bluuebunny/crossref_metadata_2025 huggingface dataset:
P3467Tricuspid annular isovolumic acceleration is more useful for the assessment of right ventricular systolic function in patients after repair of tetralogy of Fallot with pulmonary regurgitation
Authors: Toyono M , Yamada S , Aoki-Okazaki M , Takahashi T
Published: October 2019

Introduction

The detrimental impact of pulmonary regurgitation (PR) on right ventricular (RV) function of patients after repair of tetralogy of Fallot (TOF) is recognized. Although tricuspid annular isovolumic acceleration (IVA) is useful for the evaluation of RV function, it requires complicated measurement. Tricuspid annular plane systolic excursion (TAPSE) is measured easily and has also been validated as a marker of RV systolic function.

Hypothesis

We assessed the hypothesis that IVA has advantage to the stratification of the detrimental impact of PR on RV systolic function after TOF repair compared with TAPSE.

Methods

We prospectively examined patients after TOF repair. Patients <1 year after the repair, those with the history of sustained arrhythmia and those who required concomitant tricuspid and/or pulmonary valve surgery were excluded from the study. IVA was measured by dividing the myocardial velocity during isovolumic contraction by the time interval from the onset of the myocardial velocity during the isovolumic contraction to the time at the peak velocity of this wave. TAPSE was measured using M-mode echocardiography with the M-line passing through the lateral annulus of tricuspid valve in the apical 4-chamber plane. PR jets were evaluated in the parasternal short-axis plane. PR degree was assessed by the number of correspondence to the following conditions; 1) diastolic flow reversal in the main pulmonary artery, 2) diastolic flow reversal in the branch pulmonary arteries, 3) pressure half-time of PR signal <100 msec and 4) the ratio of the duration of the PR signal to the total duration of diastole <0.77. PR degree was graded from 0 to 4.

Results

Twenty-two patients were enrolled to the study. Age, female, period after the TOF repair and body height of the patients were 11±6 years, 55%, 9±5 years and 137±28 cm, respectively. In all the patients, IVA and TAPSE were 160±27 cm/sec2 and 12±2 mm, respectively. PR degrees were graded as 2, 3 and 4 in 4, 14 and 4 patients, respectively. By the Kruskal-Wallis test, only IVA showed a significant difference among the 3 PR degrees.

Conclusion

In conclusion, IVA can be a useful index for the stratification of RV function in patients after TOF repair with various degrees of PR.
P3479Sequential stimulation and inhibition of lysophosphatidic acid receptor 4 are critical for cardiac differentiation and repair
Authors: Cho H J , Lee J W , Lee C S , Ryu Y R , Kim H S , Yang H M
Published: October 2019

Background

The clinical application of cell therapy to repair the damaged heart needs to understand the precise differentiation process of stem cells and the characteristics of cardiac progenitor cells.

Purpose

We examined the cardiac-specific markers that expressed on the cell surface and determined their functional significance during cardiac differentiation.

Methods and results

We screened cell-surface expressing proteins on cardiac progenitor cells at differentiation day 3 compared to undifferentiated pluripotent stem cells (PSCs). Among candidates, we identified lysophosphatidic acid receptor 4 (LPAR4) that is a G protein-coupled receptor. During in vitro differentiation of mouse PSCs toward cardiac cells, LPAR4 expression peaked for 3–5 days and then and declined immediately. Also in vivo, LPAR4 was specifically expressed in the early stage of heart development in embryos and disappeared completely in adults, suggesting that stimulatory signal of LPAR4 at an early stage should be shut off for further progression of differentiation. We next have identified the LPAR4 downstream signaling molecule, p38MAPK, by comparing PSCs and LPAR4 knockdown PSCs. In both mouse and human PSCs, ODP (LPAR4 specific agonist) followed by p38MAPK blocker (SB203580) treatment significantly increased cardiac differentiation efficiency. Furthermore, we investigated whether LPAR4 is the maker for adult cardiac progenitor cells. We found that LPAR4-positive cells were rarely present in normal adult mouse hearts, but LPAR4-positive cells were increased when the heart was damaged. LPAR4-positive cells from adult hearts differentiated into cardiomyocytes. After myocardial infarction (MI), the sequential stimulation and inhibition of LPAR4 with ODP and p38MAPK blocker resulted in the reduction of infarct size and improvement of left ventricular dysfunction.

Conclusion

We demonstrated that LPAR4 is a cardiac progenitor-specific marker and its functional significance during cardiac differentiation and regeneration. Our findings provide a new insight in cell-free cardiac repair by the modulation of progenitor-specific downstream signaling.

Acknowledgement/Funding

Grants from “Strategic Center of Cell and Bio Therapy” (grant number: HI17C2085) and “Korea Research-Driven Hospital” (HI14C1277)
P3488Mechanistic insight on the cardioprotective effect of levosimendan against doxorubicin induced cardiomyopathy: Pivotal role of PKA signaling
Authors: Efentakis P , Varela A , Sanoudou D , Davos C , Klinakis A , Papapetropoulos A , Cokkinos D V , Iliodromitis E K , Wenzel P , Andreadou I
Published: October 2019

Background

Levosimendan (LEVO) an inodilator indicated for the treatment of heart failure exerts multifaceted cardioprotective effects. Case-studies indicate protection against doxorubicin (DXR)-induced cardiotoxicity, but this effect remains elusive. We have previously shown that LEVO exerts cardioprotection against DXR-induced cardiomyopathy in a rat in vivo model, in a PKA/PKG-dependent manner.

Purpose

We sought to elucidate the mechanism of LEVO's induced cardioprotection and clarify the contribution of PKG and PKA pathways converging onto phospholamban (PLN).

