Higher free triiodothyronine is associated with non-alcoholic fatty liver disease in euthyroid subjects: the Lifelines Cohort Study

ObjectiveOvert hypothyroidism confers an increased risk of non-alcoholic fatty liver disease (NAFLD). The liver plays a crucial role in the metabolism of cholesterol and triglycerides; thyroid hormones interact on hepatic lipid homeostasis. Thyroid function within the euthyroid range affects a number of health issues, including atherosclerosis development and biochemical markers of increased cardiovascular risk. However, the association of thyroid hormones with NAFLD in euthyroid subjects has not been unequivocally established. We therefore determined associations of thyroid hormone parameters with NAFLD among euthyroid subjects.MethodsThe study was conducted in the Lifelines Cohort Study, a population-based cohort study of participants living in the North of the Netherlands. Only euthyroid subjects (thyroid-stimulating hormone (TSH) 0.5–4.0 mU/L, free thyroxine (FT4) 11–19.5 pmol/L and free triiodothyronine (FT3) 4.4–6.7 pmol/L) older than 18 years were included. Exclusion criteria were participants with excessive alcohol use, known hepatitis or cirrhosis, liver functions ≥ three times the upper limit, current cancer, non-white ancestry, previous or current use of thyroid medication and current use of lipid or glucose lowering medication. A priori defined liver biochemistry, thyroid function parameters and metabolic syndrome (MetS) were studied. NAFLD was defined by using the validated Fatty Liver Index (FLI); FLI ≥ 60 was categorized as NAFLD. A P < 0.01 was considered significant.ResultsFLI ≥ 60 was found in 4274 (21.1%) of 20,289 individuals (62.1% male, median age 46 years) with increased prevalence of MetS (P < 0.0001). In age- and sex-adjusted analysis FLI ≥ 60 was independently associated with a higher FT3 (OR 1.34, 95% CI 1.29–1.39, per SD increment, P < 0.0001) and a lower FT4 (OR 0.73, 95% CI 0.70–0.75, P < 0.0001) but not by TSH. The strongest association was found for the FT3/FT4 ratio (OR 1.44, 95% CI 1.39–1.49, P < 0.0001). These associations remained similar after additional adjustment for the presence of MetS. In subjects with enlarged waist circumference, TSH and FT4 were lower while FT3 was higher, resulting in an increased FT3/FT4 ratio (P < 0.0001).ConclusionsEuthyroid subjects with suspected NAFLD are characterized by higher FT3, lower FT4 and higher FT3/FT4 ratio, probably consequent to central obesity.     

Low GFR amplifies the association between coronary three-vessel disease and all-cause mortality

Background and aimThree vessels disease (3VD) has been associated with worse prognosis and higher mortality. Chronic kidney disease (CKD) is an independent risk factor for premature death, mostly due to coronary artery disease (CAD).We aim to examine the prognostic impact of 3VD on all-cause mortality in a cohort of high cardiovascular risk subjects undergoing coronary angiography (CA) and to explore whether low eGFR (<60 ml/min/1.73 m²) modulates the risk of all-cause mortality associated to 3VD.Methods and resultsOne-thousand-seventeen subjects (759 M, mean age 68.4 ± 11 years) consecutive subjects undergoing CA from 2016 to 2018 were evaluated. Subjects were classified according to the severity of CAD as follows: group “three vessels disease” (3VD), and “no three vessels disease” (No 3VD). Serum creatinine was measured to estimate glomerular filtration rate (eGFR). The whole population was divided into 4 groups (A, B, C, D), according to the presence/absence of low eGFR and/or 3VD. One-hundred-fourteen deaths occurred (median follow-up:44 months). The risk of death in subjects with 3VD was almost 2-time higher than subject without 3VD (adjusted HR = 1.61; 95% CI 1.094–2.373, p = 0.0157). Among 4 subgroups, subjects with low eGFR and 3VD (Group D) had the highest risk of death (adjusted HR = 3.881; 95% CI 2.256–6.676, p < 0.0001).ConclusionsLow eGFR significantly amplifies the risk of all-cause mortality associated to 3VD. Our results strengthen the role of kidney disease as a risk multiplier for cardiovascular and all-cause mortality and highlight the need to prevent its onset and progression.     

