bluuebunny/crossref_metadata_2025 huggingface dataset:
Usefulness of diastolic dysfunction score in predicting long-term prognosis of acute myocardial infarction patients with preserved ejection fraction
Authors: Bae S.A , Kim K.H , Kim H.Y , Park H.J , Cho J.Y , Yoon H.J , Park J.C
Published: November 2020

Background

To investigate the usefulness of left ventricular diastolic dysfunction (LVDD) score in the prediction of future major cardiovascular events (MACEs) in acute myocardial infarction (AMI) patients with preserved ejection fraction (EF).

Methods

Among 2,539 AMI patients from January 2012 to December 2015, a total of 1,374 patients with preserved EF and no atrial fibrillation were enrolled and were followed up for 3 years. Four parameters which were used for the categorization of DD in the current 2016 recommendation of American Society of Echocardiography (ASE) (septal e' <7cm/s, E/e' >14, tricuspid regurgitation velocity >2.8m/s, and LAD >40mm) were used for DD scoring. The integer score was assigned to each parameter as 1 point. The development of MACEs including death, recurrent MI, any revascularization, or hospitalization due to heart failure (HHF) was evaluated.

Results

Study subjects were divided into 5 groups by the current 2016 ASE criteria; LVDD score 0 (n=354), score 1 (n=496), score 2 (n=333), score 3 (n=139), and score 4 (n=52). During 3 years of clinical follow up, MACEs were developed in 271 patients; 142 death, 74 recurrent MI, 99 revascularization, and 32 HHF. MACEs were significantly increased as LVDD scores were increased; MACEs in LVDD score 0 (n=43, 12.1%), score 1 (n=73, 14.7%), score 2 (n=73, 21.9%), score 3 (n=51, 36.7%), and score 4 (n=31, 59.6%), (ptrend <0.001). On Kaplan-Meier survival curve analysis, MACEs free survival was significantly lower as LVDD scores were increased (Figure 1).

Conclusion

The present study demonstrated that MACEs were significantly increased as LVDD scores were increased in AMI patients with preserved EF. Therefore, it is suggested that this novel scoring system by using the current 2016 ASE criteria for diastolic function evaluation may provide comprehensive risk assessment and thus would be useful in predicting upcoming CV events in AMI patients with preserved EF.

MACE free survival according to the LVDD

Funding Acknowledgement

Type of funding source: None
Is it important to maintain the reverse remodeling?
Authors: Furquim S.R , Ferreira J.C.L.A , Mario A.D.S , Biselli B , Gomes B.R , Chizzola P.R , Salemi V.M.C , Munhoz R.T , Bocchi E.A , Ayub-Ferreira S.M
Published: November 2020

Background

Consistent advances in Heart Failure (HF) treatment have generated a new phenotype: reverse remodelling (RR). These patients have better outcomes than those who don't achieve the RR, however little is known about the long-term remodelling maintenance and its predictors or about a new worsening on ejection fraction (EF).

Purpose

To analyze the difference between patients who maintain the RR, those who can not maintain it and those who have not improved.

Methods

Observational study that analyzed features in outpatients with HF and initial EF lower than 40%, an intermediary EF, and last EF in 2014, 2015 and 2016, with a minimal interval of 6 months. Patients were divided into 3 groups: Negative RR (NRR - All EF <40%); non-maintained RR (NMRR – 2nd EF >40% and 3rd EF<40%) and Maintained RR (MRR – 2nd and 3rd EF >40%). Comparisons were made by Kruskal-Wallis test and the survival was analyzed by Kaplan Meyer and Log-Rank tests.

Results

1762 medical records were analyzed and 1484 were included. 993 patients had NRR, 201 patients had NMRR and 290 patients had MRR. The initial EF was lower in the NRR group. In the first 3 years, the groups NMRR and MRR improve the EF by 16.4% (±1.2) and 18.1% (±1.1), respectively. During the next 3 years, the NMRR group lost this improvement (−16.1% ±1.1), while the MRR group maintained it (0.7% ±1.4). The MRR group had more hypertension (0.75±0.05) as comorbidity, while the NMRR had more myocardial infarction (0.39±0.07) and myocardial revascularization (0.17±0.05). Chagasic and alcoholic aetiologies predominated in the NRR group (0.05±0.01 and 0.19±0.02) and these patients had less valvar cause (0.04±0.01). The NMRR group had more ischemic aetiology (0.41±0.07), and the MRR had more hypertensive (0.22±0.05). General survival was different between the three groups (p<0.001) major in MRR, NMRR and NRR group, respectively. Survival after the last EF also was significantly different between the groups (p<0.001) with the same pattern.

Conclusion

Achieving RR is important, but maintaining it can bring better outcomes and prognosis. Therefore, it is important to identify factors and therapeutic goals for the RR maintenance.

Figure 1

Funding Acknowledgement

Type of funding source: None
Dapagliflozin improves left ventricular myocardial longitudinal function in people with type 2 diabetes
Authors: Brown A.J.M , Gandy S , McCrimmon R , Struthers A , Lang C
Published: November 2020

Background/Introduction

Asymptomatic left ventricular (LV) dysfunction is highly prevalent in patients with type 2 diabetes mellitus (T2DM). Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to reduce all-cause mortality and hospitalisations for heart failure in patients with T2DM. The underlying mechanisms for these cardiovascular benefits are unclear. In the Dapa-LVH trial, we had previously shown that dapagliflozin treatment significantly reduces LV mass (LVM) compared to placebo in patients with T2DM and LV hypertrophy (LVH).

