bluuebunny/crossref_metadata_2025_split huggingface dataset:
P1622Cancer drugs induce functional and structural impairment in adult cardiomyocytes
Authors: Altomare C , Biemmi V , Torre E , Rocchetti M , Ferrandi M , Pernigoni N , Barile L , Milano G , Vassalli G 
Published: October 2019

Abstract

Introduction
The addition of anti-human epidermal growth factor receptor 2 (HER2; ErbB2) monoclonal antibody Trastuzumab (TRZ) to Doxorubicin (DOXO) chemotherapy is associated with a synergistic increase in cardiac toxicity. While previous studies have addressed the toxicity of both agents on isolated cardiomyocytes (CMs), little is known regarding this process in vivo, especially with respect to electrophysiological changes.

Purpose
To investigate electrical and structural changes in LV and RV CMs using an in vivo rat model of DOXO/TRZ cardiotoxicity.

Methods
Rats received 6 IP injections of either DOXO or TRZ over a 2-week period, or 6 doses of DOXO followed by 6 doses of TRZ (COMBO), or saline as a control. In-vivo echocardiography was performed. Electrical activity and Ca2+ handling were assessed in LV and RV CMs from rat hearts. Single cell patch-clamp and field stimulation experiments were performed. Spontaneous sarcoplasmic reticulum Ca2+ release events (Ca2+ sparks) were recorded at x100 magnification in line-scan mode (sampling rate 0.7 kHz) from 2 μM Fluo4-AM loaded CMs. To assess T-tubular disarray, CMs were incubated with di-3-ANEPPDHQ and periodic component was quantified by Fast Fourier Transform (FFT) analysis of confocal microscopy images.

Results
DOXO, and to a greater extent COMBO treatment was associated with significant increases in both LV end-systolic and end-diastolic volumes, and decreases in LVEF and fractional shortening. By contrast, TRZ alone merely increased LV end-systolic volume. Electrophysiological studies showed increases in action potential duration (APD), beat-to-beat variability of repolarization (BVR), delayed after depolarizations (DADs), and Ca2+-sparks in both DOXO and COMBO groups. Stimulated intracellular Ca2+ transients (1,2 and 4 Hz) showed significant changes with respect to time to peak, tau decay, amplitude, and fractional release in the DOXO group. These changes were associated with a significant downregulation of sarco/endoplasmic reticulum Ca2+ ATPase pump (SERCA) expression. From a structural viewpoint, these changes were associated with T-tubular disarray in the DOXO and COMBO groups.

Conclusions
DOXO, and to a greater extent COMBO treatment (but not TRZ alone) cause LV dysfunction in vivo. Moreover, both DOXO and COMBO treatments, but not TRZ alone, induce electrophysiological abnormalities and both structural and functional changes in the sarcoplasmic reticulum. These findings provide novel insights into the cellular mechanisms of CM dysfunction and arrhythmias associated with combined DOXO/TRZ therapy.

Acknowledgement/Funding
Swiss League against Cancer
P1664Pharmacological treatment patterns in heart failure: a real world cohort study
Authors: Bosco-Levy P , Favary C , Jove J , Lassalle R , Moore N , Droz-Perroteau C 
Published: October 2019

Abstract

Background
Although the efficacy and safety of existing therapies of heart failure (HF) have been demonstrated in clinical trials in the last 35 years, little is known about the treatment patterns of HF in clinical practice, especially in France.

Objectives
To describe the treatment initiation patterns and the subsequent treatment changes among HF patients, in the first year following an incident hospitalisation for HF, in a French real-world setting.

Methods
A cohort of patients aged 40 years old and older, with an incident hospitalisation for HF between January 1, 2008 and December 31, 2013, was identified in the EGB, a 1/97 permanent random sample of the French nationwide claims database. All patients who died during the index hospitalization or with a period of at least 3 consecutive months with no healthcare dispensing recorded were excluded. All included patients were followed one year. HF drugs of interest were: beta blockers (BB), angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARBs), aldosterone antagonists (AA), diuretics, digoxin or ivabradine. Drug exposure was assessed quarterly using a Proportion of Days Covered >66% (>60 days out of the 90 days of the quarter covered by the treatment of interest), by considering HF drugs individually or in combination. Drug changes were assessed between each quarter over the first year of follow-up.

