bluuebunny/crossref_metadata_2025 huggingface dataset:
P1474Simpsons Triplane versus Biplane for left ventricle ejection fraction after myocardial infarction
Authors: Bras D , Reis C , Andrade M J , Ribeiras R , Mendes M
Published: October 2019

Introduction

Simpson's biplane (SBP) ignores the apical long-axis plane. It is estimated that 40% of myocardial infarction (MI)-related segmental abnormalities are located in this plane. The real-time triplane (RT3P) overcomes this issue, allowing to obtain all apical views simultaneously, at the same cardiac cycle. This method could be a more precise and reliable alternative to SBP in ejection fraction (EF) quantification in this setting.

Purpose

The authors aimed to compare EF assessed by two quantification methods, SBP and RT3P, using quantitative three-dimensional echocardiography (3DE) as the reference method, in patients with MI.

Methods

We have prospectively gathered data from 52 adult patients, which had recent or past history of MI. Exclusion criteria were the presence of atrial fibrillation, unknown coronary anatomy, significant valvular disease, left branch block, ventricular pacing and poor definition of endocardial borders.

Estimation of EF by SBP, RT3P and 3DE was performed in all patients and gathered by two experienced operators. The two operators were blinded for the coronary angiography results before volume quantification. They were also blinded for their own measurements, as well as for the other operator's measurements.

Spearman's correlation and linear regression were performed for correlation analysis. Bland-Altman plot was used for agreement assessment among the different methods. Interobserver agreement was assessed by Cohen's kappa.

Results

Patient characteristics are shown in table 1. EF calculation was feasible in all patients.

There were excellent correlations between EF measured by SBP vs 3DE and RT3P vs 3DE (r=0.813 and r=0.9 respectively).

Test of equality between two correlation coefficients confirmed that EF by RT3P method is significantly more correlated with the reference method, compared with EF by SBP (p=0.004).

We have also performed a further analysis to study this results in special subsets. In anterior MI subset, EF by RT3P correlated by 0.909 with 3DE, versus 0.826 from EF by SBP (p=0.019). In inferior MI subset, EF by RT3P correlated by 0.779 with the reference method, versus 0.706 from EF by SBP (p=0.246).

Fig 1 Correlation and Bland-Altman plot

Conclusions

Estimation of EF using SBP and RT3P methods by experienced operators strongly correlate with EF determined by 3DE. The RT3P method showed the strongest correlation between the two methods, which may point to its usefulness in the evaluation of EF in patients with anterior wall motion abnormalities after myocardial infarction.
P1483Serial changes in peak left atrial strain predicts diastolic remodelling following percutaneous revascularisation for ST-segment elevation myocardial infarction
Authors: Vo T , Nguyen T , Chen A , French J , Otton J , Mussap C , Richards D , Dimitri H , Thomas L
Published: October 2019

Background

Echocardiographic 2D speckle tracking peak left atrial (LA) strain reflects LA reservoir function. Limited studies have reported the relationship between peak LA strain and diastolic dysfunction. In addition, adverse diastolic remodeling (ADR) has been reported, to have better prognostic value than single diastolic function assessment following ST-elevation myocardial infarction (STEMI).

Purpose

We examined the relationship between serial changes in echocardiographic peak LA strain and diastolic function in STEMI patients.

Methods

186 percutaneously revascularized first presentation STEMI patients (87% male, 56.9±10.6 years) underwent serial TTE at baseline (2–7 days) and at follow-up (8–10 weeks) post-STEMI. Peak LA reservoir strain measurements were analysed from apical 2-, 3- and 4- chamber views. Diastolic function was graded as per 2016 guidelines: normal, grade 1, grade 2 and grade 3. ADR was defined as worsening of diastolic function grade (≥1) from baseline to follow-up, or persistent grade 3.

Results

Lower baseline peak LA strain was associated with grade 2 and grade 3 diastolic dysfunction compared to normal and grade 1 function at follow-up (p<0.05, see figure and table). Change in LA strain was less with worsening grades of diastolic function (see table). ADR was seen in 33 patients. Lower baseline peak LA strain predicted ADR (B=0.86 (0.80–0.92), p<0.0001). In addition, a reduction in peak LA strain at follow up was independently associated with ADR (B=0.91 (0.84–0.97), p=0.007) (see figure).

Diastolic function grades with LA strain Follow-up diastolic function Baseline peak LA strain (%) Follow-up peak LA strain (%) Change in peak LA strain (%) Normal (n=91) 35.70±6.38 40.97±8.10 5.26±6.07 Grade 1 (n=61) 30.70±6.97 34.54±8.77 3.84±6.32 Grade 2 (n=17) 23.95±6.11 25.49±5.93 1.54±4.70 Grade 3 (n=17) 23.66±8.07 23.49±10.64 −0.17±7.44 Data presented as mean ± SD.

Peak LA strain vs diastolic function

Conclusion

Peak LA strain is associated with diastolic function following STEMI and differentiates normal diastolic function from diastolic dysfunction. Serial changes in peak LA strain correlated with diastolic remodelling. Longer-term follow-up is required to determine the prognostic value of changes in peak LA strain, and diastolic remodelling.
P1499Data-driven clustering unveils the adaptive remodeling of athlete heart: an echocardiographic study from 2017 Taipei summer universiade
Authors: Huang K
Published: October 2019

Background

Sport-specific adaptations of the athlete's heart are still under investigation. This study sought to provide a proof-of-concept for hierarchical clustering of echocardiography-derived parameters in unfolding the adaptations and to make a comparison between hypothesis-driven and data-driven approaches for characterizing the athlete's heart.

Methods

Anthropometric, echocardiographic and electrocardiographic assessments were collected during the peri-participation cardiovascular examination of 2017 Summer Universiade. Besides standard echocardiography and strain measurements, ventricular-arterial coupling was assessed by the ratio of effective arterial elastance (Ea) to left ventricular end-systolic elastance (Ees), using a modified single-beat algorithm to calculate Ees.