Purpose

The objective of this sub-study of the Dapa-LVH study was to assess whether dapagliflozin treatment improves LV myocardial longitudinal function and LV diastolic function in patients with T2DM and LVH.

Methods

We randomly assigned 66 people (mean age 67±7 years, 38 males) with T2D, LVH with a normal LV ejection fraction to receive dapagliflozin 10mg once-daily or placebo for 12 months. The primary endpoints were change in global longitudinal strain (GLS) and LV diastolic function defined as the ratio of mitral inflow E to mitral e' annual velocities assessed using echocardiography. Secondary endpoints were left ventricular and atrial volumes assessed using cardiac magnetic resonance.

Results

Dapagliflozin treatment resulted in a median increase in GLS of −1.64±2.5% vs placebo −0.2±1.8; p=0.024, with a mean difference of −1.4% (95% CI: −2.7 to −0.2). There was a trend towards a reduction left atrial area with a median change in left atrial area of the dapagliflozin group −0.5±3.75 cm2 vs placebo group 0.0±3.5 cm2; p=0.088), leading to an absolute mean difference of −1.29cm2 (95% CI: −3.01 to 0.44). There was no significant difference between dapagliflozin and placebo in E/e' and in LV volumes.

Conclusion

Dapagliflozin treatment improved LV myocardial longitudinal function which may suggests it may improve subclinical LV dysfunction.

Funding Acknowledgement

Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): This study was funded by an Externally Sponsored Research grant from Astra Zeneca – (grant number ESR-14-10168
Pulmonary vein isolation for atrial fibrillation patients with reduced left ventricular ejection fraction
Authors: Ikenouchi T , Inaba O , Kono T , Murata K , Takamiya T , Inamura Y , Sato A , Nitta J , Takahashi Y , Goya M , Sasano T
Published: November 2020

Background/Introduction Pulmonary vein isolation (PVI) is a cornerstone of curable treatment for atrial fibrillation (AF). Left ventricular (LV) ejection fraction (EF) occasionally improves after PVI in AF patients with reduced LVEF (rEF), the mechanism of which is not fully understood. CASTLE-AF trial have demonstrated that PVI with radiofrequency (RF) catheter for AF patients with rEF can reduce their mortality and heart failure. Nevertheless there are limited data about the clinical outcome of the PVI for patients with impaired LV function.

Purpose

This study was to evaluate the efficacy of PVI and improvement of LVEF after the procedure in AF patients with rEF.

Methods

A total of 2709 consecutive AF patients (age 65±39 y/o, male 67%) underwent their first PVI with cryoballoon or RF catheter in our facility from April 2014 to March 2019, and retrospectively analyzed. All the patients underwent echocardiogram before and half to one year after the procedure. Patients with LVEF under 40% before the PVI were selected (n=111) and divided into two groups based on whether there were specific etiologies of LV function impairment (group A) or not (group B).

Results

There were no significant difference in mean LVEF between group A (n=40) and group B (n=71) (32±6% vs 33±6%, p=0.12). The major etiology of rEF in group A were old myocardial infarction (n=20, 18%), hypertensive heart disease (n=6, 5.4%), and dilated cardiomyopathy (n=5, 4.5%). After mean follow-up of 2.7 years, there were no significant difference in clinical outcome after the procedure between two groups (1-year Kaplan–Meier event rate estimates; 72.2% vs 72.9%; p=0.85). The change amounts of LVEF after the PVI were significantly higher in group B (20±14%) compared to group A (2±10%) (p<0.001). Multivariable Cox regression analysis revealed that age was the independent significant predictors of EF improvement over 10% in group B (p=0.048).

Conclusions

In AF patients with reduced LVEF, there were no significant difference in efficacy of PVI between those who have specific etiologies of LV function impairment other than AF and who have not. The improvement of LVEF after PVI was significantly larger in patients without specific etiologies compared to those with.

Funding Acknowledgement

Type of funding source: None
Dapagliflozin reduces the risk of hyperkalaemia in patients with heart failure and reduced ejection fraction: a secondary analysis DAPA-HF
Authors: Kristensen S.L , Docherty K.F , Jhund P.S , Bengtsson O , Demets D.L , Inzucchi S.E , Kober L , Kosiborod M.N , Langkilde A.M , Martinez F.A , Ponikowski P , Sabatine M.S , Sjostrand M , Solomon S.D , McMurray J.J.V
Published: November 2020

Background

Hyperkalaemia often limits the use of mineralocorticoid receptor antagonists (MRAs) in patients with heart failure and reduced ejection fraction (HFrEF), denying these patients a life-saving therapy.

Purpose

To determine whether treatment with the sodium-glucose cotransporter 2 (SGLT-2) inhibitor dapagliflozin reduces the risk of hyperkalaemia associated with MRA use in patients with HFrEF.

Methods

The risk of developing mild hyperkalaemia (potassium >5.5 mmol/L) and moderate/severe hyperkalaemia (>6.0 mmol/L) was examined in the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF) according to background MRA use, and randomized treatment assignment, by use of Cox regression analyses.

Results

Overall, 3370 (70.1%) patients in DAPA-HF were treated with an MRA. Mild hyperkalaemia and moderate/severe hyperkalaemia occurred in 182 (11.1%) and 23 (1.4%) patients treated with dapagliflozin as compared to 204 (12.6%) and 40 (2.4%) of patients given placebo (Table and Figure). This yielded a hazard ratio (HR) of 0.86 (0.70–1.05) for mild hyperkalaemia and 0.50 (0.29, 0.85) for moderate/severe hyperkalaemia, comparing dapagliflozin to placebo.

