bluuebunny/crossref_metadata_2025 huggingface dataset:
Regional levels of tenascin- C in patients with heart failure and atrial fibrillation
Authors: Grosse A , Mettke F , Kirsch K , Gruen K , Franz M , Schulze P C , Surber R
Published: November 2023

Background

Tenascin-C (TNC) is an extracellular matrix glycoprotein that is upregulated at high levels during active tissue remodeling. The serum concentration of TNC has been reported to be increased in patients with several cardiac diseases. The aim of this study was 1) to measure the TNC plasma level in heart failure (HF) and atrial fibrillation (AF) patients compared to patients without structural heart disease and 2) to search for a local production in the heart.

Methods

This study included 13 patients with HF who underwent CRT- implantation (CRT- group), 13 patients with persistent AF who underwent left atrial catheter ablation (AF- group) and 13 patients without structural heart disease or AF, who underwent electrophysiological study (Control- group). Blood was collected at the beginning of the procedures from the coronary sinus (CS), superior vena cava (SVC) and aorta (Ao). Level of TNC-B (ng/dl) in the CS (TNC-CS), SVC (TNC-SVC) and aorta (TNC-Ao) was measured.

Results

Patients characteristics: CRT- group: mean age 74y, 8 male, LV- EF 32%, 3 with a history of atrial fibrillation. AF- group: mean age 68y, 9 male, LV- EF 55%. Control- group: mean age 54y, 9 male, LV- EF 65%.

The TNC level in the SVC was in the CRT group significant elevated (6125 ± 2030 ng/ml vs 475 ± 238 ng/ml in controls (p<0.01). In the AF group the TNC level in the SVC as well was significantly higher 4983 ± 1814 ng/ml vs 475 ± 238 ng/ml in controls (p<0.01). The TNC level of the CRT- and the AF- group were not significant different (p= 0.219) (Figure 1). No significant differences were noted at the various collection sites (CS, SVC and aorta) between the 3 groups (p = 0.38).

Discussion

The TNC serum levels in HF- and AF- patients are elevated compared to a control group without structural heart disease and without a history of AF. We could not determinate, the source of serum TNC, differences in the level of TNC between CS and SVC and aorta were not visible. Whether an effective treatment of HF and AF will lower TNC levels and slow the disease progression needs to be evaluated in further studies.
Selenium deficiency is associated with anemia in heart failure patients - The HARVEST Study
Authors: Molvin J , Jujic A , Holm H , Dieden A , Korduner J , Zaghi A , Nezami Z , Bergmann A , Schomburg L , Magnusson M
Published: November 2023

Background

Heart failure (HF) patients with anemia have worse clinical outcomes with increased hospitalization rates, decreased exercise tolerance, and higher mortality compared to those without anemia. Previous studies have indicated a correlation between selenium deficiency and anemia in healthy elderly individuals and in pregnant women. The BIOSTAT-CHF study reported that HF patients with higher selenium levels were less likely to have anemia or iron deficiency. These studies suggest that selenium deficiency can lead to the development of anemia. However, studies regarding this association in HF patients are limited.

Purpose

The purpose of this study was to examine the relationship between selenium deficiency, measured by selenoprotein P (SELENOP) levels, and anemia, hemoglobin levels, and iron state in subjects with acute HF.

Methods

SELENOP, a well-validated plasma marker of selenium status, was measured in 320 subjects hospitalized for HF in the Swedish HeArt and bRain failure inVESTigation trial (the HARVEST study). Of these subjects, 310 had complete data on all covariates. Prior to analyses, skewed variables were ln-transformed. The relationships between continuous SELENOP levels and 1) Hb levels, 2) anemia (Hb < 115 g/L (women), < 130 g/L (men)), and 3) iron status (as measured by transferrin receptor 1 (TfR1) which increase in iron deficiency) were evaluated using multivariable logistic and linear regression models adjusting for age, sex and renal function (cystatin C). Additionally, selenium deficiency was defined as SELENOP levels in the lowest quartile and its association with anemia, hemoglobin, and iron state was explored in multivariable logistic and linear models.

Results

Anemia was present in 133 subjects (42.9%). SELENOP levels were positively correlated with hemoglobin levels (0.238; p = 2.3x10-5) and negatively associated with TfR1 levels (-0.238, p = 2.0x10-6). In multivariable linear regression models, each 1 standard deviation increase in SELENOP was linked to higher Hb levels and lower TfR1 levels (Table 1). Furthermore, selenium deficiency was associated with lower Hb levels, higher TfR1 levels, and higher odds of anemia in HF patients (Table 1).

Conclusions

In acute heart failure patients, lower levels of selenoprotein P were associated with lower hemoglobin levels, higher transferrin receptor 1 levels, and a higher prevalence of anemia.
Cardiac Troponin T level is not a predictor of mortality in patients with post-cardiotomy shock supported with venoarterial extracorporeal membrane oxygenation
Authors: Celinska-Spodar M , Marta Zaleska-Kociecka M , Ilona Kowalik I , Kusmierczyk M , Kusmierski K , Sitkowska-Rysiak E , Szymanski J , Stepinska J
Published: November 2023

Background

The prognostic significance of a dominant biomarker of cardiac injury, troponin, is unexplored in patients with post-cardiotomy cardiogenic shock supported with venoarterial extracorporeal membrane oxygenation (PCCS–VA-ECMO).

Aims

We sought to investigate the association of early postoperative troponin T with short- and long-term mortality in patients supported with VA-ECMO in the postoperative period.

Methods

We analyzed 1457 troponin measurements of 102 patients with PCCS–VA-ECMO treated between 2013–2018 in a cardiosurgical and transplantation centre. We focused on the relation of troponin concentration 24–48 hours after surgery and 24–48 hours after VA-ECMO implantation and peak troponin value with VA-ECMO weaning, 90-day and one-year mortality.