Results

A total of 598 elite athletes (348 male, mean age 23±2.5 years) engaged 24 disciplines were grouped by Mitchell's classification. The hypothesis-driven approach showed significant differences in heart rate, ventricular size, and stroke volume when classified by dynamic levels. Adaptations of ventricular function were not found. Contrarily, the data-driven approach not only hierarchically clustered athletes with more manifest morphologic remodeling, more proportions playing high dynamic sports but also showed a functional propensity of lower Ea and Ees, supranormal diastolic function and preserved ventricular-arterial coupling with ample pumping reserve.

Phenotype heatmaps of athletes

Conclusions

The hierarchical clustering can analyze numerous echocardiography-derived phenotypes pertaining to an individual athlete as well as discern an adaptive propensity of the athlete's heart to be the resting status of a reservoir-rich pump. This pilot demonstration of the data-driven approach in figuring out integrated physiologic adaptations with remodeling-relevant geometry and function leads to a fundamentally improved understanding of the athlete's heart and then will be applicable to various domains.
P1506Pulmonary decongestion pattern during stress lung ultrasound
Authors: Arbucci R O , Scali M C , Zagatina A , Cortigiani L , D'Andrea A , Borguezan Daros C , Wierzbowska-Drabik K , Djordjevic-Dikic A , Simova I , Amor M , Vargas Mieles P E , Merlo P M , Lowenstein J A , Ciampi Q , Picano E
Published: October 2019

Background

B-profile detected by lung ultrasound (LUS) during stress echocardiography (SE) consists in B-lines with lung sliding and mirrors extra-vascular lung water accumulation (“wet lung”), more often found with ischemic regional wall motion abnormalities (RWMA) and/or diastolic dysfunction. B-lines present at rest may also decrease during stress.

Aim

To assess the frequency and functional correlates of decreasing B-profile (“drying lung” pattern) during SE.

Methods

We prospectively performed transthoracic echocardiography (TTE) and LUS evaluation at rest and peak stress in 780 patients with B-lines at rest referred for exercise (n=387), vasodilator (n=324) or dobutamine (n=69) SE for known/suspected coronary artery disease (CAD) and/or heart failure (HF). Recruitment occurred in 17 certified labs of 8 countries with the ABCD protocol, including regional wall motion abnormalities with wall motion score index (WMSI), B-lines, left ventricular contractile reserve (LVCR based on force, systolic blood pressure/end-systolic volume) and Doppler-based coronary flow velocity reserve (CFVR, available in 473 patients). By LUS, we adopted the 4-site simplified scan, each site scored from 0=normal A-lines, to 10=coalescing B-lines. By selection, all patients had resting B-lines score ≥2. Invasive or noninvasive coronary angiography was available in 208 patients.

Results

Two B-lines stress patterns were identified: Group 1, increase or unchanged pattern (B-line stress score ≥ rest, n=698, 89%); Group 2, decrease-disappearance pattern (B-line stress score < rest for ≤2 points, n=82, 11%). Group 1 showed higher prevalence of inducible ischemia (Group 1 = 74/698 vs. Group 2 = 5/82, 11% vs. 6%, p<0.001), abnormal LVCR (Group 1 = 403/698 vs. Group 2 = 36/82, 58% vs. 42%, p=0.012) and impaired CFVR (Group 1 = 173/433 vs. Group 2 = 5/40, 40 vs. 12%, p<0.001): see figure. Two- or three-vessel coronary artery disease was also more frequent in fixed-worsening pattern (Group 1 = 88/191 vs. Group 2 = 3/17, 46 vs. 17%, p=0.024). Multivariate logistic regression analysis identified peak Force (Odds Ratio, OR, 1.039, 95% Confidence Intervals, CI: 1.006–1.074, P=0.022), stress-rest Δ-WMSI (OR 0.190, 95% CI 0.086–0.419, P<0.001) and normal CFVR (OR=1.754, 95% CI: 1.147–2.682, P=0.010) as significant predictors of drying lung pattern.

Disappearing BLines

Conclusion

About one out of 10 patients with resting B-lines exhibit a decrease-disappearance pattern during stress. They show a more benign coronary anatomic, myocardial functional and coronary physiological profile compared to patients with the fixed-worsening pattern. The drying lung pattern is more often accompanied by a strong (higher peak force), non-ischemic and warm heart (with normal CFVR).
P1526Pre-dialysis left atrial function assessed by two-dimensional speckle tracking echocardiography as a predictor of upcoming heart failure in hemodialysis patients
Authors: Park H , Kim M , Jeong H K , Kim K H , Cho J Y , Yoon H J , Park J C
Published: October 2019

Background

Left atrial global longitudinal strain (LA GLS) by 2-dimensional speckle tracking echocardiography is a useful tool to assess LA function and left ventricular (LV) diastolic function. The authors assessed prognostic value of LA GLS, and other diastolic functional parameters in patients undergoing hemodialysis.

Methods

A total of 78 (49 male) patients undergoing hemodialysis who checked echocardiography due to heart failure (HF) symptoms were included for this analysis. Echocardiography wasperformed at the same day of, and before hemodialysis session. Besides conventional echocardiographic measurements, GLS of the LA and the LV were checked and compared. Incidence of rehospitalization due to HF symptoms during mean follow up duration of 381.4±197.5 days was investigated and echocardiographic parameters were compared between patients who experienced rehospitalization and who did not.