Conclusions

Patients with HFrEF and taking a MRA who were randomized to dapagliflozin had half the incidence of moderate/severe hyperkalaemia, compared with those randomized to placebo.

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): DAPA-HF study was funded by AstraZeneca
Chronic obstructive pulmonary disease in heart failure: influence on circulating biomarkers and outcome
Authors: Aimo A , Vergaro G , Januzzi J , Richards A.M , Lam C.S.P , Latini R , Anand I.S , Ueland T , Brunner-La Rocca H.P , Bayes-Genis A , De Boer R.A , Gaggin H.K , Huber K , Passino C , Emdin M
Published: November 2020

Background

Chronic obstructive pulmonary disease (COPD) is common in patients with chronic heart failure (CHF).

Purpose

We aimed to explore the impact of COPD on HF biomarkers (N-terminal fraction of pro-B-type natriuretic peptide [NT-proBNP], high-sensitivity troponin T [hs-TnT], and soluble suppression of tumorigenesis-2 [sST2]) and outcome.

Methods

Individual data from 14 cohorts of patients with stable chronic HF and NT-proBNP and hs-TnT values were analysed. Patients with known COPD status were evaluated.

Results

Patients (n=13,178) were aged 67 years (58–75), 75% males, and 76%, 11%, 13% with HF with reduced, mid-range, or preserved ejection fraction (HFrEF/HFmrEF/HFpEF), respectively. Patients with COPD were older than those without COPD (age 71 years [64–77] vs. 66 [57–75]; p<0.001), more frequently males (79% vs. 74%; p<0.001), had more often ischaemic HF (54% vs. 52%; p<0.001), and HFpEF (14% vs. 12%; p=0.011), but not HFpEF (12% vs. 11%; p=0.097). COPD patients had also more severe dyspnoea (44% in NYHA class III-IV vs. 31%; p<0.001), and slightly worse renal function (median estimated glomerular filtration rate [eGFR] 58 mL/min/1.73 m2 [44–74] vs. 60 [46–67]; p<0.001). Patients with COPD had higher NT-proBNP (1501 ng/L [642–3333] vs. 1225 ng/L [476–2902]; p<0.001), hs-TnT (22 ng/L [13–38] vs. 17 ng/L [9–30]; p<0.001), and sST2 (30 ng/mL [22–45] vs. 29 [21–43]; p<0.001).

Over a median follow-up of 2.1 years (1.5–3.7, range 0–18 years), 3,865/12,489 patients (31%) died; among them, 2,443/12,450 (20%) died for cardiovascular causes; 3,373/12,469 patients (27%) were hospitalized for HF over 35 months (15–63, range 0–216 months). Patients with COPD had a significantly higher all-cause mortality, cardiovascular mortality, and worse survival free from HF hospitalization (all p<0.001; Figure). In a model including age, gender, ischaemic vs. non-ischaemic aetiology, eGFR, HFrEF/HFmrEF/HFpEF, and NYHA class III-IV, COPD retained independent prognostic significance from NT-proBNP for 1-year all-cause (p=0.009) and cardiovascular mortality (p=0.022), 5-year all-cause (p<0.001) and cardiovascular mortality (p=0.011) as well as 3- (p=0.033), 6- (p=0.019) and 12-month HF hospitalization (p=0.033). COPD lost its independent prognostic significance when hs-TnT and sST2 were included in the model.

Conclusions

COPD in HF is characterized by higher NT-proBNP, hs-TnT and sST2 levels. COPD adds prognostic significance over NT-proBNP alone, but not over the combination of NT-proBNP, hs-TnT, and sST2.

Funding Acknowledgement

Type of funding source: None
Heart failure hospitalization trends during a very long-term follow-up up to 18 years
Authors: Zamora E , De Antonio M , Domingo M , Santiago-Vacas E , Codina P , Santesmases J , Troya M.I , Diez-Quevedo C , Boldo M , Alonso N , Gonzalez B , Rivas C , Nunez J , Lupon J , Bayes-Genis A
Published: November 2020

Background

Heart Failure (HF) is the first cause of hospitalizations in people older than 65 years. Often patients suffer recurrent hospital admissions.

Objective

To assess recurrent HF-related hospitalizations during very long-term follow-up in a cohort of HF outpatients managed in an ambulatory structured HF Unit.

Methods

End of follow-up was 31.8.2019 (at least 1-year follow-up for alive patients, up to 18 years). Heart failure hospitalizations were defined as unplanned hospitalizations of at least 24 hours due to worsening heart failure and were identified from clinic records, hospital wards, or electronic Catalan history record. Death was recorded from the same sources and Spanish Health System and Spanish Death Registry. Lost information during follow-up was adequately censored (1 patient for survival status and 37 for HF-related hospitalizations).

Results

A total of 2355 patients were included. Follow-up span a total of 12,472 patients-years. 1682 HF-related hospitalizations were recorded in 725 patients (13.5 per 100 patients-years). Number of admissions ranged from 0 in 1630 patients to 22 in 1 patient (patients with hospitalizations, median 2 [Q1-Q3, 1–3]; 118 patients had 4 or more hospitalizations). HF hospitalization density incidence was higher during the 10 first years in patients with HF hospitalizations in the precedent year before HF Clinic baseline visit (table). By contrast, if only patients who died during follow-up were considered (N=1299), hospitalization trends significantly increased in their last period of life: 11.7%, 8.9%, 13.6%, 20.8% and 44.9% from the first to the last period (quintile) of their trajectory, respectively.