Results

The median troponin T 24–48 hours following VA-ECMO implantation was 1338 ng/L [Q1–Q3: 526–2727, 90-day survivors 1529 ng/L (Q1–Q3: 836–5791) vs. non-survivors 1294 ng/L (Q1–Q3: 316–2657); P = 0.146]. The median peak troponin was 3583 ng/L [Q1–Q3: 1710–9238, 90-day survivors 3337 ng/L (Q1–Q3: 1863–12305) vs. non-survivors 3666 ng/L (Q1-Q3: 1462–9238); P = 0.709]. Multivariate models of troponin analysis: for VA-ECMO explanation, in-hospital, 90-day and 1-year mortality showed no relation between troponin and mortality. Age, urgency, type and number of procedures, left ventricle ejection fraction before surgery, Euroscore II result, cardiac arrest prior to VA-ECMO implantation or duration of VA-ECMO did not correlate with the extent of troponin release. The strongest risk factor for short- and long-term mortality was the need for hemodiafiltration [HR 2.4].

Conclusions

Isolated early Troponin T release and peak troponin T were not associated, while organ complications were linked with VA-ECMO weaning or short- and long-term prognosis. The results underscore the multiorgan implications of PCCS in determining survival.
Strategic noninvasive multimodal assessment of cardiac performance in patients with heart failure
Authors: Cho J S , Kim M J , Lee K S , Lee M H , Kim D W , Kim T S , Park M W
Published: November 2023

Aims

We sought to evaluate whether a noninvasive combination assay targeting left ventricular filling pressure (LVFP) would be useful for risk stratification of patients with heart failure (HF). Although abnormal LVFP is inevitably related to HF outcomes, its noninvasive application remains difficult in daily practice.

Methods

This prospective observational study enrolled consecutive hospitalized HF patients. According to the baseline N-terminal pro-B-type natriuretic peptide (NT-proBNP) and Doppler echocardiographic diastolic assessments, patients were classified into three groups: normal range of both LVFP and NT-proBNP (Group 1), normal range of LVFP but elevated NT-proBNP (Group 2), and elevated LVFP and NT-proBNP (Group 3). The primary endpoints were the composite adverse cardiovascular events.

Results

Event-free survival in Group 2 (n = 56, mean age of 65.4±12.4) was better than that in Group 3 (n = 45, mean age of 68.5±11.5) but worse than that in Group 1 (n = 123, mean age of 61.4±10.5) (log-rank p <0.001). Cardiopulmonary exercise test (CPET) findings were compatible with these findings. Left atrial strain showed better risk stratification than left atrial volume index. Serial addition of left atrial assessment and CPET in the model incrementally enhanced the predictive power of LVFP-based stratification for adverse events.

Conclusions

The strategic combination of NT-proBNP, echocardiographic LVFP and left atrial function, and CPET is helpful to predict adverse clinical outcomes in patients with HF. The larger the number of combined cardiac performance indicators, the better the noninvasive risk-stratification was.
Prognostic significance of growth differentiation factor-15 across the BMI spectrum in patients with chronic heart failure: Insights from the SUPPORT trial
Authors: Teramoto K , Nochioka K , Sakata Y , Nishimura K , Shimokawa H , Yasuda S
Published: November 2023

Background

Obesity is a risk factor for cardiovascular diseases including heart failure (HF), yet patients with obesity have better outcomes than their leaner counterparts in HF (i.e. the obesity paradox). We sought to investigate whether growth differentiation factor-15 (GDF15), an emerging biomarker in HF reflecting inflammation and oxidative stress, is a prognostic indicator across the body mass index (BMI) spectrum in chronic heart failure (CHF).

Methods

Serum levels of GDF15 and its prognostic significance across BMI were examined in a total of 1,040 Japanese patients with CHF enrolled in a randomized clinical trial of the SUPPORT trial (supplemental benefit of an angiotensin receptor blocker in hypertensive patients with stable heart failure using olmesartan) (mean age 66.0±9.9 years, 26% female). Patients were categorized into four groups: underweight (BMI <18.5 kg/m2; n = 56), normal (BMI 18.5-22.9; n = 304), overweight (BMI 23-24.9; n = 257), and obese (BMI ≥25; n = 423) defined based on the WHO recommendation for Asian-Pacific population.

Results

The underweight group consisted of older patients with a higher prevalence of NYHA class III and reduced left ventricular ejection fraction (LVEF) compared to obese patients (mean age 69.0 vs 64.7 years, NYHA class III 17.9 vs 5.9%, and mean LVEF 49.3 vs 55.5%; all p<0.05). Median GDF15 level in the underweight group was higher (1,864 pg/mL [IQR 1,070-2,626]) but was similar in overweight and obese groups (1,285 [953, 1772] and 1,220 [888-1,789], respectively) compared to normal BMI group (1,276 [879-2,018]). During follow-up (median 10.3 years), 540 composite events of HF hospitalization or all-cause death occurred. The risk was higher in the underweight group (adjusted HR 1.8, 95%CI [1.3-2.5]) and lower in the obesity group (adjusted HR 0.8 [95% CI 0.6-0.9]) compared to the normal BMI group. An increased GDF15 incurred a consistently higher risk from underweight to obese groups; per unit increase in logGDF15 (pg/mL) was associated with 4.1, 2.4, 1.7 and 2.4 times higher risk, respectively. The optimal cut-off point for discriminating those with and without the composite events was 1,343 pg/mL in overall patients. This cut-off value performed well as a prognostic indicator across the continuous BMI spectrum including those with higher BMI (Figure).

