bluuebunny/crossref_metadata_2025 huggingface dataset:
Heart failure with reduced ejection fraction: predicting exercise intolerance with echocardiography
Authors: Azul Freitas A , Ferreira C , Goncalves V , Martinho S , Almeida J , Rosa J , Campos G , Jorge E , Goncalves L
Published: October 2021

Introduction

Cardiopulmonary exercise testing (CPET) is routinely used in the prognostic evaluation of patients with heart failure with reduced ejection fraction (HFrEF). Left ventricular ejection fraction (LVEF) is a strong prognostic marker but have shown a bad correlation with exercise capacity. The aim of this study is to assess the relationship between echocardiographic parameters and exercise capacity in HFrEF patients.

Methods

We retrospectively assessed all patients with HFrEF submitted to CPET and echocardiography between March and September of 2019. 73 patients were eligible for analysis. ANOVA test was used to compare Weber class groups regarding echocardiographic parameters. Multivariate linear regression with a stepwise approach was used to assess independent predictors of peak VO2 uptake. ROC curves were compared to assess the best parameter to discriminate a peak VO2 <10 ml/kg/min (Weber class D).

Results

Mean age was 53.4±11.7 years with 72.6% being male. Mean LVEF was 29.2±7.7% and mean peak VO2 was 13.4±3.8 ml/kg/min. Between the Weber class groups, significant differences were found in left (LV) and right ventricular (RV) longitudinal strain (P<0.001 and P=0.005 respectively), in the left and right atrial reservoir strain (P=0.009 and P<0.001 respectively), in pulmonary velocity acceleration time (P=0.002) and in maximal tricuspid regurgitation velocity (TRmax) (P=0.014). Left ventricular ejection fraction, tricuspid annular plane systolic excursion, and ratio E/e' were not significantly different among exercise capacity groups. Additionally, only RV longitudinal strain (r2=0.225, P=0.008) and TRmax (r2=0.073, P=0.030) were independent predictors of peak VO2. RV longitudinal strain showed the best accuracy in discriminating a Weber class of D (AUC=0.731, 95% CI: 0.613–0.848, P=0.005) with a calculated cut of −8.6% and with a negative predictive value of 95%.

Conclusion

RV longitudinal strain and TRmax seem to be the best echocardiographic predictors of exercise intolerance in patients with HFrEF. Since CPET is not widely available, these echocardiographic parameters can be clinically useful as a surrogate prognostic factor.

Funding Acknowledgement

Type of funding sources: None.
Impact of endocardial leads on the effectiveness of interventional edge-to-edge repair of tricuspid regurgitation
Authors: Goebel B , Salomon C , Abdulrahman M , Richter S , El Garhy M , Costello-Boerrigter L , Lapp H , Lauten P
Published: October 2021

Background

A considerable proportion of patients who are considered for percutaneous tricuspid valve edge-to-edge repair (pTVR) interventions have endocardial lead induced tricuspid regurgitation (TR). The aim of this study was to examine the impact of lead-leaflet interaction on the effectiveness of pTVR.

Methods

For each patient, the lead position within the tricuspid valve (central, commissural, or towards one of the three leaflets) and the type of lead-leaflet interaction (leaflet impingement or adhesion) were identified during thorough 2D/3D transthoracic and transesophageal echocardiography examinations. Before and after pTVR, echocardiographic data, including 3D full-volume datasets, were obtained and quantified. TR severity was graded from 1+ to 5+, based upon the effective regurgitant orifice area by the PISA method (EROAPISA) and the vena contracta area (VCA3D) as measured by multiplanar reconstruction from a 3D color Doppler loop. Maximal diastolic tricuspid annulus area from a 3D zoom image, tricuspid tenting area, and right atrial volume were quantified. Right ventricular assessments included ejection fraction (RVEF3D) and diastolic (RVVd3D) and systolic (RVVs3D) volumes.

Results

Out of 99 patients who underwent pTVR at our hospital, 38 patients had implanted cardiac devices of the following types: pacemakers (n=25, 66%), cardiac defibrillators (n=7, 18%), and biventricular pacemakers (n=6, 16%). In 24 (63%) of these device patients, TR grade was ≤2+ after pTVR. In 14 of the device patients, TR grade remained severe after intervention (Grade 3+ in 15%, grade 4+ in 11%, and Grade 5+ in 11% of the device group). In comparison, in 78% of patients without endocardial leads, only moderate TR was achieved after pTVR. Figure 1 shows the distribution of lead positions within the tricuspid valve. A relevant lead-leaflet interference (rLLI) for pTVR interventions was defined as impingement or adhesion in the target area of the coaptation device (anteroseptal or posteroseptal). Binary logistic regression analysis showed an increase risk (Odds ratio 11, R2 0.34, 95% CI 0.019–0.44, p=0.003) for a suboptimal pTVR result (TR grade >2+ after intervention) in patients with rLLI. Although patients with rLLI (n=17) had significantly higher VCA3D values as compared to patients without rLLI (n=21), it was not predictive for pTVR results. Echocardiographic parameters of right ventricular and tricuspid valve dimensions showed only a trend to higher values in the group with rLLI (Table 1).

Conclusion

Endocardial lead induced TR negatively impacts the effectiveness of pTVR irrespective of the initial degree of TR.

Funding Acknowledgement

Type of funding sources: None.
Death of a child and the risk of heart failure: a population-based cohort study from Denmark and Sweden
Authors: Wei D , Li J , Chen H , Janszky I , Ljung R , Fang F , Laszlo K.D
Published: October 2021

Background

Increasing evidence suggests that the death of a child is associated with increased risks of ischemic heart diseases and atrial fibrillation and the association is in part attributable to stress-related mechanisms. However, knowledge regarding the risk of heart failure (HF) after the death of a child is very limited.