Conclusions

HF hospitalizations occur during the whole HF trajectory, with an increasing trend at the end of the every patient trajectory.

Funding Acknowledgement

Type of funding source: None
Patients with heart failure and a LVEF less than 40% present an overall lower health related quality of life than those with LVEF between 40% and 60%: a multinational real-world survey in EU
Authors: Proudfoot C , Fonseca A.F , Lahoz R , Corda S , Cotton S , Jackson J , Studer R
Published: November 2020

Background and purpose

Heart Failure (HF) is associated with symptoms such as dyspnoea and fatigue which can impact patients' health related quality of life (HRQoL). This study aimed to characterize and assess the HRQoL of patients with HF and left-ventricular ejection fraction (LVEF) <40% versus those with ≥40%-60%.

Methods

A cross-sectional study of patients with HF was conducted in France, Germany, Italy, Spain and United Kingdom. Patient record forms (PRFs) were completed by 257 cardiologists and 158 general practitioners (GPs) for consecutively consulting patients. The same patients were invited to provide patient-reported outcomes including self-completion questionnaires, Minnesota Living with Heart Failure Questionnaire (MLHFQ) and EQ-5D-5L VAS.

Results

204 HF patients with LVEF <40% (mean age 67.7 years) and 600 patients with LVEF ≥40–60% (mean age 68.9 years) were included. Proportion of males was significantly higher in the lower LVEF group (73.5% vs. 61.2%, p=0.0017). Overall, the patients with lower LVEF more frequently presented with comorbidities than those with LVEF ≥40–60% (p<0.05, Figure 1). NYHA stage III/IV (35.8%/7.4% vs. 15.3%/0.8%) as well as self-reported HF symptoms were more frequently reported in the lower LVEF group (p<0.05, Figure 1). Similarly, patients with LVEF <40% reported statistically significantly worse HRQoL compared to those with LVEF ≥40–60% (Table 1).

Conclusions

The HRQoL of all HF patients with LVEF ≤60% appears impacted, while those with LVEF <40% had significantly worse HRQoL than those with LVEF ≥40–60%. These differences in HRQoL may not only be related to the LVEF but also to the overall characteristics of these patients. Addressing the HRQoL burden for patients should be a key aspect of HF management strategies for all HF patients.

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Novartis Pharma AG
Clinical significance of the relative apical sparing pattern of longitudinal strain in patients with cardiac amyloidosis
Authors: Saito M , Nakao Y , Higaki R , Kawachi Y , Yokomoto Y , Ogimoto A , Suzuki M , Kawakami H , Hiasa G , Okayama H , Inoue K , Ikeda S , Yamaguchi O
Published: November 2020

Background

The relative apical sparing pattern (RASP) of left ventricular (LV) longitudinal strain (LS) is frequently associated with cardiac amyloidosis (CA). However, some patients with CA do not show the RASP, and their clinical characteristics have not been fully clarified. We sought to investigate the clinical significance of RASP in patients with CA.

Methods

One hundred consecutive CA patients who were diagnosed by biopsy or myocardial pyrophosphate scintigraphy and evaluated for RASP (mean age: 76 years, male: 77%, LV mean wall thickness: 13.5 mm, light-chain [AL] type: 33 cases, transthyretin [TTR] type: 67 cases) were retrospectively enrolled. The RASP was semi-quantitatively and quantitatively assessed. Semi-quantitative RASP was defined as reduction of LS (≥−10%) in ≥5 (of 6) basal segments relative to preserved LS (<−15%) in ≥1 apical segment. Quantitative RASP was calculated according to the following formula: Quantitative RASP = [Average apical LS] / [Average basal LS + Average mid LS]. We adapted three validated thresholds (>1.00, >0.90, and >0.87) according to the literature.

Results

Semi-quantitative and binalized quantitative RASP (>1.00, >0.90, and >0.87) were observed in 55, 55, 63, and 65 patients, respectively. RASP in each definition was more prevalent in the TTR group than in the AL group. Additionally, RASP was significantly associated with higher LV wall thickness even after adjustment for the CA subtypes (all, p<0.05, Figure). After the RASP assessment, 35 all-cause deaths and 26 cardiac deaths were observed during the follow-up period (median, 1.1 years). Although these events were significantly associated with poor nutrition, lower blood pressure, higher New York Heart Association class, and the AL group, no association was found with RASP and LV wall thickness.

Conclusions

The incidence of RASP is low in the case of thin LV wall thickness in CA patients, which may indicate the difficulty of early diagnosis of CA using RASP in patients with mild LV hypertrophy. The prognostic prediction using RASP may be challenging in this cohort.

Figure 1

Funding Acknowledgement

Type of funding source: None
Impact of pulmonary wave reflection in heart failure: right ventricular-arterial coupling
Authors: Hayama H , Uejima T , Okazaki O , Hara H , Hiroi Y
Published: November 2020

Background

Pulmonary wave reflection, an important loading component on RV, would help better describe right ventricular (RV) – arterial uncouplingin type II pulmonary hypertension (PH).

Methods

This study included 105patients with type II PH (age = 72±13 years old, ejection fraction = 47±21%). Pulmonary wave reflection was characterised by estimating pressure and velocity profiles from Doppler measurement and separating pressure waveform into forward (Pf) and backward pressure (Pb) waves based on the concept of wave intensity. The relationship of RV strain against Pb or pulmonary artery systolic pressure (PASP) was compared between patients with and without subsequent event of worsening heart failure, using discriminant analysis.

