one group) and with preeclampsia and pregnancy induced hypertension (another group) demonstrated endogenous vasoinhibin concentrations in the range of 5-340 ng/ml. Immunoactive vasoinhibin levels were significantly higher in preeclampsia serum compared to healthy pregnancy serum (mean 63.09 ± 22.15 SD vs. 19.67 ± 13.34 ng/ml, p = 0.0003), as was the bioactive vasoinhibin level as determined by the HUVEC proliferation assay (56.12 ± 19.83 vs. 13.38 ± 4.88 ng/ml, p < 0.0001). There was a correlation between the concentration of vasoinhibin measured by ELISA and the HUVEC proliferation assay (Pearson r = 0.95, p < 0.0001). Healthy serum demonstrated a proangiogenic effect in the CAM assay (p < 0.05, compared to control), while serum from preeclamptic patients demonstrated an antiangiogenic effect (p < 0.05 vs. control), as did recombinant human vasoinhibin and a synthetic circular retro-inverse vasoinhibin analogue (CRIVi45-51). The antiangiogenic effects in the CAM assay and the inhibition of HUVEC proliferation were abolished by addition of the ELISA anti-vasoinhibin monoclonal antibody, but not by mouse IgG. Discussion: These results demonstrate the first quantitation of endogenous vasoinhibin in human sera and the elevation of it levels and antiangiogenic activity in sera from women with preeclampsia. The development and implementation of a quantitative assay for vasoinhibin overcomes a long-standing barrier and suggests the thorough clinical verification of vasoinhibin as a relevant biomarker.

Effect of anaemia and iron deficiency in heart failure with mildly reduced ejection fraction.

OBJECTIVE: The present study aims to clarify the prevalence and prognostic impact of anaemia and iron deficiency in patients with heart failure with mildly reduced ejection fraction (HFmrEF). BACKGROUND: The prognostic impact of anaemia and iron deficiency in HFmrEF has not yet been clarified. METHODS: Consecutive patients with HFmrEF were retrospectively included at one institution from 2016 to 2022. Patients with anaemia (i.e. haemoglobin <13 g/dL in males and < 12 g/dL in females) were compared to patients without, respectively patients with or without iron deficiency. The primary endpoint was all-cause mortality at 30 months (median follow-up), secondary endpoints comprised HF-related rehospitalisation. RESULTS: Two thousand one hundred and fifty four patients with HFmrEF with a median haemoglobin level of 12.2 g/dL were included. Anaemia was present in 52% of patients with HFmrEF and associated with a higher risk of all-cause mortality (44% vs. 18%; HR = 3.021; 95% CI 2.552-3.576; p =.001) and HF-related rehospitalisation (18% vs. 8%; HR = 2.351; 95% CI 1.819-3.040; p =.001) at 30 months, which was confirmed after multivariable adjustment. Although iron status was infrequently assessed in anaemics with HFmrEF (27%), the presence of iron deficiency was associated with higher risk of rehospitalisation for worsening HF (25% vs. 15%; HR = 1.746; 95% CI 1.024-2.976; p =.038), but not all-cause mortality (p =.279) at 30 months. CONCLUSION: Anaemia and iron deficiency are very common in atleast half of patients with HFmrEF and independently associated with adverse long-term prognosis.

Effect of Heart Failure Pharmacotherapies in Patients with Heart Failure with Mildly Reduced Ejection Fraction.

