bluuebunny/crossref_metadata_2025 huggingface dataset:
Determinants of sudden cardiac death after heart transplantation
Authors: Bonnet G , Coutance G , Waldmann V , Aubert O , Asselin A , Raynaud M , Racape M , Bories M.C , Varnous S , Bruneval P , Leprince P , Marijon E , Loupy A , Jouven X
Published: November 2020

Background

Heart transplant recipients are at high-risk of sudden cardiac death (SCD). However, risk factors of SCD in heart recipients remained poorly described.

Objective

To assess the predictors of SCD beyond the first-year post-transplant.

Methods

We enrolled consecutive patients transplanted between 2004 and 2017 in two French referral centers. We excluded patients deceased during the first year. Patients underwent an evaluation at the day of transplantation and during the first year, comprising clinical, biological, histological, immunological (circulating anti-HLA DSA) and interventional (cardiac allograft vasculopathy assessment) parameters. Echocardiographies were routinely performed in all included patients according to a prespecified protocol. According to the last consensus, SCD was defined as an unexpected out-of-hospital cardiac arrest without obvious non-cardiac cause, in the first hour after initiation of symptoms. Cox model analysis was used to determine the parameters associated with sudden death risk.

Results

A total of 913 patients were included. The median follow-up post-HT was 5.9 years (IQR=2.9–8.5). Among the 213 deaths after one year, 44 patients (21%) died from SCD. In this population, the incidence rate of SCD was 0,82 per 100 person-year (95% CI: 0,51–2,05). Among the 60 parameters tested in univariate analysis, we identified 2 independent factors of sudden death after 1 year post-HT: left ventricular ejection fraction (LVEF) ≤55% any time after transplantation ( HR 4.07, 95% CI 1.94–8.53, p<0.001) and the presence of circulating anti-HLA DSA at the time of transplantation (HR 2.79, 95% CI 1.37–5.68, p=0.005). The incidence rate of SCD was 2.17 per 100 person-year (95% CI: 1.42; 4.60) and 1.21 per 100 person-year (95% CI: 0.80; 2.58) in patients with FEVG<55% (n=73) and in patients with pre-formed DSA (n=260), respectively.

Conclusion

In a large multicentric and highly phenotyped cohort of heart transplant recipients, we identified two independent factors associated with SCD beyond the first year. This study provides fresh evidence of SCD assessment for improving risk stratification of HT recipients.

Funding Acknowledgement

Type of funding source: None
Vaccine-preventable diseases in hospitalized patients with heart failure: a nationwide cohort analysis
Authors: Patil S.P , Gonuguntla K , Rojulpote C , Joshi S , Borja A.J , Kumar M
Published: November 2020

Introduction

Infection related hospitalizations are common among patients with heart failure (HF), including those that could be prevented with appropriate vaccinations.

Objective

We aimed to determine the risk of vaccine preventable diseases (VPDs) in patients with HF.

Methods

We performed a population based retrospective cohort study using the United States- National Inpatient Sample (NIS) Database from 2010 to 2014. We identified patients who were admitted to the hospital with vaccine preventable diseases, namely influenza, varicella zoster infection (VZV), pneumococcal infection, meningococcal infection, diphtheria, pertussis, tetanus, hepatitis A (Hep A) and hepatitis B (Hep B) using international classification of diseases 9th revision clinical modification (ICD-9-CM) codes. In this cohort, we then identified patients with HF. Descriptive statistics were used to estimate the frequencies of various VPDs in patients with heart failure. A multivariate regression model adjusting for age, gender, race, immunosuppression (Diabetes, HIV, Organ transplantation, Malignancy) was employed to determine the risk of VPDs in patients with HF.

Results

Among a total of 11, 64,528 patients admitted with VPDs, HF was present in 1, 01,915 (8.8%).The most common VPD in patients with HF was VZV (30.7%), followed by influenza (28.2%), pneumococcal infection (20.9%) and Hep B (18.5%). Other VPDs were less common: Hep A (1.8%), diphtheria (0.4%), pertussis (0.2%), tetanus (10 patients) and meningococcal infection (0.1%). On multivariate analysis, patients with HF had increased risk of hospitalization due to influenza (aOR=1.20, 95% CI: 1.18–1.21; p<0.001) and pneumococcal infection (aOR=1.31, 95% CI: 1.29–1.33; p<0.001), but were at a lower risk of hospitalization due to VZV (aOR=0.81, 95% CI: 0.8–0.83; p<0.001), Hep B (aOR=0.78, 95% CI: 0.77- 0.8; p<0.001), Hep A (aOR=0.71, 95% CI: 0.67–0.74; p<0.001), Meningococcal infection (aOR=0.64, 95% CI: 0.52–0.78; p<0.001), diphtheria (aOR=0.79, 95% CI: 0.71–0.88; p<0.001) and tetanus (aOR=0.35, 95% CI: 0.19–0.65; p=0.001). No statistically significant association of HF was observed with pertussis (p=0.167).

Conclusion

In our study, patients with HF had a higher risk of hospital admissions secondary to influenza and pneumococcal infections and a lower risk of VZV, Hep B, Hep A, meningococcal infection, diphtheria, and tetanus related admissions when compared with non-HF patients.

Funding Acknowledgement

Type of funding source: None
Anthracycline-induced cardiotoxicity: molecular and genetic predictors for risk assessment
Authors: Grakova E , Shilov S.N , Berezikova E.N , Popova A.A , Neupokoeva M.N , Kopeva K.V , Van-Tin-Gao A.A , Ratushniak E.T , Teplyakov A.T
Published: November 2020

Objective

The objective of this study was to evaluate the role of molecular and genetic biomarkers in the development of anthracycline-induced cardiotoxicity in women with breast cancer at the 12 months after polychemotherapy.