Conclusions

The prognostic significance of GDF15 persisted across the BMI spectrum in patients with CHF. GDF15 may be useful for providing prognostic information across patients with a diverse range of BMI even in those with modest outcomes.HF events in high GDF15 across BMI
Visit-to-visit glycemic variability is associated with the incidence of heart failure with improved ejection fraction
Authors: Yang C D , Wang X Q
Published: November 2023

Background

With advanced guideline-directed therapies, a substantial portion of heart failure (HF) patients have experienced improvement of ejection fraction (EF), termed HFimpEF.

Purpose

In the present study, we sought to investigate the association between visit-to-visit glycemic variability (GV) and the incidence of HFimpEF.

Methods

From January 2013 to December 2020, 951 hospitalized HF patients with reduced EF (HFrEF, EF≤ 40%) were consecutively enrolled and followed up for around 12 months. The incidence of HFimpEF, defined as (1) an absolute EF improvement ≥10% and (2) a second EF > 40% and its relationship with visit-to-visit fasting plasma glucose (FPG) variability were analyzed.

Results

A total of 519 HFrEF patients were finally enrolled. During a mean follow-up of 12.2 ± 0.6 months, 218 (42.0%) patients developed HFimpEF. Multivariate analysis showed visit-to-visit FPG variability was independently associated with incidence of HFimpEF after adjustment for baseline HBA1c, mean FPG during follow-up and other traditional risk factors (odds ratio [OR] for highest vs. lowest quartile of CV of FPG: 0.487 [95% CI 0.257∼0.910]). Assessing FPG variability by alternative measures yielded similar results. Subgroup analysis revealed the relationship between GV and HFimpEF was only observed in HF of ischemic etiology and the association persisted significant irrespective of glycemic levels and diabetic conditions.

Conclusions

This study reveals that greater visit-to-visit FPG variability is associated with compromised development of HFimpEF independent of mean glycemic levels and diabetic conditions. Therapies targeted at improving GV might provide favorable effects on myocardial recovery in HF patients even without diabetes.Fig 1Fig 2
Continuous measurement of percutaneous oxygen saturation during 6-minute walk test is useful for stratification of the prognostic risk in patients with heart failure
Authors: Sunayama I , Min K D , Orihara Y , Ono J , Matsumoto Y , Soyama Y , Manabe E , Oboshi M , Azuma K , Sugahara M , Eguchi A , Nishimura K , Naito Y , Asakura M , Ishihara M
Published: November 2023

Background

The 6-minute walk test (6MWT) is an established test to assess the functional exercise performance and the 6-minute walk distance is strongly correlated with the functional capacity and the prognosis in patients with heart failure (HF). Also, the hypoxia during 6MWT is reported to be associated with severity of pulmonary diseases. However, no study has reported the clinical implication of sequential changes in percutaneous oxygen saturation (SpO2) during 6MWT was not investigated in HF patients.

Purpose

To prospectively clarify the association between sequential changes in SpO2 during 6MWT and prognosis in patients with HF.

Methods

In this prospective observational study, 50 patients admitted to our hospital with acute heart failure were enrolled. The 6MWT was performed at the time before discharge, after hemodynamic stability was confirmed. The average of SpO2 was calculated from data obtained at rest (3 minutes just before the test) and during 6MWT by employing the wearable pulse-oximeter which are designed to record and store the SpO2 value every seconds. Alternations in SpO2 (Δ SpO2) were analyzed by subtracting the average during 6MWT from that at rest. Patients were followed 1 year for composite outcome of heart failure-hospitalization and death).

Results

The mean age of participants was 78.8 years, and 23 (46%) were female. The mean EF was 46.1% and the number of the patients with EF≧50, 50>EF>40, 40≧EF were 22, 6, and 22, respectively. Mean NT-proBNP was 4374.5pg/ml. The mean walk distance was 250 ± 112m and the mean Δ SpO2 was 2.88 ± 4.3%. All cases were classified by walk distance and Δ SpO2; long- (>220m) vs. short-distance group (≦220m) and low- (<3.5%) vs. high-ΔSpO2 group (≧3.5%). There were no significant differences in cardiac parameters and respiratory function between long- and short-distance group as well as between low- and high-ΔSpO2 group. Kaplan-Meier analysis revealed that cardiac event rate was higher in the short-distance group than in the long-distance group (HR = 2.89, CI = 1.24-6.71, p = 0.014), and higher in the high-Δ SpO2 group than in the low-ΔSpO2 group (HR = 3.49, CI = 1.55-7.83, p = 0.002) (Figure 1A and 1B). When these classifications were combined, the patients with short-distance and low-ΔSpO2 showed remarkably high event rate of 91% (Figure 2).

Conclusions

This study showed that, compared to walk distance, ΔSpO2 was more predictive of prognosis of heart failure patients, and that the combination of ΔSpO2 and walk distance may identify the highest risk group. The elucidation of the usefulness of continuous SpO2monitoring during 6MWT as the marker for severity of heart failure and treatment effect warrants further investigation.Figure1Figure 2
MUC-16, tumour and congestive heart failure marker, is expressed on epicardial mesothelial cells and is inversely associated with epicardial fat genesis
Authors: Eiras S , Fu X , Nunez-Camano J R , De La Espriella R , Nunez J , Gonzalez-Juanatey J R
Published: November 2023

Background

CA-125 or mucin-16 (MUC-16) is a protector protein on epithelial luminal surfaces against physical stress through hydration process. However, some evidence suggests a role in fibrogenesis. MUC-16 can be detected in plasma after proteolytic cleavage with a predictive value for heart failure progression. Our main objective was to study the expression levels of this glycoprotein on epicardial mesothelial cells, its association with epicardial fat genesis, and biochemical markers.

