bluuebunny/crossref_metadata_2025 huggingface dataset:
Can left ventricle mass index predict pacemaker-induced cardiomyopathy in patients with dual chamber permanent pacemakers implanted due to complete atrioventricular block?
Authors: Hayiroglu M , Cinar T , Cinier G , Yuksel G , Pay L , Keskin K , Coskun C , Ayan G , Cicek V , Tekkesin A I
Published: October 2022

Background

Pacing induced cardiomyopathy (PICM) occurs due to high-burden right ventricular pacing. In patients with complete atrioventricular (AV) block, it is presumed to have a higher burden of right ventricular pacing. There is a lack of data regarding the relationship between PICM and pre-implantation left ventricular mass index (LVMI).

Purpose

This study aims to investigate the effect of LVMI on PICM in patients with implanted dual chamber permanent pacemakers (PPM) due to complete AV block.

Methods

PPM implanted 577 patients were divided into three groups according to admission LVMI. Mean duration of follow-up was 57±38 months. The baseline characteristics, laboratory and echocardiographic variables were compared between the groups. The independent predictors of PICM incidence and the effect LVMI on PICM were evaluated.

Results

Age, post-implantation QRS duration, left atrium anteroposterior diameter and LVMI were determined to predict long-term PICM. After adjustment for confounding baseline variables, tertile with highest LVMI had 1.9 times higher rates of long-term PICM compared to tertile with lowest LVMI, which was used as the reference group. A ROC analysis showed that the optimal cut-off value of the LVMI to predict long-term PICM was 109.8 mg/m2 with 71% sensitivity and 62% specificity (AUC: 0.68; 95% CI: 0.60–0.76; p<0.001),

Conclusion

Pre-implantation LVMI plays an important prognostic role in predicting PICM in patients with implanted dual chamber PPM due to complete AV block.

Funding Acknowledgement

Type of funding sources: None.
Global warming, renal function and heart failure: a 20-year follow-up study
Authors: Aimo A , Lupon J , Spitaleri G , Domingo M , Codina P , Santiago-Vacas E , Cediel G , Zamora E , Troya M I , Santesmases J , Romero-Gonzalez G A , Nunez J , Martini N , Emdin M , Bayes-Genis A
Published: October 2022

Background

There is a growing concern about the possible effects of global warming on human health. In HF outpatients, renal function significantly worsens during summer. More specific analyses on the impact of increasing temperatures on body homeostasis are lacking.

Purpose

We investigated the relationship between the trend of temperatures from 2002 to 2021 and renal function in heart failure (HF) outpatients.

Methods

All creatinine and estimated glomerular filtration rate (eGFR) values of HF outpatients followed at one tertiary hospital in a Mediterranean area of Spain were retrieved from electronic health records. eGFR was calculated through the CKD-EPI formula. Temperature data from the local municipality were derived from the Meteocat service; as temperatures from the years 2004–2005 were not available, these years were not analysed. Summer was defined as the timespan from June to September included. We calculated average values of creatinine and eGFR during summer and the rest of the same year, considering each patient and each year. Similarly, we averaged temperature values during summer and the rest of the same year.

Results

We derived 6,307 couples of average creatinine/eGFR values in summer and in the rest of the year from 2,194 patients. Across all the years (2002–2003 and 2006–2021), creatinine was slightly higher in summer than in the rest of the year (1.26 vs. 1.21 mg/dL, p<0.001), and eGFR was lower (65 vs. 67 mL/min/1.73 m2, p<0.001). Temperatures in summer and the rest of the year increased gradually, albeit not linearly, from 2002 to 2021 (Figure 1). The absolute (Δ) and percent changes (Δ%) in median temperatures between summer and the rest of the year increased across years (r=0.149, p=0.001 and r=0.144, p=0.002, respectively), as well as Δ and Δ% of the monthly median of maximal temperatures (r=0.119, p<0.001 and r=0.052, p<0.001, respectively) (Figure 1). The Δ and Δ% temperatures between summer and the rest of the year displayed several significant correlations with Δ and Δ% creatinine and eGFR after adjusting for several variables including age, sex, HF therapies, and creatinine outside of summer (Figure 2).

Conclusions

Over a 20-year timespan there has been an increase in 1) temperatures in summer and in the rest of the year, and 2) the temperature excursion between summer and the rest of the year. Changes in temperatures between summer and the rest of the year correlated with the magnitude of the decrease in renal function during summer, likely because of worse dehydration with higher temperatures. Therefore, the progressive rise in temperature may have detrimental effects on renal function during summer in HF outpatients.

Funding Acknowledgement

Type of funding sources: None.
Factors predicting diuretic resistance in patients with acute decompensated heart failure
Authors: Pratama A P , Hersunarti N , Soerarso R , Zahara R , Kurniawati Y , Hasanah D Y , Sukmawan R
Published: October 2022

Background

Heart failure is a leading cause of hospitalisation and mortality with high incidence and ever-increasing prevalence in the world. Although novel methods in management of acute decompensated heart failure (ADHF) have been developed, mortality and rehospitalisation rates remain high. Loop diuretics have been shown to be effective in relieving congestion and have been recommended in many heart failure guidelines. Continuous use of loop diuretics may cause complications in the form of diuretics resistance. The prevalence of diuretic resistance ranges from 20–35% in the heart failure population and has been shown to be a predictor of mortality and an increased incidence of hospitalisation. Until now there are debates in determining the clinical indicators of diuretic resistance. However, the clinical characteristics of patients with acute decompensated heart failure that predict the development of diuretic resistance have not been widely studied and previous studies have shown different results from one another.

Purpose

This study aims to identify factors that influence the occurrence of diuretic resistance in ADHF patients based on clinical profiles, medical histories, and laboratory findings.