Results
Between 2008 and 2013, 7,387 from the EGB were included in the cohort study. The mean age at baseline was 77.7 years (±12.0 years) and 51.6% were women. During the follow-up, 24.4% of patients died and 20% did not receive any HF treatment. During the first quarter following initial hospitalisation, 42.7% of patients had diuretics, 26.0% had BB, 25.7% had ACEI, 7.4% had ARB, 7.6% had AA, 4.7% had digoxin and 1.3% had ivabradine. the most frequent combination was BB/ACE/ARB (23.4%). These proportions remained globally constant in each quarter of the follow-up. The main change occurred between thee first and the second quarter and concerned 53.1% of the initially untreated patients; by the second quarter, 22.2% of them initiated a BB/ACI/ARB combination, 13% a diuretic alone, 7.4% a BB and 4.9% a BB/ACI/ARB/AA combination.

Conclusion
This study provides precious information on treatment patterns after an initial hospital admission for HF at a time when new treatments for HF are emerging.

Acknowledgement/Funding
None
P1670Incidence and prognosis of late-onset right ventricular failure following continuous-flow left ventricular assist device implantation as bridge to transplantation
Authors: Ruiz Cano M J , Schoenbrodt M , Paluszkiewicz L , Laurenroth V , Al-Khalil R , Kizner L , Gummert J , Morshuis M 
Published: October 2019

Abstract

Early right ventricular failure (RVF) remains a frequent complication and is one of the main factors associated to early mortality following left ventricular assist device (LVAD) implantation. However, late-onset RVF (LoRVF) has emerged as an increasing concern, but little is known about its incidenceand underlying mechanisms.

Methods and results
We retrospectively analysed the 1-year hemodynamic and clinical data from all patients that, between 2016 and 2018, underwent a right heart catheterization (RHC) after continuous-flow LVAD implantation as bridge to transplantation. Sixty-six patients (84% males, 53±11 years, 60% implanted in Intermacs 1–2, 52% HeartWare LVAD, 48% HM3 LVAD), out of 187 LVAD implants, were studied. LoRVF was defined as central venous pressure>18 mmHg with cardiac index<2.3 L/min/m2 during RHC.
LoRVF was present in 17 patients (25.7%) and 12 (71%) of them manifested concomitant clinical signs of RVF. Eleven of the patients who presented LoRVF (65% of the LoRVF) had a pulmonary capillary wedge pressure (PCWP)>15 mmHg. Isolated LoRVF (LoRVF criteria + PCWP≤15 mmhg) was found in 6 patients (35% of the LoRVF) and accounted for 9% of the studied population. Fifty percent of patients who presented isolated LoRVF could be successfully transplanted in high urgent status due to severe chronic RVF and 1 patient died to refractory RVF. We did not find an association between isolated LoRVF and age, renal function, type of LVAD, persistent increased pulmonary vascular resistances or the previous need of temporary right ventricular support due to early acute RVF following LVAD. There was however a significant association between the presence of atrial fibrillation and isolated LoRVF (p<0.05).
Incidence and prognosis of LoRVF

Conclusion
Late-onset RVF is a frequent complication during LVAD support as bridge to transplantation. Most of the cases are associated to a lesser degree of left ventricular unloading. The presence of isolated late-onset RVF with normal PCWP has an impact on the long-term prognosis and the need of urgent heart transplantation and is not related to early RVF following LVAD implantation or persistent increased pulmonary vascular resistance.
P1683Optimal serum uric acid levels for hypertension: 5-year cohort study
Authors: Kuwabara M , Niwa K , Hisatome I 
Published: October 2019

Abstract

Background
Although hyperuricemia is known as a risk factor for hypertension, the optimal range of serum uric acid (SUA) for preventing hypertension has not been established, especially in a healthy population.

Methods
This is a 5-year cohort study to clarify the optimal SUA for hypertension. Subjects consisted of Japanese adults between 30 and 85 years of age were enrolled in the study at our Center for Preventive Medicine, and available at enrollment (2004) and at 5-year follow-up (2009). We excluded the study subjects who were hypertensive, diabetic, dyslipidemic, had a history of gout or hyperuricemia on medications, or if they had chronic kidney disease as estimated glomerular filtration rate <60 ml/min/1.73m2. Linear and logistic regression analyses were used to examine the relationship between each 1 mg/dL of serum uric acid range and development of hypertension with multiple adjustments for age, smoking, drinking habits, body mass index and baseline systolic blood pressure.

