bluuebunny/crossref_metadata_2025 huggingface dataset:
Haemodynamic forces as predictors of cardiac remodelling and outcome in heart failure with reduced ejection fraction treated with sacubitril/valsartan
Authors: Fabiani I , Pugliese N R , Castiglione V , Pedrizzetti G , Tonti G , Chubuchny V , Becherini F , Taddei C , Gimelli A , Del Punta L , Balletti A , Masi S , Cameli M , Emdin M , Giannoni A
Published: October 2022

Background

Angiotensin receptor-neprilysin inhibitor (ARNI) is a cornerstone of treatment in heart failure (HF) with reduced ejection fraction (HFrEF), but its effectiveness shows interindividual differences.

Objectives

To evaluate the predictive value of echo-derived hemodynamic forces (HDF), together with other echocardiographic, biohumoral and cardiopulmonary parameters on a) response to ARNI after 6 months; b) adverse cardiovascular events at follow-up.

Methods

Eighty-nine consecutive HFrEF patients from two HF centers performed clinical evaluation, laboratory analyses, rest echocardiography and cardiopulmonary exercise testing. Response to ARNI at 6 months was considered in patients without HF admissions, death, or urgent heart transplant and with a ≥50% reduction in NT-proBNP levels and/or ≥10% increase in left ventricle ejection fraction. After 6 months, patients were followed up for a composite endpoint of cardiovascular death, HF-related hospitalization and new-onset atrial fibrillation.

Results

Response to ARNI was documented in 45/89 (51%) of patients. At baseline, responders and non-responders were paired in clinical assessment, conventional echocardiography, functional status and therapy. At multivariate logistic regression analysis, HDF-derived whole cardiac cycle left ventricle strength (wLVS) was the only independent predictor of ARNI response at 6 months (odds ratio 1.36, 95% confidence interval 1.10–1.67; p=0.004). A wLVS ≥3.7% showed a good accuracy in predicting ARNI response (AUC = 0.736, 0.607–0.840; p<0.0001). During a median of 33 (IQR 23–41) months, wLVS increase from baseline to 6-month (ΔwLVS) showed a high discrimination ability at time-dependent ROC analysis (optimal cut-off: ≤0.5%; AUC=0.811, 0.69–0.90; p<0.0001), stratified prognosis at Kaplan-Meier analysis (log-rank p<0.0001), and remained an independent prognostic predictor of the composite endpoint (hazard ratio 0.76, 0.61–0.95; p<0.01) even after adjusting for clinical, functional and conventional echocardiographic parameters.

Conclusions

HDF analysis may help predict ARNI response and optimize follow-up and medical/device strategies in patients with HfrEF.

Funding Acknowledgement

Type of funding sources: Public hospital(s). Main funding source(s): Fondazione Toscana Gabriele Monasterio, Pisa, Italy
Histological validation of cardiac 99mTc-DPD uptake in patients with cardiac transthyretin amyloidosis
Authors: Ungericht M , Groaz V , Messner M , Zaruba M M , Lener D , Stocker E , Kroiss A , Poelzl G
Published: October 2022

Background

Cardiac transthyretin (ATTR) amyloidosis is a progressive and fatal disease caused by the extracellular deposition of misfolded ATTR protein in the myocardium. In an era where new therapies are rapidly emerging, development of non-invasive imaging modalities to quantify amyloid burden over time is of utmost importance. Although endomyocardial biopsy (EMB) remains the gold standard in amyloid detection and typing, 99mTc-DPD scintigraphy is a widely available and accurate tool for non-invasive diagnosis of cardiac ATTR amyloidosis. However, it remains to be determined whether the degree of cardiac 99mTc-DPD uptake correlates with the histological amyloid infiltration on EMB – thus, justifying 99mTc-DPD scintigraphy as a disease monitoring tool.

Aim

This single-centre observational study aimed to compare the extent of histologic amyloid burden on EMB with the quantification of cardiac 99mTc-DPD uptake on scintigraphic planar images and SPECT/CT acquisitions in cardiac ATTR amyloidosis.

Methods

26 patients with cardiac ATTR amyloidosis were enrolled. Patients were included in case of (1) EMB-proven ATTR amyloidosis and (2) availability of 99mTc-DPD scintigraphy (reference activity: 550 MBq). Visual interpretation using the Perugini score, quantitative analysis of cardiac 99mTc-DPD uptake by planar whole-body imaging and SPECT/CT using regions of interest (ROI) were performed, and heart to whole-body ratio (H/WB) was measured. Histological amyloid load was quantified as percentage of the analysed myocardial tissue using Sulfated Alcyan Blue staining and the Fiji-ImageJ programme. Pearson's and Spearman's correlation were used for correlation analysis and assessment of agreement.

Results

ATTR patients had a median age of 77 [73–79] years and were predominantly male (85%). An abnormal Perugini score (i.e. 2 or 3) was present in 25 patients (96%), whereas 1 patient was assigned Perugini score 1 (4%). Increased cardiac tracer uptake was documented in all patients, both on 99mTc-DPD planar scintigraphy (ROImean 129±37) and SPECT/CT (ROImean 369±142). Histologic amyloid burden on EMB was 32±19% on average. It significantly correlated with Perugini score (r=0.56 p=0.003), as well as with cardiac 99mTc-DPD uptake (planar: r=0.54 p=0.006, SPECT/CT: r=0.48 p=0.018) and H/WB (r=0.41 p=0.046).

Conclusion

We have demonstrated a good correlation between histological amyloid infiltration on EMB and cardiac 99mTc-DPD uptake on scintigraphic planar images and SPECT/CT scans, illustrating the potential of 99mTc-DPD scintigraphy to yield reliable quantitative information on cardiac amyloid burden. Further investigations with a larger number of patients are needed to confirm our findings and to implement thresholds in cardiac 99mTc-DPD uptake for being used for guiding disease and therapy management.