Purpose

To study the association between the death of a child and the parents' risk of HF.

Methods

We conducted a population-based cohort study involving parents of live-born children recorded in the Danish and Swedish Medical Birth Registers during 1973–2016 and 1973–2014, respectively (n=6,717,531). We retrieved information on child death, HF diagnosis and parents' sociodemographic characteristics from several nationwide registries. We performed Poisson regression models to estimate incidence rate ratio (IRR) and 95% confidence intervals (CI) for HF.

Results

A total of 129,829 (1.9%) parents lost at least one child during the follow-up. Bereaved parents had a 35% higher risk of HF than non-bereaved parents [IRR (95% CI): 1.35 (1.29–1.41)]. The association was present not only if the child died due to cardiovascular or other natural causes [IRR (95% CI): 1.48 (1.25–1.75) and 1.35 (1.27–1.44), respectively], but also in case of unnatural deaths [IRR (95% CI): 1.32 (1.24–1.42)]. There was a trend toward a U-shaped association according to the deceased child's age at loss and the risk of HF. Bereaved parents who lost their only child or had three or more remaining live children at the time of loss had higher HF risk than those with one or two live children at the time of loss. We found no clear evidence for a difference in the association of interest over time.

Conclusions

The death of a child was associated with an increased risk of HF. The finding that not only cardiovascular and other natural deaths, but also unnatural deaths were associated with HF suggests that stress-related mechanisms may contribute to the development of HF.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Swedish Council for Working Life and Social Research and Karolinska Institutet's Research Foundation
Deep learning for mortality prediction in patients with a de-novo or worsened heart failure
Authors: Herman R , Vanderheyden M , Vavrik B , Beles M , Palus T , Kepesiova Z , Goethals M , Verstreken S , Dierckx R , Heggermont W , Bartunek J
Published: October 2021

Background

Heart failure (HF) is a heterogenous syndrome with complex pathophysiology. Biomarkers and clinical risk scores often fail to provide optimal patient-level precision in the prognostic stratification. As utilizing single observational timepoint, they do not capture the entire care pathway with variations in individual patient management. Electronic patient records provide an opportunity to develop new artificial intelligence (AI) strategies for comprehensive prognostic re-stratification reflecting diagnostic and therapeutic management.

Purpose

We sought to use deep artificial intelligence (AI) and develop an unbiased predictive algorithm for all-cause mortality in a cohort of patients hospitalized with a de novo or worsened HF.

Methods

In a cohort of 2449 HF patients hospitalized between 2011–2017, we utilized 151 451 patient exams from 422 parameters. They included clinical phenotyping, medication, ECG, laboratory, echocardiography, catheterization data or percutaneous and surgical interventions gathered on a routine clinical basis reflecting standard of care as captured in individual electronic records. The AI model development consisted of 101 iterations of repeated random subsampling splits into balanced training and validation sets.

Results

AI models yielded performance ranging from 0.83 to 0.89 AUC on the outcome-balanced validation set in predicting all-cause mortality at 30-, 90-, 180-, 360- and 720-day time-limits (Figure 1). The primary endpoint, 1-year mortality prediction model, recorded an 0.85 AUC accuracy. We observed stable model performance across all HF phenotypes: HFpEF 0.83 AUC, HFmrEF 0.85 AUC and HFrEF 0.86 AUC, respectively).

Conclusion

Our findings present a novel, patient-level, AI-based risk prediction of all-cause mortality in heart failure with a robust accuracy across its phenotypes. This suggests the potential of AI based predictive models in a point-of-care approach to guide clinical risk stratification.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): VZW Cardiovascular Research Center Aalst
Echocardiographic predictors of the effectiveness of interventional edge-to-edge repair in tricuspid valve regurgitation
Authors: Goebel B , Salomon C , Abdulrahman M , Richter S , El Garhy M , Costello E , Lapp H , Lauten P
Published: October 2021

Background

Percutaneous tricuspid valve edge-to-edge repair (pTVR) is a promising interventional technique for patients with tricuspid regurgitation (TR), but guidance regarding patient selection and echocardiographic screening is lacking. The aim of this study was to identify echocardiographic parameters which may predict pTVR success.

Methods

Before and after pTVR, echocardiographic data, including 3D full-volume datasets, were obtained and quantified. Right ventricular assessments included ejection fraction (RVEF3D) and diastolic (RVVd3D) and systolic (RVVs3D) volumes. Also evaluated were: right atrial (RA) volume, effective regurgitant orifice area by PISA method (EROAPISA), vena contracta area (VCA3D) by multiplanar reconstruction from a 3D colour Doppler loop (Figure 1a), maximal diastolic tricuspid annulus area from a 3D zoom image (Figure 1b), and tricuspid tenting area. TR severity was graded according to EROAPISA and VCA3D as grade 1+ to 5+.

Results

Patients (n=99, age 79±6 years, 48 male) with at least moderate to severe TR undergoing pTVR were consecutively included. The patients were divided into groups according to their post-pTVR TR grade. Group 1 had TR grade ≤2+, and group 2 had TR grade ≥3+.Echocardiographic parameters before pTVR for both groups are presented in Table 1. As expected, patients with TVR ≥3+ after pTVR had significantly worse pre-intervention echocardiographic measurements of TR severity, valve dimensions, and chamber volumes. ROC curves for the prediction of TR ≤2+ (mild to moderate) after pTVR (defined as VCA3D <0.75 cm2 and EROAPISA <0.4 cm2) were drawn for different echocardiographic features (Figure 2). VCA3D by 3D colour Doppler yielded the highest area under the ROC curve followed by TV anatomy measurements (Annulus area3D, Tenting area) and right atrial volume.