Does Subclinical Hypothyroidism Add Any Symptoms? Evidence from a Danish Population-Based Study

BackgroundFew studies have scrutinized the spectrum of symptoms in subclinical hypothyroidism.MethodsFrom 3 Danish Investigation on Iodine Intake and Thyroid Diseases (DanThyr) cross-sectional surveys performed in the period 1997 to 2005, a total of 8903 subjects participated in a comprehensive investigation including blood samples and questionnaires on previous diseases, smoking habits, alcohol intake, and education. From the 3 surveys we included patients with subclinical hypothyroidism (n = 376) and euthyroid controls (n = 7619). We explored to what extent patients with subclinical hypothyroidism reported 13 previously identified hypothyroidism-associated symptoms (tiredness, dry skin, mood lability, constipation, palpitations, restlessness, shortness of breath, wheezing, globus sensation, difficulty swallowing, hair loss, dizziness/vertigo, and anterior neck pain). In various uni- and multivariate regression models we searched for circumstances predicting why some patients have more complaints than others.ResultsSubclinically hypothyroid patients did not report higher hypothyroidism score [(median, interquartile range), 2 (0-4) vs 2 (0-4), P = .25] compared with euthyroid controls. Within the group of subclinical hypothyroid patients, comorbidity had the highest impact on symptoms (tiredness, shortness of breath, wheezing; all P < .001); TSH level had no impact on symptom score; and younger age was accompanied by higher mental burden (tiredness, P < .001; mood lability, P < .001; restlessness, P = .012), whereas shortness of breath was associated with high body mass index (P < .001) and smoking (P = .007).ConclusionPatients with a thyroid function test suggesting subclinical hypothyroidism do not experience thyroid disease-related symptoms more often than euthyroid subjects. In subclinical hypothyroidism, clinicians should focus on concomitant diseases rather than expecting symptomatic relief following levothyroxine substitution.     

Impact of Physical Activity on Depression After Cardiac Surgery

Background

Physical activity is associated with a lower prevalence of depressive symptoms in cardiac patients. However, the benefits of physical activity on depression perioperatively are unknown. We sought to identify independent parameters associated with depression in patients undergoing cardiac surgery.

Methods

Patients awaiting nonemergent cardiac surgery (n = 436) completed the Patient Health Questionnaire-9 (PHQ-9) to quantify depression (PHQ-9 score > 9). Physical activity was assessed with the International Physical Activity Questionnaire (IPAQ-short) and accelerometry. Data collection occurred preoperatively (Q1, n = 436), at hospital discharge (Q2, n = 374), at 3 months (Q3, n = 318), and at 6 months (Q4, n = 342) postoperatively. Patients were categorized as “depression naive”, “at risk” or “depressed” preoperatively. Physical inactivity was defined as < 600 metabolic equivalent min/wk. Independent perioperative variables associated with depression were identified with univariate and multivariate logistic regression.

Results

Depression prevalence from Q1-Q4 was 23%, 37%, 21%, and 23%, respectively. Independent associations with depression were preoperative left ventricular ejection fraction < 50% (Q1, P < 0.05), physical inactivity (Q1, P < 0.05), baseline “at-risk” (Q2, P < 0.05), and baseline “depressed” groups (Q2-Q4, P < 0.05), hospital stay > 7 days (Q2, P < 0.05), postoperative stressful event (Q3 and Q4, P < 0.05), and cardiopulmonary bypass time > 120 minutes (Q4, P = 0.05). Newly depressed patients 6 months postoperatively reported lower IPAQ-short physical activity than depression-free patients (median change, −40 min/wk (interquartile range [IQR], −495 to +255) vs +213 min/wk (IQR, +150 to +830; P < 0.05).

Conclusions

Up to 40% of patients are depressed after cardiac surgery. Preoperative depression and postoperative stressful events were the strongest independent associations postoperatively. Physical inactivity was associated with preoperative depression and new depression 6 months postoperatively.     

Platelet Reactivity and Clinical Outcomes After Drug-Eluting Stent Implantation: Results From the PTRG-DES Consortium

BackgroundThe long-term prognostic implication of platelet reactivity after percutaneous coronary intervention (PCI) is not clearly known.ObjectivesThe impacts of platelet reactivity from the PTRG-DES consortium were assessed.MethodsThe primary endpoint was the major adverse cardiac and cerebrovascular events (MACCE) including all-cause death, myocardial infarction, stent thrombosis, or stroke. Key secondary endpoints were all-cause mortality, major bleeding, and net adverse clinical events (NACE), including MACCE and bleeding.ResultsBetween 2003 and 2018, a total of 11,714 patients were enrolled and grouped into tertiles according to P2Y₁₂ reaction units (PRUs): high PRUs (≥253), intermediate PRUs (188-252), and low PRUs (<188). The Kaplan-Meier (KM) estimates of the primary outcome were significantly different across the groups; the high-PRU group showed the highest MACCE rate at 5 years (12.9%, 11.1%, and 7.0% in high-, intermediate-, and low-PRU groups, respectively; P < 0.001), as well as at 1 year (P < 0.001). The high-PRU group had the greatest KM estimates of all-cause death (8.2%, 5.9%, and 3.7%, respectively; P < 0.001) at 5 years without significant differences of major bleeding, and resultant of a higher KM estimates of NACE (15.7%, 13.6%, and 9.7%, respectively; P < 0.001). A PRU ≥252, the best cutoff value, was strongly related to MACCE (HR: 1.39; 95% CI: 1.11-1.74; P = 0.003) and all-cause death at 5 years after PCI (HR: 1.42; 95% CI: 1.04-1.94; P = 0.026). The optimal cutoff value of aspirin reaction units predicting the MACCE occurrence was ≥414 and was significantly associated with 5-year MACCE occurrence or all-cause death (P < 0.001).ConclusionsIn this large-scale cohort, high PRU was significantly associated with occurrence of MACCE, all-death death, and NACE at 5 years, as well as 1 year after PCI. (PTRG-DES Consortium [PTRG]; NCT04734028)     