Methods and results

We have used epicardial and subcutaneous fat from patients(n = 29) undergoing open heart surgery under informed consent and after approval by Ethics Committee. MUC-16 expression levels were detected on formalin-fixed paraffin-embedded epicardial fat biopsies with CA-125 antibody or real-time PCR on stored biopsies (n = 18) at -80ºC. Epicardial cells scraped with a scalpel were cultured and their MUC-16 expression was confirmed with a specific antibody and secondary fluorescent antibody. Primary cultures from epicardial stromal cells of 8 patients were obtained with collagenase digestion. After 15 days, adipogenesis was induced for 15 days with an adipogenic cocktail. Adipogenesis (AdipoQ) and mesothelial (ITLN-1) markers were quantified by real-time PCR on cells with and without adipogenesis. CA-125 expression levels were analyzed by real time-PCR on epicardial fat from 18 patients, as well as inflammation, fibrosis, stretch and adiposity markers levels on plasma by multiplex assay.

Our results showed that MUC-16 is localized on epicardial mesothelial cells but not on adipocytes. The MUC-16-stained cells can be cultured and isolated after scraping the epicardium. The isolated epicardial stromal cells with collagenase showed a positive relationship between mesothelial maker (ITLN-1) and CA125 (Figure below). The higher presence of MUC-16 levels was inversely associated with AdipoQ after adipogenesis induction. From 8 plasma studied proteins, thrombospondin-2 (TP-2), was the best associated protein with MUC-16 on epicardial fat (r = 0,472; p = 0,48).

Conclusion

Epicardial cells express MUC-16. These types of cells can be isolated and cultured for studying their cleavage regulation and modulation. Epicardial stromal cells with a higher percentage of MUC-16 reduce the epicardial fat genesis. Further studies are needed for finding the main circulating plasma levels associated with epicardial MUC-16.
Urinary biomarkers in different diuretic response groups with heart failure
Authors: Kozluca V , Akbulut Koyuncu I M , Baskovski E , Tan T S , Ozdol C , Tutar D E
Published: November 2023

Purpose

Predicting diuretic response in different hemodynamic profiles is challenging in heart failure patients. Worsening renal function with diuretic therapy leads to decision making more difficult. Spot urinary sodium is an important milestone to determine decongestion therapy intensity. Serum biomarkers are widely used for diagnosis and follow up but more urinary biomarkers can be identified for risk stratification.

Methods

We enrolled 61 patients with decompansated heart failure on the first day of admission. Baseline characteristics and urinary biomarkers were recorded. Diuretic response was classified as good or poor response groups according to spot urine sodium within second hour after first intravenous diuretic administration. Quantitative variables were specified as mean ± standard deviation, categorical variables were specified as frequency and percentage. Mean differences were assessed with Student-T test and Welch test. Statistically significant parameters were also assessed with logistic regression analysis.

Results

Only U/P creatinine ratio and urine creatinine were statistically lower in good diuretic response group (p<0.0001). Fractional excretion of urea and potassium were higher in good response group (p<0.0001 and p<0.005). Urinary sodium to potassium ratio, UNa/UCr and UK/UCr are also statistically higher in the good response group (p<0.0001). Sodium associated parameters (UNa/UK, UNa/UCr) and urinary creatinine were also significant in logistic regression.

Discussion

Urinary biomarkers are not well defined parameters in heart failure patients but these parameters may be more dynamic than serum parameters as spot urine sodium. Our data indicates that poor response group has a more prerenal phenotype than good response group.Table 1.Urine biomarker definitionsTable 2.Results
NTproBNP values for the diagnosis of congestive heart failure in dyspneic old patients regarding age
Authors: Berthelot E , Bounab R , Bailly M T , El Blidi M , Lehova X , Jourdain P
Published: November 2023

Background

The diagnosis of heart failure (HF) in elderly patients is often difficult, due to overlap of typical signs and symptoms with those of comorbidities. Plasma N-Terminal Pro-Brain Natriuretic Peptide(NTproBNP) is known to increase with age and according to comorbidities. However, the diagnostic performance of this biomarker is unclear in those patients.

Aims

This study sought to define the diagnostic accuracy of plasma NTproBNP in patients over 75 yo in a large population referred for acute dyspnea in the Assistance Publique-Hôpitaux de Paris.

Methods and Results

In this retrospective, longitudinal multicenter cohort study, we collected data from 12,974 patients aged 75 years or older who were hospitalized for acute dyspnea with NTproBNP measurement in the 48 hours after admission between 2011 and 2021 in geriatrics, cardiology and pulmonology departments. The final diagnosis was classified with the International Classification of Diseases, 10th Revision (ICD 10) as either "AHF" or "other acute respiratory failure" (OARF), represented by pulmonary embolism, COPD and pneumonia. The Mean (SD) age of our population was 84.4 (6.1) years old, and 52.7% of patients were women. 8,385 (64.6%) patients had an AHF diagnosis at discharge. Regarding age of patients, NT-proBNP threshold values was higher in patients over 85 yo, 2530 ng/L, compared to that of patients < 85 yo, 1680 ng/L. The NTproBNP threshold for ‘ruling-out’ AHF had a 79% sensitivity in patient > 85 YO and 82% sensitivity in patient 75- 85 YO. In patients > 85 compared with patient 75-85 yo, predictive positive value was 85 and 86 %, specificity was 65% and 75% and AUC was 0.77 and 0.84. Finally, despite the consideration of other clinical and biological parameters, NTproBNP level remain more discriminating for the diagnosis of AHF in old patients with comorbidities.

