bluuebunny/crossref_metadata_2025_split huggingface dataset:
4303Revisiting the weber and ventilatory classifications in heart failure by combining exercise stress echo with gas exchange phenotyping
Authors: Sugimoto T , Bandera F , Alfonzetti E , Guazzi M 
Published: October 2019

Abstract

Background
In heart failure (HF), the Weber and Ventilatory Classes are well acquired landmark reference exercise classifications for quantification of outcome. However, they have not been associated with a thorough hemodynamic phenotyping in the modern HF populations.

Methods
194 HF patients with preserved (N=41), mid-range (N=43), and reduced (N=110) ejection fraction and patients with exercise induced-dyspnea and no HF (nonHF, N=77) underwent CPET combined with Echo-Doppler with special attention for the assessment of left atrial dynamics by strain (LAS) analysis, and right ventricular (RV) to pulmonary circulation (PC) coupling assessed by transticuspid annular plane systolic excursion (TAPSE)/pulmonary arterial systolic pressure (PASP) ratio. They were also evaluated in terms of clinical outcome (mortality and HF hospitalization).

Results
Distribution and variables of interest for Weber Classes were: Class A; n=22 nonHF, no HFpEF, 3 HFmrEF, 3 HFrEF with LAS during exercise of 39±12% and TAPSE/PASP of 0.67±0.21 mm/mmHg; Class B; n=25, 7, 12, 21 with LAS during exercise of 28±14% and TAPSE/PASP of 0.56±0.25 mm/mmHg; Class C: n=27, 25, 20, 48 with LAS during exercise of 24±14% and TAPSE/PASP of 0.46±0.18 mm/mmHg; Class D; n=3, 9, 8, 38 with LAS during exercise of 17±12% and TAPSE/PASP of 0.33±0.14 mm/mmHg and Ventilatory Class I: 59, 24, 22, 39, with LAS during exercise of 31±14% and TAPSE/PASP of 0.55±0.21 mm/mmHg; Class II: 14, 9, 12, 39 with LAS during exercise of 22±13% and TAPSE/PASP of 0.45±0.21 mm/mmHg; Class III: 3, 7, 5, 20 with LAS during exercise of 16±7% and TAPSE/PASP of 0.31±0.09 mm/mmHg; Class IV: 1, 1, 4, 12 with LAS during exercise of 10±6% and TAPSE/PASP of 0.28±0.11 mm/mmHg. Significant differences among each classes in LAS during exercise and peak TAPSE/PASP (P<0.05, respectively) have been observed (Figures A and B). LAS during exercise and peak TAPSE/PASP were positively correlated with peak VO2 (R=0.45 and 0.49, P<0.05, respectively) and also negatively correlated with VE/VCO2 slope (R=−0.49 and −0.55, P<0.05, respectively). Cox proportional hazard regression analyses showed that Weber (HR=3.7, 95% CI 1.7 to 8.0, P<0.001) and Ventilatory Classes (HR=1.7, 95% CI 1.1 to 2.7, P=0.01) were independently associated with the cardiac endpoint after adjustment for age and gender. Clinical stratification according to Weber (A/B or C/D) and Ventilatory (IV or not) Classes clearly differentiated between patients with low and high clinical risk (HR=2.8, 95% CI 1.4 to 5.7, P=0.005, Figure C).

Conclusions
In patients with HF of any LVEF, Weber and Ventilatory classifications are paralleled by progressive impairment in exercise echo-derived hemodynamic parameters of left atrial function and RV to PC coupling. Peak VO2 and VE/VCO2 slope combine in a strong predictive value irrespective of type of HF.
4304Fast-SENC quantifies segmental right ventricular intramyocardial strain to assess subclinical RV dysfunction prior to changes in RV ejection fraction
Authors: Montenbruck M , Kelle S , Esch S , Andre F , Schwarz A , Korosoglou G , Steen H 
Published: October 2019

Abstract

Right ventricular ejection fraction (RVEF) identifies reduced right-side cardiac function in symptomatic patients. However, alternative metrics are needed to detect subclinical RV dysfunction before cardiac remodeling results in systemic damage. Fast-SENC intramyocardial strain (fSENC) is a unique cardiac magnetic resonance imaging (CMR) modality that measures intramyocardial RV contraction in 1 heartbeat per image plane. This prospective registry compares fSENC and RVEF based on ACC/AHA Heart Failure Stage.

