bluuebunny/crossref_metadata_2025 huggingface dataset:
Early detection of skin and cardiac amyloid deposits among asymptomatic carriers of hereditary pathogenic transthyretin mutation with normal electroneuromyography
Authors: Slama M , Eliahou L , Piekarski E , Rouzet F , Beauvais D , Beaudonnet G , Labeyrie C , Cauquil C , Adams D , Algalarrondo V
Published: November 2020

Introduction

During the last decade, disease modifying therapies have been proposed for hereditary amyloidogenic transthyretin (ATTRv) amyloidosis. It is essential to screen for disease onset among asymptomatic mutation carriers in order to trigger effective therapy as early as possible. We describe clinical and paraclinical data from ATTRv asymptomatic carriers, as a baseline assessment to detect disease onset and progression.

Methods

We retrospectively collected data of asymptomatic ATTRv carriers with normal electroneuromyography (ENMG), between March 1st 2015 and January 31st 2019, including: demographics, symptoms, physical exam, ENMG (initial and follow-up obtained in 73 patients, 56.2%), neurovegetative tests, skin biopsy (amyloid deposition, denervation), and cardiac evaluation (multimodal imaging, cardiac denervation and arrhythmias).

Results

We included 130 patients, aged 43.6 years (± 13.5), selected in family of a proband with an age of onset of 52.7 years (±15.7), 40.8% male, carrying 20 different variants of the TTR gene, including 63.8% Val30Met. Amyloid deposits on skin biopsy and/or cardiac fixation on bone scintigraphy, characteristic of amyloid infiltration, were found in 22/130 patients (16%). Skin biopsy was positive in 11 patients, and cardiac fixation on bone scintigraphy was positive in 15 patients. Amyloid infiltration was statistically associated with age (p=0.024), age difference from index case (p<0.001), electrophysiological carpal tunnel syndrome (p=0.022), interventricular septum thickness >12 mm (p<0.001), contrast enhancement in cardiac MRI (p=0.002), cardiac denervation using MIBG scintigraphy C/M ratio <1.85 (p=0.044). Multivariate analysis showed that age difference with index case and interventricular septum thickness were predictors for amyloid infiltration (OR=1.11, IC [1,04–1,19] and OR=1,76, IC [1,19–2,60]). Subgroup analysis showed electroneuromyography alteration during follow up in 11 patients (delay 26.9 months, range 10–49) with statistic association with amyloid deposits (55.6 versus 7.1% when ENMG was unchanged, p<0.001) and interventricular septum thickness (p<0.010).

Conclusion

Clinical and paraclinical assessment of asymptomatic carriers of ATTRv mutations shows that skin or cardiac amyloid infiltration may precede ENMG abnormalities in 16% of patients. This may trigger specific therapies in borderline cases. Age close to age of onset among index case and septum interventricular thickness appear as risk factors for developing electroneuromyogram alteration.

Funding Acknowledgement

Type of funding source: None
Shear wave elastography: can we estimate filing pressures?
Authors: Werner A.E , Bezy S , Orlowska M , Kubiak G , Desmet W , Delcroix M , Van Cleemput J , Ince H , D'hooge J , Voigt J.U
Published: November 2020

Background

The assessment of the left ventricular diastolic function is complex, as there is no single non-invasive parameter that provides a direct measurement of myocardial relaxation, myocardial compliance, or – as a surrogate - LV filling pressure. Estimation of diastolic function is therefore based on the combination of many parameters.

Shear wave (SW) elastography (SWE) is a novel method based on high frame rate echocardiography. SWs occur after mechanical excitation of the myocardium, e.g. after mitral valve closure (MVC), and their propagation velocity is directly related to myocardial stiffness (MS).

Purpose

The aim of this study was to investigate if velocities of natural shear waves are related to MS at end diastole (ED) and, thus, could be used to estimate left ventricular end-diastolic pressures (LVEDP) as marker of diastolic function.

Methods

So far, we have prospectively enrolled 30 patients with a wide range of diastolic function, scheduled for heart catheterization so that LV filling pressures could be invasively measured. Patients with severe aortic stenosis, mitral stenosis of any degree and a more than moderate mitral regurgitation, as well as regional myocardial abnormalities or dysfunction in the anteroseptal wall were excluded.

Echocardiography was performed immediately after catheterization. SW elastography in parasternal long axis views of the left ventricle (LV) was performed using an experimental scanner (HD-PULSE) at 1100±250 frames per second. Tissue acceleration maps were extracted from an anatomical M-mode line along the midline of the LV septum. The SW propagation velocity at MVC was measured as the slope on the M-mode acceleration map (Figure A).

Results

SW velocities at ED correlated very well with the invasively measured LVEDP (r=0.815, p<0.001, Figure B). In comparison, classical echocardiographic parameters correlated only weakly or not with LVEDP (E/A: r=0.528, p=0.036, Figure C; E/e': r=−0.169, p=0,531, Figure D) with LVEDP.

For the detection of an elevated LVEDP above 15 mmHg, a cut off value for the SW velocity at MVC of 3.75 m/s was associated with a Sensitivity of 92.9% and a Specificity of 83.3%.