OBJECTIVE: The study sought to comprehensively investigate the effect of heart failure (HF) pharmacotherapies in patients with heart failure with mildly reduced ejection fraction (HFmrEF). BACKGROUND: In the absence of randomized controlled trials, guideline recommendations concerning HF-related therapies in patients with HFmrEF are limited. METHODS: Consecutive patients hospitalized with HFmrEF were retrospectively included at one institution from 2016 to 2022. The prognostic value of treatment with beta-blockers (BB), angiotensin-converting enzyme inhibitors, receptor blockers or receptor-neprilysin inhibitor (ACEi/ARB/ARNI), mineralocorticoid receptor antagonists (MRA) and sodium-glucose transport protein 2 inhibitors (SGLT2i) was investigated for all-cause mortality at 30 months (median follow-up) and HF-related rehospitalization. RESULTS: 2,109 patients with HFmrEF were included. Treatment with BB (27.0% vs. 35%; HR = 0.737; 95% CI 0.617-0.881; p = 0.001), ACEi/ARB/ARNI (25.9% vs. 37.6%; HR = 0.612; 95% CI 0.517-0.725; p = 0.001) and SGLT2i (11.9% vs. 29.5%; HR = 0.441; 95% CI 0.236-0.824; p = 0.010) was associated with lower risk of 30-months all-cause mortality, which was still demonstrated after multivariable adjustment and propensity score matching. In contrast, MRA treatment was not associated with long-term prognosis. The risk of HF-related rehospitalization was not affected by HF pharmacotherapies. Finally, the lowest risk of long-term all-cause mortality was observed in patients with combined use of BB, ACEi/ARB/ARNI and SGLT2i (HR = 0.456; 95% CI 0.227-0.916; p = 0.027). CONCLUSION: BB, ACEi/ARB/ARNI and SGLT2i were independently associated with lower risk of all-cause mortality in patients with HFmrEF, specifically when applied as combined "HF triple therapy". Randomized studies are needed to investigate the effect of HF-related pharmacotherapies in patients with HFmrEF.

Although heart failure with mildly reduced ejection fraction (HFmrEF) affects one out of four patients with heart failure (HF), limited evidence regarding HF pharmacotherapies for the treatment of patients with HFmrEF is available. The present study investigates the treatment with beta-blockers (BB), angiotensin-converting enzyme inhibitors, receptor blockers or receptor-neprilysin inhibitor (ACEi/ARB/ARNI), mineralocorticoid receptor antagonists (MRA) and sodium-glucose transport protein 2 inhibitors (SGLT2i) on long-term outcomes using a large registry-based dataset of 2,109 patients hospitalized with HFmrEF. Treatment with BB, ACEi/ARB/ARNI and SGLT2i was independently associated with a lower risk of long-term all-cause mortality, even after multivariable adjustment and propensity score matching, specifically when applied in combination. In contrast, MRA treatment was not associated with outcomes in the present study. The present study supports the evidence that patients with HFmrEF may benefit from HF pharmacotherapies similar than patients with HF with reduced ejection fraction (HFrEF).

Predictors and Prognostic Impact of Early Acute Kidney Injury in Cardiogenic Shock: Results from a Monocentric, Prospective Registry.

INTRODUCTION: The presence of acute kidney injury (AKI) was shown to increase the risk of mortality following acute myocardial infarction; however, data regarding the prognostic impact of early AKI in patients with concomitant cardiogenic shock (CS) is limited. The study investigates predictors and the prognostic impact of AKI in patients with CS. METHODS: Consecutive patients with CS from 2019 to 2021 were included at one institution. Laboratory values were retrieved from day of disease onset (day 1) and days 2, 3, 4, and 8 thereafter. Predictors for AKI (defined as an increase of plasma creatinine >50% within 48 h referring to pre-admission or baseline creatinine on day 1 and/or the need for continuous veno-venous hemodiafiltration [CVVHDF]) and the prognostic impact of early AKI with regard to 30-day all-cause mortality were assessed. Statistical analyses included t test, Spearman's correlation, C-statistics, Kaplan-Meier, and Cox proportional regression analyses. RESULTS: A total of 219 CS patients were included with an incidence of early CS-related AKI of 52%. With an area under the curve of up to 0.689 (p = 0.001), creatine discriminated 30-day mortality in CS. Increasing lactate levels (OR = 1.194; 95% CI: 1.083-1.316; p = 0.001; per increase of 1 mmol/L) was associated with the occurrence of AKI. The presence of AKI was associated with an increased risk of 30-day all-cause mortality (63% vs. 36%; HR = 2.138; 95% CI: 1.441-3.171; p = 0.001), even after multivariable adjustment (HR = 1.861; 95% CI: 1.207-2.869; p = 0.005). Finally, highest risk of all-cause mortality was observed in patients with AKI requiring CVVHDF (75% vs. 44%; log rank p = 0.001; HR = 2.211; 95% CI: 1.315-3.718; p = 0.003). CONCLUSION: Early AKI affects more than half of patients with CS and is independently associated with 30-day all-cause mortality in CS, with highest risk of death among patients with AKI requiring CVVHDF.