Methods

This was a retrospective cohort study on patients treated due to ADHF from January-December 2019. Diuretic resistance was defined as a diuresis response less than 1400 ml in the first 24 hours after administration of 40 mg of intravenous furosemide.

Results

Data from 535 patients were analysed. The prevalence of diuretic resistance in this study was 68%. Independent predictors obtained from multivariate logistic regression analysis were Type II Diabetes Mellitus (p=0.013), history of prior iv loop diuretics >6 days (p=0.002), history of oral loop diuretic dose >80 mg/day (p=0.006), LVEF ≤49% (p=0.002), BUN ≥21 mg/dL (p<0.001) and serum chloride <98 mmol/L (p<0.001). In addition, a scoring system has been generated from the final model with AUC 0.749.

Conclusions

Independent predictors for diuretic resistance obtained from this study were DM, history of prior iv loop diuretics >6 days, history of oral loop diuretic dose >80 mg/day, LVEF ≤49%, BUN ≥21 mg/dL and serum chloride <98 mmol/L.

Funding Acknowledgement

Type of funding sources: None.
Factors associated with health-related quality of life in heart failure in 23,000 patients from 40 countries: results of the global congestive heart failure research program
Authors: Johansson I , Balasubramanian K , Bangdiwala S , Mielniczuk L , Hage C , Sharma S K , Branch K , Yonga G , Kragholm K , Sliwa K , Roy A , Stork S , McMurray J J V , Conen D , Yusuf S
Published: October 2022

Background

Poor health-related quality of life (HRQL) is common in heart failure (HF) and strongly predicts death and HF hospitalization in all regions of the world. Understanding facors associated with HRQL could therefore lead to improved prognosis in HF patients. Despite that the majority of HF occurs in low- and middle-income countries, there are limited data characterizing self-perceived health HRQL and its correlates in these settings.

Purpose

To examine clinical and social correlates of HRQL in patients with HF from high- (HIC), upper middle- (UMIC), lower middle-(LMIC) and low-income (LIC) countries.

Methods

Between 2017 and 2020, we enrolled 23,292 patients with HF (32% inpatients, 61% men) from 40 countries in the Global Congestive Heart Failure Study. We recorded HRQL at baseline using Kansas City Cardiomyopathy Questionnaire (KCCQ)-12. In a cross-sectional analysis, we compared age- and sex-adjusted mean KCCQ-12 summary scores (SS: 0–100, higher=better) between patients from different country income levels. We used multivariable linear regression examining correlations (estimates expressed as β-coefficients) of KCCQ-12-SS with sociodemographic-, comorbidity-, treatment- and symptom-covariates. The adjusted model (37 covariates) was informed by univariable findings, clinical importance and backward selection. We used partial R2-estimates to understand the contribution to the variability in KCCQ-12-SS of 4 different groups of covariates. (sociodemographic, comorbidities, treatments and signs and symptoms of congestion).

Results

Mean age was 63 years and 40% were in NYHA class III–IV. Average HRQL was 55± SD 0.5. It was 62.5 (95% CI 62.0–63.1) in HIC, 56.8 (56.1–57.4) in UMIC, 48.6 (48.0–49.3) in LMIC, and 38.5 (37.3–39.7) in LICs (p<0.0001). Strong correlates (β-coefficient [95% CI]) of KCCQ-12-SS were NYHA class III vs class I/II (−12.1 [−12.8 to −11.4] and class IV vs. class I/II (−16.5 [−17.7 to −15.3]), effort dyspnea (−9.5 [−10.2 to −8.8]) and living in LIC vs. HIC (−5.8 [−7.1 to −4.4]). Symptoms explained most of the KCCQ-12-SS variability (partial R2=0.32 of total adjusted R2=0.51), followed by sociodemographic factors (R2=0.12). Results were consistent in populations across income levels.

Conclusion

The most important correlates of HRQL in HF patients relate to HF symptom severity, irrespective of country-income level. Improved symptom control may have a big impact on HRQL, especially in LICs.

Funding Acknowledgement

Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Bayer AG
Factors of persistent limited exercise tolerance in patients after COVID-19 with normal left ventricular ejection fraction
Authors: Gryglewska K , Sakowicz A , Banach M , Maciejewski M , Bielecka-Dabrowa A
Published: October 2022

Background

Exercise intolerance de novo is one of the most common reported symptoms in patients (pts) recovering from COVID-19.

Purpose

The present study determines etiological and pathophysiological factors influencing the mechanism of exercise intolerance in the COVID-19 survivors. Therefore, the factors affecting percent predicted oxygen uptake at peak exercise VO2 (%VO2pred) in pts after COVID-19 with normal left ventricular ejection fraction were assessed.

Methods and results

The 120 consecutive patients from the Department of Cardiology recovering from COVID-19 at three to six months after confirmed diagnosis were included. The clinical examinations, laboratory test results, echocardiography using Vivid E95 – GE Healthcare, non-invasive body mass analysis using Body Composition Analyzer (Tanita Pro), and spiroergometry using The MetaSoft® Studio application were analysed. The subjects were divided into the two following groups: study i.e. pts with worse oxygen uptake (%VO2pred <80%; N=47) and control including these cases with %VO2pred ≥80% (N=73) – Table 1. Pts with %VO2pred <80% presented significantly lower global peak systolic strain (GLPS) [p=0.03], tricuspid annular plane systolic excursion (TAPSE) [p=0.002] and late diastolic filling velocity (A) [p=0.004] compared to controls – Figure 1. The male gender (p=0.007) and the percent of total body water content (TBW %) (p=0.02) were significantly higher in study in comparison to the control group. The results of multiple logistic regression model independently associated with %VO2pred were as follows: A (OR 0.4, 95% CI: 0.17–0.95; p=0.03) and gender (OR 2.52, 95% CI: 1.07–5.91; p=0.03).