Conclusions

End-diastolic shear wave velocities, measured by high frame rate shear wave elastography, showed a significant correlation with the end-diastolic filling pressure of the LV indicating a potential clinical value of the new method for a non-invasive and direct assessment of LV diastolic function. More patients will be included to confirm these findings.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): Fonds Wetenschappelijk Onderzoek Flanderen (Research Foundation Flanders)
Hybrid transcatheter and minimally invasive left ventricular reconstruction for the treatment of ischemic cardiomyopathy: mid-term results
Authors: Klein P , Van Kuijk J.P , Swaans M.J
Published: November 2020

Background

Remodelling of the left ventricle (LV) after anterior myocardial infarction can result in a pathological increase in LV volume and reduction in LV ejection fraction (EF).

Purpose

We describe the mid-term results of a novel hybrid transcatheter and minimally invasive surgical technique to reconstruct the remodelled LV by plication and exclusion of the scar and reduction of the excess volume, resulting in decreased wall stress and increased EF.

Methods

Patients were considered eligible for the procedure when the presented with symptomatic heart failure (NYHA-class II or more) and ischemic cardiomyopathy (EF<40%) after anterior myocardial infarction. All patients had a dilated LV with either an a- or dyskinetic scar in the anteroseptal wall and/or apex of >50% transmurality. An hybrid transcatheter and minimally technique was used that relies on deploying a series of paired internal and external micro-anchors to plicate fibrous scar of infarcted anterior wall myocardial tissue to reconstruct the LV.

Results

Between October 2016 and January 2020 24 patients (21 males, 3 females; mean age 61±13 years) were operated in a single Dutch centre. Procedural success was 100%. On average 2.3±0.9 anchor-pairs were used to reconstruct the LV. Comparing echocardiographic data pre- and directly postoperatively, LVEF increased from 34±9% to 44±11% (change +34%, P<0.0001) and LV-volumes decreased: LVESV 113 ml ± 54 ml to 68±41 ml (change −39%, P<0.0001) and LVEDV 166 ml ± 75 ml to 116±57 ml (change −30%, P<0.0001). One patient was converted peroperatively to full sternotomy, ECC and cardioplegic arrest because of partial dislodgement of an apical mural thrombus. After removal of the thrombus, the LV was reconstructed with 2 anchor-pairs. One patient underwent a postoperative revision because of RV restriction. After removal of 1 “RV-LV” anchor-pair, the patient made a full recovery. One patient underwent an uncomplicated minimally invasive tricuspid valve replacement because of a lesion to the tricuspid valve during the procedure. Hospital mortality was 0%. Median duration of ICU–stay was 2 days (IQR 1–46 days) and median length of hospital stay was 7 days (IQR 5–57 days). Survival at 36 months was 88%. At latest follow-up, 86% of surviving patients were in NYHA-class I-II compared to 21% preoperatively.

Conclusions

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

Revivent TC technique

Funding Acknowledgement

Type of funding source: None
Restricted mean survival time analysis in heart failure clinical trials
Authors: Perego C , Sbolli M , Specchia C , Oriecuia C , Peveri G , Fiuzat M , O'Connor C.M , Metra M , Wei L.J , Psotka M.A
Published: November 2020

Background

The hazard ratio (HR) is the most common measure used to quantify treatment effects in heart failure (HF) clinical trials. However, the HR is only valid when the proportional hazards assumption is plausible, and the HR may be difficult to interpret for clinicians and laypeople. Restricted mean survival time (RMST), defined as the average time-to-event before a specific timepoint, is an intuitive summary of group-wise survival. The difference between two RMSTs measures treatment effects without model assumptions and may communicate more clinically interpretable results.

Purpose

To evaluate statistical and clinical properties of RMST-based statistics applied to clinical trial data for treatments of HF with reduced ejection fraction.

Methods

Patient time-to-event data was reconstructed from the published primary and secondary outcome Kaplan-Meier curves from landmark HF clinical trials. We estimated the RMST-differences between treatment groups as a measure of treatment effect with published data, and compared statistical testing results and effect size values to HR analysis results.

Results

We analyzed 7 HF clinical trials, including data from a total of 27,845 patients (Table 1). RMST should be interpreted as the average number of months that the outcome is avoided over the study period. As examples: On average, treatment with enalapril for 12 months extended each patient's life by 2.2 months compared to placebo, and treatment with spironolactone for 34 months extended each patient's life by 2.2 months compared to placebo.

Conclusions

RMST-difference test statistic has identical statistical conclusions as HRs but provided an intuitive estimate of each treatment effect. RMST-based data can potentially be used to better communicate treatment effects to patients, to assist in patient-preference discussions and shared decision-making

Funding Acknowledgement

Type of funding source: None
Impacts of beta-blockers on lone term clinical outcomes in the treatment of hospitalized heart failure patients with an ejection fraction greater than 40%
Authors: Xing F , Li J.I.N.G
Published: November 2020

Background

Heart failure (HF) is a leading cause of mortality and morbidity. Beta-blocker is recommended in HF with reduced ejection fraction (EF) in order to improve clinical outcomes. While the effects of beta-blockers in HF who have an EF greater than 40% are uncertain and controversial yet.

Purpose

To Investigate the associations between beta-blockers and clinical outcomes, overall and in strata of patients with an EF of between 40% and 49% or greater than 50%.

Methods

The study cohort included 2642 HF patients hospitalized primarily for HF who had an EF greater than 40%, which was from the China PEACE Prospective Heart Failure Study. We had two Clinical outcomes: 1-year all-cause mortality and 1-year hospitalization for HF after discharge. The associations between beta-blockers and clinical outcomes were assessed using Cox proportional hazard regression models, while stratified according to EF.