Evaluating the effect of kidney function on brain volumes and dementia risk in the UK Biobank

ObjectiveTo investigate the association between kidney function with the risk of dementia and brain volumes.MethodsA total of 452,996 UK Biobank participants with calculated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR) were included. We utilized Cox proportional hazards regression models and restricted cubic spline analyses to examine the relationships between kidney function and the risk of all-cause dementia (ACD), Alzheimer's disease (AD), and vascular dementia (VD). Additionally, we explored the correlations between kidney function and brain magnetic resonance indicators among 40,380 participants.ResultsDuring a median follow-up of 12 years, 5,258 incident ACD cases were identified. The deterioration of kidney function was associated with an increased risk of ACD. When compared to eGFR ≥ 90 ml/min/1.73 m², the highest risk increase was evident for eGFRcre < 30 ml/min/1.73 m² (adjusted HR = 2.372, 95% CI: 1.444–3.897, P < 0.001), with eGFRcys showing greater significance (adjusted HR = 3.045, 95% CI: 2.212–4.191, P < 0.001), especially in relation to AD. Compared to the ACR level in the range of 3–30 mg/mmol, the category of > 30 mg/mmol was associated with an increased risk of ACD (adjusted HR = 1.720, 95% CI: 1.350–2.190, P < 0.001). Moreover, the decline in kidney function was associated with the total brain volume atrophy and reduction in certain subcortical areas.ConclusionsOur study indicates that diminished kidney function, as evidenced by a drop in eGFR and aggravated proteinuria, elevates dementia risk. Associated brain structural changes further underpin this connection from a neuro-pathophysiological perspective.     

Aspartate aminotransferase and mortality in patients with ischemic heart disease

Background and aimsEvidence on the association between aspartate aminotransferase (AST) activity and mortality of patients with ischemic heart disease (IHD) is limited. We investigated whether there is an association between AST activity and mortality in IHD patients.Methods and resultsThe study included 6857 patients with coronary angiography-proven IHD and AST activity within the reference range. AST activity measurements were available in all patients. The primary outcome was 3-year cardiac mortality. Patients were categorized in groups according to the AST activity tertiles: a group with AST within the 1st tertile (AST < 17.0 U/L), a group with AST within the 2nd tertile (AST > 17–24.5 U/L) and a group with AST within the 3rd tertile (AST > 24.5 U/L). Cardiac death (n = 297) occurred in 109, 69 and 119 patients in the 1st to 3rd AST tertiles (Kaplan–Meier estimates of mortality: 5.3%, 3.6% and 5.9%; univariable hazard ratio [HR] = 1.75, 95% confidence interval [CI] 1.30–2.36, P < 0.001 for tertile 3 vs. 2; HR = 1.13 [0.87–1.46], P = 0.370 for tertile 3 vs. 1; and HR = 0.65 [0.48–0.87], P = 0.004 for tertile 2 vs. 1). The association between AST and cardiac mortality was U-shaped. AST values <15 U/L (HR = 1.118 [1.009–1.238]) and >23 U/L (HR = 1.029 [1.003–1.056]) were associated with higher cardiac mortality compared with the reference value (21 U/L). After adjustment, the association between AST and cardiac mortality was attenuated (P = 0.133) but remained non-linear (P = 0.047).ConclusionsIn patients with IHD, AST activity was associated with the risk of cardiac mortality with a U-shaped relationship. After adjustment, the association between AST and mortality was attenuated.     