Conclusions

Males have over twice risk of persistent limited exercise tolerance after COVID-19 infection than females. The lower late diastolic filling velocity, tricuspid annular plane systolic excursion, worse global peak systolic strain, and hydration status are connected with limited exercise tolerance after COVID-19 in patients with normal left ventricular ejection fraction.

Funding Acknowledgement

Type of funding sources: None.
Profile and prognosis of patients with heart failure with recovered ejection fraction
Authors: Rocamora-Horrach M , Peiro O , Serrano I , Rodriguez J , Carrasquer A , Ferrero-Guillem M , Romeu A , Lal-Trehan N , Sanchez R , Del Moral V , Delgado J R , Bardaji A
Published: October 2022

Background

Patients with heart failure (HF) and reduced ejection fraction (rEF) have a poor prognosis. Nevertheless, in the subgroup of patients with recovered ejection fraction (recEF) prognosis is unknown.

Purpose

To analyze characteristics and prognosis in patients with HFrEF (initial EF and at one year <40%) and HFrecEF (initial EF <40% and at one year ≥40% with ≥10% absolute improvement from the initial value).

Methods

Retrospective observational study of outpatients referred to the HF unit within March/2006 and November/2021. Baseline characteristics, ecocardiographic data and follow-up were collected, discerning between patients with HFrEF and HFrecEF.

Results

A total of 346 patients (76.0% men) were analyzed with a mean of age 66.3 (IQR 57.8–74.4) years, of which 50.6% remained with rEF and 49.4% recEF. Median follow-up was 4.6 (2.8–7.9) years. Both groups had a similar risk profile albeit less prevalence of dyslipidemia in the group with recEF (43.5% vs 56.7%, p=0.015). Ischemic etiology predominated in those with rEF (41.7% vs 25.7%, p=0.002) and enolic in recEF (10.5% vs 3.4%, p=0.009). The incidence of combined event (readmission for HF or death) was lower in HFrecEF (33.6% vs 66.4%, p<0.001), as well as death (33.9% vs 66.1%, p<0.001) and readmission for HF (24.4% vs 75.6%, p<0.001). Prevalence of cardiovascular death was lower in the group with recEF (37.8% vs 61.1%, p=0.021). In the multivariate analysis, rEF was an independent predictor for the combined event (HR 2.17; 95% IC [1.45–3.25], p<0.001), as well as for global mortality and readmission for HF.

Conclusion

Patients with HFrecEF have a similar risk profile than patients with HFrEF although with better long-term prognosis.

Funding Acknowledgement

Type of funding sources: None.
History of heart failure and chronic kidney disease and the risk for all-cause death after COVID-19 during the three first waves in comparison to influenza outbreaks in Sweden
Authors: Ritsinger V , Bodegard J , Kristofi R , Thuresson M , Nathanson D , Nystrom T , Eriksson J W , Norhammar A
Published: October 2022

Background

Infection with SARS-CoV-2 (COVID-19) affects people globally causing hospitalisation and reduced life expectancy. To improve future preventive measures there is a need of extensive analysis on contributing risk factors for severe COVID-19 outcome.

Purpose

To explore how cardiorenal disease (CRD; heart failure and/or chronic kidney disease) impacted mortality in patients hospitalised for COVID-19 during the three first waves in Sweden in comparison to previous influenza outbreaks and with a sex perspective.

Methods

All patients in Sweden with a main hospital diagnosis of COVID-19 (January 2020-September 2021) or influenza (January 2015-December 2019) with previous CRD were identified in registries and compared with a reference group free from CRD but with COVID-19 or influenza. Associated risk of all-cause death during the first year was analysed using adjusted Cox proportional hazards models.

Results

In COVID-19 patients with and without prior history of CRD (n=44,866) mean age was 79.8 years (SD 11.8) and 43% were women. In influenza patients (n=8897) mean age was 80.6 (SD 11.5) years and 45% were women. COVID-19 vs. influenza was associated with higher mortality risk the first two waves (HR 1.53; 95% CI 1.45–1.62, p<0.001 and 1.52; 1.44–1.61, p<0.001) but not in the third wave (1.07; 0.99–1.14, p=0.072). The cumulative incidence of all-cause death was increased in COVID-19 patients and in influenza patients if CRD was present (Figure 1). Further, CRD was an independent risk factor for all-cause death after COVID-19 in men and women (men: 1.37; 1.31–1.44, p<0.001, women: 1.46; 1.38–1.54, p<0.001). At ages <70 years women with CRD had a similar mortality rate as men with CRD while at ages ≥70 years mortality rate was higher in men (Figure 2).

Conclusions

Outcome after COVID-19 is worse if CRD is present. In women at ages <70 years the presence of CRD attenuates the protective effect of female sex. Further COVID-19 was associated with higher mortality risk than influenza during the first two waves.

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): The Family Kamprad FoundationAstraZeneca (study sponsor)
Prediction of mortality and mode of death in heart failure using multimorbidity and clinical risk score systems: a nationwide analysis
Authors: Fauchier L , Bodin A , Bentounes S A , Bisson A , Herbert J , Genet T , Ivanes F , Angoulvant D
Published: October 2022

Heart failure (HF) is associated with a higher mortality, but modes of death may vary and their respective predictors have been insufficiently defined. Charlson comorbidity index (CCI) is a tool to quantify multimorbidity and a strong estimator of mortality. The quantifiable frailty phenotype is also predictive of mortality and disability and claims data can be used to classify individuals as frail and non-frail using the Hospital Frailty Risk Score (HFRS). CHA2DS2-VASc score was originally employed as a risk assessment tool for stroke in patients with AF but this comprehensive risk assessment score may help identify HF patients who are at high risk for mortality. We evaluated whether these tools may help to predict mortality and the different modes of death in HF.