Results

The median age was 70 (IQR: 61, 77) years, 44.8% were women, EF was (median (IQR)) 54% (46%, 62%), and 55.5% received beta-blockers at discharge. All-cause mortality and hospitalizations for HF occurred in 341 (12.91%) and 636 (24.07%) patients respectively. In the Cox proportional hazard analysis, a significant interaction between EF and beta-blocker use for mortality was observed (P=0.01 for interaction). Stratified analysis showed beta-blockers reduced risks of mortality in patients who had an EF between 40% and 49% ((hazard ratios (HR): 0.501, 95% confidence interval (CI): 0.340- 0.738, p<0.001), but not among patients with an EF of 50% or greater (HR: 0.824, 95% CI: 0.600- 1.133, p=0.233). Use of β-blockers was not associated with reduced hospitalizations in patients with EF of between 40% and 49% and greater than 50% (HR: 1.016, 95% CI: 0.712- 1.450, p=0.931; HR: 0.905, 95% CI: 0.703- 1.166, p=0.439, respectively).

Conclusion

For patients with an EF between 40% and 49%, β-blocker use was associated with a reduced risk of all-cause mortality but not HF hospitalizations. For patients with an EF of 50% or greater, there was no such association.

Funding Acknowledgement

Type of funding source: Other. Main funding source(s): This work was supported by the National Key Research and Development Program (2017YFC1310803) from the Ministry of Science and Technology of China; the CAMS Innovation Fund for Medical Science (2017-I2M-B&R-02); the 111 Project from the Ministry of Education of China (B16005).
Aerobic physical training improves skeletal muscle metabolism in heart failure patients
Authors: Galenko V , Lelyavina T.A , Bortsova M.A , Sitnikova M.Y
Published: November 2020

Purpose

To evaluate the efficiency of aerobic physical rehabilitation (PR), selected on the basis of lactate threshold achievement during cardiopulmonary exercising test (CPET), in heart failure patients with normal body mass index (BMI); to study metabolism changes in skeletal muscle fibers (MF) after PR.

Methods

100 patients; heart failure with reduced ejection fraction (HFrEF), NYHA III, mean age 52±5.2 years, ejection fraction (EF) 27.3±4.2%, BMI 23.5±2.8 kg/m2. The original estimated CPET, exercise tolerance (ET), quality of life (QOL) and echocardiography (EchoCG). Effects of physical rehabilitation were estimated on the basis of peak oxygen uptake (VO2peak), EF, QOL and ET dynamics after 6 months of training. Shin muscle biopsy was performed at baseline and after 3–6 months of training programm. In muscle samples activity of lactate dehydrogenase (LDH), succinate dehydrogenase (SDG) and alkaline phosphatase (AP) was evaluated with plag-method. Data were statistically processed using software package Statistika, 9.0.

Results

After 6 months of physical training ET increased by 9.7±0.5 points and QOL improved by 24.8±3.5 points (p1,2 <0.05), EF increased by 10.5±2.3% and VO2 peak increased by 5.2±0.5 ml/min/kg (p3,4 <0.05). After 3–6 months of training AP activity increased by 24.2% (p<0.05). LDH activity in glycolytic MF decreased by 24.4%, in oxidative MF it decreased by only 6.0% (p1 <0.05, p2>0.05). SDG activity in glycolytic MF increased by 30% and in oxidative – by 20% (p1,2 <0.05). There was a positive relation between SDG activity and VO2 peak dynamics (r=0.6, p=0.04), increase in CPET parameters was associated with AP activity (r=0.5, p=0.05).

Conclusion

Aerobic physical training in stable HFrEF patients with normal BMI was effective in improving values of EF, VO2 peak, QOL and ET;

Participating in the rehabilitation program decreased LDH activity in both oxidative and glycolytic muscle fibers; it also significantly increased AP activity and SDG activity in both oxidative and glycolytic MF. This may indicate a decrease in glycolytic metabolism activity and aerobic metabolism activation;

The relation between the increase in exercise tolerance and endothelium condition marker (AP activity in muscle tissue), SDG activity and VO2 peak dynamics has been revealed.

Funding Acknowledgement

Type of funding source: Public grant(s) – EU funding. Main funding source(s): Project was partially funded by the Russian Science Foundation grant 16-15-1017
The comparison between two different exercise training programs on the mobilization of endothelial progenitor cells in patients with chronic heart failure
Authors: Kourek C , Psarra K , Alshamari M , Delis D , Mitsiou G , Ntalianis A , Panagopoulou N , Papadopoulos C , Nanas S , Karatzanos E
Published: November 2020

Background

Vascular endothelial dysfunction is an underlying pathophysiological feature of chronic heart failure (CHF). Endothelial progenitor cells (EPCs) are being used as an index of vascular endothelial function. Cardiac rehabilitation (CR) programs have been shown to stimulate the mobilization of EPCs in CHF patients. However, the effect of different exercise training programs on the EPCs in CHF patients has not been investigated.

Purpose

The purpose of the study was to assess the effect of 2 different exercise training programs on the mobilization of EPCs in patients with CHF and investigate if there were differences between them.

Methods

Forty-four consecutive patients (35 males) with stable CHF [mean±SD, Age (years): 56±10, EF (%): 33±8, Peak VO2 (ml/kg/min): 18.4±4.4] enrolled a 36-session CR program and they were randomized in one exercise training protocol; either high-intensity interval training (HIIT) or HIIT combined with muscle strength (COM). Venous blood was drawn at rest before and after the CR program. Five circulating endothelial populations were identified and quantified by flow cytometry (Table 1). EPCs values are expressed as cells/million enucleated cells in medians (25th-75th percentiles).

