bluuebunny/crossref_metadata_2025 huggingface dataset:
P1510Values of left ventricular area strain during 4D-strain-stress echocardiography with adenosine triphosphate in healthy subjects
Authors: Nelassov N , Morgunov M , Doltmurzieva N , Sidorov R , Arzumanjan E , Eroshenko O , Safonov D , Kreneva E , Zatonsky S
Published: October 2019

Background

Use of adenosine triphosphate (ATP) instead of adenosine in stress echocardiography is more cost-effective. Earlier we have proposed new ATP stress echocardiography algorithm (Figure). This modified algorithm includes 1) stepwise increase in dose of ATP in the absence of signs of adequate vasodilation (decrease in systolic blood pressure and increase in heart rate), 2) triple registration of echocardiographic data sets (before ATP infusion, during phase of adequate vasodilation and 5 minutes after the termination of ATP infusion).

Purpose

In this study we aimed to a) assess the safety of ATP high doses infusion algorithm, b) determine the values of left ventricular (LV) systolic global and segmental area strain (AS) during 4D-strain-stress echocardiography with ATP in healthy volunteers.

Material and methods

13 healthy subjects (male 9, mean age 35.3±11.0 years) underwent ATP LV 4D strain-stress-echocardiography (Vivid E95, AFI technology). Mean values of global and regional (16 segments model) AS were determined.

Results

4 subjects appeared to be “non responders” to initial dose of ATP 140 μg/kg/min. In three subjects it was necessary to increase the dose of ATP to 175 and in one to 210 μg/kg/min in order to achieve adequate vasodilation. No major side effects of ATP infusion (complete heart block, bronchospasm, myocardial infarction) were registered and no aminophylline injections were required. In all cases interpretable 4D LV Echo data sets for automatic strain analysis were obtained. Mean values of global systolic AS in healthy individuals before, at time and after ATP infusion were −25.8±4.8, −27.2±4.4 and −25.7±4.8%, respectively. Mean values of systolic AS in each of 16 segments were also calculated (Table).

LV segment AS before ATP (%) AS ATP infusion (%) AS after ATP (%) LV segment AS before ATP (%) AS ATP infusion (%) AS after ATP (%) 1 −29.6±11.3 −31.2±11.1 −28.6±8.3 9 −27.8±6.5 −29.3±6.8 −30.8±6.0 2 −26.6±8.5 −28.2±4.9 −26.2±7.3 10 −26.1±5.2 −274±5.5 −25.8±6.0 3 −25.6±6.8 −29.6±5.2 −27.2±7.2 11 −25.3±6.1 −26.1±7.5 −24.9±5.3 4 −26.2±7.2 −24.9±9.1 −25.2±6.7 12 −28.1±7.3 −28.5±6.1 −25.3±5.6 5 −26.5±6.8 −29.3±10.9 −24.3±7.7 13 −22.9±6.5 −23.4±6.5 −23.2±6.4 6 −25.2±6.7 −26.0±7.9 −25.5±7.0 14 −25.7±7.6 −28.5±6.0 −26.2±6.8 7 −24.8±7.3 −25.6±6.1 −22.8±6.0 15 −26.5±6.5 −29.8±6.0 −28.5±5.5 8 −25.8±6.6 −26.5±5.6 −25.8±5.5 16 −24.2±7.1 −25.4±6.2 −25.1±6.6

Conclusions

4D strain-stress-echocardiography ATP infusion algorithm is safe and well tolerated by patients. Values of LV systolic global and segmental AS in healthy subjects were determined.
P1521In a 36-week placebo-controlled phase 2 trial in patients with non-alcoholic steatohepatitis (NASH), treatment with MGL-3196 (resmetirom) significantly reduces atherogenic lipoprotein particles
Authors: Taub R , Frias J P , Baum S J , Hsia S , Harrison S
Published: October 2019

Background

MGL-3196 is a liver-directed, orally active, highly selective thyroid hormone receptor-β agonist being developed for the treatment of non-alcoholic steatohepatitis (NASH). In a 36-week Phase 2 NASH study, MGL-3196 treatment compared with placebo (PbO) resulted in significant reductions in hepatic fat, liver enzymes, NASH on liver biopsy, and atherogenic lipids including low-density lipoprotein cholesterol (LDL-C) and triglycerides. Most NASH patients die of cardiovascular disease (CVD), and, in NASH patients, CV risk correlates better with LDL particle than LDL-C levels.

Purpose

To determine the effects of MGL-3196 on lipoprotein particle concentrations in patients with NASH.

Methods

MGL-3196–05 (NCT02912260) is a 36-week multicenter, randomized, double-blind, placebo controlled study of NASH patients assessed with serial liver imaging and liver biopsies. Patients received 2:1 MGL-3196 80 mg (blinded ± 20 mg dose adjustment possible at Week 4 based on Week 2 pharmacokinetic data) or placebo once daily, for 36 weeks. Lipoprotein particle concentrations were assessed in fasting blood samples at baseline and Week (Wk) 36.

Results

As shown (Table), MGL-3196 significantly reduced the level of lipoprotein particles, with greater reductions in patients with baseline (BL) LDL-C ≥100 mg/dL and the patient group with higher MGL-3196 exposures (High exp).