Methods
A single center, prospective registry of MRI scans acquired with a 1.5T scanner were evaluated for conventional CMR diagnostics including RVEF. In addition, fSENC scans were acquired and processed with the MyoStrain software to quantify intramyocardial RV strain. Two short axis scans (basal & midventricular) were used to calculate strain in 6 longitudinal RV segments while two long axis scans (3-chamber & 4-chamber) were used to calculate 5 circumferential RV segments.
CMR and fSENC metrics were compared based on progression of heart failure in which the ACC/AHA Heart Failure stage was determined by CMR findings including LGE in cases in which contrast was injected. HF Stages B and C were separated into different degrees of structural heart disease with “−” representing lower levels and “+” higher levels to provide better delineation of progression of heart dysfunction leading to heart failure.

Results
A total of 977 scans in 779 patients were included in the study. Patients had an average (± stdev) age of 55 (17) yrs and BMI of 26 (5) kg/m2; 48% had arterial hypertension, 12% diabetes mellitus, 33% moderate or severe valvular heart disease, 25% cancer, 7% atrial fibrillation, and 24% coronary artery disease.
Figure 1 shows the relationship between % normal RV myocardium (RV fSENC <−17%) and CMR RVEF in the y-axis versus modified ACC/AHA Heart Failure Stage in the x-axis respectively.
Figure 1

Conclusion
Segmental fSENC detects subclinical RV dysfunction well before changes in RVEF. The ability to directly measure intramyocardial RV strain allows quantification various subclinical right heart diseases, the impact and monitoring of pharmacological therapiesand device interventions on RV function.
4310Left ventricular myocardial mass index is a predictor of clinical outcomes in patients with Fabry disease
Authors: Moiseev S , Karovaikina E , Bulanov N , Moiseev A , Fomin V 
Published: October 2019

Abstract

Fabry disease (FD) is a rare lysosomal storage disorder characterized by severe complications in young patients. The aim of the study was to determine predictors of clinical outcomes in patients with FD.

Methods
The diagnosis of FD was confirmed by enzymatic and genetic studies. The outcomes included death and a composite of end-stage renal disease (ESRD), cardiac (clinically significant arrhythmia and cardioverter/pacemaker implantation) and cerebrovascular (transient ischemic attack, stroke) events. Cox regression model was used to examine the risk of clinical outcomes.

Results
One hundred adult patients (65 males and 35 females, median age 40 [32; 50.8] years) with a definite diagnosis of FD were enrolled in our study. The majority of patients had classic phenotype (94.2%) and missense mutations in the GLA gene (69.0%). Forty-seven patients (38 males and 9 females) experienced clinical outcomes which included arrhythmias in 10 patients (atrial fibrillation in 8 of thems), ESRD in 33 patients, and cerebrovascular events in 8 patients. The median age of the first outcome was 39 (32; 49) years. In males, the outcomes occurred more frequently than in females (58.5% vs. 25.7%, respectively, p=0.002). Eleven males died at the median age of 43 (37; 46) years. All of them had ESRD. The most frequent cause of death was sudden cardiac death (n=9). Left ventricular myocardial mass index (LVMMI) was higher among patients with outcomes than in patients without outcomes (153 g/m2 [102; 203] vs. 92 g/m2 [78; 122], respectively, p<0.0001). However, there was no correlation between LVMMI and cardiac events (p=0.12). Using Cox regression analysis, LVMMI (HR 1.01 [1.002; 1.02], p=0.015), eGFR <60 ml/min/1.73m2 (HR 3.79 [1.87; 7.66], p<0.0001) and albuminuria>300 mg/day (HR 1.29 [1.04; 1.59], p=0.022) were associated with a higher risk of a composite outcome after adjustment for gender and age. Albuminuria>300 mg/day (HR 1.57 [1.05; 2.35], p=0.029) and LVMMI (HR 1.006 [1; 1.012], p=0.038) were predictors of death after adjustment for gender. However, this effect has been lost after adjustment for hemodialysis duration. The type of mutation in the GLA gene was not a predictor of clinical outcomes.