Results

16 (20.1%) patients experienced rehospitalization due to HF. HF rehospitalization group had significantly low baseline LV ejection fraction (55.7±7.2 vs. 61.3±7.1%, p=0.006) and LV GLS (14.7±3.4 vs. 18.2±3.9%, p=0.002), while LV geometry (LV end-diastolic volume index and LV wall thickness) did not show significant differences. In HF rehospitalization group, baseline LA function and diastolic function were significantly impaired as reflected by LA GLS (18.8±2.6 vs. 23.8±3.6%, p<0.001), E/E' ratio (20.8±3.3 vs. 15.8±4.6%, p<0.001), and right ventricular systolic pressure (61.4±9.6 vs. 53.4±12.8%, p=0.022). LA end-systolic volume index was not significantly different between the 2 groups. Among various echocardiographic parameters, receiver operation characteristic curve analysis revealed that LA GLS had the strongest power (cutoff value 20.6%, sensitivity 0.813 and specificity 0.790, area under curve 0.849) in prediction of future rehospitalization due to HF.

Predictor of future HF: ROC analysis

Conclusions

The present study demonstrated that functional changes of the LA as measured by LA GLS before hemodialysis session can be used as an echocardiographic parameter to predict future rehospitalization due to HF. Further studies are required to evaluate prognostic value of LA function in predicting other cardiovascular events in hemodialysis patients.
P1529Coronary and aortic atheroma are not identical diseases: A calcium score comparative study in 1010 patients with a normal SPECT
Authors: Foult J.-M , Katsahian S , Nevoret C , Hoffman O , Sabouret P , Attal B , Friedlander G
Published: October 2019

Calcium scores of the coronary arteries (CCS) and – more recently – of the the thoracic aorta (TCS), have been established as risk markers for cardiovascular events. Yet, little is known about the relationship between these two calcium scores.

In this study, CCS and TCS were compared in 1010 patients with a normal SPECT. Mean age was 64.5±8.7 yrs with 73.4% of men. CCS and TCS ranged between 0 and 5827 for CCS and from 0 to 58600 for TCS, with means of 281.1 and 1206 respectively. Such a difference was expected since the vascular surface of the thoracic aorta is approximately 5 times larger than that of the coronary arterial tree. Both CCS and TCS increased with the number of risk factors (p=0.000841 and p=0.000579)

No significant relation was found between CCS and TCS for the entire group. However, when adopting a best-fitting curve model, 2 populations could be clearly identified: those with predominant TCS (N=552), and those with a- relatively- predominant CCS – (N=458).

In each of these two groups, CCS and TCS were significantly related (r=0.63 and 0.69 respectively p<2.2e-12). Both groups had a comparable exposition to smoking and diabetes, but Group1 patients had more dyslipemia and high blood pressure than group 2 patients.

Conclusion

Calcified atheroma was frequently observed In patients with a normal SPECT, but no significant relation existed between CCS and TCS; patients with a predominant atheroma of the coronary arteries were not the same than patients with a predominant atheroma of the aorta, with both groups having different expositions to risk factors. This suggests that atheroma of the coronary arteries and of the thoracic aorta are close but not identical diseases.
P1571Atrial fibrillation is an independent predictor of mortality in hospitalized cancer patients
Authors: Malik A H , Shetty S , Malik S
Published: October 2019

Background

Atrial fibrillation (AF) is prevalent in patients with cancer. We performed a study to evaluate the outcomes associated with hospitalised cancer patients with AF.

Methods

The Nationwide Inpatient Sample was used to identify patients with a cancer diagnosis, who were found to have atrial fibrillation from the years 2002–2014. Descriptive statistics for mortality were calculated using univariate and multivariate model for each cancer, and we identified the type of cancer associated with the highest inpatient mortality. We also calculated the percentage of hospital mortality attributable to AF.

Results

12,410,290 (nationwide estimate) patients with a cancer diagnosis were identified, and 8.2% of them had AF. In a multivariate adjusted model for various relevant comorbidities, age, gender and race, AF was also found to be an independent risk factor for higher in-hospital mortality in cancer patients, odds ratio (OR) 1.25 (95% CI 1.23, 1.28, p<0.0001). Colon cancer was found to be associated with the worst outcomes and the highest mortality. In cancer patients, the incident percentage of hospital mortality attributed to AF was 46.7%, population attributable mortality risk of was 7.17%, and number needed to harm was 21 (p<0.0001).

Conclusion

AF conferred significant morbidity and was found to be an independent risk factor for increased mortality in hospitalised patients with cancer. Colon cancer was found to have the strongest association of worst outcomes in hospitalized patients with AF.

Acknowledgement/Funding

None
P1578Outcomes in patients with renal impairment and myocardial injury or infarction identified by high-sensitivity cardiac troponin testing: a secondary analysis of the High-STEACS trial
Authors: Gallacher P J , Miller-Hodges E , Shah A , Anand A , Lee K K , Chapman A R , Farrah T , Halbesma N , Blackmur J , Newby D E , Mills N L , Dhaun N
Published: October 2019

Background

Patients with renal impairment are at increased risk of myocardial infarction (MI), but the interpretation of cardiac troponin is challenging in this setting. The use of high-sensitivity cardiac troponin (hs-cTn) assays increases the detection of myocardial injury, yet may contribute to uncertainty in the diagnosis of MI in those with renal impairment.

Purpose

To describe the diagnosis and outcomes of patients with myocardial injury or infarction identified using a hs-cTnI assay, stratified by renal function.

Methods

In a pre-specified secondary analysis of a stepped-wedge cluster-randomised controlled trial, we identified consecutive patients with a hs-cTnI concentration greater than the sex-specific 99th centile between June 2013 and March 2016. The diagnoses of type 1 or type 2 MI were adjudicated and classified according to the 4th Universal Definition of Myocardial Infarction. Renal impairment was defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73m2.The primary outcome of type 1 or type 4b MI or cardiovascular death was compared in patients with and without renal impairment at 1 year.