Methods

Based on the France nationwide administrative hospital-discharge database, the analysis focused on all patients with HF hospitalized in France in 2012, with at least 5 years of complete follow-up (or dead earlier) as described by others. We identified 371,848 consecutive patients hospitalized with HF seen in 2012 and followed until December 2019. Adverse outcomes were investigated during follow-up. CHA2DS2VASc score, CCI and HFRS were calculated for each patient.

Results

Among these 371,848 patients with HF, 220,774 patients died during a follow-up of 4.0±2.8 years (median 4.8) (yearly rate 14.8%, 31.3% cardiovascular and 68.6% non-cardiovascular deaths). Death occurred more often in patients with higher CHA2DS2VASc, CCI and HFRS scores. HFRS was a better predictor of total mortality than CCI and CHA2DS2VASc score (see C-statistics in Table 1). However, the CHA2DS2VASc score was a better predictor of cardiovascular mortality than CCI and HFRS. By contrast, HFRS was a better predictor of non-cardiovascular mortality than CCI and CHA2DS2VASc score. The optimal predictive performances were better for non-cardiovascular death than for cardiovascular death.

Conclusion

Multimorbidity and frailty assessed with HFRS demonstrated better performances in predicting total mortality and non-cardiovascular mortality than CCI and CHA2DS2VASc score in HF patients. By contrast, CHA2DS2VASc score was a better predictor of cardiovascular mortality than CCI and HFRS in these patients.

Funding Acknowledgement

Type of funding sources: None.
CRT-D non-responders have worse cardiovascular outcome than patients after primary ICD implantation with similar baseline left ventricular ejection fraction
Authors: Toth A , Nagy L , Racz V , Szuromi L , Sandorfi G , Jenei C S , Szabo K , Csanadi Z
Published: October 2022

Background

Cardiac resynchronisation therapy (CRT) fails to improve echocardiographic parameters and outcome in 20–40% of heart failure (HF) patients with reduced ejection fraction (EF) referred to as CRT non-responders (CRT-NR). The aim of this study was to compare the outcomes of CRT-NR patients who received a CRT defibrillator (CRT-D) device with patients after primary implantable cardioverter-defibrillator (ICD) implantation for impaired left ventricular (LV) function.

Methods

CRT-NR status was defined as no or less than 10% improvement in LV EF 12 months post implantation. CRT-NR patients and those after primary ICD implantation for LV EF<35% were identified in our database between 2010 and 2019. CRT-NR patients were further categorized as progressors (decrease in LV EF ≥5%) or non-progressors (LV EF change between +9 to −5%). Primary endpoint was all-cause mortality or the need for heart transplantation during follow-up. Statistical significance was assessed by Log-rank test of Kaplan-Meier survival analysis.

Results

151 CRT-NR patients and 219 patients after primary ICD implantation were identified with a mean ± SEM follow-up of 43.7±2.5 and 47.3±2.2 months, respectively. Baseline (preoperative) LV EFs were higher (p<0.05) for the overall CRT-NR group (EF = 27.4±0.4%) than for the ICD group (EF = 25.2±0.3%) Further, both CRT-NR subgroups of progressors (n=49; EF = 28.6±0.7%) and non-progressors (n=102; EF = 26.9±0.5%) had also significantly higher baseline LV EF as compared to ICD patients (p<0.05). No statistical significance was found between the two CRT-NR subgroups.

Event free median survival for the overall CRT-NR group (55.6 months) was significantly worse than for the ICD group (79.6; p<0.05). This difference was driven by progressor patients who had a significantly worse event free survival (37.8 months, p<0.05) than ICD patients, while vent free survival in non-progressors (60.8 months) was comparable to ICD patients (p=0.18).

Conclusion

Progressor subgroup of CRT-NR have worse outcome as compared to non-progressors and also to those after primary prevention ICD implantation. The poor prognosis of these patients should have implications for timely decision regarding all therapeutic measures currently available for the management of heart failure.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Project no. TKP2021-EGA-18 has been implemented with the support provided from the National Research, Developement and Innovation Fund of Hungary, financed under the TKP2021-EGA funding scheme
Temporal trends in first rehospitalisation for heart failure between 1997 and 2017. trends in hospitalization characteristics and prognostic impact
Authors: Arulmurugananthavadivel A A , Holt A H , Parveen S P , Lamberts M L , Gislason G H G , Torp-Pedersen C T P , Andersson C A , Butt J H B , Petrie M C P , McMurray J M , Fosbol E L F , Kober L K , Schou M S
Published: October 2022

Background

Neurohormonal blockade/modulation has improved life expectancy in HF, but it is unknown whether the time between a first hospitalisation for HF and the first rehospitalisation has increased.

Purpose

To investigate temporal trends of time between first hospitalisation for HF and first rehospitalisation for HF.

Methods

Using nationwide registers, 43,176 patients with a first hospitalization of HF during 1997–2017 were included. Temporal trends in a) time to first rehospitalisation for HF and b) mortality and rehospitalisation for HF after first rehospitalisation for HF were investigated, as was length of stay and inpatient mortality during first rehospitalisation. Rehospitalisation within 30 days was considered the same event as the index diagnosis.

Results

Between 1997 and 2017, the time between first hospitalisation for HF and first rehospitalisation increased from a median of 351 days to 464 days. During first rehospitalisation for HF, the median length of stay decreased from 6 days to 3 days, in-hospital death decreased from 10% to 6%, and the 90-day absolute risk of death after rehospitalisation decreased from 25% to 19% (Figure 1). After the first rehospitalisation for HF, the 1-year age-standardized mortality and HF rehospitalisation rates decreased, during 1997–2017, from 43 to 30/100-person and 35 to 25/100-person, respectively (Figure 2). Reductions in 5-year mortality and HF hospitalization were also observed. After discharge, an increasing number of patients were started on ACE-I or ARB (1997–2017: 73.7%–79.4%), beta-blockers (1997–2017: 33.7%–83.0%), and MRAs (1997–2017: 43.1%–49.7%) within 90 days after hospitalisation.