Methods

As previously observed, LEVO at a dose of 24μg/kg protects against DXR cardiotoxicity, with protein kinase B (Akt)/ endothelial nitric oxide synthase (eNOS) and protein kinase A and G (PKA/PKG) pathways emerging as the main contributors to cardioprotection. Moreover, phospholamban seems to be the end-target of the signaling cascade. To verify the contribution of phospholamban, phospholamban deficient mice (PLN−/−) were assigned to PLN−/−/DXR (18mg/kg) and PLN−/−/DXR+LEVO (acute) (LEVO bolus, 24 μg/kg) groups for 14 days. Echocardiographic analysis was conducted in all groups and protocols. Furthermore, in order to solidify the mechanism of LEVO-mediated cardioprotection, primary adult ventricular murine cardiomyocytes (AVMCs) were isolated and treated with doxorubicin or/and LEVO as well with L-NAME, DT-2 and H-89 (eNOS, PKG and PKA inhibitors, respectively) and cardiomyocyte-toxicity was assessed.

Results

In the transgenic PLN−/− mice, LEVO did not exert cardioprotection, whilst the co-administration of doxorubicin and levosimendan led to an impaired Left ventricular function [FS (%): PLN−/−/Control: 39.01±0.42 vs PLN−/−/DXR: 38.12±0.51 in (NS); PLN−/−/DXR+LEVO: 35.38±0.86 (**p<0.01 vs PLN−/−/Control, *p<0.05 vs PLN−/−/DXR]. The latter data suggest that phospholamban is crucial for LEVO's cardioprotective effect. Finally, by investigating the contribution of different molecular pathways -shown to be induced by LEVO in vivo- on the AVMCs, we found that only PKA inhibition by H-89, abrogated LEVO-mediated cytoprotection, indicating that the effect is cAMP-PKA dependent.

Conclusions

Single-dose LEVO prevented DXR cardiotoxicity through a cAMP-PKA-phospholamban pathway, highlighting the role of inotropy in DXR cardiotoxicity. These preclinical data can stand as promising grounds for further clinical investigations.
P3507Heterozygous cardiomyocyte-specific deletion of ErbB4 sensitizes to development of pregnancy-related cardiomyopathy
Authors: Feyen E , Vermeulen Z , Dugaucquier L , Hilfiker-Kleiner D , Segers V F M , De Keulenaer G W
Published: October 2019

Background

Peripartum cardiomyopathy (PPCM) is a potentially life-threatening disease in women without known cardiovascular disease; PPCM is characterized by left ventricular (LV) systolic dysfunction towards the end of pregnancy and/or in the first months postpartum. The underlying mechanisms of PPCM are incompletely understood, but there is recent evidence that impaired cardiomyocyte expression of the tyrosine kinase ErbB4 receptor plays a role. ErbB4 is the main receptor of neuregulin-1, a protective and regenerative paracrine factor in the heart. Homozygous deletion of ErbB4 is lethal.

Purpose

To test the hypothesis that mice with heterozygous (HZ) cardiomyocyte-specific deletion of ErbB4 (ErbB4+/−) are more susceptible to PPCM.

Methods

Cardiac morphology and function was evaluated by echocardiography with a Vevo 2100 Imaging System during 2 pregnancies and 6 weeks postpartum (n=7–9) or during non-pregnant control conditions in HZ (ErbB4+/−) and wild type controls (n=9–10). Then, hearts were excised for analyses of myocardial fibrosis, macrophage infiltration, capillary density and cardiomyocyte cross sectional area.

Results

When compared to pregnant wild type controls, pregnant ErbB4+/− mice developed significant LV dilatation (2 weeks after the 2nd delivery: LVIDd +16% ± 2%, p<0.05) and dysfunction (6 weeks after the 2nd delivery: EF −23% ± 3%, p<0.001), increased heart to body weight ratio (+7% ± 4%, p<0.05) and increased cardiomyocyte cross sectional area (+28% ± 7%, p<0.01). Non-pregnant ErbB4+/− mice also developed LV dilatation and dysfunction, albeit slower than pregnant ErbB4+/− mice. On histology, however, myocardial tissue of pregnant ErbB4+/− mice did not show macrophage infiltration, neither fibrosis, nor reduced capillary density.

Conclusions

Heterozygous cardiomyocyte-specific deletion of ErbB4 sensitizes to peripartum LV dilatation and cardiomyocyte hypertrophy and systolic dysfunction without profound cardiac injury, features that are frequently present in PPCM patients and may explain their high chance for recovery. These data reinforce a compensatory role for neuregulin-ErbB4 signaling during hemodynamic overload, and confirm that this signaling pathway is important to protect the maternal heart during peripartum stress.

Acknowledgement/Funding

Fund scientific research Flanders; University Antwerp
P3508A novel mouse model of sleep-disordered breathing is associated with contractile dysfunction and CaMKII overexpression
Authors: Lebek S , Schach C , Reuthner K , Tafelmeier M , Camboni D , Rupprecht L , Schmid C , Maier L S , Arzt M , Wagner S
Published: October 2019

Background

Patients with sleep-disordered breathing (SDB) develop arrhythmias and contractile dysfunction, but the mechanisms are poorly understood, possibly due to the lack of mouse models that mimic airway obstruction in spontaneously sleeping mice. Interestingly, New Zealand obese mice have been shown to develop airway obstruction with inspiratory flow limitation resulting in apneas, but these mice also develop diabetes.

Purpose

We developed a novel mouse model of increased airway obstruction in spontaneously sleeping lean mice and investigated the impact on sleep-related apneas and contractile function.

