bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic value of relative wall thickness in heart failure with preserved ejection fraction: what is the best method for its calculation?
Authors: Pires M , Santos J.M , Correia J , Neto V , Ferreira G , Costa Cabral J , Almeida I
Published: October 2021

Background

The HFA-PEFF diagnostic algorithm is a recently published tool to help in the diagnosis of heart failure with preserved ejection fraction (HFpEF). One of the echocardiographic diagnostic criteria is left ventricular (LV) relative wall thickness (RWT), an index of LV concentricity. LV wall thickness can be measured by echocardiography at the posterior wall (PW) and/or the interventricular septum (IVS) in parasternal long axis view. There are three methods of RWT calculation: RWTPW= 2xPW/LV dimension at end diastole (LVDd) – the most used method, RWTIVS = 2 x IVS / LVDd and RWTPW + IVS = (PW + IVS) / LVDd. This study compares the prognostic value of these 3 methods of calculation in patients with acute HFpEF.

Methods

All patients admitted with acute HFpEF in a Cardiology Department during 7 years were included. RWT was considered elevated if superior to its median and was calculated with the 3 formulas. In-hospital mortality (IHM) was evaluated. The primary endpoint (EP) was a composite of all-cause mortality or hospitalization for HF during follow-up of 24 months. Statistical analysis used chi-square and Mann-Whitney U tests, binary logistic regressions, and Kaplan-Meier curves.

Results

478 patients were studied (61.3% female, mean age 79.4±8.3 years). Mean RWTPW, RWTIVS and RWTPW+IVS were 0.46±0.16, 0.50±0.17 and 0.48±0.16, respectively. IHM was 3.4% and primary EP occurred in 57.8%.

High RWTPW was associated with higher LV ejection fraction (LVEF) (p<0.001). Patients with high RWTIVS were older (p=0.044). High RWTPW+IVS was associated with higher left atrial area (p=0.037) and higher LVEF (p=0.002).

There was no statistically significant difference between patients with high and low RWT, calculated using the 3 formulas, in other indices that are commonly used to assess diastolic function, namely in e' and E/e'.

None of the 3 methods of RWT calculation was a predictor of IHM.

Survival analysis showed that patients with high RWTPW had higher incidence of the primary EP (43.2% vs. 16.8%, Kaplan-Meier χ2=5.99; p=0.014), but not patients with high RWTIVS (Kaplan-Meier χ2=0.23; p=0.631) or RWTPW+IVS (Kaplan-Meier χ2=1.92; p=0.166).

RWTPW was a predictor of primary EP (OR 1.81; 95% CI 1.15–2.85; p=0.011) and this result was independent from e' and E/e' (OR 2.96; 95% CI 1.08–8.10; p=0.035).

Conclusion

In this study comparing 3 formulas for calculation of RWT, RWTPW had better risk prediction during follow-up than RWTIVS or RWTPW+IVS. RWTPW was a predictor of all-cause mortality and hospitalization for HF, and was independent from e' and E/e', indexes that are also recommended in HFA-PEFF diagnostic algorithm. Therefore, the formula incorporating PW should be preferred in the evaluation of patients with suspected or diagnosed HFpEF.

Funding Acknowledgement

Type of funding sources: None.
Features of changes in the level of fibrosis markers in lipotoxic myocardial damage in patients with epicardial obesity
Authors: Gritsenko O , Chumakova G
Published: October 2021

In visceral obesity, lipotoxic myocardial damage develops, which leads to the formation of myocardial fibrosis with impaired diastolic function and the development of heart failure (HF). Currently, the search for markers of early diagnosis of left ventricular (LV) diastolic dysfunction (DD) is relevant.

Objective

To study the features of changes in the level of fibrosis markers in lipotoxic myocardial damage in patients with epicardial obesity (EO).

Materials and methods

The study included 125 men with general obesity (BMI average 33.24±3.65 kg / sq. m.). All patients underwent transthoracic echocardiography (ECG) to assess the thickness of epicardial adipose tissue (tEAT) as the equivalent of visceral obesity, as well as to diagnose DD LV. According to the results of echocardiography, the patients were divided into 2 groups: EO(+) with epicardial fat thickness (tEAT) ≥7 mm (n=78); EO(−) with tEAT <7 mm (n=40). DD LV was detected in 7 patients, who were subsequently excluded from the analysis. All patients were assessed for profibrotic markers in the blood serum (MMP-3, collagen I, collagen III, TGF – β, VEGFA, PICP) using enzyme immunoassay. The level of free fatty acids (FFA), as early markers of lipotoxic myocardial damage, was also determined in all patients using enzymelinked immunosorbent assay. The peak untwist ratio LV was studied using speckle-tracking ECG. The exclusive criteria were the presence of coronary pathology, arterial hypertension, type 2 diabetes mellitus, as possible causes of lipotoxic myocardial damage.

Results

When studying the features of changes in the level of serum markers of myocardial fibrosis, a statistically significant increase in the level of all the studied markers was revealed in the EO(+) group compared to the EO(−) group, and a statistically significant increase in the level of FFA in the EO(+) group compared to the EO(−) group (0.84±0.02 mmol/l and 0.35±0.01 mmol/L, respectively, p=0.02). A statistically significant relationship was found between the levels of FFA and collagen III (r=0.32, p=0.03) and TGF – β (r=0.30, p=0.04). According to the results of speckle-tracking ECG in the EO(+) group, an increase in the rate of LV untwist to −125.56 (−141.0; −117.0) deg/s (p=0.003) was determined. When studying the effect of FFA as a marker of lipotoxic effect on the myocardium, a weak statistically significant relationship was revealed between the level of FFA and the rate of LV untwist (r=0.27; p=0.03) in the EO(+) group, while no such effect was found in the EO(−) group.