Conclusion

In patients 75-85 and over 85 years of age referred for acute dyspnea with NTproBNP dosage at admission, a cutoff of 1680 and 2530 ng/L respectively allow for an accurate diagnosis of AHF.
Lack of correlation between levels of surfactant B and NT-pro-NBP in acute heart failure: an admission to discharge study
Authors: Novello G , Bursi F , Bonazzi C , Furlotti N , Rusconi I , Mondellini G , Vivona P , Galluccio E , Martin D , Caretti A , Guazzi M
Published: November 2023

Background

Acute pulmonary edema (APE) is a main cause of hospitalization for heart failure (HF). Surfactant type B (Surf-B) is a sensitive biomarker of alveolar damage that has been partially studied in chronic HF unless acute HF.

Aims

To clarify the pattern of Surf-B changes compared to the gold standard NT-pro-BNP after decongestion therapy.

Methods

36 patients with acute HF due to APE (average age 74,9 ± 8,94; LVEF 36,7 ± 12,6; 61,0% males) underwent a combined evaluation of Surf-B, NT-pro-BNP levels with quantification of B-lines at hospital admission (time 0) and discharge (time 1).

Results

At time 1, the average Surf-B and NT-pro-BNP and B- lines were significantly lower compared to time 0. Interestingly, no correlation between Surf B and NT-pro-BNP was observed either at time 0 and time 1. A correlation between B-lines and Surf-B was observed only at time 0 while the correlation between NT-pro-BNP and B lines was observed just at time 1 (Table). Despite the significant average changes in Surf-B from admission to discharge, 28% of cases behaved as non-responders exhibiting a lack of reduction in Surf-B compared to NT-pro-BNP at time 1.

Conclusions

These data suggest that an organ specific biomarker of lung organ damage such as Surf-B is sensitive to decongestion therapy at a different extent compared to NT-pro-BNP with the two biomarkers that do not correlate each other. The evidence of a 28% cases of Surf-B non-responder subjects suggests that reparative process of alveolar break damage may dissociate from hemodynamic and cardiac benefits in acute HF.Table
Longitudinal association of subclinical cardiac function with cognitive function
Authors: Huynh Q , Marwick T H
Published: November 2023

Background

Cognitive impairment and heart disease frequently co-exist due to shared disease processes and pathological mechanisms. The presence of one may lead to and/or worsen the other. This bidirectional relationship between cognitive impairment and heart disease acts as a vicious cycle that increases the burden of both diseases. Our previous findings have demonstrated that cognitive impairment is a strong predictor of post-discharge readmission or death in heart failure, second only to heart failure severity. However, whether heart failure and cognitive impairment has a causal relationship remains unknown. This study sought to determine the relationship between subclinical cardiac function and cognitive function.

Methods

This study included 1977 consecutive patients (62% men, aged 73±13 years) with heart failure ranging from stage A to C. These patients were followed up for 36 months. At both baseline and follow-up, subclinical cardiac function was measured by echocardiography, and cognitive function was measured using Montreal Cognitive Assessment (MOCA). Other measurements included blood biochemistry, comorbidities, physical measurements and questionnaires.

Results

Cognitive function was strongly associated with both readmission and death in patients with heart failure, particularly among those with stage C. Among patients with heart failure stage A or B, left atrial volume index (LAVI) and E/e’ were associated with a reduction of MOCA score and higher risks of newly developed cognitive impairment at 36-month follow-up (OR = 1.04 [95% CI:1.02-1.07] per 1ml/m2 LAVI, and OR = 1.07 [95% CI:1.01-1.15] per 1 unit E/e’). Patients with cognitive impairment have significantly enlarged left atrium, compared with those with normal cognition (p<0.001). While almost all (93%) of patients with consistent cognitive impairment from baseline to follow-up had an enlarged left atrium, 71% of those who became cognitively impaired at follow-up had an enlarged left atrium.

Conclusions

The longitudinal relationship between diastolic cardiac function and cognitive function suggests a causal pathway between these two. Assessment of cognitive function is recommended in patients with impaired cardiac function.
Association between cardiac time intervals and incident heart failure after acute coronary syndrome
Authors: Bjerregaard C , Skaarup K G , Olsen F J , Iversen A , Joergensen P G , Pareek M , Galatius S , Pedersen S , Biering-Soerensen T
Published: November 2023

Background

Cardiac time intervals are sensitive markers of myocardial dysfunction that predisposes to heart failure (HF). Color tissue Doppler imaging (TDI) curved M-mode is a reliable method for measuring cardiac time intervals.

Purpose

We aimed to investigate the association between cardiac time intervals and HF in patients with acute coronary syndrome (ACS).

Methods

This was a retrospective cohort study of 580 ACS patients treated with percutaneous coronary intervention (PCI). Patients underwent an echocardiography examination performed a median of two days after PCI. By echocardiography cardiac time intervals including isovolumic relaxation time (IVRT), isovolumic contraction time (IVCT), and ejection time (ET) were obtained by TDI curved M-mode and used to derive the myocardial performance index (MPI). The outcome was incident HF. Patients with prevalent at baseline HF were excluded from the analysis.

Results

The final study sample consisted of 387 patients, 73% were male, the mean age was 64 years, 76% of the ACS events were STEMI and LVEF and GLS were 42% and -13.1%, respectively. During follow-up (median 4.3, IQR:1.0-6.7 years), 140 (36%) developed HF. In unadjusted analyses, longer combined indexes were associated with a higher risk of HF (IVRT/ET: HR 1.24 (1.07-1.43), P = 0.003, per 0.1 increase) and (IVCT/ET: HR 1.44 (1.10-1.91), P = 0.010, per 0.1 increase), and so was higher MPI (HR 1.20 (1.08-1.34),P = 0.001, per 0.1 increase). In addition, shorter ET was also associated with higher HF risk (HR 1.13 (1.07-1.18), P<0.001 per 10ms decrease). MPI and IVCT/ET showed a curvilinear association with the outcome, whereas a linear association was observed for ET and IVRT/ET to the outcome (figure 1). After multivariable adjustment for cardiovascular risk factors, only MPI (HR 1.13 (1.01-1.27), P = 0.034), ET (HR 1.09 (1.01-1.17), P = 0.025), and IVCT/ET (HR1.37 (1.04-1.81), P = 0.023) remained significantly associated with HF.