Results

Sample profiles of pressure waveforms illustrated Pb accounted for a significant proportion of total pressure (figure A). When RV strain was plotted against Pb, the distribution of both group were clearly separated, indicating significant uncoupling in patients with events, whereas when plotted against PASP, the both groups were overlapped (figure B and C).

Conclusions

Pulmonary wave reflection can better describe RV-arterial uncoupling in type II PH.

Funding Acknowledgement

Type of funding source: None
Apical sparing strain pattern observed in danon disease: insights from a global registry
Authors: Bui Q , Ma G , Kraushaar M , Escobedo V , Le B , Covarrubias E , Brambatti M , Kahn A , Bougault C , Hong K , Taylor M , Adler E
Published: November 2020

Background

Danon Disease (DD) is a rare X-linked autophagic disorder due to mutations in the Lysosomal Associated Membrane Protein 2 (LAMP-2) gene and causes severe cardiac manifestations. Measurement of longitudinal strain (LS) has been shown to provide diagnostic insights into different etiologies of hypertrophic cardiomyopathies compared to conventional echocardiographic parameters.

Purpose

The aim of this study was to describe the pattern of global and regional LS in DD.

Methods

A retrospective, international registry, using medical records provided by patients, was formed to describe the natural history of DD. Complete echocardiogram images were available for review and LS was analyzed globally and regionally (basal, mid, apex).

Results

A total of eighteen DD patients (male 72%, mean age 17.2±10 years) had sufficient quality echocardiographic images for both traditional and myocardial strain evaluation. Notable traditional echocardiographic parameters included a mean EF of 60±11%, LV mass index 200±159 g/m2, intraventricular septal diameter 17.7±10.3 mm, LV posterior wall diameter 16.1±7.7 mm, LA volume index 21.9±13 mL/m2. Global longitudinal strain was reduced with a mean of −12.1±4.9% with an observed regional strain gradient: apex (−16.6±6.6%), mid (−10.9±4.7%) and basal (−9.2±4.5%). Bull's eye plot patterns reflected an apical sparing pattern that was similar to that described in cardiac amyloidosis.

Conclusion

In this DD cohort, we describe for the first time a strain pattern characterized by reduction in global longitudinal strain with apical sparing, which was originally pathognomonic for cardiac amyloidosis. This strain pattern in conjunction with a paradoxically normal LA volume may discriminate patients with DD from other hypertrophic conditions.

Funding Acknowledgement

Type of funding source: None
Effect of tolvaptan on long-term prognosis in Japanese patients with heart failure: a systematic review and meta-analysis
Authors: Nakao Y , Saito M , Yamaguchi O
Published: November 2020

Background

Tolvaptan (TLV), a vasopressin antagonist, can promote water diuresis and overcome various disadvantages associated with conventional diuretics by ameliorating congestive symptoms and improving hyponatremia while maintaining haemodynamics and renal function. Large-scale clinical trials conducted primarily in Western countries (e.g. EVEREST trial) failed to demonstrate the beneficial effect of TLV on prognosis in patients with heart failure (HF). However, even after these clinical trials, studies on the use of TLV add-on therapy and resultant prognosis have been reported in Asian countries. Racial differences can greatly affect drug efficacy and dosing.

Purpose

We sought to investigate the long-term prognostic effect of TLV add-on therapy in Asian patients with HF.

Methods

We searched MEDLINE, Scopus, Cochrane Central, and Google Scholar for articles published till 31 December 2019. Randomized controlled trials (RCTs) and matched case-control studies that had a follow-up period of at least 6 months and that compared TLV add-on therapy and conventional therapy (control group) in Asian patients with acute decompensated HF were included. Primary and secondary outcomes analysed were all-cause mortality and HF readmission, respectively. Pooled analysis was performed using univariate effect size with random effect models. Meta-regression was performed to assess the impact of potential covariates.

Results

Nine articles that enrolled 1010 patients (the range of patients in the enrolled studies: 58–217) were included in the systematic review. All studies were performed in Japan. The weighted mean follow-up period was 15 months. The weighted mean of sodium level and ejection fraction was 139 mEq/L and 47%, respectively. TLV dose at discharge was available only in five articles, and its weighted mean value was 8.8 mg/day. In the pooled analysis, TLV add-on therapy did not improve the incidence of all-cause mortality (OR: 1.02, 95% CI: 0.69–1.52, p=0.92, I2=23) and HF readmission (OR: 0.73, 95% CI: 0.24–2.22, p=0.58, I2=89) (Figure). Furthermore, the effect of TLV add-on therapy on all-cause mortality was significantly moderated by furosemide dose at discharge in the control group (p=0.03).

Conclusions

Similar to findings of previous RCTs completed in Western countries, we found that TLV add-on therapy did not improve long-term mortality and HF readmission in Japanese patients with HF; however, mostly small-scale studies were included in our review. TLV add-on therapy might contribute to the improvement in prognosis in HF patients taking large doses of furosemide.

Forest plot of tolvaptan's effect

Funding Acknowledgement

Type of funding source: Private hospital(s). Main funding source(s): Kitaishikai
Gender differences in heart failure: results from disease-management-programs
Authors: Macare C , Groos S , Kretschmann J , Weber A , Hagen B
Published: November 2020

Introduction

Among cardiovascular conditions, heart failure shows the highest rate of mortality. Despite increased awareness, striking differences in prognosis between men and women with HF still exist in ambulatory health care. In Germany, disease-management-programs (DMP) recognized this need and launched a structured treatment program especially for HF. Indicators assessing successful prevention and quality of care within DMP include among others, referral and prescription rates of prognosis-relevant medications (beta-blockers, AC-I, AT-1-antagonists).