Conclusion

In EO, as a result of neurohumoral disorders, lipotoxic myocardial damage develops and progresses, leading to LV DD, the detection of which is probably possible with the help of the LV unwinding rate.

Funding Acknowledgement

Type of funding sources: None.
Serum uric acid is associated with the progression of left ventricular diastolic dysfunction in apparently healthy subjects
Authors: Yang C.D , Wang X.Q
Published: October 2021

Background

Left ventricular (LV) diastolic dysfunction (LVDD) which is one of major characteristics of diastolic heart failure (HF) is also prevalent in the community. Patients with LVDD are predisposed to poor cardiovascular outcomes. Serum uric acid (SUA), an important component of metabolic disorders, has been shown to have close relationship with cardiovascular events including LVDD. In the present study, we sought to investigate whether SUA is a potential predictor of LVDD progression in relatively healthy subjects.

Methods

From November 2018 to December 2019 in our Hospital, subjects who had physical examination were consecutively enrolled and followed up for ∼12 months. LVDD was graded by tissue doppler imaging (TDI). At baseline, only individuals with normal LV diastolic function or mild LVDD were finally enrolled and underwent repeated echocardiography and TDI assessment after follow-up. The incidence of LVDD progression, defined as LVDD grade 0–1 escalated to grade 2–3, and its relationship with SUA levels were analyzed. Multivariate regression models were constructed to test the predictive value of SUA for LVDD progression.

Results

A total of 1082 subjects were included in the final analysis. During a mean follow-up of 12.6 (IQR 12.0–13.8) months, the incidence of LVDD progression was 37.6% and mean change in E/e' ratio was 1.18±1.85 cm/s, which was positively correlated with baseline SUV level (Spearman's r=0.140, P<0.001). In multivariate analysis, SUA was independently associated with LVDD progression after adjustment for traditional risk factors. The highest quartile of SUA corresponded to a 1.851-fold [95% CI 1.215–2.828] increased risk for progression of LVDD as compared to the lowest quartile. A 100 μmol/L increase in SUA conferred a 1.351-fold [95% CI 1.125–1.625] higher risk of LVDD progression when treated as continuous variable. Principal component analysis revealed SUA accounted for 14.7% of the variance in patients with LVDD progression, following insulin resistance and cholesterol factor which accounted for 27.9% and 19.0%, respectively.

Conclusions

This study suggests that SUA is an independent predictor of LVDD progression in apparently healthy subjects.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Natural Science Foundation of China, Shanghai Municipal Commission of Health and Family Planning
Updated results of hybrid transcatheter and minimally invasive left ventricular reconstruction for the treatment of ischemic cardiomyopathy
Authors: Klein P , Van Kuijk J.P , Swaans M.J
Published: October 2021

Aims

Remodelling of the left ventricle (LV) after anterior myocardial infarction can result in a pathological increase in LV volume and reduction in LV ejection fraction (EF). We describe the updated results of an l hybrid transcatheter and minimally invasive surgical technique to reconstruct the negatively remodelled LV by myocardial scar plication and exclusion to rehape and reduce the excess volume, decrease the wall stress and increase LVEF.

Methods and results

Patients were considered eligible for the procedure when they presented with symptomatic heart failure (NYHA-class ≥II or more) and ischemic cardiomyopathy (EF<40%) after anterior myocardial infarction. All patients had a dilated LV with either a- or dyskinetic scar in the anteroseptal wall and/or apex of ≥50% transmurality. Hybrid transcatheter and minimally technique that relies on micro-anchoring technology is used to reconstruct the LV by plication of the fibrous scar. A series of internal and external micro anchors are brought together over a PEEK (poly-ether-ether-ketone) tether to form a longitudinal line of apposition between the LV free wall and the anterior septum from the mid-ventricle to the apex. Internal anchors are deployed by transcatheter technique on the right side of the ventricular septum through the right internal jugular vein. Paired external anchors are advanced through a left sided mini-thoracotomy and deployed on the LV epicardium (figure 1). A specialized Force Gauge is used to bring these “RV-LV” anchors together under measured compression forces. “LV-LV” anchor pairs through the LV apex beyond the distal tip of the RV complete the reconstruction.

Between October 2016 and March 2021 28 patients (23 males, 5 females; mean age 61±12 years) were operated in a single Dutch centre. Procedural success was 100%. On average 2.3±0.8 anchor-pairs were used to reconstruct the LV. Comparing echocardiographic data pre- and directly postoperatively, LVEF increased from 33±8% to 44±10% (change +35%, P<0.0001) and LV-volumes decreased: LVESV 116 ml ± 52 ml to 69±39 ml (change −35%, P<0.0001) and LVEDV 170 ml ± 72 ml to 118±55 ml (change −29%, P<0.0001). Hospital mortality was 0%. Also no strokes occurred. Median duration of ICU–stay was 2 days (IQR 1–48 days) and median length of hospital stay was 7 days (IQR 5–61 days). Survival at 48 months was 84%. At latest follow-up, 9670% of surviving patients were in NYHA-class I-II compared to 18% preoperatively.

Conclusions

Hybrid transcatheter and minimally invasive LV reconstruction is a promising novel treatment option for patients with symptomatic heart failure and ischemic cardiomyopathy after anteroseptal myocardial infarction. Updated results demonstrate that the procedure is safe and results in significant improvement in EF, reduction in LV volumes and sustained improvement in heart failure symptoms.