Methods

A total of 176 women, median age of 45,0 [42,0; 50,0] years with breast cancer without cardiovascular diseases who received anthracycline antibiotics as part of polychemotherapeutic treatment were enrolled in the study. Two-dimensional transthoracic echocardiography and 6-minute walk test were performed at baseline and at the 12 months after polychemotherapy. Serum levels of NT-proBNP, sFas-L were measured using an enzyme immunoassay after polychemotherapeutic treatment. Evaluation of gene polymorphisms of p53 protein (polymorphic marker-Arg72Pro exon 4, rs1042522) and nitric oxide synthase (NOS3, Glu298Asp, rs1799983) were carried out by polymerase chain reaction at baseline.

Results

After the 12 months of polychemotherapy all patients had breast cancer remission and were divided into 2 groups: group 1 (n=52) comprised patients with anthracycline-induced cardiotoxicity, group 2 (n=124) comprised those without it. After polychemotherapeutic treatment the median value of NT-proBNP in group 1 was higher (p<0,00001) by 52,4% than in group 2 (113 [101,8; 126,15] pg/mL and 53,8 [43,4; 63,0] pg/mL, respectively). The median value of sFas-L in group 1 was higher (p<0,00001) by 44,3% than in group 2 (125,3 [111,85; 133,95] pg/mL and 69,8 [59,8; 77,6] pg/mL, respectively). Based on ROC-analysis, sFas-L concentration of 95.8 pg/mL (sensitivity of 92.2%, specificity of 92.1%, and AUC=0,951; p=0,0001) and NT-proBNP concentration of 71.5 pg/mL (sensitivity of 99.9%, specificity of 91.9%, and AUC=0,951; p=0,0001) were identified as a cut-off values predicting the development of anthracycline-induced cardiotoxicity. The development of anthracycline-induced cardiotoxicity in women with breast cancer at the 12 months after polychemotherapy significantly was related to the presence of T/T genotype of NOS3 gene (OR = 3,059; p=0,018) and with Arg/Arg genotype of p53 protein gene (OR = 2,972; p=0,001). While, the presence of Pro/Pro the Pro53 gene genotype of p53 protein gene was related to the absence of anthracycline-induced cardiotoxicity.

Conclusion

Our data suggest that evaluation of polymorphisms gene of p53 (rs1042522) and NOS3 (rs1799983) can be recommended before polychemotherapy in women with breast cancer for the risk assessment of anthracycline-induced cardiotoxicity. The serum levels of NT-proBNP and sFas-L after polychemotherapy may be considered as non-invasive biomarkers for prediction of the development of anthracycline-induced cardiotoxicity in women with breast cancer during the 12 months after polychemotherapy.

Funding Acknowledgement

Type of funding source: None
Why do frail patients with chronic heart failure die and become hospitalised?
Authors: Sze S , Pellicori P , Zhang J , Weston J , Clark A.L
Published: November 2020

Background

Frailty is common in patients with heart failure (HF) and is associated with increased morbidity and mortality. A better understanding of the causes of hospitalisations and death in frail patients might help to tailor interventional strategies for these at-risk patients.

Purpose

We studied the cause of death and hospitalisations in ambulatory patients with HF and frailty.

Methods

We assessed frailty using the clinical frailty scale (CFS) in consecutive HF patients attending a routine follow-up visit. Those with CFS ≥5 were classified as frail. Mortality and hospitalisations were ascertained from medical records (updated systematically using an NHS electronic database), discharge letters, autopsy reports and death certificates. We studied the primary cause of death and hospitalisations within one year of enrolment.

Results

467 patients (67% male, median (IQR) age 76 (69–82) years, median (IQR) NT-proBNP 1156 (469–2463) ng/L) were enrolled. 206 (44%) patients were frail. Frail patients were more likely to not receive or receive suboptimal doses of ACEi/ARB and Beta-blockers; while non-frail patients were more likely to be treated with optimal doses.

At 1-year follow up, there were 56 deaths and 322 hospitalisations, of which 46 (82%) and 215 (67%) occurred in frail patients. Frailty was associated with an increased risk of all-cause mortality (HR (95% CI): 4.27 (2.60–7.01)) and combined mortality/ hospitalisation (HR (95% CI): 2.85 (2.14–3.80)), all p<0.001. 57% (n=26) of frail patients died of cardiovascular causes (of which 58% were due to HF progression); although deaths due to non-cardiovascular causes (43%, n=20), especially severe infections, were also common (26%, n=12). (Figure 1)

The proportion of frail patients who had non-elective hospital admissions within 1 year was more than double that of non-frail patients (46% (n=96) vs 21% (n=54); p<0.001). Compared to non-frail patients, frail patients had more recurrent (≥2) hospitalisations (28% (n=59) vs 9% (n=24); p<0.001) but median (IQR) average length of hospital stay was not significantly different (frail: 6 (4–11) vs non-frail: 6 (2–12) days, p=0.50). A large proportion of hospitalisations (64%, n=137) in frail patients were due to non-cardiovascular causes (of which 34%, 30% and 20% were due to infections, falls and comorbidities respectively). Of cardiovascular hospitalisations (36%, n=78), the majority were due to decompensated HF (67%, n=46). (Figure 1)

Conclusion

Frailty is common in patients with HF and is associated with an increased risk of mortality and recurrent hospitalisations. A significant proportion suffered non-cardiovascular deaths and hospitalisations. This implies that interventions targeted at HF alone can only have limited impact on outcomes in frail patients.

Figure 1

Funding Acknowledgement

Type of funding source: None
Diastolic and systolic function of diabetic cardiomyopathy are affected by diffuse myocardial fibrosis: a cardiac MRI study
Authors: Bojer A.S , Soerensen M.H , Gaede P , Madsen P.L
Published: November 2020

Background

Increased myocardial extracellular volume (ECV) likely is suggested to be of importance for cardiac function in type 2 diabetes (T2DM).