Results
Of 13,070 subjects enrolled at this step, we included 6,476 subjects (46.9±10.1 years old, 34.6% men) without comorbidities. The cumulative incidences of hypertension over 5 years were 5.9% in women and 12.1% in men. The lowest cumulative incidences of hypertension were 2.6% in 2.0–3.0 mg/dL of serum uric acid in women and 6.9% in 4.0–5.0 mg/dL in men. In contrast, the highest uric acid range showed highest cumulative incidence of hypertension both in women (28.6% in 8.0–9.0 mg/dL) and men (21.0% in ≥9.0 mg/dL). Hypouricemic (<2.0 mg/dL) subjects had higher cumulative incidences of hypertension than subjects with 2.0–3.0 mg/dL of serum uric acid levels, we excluded these subjects in multivariable logistic analysis. The odds ratio of 1 mg/dL increase of serum uric acid for developing hypertension was 1.395 (95% CI, 1.182–1.648) in women and 1.139 (95% CI, 1003–1.294) in men after multiple adjustments.

Conclusion
The optimal serum uric acid range for preventing hypertension was 2.0–3.0 mg/dL in women and 4.0–5.0 mg/dL in men. Higher uric acid levels increase cumulative incidence of hypertension.

Acknowledgement/Funding
None
P1719Sex-specific PCI strategies in patients with AMI and cardiogenic shock: a substudy of the culprit-shock trial
Authors: Rubini Gimenez M , Zeymer U , Desch S , De Waha-Thiele S , Ourrak T , Meyer-Saraei R , Schneider S , Fuernau G , Akin I , Savonitto S , Jeger R , Thiele H 
Published: October 2019

Abstract

Background and purpose
Women are more likely to suffer from a cardiogenic shock (CS) as the most severe complication of an acute myocardial infarction (AMI) and tend to have a higher mortality. Data concerning optimal management among women with CS are lacking. Aim of this study was therefore to better define characteristics of women suffering a CS and to investigate the influence of sex on different coronary revascularisation strategies

Methods and results
In the CULPRIT-SHOCK trial, patients with CS complicating AMI and multivessel coronary artery disease were randomly assigned to one of the following coronary revascularisation strategies: either percutaneous coronary intervention (PCI) of the culprit lesion only or immediate multivessel PCI. Primary end-point was a composite of death from any cause or severe renal failure leading to renal-replacement within 30 days after randomisation. We investigated sex-specific differences in general and according to the revascularisation strategies.
Among all 706 randomised patients 26% were women. After 30 days, the primary end-point occurred in 55% women and 49% men (p=0.20), showing a relative risk of 1.14; 95% CI 0.94–1.38; p=0.17, women vs. men. Those women were older, more frequent diabetic and had more peripheral artery disease and less frequent smokers and less often family history of coronary artery disease.
Regarding revascularisation strategy the composite end-point occurred in 55.8% women treated with the culprit-only strategy (vs. 42.4% men, p=0.04) and in 54.7% women in the multivessel group (vs. 55.6% men, p=0.99). This resulted in a no-significant difference among both groups (interaction p-value of 0.11).

Conclusions
In this large randomised trial among patients with multivessel coronary disease and CS complicating AMI, women had similar outcome for mortality and severe renal failure. Sex did not show to influence mortality and renal failure according to the different coronary revascularisation strategies. These data suggest that women and men presenting with CS should be treated equally.
P1732The additive value of pre- and post-reperfusion cardiac troponin T levels in risk stratification of patients with ST-segment elevation myocardial infarction
Authors: Coelho-Lima J , Ahmed J , Georgiopoulos G , Adil S E R , Gaskin D , Bakogiannis C , Sopova K , Ahmed F , Ahmed H , Bagnall A , Stellos K , Stamatelopoulos K , Spyridopoulos K 
Published: October 2019

Abstract

Background
Despite therapeutic advances, mortality rates following ST-segment elevation myocardial infarction (STEMI) are still alarmingly high. There is conflicting evidence regarding the prognostic role of high-sensitivity cardiac troponin T (hs-cTnT) measurements before and after primary percutaneous coronary intervention (PPCI) over traditional predictors of mortality in STEMI patients.

Purpose
To determine the additive prognostic value of pre- and 12h post-PPCI hs-cTnT levels in STEMI patients

Methods
Retrospective longitudinal study including 3,113 consecutive STEMI patients treated with PPCI at a university hospital covering a population of 1.6 million in the North East of England. Clinical, procedural, and laboratory data were prospectively collected during patient hospitalization while hs-cTnT measurements were performed at admission to the catheterization laboratory and at 12h post-PPCI. Median follow-up was 53 months. The study endpoints were in-hospital and overall mortality. Mortality data were obtained from the UK Office of National Statistics.