Results

A measure of renal function was available in 47,334 (98.0%) patients, of whom 7,933 (16.8%) had renal impairment (mean age 76±12 years; 54% female). Plasma hs-cTnI concentrations were >99th centile in 47.9% (3,800/7,933) of patients with renal impairment and 16.3% (6,439/39,401) of patients with normal renal function. In those with and without renal impairment, the adjudicated diagnosis was type 1 MI in 35.2% (1,336/3,800) and 55.8% (3,596/6,439) of patients, and type 2 MI in 12.6% (480/3,800) and 9.7% (626/6,439) of patients, respectively (P<0.001 for both). In patients with hs-cTnI concentrations >99th centile, the primary outcome occurred in 24.9% (945/3,800) of patients with renal impairment, compared to 12.1% (779/6,439) of patients with normal renal function (P<0.001). In patients with type 1 MI, the primary outcome occurred in 32.6% (436/1,336) of those with renal impairment and 11.7% (419/3,596) of those without (P<0.001). In patients with type 2 MI, the primary outcome occurred in 20.4% (98/480) and 9.9% (62/626) of patients with and without renal impairment, respectively (P<0.001).

Conclusion

Almost half of all patients with suspected acute coronary syndrome and renal impairment have hs-cTnI concentrations greater than the sex-specific 99th centile. Whilst only one in three had a diagnosis of type 1 MI, an elevated troponin concentration was associated with a poorer prognosis in those with concomitant renal impairment compared to those without, irrespective of the index diagnosis.

Acknowledgement/Funding

British Heart Foundation
P1589Thiazides and skin cancer risk: should we be worried?
Authors: Sousa J P , Puga L , Lopes J , Saleiro C , Lourenco C , Goncalves L
Published: October 2019

Introduction

Diuretic thiazides represent a first-line therapeutic option for arterial hypertension. However, this drug class is regarded as having photosensitizing properties, and, as such, may act as a carcinogen, by triggering phototoxic reactions. Whether or not its long-term use increases skin malignancy risk remains unclear.

Purpose

To examine a possible association between thiazide usage and the risk of skin cancer, namely basal cell carcinoma, squamous cell carcinoma and malignant melanoma.

Methods

MEDLINE, EMBASE, Cochrane Library and Google Scholar databases were comprehensively searched, from inception to the first of February of 2019, for observational studies mentioning thiazide diuretic usage and incidence or prevalence of cutaneous basal cell carcinoma, squamous cell carcinoma and malignant melanoma. Literature review, study selection and appraisal, including methodological quality assessment, and data extraction were independently led by two investigators. Meta-analysis was conducted using generic inverse variance outcome and, due to heterogeneity of the original studies, a random effects model. Confounder-adjusted summary relative risk (RR), with 95% confidence interval (CI), was pooled.

Results

Ten studies met eligibility criteria. Of these, six had a case-control design and the remaining were cohort studies. Overall, 7,079,530 patients were included; 125,946 were diagnosed with basal cell carcinoma, 21,775 with squamous cell carcinoma and 31,191 with malignant melanoma. One study encompassed only squamous cell carcinoma of the lip. In five articles, individual thiazides employed were not addressed, whereas three embraced solely hydrochlorothiazide and other two exclusively bendroflumethiazide. Thiazides were found to be associated with increased risk of basal cell carcinoma (six studies, RR=1.05, 95% CI=1.01–1.10, p=0.02, i2=62%), squamous cell carcinoma (seven studies, RR=1.35, 95% CI=1.05–1.74, p=0.02, i2=92%) and malignant melanoma (six studies, RR=1.17, 95% CI 1.11–1.23, p<0.ehz748.03491, i2=0%).

Conclusion

Risk of all three major forms of skin malignancy is heightened in thiazide diuretic users. Increased awareness and education, especially for those who are at high risk and under the form of intense solar irradiation avoidance, are warranted for both patients and healthcare providers.
P1600Querecetin prevents electrophysiolgical remodeling and reperfusion arrhythmias in dysmetabolic rats
Authors: Diez E R , Prado N J , Vazquez Prieto M A , Miatello R M , Ponce Zumino A Z
Published: October 2019

Background

Severe arrhythmias during reperfusion of myocardial infarctions are associated with increased mortality. High fat and fructose diet (HFFD) increases arrhythmic risk and predispose to diseases such as diabetes, hypertension, and dyslipidemia. Quercetin is a bioactive flavonol found in grapes and grapes derived products. This flavonoid has been proposed to prevent cardiovascular disease, but little is known about its electrophysiological properties.

Objective

To evaluate the electrophysiological effects of chronic quercetin administration in rats with increased arrhythmogenesis during the reperfusion due to a HFFD.

Methods

Male Wistar rats were fed for six weeks with control diet (C), HFFD (20% fat and 20% fructose w/w), HFFD supplemented with quercetin in a dose of 20 mg/kg/day (HFFDQ) or quercetin alone (Q). Isolated hearts were perfused with a Krebs-Henseleit solution and after 15 min stabilization, submitted to 10 min of regional ischemia followed by10 min of reperfusion. Epicardial action potential and arrhythmic events were analyzed.

Results

HFFD and HFFDQ developed metabolic syndrome, but action potential at 90% of repolarization lengthening only increased in HFFD (78±4 vs 55±3 ms, P<0.01 by ANOVAII). HFFD increased ventricular fibrillation incidence (HFFD 8 of 9; C 2 of 9 P=0.0152 by Fisher Exact test). Both groups treated with quercetin had low arrhythmic incidence (HFFDQ 2 of 10 and Q 1 of 9; P<0.0055 and P<0.0034, respectively when compared with HFFD). The severity of arrhythmias persisted high during reperfusion only in HFFD. Other less severe arrhythmias like salvos and extra beats occurred in similar proportion in the three other groups.