Conclusion
Left ventricular myocardial mass index was a predictor of clinical outcomes in patients with FD. Poor prognosis in our cohort was related to ESRD that accounted for all deaths.
4313Evolocumab rapidly reverses impaired coronary endothelial function in six weeks in people living with HIV and in patients with dyslipidemia
Authors: Leucker T , Gerstenblith G , Schar M , Brown T , Jones S , Weiss R , Hays A 
Published: October 2019

Abstract

Background/Introduction
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is well recognized for its importance in cholesterol metabolism. Elevated levels are associated with increased cardiovascular risk and inhibition with PCSK9 antibodies lowers cardiovascular events in patients with known coronary disease. PCSK9 levels are also elevated in people living with HIV (PLWH), and we previously reported that increased PCSK9 in PLWH is associated with impaired coronary endothelial function (CEF), a major driver for the development, progression, and clinical manifestations of coronary artery disease.

Purpose
Here we investigate the hypothesis that PCSK9 inhibition improves impaired CEF in PLWH and in patients with dyslipidemia (DL).

Methods
Cine 3T MRI was used to noninvasively measure CEF, assessed as the change in coronary cross-sectional area (CSA) from rest to isometric handgrip exercise (IHE), a known endothelial-dependent vasodilator. Eight HIV+ subjects on stable highly active antiretroviral therapy and with undetectable HIV RNA (mean age 53±9 yrs, LDLC 98±18 mg/dL, 38% on statins) and ten patients with dyslipidemia (DL) without HIV receiving evolocumab for clinical reasons (mean age 56±10 yrs, LDLC 130±28 mg/dL, 50% on statins) underwent MRI studies before and six weeks following the initiation of evolocumab 420 mg. MRI readers were blinded to group and timepoint. MRI data are presented as mean±SD for % change rest vs IHE.

Results
Prior to evolucumab, resting CSA in the two groups did not differ and IHE did not induce normal coronary vasodilation in either group; mean stress-induced CSA changes were −2.1±6.4% in HIV (p=0.27) and −0.6±4.1% in DL (p=0.46). Notably, CEF significantly improved following six weeks of evolocumab with IHE-induced CSA changes of 7.6±5.7% (p=0.006) and 5.0±3.6% (p=0.002) in the HIV and DL groups, respectively. The %-LDLC reduction with evolocumab was profound and comparable in the HIV and DL groups, 73±5% and 60±6% (p=0.19 HIV vs. DL). There was no significant correlation between the extents of LDLC reduction and of CEF improvement in either of these modest sized groups.

Conclusion
PCSK9 inhibition with evolocumab significantly improves abnormal coronary endothelial function after only six weeks in HIV+ people with normal LDLC and in HIV- people with DL. To our knowledge, these data represent the earliest (6 weeks) evidence for improvement in human coronary artery health by PCSK9 inhibition.

Acknowledgement/Funding
Amgen provided the PCSK9 monoclonal antibody (evolocumab) for this study.
4329Mega-studies in heart failure, effect dilution in examination of new therapies
Authors: Cotter O , Davison B A , Koch G , Senger S , Metra M , Voors A A , Mebazza A , Nielsen O W , Chioncel O , Pang P , Greenberg B H , Maggioni A , Sato N , Teerlink J R , Cotter G 
Published: October 2019

Abstract

Aims
All phase 3 studies in patients with acute heart failure (AHF) and HF with preserved ejection fraction (HFpEF) have failed in the last decades. We explore the likelihood that the negative results are due to chance and/or to study size and dilution of statistical power.

Methods and results
First, using simulations, we examined the probability that a positive finding in phase 2 would result in studying truly effective drugs in phase 3. We simulated phase 2 studies under six scenarios where the range of true relative risk (RR) for an outcome of interest varied from 0.5 (major benefit) to 1.15 (some harm). The proportion of simulated studies where the RR <0.8 (we assumed that a 20% or greater risk reduction reflects an effective drug) ranged from 6% to 42% across the six scenarios studied. To further simulate “real life” clinical research, we simulated a continuous surrogate outcome that was linearly related to the true RR in each simulation of each scenario. Regardless of criteria considered for a positive phase 2 trial, results suggest that even in our worst-case scenario, where overall only 6% of drugs taken into phase 2 are effective, roughly 20% of phase 3 studies, if appropriately powered, should have yielded positive results. Given this, we then explored study size in AHF research, as a potential explanation for the high failure rate in these studies. Comparison of published phase 2 and 3 clinical trials with registries in AHF suggest that populations in both large and small trials differ from “real life”. Meta-regression models suggest that both control event rates, and in the serelaxin program as an example, treatment effects, decline with increasing study size greatly reducing power (figure). This effect dilution might be explained by an increasing proportion of patients enrolled in studies who cannot benefit from the study drug.
Figure 1. Power at two-sided 0.05 significance level to detect an effect size of hazard ratio of 0.65 (left) or 0.8 (right) with a placebo event rate of 10% (top) and 20% (bottom) at N=100 at various treatment effect dilutions with increasing sample size.