Funding Acknowledgement

Type of funding sources: None.
Association of cardiothoracic ratio with heart failure hospitalization in patients with atrial fibrillation: the Fushimi AF Registry
Authors: Ikeda S , Iguchi M , Ogawa H , Minami K , Ishigami K , Doi K , Hamatani Y , Yoshizawa T , Ide Y , Fujino A , Ishii M , Masunaga N , Wada H , Abe M , Akao M
Published: October 2022

Background

Chest radiography is the most common diagnostic imaging test in clinical medicine, and the cardiothoracic ratio (CTR) is a readily available and non-invasive tool with which to assess the volume status and cardiomegaly. However, it remains unknown whether CTR on chest radiography is associated with the incidence of HF hospitalization in AF patients remains unclear.

Methods

The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Kyoto, Japan. The inclusion criterion of the registry is the documentation of AF at 12-lead electrocardiogram or Holter monitoring at any time, and there are no exclusion criteria. We started to enroll patients from March 2011, and follow-up data were available for 4,489 patients by the end of August 2021. In the present study, 3,727 patients with available data of CTR were examined. We divided the patients into two groups according to their CTR at baseline; Higher group (CTR ≥50.0%, n=2,696) and Lower group (CTR <50.0%, n=1,031), and compared the clinical background and outcomes between the two groups.

Results

The proportion of female was grater in Higher group, and the patients in Higher group were older. The patients in Higher group had higher prevalence of HF, hypertension and chronic kidney disease. During the median follow-up of 3,033 days, in Kaplan-Meier analysis, the incidence rates of HF hospitalization were higher in Higher group (Higher group: 2.5% per person-year vs. Lower group: 1.1%; p<0.01). Multivariate Cox proportional hazards regression analysis revealed that higher CTR (≥50.0%) was an independent determinant of the incidence of HF hospitalization. Furthermore, when we divided the patients into four groups based on the quartile of CTR; Q1 (CTR<49.0%), Q2 (49.0≤CTR<53.8%), Q3 (53.8≤CTR<59.0%), Q4 (59.0%≤CTR), the incidence of HF hospitalization was more frequent in patients with higher CTR, regardless of the presence or absence of prior hospitalization for HF (Figure).

Conclusion

In Japanese AF patients, patients with higher CTR had significantly higher incidence of HF hospitalization, regardless of the prevalence of prior hospitalization for HF.

Funding Acknowledgement

Type of funding sources: None.
Cardiac magnetic resonance radiomics for prediction of incident heart failure: a feasibility study in the UK Biobank Imaging cohort
Authors: Szabo L , Ruiz Pujadas E , McCracken C , Izquierdo C , Campello V M , Atehortua A , Petersen S E , Lekadir K , Raisi-Estabragh Z
Published: October 2022

Background

Cardiac magnetic resonance (CMR) radiomics is a novel image quantification technique with the potential to improve image-based disease diagnosis and prediction.

Purpose

In this proof-of-concept study, we aimed to evaluate the utility of CMR radiomics in the prediction of incident heart failure (HF).

Methods

We studied 32,121 UK Biobank participants with CMR. Incident HF was defined from linked Hospital Episode Statistics. To create a balanced cohort, we identified as comparators an equal number of randomly selected subjects who did not develop the outcome of interest during this period. Radiomics shape, first-order and texture features were extracted from short-axis cine images (left and right ventricle, left ventricular myocardium) using the Pyradiomics toolbox. Vascular risk factors (VRFs) were considered as additional predictors. Feature selection was conducted using the sequential forward selection technique and modelling was performed using Support Vector Machine (SVM) methods with 5-fold cross-validation. Models were developed using 1) VRFs alone, 2) radiomics alone, and 3) VRFs and radiomics. We determined model performance using receiver operating characteristic (ROC) curve and area under the curve (AUC) scores.

Results

Over average follow-up time of 3.7 (±1.3) years, 209 participants experienced incident HF. Among vascular risk factors, age, body size, hypertension, diabetes, high cholesterol were chosen for the incident HF predictive model (Accuracy: 0.66, AUC: 0.73) by the SVM methods. The model based on radiomics features reached a marginal improvement compared to vascular risk factors alone (Accuracy: 0.71, AUC: 0.75). The combination of VRFs and radiomics features significantly improved the performance of the model to predict incident HF compared to VRFs alone (Accuracy: 0.77; AUC: 0.83; p<0.05)

Conclusion

We demonstrate the feasibility of CMR radomics features to predict incident HF and illustrate their added value over vascular risk factors.

Funding Acknowledgement

Type of funding sources: Public grant(s) – EU funding.
Clinical and prognostic significance of left ventricular outflow tract velocity time integral (LVOT-VTI) in patients with chronic heart failure
Authors: Gentile F , Buoncristiani F , Chubuchny V , Sciarrone P , Panichella G , Bazan L , Gasperini S , Fabiani I , Taddei C , Poggianti E , Petersen C , Pasanisi E , Passino C , Emdin M , Giannoni A
Published: October 2022

Background

The echocardiographic evaluation of cardiac output relies on the product of the flow across the left ventricular outflow tract (LVOT), estimated through its velocity time integral (LVOT-VTI), and its cross-sectional area, estimated through the formula πr2. Considering the geometrical assumption behind such formula, LVOT-VTI has been proposed as a more reproducible surrogate of cardiac systolic function and showed prognostic value in the critical care setting. However, the role of such measure in patients with chronic heart failure (HF) remains unexplored.

Objective

To assess the clinical and prognostic significance of LVOT-VTI in a contemporary cohort of patients with chronic HF.

Methods

Outpatients with chronic HF with a LV ejection fraction <50% were prospectively enrolled to undergo a clinical, echocardiographic, and biohumoral assessment, and were followed-up for the endpoint of all-cause death.