Lipoprotein particles Particles (by NMR) (nmol/L) Time Point Placebo, n=34 MGL-3196 (all), n=73 MGL-3196 BL LDL-C ≥100 mg/dL, n=44; High Exp, n=25 (PbO BL ≥100 mg/dL, n=23 mean data not shown) Total LDL, mean (SD) BL 1234 (276) 1275 (328) 1443 (290) 1407 (267) Wk 36 1251 (323) 1045 (264) 1155 (248) 1090 (216) % change from BL vs PbO (SE), p value −19.6 (4.2), <0.0001 −19.8 (5.6), 0.0008 −22.8 (6.3), 0.0006 Small LDL, mean (SD) BL 746 (295) 835 (294) 887 (329) 916 (314) Wk 36 749 (343) 641 (207) 641 (234) 618 (149) % change from BL vs PbO (SE), p value −27.7 (8.9), 0.002 −34.3 (13.1), 0.01 −39.4 (14.7), 0.009 Total VLDL and Chylomicron, mean (SD) BL 56.8 (23.9) 55.9 (22.9) 61.4 (24.5) 66.0 (24.8) Wk 36 58.8 (24.4) 46.0 (21.1) 47.6 (22.9) 47.4 (23.1) % change from BL vs PbO (SE), p value −22.7 (6.9), 0.001 −27.2 (7.5), 0.0006 −34.7 (8.3), <0.0001 Large VLDL and Chylomicron, mean (SD) BL 6.3 (4.3) 8.7 (5.8) 8.9 (6.1) 10.2 (6.8) Wk 36 7.2 (4.5) 6.6 (3.9) 6.7 (4.1) 7.2 (4.7) % change from BL vs PBO (SE), p value −52.5 (11.8), <0.0001 −65.6 (15.5), <0.0001 −71.3 (17.4), 0.0001 BL, baseline; High exp, high MGL-3196 exposure based on % increase from baseline in sex hormone binding globulin, BL LDL-C ≥100, a prespecified group.

Conclusions

MGL-3196 significantly reduced atherogenic lipoprotein particles, particularly in NASH patients with greater BL hypercholesterolemia. These findings are consistent with a potentially beneficial effect of MGL-3196 on the CV risk profile in NASH patients.
P1523Comparative long-term outcomes among men and women after percutaneous coronary intervention
Authors: Procopi N , Zeitouni M , Kerneis M , Hammoudi N , Berman E , Barthelemy O , Choussat R , Guedeney P , Braik N , Silvain J , Le Feuvre C , Helft G
Published: October 2019

Background

Comparative long-term outcomes among women and men treated with percutaneous intervention (PCI) are unknown.

Objective

To describe and compare mortality and predictors of poor outcomes among men and women who underwent PCI.

Methods

Consecutive men and women admitted for PCI between 2008 and 2011 were prospectively included and followed-up in this cohort study. Major adverse cardiovascular and cerebrovascular events (MACCE) and causes of death were collected through consultations, calls and death certificate. The primary endpoint was all-cause mortality according to gender. Secondary endpoints were cardiovascular death, non-cardiovascular death and MACCEs. Last detailed cardiovascular and vital status were collected in January 2019.

Results

A total of 3524 patients including 2720 men (77.1%) and 804 women (22.8%) were followed-up for a median time of 7.0 years (IQ1: 5.4; IQ 3: 7.2). The follow-up rate was 97.6%. Women were older at baseline (70±13.1 vs. 64.6±12), smoked less often (18.9% vs. 30.4%) but suffered more frequently of hypertension (67.9% vs. 58.1%) and chronic kidney disease (42.6% vs. 22.7%). All-cause death occurred for 30.3% (n=1070) and MACCE for 40.9% (n=1443) of patients in the cohort. In unadjusted analyses, women had a higher risk of all-cause mortality (35% vs 29%, HR = 1.25, 95% CI [1.09–1.43], p=0.0015) and cardiovascular mortality (61% vs. 57%, HR = 1.31, 95% CI [1.10–1.56]) but there was no difference on occurrence of MACCE (HR = 1.079, 95% CI = [0.9271–1.221]). After adjustments for baseline cardiovascular risk factors, presentation and severity of coronary disease, women and men shared a similar risk of mortality along time (adHR = 0.90, 95% CI [0.77–1.05]).

Survival curves in women vs. men

Conclusions

In this long-term follow-up, women had a higher risk of all-cause and cardiovascular mortality after PCI in unadjusted analyses. However, gender was not independently associated with mortality after adjustment for cardiovascular risk factors.
P1536Does free thyroxine (fT4) predict risk of atherosclerotic cardiovascular disease (ASCVD)?
Authors: Anderson J L , Jacobs V , May H T , Bair T L , Benowitz B A , Lappe D L , Muhlestein J B , Knowlton K U
Published: October 2019

Background

Thyroid hormones are associated with arrhythmic risk, but their relationship to ASCVD is unclear. The Rotterdam Study* reported associations of higher fT4 and lower thyroid stimulating hormone (TSH) levels with ASCVD, including within the euthyroid range. Free T3 (fT3) was not assessed.

Methods

We tested whether fT4, fT3, and TSH levels were associated with ASCVD in Intermountain Healthcare. All patients >18 y old with an fT4 level in the electronic medical record database were included. The hormone reference ranges were divided into quartiles (Q), and associations with prevalent and incident ASCVD were assessed by multivariable regression and trend tests.

Results

A total of 212,202 patients (age = 64.4±11.2 y; 66.6% women) were included and followed for 6.1±4.4 y. Of these, 8.3%, 86.6%, and 5.1% had fT4 levels below, within, and above the reference range. CAD was prevalent in 18.9% of fT4 Q1 patients. The adjusted odds ratio (OR) for coronary artery disease (CAD) increased through (Q4/Q1 OR=1.36) and beyond (High/Q1 OR=1.71) the normal range, p-trend<0.001 (Table). Smaller incremental risks were noted for fT3 (Q4/Q1 OR=1.13; High/Q1 OR=1.25). The frequencies of incident MI (Q1=2.5%) and stroke (Q1=5.4%) were low and did not show a concentration-related risk gradient. Incident all-cause death (Q1=24.3%) increased slightly for Q4 and high fT4 (OR=1.05, 1.06) but not fT3; death also increased with low fT4 (OR=1.28). TSH showed no consistent gradient within the normal range for prevalent or incident events; however, mortality increased with both high and low TSH.