Conclusions

Between 1997 and 2017, the median time from first hospitalisation to first rehospitalisation for HF increased by 100 days, while the length of stay and in-hospital death during hospitalisation for HF decreased markedly. 1-year and 5-year mortality and HF rehospitalisation rates after first rehospitalisation for HF also decreased between 1997 and 2017.

Funding Acknowledgement

Type of funding sources: None.
Genetic analysis of Korean non-ischemic dilated cardiomyopathy using next generation sequencing
Authors: Oh J , Yoon M , Lee S H , Lee C J , Park S , Lee S H , Kang S M
Published: October 2022

Background

Non-ischemic dilated cardiomyopathy (NIDCM) is a genetic disorder that causes heart failure and life-threatening arrhythmia. However, there has been no study about the up-to-date genetic analysis for NIDCM in Korean. Therefore, we performed the genetic analysis of Korean NIDCM patients (pts) using next generation sequencing (NGS).

Methods

We analyzed clinical and echocardiographic data of 203 NIDCM in a single center from July 2017 to May 2020. All pts underwent NGS analysis with customized panel including 369 genes. Genetic variants were classified as pathogenic, likely pathogenic mutations or variants of uncertain significance regarding American College of Medical Genetics guideline.

Results

A total of 203 NIDCM pts (57±15 years old, 32.0% male, LVEF 28%) had NGS analysis. Thirty-seven (18.2%) pts had pathogenic or likely pathogenic mutations. The most prevalent mutated genes were TTN (n=16, 43.2%). TNNT2 (n=6, 16.2%), MYBPC3 (n=6, 16.2%) and MYH7 (n=3, 8.1%) mutated genes were common in the following order. The patients with positive panel mutation had no significant difference in initial LVEF (27% vs. 28%, p=0.216) and prevalence of atrial fibrillation (37.8% vs. 44.6%, p=0.454) compared with patients with negative panel mutation. During the median follow-up period of 40 months, there was no significant difference in composite outcome (all-cause death, heart transplantation, LVAD, heart failure re-admission, fatal arrhythmia) (35.3% vs. 32.2%, p=0.729) or presence of improved EF (≥10 points increase from baseline LVEF, and a second measurement of LVEF >40%) (41.2% vs. 50.0%, p=0.354) between the two groups.

Conclusion

This is the first study of NGS analysis in Korean NIDCM pts. We could find disease-related pathogenic or likely pathogenic mutations in 18.2% NIDCM patients. Further prospective, large study should be warranted to elucidate the effect of genetic mutation in clinical manifestation and prognosis of NIDCM in Korean population.

Funding Acknowledgement

Type of funding sources: None.
The prognostic role of galectin-3 and endothelial function in patients with heart failure according to left ventricular ejection fraction classification HF group
Authors: Tsigkou V , Siasos G , Oikonomou E , Zaromitidou M , Mourouzis K , Dimitropoulos S , Bletsa E , Gouliopoulos N , Stampouloglou P K , Panoilia M E , Marinos G , Tsioufis K , Vavuranakis M , Tousoulis D
Published: October 2022

Background

Heart failure (HF) is nowadays classified in HF with reduced ejection fraction (HFrEF), HF with mildly-reduced EF (HFmrEF) and HF with preserved EF (HFpEF). Endothelial dysfunction, increased arterial stiffness and galectin-3, a biomarker of myocardial fibrosis, have been linked to major adverse cardiovascular events (MACE) in patients with ischemic HF.

Purpose

The purpose of this prospective, follow-up study was to investigate in patients with stable ischemic HF the prognostic role of circulating galectin-3 levels, endothelial function and arterial stiffness according to left ventricular ejection fraction classification.

Methods

In this study we prospectively enrolled 340 patients with stable ischemic HF. Patients were categorized in HFrEF (when EF below or equal to 40%), HFmrEF (when EF is more than 40% and below/equal to 49%) and HFpEF (when EF is more/equal to 50% along with the presence of structural or functional dysfunction and/or elevated natriuretic peptides) according to recent guidelines upon 2D echocardiographic assessment. We evaluated flow-mediated dilatation (FMD) of brachial artery as a marker of endothelial function, carotid-femoral pulse-wave velocity (PWV) as a marker of arterial stiffness and galectin-3 levels as a biomarker of fibrosis. Patients were followed-up for MACE and the primary endpoint was defined as cardiovascular death, myocardial infarction, coronary revascularization, stroke, and hospitalization due to HF.

Results

Interestingly, FMD values exhibited a stepwise improvement according to LVEF (HFrEF: 4.74±2.35% vs. HFmrEF: 4.97±2.81% vs. HFpEF: 5.94±3.46%, p=0.01) which remained statistically significant after the evaluation of possible confounders including age, sex, cardiovascular risk factors and number of significantly stenosed epicardial coronary arteries (b coefficient: 0.990, 95% CI: 0.166–1.814, p=0.019). Multivessel coronary artery disease (CAD) was more frequent in the group of HFrEF (HFrEF: 56% vs. HFmrEF: 64% vs. HFpEF: 73%, p=0.049). Nevertheless, PWV did not display any association with LVEF. Patients who presented MACE exhibited worse FMD values (4.51±2.35% vs. 5.32±2.67%, p=0.02) and the highest tertile of galectin-3 was linked to more MACEs (36% vs. 5.9%, p=0.01).