Results

In both HIIT and COM groups, the mobilization of all circulating endothelial populations increased after the CR program (p<0.05, Table 1). However, there was no difference in the mobilization of EPCs between HIIT and COM groups (p>0.05, Table 1).

Conclusion

A 36-session cardiac rehabilitation program increases the mobilization of endothelial progenitor cells in patients with chronic heart failure. High-intensity interval exercise training and HIIT combined with muscle strength have similar beneficial effect on endothelial progenitor cells, and therefore on vascular endothelial function.

Funding Acknowledgement

Type of funding source: Public grant(s) – EU funding. Main funding source(s): Co-financed by Greece and the European Union (European Social Fund- ESF) through the Operational Programme “Human Resources Development, Education and Lifelong Learning” in the context of the project
Regional muscle-adipose distribution is different in patients with heart failure with preserved or reduced ejection fraction
Authors: Ishikawa H , Izumiya Y , Shibata A , Yoshida T , Hayashi H , Ichikawa Y , Yamaguchi Y , Kitada R , Ehara S , Yoshiyama M
Published: November 2020

Background

Epicardial adipose tissue (EAT) has been recognized to contribute inflammatory activity and atherosclerosis. On the other hand, it has been reported that the volume of EAT is lower in non-ischemic heart failure (HF) patients than healthy individuals. However, the difference in regional muscle-adipose distribution including EAT between HF with preserved ejection fraction (HFpEF) and HF reduced ejection fraction (HFrEF) has not been investigated. In addition, we investigated whether distribution of body composition contributed to exercise capacity.

Methods

The study included 105 non-ischemic HF patients diagnosed by cardiac catheterization between September 2017 and November 2019. Epicardial, abdominal and thigh muscle and adipose tissue volume were measured by computed tomography (CT), and exercise tolerance was evaluated by symptom-limited cardiopulmonary exercise test.

Results

Patients were divided into 2 groups according to the left ventricular ejection fraction, ≥40% as HFpEF (n=28) or <40% as HFrEF (n=77). There was no significant difference comorbidity, including hypertension, dyslipidemia, chronic kidney disease, and body mass index. Plasma B-type natriuretic peptide level was significantly higher in HFrEF than HFpEF group (146.2 vs 393.2 pg/ml, p<0.01), whereas, high-sensitive troponin T level was not different between two groups. Although there was no significant difference in BMI between two groups, the volume of EAT was significantly higher in HFpEF than HFrEF group (81.8 vs 136.4 ml, p=0.01). On the other hand, HFpEF had more thigh adipose tissue compared with HFrEF group (54.6 vs 42.1 ml, p=0.03). There were negative correlations between EAT volume and parameters of exercise capacity such as anaerobic threshold (r=−0.42, p<0.01) and peak VO2 (r=−0.32, p<0.01). Muscle volume itself does not corelate with these parameters.

Conclusion

In patient with nonischemic HF, the pattern of regional adipose distribution may have important role in pathologically. HFpEF and HFrEF has different pattern despite similar body mass index. These differences may be related to impaired exercise tolerance in these 2 different types of HF.

Correlation between EAT and AT, peak VO2

Funding Acknowledgement

Type of funding source: None
Prognostic significance of 2019 Asian Working Group for Sarcopenia update on definition of sarcopenia
Authors: Saito K , Matsue Y , Kamiya K , Saito H , Ogasahara Y , Kitai T , Konishi M , Maekawa E , Iwata K , Jujo K , Wada H , Kasai T , Nagamatsu H , Momomura S , Kagiyama N
Published: November 2020

Background/Introduction

Sarcopenia plays a major role in the pathophysiology of frailty and is associated with worse outcome in the elderly population including patients with heart failure. A recent update of the most common definition of sarcopenia in Asia, Asian Working Group for Sarcopenia (AWGS2019), included significant changes in the diagnostic algorithm with newly dividing sarcopenia into severe and “non-severe” sarcopenia.

Purpose

The objective of this study was to evaluate the differences between AWGS2014 and AWGS2019 in patients with heart failure.

Methods

In the multicenter prospective FRAGILE-HF registry, which included elderly (≥65 years old) patients who were hospitalized with heart failure, we studied 865 patients (80±8 years old, 42% female). All-cause death in 1-year follow-up was tracked.

Results

Based on the original version of AWGS (AWGS2014), 183 patients (21%) were diagnosed with sarcopenia, which was associated with higher age, lower physical performance, less muscle mass, and greater heart failure risk (all p<0.001) as well as higher rate of all-cause death (HR 1.90, p=0.004 after adjustment by multivariable regression). Those patients with sarcopenia by AWGS2014 were reclassified mainly to severe sarcopenia (155, 84.7%) by AWGS2019, and 25 (13.7%) and 2 (1.1%) were classified into sarcopenia and non-sarcopenia. Meanwhile, 24 (3.5%) and 4 (0.6%) of patients without sarcopenia by AWGS2014 were reclassified into sarcopenia and severe sarcopenia, respectively. Although severe sarcopenia by AWGS2019 was associated with higher age, lower physical performance, less muscle mass, and greater heart failure risk (all p<0.001), patients with “non-severe” sarcopenia was rather younger (p<0.001) and had better physical performance (p=0.021) despite less muscle mass (p<0.001) than those without sarcopenia. Multivariate Cox analysis demonstrated severe sarcopenia by AWGS2019 was an independent prognostic factor (HR 1.77, p=0.014), but “non-severe” sarcopenia was not (HR 1.52, p=0.37). The prognosis of patients who were reclassified from non-sarcopenia to sarcopenia or severe sarcopenia were comparable to those remained non-sarcopenia. When added to other risk factors, the prognostic predictability of AWGS2019 was significantly lower than AWGS2014 (net reclassification improvement −0.26, p=0.025).