Prognostic Implications of Type 2 Diabetes Mellitus in Heart Failure with Mildly Reduced Ejection Fraction.

BACKGROUND: Data regarding the characterization and outcomes of diabetics with heart failure with a mildly reduced ejection fraction (HFmrEF) is scarce. This study investigates the prevalence and prognostic impact of type 2 diabetes in patients with HFmrEF. METHODS: Consecutive patients with HFmrEF (i.e., left ventricular ejection fraction 41-49% and signs and/or symptoms of HF) were retrospectively included at one institution from 2016 to 2022. Patients with type 2 diabetes (dia-betics) were compared to patients without (i.e., non-diabetics). The primary endpoint was all-cause mortality at 30 months. Statistical analyses included Kaplan-Meier, multivariable Cox regression analyses and propensity score matching. RESULTS: A total of 2169 patients with HFmrEF were included. The overall prevalence of type 2 diabetes was 36%. Diabetics had an increased risk of 30-months all-cause mortality (35.8% vs. 28.6%; HR = 1.273; 95% CI 1.092-1.483; p = 0.002), which was confirmed after multivariable adjustment (HR = 1.234; 95% CI 1.030-1.479; p = 0.022) and propensity score matching (HR = 1.265; 95% CI 1.018-1.572; p = 0.034). Diabetics had a higher risk of HF-related rehospitalization (17.8% vs. 10.7%; HR = 1.714; 95% CI 1.355-2.169; p = 0.001). Finally, the risk of all-cause mortality was increased in diabetics treated with insulin (40.7% vs. 33.1%; log-rank p = 0.029), whereas other anti-diabetic pharmacotherapies had no prognostic impact in HFmrEF. CONCLUSIONS: Type 2 diabetes is common and independently associated with adverse long-term prognosis in patients with HFmrEF.

Diagnostic and Prognostic Value of Aminoterminal Prohormone of Brain Natriuretic Peptide in Heart Failure with Mildly Reduced Ejection Fraction Stratified by the Degree of Renal Dysfunction.

Limited data concerning the diagnostic and prognostic value of blood-derived biomarkers in heart failure with mildly reduced ejection fraction (HFmrEF) is available. This study investigates the diagnostic and prognostic value of aminoterminal prohormone of brain natriuretic peptide (NT-proBNP) in patients with HFmrEF, stratified by the estimated glomerular filtration rate (eGFR). Consecutive patients with HFmrEF were retrospectively included at one institution from 2016 to 2022. First, the diagnostic value of NT-proBNP for acute decompensated heart failure (ADHF) was tested. Thereafter, the prognostic value of NT-proBNP levels was tested for 30-months all-cause mortality in patients with ADHF. From a total of 755 patients hospitalized with HFmrEF, the rate of ADHF was 42%. Patients with ADHF revealed higher NT-proBNP levels compared to patients without (median 5394 pg/mL vs. 1655 pg/mL; p = 0.001). NT-proBNP was able to discriminate ADHF with an area under the curve (AUC) of 0.777 (p = 0.001), with the highest AUC in patients with eGFR ≥ 60 mL/min (AUC = 0.800; p = 0.001), and no diagnostic value was seen in eGFR < 30 mL/min (AUC = 0.576; p = 0.210). Patients with NT-proBNP levels > 3946 pg/mL were associated with higher rates of all-cause mortality at 30 months (57.7% vs. 34.4%; HR = 2.036; 95% CI 1.423-2.912; p = 0.001), even after multivariable adjustment (HR = 1.712; 95% CI 1.166-2.512; p = 0.006). In conclusion, increasing NT-proBNP levels predicted the risk of ADHF and all-cause mortality in patients with HFmrEF and preserved renal function; however, NT-proBNP levels were not predictive in patients with HFmrEF and eGFR < 30 mL/min.