Conclusions

FMD values have a linear improvement according to LVEF increase in patients with ischemic HF and worse values are linked to more MACEs. Higher levels of galectin-3 might be used for risk stratification of patients with ischemic HF.

Funding Acknowledgement

Type of funding sources: None.
Prognostic value of estimating appendicular muscle mass in heart failure using creatinine/cystatin C
Authors: Sunayama T , Matsue Y , Dotare T , Maeda D , Yatsu S , Ishiwata S , Nakamura Y , Akama Y , Tsujimura Y , Suda S , Kato T , Hiki M , Kasai T , Minamino T
Published: October 2022

Objectives

As heart failure with concomitant sarcopenia has a poor prognosis, simple methods for evaluating the appendicular skeletal muscle mass index (ASMI) are required. Recently, a model incorporating anthropometric data and the sarcopenia index, that is, the ratio of serum creatinine to cystatin C (Cre/CysC), was developed to estimate the appendicular skeletal muscle mass. We hypothesized that this model would be superior to the previous model, which uses only anthropometric data to predict the prognosis. This study aimed to compare the prognostic value of low ASMI as defined by the biomarker and anthropometric models in patients with heart failure.

Methods

Among 847 patients, we estimated ASMI using an anthropometric model consisting of age, body weight, and height in 791 patients and a biomarker model that incorporates age, body weight, hemoglobin, and Cre/CysC in 562 patients. Patients were divided into low and non-low ASMI groups according to the ASMI estimated by each model, using the cut-off proposed by the Asian Working Group for Sarcopenia. The primary outcome was all-cause mortality.

Results

Overall, 53.4% and 39.1% of patients were diagnosed with low ASMI by anthropometric and biomarker models, respectively. The agreement of the diagnosis of low ASMI between the two models was poor, with a kappa coefficient of 0.56 (95% confidence interval: 0.49–0.63). Kaplan-Meier curves showed that a low ASMI was significantly associated with all-cause death in both models. However, this association was retained after adjustment for other covariates in the biomarker model (hazard ratio: 2.60, p=0.003), but not in the anthropometric model (hazard ratio: 0.70, p=0.257).

Conclusions and implications

Among patients hospitalized with heart failure, a low ASMI estimated using the biomarker model, but not the anthropometric model, was significantly associated with all-cause mortality.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Japan Agency for Medical Research and Development
Analysis of novel cardiac biomarkers in diagnosis of decompensated heart failure
Authors: Froehling T , Mirna M , Paar V , Shomanova Z , Van Almsick V , J Motloch L , Semo D , Makowski L , Rukosujew A , Sindermann J R , Reinecke H , Lichtenauer M , Pistulli R
Published: October 2022

Aims

Heart failure (HF) remains a major therapeutic and diagnostic challenge. In this study we aimed to analyze the predictive potential of four novel cardiovascular biomarkers – soluble urokinase-type plasminogen activator receptor (suPAR), vascular cell adhesion molecule (CAM-1), heart-type fatty acid binding Protein (H-FABP) and growth/differentiation factor 15 (GDF-15) in detecting cardiac decompensation in patients with HF.

Methods

In total, 136 patients (40 decompensated HF, 96 compesated HF) were retrospectively enrolled and the serum biomarker concentrations of GDF-15, suPAR, H-FABP and CAM-1 were analyzed by Enzyme Linked Immunosorbent Assay (ELISA). Biomarker concentrations were correlated with clinical and biochemical parameters of enrolled patients, the predictive value for detecting cardiac decompensation was assessed by ROC-plots, as well as univariate and multivariate logistic regression analysis. Cut-offs for cardiac decompensation were calculated by means of the Youden index.

Results

A significant increase in the levels of suPAR (1.6-fold change, p<0.0001), CAM-1 (1.6-fold change, p<0.0001), HFABP (2.2-fold change, p=0.0458) and GDF-15 (1.7-fold change, p=0.0009) was detected in all patients with decompensated HF compared to patients with compensated HF. In univariate logistic regression analysis, plasma concentrations of GDF-15, H-FABP, suPAR and CAM-1 were significantly associated with the risk for cardiac decompensation. For GDF-15, suPAR and CAM-1, this association remained significant even after correction for confounders in a multivariate logistic regression analysis. Additionally, AUCs (GDF-15: 0.759, 95% (0.683–0.866), suPAR: 0.838, 95% (0.750–0.926), CAM-1: 0.838, 95% (0.750–0.926)) and optimal cut-offs (GDF-15: 1404.8835 pg/ml, suPAR: 4774.027 pg/ml, CAM-1: 4.74027 ng/ml) of the biomarkers were calculated. Correlation analyses found clinical and biochemical parameters such as creatinine as well as inflammatory marker CRP to be significantly correlated with novel biomarkers (r>0.3, p<0.001. In conjunction with the results for the AUC of NTproBNP (AUC=0.785), suPAR (AUC=0.838) and CAM-1 (AUC=0.838 more accurately prediced cardiac decompensation in heart failure than NTproBNP (Figure 1).

Conclusion

In conclusion, the investigated novel cardiovascular biomarkers could be a valuable tool to facilitate therapeutic decisions in patients with HF and suspicion of cardiac decompensation. Parameters such as renal function should be taken into account.

Funding Acknowledgement

Type of funding sources: None.
Exercise MR-proANP unmasks latent right heart failure in CTEPH
Authors: Kriechbaum S D , Birmes J , Wiedenroth C B , Gruen D , Vietheer J , Richter M J , Guth S , Roller F , Liebetrau C , Hamm C W , Keller T , Rieth A
Published: October 2022

Background

Chronic right heart failure is the major determinant of outcome in chronic thromboembolic pulmonary hypertension (CTEPH). Thus, its early detection is crucial for optimal patient management. Hemodynamic assessment with invasive right heart catheterization and the measurement of natriuretic peptides at rest are established diagnostic tools in this context. An elevated right atrial pressure (RAP) is a sensitive parameter of right right heart failure. Mid-regional pro-atrial natriuretic peptide (MR-proANP) is a natriuretic peptide that reflects right atrial stress levels.