Effectiveness of Switching From Intravenous to Subcutaneous Infliximab in Patients With Inflammatory Bowel Diseases: the REMSWITCH Study

Background and AimsWe assessed the effectiveness of switching from intravenous to subcutaneous infliximab in patients with inflammatory bowel diseases (IBDs) treated with or without intensified intravenous regimen.MethodsIn this multicenter observational study, IBD patients in clinical remission (partial Mayo score ≤2 or Harvey-Bradshaw index ≤4) were switched to a unique dose of subcutaneous infliximab (120 mg every other week). Pharmacological and biological data were collected at baseline, visit 1 (4–8 weeks postswitch), visit 2 (8–16 weeks postswitch), and visit 3 (16–24 weeks postswitch). Relapse was defined as clinical relapse or fecal calprotectin increase ≥150 μg/g compared with baseline.ResultsAmong 184 eligible patients, 72.3% (n = 133 of 184) agreed to switch to subcutaneous infliximab. At visit 3, a relapse occurred in 10.2% (n = 6 of 59), 7.3% (n = 3 of 38), 16.7% (n = 3 of 18), and 66.7% (n = 10 of 15) (P < .001) of patients receiving 5 mg/kg every 8 weeks, 10 mg/kg every 8 weeks, 10 mg/kg every 6 weeks, and 10 mg/kg every 4 weeks, respectively. Dose escalation to 240 mg every other week led to recapture clinical remission in 93.3% (n = 14 of 15). Infliximab serum levels increased after the switch (P < .0001) except for patients receiving 10 mg/kg every 4 weeks. In multivariable analysis, 10 mg/kg every 4 weeks regimen (odds ratio, 12.4; 95% confidence interval, 1.6–98.4; P = .017) and fecal calprotectin >250 μg/g at baseline (odds ratio, 5.4; 95% confidence interval, 1.1–27.6; P = .042) had a higher risk of relapse as well as reduced (41.7%) or stable (36.8%) infliximab serum levels between baseline and visit 1 compared with increased serum levels (12.7%) (P = .020 and P = .019, respectively). Patients’ acceptability (10-point scale) was improved by the switch (6.9 ± 1.6 vs 8.6 ± 1.4; P < .0001). No severe adverse event was reported.ConclusionsSwitching from intravenous to subcutaneous infliximab 120 mg every other week is safe and well accepted, leading to a low risk of relapse in IBD patients except for those receiving 10 mg/kg every 4 weeks requiring 240 mg every other week.     

Simultaneous Hybrid Coronary Revascularization vs Conventional Strategies for Multivessel Coronary Artery Disease: A 10-Year Follow-Up

BackgroundAlthough evidence is sufficient to confirm that hybrid coronary revascularization (HCR) is safe and effective in the short term, its value in the long run is debatable.ObjectivesThis study sought to compare the long-term outcomes of HCR with coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) for multivessel disease.MethodsThree groups of patients, 540 each, receiving HCR, CABG, or PCI between June 2007 to September 2018, were matched using propensity score matching. Patients were stratified by EuroSCORE (European System for Cardiac Operative Risk Evaluation) II (low ≤0.9; 0.9 < medium <1.5; high ≥1.5) and SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score (low ≤22; 22 < medium <33; high ≥33). Major adverse cardiac and cerebrovascular events (MACCE) and Seattle Angina Questionnaire (SAQ) scores were compared among the 3 groups.ResultsIn terms of MACCE and SAQ, HCR performed similarly to off-pump CABG but significantly outperformed PCI (P < 0.001). In the low-to-medium EuroSCORE II and medium-to-high SYNTAX score tertiles, MACCE rates in the HCR group were significantly lower than those in the PCI (EuroSCORE II: low, 30.7% vs 41.2%; P = 0.006; medium, 31.3% vs 41.7%; P = 0.013; SYNTAX score: medium, 27.6% vs 41.2%; P = 0.018; high, 32.4% vs 52.7%; P = 0.011) but were similar to those in the CABG group. In the high EuroSCORE II stratum, HCR had a lower MACCE rate than CABG (31.9% vs 47.0%; P = 0.041) and PCI (31.9% vs 53.7%; P = 0.015).ConclusionsCompared with conventional strategies, HCR provided satisfactory long-term outcomes in MACCE and functional status for multivessel disease.     

Association Between Drug-Eluting Stent Type and Clinical Outcomes in Patients With Chronic Kidney Disease Undergoing Percutaneous Coronary Intervention

Background

The comparative efficacy of first- vs second-generation drug-eluting stents (DESs) in patients with chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI) is unknown.

Methods

A retrospective analysis of consecutive patients undergoing PCI at a tertiary PCI center from 2007-2011 was performed, with linkage to administrative databases for long-term outcomes. CKD was defined as creatinine clearance (CrCl) < 60 mL/min. Propensity matching by multivariable scoring method and Kaplan-Meier analyses were performed.