Prognosis of cardiogenic shock with and without acute myocardial infarction: results from a prospective, monocentric registry.

OBJECTIVE: The study investigates the prognostic impact of cardiogenic shock (CS) stratified by the presence or absence of acute myocardial infarction (AMI). BACKGROUND: Intensive care unit (ICU) related mortality in CS patients remains unacceptably high despite improvement concerning the treatment of CS patients. METHODS: Consecutive patients with CS from 2019 to 2021 were included monocentrically. The prognostic impact of CS related to AMI was compared to patients without AMI-related CS. The primary endpoint was 30-day all-cause mortality. Statistical analyses included Kaplan-Meier analyses, multivariable Cox proportional regression analyses and propensity score matching. RESULTS: 273 CS patients were included (AMI-related CS: 49%; non-AMI-related CS: 51%). The risk of 30-day all-cause mortality was increased in patients with AMI-related CS (64% vs. 47%; HR = 1.653; 95% CI 1.199-2.281; p = 0.002), which was still observed after multivariable adjustment (HR = 1.696; 95% CI 1.153-2.494; p = 0.007). Even after propensity score matching (i.e., 87 matched pairs), AMI was still an independent predictor of 30-day mortality (HR = 1.524; 95% CI 1.020-2.276; p = 0.040). In contrast, non-ST-segment AMI (NSTEMI) and STEMI were associated with comparable prognosis (log-rank p = 0.528). CONCLUSION: AMI-related CS was associated with increased 30-day all-cause mortality compared to patients with CS not related to AMI. In contrast, the prognosis of STEMI- and NSTEMI-CS patients was comparable.

C-reactive protein and procalcitonin during course of sepsis and septic shock.

OBJECTIVE: The study investigates the diagnostic and prognostic value of C-reactive protein (CRP) and procalcitonin (PCT) in patients with sepsis and septic shock. BACKGROUND: Limited data regarding the prognostic value of CRP and PCT during the course of sepsis or septic shock is available. METHODS: Consecutive patients with sepsis and septic shock from 2019 to 2021 were included monocentrically. Blood samples were retrieved from the day of disease onset (day 1), day 2, 3, 5, 7, and 10. Firstly, the diagnostic value of CRP and PCT for the diagnosis of a septic shock, as well as for the discrimination of positive blood cultures, was tested. Secondly, the prognostic value of the CRP and PCT was tested for 30-day all-cause mortality. Statistical analyses included univariable t-tests, Spearman's correlations, C-statistics, and Kaplan-Meier analyses. RESULTS: A total of 349 patients were included, of which 56% had a sepsis and 44% a septic shock on day 1. The overall rate of all-cause mortality at 30 days was 52%. With an area under the curve (AUC) of 0.861 on day 7 and 0.833 on day 10, the PCT revealed a superior AUC than the CRP (AUC 0.440-0.652) with regard to the discrimination between patients with sepsis and septic shock. In contrast, the prognostic AUCs for 30-day all-cause mortality were poor. Both higher CRP (HR = 0.999; 95% CI 0.998-1.001; p = 0.203) and PCT levels (HR = 0.998; 95% CI 0.993-1.003; p = 0.500) were not associated with the risk of 30-day all-cause mortality. During the first 10 days of ICU treatment, both CRP and PCT declined irrespective of clinical improvement or impairment. CONCLUSION: PCT was a reliable diagnostic tool for the diagnosis of septic shock compared to CRP. Both CRP and PCT were shown to have poor predictive value with regard to 30-day all-cause mortality and were not associated with the risk of all-cause mortality in patients admitted with sepsis or septic shock.