There is a growing recognition of exercise diagnostics in the assessment of right heart failure, particularly in patients with normal or borderline findings at rest. There are no data on the dynamics of MR-proANP in correlation to RAP during physical exercise.

Purpose

The present study was designed to investigate the dynamics of RAP and MR-proANP during physical exercise in patients with CTEPH and to determine whether these parameters might serve as a tool to measure exercise-dependent atrial stress as an indicator of right heart failure.

Methods

This observational cohort study included 100 CTEPH patients who underwent right heart catheterization during physical exercise (eRHC). Blood samples for MR-proANP measurement were taken prior, during, and after eRHC. MR-proANP levels were correlated to RAP levels at rest, at peak exercise (eRAP), and during recovery. RAP at rest ≤7 mmHg was defined as normal and eRAP >15 mmHg as suggestive of right heart failure.

Results

During eRHC mean RAP increased from 6±4 mmHg to 16±7 mmHg (p<0.001). MR-proANP levels and dynamics correlated with RAP at rest (rs=0.61; p<0.001; figure 1a) and at peak exercise (rs=0.66; p<0.001; Figure 1b). Furthermore, the relative percent increase in MR-proANP correlated with the relative percent increase in eRAP (rs=0.52; p<0.001; Figure 1c) Logistic regression analysis revealed the peak MR-proANP level (B=0.058; p=0.004) and the right atrial area (B=0.389; p<0.001) to be associated with eRAP dynamics. A peak MR-proANP level ≥139 pmol/L (AUC=0.81) and recovery level ≥159 pmol/L (AUC=0.82) predicted an eRAP >15 mmHg. Physical exercise unmasked RH failure in 39% of patients with normal RAP at rest; they were also characterized by a more distinct increase in MR-proANP levels (p=0.005) and higher peak (p<0.001) and recovery levels (p<0.001).

Conclusions

RAP and MR-proANP dynamics unmask manifest and latent right heart failure in CTEPH patients, which may be useful in estimating prognosis.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): SFB 1213 area CP-01 projectWilliam G. Kerckhoff-FoundationKerckhoff Heart Research Institute (KHFI)German Center for Cardiovascular Research (DZHK)
Heart failure is associated with low circulating levels of secreted frizzled receptor protein 5 (Sfrp5)
Authors: Kelly C , Chu M , Untaru R , Assadi-Khansari B , Chen D , Croft A , Horowitz J , Sverdlov A L , Ngo D T M
Published: October 2022

Background/Introduction

Obesity and metabolic dysregulation are closely associated with the pathophysiology of multiple cardiovascular diseases (CVD). To date, the pathophysiological mechanism(s) of obesity and its link with cardiovascular systems remain largely unknown. Adipose tissue inflammation as a result of excessive fat expansion in obesity, leading to increased systemic production of growth factors and recruitment of inflammatory cells have been postulated to be a major factor. Secreted frizzled-related protein 5 (SFRP5) is an anti-inflammatory adipokine that is linked with obesity and metabolic regulation and has been indicated to affect cardiovascular functions. Currently, the role of circulating SFRP5 levels as a biomarker for cardiovascular diseases are poorly understood, with studies yielding discordant results.

Purpose

This study aims to evaluate the relationship between circulating SFRP5 and cardiovascular functions in a cohort of patients with established CVD.

Methods

Patients (n=262, 148 male (56.5%), age (68±11 yrs)) presenting to the cardiology unit for cardiovascular investigations were recruited into the study. Plasma SFRP5 levels were measured via enzyme-linked immunosorbent assay (ELISA). Associations between plasma SFRP5 levels, cardiovascular functions, and patients' co-morbidities were analysed using univariate and multivariate analyses.

Results

Plasma SFRP5 levels were significantly lower in patients presenting with: heart failure (HF) vs non-HF (median; (10.7 vs 31.0; p<0.001); coronary artery disease (CAD) vs non-CAD; (11.0 vs 33.8; p<0.001); and atrial fibrillation (AF) vs non-AF; (11.2 vs 23.2; p=0.001). On univariate analyses, SFRP5 levels also significantly positively correlated with left ventricular ejection fraction (LVEF) (r=0.52, p<0.001), estimated glomerular filtration rate (eGFR) (r=0.16, p=0.02), total cholesterol levels and triglycerides (r=0.29, p<0.001; r=0.17, p<0.01 respectively). Low SFRP5 levels were correlated with high C-reactive protein (CRP) and E/E' (r=−0.29, p<0.001, r=−0.30, p<0.001, respectively). Patients with HF, CAD, statin use, low LVEF, low triglycerides, high CRP and high eGFR were associated with lower SFRP5 levels independent of age, BMI or diabetes on multivariate analysis (overall model r=0.729, SE=0.638).

Conclusion

Our results show that low plasma SFRP5 levels are independently associated with HF, CAD, and impaired systolic and diastolic functions. These results suggest that SFRP5 may regulate cardiovascular functions independent of obesity and metabolic regulations.

Funding Acknowledgement

Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Heart Foundation of Australia Future Leader FellowshipsNSW Ministry of Health EMC FellowshipHeart Foundation of Australia Future Leader Fellowship
MR-proADM is a strong independent predictor of long-term all-cause mortality risk in patients with chronic heart failure: results from the E-INH study
Authors: Kerwagen F , Sahiti F , Sehner S , Albert J , Cejka V , Moser N , Morbach C , Gueder G , Frantz S , Ertl G , Angermann C E , Stoerk S
Published: October 2022

Background

Mid-regional proadrenomedullin (MR-proADM) is a blood biomarker indicating critical illness. Its short-term prognostic relevance has been investigated in several conditions including heart failure (HF). Yet, the long-term prognostic utility is unknown.