Results

Finally, 971 patients were enrolled (71±12 years, 72% men, 50% ischemic etiology, LVEF 35±9%). Most patients showed a NYHA class I-II (74%) and were treated with ACE-inhibitors/ARBs or ARNI (81%), beta-blockers (95%), and mineralocorticoid receptor antagonists (71%). Patients were distinguished in three subgroups according to LVOT-VTI tertiles <19 (n=324), 19–24 (n=324), or ≥24 (n=323). Compared with the other two subgroups, patients with LVOT-VTI <19 showed worse NYHA class, lower LVEF and tricuspid annular plane systolic excursion (TAPSE), and higher E/e', left atrial volume index (LAVi), estimated systolic pulmonary arterial pressure (sPAP), and NT-proBNP concentration (all p<0.001). No differences were observed as for patients' age, HF etiology, and therapies (all p>0.05). Over a median follow-up of 22 (9–34) months, 103 (11%) patients met the primary endpoint. LVOT-VTI significantly stratified the risk of death, observing 65 (20%), 21 (7%), and 17 (5%) events across the subgroups with values <19, 19–24, or ≥24 (log-rank 33, p<0.001). At multivariable regression analysis, LVOT-VTI <19 (HR 2.06 [95% 1.21–3.49], p=0.008), but not LVEF <30% (p=0.614) was an independent predictor of all-cause death in a model adjusted for age, sex, ischemic etiology, renal function, hemoglobin, E/e', LAVi, TAPSE, sPAP, and NT-proBNP.

Conclusion

LVOT-VTI is associated with disease severity and is a strong predictor of all-cause death in patients with chronic HF.

Funding Acknowledgement

Type of funding sources: None.
Prevalence of abnormalities on cardiac MRI in unselected patients after recovery from acute SARS-CoV-2 infection and correlation with markers of immunity and coagulation: the SETANTA study
Authors: Colleran R , Byrne R J , Cradock A , O Ciardha D , McKeogh S , Wilson H , Mansur A , Bisset J , Cantwell G , Hannan M , Fitzgibbon M , O Donnell J , Rai H , Byrne R A
Published: October 2022

Background

Previous studies have reported ongoing cardiac inflammation as assessed by cardiac magnetic resonance imaging (CMR) in a significant proportion of patients several months after recovery from SARS-CoV-2 infection, many of whom had no or minimal symptoms at the time of infection.

Purpose

The aim of SETANTA was to investigate the prevalence of cardiac abnormalities by CMR in unselected patients in Ireland after acute SARS-CoV-2 infection and the correlation with immunological response and biomarkers of coagulation.

Methods

This was a prospective, observational, community-based study (clinicaltrials.gov identifier NCT04823182). Consecutive patients recovered from recent SARS-CoV-2 infection at 3 primary care sites were invited to participate. Key inclusion/exclusion criteria and outcomes of interest are shown in Figure 1.

Results

100 participants were enrolled (Feb-Sept 2021) at a median of 188 (IQR, 125, 246) days after positive SARS-CoV-2 swab. At index infection, 18% and 35% reported severe and moderate symptoms, respectively; 14% were hospitalized; 3% were admitted to intensive care for ventilatory support. At enrolment, 83% had ongoing symptoms. 85% had detectable SARS-CoV-2 antigens. CMR and laboratory findings are shown in Figure 1.

Conclusion

Among an unselected cohort of patients recovered from acute SARS-CoV2 infection, we report a low prevalence of cardiac abnormalities by CMR, despite a high prevalence of moderate/severe symptoms at presentation and a high prevalence of persistent symptoms. Correlation with biomarkers of immunity and coagulation will be available at ESC 2022.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): WomenAsOne
Safety and efficacy of SGLT2 inhibitors in diabetic and non-diabetic heart failure patients, a meta-analysis of randomized controlled trials
Authors: Awad A K , Tarek Hasan M , Shih M , N Attia A , Aboeldahab H , Bendary M , Bendary A
Published: October 2022

Background

Heart failure (HF) is the most common cardiovascular causes of hospitalization in people over 60 years affecting about 64.3 million people worldwide. Few studies have investigated sodium glucose like transporter-2 inhibitors (SGLT-2I) role in diabetic and non-diabetic patients with HF.

Objective

We conducted our meta-analysis to further investigate SGLT-2I role in diabetic and non-diabetic HF patients.

Methods

PubMed, Scopus, web of science, and Embase were searched. All clinical trials that compared the effect of SGLT2 inhibitors versus placebo on heart failure patients were included. Dichotomous data were extracted, pooled as risk ratio (RR) with 95% confidence interval, and analyzed via RevMan version 5.3 for windows using Mantel Haenszel (M-H) method.

Results

Twelve randomized clinical trials were included for analysis with a total number of 69024 patients. SGLT2I significantly lowered the risk of hospitalization for heart failure (HHF) in diabetic (RR=0.68, 95% CI 0.63–0.74) and non-diabetic patients (RR=0.75, 95% CI 0.62–0.89). Also, it significantly lowered mortality risk in both diabetic (RR=0.87, 95% CI 0.77–0.99) and non-diabetic patients (RR=0.93, 95% CI 0.70–1.23). Further analyses for serious adverse events were conducted, and SGLT-2I showed a significant lower risk in diabetic (RR=0.94, 95% CI 0.90–0.98) and non-diabetic patients (RR=0.72, 95% CI 0.38–1.39), yet with no observed difference over placebo in the risk of stroke.

Conclusion

SGLT2 inhibitors showed a favorable effect in lowering cardiovascular mortality, HHF, and stroke in diabetic patients with heart failure. In non-diabetic patients, they significantly reduce HHF, yet with no difference on cardiovascular mortality and stroke. Therefore, more trials are needed to establish their effect in non-diabetic patients.

Funding Acknowledgement

Type of funding sources: None.
Impact of atrial flow regulator implantation on survival in patients with heart failure with reduced and preserved ejection fraction: a post-hoc analysis of the PRELIEVE study
Authors: Lauder L , Bergmann M , Paitazoglou C , Ozdemir R , Iliadis C , Bartunek J , Lauten A , Keller T , Weber S , Sievert H , Anker S D , Mahfoud F
Published: October 2022

Purpose

This analysis aims to assess the theoretical impact of atrial flow regulator implantation on mortality by comparing the observed survival rate with the median predicted probability for one-year survival.