Purpose

We analysed the effect of increasing ECV on cardiac myocardial structure and function and association to typical complications related to diabetes

Methods

296 patients (pt.) with T2DM and 25 controls were recruited. Cardiac magnetic resonance scan with adenosine stress and gadolinium was performed. Left ventricle (LV) diastolic function was evaluated by echo Doppler.

Results

246 pt. scan and all control scans were available for analysis. ECV was significantly different between pts. and controls (29.5±3.3 vs 26.1±1.5, P<0.001). Pts. were grouped in ECV percentiles: ≤25, 25–75, and ≥75. Pts. with ECV in the highest percentile had lowered LV ejection fraction (LVEF) and increased LV end-diastolic (EDV) and end-systolic (ESV) volumes, and left atrial (LA) maximal volume. No difference was found on LV mass. With increasing ECV a lowered LV myocardial perfusion index (MPRI) and an increased prevalence of albuminuria, retinopathy, and autonomic neuropathy was found. Of interest, with increasing ECV lateral as well as septal e' were lowered and the E/e' increased.

Conclusions

In combination with lowered myocardial perfusion but independently of myocardial hypertrophy, myocardial interstitial diffuse fibrosis is related to the diastolic dysfunction of diabetic cardiomyopathy.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): NSR hospital, Denmark and the Danish Heart Foundation
The incidence, clinical significance of depression and its clinical course after a cardac device implantation in patients with severe heart failure
Authors: Podolecki T , Pudlo R , Mazurek M , Jedrzejczyk-Patej E , Koziel M , Sokal A , Kowalski O , Lenarczyk R , Kalarus Z
Published: November 2020

Aim

To assess the incidence, clinical significance of depression and the impact of a cardioverter-defibrillator (ICD) or cardiac resynchronization therapy-defibrillator (CRT-D) implantation on psychiatric status in patients with heart failure (HF).

Methods

The prospective, single-center study encompassed 575 consecutive HF patients implanted with a CRT-D or ICD. Finally, the study population consisted of 494 subjects (186 ICD and 308 CRT-D patients), as 81 patients taking antidepressants were excluded from the analysis. All patients underwent psychiatric examination at the time of implantation, and the assessment of psychiatric status was repeated after 3, 6, 12 and 24 months. The study population was divided into 4 groups: Group 1 encompassed 101 (20.4%) patients with persistent depression, Group 2 constituted of 95 (19.2%) patients with depression that developed after ICD/CRT-D implantation, whereas 43 (8.7%) patients with remission of depression comprised Group 3, and Group 4 encompassed 255 (51.6%) patients with never diagnosed depression. Data on long-term follow-up (median 34.1 months) were screened to identify patients who developed a composite endpoint defined as death or hospitalization for decompensated HF.

Results

The cumulative incidence of depression at the baseline assessment was 39.1%. Depression developed in 95 (27.1%) patients, whereas remission of depression was observed in 43 (29.9%) subjects after ICD/CRT-D implantation. ICD intervention (HR 3.3) and increase in NYHA class by at least one class (HR 2.6) were the independent risk factors for depression development, whereas mitral regurgitation reduction (HR 1.9), as well as improvement in NYHA class by at least one class (HR 2.4) were the independent predictors for depression remission. Patients with persistent depression (Group 1) and those with newly developed depression (Group 2) were at significantly higher risk of a composite endpoint compared to patients in Group 3 and Group 4 (Table 1).

Conclusions

Depression is a common comorbidity associated with HF, as it affects 4 of 10 HF patients. ICD intervention and HF worsening are the strongest predictors for depression development after ICD/CRT-D implantation. Depression is a strong, independent risk factor of poor outcomes in HF population.

Funding Acknowledgement

Type of funding source: None
Pattern and predictors of one-year mortality in heart failure: China PEACE Prospective Heart Failure Study
Authors: Li J , Zhang L , Liu J , Bai X , Zhang H , Huo X
Published: November 2020

Background

Heart failure (HF) is a global public health problem, which causes high mortality.

Purpose

To characterize the pattern of 1-year mortality, including the rate and timing of death, and to identify clinical and non-clinical factors predicting 1-year all-cause mortality after hospitalization for HF.

Methods

We prospectively enrolled patients who were hospitalized primarily for HF and discharged alive from 52 hospitals across 20 provinces in China between August 2016 and May 2018, and followed them up by face-to-face interview or telephone. Patients' fatal status were ascertained according to investigators' report and national death registration. Cognitive function was measured by Mini-Cog score and health status was measured by Kansas City Cardiomyopathy Questionnaire (KCCQ). We fitted a Cox proportional hazards model accounting for hospital as random effects to identify patient characteristics associated with 1-year all-cause mortality.

Results

Among 4899 patients, 4882 (97.7%) completed 1-year follow-up. The median (IQR) age was 67 (57, 75) years and 37.5% were women. The main etiology of HF was ischemic heart disease (53.1%), 66.0% of patients had history of HF before the index hospitalization. Among 813 deaths within one year after discharge, 13.4% and 58.4% occurred within one months and six months, respectively. Systolic blood pressure <100mmHg at admission (hazard ratio [HR] 2.33, 95% CI 1.76–3.08), NYHA class IV (HR 1.37, 95% CI 1.1–1.7), anemia (HR 1.3, 95% CI 1.1–1.54), hs-cTNT≥18 ng/L (HR 1.84, 95% CI 1.53–2.22), hyponatremia (HR 1.66, 95% CI 1.38–1.98), LVEF<40% (HR 1.25, 95% CI 1.02–1.53), QRS interval≥120mms (HR 1.19, 95% CI 1.02–1.4), Cognitive impairment (HR 1.25, 95% CI 1.07–1.46) and low KCCQ score (HR 1.24 per 25 score decrease, 95% CI 1.11–1.39) were associated with higher risks of 1-year all-cause mortality. In contrast, female (HR 0.83, 0.7–0.99), sleep apnea syndrome (HR 0.55, 95% CI 0.35–0.88) were associated with lower risks of 1-year all-cause mortality.