Funding Acknowledgement

Type of funding sources: None. Figure 1
The odyssey to dethrone LV ejection fraction continues: the prognostic value of LV global function index in heart failure
Authors: Rocha B , Cunha G , Sousa J.A , Maltes S , Freitas P , Brizido C , Strong C , Ribeiras R , Andrade M.J , Aguiar C , Ferreira A , Mendes M
Published: October 2021

Background

Left Ventricular (LV) Global Function index (LVGFi) is a parameter that combines data from global systolic performance and volumetric anatomical information, measurable by non-contrast Cardiac Magnetic Resonance (CMR). We aimed to evaluate whether LVGFi predicts major cardiovascular outcomes and outperforms LV ejection fraction (LVEF) in Heart Failure (HF).

Methods

We conducted a retrospective single-centre study of consecutive patients with HF who were referred to and had a LVEF <50% at CMR. Other than inadequate images for endocardial or epicardial border delineation, there were no exclusion criteria. LVEF was determined by 3D measurement. LVGFi was calculated as the LV stroke volume to the LV global volume ratio (Figure 1). The primary endpoint was a composite of time to all-cause death or HF hospitalization.

Results

The cohort was comprised of 433 HF patients (mean age 64±12 years, 74.1% male, ischaemic HF 53.1%, NYHA I-II 83.9%) with a mean LVEF of 33.5±10.0% and LVGFi of 22.8±7.4%. Over a median follow-up of 27 (17–37) months, 85 (19.6%) met the primary endpoint and 42 (9.7%) died. Patients with an event of the primary endpoint had markers of more severe HF, as noted by a reduced functional capacity (NYHA I-II: 63.5 vs. 89.0%; p<0.001) and increased natriuretic peptides [NT-proBNP: 2664 (1022–27242) vs. 791 (337–7258); p<0.001). Likewise, CMR showed higher LV volumes (e.g., LV end-diastolic volume index: 137±50 vs. 120±43mL/m2; p=0.001) and reduced LV performance indices, namely LVEF (29.2±10.6 vs 34.5±9.6%; p<0.001) and LVGFi (19.8±7.4 vs 23.6±7.3%; p<0.001). Both LVEF and LVGFi independently predicted the primary endpoint in multivariate analysis (separately imputed into a model adjusted for NYHA, NT-proBNP and creatinine). The LVEF model was more powerful than that of LVGFi. Similarly, LVGFi did not provide incremental prognostic information over LVEF in c-statistics analysis (0.653 vs. 0.622; p=0.645) (Figure 2).

Conclusion

While LVGFi independently predicted major outcomes in patients with HF and LVEF <50%, it did not surpass LVEF. Our findings contrast to those demonstrating LVGFi as a powerful variable that outperforms LVEF in hypertrophic cardiomyopathy, cardiac amyloidosis, and healthy subjects at risk of developing structural heart disease. We hypothesize that LVGFi might be primarily useful in the prognostic stratification of patients with preserved LVEF.

Funding Acknowledgement

Type of funding sources: None. Figure 1Figure 2
Kidney function derangements during summer in ambulatory heart failure patients
Authors: Spitaleri G , Cediel G , Santiago-Vacas E , Codina P , Domingo M , Zamora E , Santesmases J , Diez-Quevedo C , Troya M , Boldo M , Alonso N , Gonzalez B , Nunez J , Lupon J , Bayes-Genis A
Published: October 2021

Background

Heart failure (HF) is characterized by alterations in kidney function that are associated with poor prognosis and can be related to the evolution of the disease or induced by medical treatment. High temperatures during summer may result in some degree of dehydration, especially in patients treated with diuretics, and may contribute to transient glomerular filtration rate (eGFR) reduction.

Objective

To assess creatinine and eGFR changes during summer in ambulatory heart failure patients.

Methods

Consecutive patients with HF admitted at our HF Clinic (Spain) from August 2001 to December 2020 were included. eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. We included in the analysis creatinine and eGFR values that were assessed at planned visits only, discarding urgent renal function assessments. Creatinine and eGFR values were grouped according to the period of the year (summer [from June to September, both included] vs. the rest of the year). Changes in creatinine and eGFR between the rest of the year and summer for each patient were evaluated using paired samples t-test.

Results

Out of 37360 creatinine and eGFR values, 25458 were included in the analysis for a total of 2423 patients (median number of observations for each patient: 8, IQR 4–15). Mean creatinine and eGFR were 1.4±1.0 mg/dl and 63.0±27.7 ml/min, respectively. Table 1 shows baseline patient characteristics. Creatinine increased significantly during summer (1.44±0.9 mg/dl vs. 1.48±1.1 mg/dl, p<0.001). Similarly, eGFR was lower in summer as compared to the rest of the year 60.6±25.4 ml/min vs. 59.4±26.0 ml/min, p<0.001.

Conclusions

In ambulatory HF patients in a Mediterranean area, we found significant worsening of renal function during summer, likely related to an imbalance between water intake and fluid loss. To prevent summer-driven kidney stress, diuretic treatment should be carefully adjusted during the hottest months of the year.

Funding Acknowledgement

Type of funding sources: None. Table 1
Prognostic significance of N-Terminal Pro-BNP in patients with COVID-19 pneumonia without previous history of heart failure
Authors: Selcuk M , Keskin M , Cinar T , Gunay N , Dogan S , Cicek V , Kilic S , Asal S , Yavuz S , Keser N , Orhan A.L
Published: October 2021

Introduction

The objective of the present research was to evaluate the possible association between the N-terminal pro-brain type natriuretic peptide (NT-proBNP) levels and in-hospital mortality in coronavirus disease 2019 (COVID-19) pneumonia patients who did not have pre-existing heart failure (HF).

Methods

A total of 137 consecutive patients without pre-existing HF and hospitalized due to COVID-19 pneumonia were enrolled into the current research. The main outcome of the research was the in-hospital death. The independent parameters linked with the in-hospital death were determined by multivariable analysis.