Conclusion

A thorough evaluation of TR and valve dimensions by 3D echocardiography, particularly the evaluation of VCA3D by 3D colour Doppler, aids in the prediction of the probability of pTVR success.

Funding Acknowledgement

Type of funding sources: None.
Prevalence of and factors associated with undiagnosed stage 3 chronic kidney disease in patient with a history of heart failure: a report from REVEAL-CKD
Authors: Wittbrodt E , Kushner P , Barone S , Kumar S , Chen H , Jarbrink K , Abdul Sultan A , Garcia Sanchez J.J , Tangri N
Published: October 2021

Background

Chronic kidney disease (CKD) is a serious debilitating condition affecting 10% of the world's population, yet it remains largely under recognised even among patients with pre-existing comorbidities. Approximately 5% of patients with CKD have a history of heart failure (HF), however factors associated with undiagnosed CKD in patients with multimorbidity remain unclear.

Purpose

REVEAL-CKD is a multinational initiative to assess undiagnosed CKD. This analysis aims to assess prevalence and factors associated with undiagnosed stage 3 CKD in patients with heart failure.

Methods

From the US, we utilised TriNetX, a federated research network providing statistics on electronic health records. Adult patients, with two consecutive estimated glomerular filtration rate (eGFR) measurements ≥30 and <60 mL/min/1.732 at least 90 days apart were identified between 2015–2020. HF status was ascertained by ICD codes prior to the index date (date of the second eGFR measurement). Patients with no ICD code for CKD at any time before or up to 6 months after the index date were considered to have undiagnosed CKD.

Results

The study cohort included 31,263 patients with eGFR values indicating stage 3 CKD and pre-existing HF with mean age of 72 years (standard deviation: 11 years). The overall prevalence of undiagnosed CKD was 48.5% (n=15,159, 95% Confidence Interval: 47.9–49.0). Prevalence of undiagnosed CKD increased with age, was greater than 50% in female patients and was between 38% and 46% in patients with other pre-existing comorbidities (Table 1). Compared to patients with diagnosed CKD, the undiagnosed group had more females (41% versus 60%) and a had higher proportion of patients in the older age group (≥75 years: 43% versus 52%). Fewer undiagnosed CKD patients had pre-existing comorbidities than those with diagnosed CKD.

Conclusion

This study suggests that a large proportion of either older or female patients with baseline HF comorbidity have undiagnosed CKD. These results suggest that an opportunity exists for more proactive CKD diagnosis and monitoring of patients with comorbidities

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): AstraZeneca
Decreasing time on sick leave for patients with heart failure in Sweden during two decades
Authors: Ekestubbe S , Giang Kok W , Lindgren M , Rosengren A , Schioler L , Schaufelberger M
Published: October 2021

Background

Heart failure (HF) is increasing in people of working age in Sweden (1). Given high morbidity and reduced quality of life among HF patients (2, 3), working capacity could be greatly affected, however, studies are scarce.

Purpose

To determine trends in sick leave rates following a first hospitalization for HF in Sweden 1995–2015 compared to controls matched by age and sex.

Methods

In Sweden, people who cannot work receive sickness benefit. Sickness benefit pay days are registered by Statistics Sweden. We identified all patients aged 18–60 years with a first hospitalization for HF in Sweden 1995–2012 in the National Patient Register (NPR). For each case we selected 2 controls matched for age and sex. Cases and controls were split into age groups, <45 years and 45–60 years. Age, sex and comorbidities were recorded. Paid sickness benefit days were recorded during the index year and the two subsequent years.

Results

A total of 24,677 cases and 65,923 controls were included, mean age for the younger and older age group 36.6 and 54.5 years, and proportion of women 35.3% and 23.8%, respectively. In 1995, the proportion of time on sickness benefit in patients <45 years was on average 28%, decreasing to 15% in 2012, with corresponding estimates for patients 45–60 29% and 17%, shown by index year for cases and controls for patients <45 years in Figure 1 and for patients 45–60 years in Figure 2.

Conclusion

Patients had a longer time on sick leave than controls over the study period. Time on sickness benefit initially declined over the course of the study period for both patients and controls, but the last years of the study period this decline stalled for both patients and controls.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by the Swedish state under an agreement between the Swedish government and the County Councils Concerning Economic Support of Research and Education of Doctors [ALFGBG-717211, ALFGBG-433211, ALFGBG-725081]; the Swedish Heart and Lung Foundation [2013-0307, 2018-0419, 2018-0589]. Figure 1Figure 2
Impact of COVID-19 on heart failure hospitalizations: one year after
Authors: Gonzalez-Manzanares R , Heredia Campos G , Fernandez-Aviles Irache C , Resua Collazo A , Pericet-Rodriguez C , Gallo-Fernandez I , Fernandez-Ruiz A , Carnero Montoro L , Oneto-Fernandez M.J , Luque-Moreno A , Paredes-Hurtado N , Pastor-Wulf D , Lopez-Baizan J , Castillo-Dominguez J.C , Anguita M
Published: October 2021

Background

Coronavirus disease 2019 (COVID-19) rapidly spread worldwide since it first emerged in December 2019, with more than 100 million cases reported to date, causing a great impact on healthcare systems. Heart failure (HF) is a major health problem. It affects about 10 million people in Europe and is the leading cause of hospitalization for patients older than 65 years. During the first wave of COVID-19 there was an important decrease in HF hospitalizations. Data regarding HF admissions during the second and third waves and inter-waves periods is scarce.

Purpose

To examine the impact of COVID-19 on HF hospitalizations during the first year of the pandemic and to compare the clinical characteristics and in-hospital outcomes of patients admitted during the three pandemic waves with those admitted the previous year during the same periods.