Results

Of 6481 patients with available CrCl values undergoing a first PCI during the study period, 1658 (25%) had CKD. First- and second-generation DESs were implanted in 320 (19.3%) and 128 (7.7%) patients with CKD, respectively. At 2 years, no significant differences were observed between first-generation (n = 126) and second-generation (n = 126) propensity-matched DES cohorts for the outcomes of death (19% vs 16%; P = 0.51), repeat revascularization (10% vs 10%; P = 1.00), and major adverse cardiovascular and cerebrovascular events (MACCE) (36% vs 37%; P = 0.90). The 2-year Kaplan-Meier survival was also similar (P = 0.77). In patients with CKD, second-generation DES type was not an independent predictor for death (P = 0.49) or MACCE (P = 1.00).

Conclusions

Although the use of first- and second-generation DESs was associated with similar 2-year safety and efficacy in patients with CKD, our results cannot rule out a beneficial effect of second- vs first-generation DESs owing to small sample size. Future studies with larger numbers of patients with CKD are needed to identify optimal stent types, which may improve long-term clinical outcomes.     

Changes in thyroid function in patients with liver failure and their clinical significance: A clinical study of non-thyroidal illness syndrome in patients with liver failure

BackgroundNon-thyroidal illness syndrome (NTIS) develops in a large proportion of critically ill patients and is associated with high risk for death. We aimed to investigate the correlation between NTIS and liver failure, and the short-term mortality of patients with these conditions.MethodsThe clinical data of 87 patients with liver failure were collected retrospectively, 73 of them were randomly selected for an observational study and to establish prognostic models, and 14 for model validation. Another 73 sex- and age-matched patients with mild chronic hepatitis were randomly selected as a control group. Serum free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) were measured. The clinical characteristics of patients with liver failure and NTIS were analyzed. The follow-up of patients lasted for 3 months. Additionally, the values for predicting short-term mortality of model for end-stage liver disease (MELD), Child-Turcotte-Pugh (CTP), chronic liver failure-sequential organ failure assessment (CLIF-SOFA) scores, FT3-MELD model, and FT3 were evaluated.ResultsThe observation group had significantly lower FT3 (2.79 ± 0.71 vs. 4.43 ± 0.75 pmol/L, P < 0.001) and TSH [0.618 (0.186-1.185) vs. 1.800 (1.570-2.590) mIU/L, P < 0.001], and higher FT4 (19.51 ± 6.26 vs. 14.47 ± 2.19 pmol/L, P < 0.001) than the control group. NTIS was diagnosed in 49 of the patients with liver failure (67.12%). In the observation group, patients with NTIS had a higher mortality rate than those without (63.27% vs. 25.00%, P = 0.002). Across the whole cohort, the 3-month mortality was 50.68%. The international normalized ratios (INR) were 2.40 ± 1.41 in survivors and 3.53 ± 1.81 in deaths (P = 0.004), the creatinine (Cr) concentrations were 73.27 ± 36.94 µmol/L and 117.08 ± 87.98 µmol/L (P = 0.008), the FT3 concentrations were 3.13 ± 0.59 pmol/L and 2.47 ± 0.68 pmol/L (P < 0.001), the MELD scores were 22.19 ± 6.64 and 29.57 ± 7.99 (P < 0.001), the CTP scores were 10.67 ± 1.53 and 11.78 ± 1.25 (P = 0.001), and the CLIF-SOFA scores were 8.42 ± 1.68 and 10.16 ± 2.03 (P < 0.001), respectively. FT3 was negatively correlated with MELD score (r = −0.430, P < 0.001). An FT3-MELD model was established by subjecting FT3 concentration and MELD score to logistic regression analysis using the following formula: Logit(P) = −1.337 × FT3+0.114 × MELD+0.880. The area under the receiver operating characteristic (ROC) curve was 0.827 and the optimal cut-off value was 0.4523. The corresponding sensitivity and specificity were 67.6% and 91.7%. The areas under the ROC curve for FT3 concentration, MELD score, CTP score, and CLIF-SOFA score were 0.809, 0.779, 0.699, and 0.737, respectively.ConclusionsPatients with liver failure often develop NTIS. FT3-MELD score perform better than CTP and CLIF-SOFA scores in predicting mortality in patients with liver failure. Thus, the FT3-MELD model could be of great value for the evaluation of the short-term mortality of such patients.     