Methods and results

Male C57BL6 mice at 8–12 weeks of age were subjected to polytetrafluoroethylene (PTFE) injection (100 μl) into the tongue. This resulted in an increased tongue volume and reduced pharyngeal luminal diameter. Conscious mice behave normal and there was no difference in body weight between PTFE injected mice and untreated littermates (control). Whole body plethysmography was used to monitor spontaneous breathing for 8h in a quiet environment. Interestingly, compared to control, mice with PTFE injection showed a significantly increased frequency of apneas (lasting >1s, fig. A, * indicated P<0.05, t-test). Echocardiographic analysis revealed that ejection fraction was significantly reduced in PTFE-treated mice 8 weeks after surgery (vs. control, fig. B). In accordance, the developed force of isolated papillary muscles from hearts of PTFE mice was significantly reduced compared to control (fig. C). Ca/calmodulin-dependent protein kinase II (CaMKII) has been implicated in the development of heart failure. Intriguingly, compared to control, CaMKII expression was significantly increased in ventricular heart homogenates of PTFE-treated mice (fig. D). Moreover, the magnitude of CaMKII overexpression correlated significantly with the frequency of apneas (fig. E). Papillary muscle post-pause contractions can be used as measure of diastolic sarcoplasmic reticulum (SR) Ca leak, which is known to be enhanced by CaMKII. Compared to control, post-pause contraction amplitude was significantly smaller in PTFE-treated mice, indicating an increased SR Ca leak (fig. F).

Figure 1

Conclusion

PTFE injection in mice results in an increased frequency of spontaneous apneas. PTFE-treated mice develop mild contractile dysfunction, which is accompanied by CaMKII overexpression. This novel mouse model offers great opportunities for investigation of sleep-related breathing disorders.

Acknowledgement/Funding

This study was supported by the Medical Faculty of the University of Regensburg (ReForM programme).
P3516Sex differences in cardiac function and muscular dystrophy in lamin A/C genotype positive family members
Authors: Skjolsvik E , Dejgaard L A D , Lie Ø.H , Klaboe L G , Hasselberg N E , Orstavik K , Edvardsen T , Haugaa K H
Published: October 2019

Background

Lamin A/C dilated cardiomyopathy is a highly penetrant inheritable cardiomyopathy with some patients developing muscluar dystrophy. Studies have indicated higher morbidity and mortality in men compared to women with lamin A/C.

Purpose

To explore sex differences in cardiac function, arrhythmias and muscular dystrophy in lamin A/C genotype positive family members of lamin A/C probands.

Methods

We included consecutive lamin A/C genotype positive family members recruited for cardiological evalutation based on the identification of lamin A/C genotype by cascade genetic screening. Cardiac function was assessed by echocardiography. Impaired cardiac function was defined according to guidelines as left ventricular ejection fraction (LVEF) <52% in men, <54% in women. Presence of AV-block, atrial fibrillation and ventricular arrhythmias were evaluated by12-lead ECG, Holter monitoring, and interrogation of cardiac implantable electronic devices. Presence of muscular dystrophy was assessed retrospectively from medical records, and defined as present or not based on description of typical symptoms and/or findings on neurological exam.

Results

We included 55 lamin A/C genotype positive family members (age 35±15 years, 49% female). Men were younger at time of evaluation (31±15 years vs. 40±14 years, p=0.047). Despite lower age, men had significantly lower LVEF (48±12% vs. 55±9%, p=0.016) (Figure left panel), and showed worse survival free from impaired cardiac function compared to women (log rank p=0.019) (Figure, mid panel). Male sex was a marker for impaired cardiac function when adjusted for age (adjusted OR 5.3 [95% CI; 1.5–18.8]). Women had higher prevalence of muscular dystrophy compared to men (35% vs. 0%, p=0.004) (Figure right panel). We observed no sex related differences for AV-block, atrial fibrillation, nor ventricular arrhythmias.

Conclusions

Male lamin A/C genotype family members had earlier penetrance and more frequently impaired cardiac function compared to women. AV-block and arrhythmic disease did not differ. Muscular dystrophy was more frequent in women. These findings indicate sex differences in the phenotypical expression of lamin A/C disease.
P3524Biomechanic and neuroautonomic adaptation to acute blood volume displacement in patients with ischemic dilated cardiomyopathy
Authors: Scicchitano P , Acanfora D , Massari F , De Palo M , Acanfora C , Cortese F , Antonelli Incalzi R , Ciccone M M
Published: October 2019

Background

Chronic heart failure (CHF) is associated with neuroautonomic unbalance.

Purpose

We aimed at verifying the biomechanical and neuroautonomic adaptation to tilt test-induced volume displacement in patients with ischemic CHF.

Methods

Fifty-four CHF patients with a previous inferoapical/inferolateral (IA-IL) or basal/apical septal (BS-AS) myocardial infarction, free from residual ischemia, were enrolled. They underwent head-up tilt test, radionuclide ventricular function monitoring using the ambulatory ventricular function monitoring device (VEST), sympatho-vagal balance evaluation (low [LF] and high [HF] frequencies) and isoproterenol test (CD25).

Results

IA-IL patients had lower values of stroke volume, cardiac output and ejection fraction.The end-diastolic volume (EDV) increased in the IA-IL group (F=36.41, P<0.001) during tilt-test, more than BS-AS patients (F=4.12, P<0.05). The end-systolic volume (ESV) similarly increased in both groups. Norepinephrine (IA-IL Supine→ Tilting 499.5±28.8 → 719.3±41.5 pg/ml vs BS-AS Supine → Tilting 533.9±33.3 → 768.8±47.9 pg/ml, P<0.001) and epinephrine plasma concentrations (IA-IL Supine → Tilting 125.7±9.8 → 193.7±9.6 pg/ml vs BS-AS Supine → Tilting 118.8±8.9 → 191.7±10.2 pg/ml, P<0.001) increased in both groups.