Of note, left ventricular ejection fraction (LVEF) significantly modified the association between ET and HF (p for interaction = 0.002), such that ET was associated with HF even in those with preserved LVEF (>40%) (HR 1.13 (1.02-1.24, P = 0.017, per 10ms decrease), but not in those with reduced LVEF (HR 1.02 (0.96-1.08), P = 0.56, per 10ms decrease). These findings also persisted after adjustment for cardiovascular risk factors.

Conclusion

Shortened ET, prolongation of combined indexes, and higher MPI were associated with an increased risk of incident HF. In addition, shortening of the ET was associated with an increased risk of HF in patients with preserved systolic function by LVEF.
The acute hemodynamic effects of sodium lactate infusion: increased cardiac output and decreased afterload in a randomized trial in pigs
Authors: Hoersdal O , Moeslund N , Berg Hansen K , Nielsen R , Moeller N , Eiskjaer H , Wiggers H , Gopalasingam N
Published: November 2023

Background

Lactate is traditionally acknowledged as a by-product of anaerobic glucose metabolism. Recently, however, lactate has been proven to be a preferred oxidative substrate for stressed myocardium. Studies have shown that exogenous lactate infusion provides beneficial hemodynamic effects including increased cardiac output (CO). Nevertheless, the exact mechanism of action underlying the hemodynamic effects of lactate infusion has not been fully elucidated.

Aim

To identify the cardiovascular mechanisms behind the acute hemodynamic effects of exogenous sodium lactate infusion in an experimental model of healthy human-sized pigs.

Methods

We performed a randomized, assessor-blinded crossover study in eight female 60 kg pigs. In randomized order, the pigs received an infusion with 1 M sodium lactate for two hours and a control infusion with iso-osmolar and isovolumetric sodium chloride for two hours. The two infusion periods were separated by a one-hour washout period. We measured CO and pulmonary pressures hourly with a pulmonary artery catheter. A pressure-volume admittance catheter was inserted in the left ventricle to assess measures of cardiac efficiency, contractility, afterload, and preload. Hemodynamic measures as arterial blood pressure, heart rate, and mixed venous saturation (SvO2) were measured hourly as well.

The study followed the principles of laboratory animal care (NIH Publication no. 85-23 revised 1985) and national and European legislations.

Results

Lactate levels increased by 9.9 mmol/L (95% CI 9.1 to 11.0) and CO increased by 2.0 L/min (95% CI 1.2 to 2.8) during lactate infusion as compared with the control period (figure 1). During lactate infusion, ejection fraction increased by 16.0 percentage points (95% CI 1.9 to 31.0) and heart rate by 21 bpm (95% CI 9 to 32) compared with control. Arterial elastance decreased by -1.1 mmHg/ml (95% CI -2.1 to -0.18).

Lactate infusion also increased cardiac efficiency, SvO2, arterial pH, and arterial glucose concentration significantly. The infusion of lactate led to no changes in systemic arterial pressure nor pulmonary pressures including pulmonary artery wedge pressure. Also, no changes were found in left ventricle end systolic elastance (contractility). Futhermore, no change in left ventricle end-diastolic volume or -pressure (preload) were observed during lactate infusion compared with the control (figure 2).

Conclusion

High dose lactate infusion increased cardiac output by reducing afterload. No changes in left ventricular contractility or -preload were observed.Fig 1:Lactate concentration and COFig 2:Changes of endpoint parameters
Effects of dapagliflozin in heart failure with preserved ejection fraction and chronic obstructive pulmonary disease: an analysis of the DELIVER trial
Authors: Butt J , Lu H , Kondo T , Bachus E , De Boer R A , Hernandez A , Inzucchi S , Jhund P S , Kosiborod M , Lam C , Martinez F , Shah S J , Vaduganathan M , Solomon S D , Mcmurray J J V
Published: November 2023

Introduction

Chronic obstructive pulmonary disease (COPD) is a common comorbidity in heart failure (HF) with preserved ejection fraction (HFpEF) and associated with worse outcomes.

Purpose

We investigated the relationship between COPD status and outcomes, and the efficacy of dapagliflozin, compared with placebo, according to COPD status in patients with heart failure (HF) with preserved ejection fraction (HFpEF) randomized in DELIVER.

Methods

A total of 6,263 patients with HF with New York Heart Association functional class II-IV, left ventricular ejection fraction >40%, evidence of structural heart disease, and elevated N-terminal pro–B-type natriuretic peptide levels were randomized to dapagliflozin or placebo. Clinical outcomes and the effect of dapagliflozin, according to COPD status at baseline, were examined. The primary outcome was a composite of cardiovascular death or worsening HF.

Results

Of the 6,261 patients with data on baseline COPD, 692 (11.1%) had a history of COPD. Compared with patients without COPD, those with COPD were older, more often men and current smokers, and they had a higher BMI, but lower systolic blood pressure. Patients with COPD also had a longer duration of HF, a higher rate of prior HF hospitalization, higher NT-proBNP, and worse NYHA functional class and KCCQ-TSS. The risk of the primary endpoint was higher in patients with COPD compared with those without COPD (adjusted HR: 1.29 (95% CI: 1.09-1.52). The benefit of dapagliflozin on the primary outcome was consistent irrespective of COPD status: no COPD, HR: 0.82 (95% CI: 0.72-0.93); COPD, HR: 0.84 (95% CI: 0.63-1.12) (Pinteraction = 0.92). Consistent effects were observed for HF hospitalization, cardiovascular death, and all-cause mortality (Table). Dapagliflozin, as compared with placebo, increased (improved) the KCCQ-TSS from baseline to 8 months to a similar extent in patients with and without COPD (Pinteraction = 0.75) (Table). Adverse events and treatment discontinuation were not more frequent with dapagliflozin than with placebo irrespective of COPD status.