Inverse association between habitual polyphenol intake and incidence of cardiovascular events in the PREDIMED study

Background and aimsEpidemiologic and biological evidence supports an inverse association between polyphenol consumption and the risk of cardiovascular disease (CVD). However, no previous studies have prospectively evaluated the relationship between polyphenol intake and the incidence of CVD in such a comprehensive way. The aim was to evaluate the association between intakes of total polyphenol and polyphenol subgroups, and the risk of major cardiovascular events (myocardial infarction, stroke or death from cardiovascular causes) in the PREDIMED study.Methods and resultsThe present work is an observational study within the PREDIMED trial. Over an average of 4.3 years of follow-up, there were 273 confirmed cases of CVD among the 7172 participants (96.3%) who completed a validated 137-item food frequency questionnaire (FFQ) at baseline. Polyphenol consumption was calculated by matching food consumption data from the FFQ with the Phenol-Explorer database on polyphenol content of each reported food. After multivariate adjustment, a 46% reduction in risk of CVD risk was observed comparing Q5 vs. Q1 of total polyphenol intake (HR = 0.54; 95% confidence interval [CI] = 0.33–0.91; P-trend = 0.04). The polyphenols with the strongest inverse associations were flavanols (HR = 0.40; CI 0.23–0.72; P-trend = 0.003), lignans (HR = 0.51; CI 0.30–0.86; P-trend = 0.007), and hydroxybenzoic acids (HR = 0.47; CI 0.26–0.86; P-trend 0.02).ConclusionGreater intake of polyphenols, especially from lignans, flavanols, and hydroxybenzoic acids, was associated with decreased CVD risk. Clinical trials are needed to confirm this effect and establish accurate dietary recommendations. Clinical trial registry: International Standard Randomized Controlled Trial Number (ISRCTN of London, England) 35739639.     

Heightened Dependence of Left-Heart Filling Pressures on Right-Heart Failure in Congenital Heart Disease

BackgroundPulmonary artery wedge pressure (PAWP) is often elevated in patients with right-sided congenital heart disease (CHD), raising the possibility of coexisting left-heart disease, but pressure-volume relationships in the left and right sides of the heart influence one another through interdependence, which may be amplified in patients with CHD.MethodsWe hypothesized that increases in PAWP in patients with CHD would be more strongly related to ventricular interdependence compared with patients who have isolated left-heart disease such as heart failure with preserved ejection fraction (HFpEF). Ventricular interdependence was assessed by the relationship between PAWP and right-atrial pressure (RAP), RAP/PAWP ratio, and the left-ventricular (LV) eccentricity index.ResultsPAWP was elevated (≥15 mm Hg) in 49% of patients with CHD (n = 449). There was a very strong correlation between RAP and PAWP in CHD (r = 0.81, P < 0.001) that greatly exceeded the respective correlation in HFpEF (n = 160; r = 0.58, P < 0.001; P < 0.001 between groups). RAP/PAWP ratio and LV eccentricity index were higher in CHD than HFpEF (1.26 ± 0.18 vs 1.05 ± 0.14, P = 0.007) and (0.80 ± 0.21 vs 0.59 ± 0.19, P < 0.001), respectively. RAP (but not PAWP) was an independent predictor of death/transplant (hazard ratio 1.86 per 5 mm Hg, 95% confidence interval, 1.39-2.45, P = 0.002).ConclusionsLeft-heart filling pressures are commonly elevated in right-sided CHD, but this is related predominantly to right-heart failure and enhanced ventricular interdependence rather than left-heart disease. These data provide new insight into the basis of abnormal left-heart hemodynamics in patients with CHD and reinforce the importance of therapeutic interventions targeted to the right heart.     

Optical coherence tomography angiography (OCTA) findings in juvenile idiopathic arthritis

Aim of the workTo report optical coherence tomography angiography (OCTA) findings in juvenile idiopathic arthritis (JIA) patients and to study the relation to disease activity.Patients and methodsThe study included 20 JIA patients (38 eyes) who underwent ophthalmologic and rheumatologic examination plus OCT/OCTA. Juvenile arthritis disease activity score (JADAS27) was assessed, and patients were divided into those with no/low activity (group 1; n = 13) and moderate/severe activity (group 2; n = 7). OCTA findings were compared with 11 control (11 eyes).ResultsThe study included 20 JIA-U patients (38 eyes) with a mean age of 10.7 ± 2.6 years and disease duration of 72.5 ± 34.7 months and they were 9/20 (45 %) females. 13(65 %) patients had no/mild activity (group 1, 25 eyes) while 7(35 %) had moderate to severe activity (group 2, 13 eyes). The mean foveal superficial and deep capillary plexuses (SCP/DCP) vascular density (VD) were significantly lower in patients with moderate/severe activity (3x3 scan: p = 0.001 and p < 0.001; 6x6 scan p = 0.008 and p = 0.001 respectively). The foveal avascular zone (FAZ) 3x3 and 6x6 scans were significantly increased and the central macular thickness (CMT) decreased in patients with moderate/severe disease activity (p < 0.001, p = 0.001, and p = 0.001). Fovea SCP VD in 6x6 and 3x3 scans were significantly different between JIA subtypes (p = 0.01 and p = 0.03, respectively), with less VD in oligoarticular type. FAZ, CMT and DCP-VD significantly correlated with visual analogue scale (r = 0.58, p < 0.001; r = ?0.5, p = 0.01; r = ?0.58, p < 0.001, respectively).ConclusionsNon-invasive OCTA-derived vascular parameters of the macula could be potential biomarkers for evaluating the severity of the systemic disease activity in JIA patients.     