LF/HF ratio not-significantly increased in IA-IL patients and decreased in BS-AS. CD25 was similar in IA-IL and BS-AS patients (IA-IL patients = 4.6±0.94 μg and BS-AS patients = 5.0±1.06 μg, P=0.79). The severity of ventricular dysfunction rather than its site correlated with the unbalance in biomechanical and neuroautonomic response.

Conclusions

Ischemic CHF patients showed altered biomechanical adaptation to volume displacement and compensatory sympathetic overdrive. Caution should be used with drugs interfering with the sympathetic response due to increased risk of syncope in response to volume displacement.

Acknowledgement/Funding

None
P3526Heart Failure hospitalization and mortality in non-valvular Atrial Fibrillation: The ENGAGE-AF TIMI 48 Trial
Authors: Inciardi R M , Giugliano R , Nordio F , Ruff C , Antman E , Rutman H , Braunwald E , Solomon S D
Published: October 2019

Introduction

Atrial Fibrillation (AF) is associated with increased risk of cardiovascular (CV) morbidity and mortality. Heart Failure (HF) represents the most common CV complication, more common than thromboembolic events.

Purpose

We aimed to determine clinical factors associated with HF hospitalization and mortality in a contemporary cohort of patients with AF without previous history of HF.

Methods

The Effective Anticoagulation with Factor Xa Next Generation in AF–Thrombolysis in Myocardial Infarction 48 (ENGAGE-AF TIMI 48) study tested the oral factor Xa inhibitor edoxaban in comparison with warfarin for the prevention of stroke or systemic embolism, in 21,105 patients with AF. We assessed the composite endpoint of HF hospitalization, death due to HF or sudden cardiac death in 8981 patients without a history of HF. Cox proportional hazard models were used to evaluate the significant clinical predictors associated with the endpoint of interest.

Results

Over a median follow-up of 2.8 years, 589 patients (6.5%) experienced the composite endpoint. Older patients, cardiovascular risk factors (hypertension, diabetes, heart valve disease), history of stroke and coronary artery disease, impaired renal function (ClCr ≤50 ml/min), heart rate at baseline and diuretic use were associated with increased risk of the composite endpoint (model c-statistic 0.66) (Figure 1). Outcomes were not affected by randomization to edoxaban or warfarin. In patients with available cardiac-derived biomarkers, elevated levels of both NT-proBNP and Troponin I were significantly associated with the endpoint after adjustment for the clinical predictors (Figure 1). The addition of the biomarkers to clinical predictors enhanced risk estimation (c-statistics 0.69, NRI 0.40, IDI 0.01, all p<0.001 for NT-proBNP and c-statistics 0.70, NRI 0.43, IDI 0.03, all p<0.001 for Troponin I).

Figure 1

Conclusions

HF hospitalization and mortality are important complications in AF patients without a history of HF. The addition of cardiac biomarkers to clinical characteristics enhances risk estimation. These findings may improve risk stratification.
P3530Right ventricular remodelling as part of the cardiorenal syndrome
Authors: Verikas D , Bugaite J , Gabartaite D , Cerlinskaite K , Krivickiene A , Zaliaduonyte-Peksiene D , Kavoliuniene A , Mebazaa A , Celutkiene J
Published: October 2019

Introduction

The relationship of glomerular filtration rate (GFR) to the remodelling of right (RV) and left ventricle (LV) in acute settings is not well studied.

Purpose

To investigate the relationship of renal function to LV and RV echocardiographic parameters in acute dyspnoea patients.

Methods

Echocardiography was performed in 438 patients with acute dyspnoea in prospective multicentre observational study during the first 48 hours after presentation. Echocardiographic quantification included the following parameters: tricuspid annular plane systolic excursion (TAPSE), velocity of the tricuspid annular systolic motion (RV S'), RV fractional area change (FAC), RV basal diameter, entire RV strain, strain of free RV wall, inferior vena cava (IVC) and LV parameters. Patients were divided into groups according to the GFR (ml/min/1.73m2): Normal or mildly decreased GFR (≥60), moderately decreased GFR (30–59) and severely decreased GFR (≤29). Data were analysed using One-way ANOVA.

Results

Mean GFR in this cohort was 63±26 ml/min/1.73m2. The severity of RV remodelling and venous congestion was significantly different in three subgroups of renal dysfunction.

The distribution of parameters Normal or mildly decreased GFR Moderately decreased GFR Severely decreased GFR N=233 (52%) N=166 (38%) N=39 (9%) TAPSE (cm) 1.8±0.3 1.5±0.5 1.4±0.4* RV FAC (%) 41±15 38±13 29±12*§ RV S' (cm/s) 11.0±3.3 9.7±3.4 9.1±4.2*§ Strain of RV free wall (%) −19±7 −16±6 −13±5*§ Strain of entire RV (%) −15±5 −12±5 −11±5* IVC collapsibility (%) 46±26 38±25 36±28* PASP (mmHg) 44±16 48±15 51±16*§ LVEF (%) 43±15 38±14* 46±16§ LV internal diameter in diastole (cm) 4.6±2.1 4.3±2.3 4.4±2.0 LV myocardial mass index (g/m2) 119±40 122±39 114±25 NT-proBNP (ng/l) 1485 [471; 3409] 5282 [1499; 10695] 6677 [1971; 15522]*§ Troponin T (ng/l) 55±18 92±19* 95±12* Admitted due to AHF (%) 59 72* 67 Admitted due to pulmonary causes (%) 22 21 28 *p<0.05 compared to GFR ≥60 ml/min/1.73m2, §p<0.05 compared to GFR (30–59 ml/min/1.73m2).

Conclusions

The progressive impairment of renal function coupled with larger congestion is associated with a significant right-sided but not left-sided ventricular remodelling in acute dyspnoea patients.