Aim

To evaluate gender differences in heart failure therapy in the State of North-Rhine Westfalia, Germany.

Methods

Cross sectional analysis of the 2018 cohort (n=84.398, mean age 79±10.2 yrs., male 61.5%). Logistic regression analyses were run on referrals and prescription of beta-blockers, ACE-I and AT-1-antagonists (all, yes/no). Models tested for gender effects and included known covariates e.g. age and duration of participation (in yrs.) and comorbidities (diabetes, lipid disorder, hypertension, smoking, all yes/no).

Results

Logistic regression models indicated that gender significantly affected referral rates, OR 1.15, CI-95% 1.09–1.20 and OR 1.15, CI-95% 1.09–1.20, for referrals to hospitals and other physicians. Men received higher rates of referrals to other physicians and other institutions (26.5 vs. 14.2%) and (6.4 vs. 3.5%) than women. Prescription rates were also significantly associated with gender: OR 1.23, CI-95% 1.19–1.27, OR 1.36, CI-95% 1.29–1.43, and OR 0.79, CI-95% 0.72–0.87, for beta-blockers, ACE-I and AT-1-antagonists, respectively. Men received beta-blocker and ACE-I more often (33.8 vs. 4.4% and 28.6 and 8.1%); women had higher rates of AT-1- antagonist prescription (1.2 vs. 5.5%).

Conclusion

Although, as previously shown work indicated, differences decrease over time, marked gender differences in referral and prescription rates in heart failure still exist in ambulatory health care settings. These results indicate that secondary prevention in women with HF needs to improve.

Funding Acknowledgement

Type of funding source: None
Technology-supported home monitoring in heart failure patients
Authors: Rahimi K , Nazarzadeh M , Pinho-Gomes A.C , Woodward M , Salimi-Khorshidi G.H , Ohkuma T , Fitzpatrick R , Tarassenko L , Denis M , Cleland J
Published: November 2020

Background

Digital health promises to enhance the prevailing episodic models of chronic heart failure (HF) care.

Purpose

We aimed to test the hypothesis that digital home monitoring with centralised specialist support for remote management of HF and major vascular comorbidities is more effective in optimising medical therapy and improving patients' quality of life than digital home monitoring alone.

Methods and results

In a two-armed partially blinded parallel randomised controlled trial, seven sites in the United Kingdom recruited a total of 202 adults with HF (71.3 years SD 11.1; mean left ventricular ejection fraction 32.9% SD 15.4). Participants were selected for being at high risk of adverse outcomes or high potential to benefit from remote management. Participants in both study arms were given an internet-enabled tablet computer, Bluetooth-enabled blood pressure monitor and weighing scales for health monitoring. After a run-in period, participants randomized to intervention received additional regular feedback to support self-management and their primary care doctors received instructions on blood investigations and pharmacological treatment. The primary outcome was the use of recommended medical therapy, for chronic HF and major comorbidities, measured as a composite opportunity score. Co-primary outcome was change in physical score of Minnesota Living with Heart failure questionnaire.

At the end of the trial, the weighted opportunity score was 0.54 (CI 95% 0.46, 0.62) in the control group and 0.61 (CI 95% 0.52, 0.70) in the intervention arm (p for mean difference=0.25). Physical well-being of participants did not differ significantly between the groups either (p=0.55).

Conclusions

Central provision of tailored specialist management in a multimorbid HF population was feasible. However, there was no strong evidence for improvement in use of evidence-based therapies nor health-related quality of life.

Figure 1

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): National Institute for Health Research (NIHR) Health Services Research and Delivery; NIHR Career Development Fellowship
Dapagliflozin in a real-world population with chronic heart failure: how many would be eligible?
Authors: Maltes S.F.C , Rocha B.L , Cunha G.L , Presume J.P , Campos L , Henriques C , Rodrigues C.A.P.F , Araujo I , Fonseca M.C
Published: November 2020

Background

In patients with heart failure (HF) and reduced left ventricle ejection fraction (LVEF), the sodium-glucose cotransporter inhibitor (iSGLT2) dapagliflozin has recently been shown to reduce the risk of worsening heart failure or death from cardiovascular causes in the DAPA-HF trial. Results of iSGLT2 in HF with preserved LVEF are awaited. Our goal was to investigate how many patients in a real-world setting would be eligible for dapagliflozin according to the DAPA-HF criteria.

Methods

This is a single-center retrospective study enrolling consecutive patients followed in an HF Clinic from 2013 to 2019. The key DAPA-HF inclusion criteria [i.e., Left Ventricular Ejection Fraction (LVEF) <40% and NT-proBNP >600pg/mL (or >900pg/ml if AF)] and exclusion criteria [estimated glomerular filtration rate (eGFR) <30ml/kg/1.73m2, systolic blood pressure (SBP) <95mmHg] were considered.

Results

Overall, 479 patients (mean age 75.7±12.8 years; 50.4% male; 78.8% with hypertension; 45.0% with an eGFR <60ml/min/1.73m2; 36.5% with type 2 diabetes mellitus; 33.5% ischaemic HF) were assessed. Of these, 155 (33.2%) patients had LVEF <40%. Patients had a mean SBP of 131±28 mmHg, a median eGFR of 48 (IQR 33–65) ml/min/m2 and a NT-proBNP of 2183 (IQR 1010–5310) pg/mL Overall, according to the DAPA-HF trial key criteria, 88 patients (18.3%) would be eligible for dapagliflozin. The remainder would be excluded due to a LVEF>40% (67.5%), eGFR <30 ml/min/1.73m2 (19.4%), NT-proBNP <600 pg/mL (or <900 pg/mL if AF) (16.7%) and/or SBP <90mmHg (2.1%) (figure 1). If we limit the analysis to those with a LVEF <40%, 56.7% would be eligible for dapagliflozin. The remainder would be excluded due to a eGFR <30ml/kg/1.73m2 (20%), NT-proBNP <600 pg/mL (or <900 pg/mL if AF) (16.1%) and/or SBP <90mmHg (8.4%) (figure 1).