Methods

The prospective, multicentre, open-label, non-randomised PRELIEVE study assessed the safety and efficacy of the atrial flow regulator in patients with symptomatic HFrEF (left ventricular ejection fraction (LVEF) ≥15% and <40%) or HFpEF (LVEF ≥40% and <70%) and elevated PCWP (≥15mmHg at rest or ≥25mmHg during exercise). In this analysis, after the first 60 patients completed twelve months of follow-up, the theoretical impact of atrial flow regulator implantation on survival was assessed by comparing the observed mortality rate with the median predicted probability for one-year mortality. Each subject's risk of mortality was predicted from individual baseline data using the Meta-Analysis Global Group in Chronic HF (MAGGIC) prognostic model.

Results

A total of 87 patients had undergone successful device implantation for the treatment of HFrEF (53%) and HFpEF (47%). Sixty patients had a complete twelve-month follow-up. The median follow-up was 351 days (interquartile range [IQR] 202–370). A total of six (7%) patients died during follow-up (8.6 deaths per 100 patient-years; 95% confidence interval [CI] 2.7 to 15.5), all of which had HFrEF. The median predicted mortality rate for the overall study population was 12.2 deaths per 100 patient-years (95% CI 10.2 to 14.7). While the observed mortality rate (0 deaths per 100 patient-years) was significantly lower than the median predicted mortality rate (9.3 deaths per 100 patient-years; 95% CI 8.4 to 11.1) in patients with HFpEF (−9.3 deaths per 100 patient-years; 95% CI −11.1 to −8.4), there was no difference in patients with HFrEF (−3.6 deaths per 100 patient-years; 95% CI −9.5 to 3.0) (Figure 1). Four deaths were HF-related deaths (5.7 HF-related deaths per 100 patient-years; 95% CI 1.4 to 11.9; 10.8 HF-related deaths per 100 patient-years; 95% CI 2.5 to 23.1 in the HFrEF subgroup).

Conclusion

In patients with HFpEF, the mortality rate following atrial flow regulator implantation was lower than the predicted mortality rate. These findings need to be confirmed by larger randomised, controlled trials.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): Occlutech International AB
Alcohol abstinence vs. persistent alcohol consumption in alcoholic cardiomyopathy: impact on long-term prognosis
Authors: Cediel Calderon G , Lopez H , Domingo M , Codina P , Santiago E , Borrellas A , Gonzalez B , Rivas C , Crespo E , Pulido A , Velayos P , Barcelo E , Lupon J , Bayes-Genis A
Published: October 2022

Background

Alcoholic Cardiomyopathy (ACM) remains a prevalent form of toxic-induced heart damage. Whether ACM prognosis depends on the persistence of alcohol consumption is a matter of debate.

Purpose

We sought to determine predictors of adverse events during long-term follow-up and left ventricular ejection fraction (LVEF) changes between abstainers and non-abstainers.

Methods

Consecutive patients admitted to a HF clinic from 2001 to 2020 with ACM were included. The primary endpoint was the composite of all-cause death or HF hospitalization. HF hospitalization was analyzed as a secondary outcome. Changes in LVEF at 1- and 3-years follow-up according to discontinuation of alcohol consumption was also analyzed. Multivariable Cox regression analyses were performed using the competing risk strategy for the secondary endpoint.

Results

A total of 122 patients were included with a mean age of 57.8±10.0 years and 95.1% (n=116) of males. The mean LVEF was 27.5% ± 10.6 and 11.5% (n=14) exhibited NYHA functional class 3. A total of 92 (75.4%) patients remained abstinent during follow-up; the rest continued with at least moderate alcohol intake. After a median follow-up of 6.8 years (interquartile range: 3.2 to 11.3 years), 59 (48.4%) presented the primary endpoint (45 [36.9%] died and 34 [27.9%] experienced HF readmission). Independent predictors of the primary outcome were age (hazard ratio [HR]: 1.03; 95% confidence interval [CI]: 1.00–1.06; p=0.042), hemoglobin (HR: 0.68; 95% CI: 0.56–0.82; p<0.001) and alcohol abstinence (HR: 0.35; 95% CI: 0.20–0.61; p<0.001). Predictors of HF readmission were hemoglobin (HR: 0.65; 95% CI: 0.50–0.83; p=0.001) and alcohol abstinence (HR: 0.39; 95% CI: 0.17–0.92; p=0.032). Improvement in LVEF was higher in abstainers (27.5±10.6% from baseline to 46.7±13.1% and 49.1±14.3% at 1- and 3-years respectively) than in non-abstainers (27.8±10.3% to 40.3±14.0% and 39.2±16.3% at 1- and 3-years respectively), being these changes in LVEF significantly different between both groups (p=0.004).

Conclusions

Patients with ACM and who remain abstainers during follow-up exhibit better outcomes and higher LVEF improvement in comparison to non-abstainers. These findings should help to inform lifestyle modification for patients with ACM.

Funding Acknowledgement

Type of funding sources: None.
Increasing the class of foundational medication for heart failure is associated with improved prognosis in hospitalized patients with heart failure with reduced or mildly reduced ejection fraction
Authors: Ito M , Maeda D , Matsue Y , Shiraishi Y , Dotare T , Sunayama T , Nogi K , Kohsaka S , Yoshikawa T , Saito Y , Minamino T
Published: October 2022

Aim

To clarify the association between changes in the number of foundational medications for heart failure (FMHF) during hospitalization for worsening heart failure and post-discharge prognosis.