Conclusion
These data suggest that it is unlikely that the very high rate of negative AHF phase III trials can be explained by chance alone. Potentially, our tendency to increase sample size does not necessarily increase statistical power, due to more heterogenous populations leading to reduced event rates and treatment effects.
P3095Left ventricular thrombus formation after ST-elevation myocardial infarction: a prospective observational CMR study
Authors: Holzknecht M , Reinstadler S J , Reindl M , Tiller C , Mayr A , Klug G , Metzler B 
Published: October 2019

Abstract

Background
Left ventricular (LV) thrombus formation is a severe complication after acute ST-segment elevation myocardial infarction (STEMI). The incidence and determinants of LV thrombus formation are still a matter of controversy.

Purpose
We aimed to assess the incidence as detected by cardiac magnetic resonance (CMR) imaging as well as the determinants of LV thrombus formation in contemporary reperfused STEMI patients.

Methods
This prospective observational study included 530 consecutive STEMI patients treated with primary percutaneous coronary intervention (PCI). Comprehensive CMR was performed at a median of 3 days (interquartile range 2–4 days) after symptom onset for the evaluation of LV thrombus formation as well as LV function and infarct severity.

Results
LV thrombi were detected in 17 patients (3.2% of the overall cohort). The incidence of LV thrombi in anterior STEMI patients (n=247) was 6.9%. In all patients presenting with LV thrombus left anterior descending artery (LAD) was identified as culprit lesion. The occurrence of thrombi was significantly associated with reduced LV ejection fraction (LVEF) (p<0.001), larger LV end-diastolic volume (p<0.001) and LV end-systolic volume (p<0.001), larger areas of microvascular obstruction (MVO) (p=0.003) and larger infarct size (IS) (p<0.001). Furthermore, increased levels of peak high sensitivity cardiac Troponin T (p<0.001) and hyperlipidaemia (p=0.038) were significantly related to LV thrombi. In multivariable analysis including IS, LVEF and MVO, only LVEF (odds ratio: 0.91 (95% confidence interval: 0.87–0.96); p=0.001) emerged as independent predictor of LV thrombus formation.

Conclusion
The risk of LV thrombus formation remains considerable in contemporary treated STEMI patients, especially in those with LAD as culprit lesion. Among CMR parameters of LV dysfunction and infarct severity, only baseline LVEF, but not IS or MVO, independently predicted LV thrombus formation after STEMI.
P3098Association with coronary high-intensity plaque on T1-weighted magnetic resonance imaging and circulating levels of malondialdehyde-modified low-density lipoprotein
Authors: Hiraya D , Sato A , Hoshi T , Ichinohe T , Sakai S , Watabe H , Ieda M 
Published: October 2019

Abstract

Objectives
This study aimed to evaluate the association with coronary high-intensity plaque (HIP) on non-contrast T1-weighted magnetic resonance imaging (T1WI) and circulating levels of malondialdehyde-modified low-density lipoprotein (MDA-LDL).

Methods
A total of 139 patients with coronary artery stenosis (>70%) were imaged with non-contrast T1WI by using a 1.5-T magnetic resonance system (HIP: n=60, non-HIP: n=79). HIP was defined as a signal intensity of coronary plaque to cardiac muscle ratio (PMR) of ≥1.4. At admission, circulating levels of MDA-LDL and other lipid-related markers (triglyceride, HDL, LDL, Lp(a), RLP-C, and EPA/AA) were measured.

Results
Circulating levels of MDA-LDL (p=0.001) and LDL (p=0.041) were significantly higher in patients with HIP than those without, whereas the other lipid-related markers were not significantly different between both groups. In multivariable logistic regression analysis, MDA-LDL levels were independently associated with the presence of HIP (OR 1.03; 95% CI, 1.00–1.06, p=0.015) after adjusting for cofounding factors (age, sex, triglyceride, LDL, Lp(a), RLP-C, and EPA/AA). The optimal MDA-LDL threshold for predicting coronary HIP was 90.4 U/L, identified by the receiver operating characteristic curve.