Conclusion

In China, one in six patients hospitalized for HF die within 1-year, with the majority occurring during the first 6 months after hospital discharge. Both clinical and non-clinical factors predict 1-year mortality.

Funding Acknowledgement

Type of funding source: Other. Main funding source(s): The National Key Research and Development Program from the Ministry of Science and Technology of China; the CAMS Innovation Fund for Medical Science; the 111 Project from the Ministry of Education of China
Direct comparison of BNP and NT-proBNP for mortality prediction in patients with acute dyspnea
Authors: Wussler D , Belkin M , Strebel I , Kozhuharov N , Sabti N , Nowak A , Michou E , Flores D , Gualandro D , Breidthardt T , Mueller C
Published: November 2020

Background

It is unclear whether BNP or NT-proBNP, their admission or discharge measurement or percentage change during hospitalization are preferable for mortality prediction in patients with acute dyspnea.

Purpose

To directly compare BNP and NT-proBNP regarding their potential in mortality prediction in patients with acute dyspnea and in patients with dyspnea due to AHF.

Methods

In a prospective multicenter diagnostic study the presence of AHF was centrally adjudicated by two independent cardiologists among patients presenting with acute dyspnea. The levels of BNP and NT-proBNP were measured at presentation and discharge. Patients were stratified according to their natriuretic peptide response (responders vs. non-responders: natriuretic peptide decrease ≥25% vs. <25% before discharge). Prognostic accuracy for 720-day mortality was quantified using the area under the receiver-operating-characteristic curve (AUC). Cox proportional hazard models were constructed to identify significant predictors for 720-day mortality.

Results

Among 1156 patients presenting with acute dyspnea, 353 (30.5%) died within 720 days of follow-up. Prognostic accuracy for death at 720 days was significantly higher for discharge compared to admission measurements for BNP (AUC 0.750 vs. 0.711, p<0.001) and NT-proBNP (AUC 0.769 vs. 0.720, p<0.001). When directly comparing discharge measurements, NT-proBNP levels exhibited a significantly higher accuracy (p=0.013). 632 (54.6%) and 600 (51.9%) patients were BNP and NT-proBNP non-responders, respectively. Among BNP and NT-proBNP non-responders 202 (32%) and 207 (34.5%) patients died within 720 days of follow-up. After adjusting for common covariates NTproBNP response was the strongest predictor for 720-day mortality in a Cox regression model (Hazard ratio for NT-proBNP non-responders: 2.096 (95% CI 1.550–2.835), p<0.001). Results were confirmed in a sensitivity analysis of 687 (59.4%) patients with adjudicated AHF.

Conclusion

Percentage change of NT-proBNP during hospitalization seems to be the strongest predictor for long-term mortality in patients with acute dyspnea in general and in those with dyspnea due to AHF in particular.

ROC curve for direct comparison

Funding Acknowledgement

Type of funding source: None
Urinary chlorine: a potential biomarker of diuretic resistant patients
Authors: Zegri Reiriz I , Garcia-Coscuella D , Moreno T , Ortega R , Ruiz A , Mesado N , Aran F , Brossa V , Camprecios M , Lopez L , Roig E , Mirabet S
Published: November 2020

Background

Natriuresis is gaining growing interest in identifying diuretic resistance (DR) patients. However, it has not been proved useful beyond the first day with intravenous (iv) furosemide. Moreover, data regarding urinary chlorine (uCl) or urinary potassium (uK) are scarce. We sought to assess the urine electrolyte pattern in acute heart failure (AHF) outpatients to identify those who will present DR.

Methods

Single-center prospective registry of outpatients with AHF who need iv furosemide. In visit 1 (V1), baseline spot urine sample was collected. Furosemide iv bolus plus intensification of oral diuretics were performed. In control visit (V2), baseline spot urine sample was collected and congestion data were evaluated. Urine electrolytes were assessed in relation to DR (defined as need of iv furosemide in V2 due to persistent congestion).

Results

From June to December 2019, 76 patients were included: median age of 75.5 years (68.2–82), glomerular filtration 40 ml/min/1.73m2 (29.2–59.2) and NT-proBNP 3340 ng/L (1296–7044).

In V1, DR patients showed higher levels of uK and lower uNa/uK than NDR (p=0.014 and p=0.007, respectively). In V2, after a median of 6 (6–15) days of intensified diuretic treatment, uNa and uCl dropped with adequate decongestion but not in DR patients (p=0.020 and p=0.001, respectively). Thus, DR patients showed in V2 higher uCl and similar uNa than NDR (table).

Conclusions

After several days of intensified diuretic treatment, uCl and uNa dropped during proper decongestion but not in DR patients, showing higher levels of uCl than NDR. Mantained levels of uCl could help to identify patients with persistent congestion.

Funding Acknowledgement

Type of funding source: None
N-terminal pro-B-type natriuretic peptide in the diagnosis of acute heart failure
Authors: Lee K.K , Doudesis D , Anwar M , Astengo F , Japp A , Tsanas A , Shah A.S.V , Januzzi J.L , Mills N.L
Published: November 2020

Background

N-terminal pro-B-type natriuretic peptide (NT-proBNP) testing can aid in the evaluation of patients with suspected acute heart failure. Current approaches are based on thresholds selected to give good negative and positive predictive value, however the optimal means to utilise NT-proBNP is uncertain.