Methods and results

We retrospectively analyzed a combined dataset of three large-scale registries of hospitalized patients with heart failure in Japan (NARA-HF, WET-HF, and REALITY-AHF) and included patients already diagnosed with heart failure with reduced or mildly reduced left ventricular ejection fraction (HFr/mrEF) before admission. Patients were stratified by changes in the number of prescribed FMHF classes, namely angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, beta blockers, and mineralocorticoid receptor blockers, from admission to discharge. The primary endpoint was defined as the combined endpoint of heart failure rehospitalization and all-cause death within 1-year of discharge. The cohort consisted of 1,113 patients, and 482 combined endpoints were observed. In total, 413 (37.1%) patients were on increased FMHF (increased group), 607 (54.5%) remained unchanged (unchanged group), and 93 (8.4%) had a decreased number of FMHF (decreased group) at discharge compared to the time of admission. In multivariable analysis, the increased group was associated with a significantly lower incidence of the primary endpoint compared with the unchanged group (hazard ratio 0.56, 95% confidence interval 0.45–0.60; P<0.001) and decreased group (hazard ratio 0.58, 95% confidence interval 0.40–0.84; P=0.004).

Conclusion

Increasing the number of FMHF cases during heart failure hospitalization is associated with a better prognosis in patients with HFr/mrEF.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): REALITY registry was funded by the Cardiovascular Research Fund of Japan.WET-HF registry was supported by a Grant-in-Aid for Young Scientists (Y.S. JSPS KAKENHI, 18K15860).
Effect of diuretic down-titration on pulmonary congestion assessed by lung ultrasound when introducing sodium-glucose cotransporter 2 inhibitors
Authors: Domingo M , Teis A , Alonso N , Julian T , Bares D , Barcelo E , Revuelta-Lopez E , Gonzalez B , Codina P , Cediel G , Santiago-Vacas E , Santesmases J , Zamora E , Lupon J , Bayes-Genis A
Published: October 2022

Background

Mechanistic pathways of sodium-glucose cotransporter 2 inhibitors (SGLT2i) benefits in heart failure (HF) remain unclear.

Purpose

To investigate the effects of SGLT2i and simultaneous diuretic down-titration on pulmonary congestion assessed by lung ultrasound (LUS) and by HF biomarkers.

Methods

Prospective observational study in outpatients with HF and type 2 diabetes assigned to a SGLT2i. LUS was performed at baseline (just before starting SGLT2i), at 15 days and at 3-months of follow-up. Eight thoracic areas were examined. Diuretic regime was reduced at baseline, when LUS and clinical assessment allowed. The main outcome was short-time change in B-lines sum. Secondary endpoints evaluated N-terminal pro-B-type natriuretic peptide (NTproBNP), cancer antigen 125 (CA125) and interleukin-1 receptor-like 1 (ST2)

Results

88 patients were included (age, 66.8±9.9 years; 93.2% male; 77.3% in NYHA II functional class; 75% treated with loop diuretics). The median of lines B was 2 (RIQ 1–4), 2 (RIQ 1–4) and 2 (RIQ 0–4) at the initial visit, 15 days and 3 months, respectively (initial vs. 3 months, p=0.21) (Table 1). The number of patients treated with loop diuretics decreased from 66 to 33 (p<0.001) and the mean dose of furosemide (or equivalent) in those who continued decreased from 61±5 mg/day to 45.8±20 mg/day (p<0.001). There were no hospitalizations for HF in the 3 months of follow-up. None of the biomarkers showed statistically differences at 3 months of follow-up (Table 1).

Conclusions

The introduction of SGLT2i allowed a significant reduction of diuretics in chronic HF patients and diabetes, without evidence of worsening lung congestion assessed neither by LUS nor by HF biomarkers.

Funding Acknowledgement

Type of funding sources: None.
SGLT2i uptake among heart failure patients with reduced ejection fraction: ongoing prescriber hesitancy and how to address this
Authors: Soh B W T , Balfe C , O Brien K , Glasgow J , Forkin A , Sim W H , Muradagha H , Abbas S , Arnous S , Kiernan T
Published: October 2022

Background

The evidence of mortality benefit from sodium-glucose transport protein 2 inhibitors (SGLT2i) in the management of heart failure with reduced ejection fraction (HFrEF) has been observed since 2019. Its first-line use in HFrEF, regardless of diabetes status, has been recommended by The European Society of Cardiology (ESC) since September 2021. Yet prescriber hesitancy surrounding SGLT2i use is still an under investigated issue resulting in centres falling short of gold-standard care. A simple review of pharmacotherapy pattern can alert clinicians to under prescribing of SGLT2i inhibitors and respond by improving adherence to guidelines.

Purpose

To describe the pharmacotherapy pattern of HFrEF patients attending an outpatient (Heart Failure Support Unit) HFSU in Ireland.

Methods

A retrospective analysis was performed in HFrEF patients actively attending the HFSU. Active attendance was considered a single engagement with the service between 1st January 2021 and 31st December 2021, and patients who have not died, been transferred to another service, or loss to follow-up. Information collected from digital records included patient demographic, comorbidities, baseline investigations, and pharmacotherapy pattern. Sensitivity analysis was performed for patients with type 2 diabetes (T2DM).

Results

156 HFrEF patients were actively attending the HFSU. The mean age was 72.1 (±12.5) years and majority were male 114 (73.1%). The following pharmacotherapy pattern was revealed: angiotensin-converting enzyme inhibitors/ angiotensin II receptor blockers (ACEi/ARBs) 80 (51.3%), ARNi 55 (35.3%), β-blockers 142 (91.0%), mineralocorticoid receptor antagonist (MRA) 58 (37.2%), SGLT2i 9 (5.8%) and Ivabradine 9 (5.8%). Sensitivity analysis for T2DM patients (n=45) reveals a pattern of ACEi/ARBs 46.7%, ARNi 37.8%, β-blockers 95.6%, MRA 42.2%, SGLT2i 20.0% and Ivabradine 8.9%. All 9 instances of SGLT2i use were in T2DM patients. Since identification of SGLT2i under-prescribing, an interim review on 28th February 2022 revealed that total SGLT2i prescription had increased by 19 (211.1%), all of which were outside the T2DM population.

Conclusions

SGLT2i is still under prescribed for HFrEF management and prescriptions have the tendency to be restricted to T2DM patients. Identification of pharmacotherapy pattern can alert clinicians to prescriber hesitancy and increase new SGLT2i prescriptions outside the T2DM population.