Levosulpiride for the treatment of diabetic macular oedema: a phase 2 randomized clinical trial.

BACKGROUND/OBJECTIVE: The prokinetic levosulpiride elevates vasoinhibin levels in the vitreous of patients with proliferative diabetic retinopathy (PDR) suggesting clinical benefits due to the anti-vasopermeability and anti-angiogenic properties of vasoinhibin. We investigated the biological activity of levosulpiride in centre-involving diabetic macular oedema (DME). PATIENTS/METHODS: Prospective, randomized, double-blinded, dual-centre, phase 2 trial in patients with centre-involving DME orally treated with placebo (n = 17) or levosulpiride (n = 17) for 8 weeks or in patients with PDR undergoing elective pars plana vitrectomy and receiving placebo (n = 18) or levosulpiride (n = 18) orally for the 1 week before vitrectomy. RESULTS: Levosulpiride improved changes from baseline in best-corrected visual acuity (p ≤ 0.037), central foveal thickness (CFT, p ≤ 0.013), and mean macular volume (MMV, p ≤ 0.002) at weeks 4, 6, and 8 compared to placebo. At 8 weeks, the proportion of eyes gaining ≥5 ETDRS letters at 4 m (41% vs. 28%), losing ≥21 µm in CFT (55% vs. 28%), and dropping ≥0.06 mm3 in MMV (65% vs. 29%) was higher after levosulpiride than placebo. The overall grading of visual and structural parameters improved with levosulpiride (p = 0.029). Levosulpiride reduced VEGF (p = 0.025) and PlGF (p = 0.008) levels in the vitreous of PDR patients. No significant adverse side-effects were detected. CONCLUSIONS: Oral levosulpiride for 8 weeks improved visual and structural outcomes in patients with centre-involving DME by mechanisms that may include intraocular upregulation of vasoinhibin and downregulation of VEGF and PlGF. Larger clinical trials evaluating long-term efficacy and safety are warranted.

Platelet Count During Course of Cardiogenic Shock.

The study investigates the prognostic value of the platelet count in patients with cardiogenic shock (CS). Limited data regarding the prognostic value of platelets in patients suffering from CS is available. Consecutive patients with CS from 2019 to 2021 were included at one institution. Firstly, the prognostic value of the baseline platelet count was tested for 30-day all-cause mortality. Thereafter, the prognostic impact of platelet decline during course of intensive care unit (ICU) hospitalization was assessed. A total of 249 CS patients were included with a median platelet count of 224 × 10 6 /ml. No association of the baseline platelet count with the risk of 30-day all-cause mortality was found (log-rank p = 0.563; hazard ratio [HR] = 0.879; 95% confidence interval [CI] 0.557-1.387; p = 0.579). In contrast, a decrease of platelet count by ≥ 25% from day 1 to day 3 was associated with an increased risk of 30-day all-cause mortality (55% vs. 39%; log-rank p = 0.045; HR = 1.585; 95% CI 0.996-2.521; p = 0.052), which was still evident after multivariable adjustment (HR = 1.951; 95% CI 1.116-3.412; p = 0.019). Platelet decrease during the course of ICU hospitalization but not the baseline platelet count was associated with an increased risk of 30-day all-cause mortality in CS patients.

Vasoinhibin's Apoptotic, Inflammatory, and Fibrinolytic Actions Are in a Motif Different From Its Antiangiogenic HGR Motif.