Methods

Embase, Medline and Cochrane central register of controlled trials were searched for studies evaluating NT-proBNP in patients with suspected acute heart failure. Individual patient-level data was requested and diagnostic performance for the guideline-recommended rule-out (300 pg/mL) and age-specific rule-in (450, 900 and 1,800 pg/mL) thresholds were evaluated with random-effects meta-analysis. A generalised linear mixed model was developed and validated as a decision-support tool that combines NT-proBNP with clinical characteristics to report the probability of acute heart failure (0–100) for an individual patient.

Results

Fourteen studies from 13 countries provided individual patient-level data in 10,365 patients, of which, 43.9% (4,549/10,365) had an adjudicated diagnosis of acute heart failure. At the rule-out threshold, the negative predictive value (NPV) was 94.6% (91.9%-96.4%), with significant heterogeneity across patient subgroups (see Figure). At the rule-in thresholds, the positive predictive values (PPV) for those <50 years, 50–75 years, and >75 years were 61.0% (55.3%-66.4%), 72.7% (62.1%-81.3%) and 80.5% (71.1%-87.4%), respectively. In patients without prior heart failure, our model had good discrimination and calibration (area under the curve of 0.931 [0.925–0.938], Brier score of 0.094). A score of <5.6 and ≥45.2 identified 42.3% of patients as low-probability of acute heart failure (NPV 98.5%, 97.6%-99.1%) and 30.5% as high-probability (PPV 75.1%, 67.7%-81.3%) with consistent performance across subgroups.

Conclusions

The diagnostic performance of NT-proBNP thresholds to rule-out and rule-in acute heart failure varies across patient subgroups. A model that uses NT-proBNP as a continuous measure provides a more consistent and individualised approach.

NPV of NT-proBNP threshold of 300 pg/mL

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): British Heart Foundation
Prognostic value of pulmonary-systemic pressure ratio and fibrosis-4 index in patients admitted for acute decompensated heart failure
Authors: Yamada T , Watanabe T , Morita T , Furukawa Y , Tamaki S , Kawasaki M , Kikuchi A , Kawai T , Seo M , Nakamura J , Kayama K , Kawahira M , Fukunami M
Published: November 2020

Background

Concomitant presence of pulmonary hypertension in heart failure (HF) is associated with increased adverse events and may be related to interventricular uncoupling and impaired cardiac efficiency. An increased mean pulmonary artery pressure to mean systemic arterial pressure ratio (MPS ratio), a marker of interventricular coupling and efficiency, is reported to be associated with worse clinical outcomes in patients with advanced HF. On the other hand, cardiohepatic interactions have been a focus of attention in HF, and liver dysfunction in HF patients is caused by liver congestion, which is related to liver stiffness. It has been recently shown that liver stiffness assessed by non-invasive fibrosis marker such as Fibrosis-4 (FIB4) index predicts the mortality in HF patients. However, there is no information available on the prognostic value of the combination of MPS ratio and FIB4 index in patients with acute decompensated heart failure (ADHF).

Methods and results

We studied 238 patients admitted for ADHF, who underwent right heart catheterization at the admission and were discharged with survival. MPS ratio was obtained at the admission. FIB4 index was calculated by the formula: age (yrs) × AST [U/L] / (platelets [103/μL] × √(ALT[U/L])). FIB4 index >2.67 was defined as abnormal, as previously reported. During a follow up period of 5.2±4.4 yrs, 93 patients died. At multivariate Cox analysis, MPS ratio (p=0.01) and FIB4 index (p=0.01) were significantly associated with the total mortality, independently of creatinine level and prior heart failure hospitalization, after the adjustment with hemoglobin, albumin levels and body mass index. The patients with both MPS ratio ≥0.388 (determined by ROC analysis; AUC 0.613 [0.541–0.687]) and abnormal FIB4 index had a significantly increased risk of the total mortality than those with either greater MPS or abnormal FIB4 index and none of them (52% vs 40% vs 28%, p=0.0068, respectively).

Conclusion

The combination of MPS ratio and FIB4 index might be useful for stratifying ADHF patients at higher risk for the total mortality.

Funding Acknowledgement

Type of funding source: None
The clinical impact of delirium in the patients with acute decompensated heart failure
Authors: Aikawa Y.A , Noguchi T.N , Morii I.M
Published: November 2020

Background

Delirium is frequent in-hospital complication in patients with illness. However, the clinical impact of delirium on cardiovascular mortality has not been fully addressed in patients with acute decompensated heart failure (ADHF).

Methods

Between April 2016 and May 2019, 474 consecutive patients with ADHF admitted to our institution were enrolled and followed for 6 months after discharge. Delirium was defined according to the Intensive Care Delirium Checklist. To compare the clinical outcome, we divided study patients into 3 groups according to the presence or absence of delirium: non-delirium (ND) (n=349), improved-delirium during hospitalization (ID) (n=68), and prolonged delirium (PD) (n=57).

Results

One hundred twenty-five (26.4%) patients developed delirium. During hospitalization, PD had higher incidence of all-cause death, cardiovascular death, and worsening heart failure compared with ND and ID (20.0% vs. 3.7% and 2.9%, 10.9% vs. 2.5% and 1.4%, 21.8% vs. 2.5% and 4.3%, p<0.001, respectively). Multivariable analysis identified the presence of frailty (OR: 8.56, 95% CI: 3.46–23.7) and dementia (OR: 7.34, 95% CI: 3.52–15.9), use of H2-blocker (OR: 3.41, 95% CI: 1.08–10.9) and plasma level of CRP (OR: 1.30, 95% CI: 1.06–1.61) as significant independent determinants of delirium. Also, in multivariable analysis, the development of frailty (OR: 5.51, 95% CI: 2.80–11.5), delirium (OR: 4.59, 95% CI: 2.23–9.66) and age (OR: 1.06, 95% CI: 1.03–1.11) were the independent determinants of composite endpoint with in-hospital death and discharge to other than home. Early treatment of delirium performed significantly higher in ID than PD (55.7% vs. 29.1%, p=0.003).