Funding Acknowledgement

Type of funding sources: None.
Maximum dose sacubitril/valsartan in heart failure with reduced ejection fraction: does atrial fibrillation compromise the benefits?
Authors: Monteiro E , Barbosa J , Guimaraes J , Fernandes D , Costa G , Gomes R , Rosa J , Campos G , Costa S , Baptista R , Franco F , Madeira M , Goncalves L
Published: October 2022

Background

In the PARADIGM-HF trial, sacubitril/valsartan (SV) was shown to be superior to enalapril in reducing hospitalizations for worsening heart failure (HF), cardiovascular mortality, and all-cause mortality in patients with heart failure with reduced ejection fraction (HFrEF). The 2021 ESC Guidelines recommends SV as a replacement for angiotensin-converting-enzyme inhibitors to reduce the risk of HF hospitalization and death. There is little information regarding the effects of SV according to atrial fibrillation (AF) status.

Purpose

The aim of this study was to compare the effects of maximum dose SV regarding symptomatic improvement, change in natriuretic peptides levels (NP) and left ventricular ejection fraction (LVEF) in patients with HFrEF with and without AF.

Methods

Retrospective analysis of 137 patients with HFrEF on maximum dose SV (97/103mg twice daily). Patients were divided into two groups according to AF status. Age, gender, relevant comorbidities, usual medication, baseline symptomatic status, NP levels and LVEF were assessed using the Mann-Whitney U or χ2 test (according to variable type) to ensure comparability between groups. Variation in NYHA class, NP levels and LVEF between baseline and 6-month follow-up was evaluated and compared between groups.

Results

Comparison between groups is presented in Table 1. In our studied population, ischemic aetiology was more common in the sinus rhythm group (49.5% vs 30.4%; p 0.034). There were no significant differences between groups regarding age, gender, hypertension, diabetes, and beta-blocker and mineralocorticoid receptor antagonist usage. At baseline, the AF group had higher NT-proBNP levels [median 1421 mg/dL (IQR 743–3087) vs 467 mg/dL (IQR 140–797); p<0.001]. There were no significant differences regarding baseline NYHA class or LVEF. After 6 months of follow-up, reductions in NYHA class [−1 (IQR −2, −1) for AF; −1 (IQR −1, 0) for SR; p=0.437] and NT-proBNP levels [−358 mg/dL (IQR −2275, −47) for AF; −162 mg/dL (IQR −364, 27) for SR; p=0.156], as well as LVEF improvement [11% (IQR 3–15) for AF; 12% (IQR 7–21) for SR; p=0.201], displayed no statistically significant differences between the two groups.

Conclusions

Our study shows that the beneficial effects of SV on symptomatic status, NP levels and LVEF were not compromised by the presence of AF at baseline.

Funding Acknowledgement

Type of funding sources: None.
Relationship of tafamidis binding site occupancy, transthyretin stabilization, and disease modification in tafamidis treated transthyretin amyloid cardiomyopathy patients
Authors: Moody A T , Tess D A , Li Z , Bulawa C , Fleming J , Maurer T S
Published: October 2022

Introduction

Tafamidis inhibits progression of transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) by binding TTR tetramer and inhibiting its dissociation to monomers which can denature and result in amyloid fibril formation and deposition in cardiac tissue.

Purpose

While the phase 3 ATTR-ACT clinical data clearly demonstrated efficacy, quantification of TTR stabilization in patients and the degree to which the approved dose captures the full potential of the mechanism has yet to be assessed.

Methods

Isothermal titration calorimetry and subunit fraction exchange were used to determine affinities to the two binding sites on TTR. These values were used to develop a model of tafamidis binding to TTR in plasma that was applied to individual patient data to calculate TTR binding site occupancy and the change in total TTR levels induced by TTR stabilization. Population pharmacodynamic (PD) models were developed for three measures of disease progression, plasma NT-proBNP levels, Kansas City Cardiomyopathy Questionnaire – Overall Score (KCCQ-OS), and six-minute walk test (6MWT) distance, to evaluate patient response with the degree of TTR occupancy.

Results

In vitro binding data of wild-type TTR confirmed tafamidis binds two sites of TTR with negative cooperativity and provided precise estimates of the binding affinity to TTR and albumin. Modeling individual patient data of tafamidis exposure and increased TTR plasma levels using the in vitro derived binding affinity values confirms single site binding is consistent with complete tetramer stabilization. Patients given 80 mg tafamidis meglumine, the clinically approved dose for ATTR-CM, had a 92% reduction in unbound, unstabilized TTR, which correlated with a 53% decrease in NT-proBNP elevation, a 56% decrease in KCCQ-OS worsening and a 49% reduced decline in the 6MWT. For 100% receptor occupancy and stabilization, the expected effects on these measures are 58%, 61%, and 54% for NT-proBNP, KCCQ-OS, and 6MWT, respectively.

Conclusions

These results demonstrate a quantitative relationship between TTR stabilization, the mechanism of action of tafamidis, and accepted laboratory and patient-based outcomes in ATTR-CM. These results also support the value of TTR stabilization as a clinically beneficial treatment option which maintains the protein in its physiologically active form within the body.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): This study was sponsored by Pfizer.
Aggressive combined pharmacotherapy for heart failure reduces new onset atrial fibrillation
Authors: Tokutome M , Matsukawa R , Noma A , Kisanuki H , Nakashima H , Watanabe T , Sakemi T , Okabe K , Okahara A , Kawai S , Matsuura H , Masuda S , Mukai S
Published: October 2022

Backgrounds

Heart failure (HF) is a risk factor for new onset atrial fibrillation (AF), and the new onset AF is associated with a worse prognosis in HF patients. It has been reported that renin-angiotensin system inhibitor (RASi), β-blocker and mineral-corticoid receptor antagonist (MRA) prevent the new onset AF in HF patients. However, the effect of combined pharmacotherapy including angiotensin receptor neprilysin inhibitor (ARNI) and sodium glucose co-transporter 2 inhibitor (SGLT2i) on AF is unknown. We investigated the impact of contemporary regimen of combined pharmacotherapy for HF (RASi/ARNI+β-blocker+MRA+SGLT2i) on new onset AF.