Conclusion

Roughly one in every five patients in our real-world HF cohort would be eligible to start dapagliflozin according to the key criteria of the DAPA-HF trial. The main reason for non-eligibility was a LVEF >40%. These findings highlight the urgent need for disease-modifying drugs in mid-range and preserved LVEF. The results of ongoing iSGLT2 trials in these LVEF subgroups are eagerly awaited.

Funding Acknowledgement

Type of funding source: None
Increased oxygen uptake and utilization in the peripheral muscles, rather than cardiac function reserve, may be determinants of increased peak VO2 by cardiac rehabilitation in heart failure
Authors: Hasegawa H , Kono T , Sakane K , Matsuoka T , Soyama A , Murakami S , Hoshiga M
Published: November 2020

Background

Peak oxygen consumption (peak VO2) is a major prognostic parameter in heart failure (HF). Previous studies have shown a relationship between peak VO2 and impaired oxygen uptake and utilization in the peripheral muscles. The purpose of this study was to clarify the determinant of increased peak VO2 by cardiac rehabilitation (CR) in patients with HF.

Methods

We performed echocardiography during upright ramp bicycle cardiopulmonary exercise test in 30 HF patients (61±1 years of age, 80% male) before and 6 months after CR. HR reserve was determined as the change in HR from rest to peak exercise, expressed as a percentage of the predicted maximal HR reserve. Elastance index (EAI) and LV end-systolic elastance index (ELVI) were derived as the ratio of end-systolic pressure to stroke volume index and end-systolic volume index, respectively. End-systolic pressure was estimated from the equation 0.9 × brachial systolic blood pressure. Ventriculo-arterial coupling (VAC) was calculated as the quotient of EAI and ELVI. The ratio of LDEDVI to E/e' mean was used to evaluate LV diastolic compliance. Systemic vascular resistance index was calculated as mean arterial pressure divided by echocardiography calculated cardiac index and multiplied by 80. The arterial venous oxygen content difference (C (A-V) O2 gradient) was calculated by using the Fick equation as: VO2/echocardiography calculated cardiac output.

Results

Peak VO2 and C (A-V) O2 gradient were increased by CR. However, heart rate reserve, systolic reserve, VAC, diastolic reserve and vasodilation reserve were unchanged by CR (Table 1).

Conclusions

Increased oxygen uptake and utilization in the peripheral muscles, rather than cardiac function reserve, may be determinants of increased peak VO2 by CR in HF.

Table 1

Funding Acknowledgement

Type of funding source: None
Left ventricular volumes at baseline and outcome in heart failure patients undergoing cardiac resynchronization therapy
Authors: Kostyukevich M , Van Der Bijl P , Mertens B , Vo M , Marsan N.A , Delgado V , Bax J.J
Published: November 2020

Background

Studies evaluating the relationship between baseline left ventricular (LV) volumes and long-term prognosis in heart failure (HF) patients undergoing cardiac resynchronization therapy (CRT) are lacking.

Purpose

To evaluate the association of LV end-systolic and end-diastolic volumes (ESV and EDV) with long-term prognosis in patients with HF treated with CRT.

Methods

Patients from an ongoing institutional HF registry who received CRT according to contemporary guidelines were included. All patients underwent standard transthoracic echocardiography. LV volumes were measured using the biplane method during off-line analysis. Primary end-point included all-cause mortality, implantation of left ventricular assist device or heart transplantation, which were assessed according to the national death registry and case records.

Results

In total, 1165 patients with feasible LV volume assessment were included (mean age 67±10 years; 74.8% males; 55.3% with non-ischemic aetiology of HF). After a median follow-up of 75 (40; 123) months, the primary end-point occurred in 708 (60.8%) patients. Median baseline LV ESV was 151 (108; 198) ml and EDV was 202 (156; 258) ml. All patients were divided into quartiles according to the baseline EDV and ESV: those with larger volumes were significantly younger, more frequently male and had longer QRS durations (p<0.001). Heart failure aetiology, glomerular filtration rate, quality of life and 6-minute walking test distance did not differ significantly between the groups (p>0.05). To investigate the association between long-term prognosis and baseline LV volumes (EDV and ESV), a Cox proportional hazards model was constructed with variables known to influence the mortality of HF patients (age, gender, aetiology, QRS duration, and estimated glomerular filtration rate). When separately included in a multivariate analysis, baseline LV ESV and LV EDV were both independently associated with the primary end-point (p<0.001). To demonstrate hazard change across the range of LV ESV and EDV as continuous variables, an adjusted (for covariates influencing HF mortality) spline curve was drawn, showing an increased mortality risk when the baseline LV ESV and EDV are larger than 100 ml and 200 ml, respectively (Figure).

Conclusion

LV volumes before CRT implantation are independently associated with prognosis during long-term follow-up. Our findings indicate the importance of taking baseline LV remodelling into consideration to identify patients at high mortality risk after CRT implantation.