Results
Admission hs-cTnT >515ng/L (4th quartile) was independently associated with in-hospital mortality [HR=2.39 per highest to lower quartiles; 95% CI: 1.44 to 3.97; p=0.001] after multivariate adjustment for a core clinical model of in-hospital mortality prediction. Likewise, admission hs-cTnT >515ng/L independently predicted overall mortality (HR=1.25 per highest to lower quartiles; 95% CI: 1.00 to 1.57; p=0.044) after adjustment for covariates significantly associated with this endpoint. Admission hs-cTnT correctly reclassified risk for in-hospital death [net reclassification index (NRI)=44.1%, p<0.001) and overall mortality (NRI=60.4%, p<0.001). Conversely, 12h hs-cTnT was not independently associated with mortality.

Conclusion
Admission, but not 12h post-reperfusion, hs-cTnT predicts mortality and improves risk stratification in the PPCI era. These results support the role of hs-cTnT in risk stratification of post-STEMI patients and challenge the cost-effectiveness of routine 12h hs-cTnT measurements.
P1733Dynamic changes of high-sensitivity troponin I after non-invasive stress-testing
Authors: Neumann J T , Gossling A , Soerensen N , Zeller T , Blankenberg S , Sinning C , Westermann D 
Published: October 2019

Abstract

Objective
In patients with suspected coronary artery disease (CAD) and intermediate pretest probability non-invasive stress-testing is recommended in current guidelines. However, sensitivity and specificity of these tests are limited. We aimed to investigate the additional diagnostic value of high-sensitivity troponin I concentrations measured before and after stress-testing.

Methods
We included patients undergoing non-invasive stress-testing in a prospective cohort study. All patients provided written informed consent, were at least 18 years old and underwent either stress-echocardiography, stress-MRI or myocardial perfusion scintigraphy. Baseline parameters were collected by questionnaire and chart review. Blood samples were collected before, and one hour after the stress-test. Troponin was measured using the Abbott Architect high-sensitivity troponin I (hs-TnI) assay. The diagnostic performance to predict a pathological stress-test was evaluated by calculation of the area under the ROC curve (AUC) using baseline hs-TnI concentrations and the absolute change after one hour. An optimal cutoff was determined by maximization of the Youden Index. Univariate odds ratios (OR) were calculated to identify predictors for a pathological stress-test. Additionally ORs for the optimal hs-TnI cutoff were calculated in a multivarite regression with adjustment for baseline variables.

Results
In total 391 patients with a median age of 70 years were included. 66.8% were males, 83.4% had prevalent hypertension, 55.9% had dyslipidemia and 55.4% had a prior history of CAD. A pathological stress-test was reported in 21.5% and these patients had a higher cardiovascular risk profile, compared to patients with a non-pathological stress-test. The baseline hs-TnI concentrations were 4.7 ng/L in the overall population, 4.2 ng/L in patients with a non-pathological stress-test and 8.4 ng/L (p<0.001) in patients with a pathological stress-test. There was no significant hs-TnI changes one hour after stress-testing. The AUC for the baseline hs-TnI was 0.65 and the optimal cutoff was determined at 7.7 ng/L. Most cardiovascular risk factors were predictors for a pathological stress-test. The OR for an elevated hs-TnI above the optimized cutoff was 3.34 (95% CI 2.03, 5.52). In a multivariate model a baseline hs-TnI above 7.7 ng/L showed an OR of 2.07 (95% CI 1.04, 4.12; p-value 0.039)

Conclusion
In patients undergoing non-invasive stress-testing, hs-TnI concentrations did not significantly change one hour after exercise. However, an elevated troponin concentration is an independent predictor for a pathological stress-test.
P1737Influence of peripheral arterial disease on prognosis in patients with left main coronary artery disease treated with percutaneous coronary intervention
Authors: Martinez Leon A , Adeba Garcia A , Garcia Iglesias D , Florez Llano P , Flores Fuentes A , Gutierrez De La Varga L , Almendarez Lacayo M , Diaz-Chiron Sanchez L , Capin Sampedro E , Suarez Cuervo A , Avanzas Fernandez P , Garcia Perez L , Moris De La Tassa C 
Published: October 2019

Abstract

Introduction
Percutaneous coronary intervention (PCI) in patients with left main (LM) coronary artery disease is acquiring an important role in the last years as an alternative to coronary artery bypass grafting (CABG) in selected patients. The objective of the study was to evaluate predictors of mortality in patients with LM coronary artery disease treated with PCI.