Results

A total of 26 deaths with an in-hospital mortality rate of 18.9% was noted. Those who died were older with an increased frequency of co-morbidities such as hypertension, chronic kidney disease, coronary artery disease, stroke and dementia. They had also increased white blood cell (WBC) counts and had elevated glucose, creatinine, troponin I, and NT-pro-BNP levels but had decreased levels of hemoglobin. By multivariable analysis; age, NT-pro-BNP, WBC, troponin I, and creatinine levels were independently linked with the in-hospital mortality. After ROC evaluation, the ideal value of the NT-pro-BNP to predict the in-hospital mortality was found as 260 ng/L reflecting a sensitivity of 82% and a specificity of 93% (AUC:0.86; 95% CI: 0.76–0.97).

Conclusion

The current research clearly shows that the NT-proBNP levels are independently linked with the in-hospital mortality rates in subjects with COVID-19 pneumonia and without HF. Thus, we believe that this biomarker can be used as a valuable prognostic parameter in such cases.

Funding Acknowledgement

Type of funding sources: None. Figure 1
Natriuretic peptide referral thresholds and heart failure diagnosis: population-based cohort study
Authors: Taylor C , Ordonez-Mena J.M , Lay-Flurrie S , Goyder C , Jones N , Roalfe A , Hobbs F.D.R
Published: October 2021

Background

Natriuretic peptide (NP) testing is recommended by both the European Society of Cardiology (ESC) and the National Institute for Health and Care Excellence (NICE) for people presenting with symptoms of heart failure (HF) in primary care. However, ESC and NICE guidelines suggest different NP referral thresholds: ESC recommend referral at a lower NP level (BNP≥35pg/ml / NT-proBNP≥125pg/ml) compared to NICE (BNP≥100pg/ml/NT-proBNP≥400pg/ml).

Purpose

We aimed to evaluate NP test performance for HF diagnosis for ESC and NICE guideline-defined thresholds.

Methods

Population-based cohort study using linked primary and secondary care data from the Clinical Practice Research Datalink in England between 1st January 2000 and 31st December 2018. Participants were adults aged 45 years and above with a NP result: 74,233 had a BNP and 155,347 had a NT-proBNP measurement. The main outcome measures were diagnostic performance of NP test (sensitivity, specificity, positive predictive value, negative predictive value) by threshold.

Results

A total of 229,580 patients had a NP test and 21,102 (9.2%) were diagnosed with HF. The ESC NT-proBNP threshold of 125pg/ml had a sensitivity of 94.6% (94.2 to 95.0) and specificity of 50.0% (49.7 to 50.3) compared to sensitivity of 81.7% (81.0 to 82.3) and specificity of 80.3% (80.0 to 80.5) for the NICE NT-proBNP 400pg/ml threshold. For both guidelines, nearly all patients with a NP level below the threshold did not have HF (negative predictive value ESC 98.9% (98.8 to 99.0) and NICE 97.7% (97.6 to 97.8). Similar performance was found for BNP.

Conclusions

The performance of NP testing is dependent on the guideline-specified threshold for referral. In 100 people with HF, using the NICE threshold would falsely reassure 18 patients, whereas the lower ESC threshold would miss just 5 people but twice as many patients would be referred for diagnostic assessment. The optimal NP threshold for referral for HF diagnosis will depend on the healthcare setting. The trade-off between missing HF cases and overwhelming diagnostic services needs to be determined at a national level.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Institute for Health Research
The predicting system of prognosis for transthyretin amyloid cardiomyopathy
Authors: Nakashima N.N , Takashio S.T , Morioka M.M , Nishi M.N , Hirakawa K.H , Hanatani S.H , Tsujita K.T
Published: October 2021

Background

The staging systems for transthyretin amyloid cardiomyopathy (ATTR-CM) by high sensitivity cardiac troponin T (hs-cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and estimated glomerular filtration rate (eGFR) are established. However, this system is not validated in Japan.

Purpose

The aim of study was to validate and modify the predicting system by BNP, hs-cTnT and eGFR of prognosis for Japanese patients with ATTRwt-CM.

Method

We evaluated in 158 consecutive patients with wild-type ATTR-CM. Univariate analysis revealed that increased hs-cTnT and B-type natriuretic peptide (BNP) levels and impaired renal function at diagnosis were associated with poor prognosis. We defined best cutoff value as follows by ROC curve analysis; hs-cTnT >0.0565 ng/mL, BNP >285 pg/mL and eGFR <45 mL/min. We scored the index by adding 1 point for each factor and divide into low score group (0–1 point) and high score group (2–3 points).

Result

As shown figure, high score was associated with increased all-cause mortality and heart failure rehospitalization (log rank; P<0.001, respectively).

Conclusion

This simple scoring system by hs-cTnT, BNP and eGFR, was useful for predicting prognosis in patients with wild-type ATTR-CM.

Funding Acknowledgement

Type of funding sources: None.
Optimal effectiveness of heart failure management: an umbrella review examining the effectiveness of interventions to reduce (re)hospitalizations in heart failure
Authors: Hafkamp F.J , Tio R , Otterspoor L , De Greef T , Van Steenbergen G , Van Veghel D ,   Nederlands Hart Netwerk
Published: October 2021

Introduction

Heart Failure (HF) is a major health concern. It is the diagnosis with the highest readmission rates among all diseases. Nevertheless, it is estimated that up to 40% of hospitalizations are preventable. Yet, there remains a knowledge gape concerning which interventions contribute to effective prevention of HF hospitalization or readmission.

Purpose

This umbrella review, therefore, aims to systematically review all published meta-analysis conducted in the past 10 years that examined the effectiveness of interventions in reducing HF-related (re)hospitalization in heart failure patients.