Methods

Data from a tertiary Heart Failure Unit in Southern Spain between 1 March 2020 and 28 February 2021 were compared to the corresponding time period in the previous year. The impact of the pandemic on weekly hospitalizations was assessed using a Poisson Regression model, with year, season and pandemic wave as covariates. Clinical characteristics and in-hospital outcomes of patients admitted during the three waves were compared to those admitted during the same periods one year after.

Results

A significantly lower weekly number of admissions for HF was observed during the three pandemic wave periods compared to all other included periods (inter-wave periods and same periods in the previous year) (p=0.002, IRR 0.81, 0.77–0.86). Figure 1 shows monthly HF admissions between 1 March 2020 and 28 February 2021 (pandemic year) and the previous year, as well as COVID-19 hospitalized cases in our area. Clinical characteristics and in-hospital outcomes of patients admitted during the COVID-19 waves and the same periods in the previous year are shown in Figure 2. Patients admitted during the COVID-19 waves were younger, and fewer had diabetes mellitus (DM), atrial fibrillation (AF) and valvular heart disease (VHD). There were no differences in clinical outcomes (intensive care unit admission, in-hospital mortality).

Conclusion

There was decline in HF hospitalization during the three waves of the pandemic year, but not during the inter-wave periods. Patients admitted during the wave periods had some clinical differences but similar in-hospital outcomes.

Funding Acknowledgement

Type of funding sources: None. Figure 1Figure 2
Concordance between quantitative and semi-quantitative analysis of Tc-99m-pyrophosphate scintigraphy for the diagnosis of transthyretin cardiac amyloidosis in patients with HFpEF
Authors: Murat S , Yalvac H.E , Mert G.O , Sivrikoz I.A , Cavusoglu Y
Published: October 2021

Background

Transthyretin (TTR) cardiac amyloidosis (CA) is an underdiagnosed cause of heart failure with preserved ejection fraction (HFpEF). Cardiac scintigraphy with 99mTechnetium-pyrophosphate (99mTc-PYP) is referred as a simple, non-invasive and reliable method in the diagnosis of TTR-CA. American Society of Nuclear Cardiology Practice Points recommends two interpretative approaches: the quantitative heart-to-contralateral lung ratio (H/CL) at 1 hour or the semi-quantitative visual assessment at 3 hours after radiotracer injection.

Purpose

In this study, we evaluated the concordance between semi-quantitative and quantitative approaches in the diagnosis of TTR CA in patients with HFpEF.

Methods

This single-center, prospective study included 78 patients who had a diagnosis of HFpEF according to 2016 ESC HF guidelines. 99mTc-PYP cardiac scintigraphy was performed in 43 patients who have ≥2 red flags for TTR-CA including left ventricular hypertrophy (LVH) (wall thickness ≥12 mm), biventricular hypertrophy, sparkling pattern, reduction in longitudinal strain with apical sparing, thickening of the interatrial septum (>6mm), low-voltage, pseudo infarct pattern or atrioventricular block on ECG. In the absence of monoclonal protein in the serum and urine, Grade 2 to 3 myocardial uptake in semi-quantitative analysis at 3 hours or a H/CL ratio of ≥1.5 in quantitative analysis at 1 hour post injection of 99mTc-PYP is considered positive for TTR-CA. Grade 2–3 uptake with a H/CL ratio ≥1.5 or Grade 0–1 uptake with a H/CL ratio <1.5 were considered as concordant results. Grade 2–3 uptake with a H/CL ratio <1.5 or Grade 0–1 uptake with a H/CL ratio ≥1.5 were considered as discordant results.

Results

Mean age of study population was 68.26±9.97 years. 17 (39.5%) of 43 patients who underwent 99mTc-PYP cardiac scintigraphy showed a Grade 2 or 3 cardiac uptake and in these patients with Grade 2–3 uptake, 11 patients (65%) had a H/CL ratio ≥1.5 (concordant results) and 6 patients (35%) had a H/CL ratio <1.5 (discordant results). 26 (60.5%) of 43 patients showed Grade 0–1 cardiac uptake. All patients (100%) with Grade 0–1 uptake had a H/CL ratio <1.5 and therefore, showed concordant results. Overall, 37 (86%) patients had concordant and 6 (14%) patients had discordant results (Table 1).

Conclusion

The results of this study showed that although there was a high agreement between semi-quantitative and quantitative analysis of 99mTc-PYP cardiac scintigraphy, 14% of patients have discordant results and need further workup to confirm TTR-CA in patients with HFpEF.

Funding Acknowledgement

Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Pfizer independent grant.
Patients with suspected cardiac amyloidosis. Role of endomyocardial biopsy
Authors: Aguilera C , Oteo Dominguez J.F.O.D , Garcia Izquierdo Jaen E.G.I.J , Dominguez Rodriguez F.D.R , Garcia Touchard A.G.T , Fernandez Diaz J.A.F.D , Del Trigo Espinosa M.T.E , Arellano Serrano C.A.S , Sabater Altagracia Y.S.A , Goicolea Ruigomez F.J.G.R , Garcia Pavia P.G.P , Salas Anton C.S.A , Segovia Cubero J.S.C
Published: October 2021

Introduction

Between the indications for endomyocardial biopsy (EMB) is the study of patients with heart failure associated with restrictive or infiltrative cardiomyopathy, such as cardiac amyloidosis if another workup is inconclusive. Although a risk-procedure, EMB is recommended in clinical scenarios in which the unique prognostic and diagnostic value of the information gained is felt to outweigh the procedural risks.

Purpose

We want to know the diagnostic value of EMB in the scenario of suspected cardiac amyloidosis and the role of the place of EMB for diagnosis.