Vasoinhibin, a proteolytic fragment of the hormone prolactin, inhibits blood vessel growth (angiogenesis) and permeability, stimulates the apoptosis and inflammation of endothelial cells, and promotes fibrinolysis. The antiangiogenic and antivasopermeability properties of vasoinhibin were recently traced to the HGR motif located in residues 46 to 48 (H46-G47-R48), allowing the development of potent, orally active, HGR-containing vasoinhibin analogues for therapeutic use against angiogenesis-dependent diseases. However, whether the HGR motif is also responsible for the apoptotic, inflammatory, and fibrinolytic properties of vasoinhibin has not been addressed. Here, we report that HGR-containing analogues are devoid of these properties. Instead, the incubation of human umbilical vein endothelial cells with oligopeptides containing the sequence HNLSSEM, corresponding to residues 30 to 36 of vasoinhibin, induced apoptosis, nuclear translocation of NF-κB, expression of genes encoding leukocyte adhesion molecules (VCAM1 and ICAM1) and proinflammatory cytokines (IL1B, IL6, and TNF), and adhesion of peripheral blood leukocytes. Also, intravenous or intra-articular injection of HNLSSEM-containing oligopeptides induced the expression of Vcam1, Icam1, Il1b, Il6, and Tnf in the lung, liver, kidney, eye, and joints of mice and, like vasoinhibin, these oligopeptides promoted the lysis of plasma fibrin clots by binding to plasminogen activator inhibitor-1 (PAI-1). Moreover, the inhibition of PAI-1, urokinase plasminogen activator receptor, or NF-κB prevented the apoptotic and inflammatory actions. In conclusion, the functional properties of vasoinhibin are segregated into 2 different structural determinants. Because apoptotic, inflammatory, and fibrinolytic actions may be undesirable for antiangiogenic therapy, HGR-containing vasoinhibin analogues stand as selective and safe agents for targeting pathological angiogenesis.

Outcome of Patients With Cardiogenic Shock and Previous Right Ventricular Impairment Represented by Decreased Tricuspid Annular Plane Systolic Excursion and Tricuspid Annular Plane Systolic Excursion to Pulmonary Artery Systolic Pressure Ratio.

This study investigates the prognostic impact of known decreased ratio of tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP) and TAPSE in patients with cardiogenic shock (CS). In patients with pulmonary artery hypertension and in critically ill patients, decreased TAPSE and TAPSE/PASP ratio are known to be negative predictors. However, studies regarding the prognostic impact in patients with CS are limited. Consecutive patients with CS from June 2019 to May 2021 treated at a single center were included. Medical history including echocardiographic parameters such as TAPSE and PASP was documented for each patient. The primary endpoint was all-cause mortality at 30 days. Statistical analyses included univariable t test, Spearman's correlation, C-statistics, Kaplan-Meier analyses, and Cox proportional regression analyses. A total of 90 patients with CS and measurement of TAPSE and TAPSE/PASP ratio were included. TAPSE and TAPSE/PASP ratio measured several months before intensive care unit admission were both able to predict 30-day survival in CS patients, and were both lower in 30-day nonsurvivors. TAPSE/PASP ratio <0.4 mm/mmHg (log-rank p = 0.006) and TAPSE <18 mm (log-rank p = 0.004) were associated with increased risk of 30-day all-cause mortality. After multivariable adjustment, TAPSE/PASP ratio <0.4 mm/mmHg was not able to predict 30-day all-cause mortality, whereas TAPSE <18 mm was still significantly associated with the primary endpoint (hazard ratio 2.336, confidence interval 1.067 to 5.115, p = 0.034). In consecutive patients presenting with CS, compared to TAPSE alone, previously determined TAPSE/PASP ratio did not improve risk prediction for 30-day all-cause mortality.

D-Dimer Levels and the Risk of 30-Day All-Cause Mortality in Cardiogenic Shock Stratified by Etiology.