Angiographic Functional Scoring of Coronary Artery Disease Predicts Mortality in Patients With Severe Aortic Stenosis Undergoing TAVR

Background/purposeCoronary artery disease (CAD) is common in patients undergoing transcatheter aortic valve replacement (TAVR), although its prognostic significance is questionable. Significant CAD stratified using SYNTAX score (SS) has been associated with greater mortality, yet it is unknown whether the functional impact of CAD also impacts outcomes in this cohort. DILEMMA score (DS) is a validated angiographic functional scoring tool that correlates with fractional flow reserve and instantaneous wave-free ratio.This study sought to assess the functional impact of CAD on outcomes in patients undergoing TAVR for severe aortic stenosis (AS).Methods/materials229 patients were included in this analysis. Patients underwent angiographic DS and SS and were classified using predefined values. The primary endpoint was one-year all-cause mortality, with secondary endpoints of 30-day major adverse cardiac and cerebrovascular events (MACCE).ResultsThe mean age was 83.9 ± 0.5 years (55.0% female), with 11.8% all-cause mortality. CAD defined by ≥30% stenosis in any vessel was not associated with adverse outcomes (HR = 1.08, p = 0.84). However, the risk of one-year mortality was greater in patients with either SS > 9 (20.8% vs. 9.4%, HR 2.34, p = 0.03) or DS > 2 (18.4% vs. 8.5%, HR = 2.28, p = 0.03). Both scoring systems were also associated with 30-day MACCE (both p < 0.05). After multivariate adjustment, independent predictors of one-year mortality were DS > 2 (HR = 2.29, p = 0.04), left ventricular ejection fraction <50% (HR 2.66, p = 0.04) and COPD (HR 2.43, p = 0.04).ConclusionOur results demonstrate that angiographic functional scoring is independently predictive of both 12-month mortality and 30-day MACCE following TAVR.     

A Combined-Biomarker Approach to Clinical Phenotyping Renal Dysfunction in Heart Failure

BackgroundDifferentiating heart failure (HF) induced renal dysfunction (RD) from intrinsic kidney disease is challenging. It has been demonstrated that biomarkers such as B-type natriuretic peptide (BNP) or the blood urea nitrogen to creatinine ratio (BUN/creat) can identify high- vs low-risk RD. Our objective was to determine if combining these biomarkers could further improve risk stratification and clinical phenotyping of patients with RD and HF.Methods and ResultsA total of 908 patients with a discharge diagnosis of HF were included. Median values were used to define elevated BNP (>1296 pg/mL) and BUN/creat (>17). In the group without RD, survival was similar regardless of BNP and BUN/creat (n = 430, adjusted P = .52). Similarly, in patients with both a low BNP and BUN/creat, RD was not associated with mortality (n = 250, adjusted hazard ratio [HR] = 1.0, 95% confidence interval [CI] 0.6–1.6, P = .99). However, in patients with both an elevated BNP and BUN/creat those with RD had a cardiorenal profile characterized by venous congestion, diuretic resistance, hypotension, hyponatremia, longer length of stay, greater inotrope use, and substantially worse survival compared with patients without RD (n = 249, adjusted HR = 1.8, 95% CI 1.2–2.7, P = .008, P interaction = .005).ConclusionsIn the setting of decompensated HF, the combined use of BNP and BUN/creat stratifies patients with RD into groups with significantly different clinical phenotypes and prognosis.     