Methods

We prospectively collected patients from our center with infiltrative cardiomyopathy and suspected cardiac amyloidosis who were referred to perform EMB. We gathered data on diagnostic profitability considering two different groups: those with samples from the right ventricle (group 1) and those with samples from the left ventricle (group 2; 90.8% with transradial approach). We consider major complications myocardial perforation, pericardial tamponade, arrhythmias, or bleeding with hemodynamic instability and death.

Results

We collected data from 111 patients referred for EMB for infiltrative cardiomyopathy suspicion. We present the results in table 1. The most common diagnosis was cardiac amyloidosis for wild-type transthyretin (43.48% in group 1 and 58.46% in group 2). There were no complications in the patients with confirmed cardiac amyloidosis in group 2.

Conclusions

In our EMBs for infiltrative cardiomyopathy suspicion we found that patients undergoing left-sided EMB had a shorter time of X-ray exposure and less time of admission without any other risk associated. So, we conclude that EMBs performed in the left heart are secure and comfortable for patients and physicians.

Funding Acknowledgement

Type of funding sources: None.
Internal jugular vein ultrasound in patients with chronic congestive heart failure
Authors: Thacker P , Amaratunga D , Shah K , Watson R , Singh A , Allen D , Shirani J
Published: October 2021

Background

Bedside assessment of intravascular volume in patients with chronic congestive heart failure (CHF) is often difficult. Under- and over-diuresis are common causes of morbidity and readmissions in these patients.

Purpose

We hypothesized that ultrasound assessment of the internal jugular vein would be easier and more reproducible than clinically assessing jugular venous pressure (JVP). Our goal was to create a bedside test that would be simpler to learn than inferior vena cava (IVC) assessment and easier to perform in obese patients.

Methods

Adults with HF (n=53, 52% men, mean age 65 years, mean BMI 29.6 kg/m2, mean LVEF 44%) scheduled for right heart catheterization (RHC) had an ultrasound of their right internal jugular (RIJ) vein performed immediately prior. Cross-sectional area of RIJ was measured during normal breathing with patients at 90 and 45 degrees recumbency and was indexed by height (RIJI). JVP was also assessed clinically. Results were compared to right atrial pressure (RAP) measured by RHC. Operators were blinded to RHC results and vice versa.

Results

JVP was correctly assessed clinically in only 43%. RIJI at 90 and 45 degrees were significantly larger in patients with elevated RAP compared to euvolemic patients (Table). At 90 degrees, RIJI of >15 predicted a RAP of >10 mmHg with 68% sensitivity and 72% specificity. At 45 degrees, RIJI of >10 predicted a RAP of >10 mmHg with 94% sensitivity and a negative predictive value of 80% (Table). Simply being able to see the RIJ at 90 degrees (n=34) had an 82.4% positive predictive value for elevated RAP. IVC data could not be obtained on 23% of patients due to body habitus or inability to lay flat.

Conclusion

Ultrasonographic RIJI is more accurate than clinical assessment in patients with CHF and can be accurately performed even in obese patients. It requires only a basic linear ultrasound probe and was easily performed by clinicians at various stages of training with reproducible results. With the increased availability of bedside ultrasound in clinical practice, it is a feasible method of evaluating chronic CHF patients.

Funding Acknowledgement

Type of funding sources: None.
The discongruence index, a simple predictor of cardiac remodeling after transcatheter aortic valve replacement
Authors: Islas F , De Agustin A , Jimenez P , Nombela L , Marcos Alberca P , Seabra D , Olmos C , Lepori A , Mahia P , Perez De Isla L
Published: October 2021

Background

Aortic stenosis causes several changes in left ventricular (LV) geometry and function; cardiac remodeling after transcatheter aortic valve replacement (TAVR) is variable among patients and it is not clearly defined. The aim of this study is to identify factors associated with LV functional and structural recovery.

Methods

428 patients were retrospectively studied; all patients underwent transthoracic echocardiography prior to TAVR; specific measurements such as maximum internal diameter of the prosthetic valve, nominal loss and percentage of nominal loss regarding to valve size, as well as the discongruence index (Prosthesis size/BSA) were evaluated at discharge and 1-year follow up. Positive cardiac remodeling (PCR) was considered if patients had a reduction of ≥20% of left ventricle mass index (LVMi) and ≥10% of end-diastolic volume index (LVEDVi).

Results

Mean age of the cohort was 83±5.6 years, 55% were female (n=236), mean aortic valve area was 0.7±0.2cm2; mean LVMi and LVEDVi were 129.4±35.4gr/m2 and 54.5±22ml/m2 respectively. LVMi reduction ≥20% was observed in 30% (n=128) of patients; LVEDVi reduction ≥10% was observed in 44% (n=188) of patients. A total of 107 patients (25%) showed PCR. Female patients showed more PCR (p=0.04). Discongruence index was significantly higher in patients with PCR (15.5±1.9 vs 14.5±1.8, p=0.01) and was significantly associated to LVMi (121.5±28.9 vs 150.8±41.1g/m2) and LVEDVi individually (55.1±17.2 vs 42.7±16.7ml/m2; p<0.01). Left ventricular ejection fraction (LVEF) had a statistically significant increase among patients with PCR (53.2±14.9 vs 56.7±11.5, p=0.04) global longitudinal strain showed improvement at 1-year follow-up as well, although not statistically significant (−17.3±3.7 vs −18.3±3.4 p=0.53).

Conclusions

The discongruence index is a simple and feasible parameter that can predict positive cardiac remodeling after TAVR which can have a significant impact in clinical outcome of patients.