Methods

An electronic literature search was performed in PubMed, Web of Science, PsycInfo, Cochrane Reviews, CINAHL and Medline to identify eligible studies published in English language from January 2010 up to the end of June 2020. To synthesize the data, a best-evidence synthesis was used in which meta-analyses were classified based on level of validity.

Results

A total of 54 meta-analyses were included which encompassed 262 unique RCTs (Figure 1). Strong evidence suggested that cardiac rehabilitation was inversely related to heart failure hospitalization. Furthermore, moderate evidence was found for the effectiveness of telemonitoring, loop diuretics and RAAS inhibitors in reducing HF-related hospitalizations. Furthermore, limited evidence suggested that multidisciplinary clinic or self-management promotion programs, catheter ablation, mitral valve therapy, CRT, SLGT-II inhibitors, statins, or ultrafiltration were negatively related to HF-hospitalization. Additionally, there remains conflicting evidence regarding the effect of cell therapy on HF-hospitalization. No evidence was found that anticoagulation or class II antiarrhythmics could reduce HF-related hospitalizations.

Conclusion(s)

This umbrella review is the first known review to highlight different levels of evidence regarding the effectiveness of several interventions in reducing HF-related hospitalization. It could guide future guideline development in optimizing care pathways for heart failure patients.

Funding Acknowledgement

Type of funding sources: None.
Tends in beta-blocker administration and in prevalence of indications for their usage in heart failure with preserved ejection fraction: an analysis of randomized clinical trials
Authors: Kokhan E , Kiyakbaev G , Kobalava Z.H
Published: October 2021

Background

Despite the lack of data supporting their benefits, beta-blockers (BBs) frequently prescribed for heart failure with preserved ejection fraction (HFpEF). This may be due to the other indications (coronary heart disease, atrial fibrillation, etc.) on the one hand and due to clinical inertia with translation evidence from heart failure with reduced ejection fraction to HFpEF on the other.

Purpose

To assess the trends in BBs administration and prevalence of the possible indications for their usage (hypertension, atrial fibrillation, coronary heart disease, myocardial infarction) in the participants of the randomized clinical trials (RCTs) of HFpEF.

Methods

A systematic literature search of PubMed database was performed. RCTs of pharmacological treatment of HFpEF carried out between 1993 and 2019 were used. Studies of the effectiveness of BBs usage, or studies performed in specific populations (HFpEF+coronary heart disease or HFpEF+hypertension, etc.) were excluded. Features at enrolment date and data on the frequency of BBs admission and the prevalence of hypertension, atrial fibrillation, coronary heart disease, and myocardial infarction were extracted. The trends over time of enrolment were analyzed using the Mann-Kendall test.

Results

Of the 718 filtered publications, 14 RCTs met the inclusion and exclusion criteria fully. In the most recent trials, up to 75–80% of patients received BBs. Time trends analysis revealed that between 1993–2019 years the frequency of BBs use among the participants of the RCTs of HFpEF significantly increased (tau=0.51, p=0.014). No such change was observed in the prevalence of coronary heart disease, myocardial infarction, hypertension, and atrial fibrillation (all p>0.05). Prevalence of hypertension and atrial fibrillation showed a tendency toward increasing (tau=0.4, p=0.055 and tau=0.043, p=0.063, respectively) which became statistically significant for atrial fibrilation with the exclusion of the ALDO-DHF study (tau=0.5; p=0.042). The prevalence of myocardial infarction tended to decrease over time (tau=−0.73; p=0.06).

Conclusion

Over the last 20 years, the proportion of patients who used BB at enrolment in RCTs of HFpEF increased significantly. There was no statistically significant increase in the prevalence of the formal indications for their usage such as atrial fibrillation, hypertension, coronary heart disease or myocardial infarction. This fact requires attention since some retrospective studies have revealed that BBs use in HFpEF patients is associated with an increased risk of hospitalizations.

Funding Acknowledgement

Type of funding sources: None.
Novel antisense therapy targeting microRNA-132 in patients with heart failure
Authors: Taubel J , Hauke W , Rump S , Viereck J , Batkai S , Poetzsch J , Rode L , Weigt H , Genschel C , Lorch U , Theek C , Levin A.A , Bauersachs J , Solomon S.D , Thum T
Published: October 2021

Background

Cardiac microRNA-132-3p (miR-132) levels are increased in patients with heart failure (HF) and mechanistically drive cardiac remodelling processes. CDR132L, a specific antisense oligonucleotide, is a first-in-class miR-132 inhibitor that attenuates and even reverses HF in preclinical models.

Purpose

The aim of the current clinical Phase 1b study was to assess safety, pharmacokinetics, target engagement, and exploratory pharmacodynamic effects of CDR132L in patients on standard-of-care therapy for chronic ischaemic HF in a randomized, placebo-controlled, double-blind, dose-escalation study.

Methods

Patients had left ventricular ejection fraction between ≥30% and <50% or amino terminal fragment of pro-brain natriuretic peptide (NT-proBNP) >125 ng/L at screening. Twenty-eight patients were randomized to receive CDR132L (0.32, 1, 3, and 10 mg/kg body weight) or placebo (0.9% saline) in two intravenous infusions, 4 weeks apart in four cohorts of seven (five verum and two placebo) patients each.

Results

CDR132L was safe and well tolerated, without apparent dose-limiting toxicity. A pharmacokinetic/pharmacodynamic dose modelling approach suggested an effective dose level at ≥1 mg/kg CDR132L. CDR132L treatment resulted in a dose-dependent, sustained miR-132 reduction in plasma. Patients given CDR132L ≥1 mg/kg displayed median 23.3% NT-proBNP reduction, vs. 0.9% median increase in the control group. CDR132L treatment induced significant QRS narrowing and positive trends for cardiac fibrosis biomarkers.