Methods
Prospective and observational study of consecutive patients referred to our centre for coronary angiography, with LM coronary artery disease, whom PCI was decided in a “Heart team” as a strategy for revascularization between July 2015 and December 2017. Baseline clinical, analytical and coronary angiography data were collected. Follow-up was conducted in person or by telephone for a minimum of one year. We analysed the predictive variables of mortality by means of an uni and multivariate logistic regression model. In addition, a survival analysis was performed.

Results
A total of 191 patients were recruited. The average age was 72 years (±11.4), 79% males. 42% had previous documented coronary artery disease. PCI was performed in the context of acute coronary syndrome in 81% of them. The mean follow-up period was 17.9 months (± 8.3). After multivariate analysis, the following variables remained as independent predictors of mortality: the hemodynamic situation of the patient, assessed by the Killip-Kimball scale (OR 1.58, 95% CI 1.03–2.43; p=0.04) and the presence of peripheral arterial disease (PAD) (OR 2.61, 95% CI 1.03–6.67; p=0.04) (table 1). The ROC curve of the multivariate model showed an AUC of 0.796 (figure 1A). In the survival analysis, patients with PAD had a significantly lower survival, with a median survival of 6 months, compared to 13.9 months in those without PAD, with p=0.008 (figure 1B).
Uni and multivariate analysis Univariate analysis Multivariate analysis OR (95% CI) p OR (95% CI) p Killip-Kimbal scale 1.94 (1.39–2.72) 0 1.58 (1.03–2.43) 0.04 LVEF 0.96 (0.93–0.99) 0.01 0.99 (0.95–1.03) 0.46 Mitral regurgitation 2.54 (1.12–5.63) 0.02 1.60 (0.55–4.56) 0.38 Number of affected vessels 1.96 (1.24–3.29) 0.01 1.78 (1.03–3.37) 0.05 PAD 2.54 (1.16–5.49) 0.02 2.61 (1.03–6.67) 0.,04
Figure 1

Conclusion
Although PCI revascularization of LM coronary artery disease is an attractive alternative to CABG in selected patients, a word of caution should be raised in patients with PAD, as in the present study this variable was an important predictor of short-medium term mortality.
P1740Clinical impact of symptom onset-to-balloon time and door-to-balloon time on 1-year adverse event in patients with ST-segment elevation myocardial infarction
Authors: Kim G , Choi W , Kim J , Ahn T 
Published: October 2019

Abstract

Background and objectives
The impact of treatment delays to reperfusion on patient mortality after primary percutaneous coronary intervention (PCI) for ST elevation myocardial infarction (STEMI) is controversial. we evaluated the relation between the delay in the time to reperfusion during primary PCI and the 1-year clinical outcome of patients with STEMI treated by primary angioplasty.

Methods
The study enrolled 6,676 patients (age, 62.5±12.6 years; 26.5% female) with STEMI who underwent primary angioplasty onset between November 2005 and March 2012 from the KAMIR and KorMI Registry. The patients were divided into three groups according to the symptom onset-to-balloon (STB) time: group I, II, III (≤180 minutes, >180 ∼ ≤360 minutes, >360 minutes), and divided into three groups according to the door-to-balloon (DTB) time: group A, B, C (≤90 minutes, >90 ∼ ≤120 minutes, >120 minutes). The 1-year cardiac death and major adverse cardiac event (MACE) rates were compared among the three groups of time variables

Results
The cardiac death rate was 7.9% and MACE rate was 16.9% at one year follow-up. The 1-year cardiac death rate among STB time groups were significantly higher in group II (95% CI=1.05–2.60:p=0.030) and group III (95% CI=1.14–2.74:p=0.011), while that among DTB time groups were not significantly different based on a multivariate Cox proportional analysis, which was adjusted by age, sex, diabetes mellitus, hypertension, systolic blood pressure, left ventricular ejection fraction, peak level of CK-MB, anterior myocardial infarction. The 1-year MACE rate were not significantly different among STB time groups and DTB time group A, B, but was significantly higher in group C (95% CI=1.08–1.58:p=0.006).

Conclusions
These results suggest that, in patient with STEMI treated by primary angioplasty, STB time rather than DTB time was related 1-year clinical outcome especially cardiac death after adjustment for baseline characteristics. Therefore, all efforts should be made to shorten the total ischemic time in patients with acute myocardial infarction