Methods

We conducted a post-hoc analysis of the Extended Interdisciplinary Network for Heart Failure (E-INH) study, which investigated the long-term effects of a HF nurse-led remote patient care program (HeartNetCare-HFTM [HNC]). Patients from nine regional centers in Germany hospitalized with HF and a left ventricular ejection fraction (LVEF) <40% were randomized into HNC vs. Usual Care. MR-proADM and other standard biomarkers for disease progression and systemic inflammation were measured from venous blood collected at study inclusion, i.e. during index hospitalization. The prognostic utility was assessed using Kaplan-Meier plots and Cox proportional hazard models, and compared with other biomarkers by ROC curves.

Results

From 919 out of the 1022 recruited patients (90%), baseline levels of MR-proADM were available: median MR-proADM 0.89 (quartiles 0.63, 1.28) nmol/l; mean age 68±12 years; 28% women; 45% in class III or IV of the New York Heart Association (NYHA) classification.

Median LVEF was 31 (25, 37) %. Median levels of NT-proBNP, high sensitive C-reactive protein (hsCRP), tumor necrosis factor (TNF)-a, and interleukin-6 (IL-6) were 3045 (1087, 7759) pg/ml, 9.2 (3.3, 25.2) mg/l, 13.4 (10.4, 17.5) pg/ml, and 4.9 (2.0, 11.4) pg/ml, respectively. Higher levels of MR-proADM at baseline were associated with age, female sex, NYHA class, NT-proBNP, hsCRP, IL-6, and TNF-α, while there was an inverse association with LVEF.

In the course of 10 years of follow-up, 691 (68%) patients died. Unadjusted MR-proADM strongly predicted all-cause death when used as a continuous variable (HR 1.31 per nmol/l, 95% CI 1.26–1.37; p<0.001) or when grouped into quartiles (HR 1.85, 95% CI 1.71–2.0; p<0.001). Adjustments for age, sex and NYHA functional class did not materially alter the strong association. Plotting quartiles of MR-proADM in a Kaplan-Meier curve (see Figure 1) confirmed this findings. As shown in Figure 2, MR-proADM had the highest area under the curve (AUC) in ROC analysis when compared to other biomarkers.

Conclusion

MR-proADM appears to be a strong and independent predictor for long-term all-cause mortality risk in HF with reduced ejection fraction (HFrEF). Therefore, assessing MR-proADM may contribute to better categorization of risk and tailored care. Its clinical utility needs to be investigated in future studies.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): BMBF
Dynamic changes of left atrial function during supine ergometry: evidence for interplay with left ventricular function and dynamic changes of pulmonary pressure
Authors: Armenis I , Ritsatos K , Gonteva M , Kyrzopoulos S , Tsiapras D , Athanassopoulos G
Published: October 2022

Introduction

Despite the pivotal role of left atrial (LA) function in a variety of cardiac pathologies, it has been studied mainly at rest.

Aim

Aim of the study was to assess the effect of semisupine exercise ergometry (Ex) on LA function, by volumetric and strain parameters and to interrogate relationships with left ventricular (LV) function and noninvasive hemodynamics.

Patients and methods

Eighty-two patients (female 26, age: mean/SD 61/15) referred for Ex were studied. The following parameters were estimated by 2 D echo: LV systolic (LVvolsyst) and diastolic (LVvoldiast) volume, ejection fraction (LVEF), stroke volume (LVsv), LA minimum (LAvolmin) and maximal volume (LAvolmax), LA emptying fraction [LAEF), LA reservoir volume (LAvolres = LAvolmax − LAvolmin), LA reservoir fraction (LAresFR = LAvolres/LVsv), LA conduit volume (LAcondvol = LVsv − LAvolres) and LA conduit fraction (LAcondFR = LAcondvol/LVsv). LV strain (LVSR) and LA strain (LASR) were estimated by 2D analysis. Peak tricuspid gradient (TRpg) was also estimated. Parameters were measured at rest R and Ex and the respective % changes (%d) were calculated.

Results

SBE performance was efficient with a % achieved target heart rate 73/9 and workload Watts 96/21. Systolic blood pressure increased from 139/53 to 179/31. Parameters with significant change during Ex are in the table (all p<0.001).

LVSRr and LVEFr were both related inversely with LAvolresR (r=−0.39/p=0.001 and r=−0.24/p=0.05) and LAresFRr (r=−0.34/p=0.001 and r=−0.25/p=0.04). LVEFr was related inversely with LAcondRFr r=−0.24/p=0.04). LVSR was related inversely with LAvolresEx (r=−0.43/p=0.001). LVSREx was related inversely with LAvolresR (r=−0.24/p=0.04) and LAcondRFr (r=−0.25/p=0.04).

The %dLVSR was related inversely with LAEFr (r=−0.25/p=0.04). The %dLVEF was related inversely with LAresFREx (r=−0.27/p=0.03) and LAcondRFr (r=−0.27/p=0.03).

The % increase in TRpg during SBE was positively related with LAresFREx r=0.30/p=0.04 and inversely with LAcondFREx (r=−0.30/p=0.04) (Figure 1).

Conclusion

SBE induces LA dynamic changes in a spectrum of volumetric and strain indices. Dynamic changes of LV are related with reservoir and conduit LA function. LA reservoir and conduit function during SBE are related with the induced dynamic changes of pulmonary pressure, thus further supporting the clinical relevance of the respective evaluation.

Funding Acknowledgement

Type of funding sources: None.