Conclusions

About a half of “non-severe” sarcopenia in AWGS2019 were patients without sarcopenia in AWGS2014. The prognosis of such patients who were newly diagnosed as sarcopenia was good, resulting in low overall prognostic predictability of AWGS2019. A further consideration for diagnostic algorithms of sarcopenia may be warranted in patients with heart failure.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): Japan Heart Foundation
Predictors of 5-year mortality in patients with congestive heart failure and implanted devices for cardiac resynchronization therapy
Authors: Soldatova A , Kuznetsov V.A , Dyachkov S.M
Published: November 2020

Cardiac resynchronization therapy (CRT) has a wide range of therapeutic benefits including reduction in hospitalizations and death in appropriately selected patients, while the appropriate selection remains the cornerstone of CRT. Apart from the current selection criteria, many additional factors may play an incremental role affecting cardiac prognosis and CRT efficacy.

Aim

To examine the ability of a multiparametric score to predict 5-year mortality in patients with congestive heart failure (HF) treated with CRT.

Methods

The study enrolled 218 HF patients (83% men, 17% women; mean age of 58.7±10.7 years) with left ventricular ejection fraction (LVEF) ≤35%, NYHA class II-IV. 130 patients (59.6%) had ischemic etiology of HF (84 with prior myocardial infarction), 88 patients (31.4%) – non-ischemic cardiomyopathy. 57.3% of patients had left bundle branch block (LBBB), mean QRS width was 150.5±38.4 ms.

Results

The mean follow-up period was 38.8±20.9 months. The 5-year survival was 69.3%. Points were calculated from 11 parameters identified as factors associated with all-cause mortality in multivariate analysis: gender (female – 0, male – 1); etiology of HF (non-ischemic – 0, ischemic – 1); history of myocardial infarction (no – 0, yes – 1); NYHA (II or III – 0, IV – 1); QRS (≥150 ms or ≤120 ms + 3 parameters of mechanical dyssynchrony – 0, 120–149 ms – 1); rhythm (sinus or radiofrequency ablation of atrial fibrillation (AF) – 0, AF – 1); LBBB (LBBB – 0, non-LBBB – 1); LVEF (>30% – 0, ≤30% – 1); frailty (not frail – 0, frail – 1); PR interval (<200 ms – 0; ≥200 ms – 1); NT-proBNP (median value) (<1788 pg/ml – 0, ≥1788 pg/ml – 1). To calculate the score, the sum of points was divided by the number of parameters. If less than 3 items were missing the denominator adjusted accordingly. The 5-year survival rate for patients with highest tertile score (>0.44; n=43) was 43.1%, for middle tertile (0.44≤ score ≥0.22; n=124) – 73.4% and 88.4% for lowest tertile (<0.22; n=51) (Log rank p<0.001).

Conclusions

Multiparametric score can be used to predict 5-year mortality in patients with CRT.

Survival curves in groups by tertiles

Funding Acknowledgement

Type of funding source: None
Improving quality of life post left ventricular assist device surgery with CardioMEMS hemodynamic guided management
Authors: Veenis J.F , Radhoe S.P , Brugts J.J
Published: November 2020

Background/Introduction

Left ventricular assist device (LVAD) surgery improves quality of life (QoL) in chronic heart failure patients. Hemodynamic optimization of the LVAD therapy can improve patient outcomes, and potentially further improve QoL in these patients.

Purpose

In this analysis, we assessed the improvement of the QoL post-LVAD surgery in patients with hemodynamic guided management by the CardioMEMS.

Methods

Ten patients suffering from chronic heart failure, who underwent (semi-)elective LVAD surgery and participated in the HEMO-VAD pilot study, were included in this analysis. All patients received a CardioMEMS sensor pre-LVAD surgery. The daily hemodynamic readings were used to guide patient management, pre- and post LVAD surgery. The aim was to normalize and keep the mean pulmonary artery pressure (mPAP) normalized (≤25 mmHg). For this analysis, patients were divided into those with a normal mPAP at all the scheduled follow-up moments at 3, 6, and 9 months post-LVAD surgery and those with an elevated mPAP during at least one of the follow-up moments. QoL was assessed by the EQ-5D-5L, KCCQ and PHQ-9 questionnaires at baseline (pre-LVAD surgery) and 3, 6 and 9 months post-LVAD surgery.

Results

The median age was 60 [52–63] years, and 70% of patients were men. In the hemodynamic normalized patients, QoL improved significantly between pre-LVAD surgery and the post-LVAD surgery follow-up moments, while no significant improvement was observed in the non-hemodynamic normalized patients. An increase of 37 points on the overall summary score of the KCCQ (p=0.046) was observed in the hemodynamic normalized patients, compared to a 22 points increase in the non-hemodynamic normalized patients (p=0.655), similar improvements were observed for the clinical summary score of the KCCQ, the visual analog scale of the EQ-5D and in the PHQ-9. Additionally, a trend towards a bigger improvement in the QoL was observed in the hemodynamic normalized patients, compared to the non-hemodynamic optimized patients (Figure).

Conclusion(s)

Successful hemodynamic management of LVAD patients, guided by CardioMEMS improves the QoL during the first year post-LVAD surgery. Patients who were hemodynamically normalized had a better QoL, and a bigger improvement in QoL from baseline, compared with non-hemodynamically optimized LVAD patients.