Acknowledgement/Funding

The work was supported by the Research Council of Lithuania, grant Nr. MIP-049/2015 and approved by Lithuanian Bioethics Committee, Nr. L-15-01.
P3532Quantifying hemodynamic cardiac stress and cardiomyocyte injury in hypertensive and normotensive acute heart failure
Authors: Kozhuharov N , Wussler D , Twerenbold R , Walter J , Du Fay De Lavallaz J , Flores D , Strebel I , Breidthardt T , Mueller C
Published: October 2019

Background

Better characterization of the different pathophysiological mechanisms involved in normotensive and hypertensive acute heart failure (AHF) might help to develop novel individualized treatment strategies.

Methods

The extent of hemodynamic cardiac stress and cardiomyocyte injury was quantified by measuring B-type natriuretic peptide (BNP) as well as high-sensitive cardiac troponin T (hs-cTnT) in 1,152 unselected patients presenting with AHF to the emergency department (derivation cohort). Systolic blood pressure (SBP) of 90 - 140 mmHg at presentation was used to define normotensive AHF. Findings regarding hemodynamic cardiac stress and cardiomyocyte injury were validated in a second independent AHF cohort (validation cohort; n=324).

Results

In the derivation cohort 667 (58%) patients had hypertensive AHF. Hemodynamic cardiac stress, as quantified by BNP levels, was significantly higher in normotensive AHF as compared to hypertensive AHF (1,105 pg/mL versus 827 pg/mL, p<0.001). In addition, the extent of cardiomyocyte injury, as quantified by hs-cTnT, was significantly higher in normotensive AHF as compared to hypertensive AHF (41 ng/L versus 33 ng/L, p<0.001). These findings were confirmed in the validation cohort.

Table 1. Cardiac stress and myocardial necrosis as quantified by BNP and hs-cTnT plasma concentrations Overall Hypertensive AHF Normotensive AHF p-value BNP in pg/ml, median (IQR) 974 (536–1,712) 827 (448–1,419) 1,105 (611–1,956) <0.001 hs-cTnT in ng/L, median (IQR) 37 (22–67) 33 (19–59) 41 (24–71) <0.001 BNP = B-type natriuretic peptide; hs-cTnT = high-sensitivity cardiac Troponin T; IQR = inter-quartile range.

Figure 1

Conclusion

Biomarker profiling revealed that the extent of hemodynamic stress and cardiomyocyte injury is different in patients with normotensive and hypertensive AHF. This characterization could help to understand AHF phenotypes better, which in turn may lead to more specific management in future, thus improving the dismal prognosis in these patients.

Acknowledgement/Funding

European Union, Swiss National Science Foundation, Swiss Heart Foundation, Cardiovascular Research Foundation Basel, University of Basel
P3533The other side of the medallion in heart failure: Reverse Metabolic Syndrome
Authors: Ozcan Cetin E H , Cetin M S , Yaman N M , Ozeke O , Topaloglu S , Aras D , Temizhan A
Published: October 2019

Background

As a risk factor for developing heart failure, metabolic syndrome (MetS) is associated with a reduced heart failure mortality. This paradox is also seen in most of the chronic diseases and also in the elderly population. Parameter changes representing the deteriarion of the balance in favor of catabolism including the low body mass index (BMI) and low blood pressure as well as low blood cholesterol have been associated with poor prognosis in several populations. Apart from high-density lipoprotein, which is further decreased, inverted changes in the components of MetS have been seen in heart failure population which led to the introduction of the concept of the “reverse metabolic syndrome” (RMetS).

Purpose

We aimed to investigate the effect of MetS and RMetS on hemodynamic parameters and long-term prognosis in patients with heart failure and reduced ejection fraction (HFrEF).

Methods

400 consecutive patients who were followed with HFrEF and performed right heart catheterization were examined. 96 patients with cardiac cachexia and morbid obesity were excluded and the remaining 304 patients with BMI 18–40 kg/m2 were included. The presence of MetS is defined according to the NCEP-ATP III criteria. RMetS was accepted as having BMI <22 kg/m2 with total cholesterol level <160 mg/dL and/or systolic or diastolic blood pressures <110 mmHg and <70 mmHg respectively. Composite endpoint (CEP) was defined as either of the occurrence of all-cause mortality, assist device implantation or cardiac transplantation. Endpoints were analyzed in two step approach: first we grouped patients accoding to the presence of MetS, then we added the RMetS category and stratifed patients into three groups as metabolic syndrome, reverse metabolic syndrome and metabolic healthy

Results

304 patients were followed up for a median of 16 (0–48) months. 110 patients had all-cause mortality and 148 patients had CEP. In the first step, patients with MetS (110 patients) had reduced all-cause mortality and CEP than patients without MetS (194 patients). In the second step, RMetS group had the highest all-cause mortality and CEP (chi-square: 22.187 p<0.001 and chi-square: 30.980, p<0.001, respectively) Cardiac output, cardiac index were lower and PCWP was higher in RMetS group. The endpoints were similar between MetS group and metabolically healthy patients.

Conclusion

Although individuals with MetS seem to have a better prognosis than patients without MetS, the latter group contains RMetS population, which had the poorest prognosis. This population may contribute to the false- assumption of the relative better findings of MetS population with regard to the non-MetS population. Further clinical studies are needed to clarify this pathologic phenomenon.
P3541Change in left ventricular ejection fraction and outcome in heart failure patients with mid-range ejection fraction: from the HIJ-HF prospective study
Authors: Tsukamoto K , Suzuki A , Shiga T , Sakai M W , Tanaka Y , Kouno E , Osada A , Matsuura J , Hayashi N , Nagara K , Ogiso M W , Nomura H , Kikuchi N , Hagiwara N
Published: October 2019

Introduction

Heart failure (HF) is categorized on the basis of the eft ventricular ejection fraction (LVEF). The European Society of Cardiology has proposed mid-range EF (HFmrEF) as a new category of HF that includes patients with an LVEF of 40–49%. However, the clinical characteristics, change in LVEF following treatment, and outcome of patients with HFmrEF remain clear.