Impact of circulating cathepsin K on the coronary calcification and the clinical outcome in chronic kidney disease patients

Chronic kidney disease (CKD) is a cause of coronary artery calcification (CAC) and an independent predictor of major adverse cardiac and cerebrovascular events (MACCE). Cathepsin K (CatK) is a lysosomal cysteine protease which affects vascular calcification and glucose metabolism disorder. We investigated the relationships among CatK, CAC, diabetes mellitus (DM) and MACCE in CKD patients. 113 consecutive CKD patients were enrolled. Their CAC was evaluated by computed tomography. Their plasma CatK level was measured by ELISA. They were divided into two groups by CatK levels and followed up for up to 3 years. The impact of CatK was analyzed in all participants, diabetic patients and non-diabetic patients. Kaplan–Meier analysis demonstrated a significant higher incidence of MACCE in the high CatK group (P = 0.028). The CatK level was significantly higher in patients with MACCE compared to that in patients without MACCE (P = 0.034). Cox’s model revealed the higher plasma CatK and BNP level as independent predictors of MACCE (P = 0.043 and P < 0.01, respectively). Only in non-diabetic patients, there was a significant correlation between CatK and CAC score, and high CatK group had a significant higher level of LDL-C and LDL-C/HDL-C ratio (P < 0.05 and P < 0.001, respectively) than low CatK group. And these lipid disorders were independent predictors of CatK elevation. In CKD patients, our results indicated an impact of higher CatK level on their MACCE. The significant association among the CatK level, CAC and MACCE was found in non-diabetic CKD patients.     

Minor Myocardial Damage is a Prevalent Condition in Patients With Acute Heart Failure Syndromes and Preserved Systolic Function With Long-Term Prognostic Implications. A Report From the CIAST-HF (Collaborative Italo-Argentinean Study on Cardiac Troponin T in Heart Failure) Study

BackgroundHalf of patients with acute heart failure syndromes (AHFS) have preserved left ventricular ejection fraction (PLVEF). In this setting, the role of minor myocardial damage (MMD), as identified by cardiac troponin T (cTnT), remains to be established.AimTo evaluate the prevalence and long-term prognostic significance of cTnT elevations in patients with AHFS and PLVEF.Patients and MethodsThis retrospective, multicenter, collaborative study included 500 patients hospitalized for AHFS with PLVEF (ejection fraction ≥40%) between October 2000 and December 2006. Blood samples were collected within 12 hours after admission and were assayed for cTnT. MMD was defined as a cTnT value of ≥0.020 ng/mL.ResultsMean age was 73 ± 12 years, 47% were female, 38% had an ischemic etiology, and New York Heart Association (NYHA) class was 2.2 ± 0.7. Mean cTnT value was 0.149 ± 0.484 ng/mL, and cTnT was directly correlated with serum creatinine (Spearman's Rho = 0.35, P < .001) and NYHA class (0.25, P < .001). MMD was diagnosed in 220 patients (44%). Patients with MMD showed lower left ventricular ejection fraction (P < .05), higher serum creatinine (P < .001), higher prevalence of ischemic etiology and diabetes mellitus, a worse NYHA class (P < .001), and higher natriuretic peptide levels (P < .001) as compared with patients without MMD. At 6-month follow-up, overall event-free survival was 55% and 75% in patients with and without MMD (P < .001), respectively. On multivariate Cox regression analysis, only NYHA class (HR = 1.50; P = .002) and MMD (HR = 1.81; P = .001) were identified as predictors of events.ConclusionsIncreased cTnT levels were detected in approximately 50% of patients with AHFS with preserved systolic function, and were found to correlate with clinical measures of disease severity. The presence of MMD was associated with a worse long-term outcome, lending support to cTnT-based risk stratification in the setting of AHFS.     

High-normal serum uric acid predicts the development of chronic kidney disease in patients with type 2 diabetes mellitus and preserved kidney function

AimsWe evaluated whether high-normal serum uric acid (SUA) levels can predict the development of chronic kidney disease (CKD) in patients with type 2 diabetes mellitus and preserved kidney function at baseline.MethodsThis was a retrospective observational longitudinal study of patients presenting at the Department of Endocrinology and Metabolism, Pusan National University Hospital. A total of 512 patients with type 2 diabetes mellitus and preserved kidney function (estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73 m²) and normouricemia were included. The main outcome was development of CKD of stage 3 or greater. The patients were divided into four groups according to quartiles of SUA levels.ResultsDuring the follow-up period, 62 (12.1%) patients had progressed to CKD 3 or greater. The group with the highest-normal range of SUA (Q4) showed a higher cumulative incidence of CKD stage 3 or greater than that of the other lower quartiles (Q4 vs. Q3; P = 0.037, Q4 vs. Q2; P < 0.001, Q4 vs. Q1; P < 0.001). In a univariate analysis, Q4 was significantly associated with the development of CKD 3 or greater (log-rank statistic, 31.93; P < 0.001). In a multivariate analysis, Q4 (hazard ratio, 2.97; 95% confidence interval, 1.15–7.71; P = 0.025) showed a significant association with CKD 3 or greater.ConclusionsHigh-normal SUA may predict the occurrence of CKD stage 3 or greater in patients with type 2 diabetes mellitus and preserved kidney function.