Figure 1. Absolute and paired change in A EQ-5D-5L index value; B EQ-5D-5L visual analog scale, C KCCQ clinical summary score, D KCCQ overall summary score, E PHQ-9 score from baseline to 9 months of follow-up according to hemodynamically optimized status

Funding Acknowledgement

Type of funding source: Public hospital(s). Main funding source(s): This work was supported by Abbott with an independent research grant, partially covering personnel costs. This study was investigator-initiated and was designed, conducted, interpreted and reported independently of the funder.
Multi-year improvement in autonomic tone, baroreceptor sensitivity, and cardiac electrical stability using vagus nerve stimulation in patients with HFrEF in the ANTHEM-HF study
Authors: Nearing B.D , Libbus I , Anand I.S , Dicarlo L.A , Kenknight B.H , Verrier R.L
Published: November 2020

Background

HFrEF patients experience long-term deterioration of autonomic function and cardiac electrical stability linked to increased sudden cardiac death risk. ANTHEM-HF (NCT01823887) reported improved baroreceptor sensitivity (heart rate turbulence, HRT), heart rate variability (rMSSD), and reduced cardiac electrical instability (T-wave alternans, TWA) after 12 months of chronic vagus nerve stimulation (VNS). It is unknown whether these benefits persist long-term.

Methods

HRT, rMSSD, TWA, and VT occurrence were evaluated during chronic VNS in all patients with symptomatic HFrEF with available 36-month follow-up data (n=25). ECGs were analyzed before Autonomic Regulation Therapy system implantation (LivaNova USA) and after chronic cervical VNS.

Results

Improvement in HRT slope persisted at 24 months (8.1±1.2 ms/RR interval, p=0.02) and 36 months (7.9±0.9 ms/RR interval, p=0.03) of VNS compared to baseline. RMSSD increase continued at 24 months (34.6±2.7 ms2, p<0.02) and 36 months (36.4±2.0 ms2, p=0.002). Peak TWA levels remained reduced at 24 months (47.8±1.3 μV, p<0.0001) and 36 months (46.1±1.6 μV, p<0.0001). No sudden death, VF, or sustained VT occurred, and patients with nonsustained VT decreased from 11 (44%) at baseline to 1 (5%) at 24 months (p<0.003) and 2 (11%) at 36 months (p<0.02).

Conclusion

In patients with HFrEF, chronic VNS appears to confer persistent 3-year improvements in autonomic tone, baroreceptor sensitivity, and cardiac electrical stability.

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): LivaNova PLC
Symptomatic endpoint responder rates to BAROSTIM Therapy
Authors: Abraham W.T , Lindenfeld J , Weaver F , Zannad F , Zile M , Galle E , Schafer J , Bahu M
Published: November 2020

Background

Patients with heart failure with reduced ejection fraction (HFrEF) have varying responses to symptomatic endpoints with device-based HF therapies.

Purpose

Evaluate the symptomatic response to baroreflex activation therapy (BAT) at six months.

Methods

In a trial of subjects with NYHA Class II (recently III) or III HFrEF, left ventricular EF≤35%, guideline directed medical HF therapy (GDMT), no indication for cardiac resynchronization therapy, and NT-proBNP<1600 pg/ml, 264 subjects were randomized to BAROSTIM therapy plus GDMT (BAT group) or GDMT alone (Control group). Six-minute hall walk (6MHW), Minnesota Living with HF (QOL) and NYHA Class were analyzed. Clinically relevant responders were defined by 6-month improvement in 6MHW>10%, QOL>5 points or improvement in at least one NYHA class; super responders were defined by 6-month improvement in 6MHW>20%, QOL>10 points or improvement to NYHA class I.

Results

Both clinically relevant and super responders were significantly higher in BAT versus Control subjects for all symptomatic endpoints. In BAT subjects, 72% had clinically relevant improvements in ≥2 endpoints compared to 29% of Control subjects (p<0.001), and 28% of BAT subjects had super responder improvements in ≥2 endpoints versus 10% of Control subjects (p<0.001).

Conclusion

Among subjects with symptomatic HFrEF, treatment with BAT resulted in clinically relevant and super responder rates. The BAT clinically relevant and super responder rates are similar to those seen with CRT, in CRT-indicated patients.

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): CVRx, Inc.
Selfcare management intervention in heart failure (SMART-HF) -a multicentre randomized controlled trial
Authors: Sahlin D.S , Melander O , Gerward S
Published: November 2020

Background

Clinical studies evaluating home-based interventions for heart failure (HF) patients are performed on patients that are too young, too often male and predominately have reduced ejection-fraction (EF). The Selfcare Management Intervention in Heart Failure (SMART-HF) study was designed to evaluate a digital intervention enhancing self-care behaviour in a more generalizable population. The aim was to see if the intervention could reduce in-hospital care due to HF.

Methods

SMART-HF was a randomized controlled trial, recruiting patients from seven centres in Region Skåne. Patients were randomized 1:1 to a control group (CG) receiving standard care or an intervention group (IG) who were equipped with the digital intervention. The intervention educates the patient about HF and supports the patient with medication and symptom monitoring, also notifying the patient in case of deterioration. The primary outcome was number of in-hospital days due to HF after 240 days follow-up.