Conclusion

This study suggested that PD contributed to increasing in-hospital events in the patients with ADHF and significance of early screening and treatment for delirium.

Figure 1. Outcomes during hospitalization

Funding Acknowledgement

Type of funding source: None
Integrated analysis of DNA methylation profile in HLA-G gene and imaging in coronary heart disease
Authors: Benincasa G , Schiano C , Infante T , Franzese M , Casale R , Della Mura N , Fiorito C , Mansueto G , Soricelli A , Nicoletti G.F , Salvatore M , Napoli C
Published: November 2020

Aims

Immune endothelial inflammation, underlie coronary heart disease (CHD) related phenotypes, could provide new insight into the pathobiology of the disease. We investigated DNA methylation level of the unique CpG island of HLA-G gene in CHD patients and evaluated the correlation with cardiac computed tomography angiography (CCTA) features.

Methods

Thirty-two patients that underwent CCTA for suspected CHD were enrolled for this study. Obstructive CHD group included fourteen patients, in which there was a stenosis greater than or equal to 50% in one or more of the major coronary arteries detected; whereas subjects with Calcium (Ca) Score=0, uninjured coronaries and with no obstructive CHD were considered as control subjects (Ctrls) (n=18). For both groups, DNA methylation profile of the whole 5'UTR-CpG island of HLA-G was measured. The plasma soluble HLA-G (sHLA-G) levels were detected in all subjects by specific ELISA assay. Statistical analysis was performed using R software.

Results

For the first time, our study reported that 1) a significant hypomethylation characterized three specific fragments (B, C and F) of the 5'UTR-CpG island (p=0.05) of HLA-G gene in CHD patients compared to Ctrl group; 2) hypomethylation level of one specific fragment positively correlated with coronary Ca score, a relevant parameter of CCTA (p<0.05) between two groups.

Conclusions

Our results showed that reduced levels of circulating HLA-G molecules could derive from epigenetic marks inducing hypomethylation of specific regions into 5'UTR-CpG island of HLA-G gene in CHD patients with obstructive coronary stenosis vs non critical stenosis group.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): Italian Minister of Health
Hemodialysis patients with better coronary flow reserve and nutrition status have surprising prognosis
Authors: Imaoka T , Umemoto N , Oshima S
Published: November 2020

Background

In clinical setting, ischemic heart disease is a challenging problem in hemodialysis (HD) population. Coronary flow reserve (CFR) measured by 13 ammonia positron emitting tomography (13NH3PET) is an established and reliable modality for detecting coronary artery disease. Furthermore, some prior studies show CFR is an important and independent predictor for cardiovascular event and mortality. On the other hand, HD patients with malnutrition status have poor prognosis. We have reported about the relationship between cardiovascular events and geriatric nutrition risk index (GNRI). Now, we wonder the predictability of combination of CFR and GNRI.

Methods and result

We collected 438 consecutive HD patients who received 13NH3PET in our hospital suspected for ischemic heart disease. 29 patients were excluded due to undergoing coronary revascularization within 60 days, 103 patients were excluded due to incomplete database. In total, 306 HD patients were classified into 4 group according the median value of CFR (1.99) and GNRI (97.73); Low CFR Low GNRI group (n=77), High CFR and Low GNRI group (n=76), Low CFR High GNRI group (n=78) and High CFR High GNRI group (n=75). We collected their follow up data up to 1544 days (median 833 days) about all-cause mortality and cardiovascular (CV) mortality. Surprisingly, there is no mortality event in High CFR High GNRI group. We analyzed about all-cause mortality, CV mortality. Kaplan-Meyer analysis shows there are statistically intergroup differences in each (all-cause mortality; log rank p<0.01, CV mortality; log rank p=0.02). Furthermore, we calculated area under the curve (AUC) analysis, net reclassification improvement (NRI) and integrated discrimination improvement (IDI)m adding GNRI and CFR on conventional risk factors. There are intergroup differences for all-cause mortality in AUC [conventional risk factors, +GNRI, +GNRI+CFR; 0.70, 0.72 (p=0.29), 0.79 (p<0.01)], NRI [+GNRI; 0.32 (p=0.04), +GNRI+CFR 0.82 (p<0.01)] and IDI [+GNRI; 0.01 (p=0.05), +GNRI+CFR 0.09 (p<0.01)].

Conclusion

HD patients with low CFR and malnutrition status has statistically significant poorer prognosis comparing HD patients with high CFR and without malnutrition status. Adding combination of GNRI and CFR on conventional risk factors improves the predictability of HD population's prognosis.

Funding Acknowledgement

Type of funding source: None
The detection of multivessel coronary artery disease: the value of quantitative myocardial blood flow and coronary flow reserve assessment
Authors: Zavadovskiy K , Mochula A , Maltseva A , Boshchenko A , Baev A , Andreev S , Liga R , Gimelli A
Published: November 2020

Background/Introduction

The recent Cadmium-Zinc-Telluride (CZT) camera for MPS allows evaluating absolute MBF and CFR, possibly increasing the accuracy in detecting of multivessel CAD.

Purpose

To evaluate the accuracy of myocardial blood flow (MBF) and coronary flow reserve (CFR) quantitation performed by myocardial perfusion scintigraphy (MPS) for the detection of multivessel coronary artery disease (CAD).