Conclusions

This study is the first clinical trial of an antisense drug in HF patients. CDR132L was safe and well tolerated, confirmed linear plasma pharmacokinetics with no signs of accumulation, and suggests cardiac functional improvements. The indicative efficacy of this drug is very encouraging justifying additional clinical studies to confirm the beneficial CDR132L pharmacodynamic effects for the treatment of HF.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): Cardior Pharmaceuticals GmbH
Lack of pro-arrhythmic potential for the novel soluble guanylate cyclase stimulator vericiguat: results from preclinical studies
Authors: Himmel H , Lagrutta A , Voemel M , Rupesh A.P , Imredy J.P , Johnson T , Vinzing M
Published: October 2021

Introduction

Vericiguat is an orally-administered soluble guanylate cyclase stimulator, developed for the treatment of symptomatic chronic heart failure (HF) in adult patients who have had a previous decompensation event. At the maximum therapeutic dose of 10 mg once daily in patients with HF, the protein-unbound plasma concentrations of vericiguat and its major pharmacologically inactive N-glucuronide metabolite M-1 are approximately 18 nmol/l and 43 nmol/l, respectively. As part of an integrated risk assessment, vericiguat and its M-1 metabolite were characterised electrophysiologically in vivo and in vitro. This was performed according to the International Council for Harmonisation standard S7B guideline and to recent related “best practice” revisions (draft ICH E14/S7B Q&A), being adopted as a result of the Comprehensive In Vitro Proarrhythmia Assay (CIPA) initiative.

Purpose

To assess the potential for a proarrhythmic risk from vericiguat and its M-1 metabolite in a series of preclinical studies.

Methods

The potential for proarrhythmic risk was investigated in conscious telemetered dogs and in a series of in vitro electrophysiological studies, including mechanistic ion channel studies, using both generally accepted and CIPA voltage-clamp protocols under conditions simulating normal and diseased physiological states. The ion channels studied were hERG, hNav1.5, hCav1.2, hKvLQT1/minK and hKv4.3. Transfected human embryonic kidney cell lines were used for the hERG, hNav1.5 and hKvLQT1/minK studies; transfected Chinese hamster ovary cell lines were used for the hCav1.2 and hKv4.3 studies.

Results

In dogs, administration of vericiguat as single oral doses was associated with dose-dependent decreases in arterial blood pressure (consistent with its mode of action) and compensatory increases in heart rate (Table 1). Heart rate-corrected QT (QTc) intervals were not prolonged by vericiguat to a clinically meaningful extent. Neither vericiguat nor its M-1 metabolite inhibited cardiac ion channels (hERG, hNav1.5, hCav1.2, hKvLQT1/minK and hKv4.3) at exposure multiples of >150-fold (Table 2).

Conclusion

There was no preclinical evidence of proarrhythmic risk from the in vitro (simulating normal and diseased physiological states) and in vivo assessment of vericiguat or its major N-glucuronide metabolite M-1. This integrated risk assessment of non-clinical data supports the conclusion that administration of vericiguat 10 mg once daily in humans is not associated with meaningful QTc prolongation.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): Funding for this research was provided by Bayer AG, Berlin, Germany and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Moderate intensity exercise training in heart failure with preserved ejection fraction: functional and structural benefits (The MIET-HFpEF trial)
Authors: El Amrawy A , Hassanein M , Ayad S , Eldabe F
Published: October 2021

Background

Heart failure with preserved ejection fraction (HFpEF) represents more than one half of the heart failure cases worldwide with increased morbidity and mortality. No proven medical treatment till now have shown mortality benefit in HFpEF. This study aims to elucidate the benefits of cardiac rehabilitation (CR) in HFpEF.

Methods

Sixty patients with HFpEF were included in 2 groups with 1:1 randomization.Group1 received usual medical care plus 2–3 rehabilitation sessions per week using moderate exercise with 40–75% of heart rate reserve on treadmill (up to 60 minutes according to the functional capacity). Group 2 received only usual medical care. Comparison between the 2 groups recording the percentage of improvement in echocardiographic diastolic function parameters, Minnesota living with heart failure questionnaire (MLWHFQ) and 6 -minute walk test at baseline and after 12 weeks.

Results

Group 1 showed significant improvement in the following: a. MLWHFQ (total score mean percentage of reduction) 305.60±158.44 versus (vs) 69.44±17.71 (p<0.001).b. E/e' mean percentage of reduction 65.96±34.55 vs 18.23±13.98 (p<0.001). c. Left atrial (LA) volume index mean percentage of reduction 27.86±13.27 vs 8.03±4.40 (p<0.001). d. Pulmonary artery systolic pressure mean percentage of reduction was 33.85±14.68 vs 22.97±16.54 (p=0.02). e. 6–minute walk test 111.79±40.97 vs 46.33±11.58 (p<0.001). f. Body mass index percentage of reduction 10.17±3.64 vs 2.80±1.60 (p<0.001). g. Percentage of patients with down-grading of the degree of diastolic dysfunction: 10 patients (33.3%) vs 3 patients (10%) (P=0.028). h. However, there were no significant differences in left ventricular ejection fraction or other parameters as E/A ratio, LA dimension, isovolumetric relaxation time, degree of left ventricular hypertrophy.

Conclusion

CR not only added significant functional improvement in the quality of life and functional capacity in patients with HFpEF but also a significant structural improvement by improving the core items of diastolic function. In the light of the results of this study, we can recommend CR as a part of HFpEF management.