Methods and results

We retrospectively studied rEF and mrEF patients without AF admitted to our hospital due to decompensated HF between 2015 and 2021 (n=366). Long-term (The mean follow-up was 635±421 days) incidence of new onset AF was investigated with regard to medical therapies. Patients were divided into 2 groups; patients with ≤2 HF drugs (n=181) and patients with ≥3 HF drugs (n=185). Patients with ≤2 HF drugs group were older (77.3 vs 67.0 years old, P<0.001), had a poorer renal function (Cre: 1.66 vs 1.09 mg/dl, P<0.001), and had a higher rate of ischemic heart disease (52 vs 38%, P=0.009), whereas left ventricular systolic function was better (EF: 31.9 vs 27.3%, P<0.001). There were 19 (10.5%) new onsets AF in the ≤2 HF drugs group, whereas only 7 (3.8%) had new onsets AF in the ≥3 HF drugs group (HR 0.36, 95% CI 0.15–0.85, P=0.01). All-cause death and hospitalization for HF were fewer in the ≥3 HF drugs group. A multivariate analysis revealed that ≥3 HF drugs use was an independent negative predictor of new onset AF (HR 0.37, 95% CI 0.15–0.93, P=0.03). Even after a propensity score matching of the clinical variables, the incidence of new onset AF was consistently fewer in the ≥3 HF drugs group (HR 0.36, 95% CI 0.13–0.99, P=0.04). Finally, patients with new onset AF had a higher rate of hospitalization for HF in the studied population (HR 9.68, 95% CI 5.67–16.5, P<0.01).

Conclusion

Aggressive combined pharmacotherapy for HF may be associated with fewer new onset AF in patients with HF.

Funding Acknowledgement

Type of funding sources: None.
Effects of sacubitril valsartan on renal function in adults with heart failure: a systematic review and meta analysis of randomised controlled trials
Authors: Hernandez A V , Barboza J J , Pasupuleti V , Piscoya A , Roman Y M
Published: October 2022

Background

Sacubitril/valsartan (S/V) may have beneficial effects on renal outcomes in patients with heart failure (HF) receiving angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB).

Purpose

To systematically evaluate the effects of sacubitril/valsartan on renal function in adults with HF.

Methods

Five databases were searched for randomised controlled trials (RCTs) comparing S/V (LCZ696) vs. ACEI or ARB in adult HF patients until January 2022. Doubling serum creatinine levels was the primary outcome. Acute kidney injury (AKI)>50% decline of estimated glomerular filtration rate (eGFR), and hyperkalaemia (serum K+ >5.5 mmol/L) were secondary outcomes. Inverse variance random-effects meta-analyses were used, and effects of S/V on outcomes were described with relative risks (RR) and their 95% confidence intervals (CI). Subgroup analyses by type of HF (chronic vs. acute), and LVEF (<40% vs >40%) were performed. We used the RoB 2.0 tool for risk of bias assessments of RCTs. GRADE methods were used to rate the certainty of evidence (CoE).

Results

Eight RCTs (n=15859) were included; four in chronic HF and four in acute HF. Mean age was 66.2 (SD 5.5) years-old, and 34.1% were female. The median follow-up across RCTs was 36 weeks. In comparison to ACEI/ARB, S/V was associated with lower risk of doubling serum creatinine (RR 0.77; 95% CI 0.72–0.83; I2=0%; moderate CoE). S/V did not reduce the risk of AKI (RR 0.88; 95% CI 0.72–1.08; I2=0%; low CoE), >50% decline of eGFR (RR 0.65; 95% CI 0.37–1.17; I2=45%; very low CoE), and hyperkalaemia (RR 1.01; 95% CI 0.81–1.25; I2=44%; very low CoE). Two RCTs had high risk of bias and two had some concerns of bias. Subgroup analyses were consistent with main analyses for the primary outcome.

Conclusions

In adults with heart failure, S/V reduced doubling creatinine compared to ACEI/ARB, but did not reduce risks of AKI, >50% decline in eGFR or hyperkalaemia. Subgroup analyses by type of HF and LVEF were consistent with main analyses.

Funding Acknowledgement

Type of funding sources: None.
Is it possible to start quadruple therapy in patients with a new diagnosis of HF and reduced ejection fraction? Real-life data from the TIDY-HF registry
Authors: Esteban Fernandez A , Gomez Otero I , Rodriguez Santamarta M , Fluvia Brugues P , Pastor F , Perez Rivera J A , Bonilla J L , Lopez Fernandez S , Lopez A , Segura Aumente J M , Martinez V , Garcia Pinilla J M , Vazquez Lopez-Ibor J , Sanchez Munoz E , Sole E
Published: October 2022

Background

The 2021 European heart failure (HF) guidelines recommended treatment with an inhibitor of the renin-angiotensin-aldosterone axis (RAAS), a beta-blocker (BB), a mineralocorticoid receptor antagonist (MRA), and a cotransporter sodium-glucose type 2 inhibitor (SGLT2) in patients with HF and left ventricular ejection fraction (LVEF) ≤40%. However, there is little evidence on implementing quadruple therapy in clinical practice.

Purpose

Study the implementation of quadruple therapy in patients with a new diagnosis of HF and reduced ejection fraction in clinical practice.

Methods

A prospective multicenter registry (38 centers in Spain) was carried out, including all patients newly diagnosed with HF with LVEF ≤40% in clinical practice. Their baseline and laboratory characteristics were recorded and their pharmacological treatment: at baseline (discharged from hospitalization or first outpatient visit within a maximum period of 1 month after the echocardiographic diagnosis), one month, and 3 months later.