Results

A total of 124 patients were randomized and 118 (CG: 60, IG: 58) were included in the analysis. The mean age was 79 years, 39% were women and 45% had EF <40%. The groups were well balanced at randomization. A total of 367 HF in-hospital days were registered among 33 patients, and patients in the IG lost on average 2.2 days fewer to HF-hospitalizations than patients in the CG, a reduction by 52%, p<0.001. An unadjusted Cox-regression to analyse the event-free survival yielded a hazard ratio = 0.50 (CI:0,24–0,96), p=0.046. The self-care behaviour was 21% better in the IG, p=0.014. The median system adherence was 85% after 240 days.

Conclusions

The intervention significantly reduced HF-related in-hospital days and improved event-free survival in a representative HF-population. The findings match previous published data from studies evaluating the same intervention.

Funding Acknowledgement

Type of funding source: None
Association between clinical risk factors and left ventricular function in patients with breast cancer following chemotherapy
Authors: Yamashita K , Tanaka H , Hatazawa K , Tanaka Y , Sumimoto K , Shono A , Suzuki M , Yokota S , Suto M , Mukai J , Takada H , Matsumoto K , Minami H , Hirata K
Published: November 2020

Background

The sequential or concurrent use of two different types of agents such as anthracyclines and trastuzumab may increase myocardial injury and cancer therapeutics-related cardiac dysfunction (CTRCD), which is often the result of the combined detrimental effect of the two therapies for breast cancer patients. For risk stratification to detect the development of CTRCD, the current position paper from the European Society of Cardiology (ESC) lists several factors associated with risk of cardiotoxicity following treatment with chemotherapy. However, the association between clinical risk factors and left ventricular (LV) function in breast cancer patients is currently unclear.

Purpose

Our purpose was to investigate the impact of baseline risk factors on LV function in patients with preserved LV ejection fraction (LVEF) who have undergone anthracycline or trastuzumab chemotherapy for breast cancer.

Methods

We studied 86 breast cancer patients treated with anthracyclines, trastuzumab, or both. Mean age was 59±13 years and LVEF was 67±5%. In accordance with the current definition, CTRCD was defined as a decline in LVEF of >10% to an absolute value of <53% after chemotherapy. Based on the 2016 ESC position paper, clinical risk factors for CTRCD were defined as: (1) a cumulative total doxorubicin dose of ≥240 mg/m2, (2) age ≥65-year-old, (3) body mass index ≥30 kg/m2, (4) a previous history of radiation therapy to chest or mediastinum, (5) B-type natriuretic peptide ≥100pg/mL, (6) a previous history of cardiovascular disease, (7) atrial fibrillation, (8) hypertension, (9) diabetes mellitus, (10) current or ex-smoker.

Results

The relative decrease in LVEF after chemotherapy for patients with more than four risk factors was significantly greater than that for patients without (−9.3±10.8% vs. −2.2±10.2%; p=0.02). However, this finding did not apply to patients with more than one, two or three risk factors. Patients with more than four risk factors also tended to show a higher prevalence of CTRCD than those without (14.3% vs. 2.8%, p=0.12). Moreover, patients with more than four risk factors were more likely to have higher LV mass index (109.3±29.0 g/m2 vs. 83.2±21.0g /m2, p<0.001), lower global longitudinal strain (18.4±2.8% vs. 20.0±2.6%, p=0.06) and higher E/e' (10.4 (8.9–13.0) vs. 9.0 (7.4–10.9), p=0.06) compared to those without.

Conclusions

Association between clinical risk factors and LV dysfunction following chemotherapy became stronger with an increase in the number of risk factors in breast cancer patients, and was especially strong for patients treated with chemotherapy who had more than four risk factors. Our findings can thus be expected to have clinical implications for better management of patients with breast cancer referred for chemotherapy.

Funding Acknowledgement

Type of funding source: None
Significance of left ventricular global longitudinal strain assessment in patients with preserved ejection fraction after acute myocardial infarction
Authors: Luvsansuren B , Chimed S
Published: November 2020

Background

Depression of left ventricular function is common phenomenon after acute myocardial infarction and it's often associated with poor prognosis. However, substantial portion of patients with acute myocardial infarction had normal left ventricular function by assessment of left ventricular ejection fraction.

Purpose

In this study, we examined role of left ventricular global longitudinal strain assessment in patients who had normal ejection fraction after acute myocardial infarction.

Methods

We choose patients with acute myocardial infarction who were successfully treated with primary percutaneous coronary intervention (PCI). All of those patients had normal ejection fraction (EF≥55%) in routine echocardiographic examination within 3 days after acute myocardial infarction. Two dimensional speckle tracking echocardiography was used to assess left ventricular global longitudinal strain. Based on existence of newly onset clinical signs (pulmonary edema, lung crackles, peripherial edema etc.) of heart failure patients divided into case and control group. Patients who had other etiology or previous heart failure were excluded.

Results

A total of 153 patients with AMI were selected and newly onset heart failure is occurred in 20 patients. Left ventricular global strain was significantly different between patients with clinical heart failure and patients without clinical heart failure (−11.1±1.85% vs. −16.6±3.38%, p<0.001). After adjustment of possible predictors of impaired left ventricular function such as, age, gender, hypertension, diabetes, previous coronary artery disease, cardiac troponin, mitral inflow EA ratio, deceleration time, left ventricular end diastolic volume, ejection fraction, mitral annulus EE' ratio and wall motion score index, global longitudinal strain was independent predictor of clinical heart failure (odds ratio 1.79, 95% CI 1.22–2.65, p=0.003). Adding global longitudinal strain into above mentioned predictors of clinical heart failure after acute myocardial infarction is associated with significantly increased c-statistic (0.93, 95% CI 0.87–0.99 vs. 0.97, 95% CI 0.94–0.99, p<0.001).