Methods

We conducted a prospective observational study of Japanese hospitalized HF patients between 2015 and 2018 at a single-center (HIJ-HF III). HFmrEF was defined as 40–49% of LVEF on echocardiography at admission. We followed these patients and performed echocardiography to assess LVEF per year after hospital discharge. Clinical outcome was death from any cause.

Methods and results

We studied 138 patients with HFmrEF (median age 71 years, 69% male). They had 32% of ischemic heart disease, 9% of New York Heart Association functional class III or IV at discharge. During median follow-up of 20 [13–28] months, we assessed change in LVEF for 110 patients with HFmrEF. One year after hospital discharge, 49 patients (44%) improved LVEF (≥50%) and 21 patients (19%) reduced LVEF (<40%). HFmrEF patients who reduced LVEF (<40%) were significantly higher mortality rate than those who improved LVEF (≥50%) (14% vs. 2%, p<0.05) (Figure).

Conclusions

This study demonstrated that 44% of HFmrEF patients improved LVEF following treatment but 19% patients reduced LVEF. Reduced LVEF was associated with poor prognosis.
P3543Rehospitalization burden in heart failure with mid-range ejection fraction and morbidity burden. Is it a distinct phenotype?
Authors: Santas Olmeda E , De La Espriella R , Minana G , Valero E , Palau P , Amiguet M , Gonzalez J , Soler M , Sanchis J , Chorro F J , Nunez J
Published: October 2019

Heart failure with mid-range ejection fraction (HFmrEF) has been recognized as a distinct HF phenotype, but wether patients on this category fare worse, similarly, or better than those with HF with reduced EF (HFrEF) or preserved EF (HFpEF) in terms of rehospitalization risk over time remains unclear. We therefore sought to characterize the mordibity burden of HFmrEF patients by evaluating the risk of recurrent hospitalizations following an admission for acute HF.

Methods

We prospectively included 2,961 consecutive patients discharged for acute HF in our institution from 2004 to 2017. Patients were categorized according to their ejection fraction (EF) obtained by an echocardiography during the index admission: HFmrEF (EF 41–49%), HFrEF (EF≤40%) and HFpEF (EF≥50%). Negative binomial regression method was used to evaluate the association between EF status and recurrent all-cause and HF-related admissions. Risk estimates were expressed as incidence ratio ratios (IRR).

Results

Mean age of the cohort was 73.9±11.1 years, 49% were women, and 46.0% had suffered from previous HF admissions. 472 patients (15.9%) had HFmrEF, 956 (32.3%) had HFrEF, and 1,533 (51.8%) had HFpEF. At a median (interquartile range) follow-up of 2.4 (4.4) years, 1,821 (61.5%) patients died and 6,035 all-cause readmissions were registered in 2,026 patients (68.4%), being 2,163 of them HF-related. Rates of all-cause readmission per 100 patients-years of follow-up were 43.4, 47.1 and 50.1 per HFrEF, HFmrEF and HFpEF categories, respectively. After multivariable adjustment, and compared to patients with HFrEF, HFmrEF status was not associated with a higher risk of all-cause or HF-related recurrent admissions (IRR=1.06; 95% confidence interval (CI), 0.93–1.20; p=0.89), and IRR=1.07; 95% CI, 0.91–1.26; p=0.389, respectively), whereas HFpEF status was associated with a non-significant increase in the risk of all-cause recurrent admissions but a similar risk of HF-related readmissions (IRR=1.10; 95% confidence interval (CI), 0.99–1.22; p=0.06, and IRR=1.01; 95% CI, 0.88–1.16; p=0.900, respectively)

Conclusion

Following an admission for acute HF, patients with HFmrEF have a similar all-cause and HF-related rehospitalization burden when compared to patients with HFrEF, by means of recurrent events analysis.
P3547Real world experience of sacubitril/valsartan: insights on tolerability and outcome from a specialised heart failure clinic
Authors: Neoh K C , Rasoul D , Hunt F , Chong D W S
Published: October 2019

Background

Sacubitril/Valsartan has been shown to improve symptoms and outcomes in patients with heart failure (HF) reduced ejection fraction in a single large randomised controlled trial. However, real-world data on its effect is limited.

Purpose

Our centre operates a dedicated HF clinic for the initiation and titration of Sacubitril/Valsartan in suitable patients. We report on patient tolerability and incidence of adverse effects. We also assessed change in New York Heart Association (NYHA) class and left ventricular ejection fraction (LVEF) post-treatment, as well as HF hospitalisation and mortality at 6 months.

Methods

We conducted a retrospective review of all patients seen in the clinic between January 2016 to January 2019. Patient demographics and pre-initiation treatments were recorded. We compared NYHA class and LVEF category as measured by echocardiography, at initiation and post-titration to the maximum tolerated dose. Data on HF admissions were obtained from electronic hospital records and mortality from a national database.

Results

A total of 179 patients were initiated on Sacubitril/Valsartan and included in the study. Mean age was 71 years (41–90), and 138 (77%) were male. Half of the patient cohort (89) had an ischaemic aetiology. Prior to initiation, all patients were established on an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. Almost all were on a beta-blocker (99%) and mineralocorticoid receptor antagonist (98%). 56 patients (31%) had a Cardiac Resynchronisation Therapy (CRT) device and 31 (17%) had an Implantable Cardioverter-Defibrillator (ICD).