Thyroid Hormone Levels and Prevalent CAD Prevalent CAD (adjusted OR) Low Normal Q1 Normal Q2 Normal Q3 Normal Q4 High fT4 (n=212,202) OR=1.08, p=0.02 OR=1.00 referent OR=1.11, p<0.001 OR=1.21, p<0.001 OR=1.36, p<0.001 OR=1.71, p<0.001 fT3 (n=30,200) OR=1.12, p<0.001 OR=1.00 referent OR=0.98, p=0.61 OR=1.02, p=0.53 OR=1.13, p<0.001 OR=1.25, p<0.001 TSH (n=183,227) OR=1.39, p<0.001 OR=1.00 referent OR=0.93, p=0.42 OR=0.88, p=0.15 OR=0.92, p=0.35 OR=1.73, p<0.001 Reference Q 1–4 are: fT4: 0.75–0.90; 0.91–1.01; 2.02–1.14; 1.15–1.50 ng/dL; TSH: 0.54–1.30; 1.31–2.04; 2.05–3.68; 3.69–6.80 uIU/mL; fT3: 2.40–2.60; 2.70–2.80; 2.90–3.10; 3.20–4.20 pg/dL.

Conclusions

Consistent with the Rotterdam Study, we found an increase in prevalent CAD with increasing fT4 levels within and beyond the normal range and, uniquely, a more modest relationship with fT3. We could not confirm a normal-range relationship between hormone levels and incident events or between TSH and prevalent disease. The relationship of fT4 levels to ASCVD is intriguing, is deserving of further study, and may have important implications for ASCVD prevention.

*A Bano, et-al. Circ Res 2017; 121:1397–1400
P1569The Impact of Multidisciplinary Cardio-Oncology Program on the Cardiovascular Outcomes in Breast Cancer Patients
Authors: Wei-Ting C , Feng Y H , Kuo Y H , Chen W Y , Huang C T , Wu H C , Wang W C , Liao C T , Chen Z C
Published: October 2019

Background

Chemo- and target therapies may induce myocardial dysfunction and lead to poor prognoses. Early detection of minor myocardial dysfunction is important for the prevention of subsequent cardiotoxicity. Cardio-oncology is a multidisciplinary field focusing on managing and preventing cardiovascular complications in cancer patients. However, whether Cardio-oncology program truly makes difference in cardiovascular outcomes remains unknown. Herein, we are sharing our experiences in our Medical Center.

Methods

Since 2014 till 2017, we recruited 154 patients with newly diagnosed breast cancer preparing for Epirubicin therapy. Echocardiography, biomarkers, six minute walking distance and cardiovascular adverse events including new onset of hypertension, stroke, myocardial infarction (MI) and mortality were recorded at baseline, three months, six months and one year. Any functional decline was reported to oncologists for the consideration of changing regimens. Otherwise, cardiologists would be consulted for cardiovascular educations and therapies. The echocardiographic and clinical records of 450 breast patients receiving Epirubicin therapy during 2010 to 2013 were also collected as comparison.

Results

Compared with the ratio of 20% patients receiving echocardiography prior to 2014, the ratio increased to 100% since Cardio-Oncology program started. Also, the drop of left ventricular ejection fraction (LVEF) from 25% attenuated to 5%. Before Cardio-Oncology Program, there were 1.7% of new onset hypertension, 0.8% of MI, 0.8% of stroke and 16.8% of mortality. Conversely, after the program, there were only 0.6% of new onset hypertension while no other cardiovascular complications were reported. Furthermore, compared with previous reports of the effectiveness of Cardio-Oncology Program, our result also displayed a superior impact on the cardiovascular outcomes.

Conclusions

Collectively, through a comprehensive monitoring and an early intervention of myocardial dysfunction post chemotherapies, Cardio-Oncology Program truly decreased the cardiovascular complications in breast cancer patients.

Acknowledgement/Funding

Chi-Mei Medical Center
P1574Predictors of mortality in hospitalized atrial fibrillation patients with cancer
Authors: Malik A H , Shetty S , Malik S
Published: October 2019

Background

Recent reports indicate an important interplay between Atrial fibrillation (AF) and cancer. There is little information regarding the outcomes of these patients. Hence, we performed a study to identify predictors of in-hospital mortality to help guide goals of care discussions.

Methods

The Nationwide Inpatient Sample was used to identify patients with a diagnosis of cancer, who were found to have AF from 2002–2014. Trend rate, patients' and hospital characteristics along with in-hospital complications and predictors of in-hospital mortality were assessed. Backward stepwise elimination technique was used to fit the multivariate regression model.

Results

Over the 13-year study period, 12,410,290 (national estimate) patients with a cancer diagnosis were identified. 1,013,735 had AF, and 10.2% of the AF patients with cancer died while hospitalised. A variety of comorbidities, in-hospital procedures and in-hospital complications increased the odds of in-hospital mortality in these patients. Also, weekend admissions, elective admissions, and rural hospitals in comparison to urban teaching and non-teaching hospitals were associated with higher in-hospital mortality.

Conclusion

Stroke, myocardial infarction, pulmonary embolism, deep venous thrombosis, acute kidney injury, congestive heart failure, sepsis, and cardiogenic shock are most significant predictors of in-hospital mortality in AF patients with cancer.

Acknowledgement/Funding

None
P1580Left atrial volume index predicts improvement in renal function after catheter ablation of atrial fibrillation
Authors: Usuda K , Kato T , Furusho H , Tokuhisa H , Tsuda T , Takashima S , Murai H , Usui S , Takamura M
Published: October 2019

Background

Atrial fibrillation (AF) increased the risk of development of kidney disease. The elimination of AF by catheter ablation is associated with improvement in renal function. However, the mechanism of cardio-renal interaction in AF has not been fully elucidated.

Purpose

We tested the hypothesis that left atrial volume index (LAVI), which is a marker of left atrial mechanical reserve, predicts improvement in renal function after restoring sinus rhythm with catheter ablation of AF.

Methods

We analyzed consecutive patients who underwent catheter ablation of AF from January 2012 to October 2018 and had completed follow-up more than 3 months after catheter ablation. Exclusion criteria were need for hemodialysis and acute hospitalization. Estimated glomerular filtration rate (eGFR) was assessed on admission and at the end of follow-up periods after catheter ablation and the difference was defined as ΔeGFR. Left atrial volume index was derived using the biplane area-length method.