Funding Acknowledgement

Type of funding source: Public grant(s) – EU funding. Main funding source(s): The author acknowledges funding received from the European Society of Cardiology in form of an ESC Training Grant
Partial normalisation of cardiac mechanics with active CRT in patients with chronic failure: a novel application of 3.0T CMR
Authors: Koshy A , Gierula J , Paton M , Swoboda P , Toms A.G , Saunderson C , Shelley D , Broadbent D , Plein S , Kearney M.T , Witte K.K
Published: November 2020

Introduction

Cardiac resynchronisation therapy (CRT) is a routine treatment for chronic heart failure (CHF) with reduced ejection fraction and conduction delay to improve prognosis. Cardiac mechanics in patients with CHF are believed to be altered from controls based on invasive and echocardiographic based data. Technological advancements in cardiac magnetic resonance (CMR) and devices enable investigation of the cardiac response to CRT over a range of heart rates.

Methods

Patients with a CRT-D device were enrolled from heart failure clinics at Leeds General Infirmary, UK. After a MRI safety assessment, a baseline device check was conducted by a cardiac physiologist. Left ventricular (LV) volumes and systolic BP were measured at baseline and heart rates of 75, 90, 100, 115, 125, and 140 (randomised order) with CRT active and intrinsic conduction. All scans were conducted using a 3.0 T Siemens Prisma MRI scanner. Analysis of the scans used commercially available software. LV contractility was derived as a ratio of the LV end systolic volume and systolic BP. A post scan device interrogation was conducted to assess for scanning safety. Control participants with a 3.0T MR-conditional dual chamber pacemakers completed a similar protocol.

Results

Scanning was conducted in 17 CRT patients and 13 controls with a pre and post device and lead interrogation. No patient experienced symptoms related to scanning or device failure. The mean LV ejection fraction at baseline in the CRT cohort was 33.7±12.9%. Left ventricular ejection fraction fell across both cohorts as paced heart rate increased with reduced deterioration in control patients and those with CRT active. Peak LV cardiac output was significantly higher during active CRT (p<0.05). LV contractility was relatively static with CRT disabled (r2=0.13, p=0.38) and improved with CRT active (r2=0.91, p=0.01) and in controls (r2=0.74, p=0.01). Peak LV strain occurred at 100bpm during active CRT and in control patients whereas CRT disabled resulted in earlier deterioration.

Conclusion

We have demonstrated improvements in cardiac output and contractility consequent to active CRT using 3.0T CMR and subsequently validated via strain analysis. CRT appears to partially normalise cardiac mechanics across the range of heart rates studied. Further work is required to explore this phenomenon on a cellular or metabolic level.

Funding Acknowledgement

Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): AK is supported by an unconditional grant provided by Medtronic
Prognostic value and usefulness of Pulmonary Artery Pulsatility index (PAPi) in evaluation of heart transplant candidates
Authors: Bellettini M , Pidello S , Gallone G , Frea S , Masetti M , Sabatino M , Boschi S , Giustetto C , Boffini M , Rinaldi M , Potena L , De Ferrari G.M
Published: November 2020

Background

Heart transplantation (HTx) is considered the best available treatment for patients with end stage heart failure. Candidate evaluation with right heart catheterization (RHC) is fundamental in order to exclude pulmonary hypertension with irreversible high pulmonary vascular resistance (PVR), which is associated with elevated post-HTx mortality. PVR, rather than directly measured, is derived by cardiac output and pulmonary artery pressures, which are strictly dependent on right ventricular (RV) function. The pulmonary artery pulsatility index (PAPi) is a hemodynamic parameter integrating the information of RV function and of pulmonary circulation, which could be useful in pre-HTx evaluation.

Purpose

We designed this study to evaluate the potential predictive influence of pre-HTx PAPi on post-HTx survival and to assess whether this index could add useful information in the pre-HTx evaluation of patients with advanced heart failure.

Methods

Consecutive adult HTx recipient at two medium-large tranplant centers between 2000 and 2017 with available data on pre-HTx RHC were retrospectively included. PAPi was calculated as the ratio of pulmonary artery pulse pressure to right atrial pressure. PAPi values in the lowest quartile were defined as reduced (PAPi<1.67). The primary endpoint was all-cause mortality at 1-year post-HTx. The association of reduced PAPi with the primary endpoint was evaluated. Cox regression was used to adjust for clinical and hemodynamic variables. Analyses stratified by PVR status (≥3 WU vs. <3 WU) were also performed.

Results

Among 655 HTx recipients (female 20,8%, age 53±11 years), median pre-HTx PAPi was 3.0 (interquartile range 1.67–5.32). Patients in the lowest versus the remaining PAPi quartiles had significantly reduced 1-year survival (78.0% vs 87.2%, p=0.006), also after adjusting for age, estimated glomerular filtration rate, total bilirubin, high PVR and urgent transplantation (adj-hazard ratio: 0.64; 95% confidence interval 0.51–0.82). When stratifying patients by estimated PVR status, reduced PAPi was associated with worse 1-year survival among patients with normal PVR (78.3% vs. 88.3% p=0.011), but not in those with increased PVR (78.0% vs. 82.6%, p=0.36) (Figure 1).

Conclusions

Pre-HTx PAPi, integrating information of RV function and pulmonary circulation, provides incremental prognostic value over traditional clinical and hemodynamic parameters among HTx recipient. The prognostic value appears important among patients with normal estimated PVR, possibly due to an underestimation of PVR in patients with impaired RV function. The integration of PAPi in the pre-HTx evaluation may lead to better patient selection and post-HTx survival.

Figure 1. 1 year survival stratified by PVR status

Funding Acknowledgement

Type of funding source: None