Funding Acknowledgement

Type of funding sources: None.
Machine learning analysis of metabolomic biomarkers for diagnosis of heart failure
Authors: Coorey C , Tang O , Yang J.Y.H , Figtree G
Published: October 2021

Background

There is emerging evidence that the pathophysiological mechanisms of heart failure are associated with alterations in serum metabolites. Such metabolomic signatures may be useful for heart failure diagnosis, stratification and prognosis.

Purpose

To evaluate the utility of including metabolomic biomarkers in addition to traditional cardiac biomarkers in a machine learning prediction model of heart failure diagnosis in the well-characterised Canagliflozin Cardiovascular Assessment Study (CANVAS) cohort.

Methods

A subgroup of the CANVAS/CANVAS-R study cohort was analysed. 101 metabolites in plasma were measured by HPLC (HILIC)-mass spectrometry. A 10-times 5-fold cross-validated support vector machine model with radial basis kernel function was constructed to predict heart failure diagnosis using traditional biomarkers alone and using the combination of traditional biomarkers and metabolomic biomarkers. Model performance and variable importance were both evaluated by area under the curve (AUC) of the receiver operating characteristics (ROC) curve. Results are shown as mean ± standard deviation.

Results

967 patients (of which 402 patients had heart failure) were included in the analysis with 341 females, mean age 63±8 years and mean body mass index (BMI) 33±5 kg/m2. All patients had diabetes mellitus with mean HbA1c 8.2±0.9%. The prediction model based on only traditional biomarkers had mean AUC 72±3% and the prediction model based on both traditional biomarkers and metabolomic biomarkers had mean AUC 80±3%. The top metabolomic biomarkers for predicting heart failure were threonine, L-homoserine, creatine and deoxyadenosine.

Conclusion

Metabolomic biomarkers improved diagnostic performance of a heart failure prediction model and captured variation not encompassed by traditional cardiac biomarkers.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): Janssen Research and Development
Impact of right ventricular function and ventriculo-arterial coupling in prognosis after percutaneous edge-to-edge mitral repair
Authors: Gordillo X , Pozo Osinalde E , Salinas Gallegos A , Jimenez Quevedo P , Mahia P , Marcos-Alberca P , Tirado G , Luaces M , Macaya C , Perez-Villacastin J , Fernandez-Ortiz A , Nombela-Franco L , De Agustin J.A
Published: October 2021

Background

Left ventricular systolic function is widely used as selection criteria for appropriateness of percutaneous edge-to-edge mitral repair in patients with significant mitral regurgitation (MR) and high surgical risk. Although right ventricular (RV) systolic function and ventriculo-arterial coupling (VAC) have demonstrated its relevance in heart failure prognosis as well, few data are available regarding this procedure.

Purpose

To study the value of baseline RV function and VAC determined by transthoracic echocardiogram (TTE) on imaging and clinical prognosis.

Methods

We evaluated all the consecutive patients in which a percutaneous mitral edge-to-edge repair with the MitraClip system was performed between 2010 and 2020 in our tertiary university hospital. Baseline RV function was considered depressed if TAPSE <16 mm, tissue Doppler S'<9.5 cm/s or fractional area change (FAC) <35% on TTE. VAC was calculated as ratio of TAPSE by pulmonary artery systolic pressure (PASP) from the same studies. Follow-up echocardiographic measurements were evaluated and clinical events were collected from medical records.

Results

We included 88 patients (64.8% males, 76±10 years) with MR grade ≥3. MR etiology was classified as functional 44.3%, organic in 35.2% and mixed in 20.5%. Previous to the procedure left ventricular systolic function was mildly depressed (LVEF 44.5±15.3%) and 33 patients (37.5%) showed an impaired RV systolic function. At 6 months TTE the prevalence of RV dysfunction lower to 27.3%. Patients with initial RV systolic dysfunction showed greater improvement in TAPSE (3.2 vs −0.53 mm; p=0.052) and FAC (8 vs 0.2%; p=0.016) at 6 months compared to those with normal baseline RV function. However, this variable was not associated with any relevant clinical event during the follow up. Baseline VAC demonstrated a significant inverse correlation with change in TAPSE (r −0.42; p=0.018), FAC (r −0.37; p=0.024) and S' (r −0.52; p=0.041) at 6 months. Among patients with initial RV impairment, VAC was lower in those who persisted with RV systolic dysfunction at 6 months (0.41 vs 0.49; p=0.054). Moreover, VAC was significantly associated with NYHA class ≥3 (0.48 vs 0.63; p=0.042) and cardiovascular hospitalization (0.53 vs 0.63; p=0.07), with a correlation with number of admissions (r −0.27; p=0.053).

Conclusion

In a percutaneous mitral edge-to-edge repair population previous presence of RV systolic dysfunction was not associated with clinical events during the follow up. Conversely, VAC was able to identify RV systolic function recovery and was associated with functional class and cardiovascular hospitalizations.

Funding Acknowledgement

Type of funding sources: None.
Estimation of possible candidates for ivabradine in rural Japan and investigation of their clinical characteristics
Authors: Saito M , Kinoshita M , Nakagawa H , Sumimoto T
Published: October 2021

Background

In Japan, ivabradine is indicated in patients with heart failure (HF) with sinus rhythm and a resting heart rate (HR) ≥75/min under standard treatment. Particularly, it is effective for HF with reduced left ventricular ejection fraction (LVEF). However, elderly people have a higher incidence of atrial fibrillation than young people, and their sinus node function is further deteriorated, resulting in a lower intrinsic HR. In addition, Japan is an ultra-aging society, especially in the countryside; therefore, the target patients for ivabradine may be limited in these regions.

Purpose

We sought to estimate the possible candidates for ivabradine and investigate their clinical characteristics in our hospital located in rural Japan.