Results

A total of 159 AF patients (paroxysmal 112 [70%], persistent 47 [30%]) were included in this study. The mean age was 65±11 years and 74% were male. During the mean follow-up period of 7.9±3.2 months, 105 patients (66%) were free from atrial tachyarrhythmias and 54 (34%) experienced the recurrence. Baseline eGFR and LAVI were not significantly different between the non-recurrence group and the recurrence group (71.0±17.4 and 75.1±22.8 mL/min/1.73m2; p=0.24, 35.7±12.5 and 37.9±15.0 ml/m2; p=0.34). ΔeGFR in the non-recurrence group was significantly greater compared with the recurrence group (+1.5±1.0 versus −4.3±1.4 mL/min/1.73m2; p=0.001). Baseline LAVI was negatively correlated with ΔeGFR in the non-recurrence group (r=−0.3; p=0.002; Figure), but not in the recurrence group (p=0.1). Multiple regression analysis in the non-recurrence group identified baseline LAVI (β=−0.35, p<0.001), baseline age (β=−0.31, p<0.001) and baseline eGFR (β=−0.59, p<0.001) as independent predictors for eGFR improvement after catheter ablation. In the patients with LAVI <34 ml/m2, age <70 years and eGFR <90 mL/min/1.73m2, the mean ΔeGFR was +6.3±1.9 mL/min/1.73m2.

Figure 1

Conclusions

LAVI, a marker of left atrial mechanical reserve, was an independent predictor of improvement in renal function after restoring sinus rhythm with catheter ablation of AF. This observation suggests that AF-related deterioration of renal function is due at least in part to impaired atrial mechanical function.
P1596Interaction of CaMKII and NaV1.8 modulates cardiac electrophysiology in human heart failure
Authors: Tirilomis P , Ahmad S , Bengel P , Pabel S , Maier L , Hasenfuss G , Dybkova N , Sossalla S T
Published: October 2019

Introduction

In human heart failure, electrical remodeling contributes to the risk of arrhythmia generation. Increased expression of Ca/Calmodulin-dependent protein kinase IIδ (CaMKIIδ) and an enhanced persistent Na current (INaL) have been linked to arrhythmogenesis. CaMKIIδ increases INaL via regulation of sodium channels thereby contributing to arrhythmias through early- and delayed-afterdepolarizations (EADs and DADs). Genome-wide association studies (GWAS) have described the implication of the neuronal sodium channel isoform NaV1.8 (SCN10A) in cardiac electrophysiology showing modulation in cardiac conduction. We showed that the expression of the isoform Nav1.8 is significantly increased in human failing cardiomyocytes and contributes substantially to the enhanced INaL.

Purpose

We investigated a potential interaction of CaMKIIδ and NaV1.8 and thereby its role in arrhythmia generation and electrophysiology in human and murine failing hearts.

Methods

Cardiomyocytes were isolated from explanted failing hearts and CaMKIIδ transgenic (TG) mice. We performed immunostainings and co-immunoprecipitation (Co-IP) to show interactions of CaMKIIδ and Nav1.8 in isolated cardiomyocytes and homogenates. Whole-cell patch clamp experiments were conducted in isolated human and murine ventricular cardiomyocytes. Additionally, Ca2+ transients were measured using epifluorescence microscopy with the Ca2+ dye fura-2 (10μmol/L) whereas Ca2+ sparks measurements were performed by using confocal microscopy with the Ca2+ dye fluo-4 (10μmol/L). PF-01247324 is a novel specific NaV1.8 inhibitor (orally bioavailable; 1 μmol/L) and autocamtide inhibitory peptide (AIP, 1 μmol/L) was used to inhibit CaMKIIδ.

Results

Co-immunoprecipitation experiments revealed an association of CaMKIIδ and Nav1.8 in human homogenates compared to healthy controls. Furthermore, immunohistochemistry stainings in isolated human cardiomyocytes showed a co-localization of CaMKIIδ and NaV1.8 at the intercalated disc and t-tubules. We observed a significant reduction of INaL integral and proarrhythmic SR-Ca2+ spark frequency (CaSpF) after addition of either PF-01247324 or the CaMKIIδ inhibitor AIP in failing human and murine ventricular cardiomyocytes. When PF-01247324 and AIP were added together, the decrease in INaL integral and CaSpF was comparable to PF-01247324 alone in human failing cardiomyocytes. Inhibition of NaV1.8 did not show an effect on Ca2+ transient amplitude or Ca2+ transient decay at different stimulation frequencies in CaMKIIδ TG cardiomyocytes.

Conclusion

Our results demonstrate the significance of both CaMKIIδ and NaV1.8 in INaL generation and their detrimental interaction. This data suggest that increased CaMKIIδ activity plays a substantial role for the activation of NaV1.8-mediated late sodium current and SR-Ca2+ leak.
P1630Improved outcome by guideline-directed medical therapy in real-world heart failure patients despite low blood pressure and renal dysfunction
Authors: Chen X , Dahlstrom U L F , Pivodic A , Fu M
Published: October 2019

Background

Among patients with heart failure and reduced ejection fraction (HFrEF), angiotensin-converting enzyme inhibitors (ACEI/ARB), β-adrenergic receptor blockers (BB) and aldosterone antagonists (AA) are guideline-directed medical therapy (GDMT) to improve prognosis and well-being. However, low blood pressure (BP) and renal dysfunction are often challenges and barriersof the clinical implementation in real-world.

Purpose

To investigate whether it is beneficial to apply GDMT in real-world patients with HFrEF despite low blood pressure and renal dysfunction.

Methods

This study initially included 51060 HF patients from the Swedish Heart Failure Registry. After the exclusion of patients with ejection fraction ≥40% (53.4%), systolic BP>100mmHg (40.0%), eGFR>45ml/min/1.73m2 (3.3.%) and those died during hospitalization (0.3%), 1386 patients were ultimately enrolled in this study. Patients were grouped into five subgroups (ACEI/ARB+BB+AA, ACEI/ARB+BB, ACEI/ARB+AA, ACEI/ARB and BB). Outcome is all cause mortality.