Conclusion

Left ventricular global longitudinal strain is independently associated with clinical heart failure in patients with preserved ejection fraction after acute myocardial infarction. Adding global longitudinal strain parameter into screening model may increase rate of precise determination of clinical heart failure after acute myocardial infarction.

Funding Acknowledgement

Type of funding source: None
Prognostic value of integrated cardiopulmonary ultrasound in inpatients with acute heart failure with preserved and reduced ejection fraction and without heart failure
Authors: Pugliese N.R , Frassi F , Frumento P , Poggianti E , Mazzola M , De Biase N , Landi P , Masi S , Taddei S , Pang P , Sicari R , Gargani L
Published: November 2020

Objective

To assess the prognostic value of B-lines integrated with echocardiography in patients admitted to a Cardiology Department, with and without acute heart failure (AHF).

Background

Lung-ultrasound (LUS) B-lines are sonographic signs of pulmonary congestion and can be used in the differential diagnosis of dyspnea to rule in or rule out AHF. Their prognostic value at admission is less established, as well as the different role in AHF with reduced and preserved ejection fraction (HFrEF and HFpEF), or patients admitted for cardiac conditions but without overt signs and symptoms of AHF.

Methods

A total of 1021 consecutive in-patients (69±12 years) admitted for various cardiac conditions were enrolled. Patients were classified into three groups: 1) acute HFrEF; 2) acute HFpEF; 3) no AHF. All patients underwent on the admission an echocardiogram coupled with LUS, according to standardised protocols.

Results

Patients were followed-up for a median of 14.4 months (interquartile range: 4.6–24.3) for death and HF readmission (composite endpoint). During the follow-up, 126 events occurred. Kaplan-Meier survival analyses showed admission B-lines >30 identified patients with worse outcome at follow-up in the overall population and each of the three groups (Figure). At multivariable analysis (Table), admission B-lines >30, EF <50%, tricuspid regurgitation velocity >2.8 m/s and tricuspid annular plane systolic excursion (TAPSE) <17 mm resulted in independent predictors of the composite endpoint. B-lines >30 had a strong predictive value in HFpEF and non-AHF, but not in HFrEF.

Conclusions

Ultrasound B-lines can detect subclinical pulmonary interstitial edema in patients thought to be free of congestion, and provide useful information not only for the diagnosis but also for the prognosis in different cardiac conditions. Their added prognostic value among standard echocardiographic parameters is stronger in patients with HFpEF compared to HFrEF.

Figure 1

Funding Acknowledgement

Type of funding source: None
Effect of empagliflozin as add-on therapy on transtubular potassium concentration gradient in patients with type 2 diabetes hospitalized for acute decompensated heart failure
Authors: Tamaki S , Yamada T , Watanabe T , Morita T , Furukawa Y , Kawasaki M , Kikuchi A , Kawai T , Seo M , Abe M , Nakamura J , Yamamoto K , Fukunami M
Published: November 2020

Background

The transtubular potassium concentration gradient (TTKG) has been reported to be a marker of renal aldosterone bioactivity, and has been shown to be a surrogate of arterial underfilling in patients with acute decompensated heart failure (ADHF). Moreover, high TTKG at discharge has been shown to be associated with poor prognosis in ADHF patients. Empagliflozin, one of the sodium glucose cotransporter 2 inhibitors, has been shown to reduce the risk of cardiovascular mortality in patients with type 2 diabetes mellitus (T2D) and cardiovascular disease. However, little is known about the effect of empagliflozin as add-on therapy on TTKG in T2D patients with ADHF.

Purpose

We sought to elucidate the effect of empagliflozin as add-on therapy on TTKG in T2D patients with ADHF.

Methods

We enrolled 58 consecutive T2D patients admitted for ADHF. On admission, enrolled patients were randomly assigned in a 1:1 ratio to either empagliflozin add-on therapy (EMPA(+)) or conventional glucose-lowering therapy (EMPA(−)). All patients in EMPA(+) group received empagliflozin (10 mg/day) throughout the study period. Left ventricular ejection fraction (LVEF) was measured at baseline using echocardiography. Body weight and vital signs, such as blood pressure and heart rate, were measured, and blood and urine samples were collected at baseline and 1, 2, 3 and 7 days after randomization. The TTKG was measured using the first morning urine samples collected on each day. TTKG was calculated according to the following equation: TTKG = (Ku/Ks)×(plasma osmolality/urine osmolality), where Ku is urine potassium concentration and Ks is serum potassium concentration, as previously reported.

Results

Thirty patients were assigned to the EMPA(+) group, and 28 patients were assigned to the EMPA(−) group. There were no significant baseline differences in LVEF, plasma B-type natriuretic peptide (BNP) level, body mass index, or serum creatinine level between the EMPA(+) and EMPA(−) groups. TTKG did not significantly differ between the two groups at baseline. However, seven days after randomization, plasma BNP level was significantly lower in the EMPA(+) group than in the EMPA(−) group (median 227 [IQR 114–381] pg/mL vs 362 [227–554] pg/mL, p=0.0294). Furthermore, TTKG of the EMPA(+) group was significantly lower at 2, 3 and 7 days after randomization (Figure).

Conclusions

This study demonstrated that empagliflozin as add-on therapy can lower TTKG in T2D patients with ADHF.

Figure 1

Funding Acknowledgement

Type of funding source: None