BACKGROUND: The study investigates the prognostic impact of D-dimer levels in patients with cardiogenic shock (CS). Although D-dimer levels were found to be associated with prognosis in various clinical settings such as heart failure or acute myocardial infarction (AMI), the prognostic role of D-dimer levels in CS patients has not yet been clarified. METHODS: Consecutive CS patients with and without concomitant AMI were prospectively included from 2019 to 2021. The prognostic impact of D-dimer levels was tested for 30-day all-cause mortality within the entire study cohort and stratified by the presence or absence of AMI. Statistical analyses included C-statistics, Kaplan-Meier, and multivariate Cox regression analyses. RESULTS: One hundred and twenty-three consecutive CS patients were included with an overall all-cause mortality at 30 days of 55%. The median D-dimer level on admission was 8.44 mg/L, whereas D-dimer levels were higher in 30-day non-survivors compared to survivors (median 13.0 vs. 5.2 mg/L; p = 0.011). D-dimer levels above the median were associated with an increased risk of 30-day all-cause mortality compared to patients with lower D-dimer levels (66% vs. 54%, log rank p = 0.050; HR = 1.594; 95% CI 0.979 - 2.594; p = 0.061), especially in patients with non-AMI-related CS (65% vs. 30%, log rank p = 0.010). The prognostic value of D-dimer levels was still demonstrated after multivariate adjustment (HR = 1.024; 95% CI 1.004 - 1.045; p = 0.020). CONCLUSIONS: D-dimer measurement may be a reliable biomarker to predict the risk of 30-day mortality in CS patients, especially in patients with non-AMI related CS.

A Machine Learning Model for the Accurate Prediction of 1-Year Survival in TAVI Patients: A Retrospective Observational Cohort Study.

BACKGROUND: predicting the 1-year survival of patients undergoing transcatheter aortic valve implantation (TAVI) is indispensable for managing safe early discharge strategies and resource optimization. METHODS: Routinely acquired data (134 variables) were used from 629 patients, who underwent transfemoral TAVI from 2012 up to 2018. Support vector machines, neuronal networks, random forests, nearest neighbour and Bayes models were used with new, previously unseen patients to predict 1-year mortality in TAVI patients. A genetic variable selection algorithm identified a set of predictor variables with high predictive power. RESULTS: Univariate analyses revealed 19 variables (clinical, laboratory, echocardiographic, computed tomographic and ECG) that significantly influence 1-year survival. Before applying the reject option, the model performances in terms of negative predictive value (NPV) and positive predictive value (PPV) were similar between all models. After applying the reject option, the random forest model identified a subcohort showing a negative predictive value of 96% (positive predictive value = 92%, accuracy = 96%). CONCLUSIONS: Our model can predict the 1-year survival with very high negative and sufficiently high positive predictive value, with very high accuracy. The "reject option" allows a high performance and harmonic integration of machine learning in the clinical decision process.

Cardiac Troponin I but Not N-Terminal Pro-B-Type Natriuretic Peptide Predicts Outcomes in Cardiogenic Shock.

This study investigates the prognostic value of cardiac troponin I (cTNI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in patients with cardiogenic shock (CS). Data regarding the prognostic value of cardiac biomarkers in CS is scarce, furthermore, most studies were restricted to CS patients with acute myocardial infarction (AMI). Therefore, consecutive patients with CS from 2019 to 2021 were included. Blood samples were retrieved from day of disease onset (day 1) and on days 2, 3 and 4 thereafter. The prognostic value of cTNI and NT-proBNP levels was tested for 30-day all-cause mortality. Statistical analyses included univariable t-tests, Spearman's correlations, Kaplan-Meier analyses and multivariable Cox proportional regression analyses. A total of 217 CS patients were included with an overall rate of all-cause mortality of 56% at 30 days. CTNI was able to discriminate 30-day non-survivors (area under the curve (AUC) = 0.669; p = 0.001), whereas NT-proBNP (AUC = 0.585; p = 0.152) was not. The risk of 30-day all-cause mortality was higher in patients with cTNI levels above the median (70% vs. 43%; log rank p = 0.001; HR = 2.175; 95% CI 1.510-3.132; p = 0.001), which was observed both in patients with (71% vs. 49%; log rank p = 0.012) and without AMI-related CS (69% vs. 40%; log rank p = 0.005). The prognostic impact of cTNI was confirmed after multivariable adjustment (HR = 1.915; 95% CI 1.298-2.824; p = 0.001). In conclusion, cTNI-but not NT-proBNP-levels discriminated 30-day all-cause mortality in CS patients.