Results

Among the study patients, 485 (35.0%) were treated with ACEI/ARB+BB+AA, 672 (48.5%) with ACEI/ARB+BB, 41 (3.0%) with ACEI/ARB+AA, 68 (4.9%) with ACEI/ARB and 120 (8.7%) with BB. Patients in ACEI/ARB+BB+AA group were younger (72.9±9.7 vs. 76.1±9.2 vs. 73.9±9.7 vs. 79.5±8.0 vs. 79.3±8.9), with higher BMI (25.4±4.5 vs. 25.5±4.7 vs. 23.7±4.2 vs. 23.4±3.8 vs. 24.7±6.3), more in NYHA I/II (30.8% vs. 33.3% vs. 1.7% vs. 18.9% vs. 24.3%). During the follow-up, all cause mortality was lowest in patients treated with ACEI/ARB+BB+AA (59% vs. 60.4% vs. 75.6% vs. 75% vs. 79.2%). After adjustement for age and gender, when compared with the ACEI/ARB+BB+AA group, the hazard ratio for ACEI/ARB+BB is 1.05 (0.91–1.23), ACEI/ARB+AA 1.16 (0.80–1.68), ACEI/ARB 1.51 (1.11–2.04), and BB 2.36 (1.86–2.98) respectively

Conclusions

In real-world HFrEF patients with low blood pressure and renal dysfunction, full medication of GDMT is associated with improved long-term survival.
P1637Rehospitalisations during 26 weeks of follow up from initiation of sacubitril/valsartan after acute decompensated heart failure: An analysis of the TRANSITION study
Authors: Pascual-Figal D , Witte K K , Wachter R , Belohlavek J , Straburzynska-Migaj E , Fonseca C , Cavusoglu Y , Pouleur A C , Mueller C , Lonn E , Noe A , Schwende H , Bao W , Butylin D , Senni M
Published: October 2019

Background

Patients with acute decompensated heart failure (ADHF) are at high risk of recurrent hospitalisations and death. In-hospital initiation of sacubitril/valsartan (S/V) reduced the risk for HF re-hospitalisation by 44% compared to enalapril in the PIONEER-HF study during the 8-week follow-up period. We aimed to describe the pattern of readmissions and their causes in the TRANSITION study, which randomised participants to pre-discharge or post-discharge initation of S/V.

Methods

TRANSITION (NCT02661217) was a randomised, open-label study comparing S/V initiation pre- vs. post-discharge (1–14 days) in haemodynamically stabilised patients with HF with reduced ejection fraction, admitted for ADHF. The primary endpoint was the proportion of patients achieving 97/103 mg S/V twice daily at 10 weeks post-randomisation. Information on rehospitalisation was collected throughout the study up to 26 weeks.

Results

A total of 493 patients received S/V in the pre-discharge arm and 489 patients in the post-discharge arm. Readmissions due to any cause were reported in 9.7% and 18.1% in the pre-discharge arm vs. 10.6% and 21.3% in the post-discharge arm within 30 days, and 10 weeks respectively. During the 26-weeks follow-up, all-cause readmission was reported in 34.5% of patients in the pre-discharge arm vs. 34.6% in the post-discharge arm. Median time to first rehospitalisation was 67 days in the pre-discharge arm (IQR: 26–110 days) and 50 days (IQR: 23–108 days) in the post-discharge arm. At least one HF hospitalisation was reported in 7.5% of patients in the pre-discharge arm and 7.4% in the post-discharge arm during 10 weeks and in 11.8% and 12.3% of patients, respectively, during 26 weeks of follow-up. Median duration of HF readmission was 7 days (IQR: 4–11 days) in the pre-discharge group and 6.5 days (IQR: 6.5–10 days) in the post-discharge arm. In total 2.6% and 5.5% patients in pre-discharge arm and 3.9% and 7% in the post-discharge arm visited an emergency room during 10 weeks and 26 weeks, respectively.

Conclusions

Initiation of S/V in patients hospitalised for ADHF either before or shortly after discharge, results in comparable rates of all cause and HF rehospitalisations, as well as emergency room visits without hospital admission over the 26 week follow-up period. HF re-hospitalisations rates at 10 weeks in TRANSITION are in line with the 8% in S/V arm reported in PIONEER-HF during the 8-weeks follow-up.

Acknowledgement/Funding

The TRANSITION study was funded by Novartis
P1655Lung ultrasound B-lines in patients with acute heart failure and comorbidities
Authors: Gargani L , Zavagli M , Barbarisi G , Marchiani C , Bandini G , Moggi-Pignone A
Published: October 2019

Background

Lung ultrasound assessment of B-lines is a sonographic method for a semi-quantitative evaluation of extravascular lung water, that can be employed to asssess and monitor pulmonary congestion in acute heart failure.

Purpose

To assess the degree and changes in B-lines during hospitalization for acute heart failure, independently of the etiology, and their correlation with patients' comorbidities.

Methods

Two-hundred and forty-one complete antero-lateral B-lines assessments were recorded in an old population of 73 patients (mean age 83.0±7.6 years, 54.8% males) admitted with a diagnosis of acute heart failure (AHF). Chronic obstructive pulmonary disease (COPD) was present in 30% patients, chronic kidney disease (CKD) was present in 31% patients, a previously known cardiac condition was present in 73% of patients. B-lines were evaluated according to standard protocol at admission (T1), at 24 hours (T2), 48 hours (T3) and at discharge (T4). NT-proBNP was assessed at admission and at discharge.

Results

Mean antero-lateral B-lines at T1 were 42±39 with a statistically significant reduction at T3 (25±23, p<0.001) and at T4 (16±22, p<0.001), but not at T2 (37±38, p=0.41) (see figure), with high variability in the percentage of B-lines reduction among patients, at all time points, and with 34% of patients with still significant pulmonary congestion at discharge (≥15 B-lines). B-lines number and changes did not differ in patients with and without COPD, CKD, or a previously known heart/valvular disease. A weak, albeit significant correlation was found between the percentage of B-lines change between admission and discharge and total diuresis (R=-0.25, p<0.05), delta (T3 values - T1 values) glomerular filtration rate (R=0.30, p<0.05) and delta NT-proBNP (R=0.31, p<0.05).