Conclusion

The above results confirm that a HFFD facilitates the occurrence of severe arrhythmias during reperfusion. Quercetin reduces arrhythmias and electrophysiological remodeling despite metabolic syndrome. Since quercetin is one of the most abundant dietary flavonoids, our results reinforce its nutraceutical potential.

Acknowledgement/Funding

I+D+i UNCuyo 2015
P1618A polymethoxy flavonoid, Nobiletin, Has a therapeutic potency against the development of heart failure through NBP1 activation
Authors: Sunagawa Y , Funamoto M , Shimizu K , Shimizu S , Katanasaka Y , Miyazaki Y , Wada H , Kan T , Hasegawa K , Morimoto T
Published: October 2019

Introduction

Maladaptive hypertrophy is being recognized as a critical event during the development of heart failure. The control of cardiac hypertrophy may be one of the therapeutic strategy for heart failure therapy. In our previous study, we screened natural compound library and found that a natural compound, Nobiletin, could inhibit cardiomyocyte hypertrophy in culture. Nobiletin has various useful effects such as anti-cancer, anti-inflammation, and anti-oxidant and may be applicable to pharmacological therapy for heart failure.

Hypothesis

We thought that nobiletin might prevent the development of heart failure in vivo and investigated the target molecule of Nobiletin in the heart.

Methods and results

In primary cardiomyocytes, Nobiletin significantly inhibited phenylephrine (PE)-induced hypertrophic responses such as increases in cell size and hypertrophic gene transcription, such as ANF and BNP. C57BL6 mice were subjected to sham or transarotic constriction (TAC). Oral administrations of Nobiletin (20 mg/kg/day) or vehicle were repeated for 8 weeks. Nobiletin treatment significantly prevented TAC-induced increases in PWT and systolic dysfunction. Nobiletin also suppressed TAC-induced myocardial cell hypertrophy, perivascular fibrosis, and hypertrophic gene transcriptions. To investigate the target molecule of Nobiletin, Nobiletin-binding proteins were purified from rat heart using biotin-conjugated Nobiletin. We identified 162 novel binding protein of Nobiletin by LC/MS-MS. One of them, Nobiletin-binding protein 1 (NBP1) related to cellular metabolic pathway. Pulldown assay demonstrated that biotin-conjugated Nobiletin, but not biotin, directly interacted with recombinant NBP1. In vitro enzyme assay showed that Nobiletin enhanced NBP1 activity. Although NBP1 knockdown could not affect PE-induced hypertrophic response gene transcriptions and cardiomyocyte hypertrophy, NBP1 knockdown failed to exhibit Nobiletin-mediated anti-hypertrophic effects. NBP1-KO mice and WT mice were subjected to sham or TAC and randomly divided into two groups: Nobiletin (20 mg/kg/day) and vehicle. After 8 weeks, Nobiletin significantly improved TAC-induced cardiac hypertrophy and systolic dysfunction in WT mice but not in NBP1-KO mice. Nobiletin also prevented TAC-induced increases in HW/BW rate, myocardial cell hypertrophy, and mRNA levels of ANF and β-MHC in WT mice but not in NBP1-KO mice.

Conclusions

In this study, we demonstrate that Nobiletin inhibits cardiomyocyte hypertrophy and the development of heart failure in vivo. NBP1 activity is required to exhibit therapeutic potency of Nobiletin for heart failure. These finding suggest that a natural compound, nobiletin, might be a candidate for heart failure agent in human.

Acknowledgement/Funding

This work was supported by JSPS KAKENHI Grant.
P1635A risk score for prediction of TIA/ischemic stroke in patients with heart failure and sinus rhythm
Authors: Hjalmarsson C , Fu M , Zverkova-Sandstrom T , Schaufelberger M , Ljungman C , Andersson B , Bollano E , Dahlstrom U , Rosengren A
Published: October 2019

Background

Prediction of ischemic cerebral events in patients with heart failure (HF) in the absence of atrial fibrillation (AF) is challenging.

Purpose

To prospectively test a staged approach to identify patients with HF and sinus rhythm who are at high risk of developing TIA/ischemic stroke (TIA/IS) during the first two years after diagnosis.

Methods

The analysis is based on patient data reported in the Swedish Heart Failure Register from January 2003 until December 2013. Patients with AF and those treated with anticoagulants were excluded. The study population was categorized in two groups according to left ventricular ejection fraction: LVEF ≤40% and LVEF >40%. Factors associated with TIA/IS were determined by univariate proportional hazard regression. The risk score included: age (1p for 65–74y; 2p for 75–84y; 3p for ≥85y), previous ischemic heart disease (1p), hypertension (1p), diabetes mellitus (1p), TIA/IS (2p), and kidney dysfunction (1p). Two-year hazard ratios with death as competing risk were computed. The probability of observing the outcome was calculated using the cumulative incidence function.

Results

A total of 16,865 patients (mean age 72.1±13.2y) were included in the study, 39.9% women; 59.7% had LVEF ≤40%. The two-year crude rate of TIA/IS, hemorrhagic stroke, and all-cause mortality were 3.3%, 0.3%, and 26%, respectively.

An incremental absolute risk for TIA/IS was observed for patients with LVEF ≤40% and score 1- ≥6: 1.6, 2.3, 3.6, 2.9, 6.3, and 7.1%, respectively. The corresponding HRs with 95% confidence interval (CI) and the patients with 0 points as reference group were: 2.8 (1.1–7.3), 4.0 (1.6–10.1), 6.6 (2.7–16.2), 5.5 (2.2–13.8), 14.4 (5.8–35.9) for score 1- ≥6, where all p-values were less than 0.05 and Wald χ2 for overall model fit <0.0001. The cumulative incidence per 1000 person-years was: 8.2 (5.4–12.5), 11.8 (8.3–16.7), 19.4 (15.1–24.8), 16.3 (12.6–21.1), 36.6 (29.4–45.4), and 42.1 (33.0–53.8), respectively.