Only 4 patients (2%) had to discontinue treatment completely due to an adverse reaction. Among them, 3 patients sustained an acute kidney injury (AKI) while 1 patient had increased breathlessness. 40 patients (22%) reported symptomatic hypotension which required dose reduction. 7 patients (4%) sustained an AKI. 2 patients reported a rash and 1 patient reported nausea.

Figure 1 shows the change in NYHA class after establishment on Sacubitril/Valsartan. Data on change in LVEF post establishment of Sacubitril/Valsartan was available in 124 patients and is shown in figure 2.

A total of 133 patients had completed titration of treatment by July 2018 and included in the analysis of 6-month outcome. 13 patients had one HF hospitalisation and all-cause mortality was 4.5% (6 patients). Only 1 patient had heart failure documented as the primary cause of death.

Change in NYHA class and LVEF

Conclusion

In our cohort of well treated HF patients with reduced ejection fraction, 40% of patients experienced an improvement in NYHA class after establishment on Sacubitril/Valsartan while 35% of patients also experienced a significant improvement in LVEF. Treatment was well tolerated and the discontinuation rate was low when managed in a dedicated HF clinic focused on initiation of Sacubitril/Valsartan.
P3550Changes in intrarenal venous flow and right ventricle-pulmonary circulation coupling from in-hospital admission to discharge in decompensated heart failure patients
Authors: Labate V , Vella A , Carenini G , Losito M , Caracciolo M M , Rovida M , Bandera F , Guazzi M
Published: October 2019

Background

Intrarenal venous blood flow (IRVF) has been used to assess renal haemodynamics in heart failure (HF). In stable euvolemic HF patients, IRVF patterns are correlated with clinical outcomes independently of conventional prognostic factors. No studies are available about the use of IRVF in decompensated HF (DHF).

Purpose

We aimed at establishing the possible clinical use of IRVF and his relationship with right ventricle (RV)-pulmonary circulation (PC) coupling in a cohort of DHF patients admitted at our clinic.

Methods

15 DHF patients (mean age 72.6±9.8 years) with signs and symptoms of volume overload underwent a transthoracic echocardiography followed by renal ultrasonography and routine laboratory tests at admission and at pre-discharge (in stable euvolemic state after diuretic treatment). The IRVF was evaluated by Venous Impedance Index (VII).

Results

At discharge after depletive treatment resulted in clinical decongestion, we observed a reduction of VII (from 0.74±0.28 to 0.42±0.40; p=0.016) associated with reduction of pulmonary pressures and better RV to PC coupling (TAPSE/PASP ratio from 0.33±0.18 to 0.46±0.15; p=0.031). No significant differences in resistive index (RI), LVEF and renal function laboratory tests were detected. Results are shown in Table 1.

Patients characteristics Admission Discharge p Value VII 0.74±0.28 0.42±0.40 0.02 LVEF (%) 43.7±17.5 42.7±16.3 0.87 TAPSE (mm) 14.9±4.1 17.1±3.6 0.14 PASP (mmHg) 51.9±15.2 39.4±11.6 0.02 TAPSE/PASP (mm/mmHg) 0.33±0.18 0.46±0.15 0.03 RI 0.8±0.1 0.7±0.1 0.11 Creatinine (mg/dL) 1.1±0.3 1.1±0.3 0.74 eGRF (mL/min/1.73 mq) 68.2±17.7 67.1±21 0.89 NT-proBNP (ng/L) 5663±5805.4 2047.2±2090.5 0.05 LVEF = left ventricular ejection fraction; BNP = natriuretic peptide; PASP = Syst art pulm press; RI = resistance index; TAPSE = tricuspid annular plane systolic excursion.

Conclusions

VII is a new non-invasive index that could identify renal hemodynamics alterations in HF patients. A high VII may be indicative of a congestive cardio renal syndrome in which an aggressive diuretic strategy can be set up with greater scientific evidence and the possibility of instrumental monitoring of its efficacy. Moreover, the development of drugs aimed at the improvement of the RV to PC coupling could lead to a better outcome in HF.
P3564Percutaneous intervention with stent improves blood pressure and renal function in patients with transplanted renal artery stenosis
Authors: Galhardo A , Kanhouche G , Feitosa G R S , Campos H O , Faccinetto A C B , Barteczko M L M , Cirenza C , Tedesco H , De Paola A , Medina J P , Barbosa A H P
Published: October 2019

Background

Transplanted renal artery stenosis (TRAS) is the main vascular complication of patients undergoing kidney transplantat, with a reported incidence ranging from 1% to 23%. Clinically important TRAS is associated with refractory hypertension, graft dysfunction and increased peak systolic velocity (PSV) above 200 cm/s. Percutaneous intervention (PI) of TRAS with or without stent is widely accepted as a viable and safe treatment option.

Purpose

To evaluate blood pressure and renal function in patients with TRAS undergoing PI in the following year.

Methods

Between January 2007 and December 2014, 310 patients with suspected TRAS underwent consecutive angiography. Of these, 173 presented significant stenosis (>60%) and were submitted to PI. Endpoints were systolic blood pressure (SBP), diastolic blood pressure (DBP), serum creatinine (Scr), number of blood pressure medications and PSV with one month and one year post intervention.

Results

The mean age was 42.89±15.03 years, 78% of the population were male, 84% received kidneys from decesed donors, 94% having received a stent. The angiographic success and complication rates were 98% and 8,4% respectively. 98.7% were on blood pressure medications with 2.13±1.05 drugs/patient. Pre-intervention values of SBP, DBP and Scr were 152.8±25.28 mmHg, 92.67±16.43 mmHg and 3.04±2.75 mg/dL, respectively. After 1 month, there was a significant reduction in SBP (138.34±19.71; p<0.0001), DBP (82.52±12.2; p<0.0001) and Scr (2.13±1.39 mg/dl, p<0.0001). Following 01 year, SBP, DBP and Scr were 133.55±17.51, p<0.0001; 83.51±11.23, p<0.0001 (Figure); and Scr 1.94±1.09 mg/dL, p<0.0001 respectively. There was a significant reduction in post-intervention PSV when compared to baseline results (422.2±148.8 vs. 237.1±104.6 m/s, p<0.0001). There was no significant difference in the number of blood pressure medications pre and post intervention (2.13 vs 2.05; p=0.68).