Dynamic changes of B-lines over time

Conclusions

In older patients hospitalized with AHF with multiple comorbidities, B-lines are present at admission and significantly reduce at 48 hours, although with high variability among different patients at all time points, and persistent significant congestion at discharge in about one third of patients. Lung ultrasound B-lines provide a specific and dynamic information about the degree and changes of pulmonary congestion, which is additive to other patient's characteristics.
P1660Therapy treatment, adherence and persistence in chronic heart failure patients: a populaion study, from 2005 to TO 2012 in Lombardy
Authors: Scalvini S , Bernocchi P , Paganoni A M , Frigerio M
Published: October 2019

Background

The treatment with angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor II blocker (ARB), beta blocker (BB), and aldosterone antagonist (AA), adherence and persistence to therapies, improve clinical status, prevent hospital admission and reduce mortality in patients with chronic heart failure (CHF).

Purpose

To analyze adherence and persistence to indicated therapies.

Methods

We analyzed, from the Lombardy healthcare system administrative database, the discharge forms of patients with HF-related diagnosis, recorded from 2000 to 2012. We evaluated the adherence using the proportion of days covered (PDC≥80%) method, adjusted for hospitalisations. Medication persistence was identified as a duration of time from initiation to discontinuation of therapy. Patient was considered non-persistent if does non-refill medication within a period of 30 days.

Results

We considered 100,784 HF patients, mean (SD) age 74.54 (11.73) years: of them 636 patients were lost from database, 71,166 were alive (71.06%) and 28,982 did not survive (28.94%) at the end of the study. The mean (SD) number of hospitalizations were 2.16 (1.48) per patient (217,422 in total) and drug prescriptions were 12.28 (7.56) per patient (1,237.784 in total). 77% of patients were treated with ACEI/ARB, 64% with BB and 37% with AA. In the table, we reported the results on adherence and persistence measures.

Prescribed Therapy Total pts, No (%) Days covered, mean (SD) Adherent pts, No (%) Persistent pts, No (%) PDC (%), mean (SD) ACEI/ARB+BB+AA 20,831 (21%) 148 (102) 2,649 (13%) 2,068 (10%) 41 (28) ACEI/ARB+BB 33,617 (33%) 237 (110) 14,528 (43%) 11,165 (33%) 65 (30) ACEI/ARB+AA 9,327 (9%) 157 (107) 1,469 (16%) 1,149 (12%) 43 (29) AA+BB 3,070 (3%) 166 (105) 518 (17%) 386 (13%) 45 (29) ACEI/ARB 23,398 (23%) 270 (103) 13,487 (58%) 10,882 (47%) 74 (28) BB 6,806 (7%) 259 (105) 3,567 (52%) 2,782 (41%) 71 (29) AA 3,735 (4%) 204 (113) 1,133 (30%) 922 (25%) 56 (31) pts, patients.

Conclusions

Findings of this database analysis suggests that while treatment with ACEI/ARB and BB is in line of European Guideline, treatment with AA is very low. Despite recommendations, treatment with a combination of two or three HF drug classes decreases further. Adherence and persistence were moderate across all HF therapies of interest, although around 70% for ACEIs, BBs alone and in combination. This analysis evidences the need to understand the reasons for a limited use of the therapeutic guidelines and the need for much more work to improve adherence and persistence to therapy in CHF patients.
P1665Identifying metabolic treatment strategies for heart failure - A meta-analytic approach
Authors: Nguyen T D , Schenkl C , Schlattmann P , Heyne E , Doenst T , Schulze P C
Published: October 2019

Background

Current expert consensus suggests modulation of cardiac glucose oxidation (GO) or fatty acid oxidation (FAO) as a therapeutic approach for heart failure (HF). However, inconsistency exists and there is no systematic evidence supporting this concept.

Objective

We conducted a systematic review of preclinical studies to assess the role of metabolic treatment in HF. We aimed to identify, via meta-analytic techniques, specific metabolic strategies that potentially improve cardiac function.

Methods

We searched PubMed, Web of Science and reference lists of identified primary studies from inception to 31 December 2018. We included all interventional studies that assessed changes in cardiac function together with those in cardiac GO and/or FAO in established animal models of HF. Two investigators extracted study characteristics and data independently. We encompassed all available measures of cardiac function in the analysis instead of selecting one single outcome. Effect sizes were calculated as Hedges' g. We used I2 to estimate heterogeneity, metaregression to explore sources of heterogeneity and contour-enhanced funnel plot to assess publication bias.

Results

Our search returned 64 reports that fulfilled the inclusion criteria (n=1532 animals). The overall effect of treatments associated with metabolic changes was 0.78±0.16 g, p<0.001. There was a high heterogeneity (I2 = 86.7%) and no signs of publication bias. Metaregression revealed that treatments associated with an increase in GO (1.09±0.13 g, p<0.001) markedly enhance cardiac function. In contrast, those associated with decreased GO may worsen outcome. Although most experts suggest inhibiting FAO to improve cardiac function in HF, we found a beneficial result with a large total effect size for approaches that boost FAO (1.69±0.65 g, p<0.01).

Conclusions

Our data highlight the role of cardiac metabolism in treating HF. Specifically, increasing GO or FAO may considerably improve cardiac function. Furthermore, the findings challenge the common notion that inhibiting cardiac FAO is protective.
P1669Frequency and patterns of implantable cardiac defibrillator therapies in patients with ventricular assist devices
Authors: Gkouziouta A , Kogerakis N , Spartalis M , Kostopoulou A , Bonios M , Voudris V , Livanis E , Adamopoulos S
Published: October 2019

Purpose

Durable ventricular assist devices (VADs) use is a life-saving therapy in patients with end-stage heart failure. These patients are at high risk for ventricular arrhythmias. The pattern of ICD therapies in these patients is not well characterized.

Methods

Our single-center retrospective cohort included 86 patients with ICDs and VADs followed at our Centre. Data collected included frequency of ICD therapies, type of therapy (appropriate vs. inappropriate; shocks vs. anti-tachycardia pacing (ATP)), and time-course of therapies.