Results

On 1th of March 2022, 349 patients were included, with baseline treatment data in 289. The mean age was 65.0±14.2 years, and 72.1% were men. The mean LVEF was 28.5±7.3%, with 57.6% in NYHA II and 29.1% in NYHA III–IV. The most frequent causes of cardiomyopathy were: ischemic (25.1%), tachycardiomyopathy (16.6%), and idiopathic (15.7%). 46.4% were dyslipidemic, 57.5% hypertensive and 33.3% diabetic. 65.1% of the patients were in sinus rhythm. Before HF diagnosis, 44.6% had been treated with RAASi, 22.8% with BB, 7.8% with MRA, 8.1% with iSGLT2, and 24.5% with diuretics. The drugs used at baseline and the changes during follow-up are shown in Table 1.

Conclusions

According to our cohort, almost 60% of newly diagnosed patients with HF and reduced LVEF start quadruple therapy during the first month after diagnosis, with sacubitril/valsartan being the preferred RAASi in most cases. The implementation of drugs with prognostic benefit is above 70% at baseline and exceeds 80% at one month of follow-up, with a progressive reduction in loop diuretics during follow-up.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Spanish Society of Cardiology
Chronic mitochondrial fusion promotor as a novel pharmacological intervention to alleviate left ventricular dysfunction in rats with chronic myocardial infarction
Authors: Piamsiri C , Jinawong K , Maneechote C , Arunsak B , Chattipakorn S C , Chattipakorn N
Published: October 2022

Background

Decreased cardiac mitochondrial fusion associated with increased mitochondrial dysfunction has been demonstrated in acute myocardial infarction pathology. However, whether this pathophysiologic process is associated with myocardial injury in chronic myocardial infarction (CMI) is still unclear. Recently, a novel pharmacological intervention to promote mitochondrial fusion using mitochondrial fusion promotor-M1 (M1) has been shown to exert cardioprotection against myocardial ischemia and reperfusion injury. However, the roles of M1 in CMI has never been investigated.

Purpose

We investigated the potential cardioprotective benefits of chronic treatment with mitochondrial fusion promotor-M1 in rats with chronic MI model.

Methods

Adult male Wistar rats were assigned to the sham group (n=5) and the CMI group (n=15), which was induced by a permanent left anterior descending coronary occlusion. After 1 week of operation, rats in the CMI group were randomly divided into 3 subgroups which was treated with one of the followings: 1) vehicle (3% DMSO/day, ip, CON, n=5), 2) enalapril (10 mg/kg/day, po, ENA, n=5), or 3) mitochondrial fusion promotor-M1 (2 mg/kg/day, ip, M1, n=5) once daily for 4 weeks. In the end, echocardiography for the left ventricular (LV) function was performed, and the heart was removed to determine the mitochondrial function and malondialdehyde (MDA) level for oxidative stress.

Results

CMI rats that received vehicle showed significantly impaired LV function and cardiac mitochondrial function as evidenced by a 60% reduction in LV ejection fraction (LVEF) along with increased mitochondrial reactive oxygen species (ROS) production, mitochondrial depolarization and mitochondrial swelling, respectively, when compared with the sham rats (Fig. 1A–D). The CMI rats also exhibited a higher cardiac tissue MDA level than those of sham rats, further indicating cardiac oxidative stress (Fig. 1E). Interestingly, chronic treatment with either enalapril or M1 effectively attenuated CMI-induced mitochondrial dysfunction and oxidative stress upregulation, thus increasing LVEF (27% improvement for both ENA and M1), when compared with the vehicle group (Fig. 1A).

Conclusion

Long-term promotion of mitochondrial fusion mitigated cardiac mitochondrial dysfunction and oxidative stress, eventually culminating in improved LV function in rats with CMI. These findings suggest that chronic modulation of mitochondrial fusion could be a promising pharmacological intervention to improve LV function in CMI.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): 1. The National Science and Technology Development Agency Thailand2. The Thailand Research Fund (RGJ)
Timing of initiation of sodium-glucose co-transporter 2 inhibitor in patients with diabetes and chronic cardiac failure
Authors: Sun W , Yan B
Published: October 2022

Purpose

Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of first hospitalization for heart failure (HHF) in patients with type 2 diabetes. We aimed to evaluate the impact of early initiation of SGLT2 inhibitors on recurrent HHF in diabetic patients with chronic cardiac failure.

Methods

We retrospectively analyzed 1,363 consecutive diabetic patients with chronic cardiac failure with index HHF between August 2015 and August 2020 in 16 public hospitals in Hong Kong who were prescribed SGLT2i (empagliflozin=1,009, 74% and dapagliflozin =354, 26%).Patients who initiated SGLT2i at discharge of index HHF were compared to those who were not. Risk of recurrent HHF was compared, using adjusted sub-distribution hazard ratios (aSHR) derived from Fine and Gray regression models, accounting for death as competing risk, adjusting for age, gender, concurrent medications. Comparisons were also conducted between initiation of SGLT2i ≤30 vs >30 days; and ≤90 vs. >90 days after discharge.

Results

Of 1,363 patients (mean age 63.9±11.6, female 34.6%), 85% had no history of previous HHF at enrollment, 11.9% had up to 2 and 3.1% and 3.1% ≥3 HHF in the past 5 years. SGLT2i was initiated in 37.4% of patients at discharge of index HHF and the median time from index HHF to SGLT2i initiation for the other patients was 4.2 (IQR: 0–20.4) months. During a median follow-up of 1.3 (IQR: 0.2–2.7) years, initiation of SGLT2i at discharge was associated with lower risk of recurrent HHF (aSHR = 0.79, 95% CI: 0.68–0.92). Similar effect was observed between SGLT2i initiation ≤30 vs. >30 days (aSHR = 0.82, 95% CI: 0.70–0.95) but not between ≤90 vs. >90 days (P=0.19).

Conclusion

Among patients with diabetes and chronic cardiac failure, the risk of recurrent HHF was reduced when SGLT2 was initiated early after index HHF.

Funding Acknowledgement

Type of funding sources: None.