In patients with LVEF >40% and score 1–≥6, the absolute TIA/IS risk was: 1.3, 3.1, 3.1, 3.3, 4.6, and 5.3%, respectively. The corresponding HRs with 95% CI and patients with 1 point as reference group was: 2.4 (1.1–5.2), 2.5 (1.2–5.3), 2.7 (1.3–5.7), 3.9 (1.8–8.2); and 4.6 (2.2–9.8), for score 1- ≥6 (all p<0.05 and Wald χ2 for overall model fit p=0.0002). The cumulative incidence per 1000 person-year was: 6.7 (3.4–13.2), 16.0 (10.8–23.8), 16.7 (12.5–22.2), 18.0 (13.9–23.4), 25.8 (19.4–34.3), and 30.6 (21.7–43.0), for score 1- ≥6, respectively.

Conclusion

In the current study, a risk score compiling age and specific comorbidity was shown to predict increased risk of TIA/IS, regardless of LVEF, during the first two years after diagnosis in patients with incident HF in sinus rhythm.
P1636Causes and risk factors for non-cardiovascular hospital readmissions among heart failure patients
Authors: Keidan T , Olmer L , Ziv A , Benderly M , Kalter-Leibovici O
Published: October 2019

Background/Introduction

Despite better patient-management and technological improvements, patients with heart failure (HF) have poor prognosis and impaired health-related quality of life (HRQoL). HF patients also experience significant non-cardiovascular morbidity leading to higher disease burden and recurrent hospitalizations, which also put a heavy burden on healthcare systems.

Purpose

To describe causes and risk factors for non-cardiovascular hospital readmissions among HF patients.

Methods

We analyzed 3,172 hospital discharge summaries for 927 patients enrolled in a clinical trial testing the efficacy of a disease management program compared to usual care between August 2007 and June 2011. The study intervention had no effect on hospital admission and mortality rates. Baseline information on patient characteristics included age, gender, LVEF, NYHA classification, 6-minute walk test, BNP level, BMI, chronic comorbidity and HRQoL score. Analysis of hospital discharge summaries included identification and coding of the primary hospital admission cause. These causes were further grouped to HF-related, other cardiovascular disease-related and non-cardiovascular causes. Information on follow-up prescription purchases of HF drugs was also collected. Factors associated with non-cardiovascular hospital admission rate were tested in multivariable models, adjusted for study group, study period and year of recruitment.

Results

Non-cardiovascular hospital admissions (of which 77% were non-elective) accounted for 45% of all hospital readmissions. Of these hospitalizations, 23% were due to infectious diseases, 13% due to gastrointestinal causes, 12% due to respiratory causes and 8% due to falls and associated trauma. Patients with two or more non-cardiovascular hospital admissions during follow-up were significantly older, more commonly female, had higher proportion of preserved LVEF (≥50%), worse baseline functional capacity and HRQoL score, and higher co-morbidity score, BNP level and mortality rates compared to other patients. Factors significantly and independently associated with higher acute non-cardiovascular hospitalization rate included [rate ratios (RRs), 95% confidence intervals (CIs)]: non-preserved vs. reduced LVEF [1.48 (1.14, 1.92)]; higher baseline comorbidity score [1.14 (1.08, 1.21) per 1-point increment]; and higher loop diuretics, beta-adrenergic receptor blockers and ACE-I/ARBs treatment level during follow-up; 4th vs. 1st quartiles: 4.13 (2.93, 6.32), 1.51 (1.07, 2.13) and 1.32 (0.96, 1.82), respectively. Baseline overweight/obesity and greater 6-min. walking distance [0.93 (0.89, 0.93) per 50m increment] were found protective.

Conclusion

This study indicates a higher disease burden and mortality rate among HF patients with recurrent non-cardiovascular hospital admissions. It provides pertinent information needed for the design and implementation of effective interventions to reduce disease burden in HF patients.
P1645Vascular endothelial growth factor-D and mortality in suspected or known coronary heart disease patients with a history of heart failure: a subanalysis of the ANOX study
Authors: Iguchi M , Suzuki M , Matsuda M , Ajiro Y , Shinozaki T , Sakagami S , Yonazawa K , Shimizu M , Funada J , Takenaka T , Wada M , Abe M , Akao M , Hasegawa K , Wada H
Published: October 2019

Background

Vascular endothelial growth factor-D (VEGF-D) is a secreted glycoprotein that can act as lymphangiogenic and angiogenic growth factors through binding to its specific receptors, VEGFR-3 (Flt-4) and VEGFR-2 (KDR/Flk-1). VEGF-D signaling via VEGFR-3 plays an important role in lipoprotein metabolisms which may contribute to coronary heart disease (CHD). Recent studies suggest that VEGF-D appears to be a biomarker of pulmonary congestion and heart failure in both dyspnea patients and the general population. However, the prognostic value of VEGF-D in suspected or known CHD patients with a history of heart failure is unknown.

Methods

Serum VEGF-D levels were measured in 253 suspected or known CHD patients with a history of heart failure undergoing elective coronary angiography, enrolled in the development of novel biomarkers related to angiogenesis or oxidative stress to predict cardiovascular events (ANOX) study, and followed up for 3 years. The primary outcome was all-cause death. The secondary outcomes were cardiovascular death, and major adverse cardiovascular events (MACE) defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke.