Evolution of Blood Pressure

Conclusion

PI with stent of TRAS was effective in improving blood pressure and renal function levels on month 1 and on year 1 with a low rate of complications.
P3574Association of the plasma aldosterone, arterial stiffness and left atrium volume index in hypertensive patients
Authors: Shavarova E , Kravtsova O A , Chomova I A , Kobalava Z D
Published: October 2019

Relative aldosterone excess is related with arterial stiffness, endothelial dysfunction and profibrotic effects on the heart. We aimed to evaluate the association of plasma aldosterone and pulse wave velocity (PWV) with left ventricular (LV) diastolic function in patients with uncomplicated arterial hypertension (AH).

Methods

The study included 74 patients (41% male), mean age 62.0±8.2 years. Among these patients 22 (30%) had diabetes mellitus, 60 (81%) had dyslipidemia, 8 (11%) were smokers. All patients undergone clinical and laboratory evaluation, echocardiography and applanation tonometry. Plasma aldosterone concentration (PAC) was measured by using overnight fasting blood sampling between 7 am and 9 am.

Results

Mean PWV was 11.3±2.4 m/s, heart rate (H) was 72±10 bpm, aortic systolic BP was 160±21 mm Hg, aortic diastolic BP was 89±10 mm Hg, aortic pulse pressure was 60±19 mm Hg, augmentation index normalized for HR of 75 beats/min (AIx75) was 15±10%, LVMI was 124±33 g/m2, LAVI was 36±6 ml/m2, E/e' was 10.8±4.6. In simple analysis PAC significantly (p<0.05) correlated with brachial (r=0.29) and aortic diastolic BP (r=0.27), LAVI (r=0.32), E/e' (r=−0.41). After adjustment in multivariate regression model gender, waist circumference, creatinine, AIx, LV global longitudinal strain relationship between E/e' and PAC was lost. E/e' was significantly associated only with female gender (β=0.64, p=0.0008). Also multivariate regression analysis showed significant association of LAVI with brachial systolic BP (β=0.41, p<0.0001), PWV (β=0.94, p<0.0001), and PAC (β=0.75, p<0.0001).

Conclusion

Brachial systolic BP, PWV and PAC were independently associated with LAVI in patients with uncomplicated AH and herewith LAVI was more dominantly influenced by increased arterial stiffness and plasma aldosterone.
P3590Impact of right ventricular branch slow flow phenomenon post percutaneous coronary intervention for acute coronary syndrome to predict sustained right ventricular dysfunction
Authors: Setoyama K , Inoue K , Miura T , Shimizu A , Anai R , Sanuki Y , Tsuda Y , Araki M , Sonoda S , Otsuji Y
Published: October 2019

Background

Although Right Ventricular dysfunction (RVD) is one of the predictor of poor prognosis, it is believed that ischemic RVD after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) restores quickly. Because right ventricular perfusion has more ischemic preconditioning compared with left ventricle, due to their complex perfusion system. However, little is known about the time courses of RVD after ACS-PCI andtheir prognosis. We evaluated the relationship between right ventricular branch slow flow phenomenon (RVB-SF) post ACS-PCI in right coronary artery (RCA) and RVD at 6–8 months follow-up.

Method

We retrospectively analyzed consecutive 82 patients who underwent PCI for ACS in proximal or mid portion of RCA from August 2011 to March 2018 in our institution. Finally, both baseline and follow-up data were obtained from 70 patients. We analyzed TIMI frame count (TFC) to confirm the presence of RVB-SF (TFC ≥40 frame) after PCI. We also analyzed right ventricular fractional area change (RVFAC) at baseline and follow-up using echocardiography to detect sustained RVD (RVFAC ≤35%).

Result

We divided the patients into two groups (RVB-SF: 36 patients, RVB non-SF: 34 patients). Patient clinical characteristics were similar in both groups (sex, age, risk factors, medication, onset to balloon time, left ventricular stroke volume, max creatine kinase). Baseline RVFAC and follow-up RVFAC was significantly smaller in RVB-SF than in RVB non-SF, respectively. (27.1±1.7% vs. 38.3±1.8%, 31.4±1.0% vs. 48.7±1.1%, P<0.0001). However, ΔRVFAC (follow-up RVFAC – baseline RVFAC) was similar between groups. The size of inferior vena cava and systolic pulmonary artery pressure at follow-up were similar in both groups (12.1±0.6 mm vs. 11.7±0.7 mm, P=0.67, 25.7±1.5 mmHg vs. 25.2±1.5 mmHg, P=0.82). In RVB non-SF, 10 patients (29.4%) were diagnosed clinical RVAMI. However, follow-up RVFAC were similar and preserved in both groups (RVAMI: 48.1±1.3%, non-RVAMI: 49.9±1.9%, P=0.85). In RVB-SF, 19 patients (52.7%) were diagnosed clinical RVAMI. Follow-up RVFAC did not improved significantly in both groups (RVAMI: 30.4±1.4% vs. non-RVAMI: 32.6±1.5%, P=0.70). Multivariate analysis showed RVB-SF was the only independent predictor of sustained RVD at 6–8 months follow-up after ACS-PCI.

Conclusion

RVB-SF findings after ACS-PCI for RCA could predict sustained RVD at mid-term follow-up, which may indicate future prolonged RVD.