Methods

Fifty-two patients with suspected or known CAD were enrolled in the study. All patients underwent CZT MPS, with the evaluation of MBF and CFR, followed by invasive coronary angiography. According to MPS and coronary angiography results, patients were divided into three groups. 1) non-obstructive CAD and normal MPS scan (control group) (n=7), 2) one vessel disease (1VD) (n=16), with significant coronary stenosis (≥70%) in one major epicardial coronary artery, 3) multivessel disease (MVD) group (n=29), with two or more major epicardial coronary arteries with (≥70%) stenoses or with ≥50% LMA stenosis.

Results

Absolute MBF and CFR were significantly reduced in patients with MVD as compared to those with 1VD [0.93 (IQR 0.76; 1.39) vs 1.94 (1.37; 2.21) ml/min/g, p=0.00012] and [1.4 (IQR 1.02; 1.85) vs 2.3 (1.8; 2.67), p=0.0004], respectively. The Syntax score correlated with global stress MBF (ρ=−0.64; p<0.0001) and CFR (ρ=−0.53; p=0.0003). ROC analysis showed higher sensitivity and specificity for stress MBF (85.2% and 81%), and CFR (88.9% and 80%) compared with semiquantitative MPS stress evaluation (69% and 69%). Multivariate regression analysis showed that only stress MBF [OR (95% CI) 0.59 (0.42–0.82); p<0.0003] was an independent predictor of MVD.

Conclusion

The use of absolute myocardial blood flow analysis with the CZT camera may identify high risk patients, such as those with multivessel disease. This approach could be used in clinical practice, increasing the accuracy in the evaluation of patients with known or suspected coronary artery disease.

Funding Acknowledgement

Type of funding source: None
Artificial intelligence-derived physiological aging is associated with coronary endothelial dysfunction
Authors: Ahmad A , Toya T , Corban M , Attia Z.I , Lopez-Jimenez F , Shelly Cohen M , Noseworthy P.A , Kapa S , Friedman P.A , Lerman A
Published: November 2020

Background

An Artificial intelligence (AI)-enabled algorithm can provide an age estimate from a single standard resting ECG. The gap between AI-estimated age (ECG age) and chronological age (Age-Gap) has been associated with total and cardiovascular mortality. We hypothesized that coronary endothelial dysfunction (CED), an early feature of coronary atherosclerosis, is associated with physiological aging, as measured by ECG age.

Purpose

The aim of this study is to investigate the association of CED, a potential index of cardiac aging, and AI-estimated physiological aging.

Methods

1902 patients with signs and/or symptoms of ischemia and with non-obstructive coronary artery disease (<40% angiographic stenosis) who underwent functional coronary angiography with intracoronary (IC) acetylcholine (Ach) infusions and a resting ECG within one year were included in this analysis. CED was defined as coronary artery constriction [%ΔCoronary artery diameter (CAD) <0] in response to IC Ach. Patients were categorized as CED+ or CED−. The ECG age were calculated by a previously-trained AI algorithm that was built using the Keras framework with Tensorflow backend and Python. The association between ECG-age and Age-Gap, with CED was investigated.

Results

Average chronological age was 50.9±12.5, ECG age was 54.1±11.6, 1261 (66%) were females. Compared to CED−, the CED+ group had more males and hyperlipidaemia (p<0.05 for both). Age-gap was significantly higher in patients with CED+ (Fig. A). Multiple regression analysis showed that CED+ was associated with Age-gap (standardized β [sβ] coefficient = 0.08, P=0.001) even after adjustment for chronological age (sβ coefficient = 0.07, P=0.001), and even after adjusting for other cardiovascular risk factors like gender and obesity (sβ coefficient = 0.07, P<0.0001). Furthermore, there is a significant gradual increase in vasoconstriction, in response to IC Ach, with increasing Age-gap (Fig. B).

Conclusion

Abnormal coronary endothelial function is associated with an increased AI-estimated age which could indicate a higher physiological age.

Funding Acknowledgement

Type of funding source: None
Thermodilution-derived resting coronary flow measurement: “a reverse dose finding study”
Authors: Gallinoro E , Colaiori I , Di Gioia G , Fournier S , Kodeboina M , Candreva A , Sonck J , Pijls N.H.J , Collet C , De Bruyne B
Published: November 2020

Background

Hyperemic absolute coronary blood flow (in mL/min) can be safely and reproducibly measured with intracoronary continuous thermodilution of saline at room temperature at an infusion rate of 20 mL/min. This study aims at assessing the best infusion rate to measure resting flow by thermodilution, i.e. low enough to avoid microvascular dilation but high enough to allow reliable thermodilution tracings

Methods and results

In 26 coronary arteries (24 patients) with angiographic non-significant stenoses, absolute flow was assessed by continuous saline thermodilution at infusion rates of 10 mL/min and 20 mL/min using a pressure/temperature sensored guide wire, a dedicated infusion catheter and a dedicated software. Average peak velocity (APV) was measured simultaneously using an intracoronary Doppler-wire. In addition, in a subgroup of 10 arteries, absolute flow and APV were also measured during saline infusion at 6 ml/min and 8 ml/min.