Results

36 patients (42%) received ICD therapy during a mean follow-up period of 13.6 months. There were 105 episodes (2.9 episodes/patient) during which ICD therapies were delivered, with a total of 379 individual arrhythmias treated (3.6 arrhythmias per episode of therapy). 61.4% of therapies were appropriate, 8.4% were inappropriate, and 31.6% were unknown. Of the 79 episodes treated with appropriate therapy, 36 episodes (46%) required ICD shocks, whereas 43 episodes (54%) were treated with ATP alone. Overall, 33% of the total cohort and 81% of patients who received therapy received at least one ICD shock. Twenty-two patients (61%) received therapy between 1–3 times, while the remainder (14 patients, 39%) received therapy 3–10 times. Eighteen (17%) episodes occurred within the first month after LVAD implantation, with 10 (10%) occurring between 1–3 months, 53 (50%) occurring between 3–12 months, and 24 (23%) occurring more than one year after VAD implantation.

Conclusion

Analysis of our VAD cohort revealed three important findings: 1. ICD therapy is very common (42%) in the first year especially after LVAD implantation; 2. Ventricular arrhythmias are highly clustered in this cohort; 3. ATP is frequently effective. These findings have important implications on device follow-up and programming for this expanding patient population.
P1671Subclinical persistent hemolysis may affect late renal function deterioration after HeartMateII implantation
Authors: Iwasaki K , Seguchi O , Mochizuki H , Kimura Y , Kumai Y , Kuroda K , Nakajima S , Watanabe T , Yanase M , Matsumoto Y , Fukushima S , Fujita T , Kobayashi J , Fukushima N
Published: October 2019

Background

Late renal function dysfunction is an increasingly recognized complication in continuous flow left ventricular assist device (CF-LVAD) patients. Although hemolysis is prevalent in CF-LVAD patients and hemolysis may deteriorate renal function, the influence of persistent hemolysis on renal function in CF-LVAD patients remains to be investigated.

Purpose

To investigate the influence of persistent hemolysis on renal function in CF-LVAD patients, using lactate dehydrogenase (LDH) as a sensitive marker of hemolysis.

Methods

Excluding patients who died or underwent pump exchange for pump thrombosis, we retrospectively reviewed 65 consecutive adults who underwent HeartMateII implantation in our center from May 2011 to October 2017. Patient characteristics, chronotropic change of estimated glomerular filtration rate (eGFR) and LDH values weekly for 4 weeks and every 4 weeks between 4 and 48 weeks after implantation were collected. Then, calculating mean LDH during 48 weeks after implantation, study population was divided into low and high mean LDH groups at the median value of mean LDH.

Results

The median value of mean LDH was 304 U/l. Compared with low LDH patients, though high LDH patients were more likely female and had smaller body surface area, there were no significant difference in pre-operative eGFR between the groups (66.0±23.7 vs. 70.2±25.7 ml/min/1.73m2, p=0.495). After 40 weeks after implantation, high LDH patients had significantly lower eGFR than low LDH patients (71.0±23.7 vs. 87.1±31.4 ml/min/1.73m2, p=0.024). In multivariate linear regression analysis, mean LDH [parameter estimate: −0.10 (95% CI: −0.17 to −0.04), p=0.003] and post-operative pulse pressure [parameter estimate: 0.71 (95% CI: 0.05 to 1.37), p=0.036] were significantly associated with eGFR change during 48 weeks after HeartMateII implantation.

Univariate and multivariate linear regression analysis for eGFR change Univariate parameter estimate 95% CI p value Multivariate parameter estimate 95% CI p value Bilirubin, mg/dl 9.97 3.82 to 16.13 0.002 6.55 −0.43 to 13.53 0.065 BNP, pg/ml 0.01 0.00 to 0.02 0.044 0.00 −0.01 to 0.01 0.528 Mean LDH during 4 to 48 weeks, U/l −0.11 −0.18 to −0.05 <0.001 −0.10 −0.17 to −0.04 0.003 Pre-operative right atrial pressure, mmHg 1.43 0.35 to 2.51 0.010 −0.06 −1.52 to 1.40 0.935 Post-operative pulse pressure, mmHg 0.77 0.03 to 1.52 0.042 0.71 0.05 to 1.37 0.036

Conclusions

High mean LDH and low pulse pressure were associated with a significant decrease in eGFR late after HeartMateII implantation. Subclinical persistent hemolysis may be associated with late renal function deterioration in CF-LVAD patients.
P1674High intensity interval exercise program in heart failure patients seems to benefit cardiac power along with aorto-ventricular mechanical pump capacity and cardiorespiratory indices
Authors: Chrysohoou C , Angelis A , Titsinakis G , Tsiachris D , Aggelopoulos P , Koulouris N G , Vogiatzis I , Tousoulis D
Published: October 2019

Background

Cardiac power has been suggested as the most power predictor of mortality in heart failure (HF) patients. In those patients aorta elastic properties and compensation is lost, systolic (and pulse) pressure are therefore reduced and associated with a decrease in ejection duration and pump efficiency. Cardiac rehabilitation programs have showed enhancement in cardiac performance and quality of life in HF patients.

Aim

Aim of this work was to evaluate the effect of high-intensity interval exercise (i.e., 30 sec at 100% of max workload, followed by 30 sec at rest, on a day-by-day 30 minutes working-out schedule for 12 weeks), on cardiac power, diastolic function indices, right ventricle performance and cardiorespiratory parameters among chronic HF patients.

Methods

72 consecutive HF patients (NYHA class II-IV, ejection fraction <50%) who completed the study (exercise training group, n=33, 63±9 years, 88% men, and control group, n=39, 56±11 years, 82% men), underwent cardiopulmonary stress test, non-invasive high-fidelity tonometry of the radial artery, pulse wave velocity measurement using a SphygmoCor device, and echocardiography before and after completion of the training program. Cardiac power output (CPO) (W) was calculated as mean arterial pressure × CO/451, where mean arterial pressure = [(systolic blood pressure − diastolic blood pressure)/3] + diastolic blood pressure.