Does Atrial Fibrillation Deteriorate the Prognosis in Patients With Septic or Cardiogenic Shock?

Atrial fibrillation (AF) is associated with increased risk of mortality in various clinical conditions. However, the prognostic role of preexisting and new-onset AF in critically ill patients, such as patients with septic or cardiogenic shock remains unclear. This study investigates the prognostic impact of preexisting and new-onset AF on 30-day all-cause mortality in patients with septic or cardiogenic shock. Consecutive patients with sepsis, or septic or cardiogenic shock were enrolled in 2 prospective, monocentric registries from 2019 to 2021. Statistical analyses included Kaplan-Meier, multivariable logistic, and Cox proportional regression analyses. In total, 644 patients were included (cardiogenic shock: n = 273; sepsis/septic shock: n = 361). The prevalence of AF was 41% (29% with preexisting AF, 12% with new-onset AF). Within the entire study cohort, neither preexisting AF (log-rank p = 0.542; hazard ratio [HR] 1.075, 95% confidence interval [CI] 0.848 to 1.363, p = 0.551) nor new-onset AF (log-rank p = 0.782, HR = 0.957, 95% CI 0.683 to 1.340, p = 0.797) were associated with 30-day all-cause mortality compared with non-AF. In patients with AF, ventricular rates >120 beats/min compared with ≤120 beats/min were shown to increase the risk of reaching the primary end point in AF patients with cardiogenic shock (log-rank p = 0.006, HR 1.886, 95% CI 1.164 to 3.057, p = 0.010). Furthermore, logistic regression analyses suggested increased age was the only predictor of new-onset AF (odds ratio 1.042, 95% CI 1.018 to 1.066, p = 0.001). In conclusion, neither the presence of preexisting AF nor the occurrence of new-onset AF was associated with the risk of 30-day all-cause mortality in consecutive patients admitted with cardiogenic shock.

Effect of Hemoglobin Levels in Patients with Cardiogenic Shock of Any Cause: Insights from a Single-Centre, Prospective Registry.

BACKGROUND: Data regarding the short-term prognostic impact of hemoglobin levels in cardiogenic shock (CS) patients is limited. The study examines the prognostic impact of hemoglobin levels in patients with CS. METHODS: Consecutive patients with CS of any etiology from 2019 to 2021 were included at one institution. Hemoglobin levels were retrieved from the day of admission (i.e., day 1), and on days 2, 3, 4, and 8 of intensive care unit (ICU) treatment thereafter. The primary endpoint was 30-day all-cause mortality. Statistical analyses included univariable t-tests, Spearman´s correlations, C-statistics, Kaplan-Meier analyses as well as multivariable logistic and Cox regression analyses. RESULTS: From a total of 250 consecutive patients admitted with CS, 54% died within 30 days. Hemoglobin levels on day 4 and on day 8 were associated with moderate discrimination for 30-day all-cause mortality (area under the curve (AUC) 0.598 - 0.666), whereas hemoglobin level on day 1 was not predictive for 30-day all-cause mortality (AUC = 0.504). There was no association with 30-day all-cause mortality when stratified by the presence of anemia (defined as hemoglobin level < 12 g/dL) on day 1 (54% vs. 55%; log rank p = 0.906; HR = 0.981; 95% CI 0.698 - 1.378; p = 0.910). However, a decrease of hemoglobin by > 2 g/dL from day 1 to day 3 of ICU treatment was associated with an increased risk of 30-day all-cause mortality (56% vs. 41%; log rank p = 0.014; HR = 1.831; 95% CI 1.108 - 3.026; p = 0.018). CONCLUSIONS: Hemoglobin levels on day 1 were not associated with prognosis in CS. However, an early decrease of hemoglobin levels from day 1 to day 3 indicated impaired short-term prognosis in CS patients.