Funding Acknowledgement

Type of funding sources: None.
Impact of the Covid-19 pandemic on the device therapy for patients with the heart failure
Authors: Hall R , Chattopadhyay R , Pugh P.J
Published: October 2021

Introduction

Hospital admissions of patients with cardiovascular disease were markedly reduced in the UK in 2020 during the Covid-19 pandemic. In many institutions, including ours, patient care was redistributed from a specialty-based approach to a ward-based system, meaning some patients being admitted and managed under the care of non-specialist teams.

Purpose

We wished to examine the impact of these changes on heart failure (HF) patients presenting during the pandemic and on appropriate delivery of complex device therapies.

Methods

The study was undertaken in a large UK teaching hospital. The institution audit programme includes cardiac device therapy provision, aiming to ensure that implantable cardioverter defibrillators and cardiac resynchronisation therapy are offered to the target population in accordance with NICE guidance [Technology Appraisal 314]. In accordance with the guidance, patients admitted to hospital with serious ventricular arrhythmia, familial cardiac condition with high risk of sudden cardiac death (SCD), surgical repair of congenital heart disease (CHD) and patients with HF and LVEF<36% were identified from hospital coding. Findings during the pandemic (March to August 2020) were compared with the same period in 2019. Fisher's exact test was used to compare proportions.

Results

Among non-HF patients, device therapy prescription was consistent in the two periods observed. Table 1 shows how many patients were eligible for device therapy and how many were offered it. Table 2 contains details of HF admissions, showing an 8% reduction in admissions during the pandemic. The proportion of patients eligible for device therapy did not change significantly. However, there was a significant reduction in the proportion of eligible patients who were offered device therapy (79% vs 94% p=0.03). In addition, during the pandemic there was a trend towards a greater chance of patients being considered too frail for device therapy (p=0.08). Among 12 patients overlooked for device therapy, 10 were not under the care of Cardiology. Among 31 patients considered too frail for device therapy, 26 were not under the care of Cardiology.

Conclusion

During the Covid-19 pandemic, a modest reduction in HF hospital admission was observed with a marked fall in identification of patients eligible for device therapy. Possible explanations include intense pressure to discharge patients quickly, an increased perception of patient frailty during a crisis and the lack of recognition of indications for device therapy when patients are under the care of non-specialists. These findings suggest that cardiac services should actively look for HF patients who may have missed out on life-saving device therapies during the pandemic.

Funding Acknowledgement

Type of funding sources: None.
Outcomes of COVID-19 infection in heart transplant recipients
Authors: Miklin D , Mantha A , Wolfson A , Vaidya A , Depasquale E
Published: October 2021

Background

Heart transplant recipients may be at increased risk for infection and adverse outcomes from infection with COVID-19. Management of these patients is complex, with limited data and no standard of care.

Purpose

We sought to describe the incidence and outcomes of COVID-19 infection in patients with a history of heart transplant.

Methods

Retrospective review of 235 heart transplant patients at a large academic medical center identified 31 patients with laboratory confirmed COVID-19 infection. Laboratory and clinical data were collected from our institution as well as other local hospitals patients had been treated at. Outcomes were followed from March 15, 2020 to March 15, 2021. All data was deidentified.

Results

In a cohort of 235 heart transplant patients, 31 patients were identified after testing positive for COVID-19 infection. The mean and median age of patients was 51.9 and 56.0 years respectively. 71% of patients were male and 29% of patients were female. The mean and median time from transplant to diagnosis was 6.54 and 6.50 years. Average ejection fraction prior to infection was 60.4%. Seventeen patients (55%) had atherosclerosis, ten patients (32%) had diabetes, fifteen patients (48%) had hypertension, and twelve patients (39%) had a history of smoking. 84% of patients were on three types of immunosuppression and 16% were on two. Eight patients (26%) were asymptomatic, six patients (19%) had acute hypoxic respiratory failure, and two patients (7%) had GI symptoms. Two patients had evidence of graft injury with mean AlloSure (donor derived cell free DNA) levels of 0.61%. Immunosuppressive regimens were decreased in 32% of patients and COVID-19 directed therapies were given in 32% of patients. The most common treatments were remdesevir (5 patients), steroids (3 patients), and bamlanivimab (2 patients). Thirteen patients (42%) were hospitalized and two patients (7%) died.

Conclusions

In a single center case series 31 patients were identified with COVID-19 infection. Nearly half of the patients required hospitalization, with one third of patients decreasing their immunosuppressive regimen and 7% mortality. Further investigation is needed to determine long term outcomes and optimal therapeutic regimen for COVID-19 in this unique population.

Funding Acknowledgement

Type of funding sources: None.
One year outcomes of heart failure multispecialty multidisciplinary team virtual meetings
Authors: Essa H , Oguguo E , Douglas H , Foster A , Walker L , Hadcroft J , Bellieu J , Kahn M , Rao A , Cuthbertson D , Akpan A , Wong C , Sankaranarayanan R
Published: October 2021

Heart Failure is frequently associated with several comorbidities such as ischaemic heard disease, diabetes mellitus, chronic obstructive pulmonary disease, chronic kidney disease and frailty. This level of complexity is best dealt with by a multispecialty multidisciplinary team (MDT) model.

This was a single centre observational study (January 2020-December 2020) that was undertaken in a British university hospital looking at effect of HF multispecialty virtual MDT meetings on HF outcomes. Patients acted as their own controls outcomes compared for equal period pre versus post MDT meeting. The multi-specialty meeting was conducted once monthly via video-conferencing. It consisted of heart failure cardiologists (from primary secondary and tertiary care), heart failure specialist nurses (hospital and community), nephrologist, endocrinologist, palliative care specialists, chest physician, pharmacist, pharmacologist and geriatrician. Recommendations were made as consensus from the multispecialty meeting. The main outcome measures were 1) number of hospitalisations and 2) outpatient clinic attendances 3) cost savings.