Method and results

We retrospectively studied 14733 consecutive patients who were suspected heart disease who underwent echocardiography between January 2006 and October 2018 in Kitaishikai Hospital located in Ozu city (Proportion of the population aged ≥65 years: 34%, in 2015) and did not take ivabradine treatment. Of these, 187 patients with hemodynamically stable condition whose E/A ratio was measured and met the criteria of LVEF <40% and HR ≥75 /min were confirmed. Of these, 153 patients reached HR <75 /min with additional intensive medication within one year after the index echocardiography (Controlled group; mean HR: 82 to 62/min). The remaining 34 patients with uncontrolled HR (Uncontrolled group; mean HR: 84 to 82/min) were considered possible candidates for ivabradine (34/14733: 0.23%, 2.6 patients per year; median age, 74 years; male, 56%; median LVEF, 32%; ischemic cardiomyopathy, 53%). In the comparison of clinical and echocardiographic parameters in these two groups, Uncontrolled group had a significantly smaller left ventricular diastolic volume index (71 [59–85] vs 82 [66–109] /ml/m2, p=0.02), left ventricular systolic volume index (50 [39–59] vs 59 [42–80] / ml/m2, p=0.04), stroke volume index (22 [18–26] vs 26 [20–32] /ml/m2, p=0.02), left atrial volume index (47 [40–64] vs 59 [45–71] /ml/m2, p=0.02), and more hemodialysis (12 vs 3%, p=0.04) than Controlled group. However, the discrimination ability of these parameters for identifying Uncontrolled group was modest (Figure).

Conclusion

In rural Japan, possible candidates for ivabradine may be rare, so daily attention should be paid. Patients with reduced ejection fraction, small left ventricle, and hemodialysis may be the possible targets for this therapy.

Funding Acknowledgement

Type of funding sources: None.
Assessing the impact of cardiovascular events on health-related quality of life outcomes in DAPA-HF
Authors: McEwan P , Qin L , Jhund P.S , Docherty K.F , McMurray J.J.V
Published: October 2021

Background

Heart failure (HF) patients are at increased risk of cardiovascular (CV) events, including hospitalisation for HF (hHF), myocardial infarction (MI) and stroke, imposing a significant burden on health related quality of life (HRQoL). DAPA-HF was a multinational clinical trial (NCT03036124) investigating the efficacy and safety of dapagliflozin for the treatment of HF with reduced ejection fraction. Patient reported outcomes were collected. The objective of this study was to estimate the impact of CV events on patient HRQoL over time, as assessed through EQ-5D-5L and Kansas City Cardiomyopathy Questionnaire (KCCQ) total symptom score (TSS) and clinical symptom score (CSS).

Methods

Mixed effects regression models were developed based on pooled individual patient data from DAPA-HF to estimate the impact of hHF, MI and stroke on patient utility (EQ-5D-5L questionnaire responses weighted according to the societal value placed on given health states), and KCCQ TSS score. Utility was estimated using UK-specific tariffs after mapping EQ-5D-5L to EQ-5D-3L values in line with NICE guidance. A subject-specific intercept was incorporated, and estimates were adjusted for the incidence of events occurring within one month prior, two to four months prior, and 4 to 12 months prior to questionnaire completion.

Results

Mean patient baseline utility was 0.716 (95% CI: 0.711, 0.722), with KCCQ TSS 73.6 (73.0, 74.2). The incidence of CV events was consistently associated with reduced patient HRQoL, assessed through either EQ-5D or KCCQ TSS. In the first month following the event, hHF was associated with a 0.083 (0.06, 0.107) reduction in patient utility, and 16.9 (14.5, 19.4) reduction in KCCQ TSS (Fig. 1). Comparing measures, the disease specific measure KCCQ appeared more sensitive than EQ-5D to changes in HRQoL following hHF events and less sensitive to changes following MI and stroke events. Comparing events using the generic EQ-5D measure, at two months post-event, patients with MI and stroke returned to baseline utility; patients with hHF remained below baseline utility at each assessment point for 12 months (Fig. 2); where patients had a mean reduction of 0.02 (0.005, 0.035) utility and 0.5 (−1.1, 2.1) KCCQ-TSS compared to those without an hHF event.

Conclusion

The incidence of cardiovascular events imposes a considerable burden on HRQoL in patients with HFrEF. HF specific events may be better characterised with a disease specific tool, whereas for wider CV events a generic tool may be preferable. The impact of hHF on HRQoL was noteworthy in its persistence across the measures used up to one year. Interventions that reduce the risk of these events have the potential to significantly improve patient quality of life.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): AstraZeneca
Impact of polypharmacy on prognosis in patients with acute decompensated heart failure: from the CURE-HF registry
Authors: Kanai M , Motoki H , Okano T , Kimura K , Minamisawa M , Yoshie K , Kato T , Saigusa T , Ebisawa S , Okada A , Kuwahara K
Published: October 2021

Background

Polypharmacy would be associated with poor prognosis in patients with heart failure (HF).

Methods

In 863 patients who discharged after treatment for HF were prospectively enrolled. Number of tablets prescribed at discharge was counted. Death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization for HF were tracked.

Results

In our study cohort (median age, 78), 447 patients experienced adverse events during median 503 days follow-up. In Kaplan-Meier analysis, a greater number of prescribed tablets was associated with future adverse cardiac events in the crude population. Although patients with the greater number of non-HF medications showed worse outcome, those of HF medications were not associate with the outcome (Figure). Furthermore, the number of tablets was an independent predictor of future cardiovascular events after adjustment for age, gender, B-type natriuretic peptide, hemoglobin, albumin, estimated glomerular filtration rate, and left ventricular ejection fraction (HR 95% CI: 1.295 (1.066–1.573), p=0.009).