Results

During the follow-up, 54 patients died from any cause, 24 died from cardiovascular disease, and 35 developed MACE. After adjustment for established risk factors, VEGF-D levels were significantly associated with all-cause death (hazard ratio [HR] for 1-SD increase, 1.44; 95% confidence interval [CI], 1.18–1.75), cardiovascular death (HR, 1.73; 95% CI, 1.32–2.25), and MACE (HR, 1.49; 95% CI, 1.14–1.89). Even after incorporation of N-terminal pro-brain natriuretic peptide, contemporary sensitive cardiac troponin-I, and high-sensitivity C-reactive protein into a model with established risk factors, the addition of VEGF-D levels further improved the prediction of all-cause death (continuous net reclassification improvement [NRI], 0.471; 95% CI, 0.176–0.766; P=0.002; integrated discrimination improvement [IDI], 0.036; 95% CI, 0.008–0.064; P=0.011) and cardiovascular death (NRI, 0.722; 95% CI, 0.326–1.118; P<0.001; IDI, 0.063; 95% CI, 0.005–0.122; P=0.033), but not that of MACE (NRI, 0.453; 95% CI, 0.100–0.805; P=0.012; IDI, 0.028; 95% CI, −0.007–0.063; P=0.116).

Conclusions

In suspected or known CHD patients with a history of heart failure undergoing elective coronary angiography, elevated VEGF-D levels may predict all-cause and cardiovascular mortality independent of established risk factors and cardiovascular biomarkers.

Acknowledgement/Funding

The ANOX study is supported by a Grant-in-Aid for Clinical Research from the National Hospital Organization.
P1720Survival analysis in a population of patients with cardiogenic shock after acute myocardial infarction: characterization of the population and identification of mortality predictors
Authors: Da Conceicao Pedro Pais J A , Picarra B , Carrington M , Santos A R , Guerreiro R A , Bras D , Congo K I S A , Carvalho J , Neves D , Aguiar J
Published: October 2019

Introduction

The presence of cardiogenic shock (CC) after acute myocardial infarction (AMI) is associated with high mortality.

Purpose

To compare the clinical characteristics, cardiac and non-cardiac complications among survivors and non-survivors of CC after AMI in order to identify predictors of in-hospital mortality.

Population and methods

An observational study involving 467 patients (P) with CC after AMI included in a national multicenter registry. Considered 2 groups: Group 1 - P with CC who died (n=190) and Group 2 - P with CC who survived (n=277). We recorded age, gender, personal history, coronary angiography and angioplasty performed, in-hospital therapy and ejection fraction, cardiac complications (Re-infarction, mechanical complications, high-grade atrial ventricular block, sustained ventricular tachycardia) and non-cardiac complications [acute renal injury (ARI), major bleeding and stroke]. Multivariate analysis was performed to identify predictors of in-hospital mortality.

Results

Mortality in patients with CC after AMI was 40.6%. Group 1 P were older (77±10 vs 68±13 years, p<0.001), presented higher prevalence of diabetes mellitus (41.8% vs 28.2%, p=0.003), previous AMI (23.8% vs. 12%, p<0.001) 7%, p=0.002), previous angor (31.9% vs 14.1%, p=0.001), heart failure (18.6% vs 8.7%, p=0.002) and peripheral arterial disease (11.8% vs 6.2%, p=0.03). There were fewer coronary angiographies (64.2% vs 87.7%, p<0.001), with no difference in the number or type of vessels with lesions in both groups, as well as inotropic therapy. With the exception of mechanical complications, more prevalent in group 1 (12.6% vs 5.4%, p=0.006), there were no differences in the prevalence of the remaining cardiac complications. Among the non-cardiac complications considered, only the presence of ARI was more prevalent in Group 1 (72.1% vs 37.5%, p<0.001). After multivariate analysis the presence of age>75 years [OR: 2.21 (CI: 1.39–3.51)], previous angor [OR: 1.91 (CI: 1.09–2.92)], LRA [OR: 3.14 (CI: 4.0–7.04)] and mechanical complications [OR: 3.82 (CI: 2.39–6.10] were independent predictors of in-hospital mortality of P with CC post-AMI.

Conclusions

Mortality in patients with CC after AMI remains high. Age>75 years, prior angor, ARI and mechanical complications are independent predictors of in-hospital mortality in P with CC post-AMI.
P1725Current spectrum and 1-year mortality of cardiogenic shock in Europe. Results of the CULPRIT-SHOCK randomized clinical trial and registry
Authors: Zeymer U , Desch S , Ouarrak T , Akin I , De Waha-Thiele S , Montalescot G , Piek J J , Huber K , Thiele H
Published: October 2019

Background

An early invasive strategy with coronary revascularization has been shown to improve prognosis in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS). Little is known about the current spectrum, treatment and 1-year mortality in patients with CS undergoing early angiography in Europe.

Methods

We evaluated baseline characteristics, treatments and 1-year outcome in a large number of patients with CS included into the prospective CULPRIT-SHOCK randomized trial and the accompanying registry. Between April 2013 and April 2017, a total of 1075 patients with cardiogenic shock were screened at 83 European centers, of whom 706 (65.6%) were included in the randomized trial RCTand 369 into the registry.

Results

The median age was 67 years and 25% were female. In total, 55% of patients had pre-hospital resuscitation, 6% underwent fibrinolysis before angiography, 65% presented with ST-elevation myocardial infarction, 15% with left bundle branch block, and 20% with non-ST-elevation myocardial infarction. The majority of patients (80%) needed mechanical ventilation. Catecholamines were used in 90% and mechanical support in 29.5% of the patients (IABP 38.5%, ECMO 22%, Impella 33%, other 7%). Total 30-day and 1-year mortality was 46% and 52%, respectively. Mechanical complications were observed in 2.1% of patients, the latter had a 30-day and 1-year mortality of 62% and 67%, respectively. The mortality related to the extent of coronary artery disease is shown in the table.