A total of 189 patients were discussed from January-December 2020. This was uninterrupted during the COVID-19 pandemic. The mean age was 70.3±18.1 years and median follow-up 6 months (range 1–13 months). The mean Charlson Co-morbidity score was 5.3±1.2 and Rockwood Frailty Score was 4.9±1. The mean number of outpatient clinic attendances avoided was 1.7±0.4. This reduced inconvenience to patients, saved patients money (transport and parking costs) and led to carbon footprint reduction. The MDT meeting total costs were £15,400 and the 31 clinic appointments they generated cost an estimated £3720. However, the MDT meetings prevented 277 clinic appointments (cost saving £33,352). Finally, the mean number of hospitalisations pre-MDT was 0.7 Vs 0.2 post MDT (p<0.01) with a saving of around 730 bed days (estimated cost-saving £260,000).

The HF multispecialty virtual MDT approach provides seamless integration of primary care community services with secondary and tertiary care. Consensus decision from MDT meetings provides holistic approach for HF patients with comorbidities and frailty, and reduces inconvenience to patients by preventing the need to attend multiple specialty clinics. This approach can also lead to significant cost-savings to the healthcare system.

Funding Acknowledgement

Type of funding sources: None.
Association of soluble ST2, M235T polymorphism of ATG with insulin resistance in diabetic patients with heart failure with preserved ejection fraction
Authors: Medentseva O , Rudyk I.S , Ovrakh T.G , Gasanov I.C , Babichev D.P , Bondar T.N
Published: October 2021

Background

It has been shown that the level of the soluble form of suppression of tumorigenicity 2 (sST2) is associated with an unfavorable course of heart failure (HF). On other hand, has been shown a strong influence of ATG polymorphism on HF development. However, the association of M235T polymorphism of ATG and sST2 level with insulin resistance in diabetic patients with HF with preserved ejection fraction (HFpEF) is still unknown.

Purpose

To investigate the association between sST2, different types of M235T polymorphism of ATG and insulin resistance in patients with HFpEF and T2DM.

Methods

A total of eighty-one patients (49 females and 32 males; mean age 62,5±7,3 years) with HFpEF and type 2 diabetes mellitus (T2DM) were examined. Twenty patients had MM genotype, 38 patients had MT genotype and 23 had TT genotype of M235T polymorphism of ATG, which was determined by using of polymerase chain reaction. sST2 was determined by using kits of reagents “PresageST2” (USA). The mean value of sST2 was determined, patients were divided according to the mean. The HOMA-IR was calculated to determine insulin resistance. All statistical tests were 2-tailed and performed in Statistica 10.0, p<0.05 was considered statistically significant.

Results

In the group of HFpEF and T2DM with sST2>24.4 ng/ml the HOMA-IR was significantly higher than in the group with sST2<24.4 ng/ml and was 16.24±1.22 and 9.30±1.30, respectively (p<0.05).

The HOMA-IR was higher in the TT genotype group compared with carriers of M allele. (p<0.05) (Table 1).

Conclusion

High circulating level of sST2 and TT genotype of the M235T polymorphism of the ATG presence was associated with increased insulin resistance in patients with HFpEF and T2DM.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): government funding Table 1
Disproportionate mitral regurgitation is associated with survival in acute heart failure with moderate range ejection fraction
Authors: Berrill M , Ashcroft E , John I , Baltabaeva A
Published: October 2021

Background

In acute heart failure (AHF) with moderate-range ejection fraction (HFmrEF) the effect of mitral regurgitation (MR) is uncertain.

Methods

103/440 consecutive patients in AHF had HFmrEF. They underwent bedside echocardiography within 24 hours of recruitment, prior to offloading, and were followed up for 2 years. The endpoint was all-cause mortality at 2 years. A novel proportionality index - where the effective regurgitant orifice is divided by the left ventricular end-diastolic volume (ERO/LVEDV)) - identified HFmrEF patients with disproportionate MR.

Results

103/440 (23.4%) patients had HFmrEF with an average EF of 44.6±2.6%. 54.4% were male, with an average age of 80.5±11.4. 47.6% had a previous diagnosis of hypertension, 28.2% diabetes and 10.7% cerebrovascular disease. Patients did not present in shock, with average systolic/diastolic blood pressures of 141.7±26.2mmHg/ 78.5±19.3mmHg, nor did they primarily present with severe infections with mean CRP of 23.2±31.7. BNP at presentation was 1179.8±1028.5ng/L. Every patient had MR, 78/103 (75.7%) had MR quantifiable by PISA. 54/78 (69.2%) had disproportionate MR, defined by an ERO/LVEDV >0.14mm2/ml. When compared to proportionate MR, disproportionate MR in HFmrEF was associated with: greater LVEDV (136.3±53.6ml vs. 103.3±39.7ml [p=0.018]), greater mitral regurgitant volumes (41.8±18.5ml vs. 21.5±12.5ml [p<0.001]) and systolic pulmonary artery pressures (60.2±21.0mmHg vs. 48.0±14.7mmHg [p=0.012]) but not left-atrial size (30.2±7.1mm2 vs. 30.2±7.8mm2 [p=0.915]). Disproportionate MR in HFmrEF was also associated with worse 2-year outcome than proportionate MR – 40.1% vs. 16.7% (HR 2.30; 95% CI 1.02–5.17 [p=0.045].

Conclusion

This is the first assessment of the effect of disproportionate volume loading secondary to MR in patients presenting in AHF with HFmrEF. Disproportionate MR was associated with worse outcome at 2 years.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): Abbott