Conclusions

COPD is common in patients with HFpEF and associated with worse outcomes. Dapagliflozin reduced the risk of worsening HF or cardiovascular death, and improved symptoms, similarly in patients with and without COPD. In addition, dapagliflozin was safe and well-tolerated, irrespective of COPD status.
Comparison study of olmesartan and valsartan on myocardial metabolism in patients with dilated cardiomyopathy trial
Authors: Park K , Jo S , Park T H
Published: November 2023

Background

Patients with dilated cardiomyopathy (DCMP) have overactivation of the renin-angiotensin-aldosterone systems, which can adversely affect myocardial metabolism. The impairment of myocardial metabolism can contribute to the progression of left ventricular remodeling and contractile dysfunction in heart failure. The objective of this study is to compare the effects of olmesartan and valsartan on myocardial metabolism in patients with DCMP.

Methods

The OVOID study (a comparison study of Olmesartan and Valsartan On myocardial metabolism In patients with Dilated cardiomyopathy) was a non-blinded, open-label, parallel-group, prospective, randomized, controlled, multicenter clinical trial. that 40 patients with DCMP. Patients with DCMP were randomized into the olmesartan or the valsartan group. To measure myocardial metabolism, 18F-fluoro-2-deoxyglucose (FDG) cardiac positron emission tomography (PET) was performed at baseline and six months after receiving the study agent. The primary endpoint was myocardial metabolism as measured by standardized uptake value ratio (SUVR) at 6 months after treatment.

Results

The baseline clinical characteristics and 18F-FDG PET data did not differ between the olmesartan and valsartan groups. LVEF rose significantly from baseline in both groups to a similar degree between the two groups (both P < 0.01). The level of N-terminal pro hormone B-type natriuretic peptide (NT-proBNP) decreased significantly from baseline in the both high- and usual-dose groups (both P < 0.01). The magnitude of NT-proBNP change was not significantly different between the two groups (P = 0.33). However, six-month follow-up 18F-FDG PET showed that SUVG value was significantly lower in the olmesartan group than the valsartan (3.76±2.12 versus 7.33±4.08, P = 0.01).

Conclusions

Compared to valsartan, six months of olmesartan therapy significantly improved myocardial metabolism in DCMP patients.
Impact of sacubitril valsartan initiation in patients with HFrEF and severe mitral regurgitation referred for percutaneous mitral repair
Authors: Arroyo Monino D F , Cortes Cortes F J , Rivadeneira Ruiz M , Alcalde Calleja A , Recio Mayoral A
Published: November 2023

Background

In patients with heart failure with reduced ejection fraction (HFrEF), the severity of functional mitral regurgitation (MR) is a major predictor of worsened symptoms and poor outcomes.

Percutaneous MR repair has been shown to improve outcomes in HFrEF with MR. However, because MR is related to abnormal myocardial function and adverse remodeling, the optimization of guideline-directed medical therapy (GDMT) could improve loading conditions, reversal remodelling and left ventricle function and also may reduce MR severity. We sought to evaluated whether the left ventricle reverse remodeling induced by the addition of sacubitril/valsartan may reduce MR severity sufficiently to avoid need for percutaneous MR repair approach.

Methods

We performed a single-center, prospective assessor-blinded study to determine the reverse remodeling response of sacubitril/valsartan therapy in HFrEF patients (NYHA class II-IV) with MR evaluated for percutaneous MR repair. Echocardiographic images were assessed offline by 2 investigators blinded to both the clinical data and timing of echocardiograms. Doses of sacubitril/valsartan were optimized to individual tolerance. A clinical and echocardiographic 1 year follow-up was performed.

Results

Thirty-nine HFrEF patients with MR grade 3-4 were included (mean age 63 years old, 69,2% male). Optimal dose of sacubitril/valsartan was reached in 63,2% of patients. After 1-year follow-up, only 1 patient died and, as we show in Table 1, a significant improvement on NYHA functional class and NT-ProBNP values were present. Left ventricle ejection fraction improved (29.7 ± 6.7% vs 41.3 ± 13.2%; P < 0.001) and left ventricular end-diastolic and end-systolic volume indexed to body surface area decreased (123.4 ± 35.7 mL/m2 vs 98.4 ± 39.7 mL/m2; P < 0.001 and 87.7 ± 30.0 mL/m2 vs 61.9 ± 35.3 mL/m2; P < 0.001, respectively). Volumetric remodeling was associated with a reduction in the degree of mitral regurgitation (64.1% grade 3 and 35.9% grade 4 at the beginning to 28.9% grade 1, 36.8% grade 2, 21.5% grade 3 and 13.2% grade 4 after one year of follow-up; [scale from 0-4]).

Conclusion

The optimization of GDMT with sacubitril/valsartan induced an improvement on functional class and a beneficial reverse cardiac remodelling, with enhancement of left ventricle function and reducing MR severity, enough in 24 patients to avoid need for percutaneous MR repair.