In 26 coronary arteries there was no significance difference in the Pd/Pa and in the APV at baseline and during the infusion of saline at 10 ml/min (Pd/Pa: 0.94±0.057 vs 0.94±0.059, p=0.82; APV: 22.2±8.40 vs 23.2±8.39 cm/s, p=0.63). In contrast, at an infusion rate of 20 mL/min, we observed a significant decrease in Pd/Pa compared to baseline (0.85±0.089 vs 0.95±0.053 vs, respectively, p<0.001) and a significant increase in APV (22.2±8.4 cm/s to 57.8±25.5 cm/s, respectively, p<0.001). The coronary flow reserve (CFR) evaluated by Doppler and intracoronary continuous thermodilution correlated well (r=0.87, 95% CI = 0.72–0.94, p<0.001) and Bland-Altman analysis documented a mean bias of −0.003 (limit of agreement −1.05 to 1.04) thus indicating the presence of resting coronary blood flow during the infusion of 10 mL/min of saline. In 10 coronary arteries saline infusions at 6 and 8 ml/min did not produce any significant changes in the Pd/Pa and in the APV compared to baseline and both Doppler and Thermodilution derived CFR correlated well at each infusion rate (6 ml/min: r=0.71, 95% CI 0.14–0.92, p=0.02; 8ml/min: r=0.78, 95% CI=0.31–0.95, p=0.007). However, with an infusion rate of 6 mL/min, an unstable thermodilution tracing was observed. Accordingly, Bland-Altman analysis showed a significantly larger dispersion of the CFR values when 6 ml/min was used to measure resting coronary flow (as compared with 8 m/min): mean bias at 6 ml/min: −0.53, limits of agreement: −2.25 to 1.20: mean bias at 8 ml/min: 0.004, limits of agreement: −0.72 to 0.73.

Conclusion

Absolute resting coronary flow can be measured by intracoronary continuous thermodilution of saline at infusion rate of 8–10 ml/min.

Funding Acknowledgement

Type of funding source: None
Role of peroxisome proliferators-activated receptor-gamma in advanced glycation end product-mediated functional loss of voltage-gated potassium channel in rat coronary arteries
Authors: Li W , Gao S.D , Hua B , Liu Q.B , Liu H.R , Li H.W
Published: November 2020

Background

Voltage-gated K+ (Kv) channels in coronary artery smooth muscle cells (CSMCs), especially the major specific Kv1 subfamily, contribute to coronary artery vasodilation. Advanced glycation end products (AGEs) have been strongly implicated in diabetes-related cardiovascular complications. Our previous study showed AGEs can impair Kv channel-mediated coronary vasodilation by reducing Kv channel activity. However, its underlying mechanism remains unclear.

Purpose

Here, we used isolated rat small coronary arteries (RSCAs) and primary CSMCs to investigate the effect of AGEs on Kv channel-mediated coronary vasodilation and the possible involvement of peroxisome proliferators-activated receptor (PPAR)-γ pathway.

Methods

RSCAs and primary CSMCs were isolated, cultured and treated with bovine serum albumin (BSA), AGE-BSA, alagrebrium (ALA, AGE cross-linking breaker), pioglitazone (PIO) and/or GW9662, and then divided into the following groups: DMEM, BSA, AGE, AGE+ALA, AGE+PIO, and AGE+PIO+GW9662. Kv channel-mediated coronary vasodilation was analyzed using wire myograph. Histology and immunohistochemistry of RSCAs were performed. Western blot was used to detect the protein expression of RAGE, the major Kv1 channel subunits expressed in CSMCs (Kv1.2/1.5), PPAR-γ, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-2 (NOX-2).

Results

AGEs markedly reduced forskolin-induced Kv channel-mediated vasodilation of RSCAs by interacting with the receptor for AGEs (RAGE), and ALA or PIO significantly reversed this effect. In both RSCAs and primary CSMCs, AGEs decreased Kv1.2 and Kv1.5 channel protein expression, inhibited PPAR-γ expression, increased RAGE and NOX-2 expression. Treatment with ALA or PIO partially reversed the effects of AGEs on Kv1.2/Kv1.5 expression, accompanied by elevation of PPAR-γ level and diminished oxidative stress.

Conclusion

AGE/RAGE axis-induced inhibition of PPAR-γ pathway and enhancement of oxidative stress may contribute to AGEs-mediated Kv channel dysfunction and coronary vasodilation in RSCAs. Our results may provide new insights into developing therapeutic strategies to manage diabetic vasculature.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): National Natural Science Foundation of China; Natural Science Foundation of Beijing (7172059)
Proteoglycan remodeling is accelerated in women with angina pectoris and diffuse myocardial fibrosis: the iPOWER Study
Authors: Mygind N.D , Holm Nielsen S , Mide Michelsen M , Pena A , Bechsgaard Frestad D , Suhrs E , Bove K.B , Genovese F , Nielsen H.B , Karsdal M , Vejlstrup N , Prescott E , Kastrup J
Published: November 2020

Background

Women with angina and no obstructive coronary artery disease (CAD) have an unfavourable prognosis, possibly due to coronary microvascular disease and diffuse myocardial fibrosis (DMF). In DMF myocardial extracellular matrix (ECM) proteins are actively remodeled by matrix metalloproteinase (MMP).

Purpose

We investigated MMP-mediated degradation of the protegoglycans biglycan and versican in women with angina pectoris and possible DMF assessed by cardiac magnetic resonance T1 mapping.

Methods

Seventy-one women with angina pectoris and no obstructive CAD were included. Asymptomatic age-matched women served as controls (n=32). Versican and biglycan were measured in serum by specific competitive enzyme-linked immunosorbent assays. T1 mapping was performed by cardiac magnetic resonance with gadolinium measuring T1 and extracellular volume (ECV).

Results

Both biglycan and versican levels were higher in symptomatic women compared with controls; 31.4 ng/mL vs. 16.4 ng/mL (p<0.001) and 2.1 ng/mL vs. 1.8 ng/mL (p<0.001), respectively (Figure 1) and were moderately correlated to global ECV (r2=0.38, p<0.001 and r2=0.26, p=0.015 respectively).

Conclusion

Turnover of biglycan and versican was increased in symptomatic compared to asymptomatic women and associated to ECV, supporting a link between angina with no obstructive CAD and fibrotic cardiac remodeling. The examined biomarkers may prove to be suitable for monitoring active ECM remodeling.

Figure 1. Levels of BGM and VCANM

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): This work was supported by The Danish Heart Foundation, the Danish Research Fund (Den Danske Forskningsfond) and by University of Copenhagen.