Conclusions

Polypharmacy was associated with poor prognosis. Although the numbers of tablets and non-HF medications were significantly associated with worse out come in HF patients, the number of HF medications was not.

Funding Acknowledgement

Type of funding sources: None.
Elevated markers of liver function are associated with poorer outcomes in HFREF: an analysis of DAPA-HF
Authors: Cowan L , Adamson C , Docherty K , Inzucchi S , Koeber L , Kosiborod M , Martinez F , Ponikowski P , Sabatine M , Solomon S , Bengtsson O , Sjostrand M , Langkilde A , Jhund P , McMurray J
Published: October 2021

Background

Abnormalities of liver tests in patients with heart failure with reduced ejection fraction (HFrEF) is a well-recognised phenomenon. We examined the prognostic value of measures of liver function in a large contemporary cohort of patients with HFrEF enrolled in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial

Methods

In this post-hoc analysis of the DAPA-HF trial we studied 4625 patients with liver function tests available at baseline. Cox proportional hazards models were used to assess the association between liver tests (total bilirubin, alkaline phosphatase [ALP], alanine transaminase [ALT], aspartate transaminase [AST]) and the Model for End-stage Liver Disease excluding INR (MELD-XI) score (calculated as 5.11 Ln [total bilirubin as mg/dL] + 11.76 Ln [creatinine as mg/dL] + 9.44), and the risk of the primary composite endpoint (hospitalisation or urgent visit for heart failure or cardiovascular death). Models were adjusted for age, sex, race, region, systolic blood pressure, heart rate, LVEF, eGFR, log-transformed NT-proBNP, NYHA class, history of hypertension, stroke, myocardial infarction, atrial fibrillation, heart failure aetiology and randomized treatment to dapagliflozin and stratified by diabetic status at baseline. An interaction term between each measure and the effect of treatment on the primary composite outcome was tested as a fractional polynomial.

Results

Total bilirubin, ALP, and MELD-XI score were associated with a higher risk of all the primary outcome (Figure 1) but not ALT or AST. These relationships persisted after adjustment: total bilirubin per log unit increase (HR=1.46; 95% CI 1.28 – 1.67, p<0.001), ALP per log unit increase (HR=1.39; 95% CI 1.15 – 1.66, p<0.001), MELD-XI per 1 SD increase (HR 1.27; 95% CI 1.13 – 1.42, p<0.001). The effect of dapagliflozin on the primary outcome was not modified by the baseline levels of either total bilirubin, ALP or MELD-XI score (Figure 2)

Conclusions

Higher total bilirubin, ALP and MELD-XI score were independently associated with a higher risk of cardiovascular death or worsening HF and may be useful routinely available biomarkers to assess prognosis. The efficacy of dapagliflozin was the not modified by baseline levels of any of these markers.

Funding Acknowledgement

Type of funding sources: None. Figure 2
Metformin improves diastolic dysfunction of non-diabetic patients with metabolic syndrome: the MET-DIME randomized trial
Authors: Santos-Ferreira D , Ladeiras-Lopes R , Sampaio F , Leite S , Vilela E , Leite-Moreira A , Bettencourt N , Gama V , Braga P , Fontes-Carvalho R
Published: October 2021

Background

Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors, including abdominal obesity, dyslipidaemia, arterial hypertension and abnormal glucose homeostasis, which occur together more frequently than by chance. Diastolic dysfunction (DD) is one of the most frequent manifestations of subclinical cardiac involvement of MetS, ultimately leading to heart failure with preserved ejection fraction. Metformin's new potential therapeutic actions include prevention of cardiac remodeling and fibrosis.

Purpose

We aimed to evaluate if metformin improves diastolic function (DF) in non-diabetic patients with MetS.

Methods

A prospective, randomized, open-label, blinded-endpoint trial was conducted over 24 months. Fifty-four non-diabetic adults with MetS and DD (defined as mean e'<10.2cm/s or <7.2cm/s for individuals 40–59 and 60–65 years old, respectively) were randomized to lifestyle counseling (control arm) or lifestyle counseling plus metformin (intervention arm) on a target dose of 1000 mg bid (figure 1). The primary endpoint was the change in mean e' velocity, assessed at 6, 12 and 24 months. Secondary endpoints included improvements in insulin resistance (HOMA-IR), functional capacity (peak oxygen uptake – VO2) and QoL (SF-36 score). Linear mixed effects modelling was used for longitudinal data analysis based on modified intention-to-treat (mITT) and per-protocol (PP) approaches.

Results

Forty-nine patients (mean age=51.8±6.4; 55% males) were included in the mITT analysis. Metformin use, on top of lifestyle counseling, led to an increase in mean e' velocity during follow-up (figure 2), with results at 24 months of +0.67±1.90cm/s (vs. −0.33±1.50cm/s in the control group, p=0.056), which reached statistical significance in PP analysis (+0.80±1.99cm/s vs. −0.37±1.52cm/s, p=0.039). In a random intercept linear mixed model adjusting for age, gender, treatment with drugs targeting the renin-angiotensin-aldosterone axis, presence of heart failure and baseline degree of DD, both mITT and PP analysis showed a statistically significant improvement of DF with metformin over time (β-coefficient=0.28, standard error (SE)=0.13, p=0.034, and β-coefficient=0.35, SE=0.14, p=0.011, respectively). This effect was independent of the observed reduction in insulin resistance. There were no differences regarding peak VO2 nor SF-36 score.

Conclusions

Treatment with metformin of non-diabetic MetS patients with DD, on top of lifestyle counseling, was associated with improved diastolic function.

Funding Acknowledgement

Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Merck Study algorithmPrimary endpoint results