In HFrEF patients with grade 3-4 mitral regurgitation, our results reinforce importance of ensuring optimal GDMT before a percutaneous mitral valve repair approach.Table 1.Changes during follow-up.
Left ventricular reverse remodeling following initiation of sacubitril/valsartan for heart failure with reduced ejection fraction and low blood pressure
Authors: Nishihara Y , Nishimori M , Sawa T , Yamauchi Y , Shiraki H , Yamashita K , Fukuda T , Hisamatsu E , Shimizu M , Hirata K , Tanaka H
Published: November 2023

Background

Sacubitril/valsartan has become an important first-line drug for symptomatic heart failure (HF) patients, especially with left ventricular (LV) ejection fraction (LVEF) < 50%. Since sacubitril/valsartan was reported to be more potent than renin-angiotensin-aldosterone system inhibitors for lowering blood pressure, HF patients with low blood pressure were not included in most clinical studies as a result of sacubitril/valsartan administration, and average systolic blood pressure of most enrolled patients was around 120 mmHg. Thus, the effect of sacubitril/valsartan on cardiovascular outcomes, especially LV reverse remodeling for HF patients with LVEF < 50% and low blood pressure, remains uncertain.

Purpose

The aim of this study was to examine the effect of sacubitril/valsartan on LV reverse remodeling after initiation of the maximum tolerated dose of sacubitril/valsartan for HF patients with LVEF < 50% and systolic blood pressure ≤ 100 mmHg, and a comparison of its efficacy with that for patients with systolic blood pressure > 100 mmHg.

Methods

We retrospectively studied 164 HF patients with LVEF < 50% who were treated with sacubitril/valsartan from two institutions. Echocardiography was performed before and 9.5 ± 5.1 months after initiation of maximum tolerated dose of sacubitril/valsartan.

Results

sacubitril/valsartan was discontinued for 17 (10.4%) as decided by the attending physician mainly due to hypotension. The prevalence of discontinuation of sacubitril/valsartan for the low blood pressure group was higher than that for the non-low blood pressure group, but the difference was not statistically significant (16.0% vs. 9.4%, P = 0.32). No serious adverse events occurred during this study. The maximum tolerated dose of sacubitril/valsartan was lower for the low blood pressure group than for the non-low blood pressure group (165 ± 106 mg vs. 238 ± 124 mg, P = 0.017). As expected, significant LV reverse remodeling was observed in the non-low blood pressure group after initiation of sacubitril/valsartan. It was noteworthy that significant LV reverse remodeling was also observed in the low blood pressure group after initiation of sacubitril/valsartan (LV end-diastolic volume: 177.3 ± 66.0 mL vs. 137.7 ± 56.1 mL, P<0.001, LV end-systolic volume: 131.6 ± 60.3 mL vs. 94.6 ± 55.7 mL, P<0.001, LVEF: 26.8 ± 10.3% vs. 33.8 ± 13.6%, P = 0.015). Relative changes in LV volumes and LVEF after initiation of sacubitril/valsartan were similar for the two groups (Figure).

Conclusions

Significant LV reverse remodeling can occur after initiation of sacubitril/valsartan even in HF patients with LVEF < 50% and systolic blood pressure ≤ 100 mmHg if tolerated. This finding is expected to offer new insights for better management of HF patients.Figure
Effects of vericiguat on redox signaling in cardiomyocyte
Authors: Harada T , Kondo H , Yamasaki H , Takahashi M , Takano M , Akioka H , Teshima Y , Yufu K , Nakagawa M , Takahashi N
Published: November 2023

Background

Reactive oxygen species (ROS) inhibits the nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway in the patients with advanced heart failure (HF) and contributes to the prognosis of HF. Vericiguat stimulates sGC independently of NO and reduced morbidity/mortality for HF patients with reduced ejection fraction. However, the effects of vericiguat on the cardiomyocyte in terms of ROS is unclear.

Purpose

We explored the cardioprotective effects of vericiguat focusing on the oxidative stress.

Methods

Cardiomyocytes isolated from the whole heart of neonatal rats were incubated with vericiguat (0μM as control, 0.1μM, 1.0μM, 10μM) for 72 hours. Administration of angiotensin II (1.0μM) was used to induce excessive ROS. Superoxide was quantified using luminometry, and whole ROS or mitochondria-derived superoxide was evaluated by using live-cell fluorescent probes. ERK 1/2 signaling pathway activity were evaluated with western blot analysis.

Results

Nicotinamide adenine dinucleotide phosphate (NADPH)-stimulated superoxide was significantly increased by the treatment of angiotensin II (40208 ± 6107 reactive light unit (RLU) / mg, p = 0.0009) and the angiotensin II-induced superoxide was significantly attenuated by vericiguat at doses of 0.1μM (28240 ± 6507 RLU / mg, p = 0.03) , 1.0μM (25221 ± 6496 RLU / mg, p = 0.007) and 10μM (8230 ± 2568 RLU / mg, p < 0.0001). Corrected total cell fluorescence value of live-cell fluorescent probes revealed that whole ROS and mitochondria-derived superoxide were significantly increased by angiotensin II treatment (525.3 ± 119.6, p = 0.004 and 945.3 ± 153.0, p <0.0001), which were attenuated by vericiguat (0.1μM, 431.2 ± 45.7, p = 0.48 and 548.1 ± 103.9, p = 0.0004; 1.0μM, 336.1 ± 109.0, p = 0.04 and 421.3 ± 111.9, p < 0.0001; 10μM, 270.0 ± 44.4, p = 0.005 and 157.7 ± 48.3, p < 0.0005) dose-dependently. Angiotensin II-induced phosphorylation of ERK 1/2 was suppressed by vericiguat at doses of 1.0μM (fold change 0.58, p = 0.04) and 10μM (fold change 0.45, p = 0.006) treatment.

Conclusion

Our results indicated that vericiguat could suppress the oxidative stress induced by angiotensin II and following activation of ERK 1/2 signaling. Suppressing the oxidative stress could lead to further activation of NO-sGC-cGMP pathway not only the stimulation by vericiguat and favorable cardio-protective cycle is expected.Quantification of superoxideQuantification of ROS or superoxide