Results

Both groups reported similar medical characteristics and physical activity status. General mixed effects models revealed that the intervention group increased 6MWT (by 13%, p<0.05); increased cycle ergometry WRpeak (by 25%, p<0.01), showed higher O2max by 31% (p<0.001) and lower VE/VCO2 (p=0.05), whereas patients in the control group showed nosignificant changes in the aforementioned indices. Also, in the intervention group Emv/Vp was decreased by 14% (p=0.06); E to A ratio by 24% (p=0.004) and E to Emv ratio by 8% (p=0.05); while Stv increased by 25% (p=0.01). Most importantly, the intervention group reduced pulse wave velocity by 9% (p=0.05) and increased augmentation index by 26%; and VTI by 4% (p=0.05); Those parameters were not significantly changed on control group (all p>0.05).

Conclusion

Hight intensity exercise rehabilitation program revealed beneficial effect on left ventricular diastolic indices and right ventricle performance. As, in those patients compensation of the aorta is also lost and the LV cannot generate the extra force necessary to completely overcome the late systolic augmented pressure, the increase in the augmented pressure (AIa) observed in the intervention group reflects the benefit in aorto-ventricular coupling and cardiac power that boosts systolic pressure and restores a positive influence in pressure, like in early stages of HF.

Acknowledgement/Funding

None
P1675Evolution of lactate dehydrogenase levels in patients with HeartMate II, HeartWare and HeartMate 3 left ventricular assist devices during first-year follow-up
Authors: Yalcin Y C , Muslem R , Papageorgiou G , Tedford R J , Constantinescu A A , Birim O C , Brugts J J , Manintveld O C , Hsu S , Leebeek F W G , Bogers A J J C , Caliskan K
Published: October 2019

Background

Lactate dehydrogenase (LDH) is considered as a biomarker of thrombotic events in patients receiving a left ventricular assist device (LVAD).

Purpose

This study aimed to investigate the evolution of LDH levels over time between patients supported with a HeartMate II (HMII), HeartMate 3 (HM3) or HeartWare (HVAD) LVAD during their first-year post implantation.

Methods

We analyzed in this multi-center retrospective study, all patients with HMII, HM3 and HVAD LVAD implanted between December 2006 and April 2017. Patients were classified into three groups based on their device type. Loess splines over time were used to depict the repeated measurements of LDH.

Results

In total, 134 patients received an LVAD (77% male, mean age 55 [46–61]), of whom 64 (48%) were HMII, 22 (16%) HM3 and 48 (36%) were HVAD. Loess splines over time indicate that there could be a considerable difference between evolution of LDH (Figure). During the first-year follow-up, 3 (5%) patients had a confirmed and 10 (16%) patients had a suspected pump thrombosis in the HMII group. For the HVAD, there were 6 (13%) patients with confirmed thrombosis and 1 (2%) case of suspected thrombosis, whereas none of the patients in the HM3 group experienced a suspected or confirmed pump thrombosis (p=0.01). The 1-year overall survival rate for HM II, HM3 and HVAD was 84%, 86% and 72% respectively (p=0.311). The overall stroke-free rate at one year was: 89%, 77% and 91% for HMII, HVAD and HM3 respectively (p=0.15).

Means of observed LDH values over time

Conclusion

During the first-year post LVAD implantation, there appear to be different evolutions of LDH levels over time in HMII device patients compared to HVAD or HM3 device patients. Given differences in baseline hemolysis levels between devices, currently used LDH thresholds for detection of impending pump thrombosis may be less sensitive and thus thresholds may be device specific.
P1685Risk factors and earliest signs of heart damage in young adults with hypertension
Authors: Chevplyanskaya O , Dudarev M V
Published: October 2019

Background

It is well known that the risk of cardiovascular complications becomes higher even in high normal BP ranges. High normal BP is usually asymptomatic in young age. It is important to establish the main risk factors and the initial signs of cardiac dysfunction at early stages of arterial hypertension (AH) formation.

Objective

To assess the prevalence of leading risk factors and to investigate the global longitudinal strain rate of left ventricle (LV) by speckle tracking (STE) method in young men with high normal pressure.

Methods

The study involved 80 patients aged 22 (20; 25) years. The first group (I) included 55 subjects with high normal office BP values (130–139/85–89 mm Hg), the second group (II) consisted of 25 subjects with office BP less than 130/85 mm Hg. Anthropometric and blood biochemical parameters were tested in all subjects. The heart status was assessed according to transthoracic echocardiography-data. The test was performed on an expert class apparatus General Electric Vivid 7 in the B and M mode by the pulse wave and color flow Doppler. LV functional status was assessed by STE with GLPS analysis. STE data was obtained in B-mode from three apical positions with a frame rate of 80–90 per minute. longitudinal peak systolic strain (LPSS) in basal, midwall and apical segments as well as a LV walls was assessed in the compared groups. The parameters tested are presented as median, interquartile range, average and standard deviation.

Results

Both groups were comparable in age. Smoking (25.9% and 28.6%, p=0.54) and total cholesterol (48,1% and 45,5%; p=0,11) were highly prevalent in groups I and II. Overweight is registered significantly more frequently in subjects with high BP (41.5% and 14.3 respectively, p=0.0009). Family history of premature cardiovascular disease, heart rate, diabetes, uric acid were comparable in both groups. The GLPS value was significantly lower in the group with high normal BP than in the reference group: −19,1 (−17,71; −20,2) and −20,9 (−20,6; −22,4) (p=0,0014). The decrease of LPSS at the basal and midwall segments was recorded more often in subjects with high normal BP (p=0.0008 and p=0.0003, respectively). LPSS in all LV walls was significantly lower in group I. LPSS in anteroseptal wall was 18.7±3.4 and 21.1±4.1, p=0.029; in anterior wall it was 19.8±2.9 and 22.3±3.0, p=0.006; in lateral wall it was 18.7±3.3 and 20.9±1.9, p=0.004; in inferolateral wall it was 18.7±3.3 and 21.1±3.2, p=0.017), in inferior was (19.8±3,1 and 22.3±2.2, p=0,002), in inferoseptal was (17.2±3.4 and 19.8±1.6, p=0.0007) in groups I and II, respectively. The nature of revealed changes in the subjects with high blood pressure requires further targeted investigation.

Conclusion

The multisegment GLPS decrease may be the earliest marker of myocardial dysfunction in the initial stages of hypertension. The contribution of overweight is evident in the persistent BP increase.