1-vessel (14%) 2-vessel (31%) 3-vessel (55%) Left main (15%) 30-day mortality 36% 44% 51% 53% 1-year mortality 39% 50% 57% 64%

Conclusions

This first report including data of the prospective CULPRIT-SHOCK randomized trial as well as the accompanying registry demonstrates the high-risk clinical characteristics of patients with AMI complicated by CS undergoing contemporary treatment. Despite an early invasive strategy mortality in patients with AMI complicated by CS in Europe is still high and is related to the extent of coronary artery disease.
P1736A novel calcium parameter, calcium ratio, can predict minimum lumen area in calcified lesions: optical coherence tomographic study
Authors: Matsuhiro Y , Nisino M , Nakamura H , Yasumoto K , Tanaka A , Nakamura D , Matsunaga Y , Yano M , Yamato M , Egami Y , Syutta R , Tanouti J
Published: October 2019

Background

Several reports have revealed that minimum lumen area (MLA) is associated with target lesion failure even with newer-generation drug-eluting stents, and calcified lesions usually induced inadequate lumen area because of stent under expansion. Contemporary debulking devices such as rotational/orbital atherectomy can modify severe calcified lesions before stenting. However, there are no optimal criteria to indicate necessity for calcium modification to obtain adequate acute gain. Therefore, we investigated useful calcium parameters correlating with MLA in the calcified lesions after stenting.

Methods

We enrolled 71 consecutive calcified lesions (71 patients) who underwent optical coherence tomography (OCT) guided percutaneous coronary intervention (PCI) between September 2016 and January 2019. Exclusion criteria included acute coronary syndrome, in-stent restenosis and lesions without any calcium or treated with rotational atherectomy. If there were several calcium lesions in one patient, we selected maximum calcium angle lesion. We compared mean reference area, pre lumen area and various calcium parameters including calcium arc, maximum thickness, depth, area, longitudinal length and calcium ratio that was maximum calcium thickness divided by nearest reference diameter in disease-free segments as much as possible in pre-PCI OCT evaluation with post-PCI lumen area at that site by simple and multiple regression analysis.

Results

Calcium ratio was an independent predictor for post-PCI lumen area in addition to mean reference area, while the others were not associated with post-PCI lumen area (table).

Results of OCT parameters Univariate analysis Multivariate analysis P value P value β Mean reference area <0.01 <0.01 0.69 Pre lumen area <0.01 0.08 0.15 Cacium arc <0.01 0.58 −0.06 Calcium maximum thickness 0.62 Calcium ratio <0.01 0.01 −0.21 Calcium area 0.02 0.64 0.05 Calcium longitudinal length 0.60 Calcium depth 0.09

Conclusion

The novel calcium measurement, calcium ratio, may be a useful predictor for post-PCI lumen area for calcified lesions.
P1781Burden of significant valvular heart disease in elderly patients presenting with acute coronary syndromes
Authors: Montalto C , Crimi G , Fortuni F , Mandurino Mirizzi A , Ferri L A , Morici N , Tortorella G , Grosseto D , Sganzerla P , Ferrario M , Savonitto S , De Servi S
Published: October 2019

Background

Elderly patients with acute coronary syndromes (ACS) represent a group seldom included in clinical trials and in whom robust data regarding mid-term impact of significant concomitant valvular heart disease are lacking.

Purpose

Our aim was to evaluate the impact of moderate-to-severe mitral regurgitation (MR), moderate-to-severe aortic stenosis (AS), or both conditions combined on a primary composite endpoint of mortality, myocardial infarction, disabling stroke and re-hospitalization for cardiovascular causes or bleeding within one year in a population of ACS patients included in the Elderly ACS 2 trial.

Methods

In the multicenter Elderly II ACS Study, 1,443 patients aged >74 y undergoing percutaneous coronary intervention (PCI) for ACS, were randomly assigned to receive prasugrel (5 mg) or clopidogrel (75 mg) and were prospectively followed for 1 year. Amongst these, 1,102 patients received full echocardiographic assessment and were included in the post-hoc analysis (Table 1).

Results

Survival analysis showed that patients presenting with moderate-to-severe MR, AS or both (Figure 1A), had worse outcome in terms of primary endpoint (p<0.001) as compared to no valve disease. A multivariable Cox regression model revealed that the presence of moderate-to-severe MR, AS or both were independent predictors of primary endpoint (HR 1.84; HR 2.8; HR 2.9 and p<0.001; p=0.004; p=0.01, respectively), regardless of age, gender, left ventricular ejection fraction, diabetes mellitus, history of cancer and total number of diseased vessels (Figure 1B).

Table 1 Overall No residual valvular heart disease Moderate-to-severe MR Moderate-to-severe AS Both Age (y) 80.68±4.50 80.40±4.42 81.47±4.45 82.92±5.42 83.23±5.42 Male gender 652 (59.2) 538 (61.6) 92 (48.4) 19 (73.1) 3 (23.1) STE-ACS 420 (38.1) 319 (36.5) 91 (47.9) 6 (23.1) 4 (30.8) Diabetes mellitus 203 (18.4) 158 (18.1) 35 (18.4) 5 (19.2) 5 (38.5) LVEF (%) 48.30±9.58 49.26±9.27 44.61±9.45 48.50±11.22 38.31±10.87 History of cancer 32 (2.9) 26 (3.0) 3 (1.6) 2 (7.7) 1 (7.7) Tot number of diseased vessel 2.31±1.05 2.28±1.04 2.49±1.05 2.04±0.87 2.54±1.13 Data are expressed as mean ± SD or count (valid %).

Figure 1

Conclusions

Moderate-to-severe MR and AS represent significant predictors of 1-year outcome in elderly patients hospitalized for ACS, even when other well-established prognostic factors are taken into account and after revascularization with PCI. Therefore, these patients should be carefully screened for the presence of valvular heart disease at the time of presentation and the need for surgical or percutaneous correction should be assessed accordingly.

Acknowledgement/Funding

None