Conclusion
MDA-LDL levels might be associated with the presence of HIP in patients with coronary artery disease.
P3104Complementary impact of glycated haemoglobin and B-natriuretic peptide on cardiopulmonary exercise capacity in patients with ischemic heart disease
Authors: Uribe-Heredia G , Arroyo-Espliguero R , Viana-Llamas M C , Piccone-Saponara L G , Alvaro-Fernandez H , Garcia-Magallon B , Castillo-Sandoval A , Toran-Martinez C 
Published: October 2019

Abstract

Background
Glycemic control, even in non-diabetes mellitus (DM) patients, has been associated with ventilation pump inefficiency leading to an impaired aerobic capacity. Brain natriuretic peptide (BNP) levels have also been correlated with exercise capacity, particularly in patients with heart failure.

Purpose
Assess the complementary impact of glycated haemoglobin (HbA1c) and BNP levels on cardiopulmonary exercise capacity in patients with ischemic heart disease (IHD).

Methods
Retrospecive cohort of 91 consecutive patients (57±10 years, 90% men; 29% type 2 DM) who underwent a cardiopulmonary exercise testing (CPX) at the beginning of an standard phase-II cardiac rehabilitation program, 2–3 months after an acute coronary syndrome.

Results
HbA1c and BNP levels correlated with peak oxygen uptake (VO2), anaerobic threshold (AT) and pulse O2 trajectory (Table). HbA1c correlated with ventilation CPX parameters (Table) and independently predicted minute ventilation (VE) and tidal volume (VT), regardless of age, waist circumference and β-blocker therapy. BNP levels correlated with echocardiographic (LVEF, left atrium size and pulmonary artery systolic pressure) and ventilation-perfusion (V/Q) mismatch parameters (Table), and independently predicted VE/VCO2-slope (P=0.037) regardless of age, echocardiographic parameters and β-blocker therapy. Patients were divided into three groups according to HbA1c levels above or below the DM diagnosis cut-off point (6.5%) and median value of BNP levels (44.6 pg/mL). VO2 and AT significantly decreased with elevated HbA1c and/or BNP levels (Figure).
CPX parameters HbA1c (%) BNP (pg/mL) r P value r P value Peak VO2 (mL/min/kg) −0.421 <0.001 −0.295 0.005 VO2 at AT (mL/min/kg) −0.352 0.001 −0.271 0.009 O2 pulse trajectory (mL/beat) −0.345 0.001 −0.235 0.025 Minute ventilation (VE) (L/min)* −0.377 <0.001 – NS Tidal volume (VT) (L)* −0.348 0.001 – NS VE/VCO2-slope – NS 0.375 <0.001 PETCO2 at AT (mmHg) – NS −0.315 0.002 HR/VO2-slope – NS 0.307 0.003 *At peak exercise. NS: Non-significant.

Conclusions
HbA1c and BNP levels were associated with a reduced cardiopulmonary capacity in IHD patients, mediated by a ventilation impairment and a ventilation-perfusion mismatching, respectively. HbA1c and BNP are independent and additive predictors of cardiopulmonary capacity.
P3105Cardiopulmonary exercise testing normal values for young athletes and non-athletes
Authors: Sydo N , Csulak E , Major D , Erdi J , Sydo T , Gyore I , Petrov I , Czimbalmos C S , Vago H , Lakatos B , Kovacs A , Allison T G , Merkely B 
Published: October 2019

Abstract

Introduction
Cardiopulmonary exercise testing (CPET) is an important diagnostic method to evaluate athletes and non-athletes, however we do not have widely accepted normal values for correct evaluation and interpretation in the young.

Goals
Our aim was to compare CPET parameters of young athletes and non-athletes and determine reference values.

Methods
Exercise tests were performed in young non-athletes, aged <18 years between 2011 to 2016 at Mayo Clinic. Athletes underwent detailed sports cardiology screening including CPET at Semmelweis University Heart and Vascular Center between 2016 and 2018. Individuals with cardiovascular disease were excluded. We created 2 subgroups in both sexes: 12–14 years (Group 1), 15–17 years (Group 2). Statistical analysis was performed using SAS with analysis of variance under the general linear model adjusting for age, body mass index and test effort based on peak respiratory exchange ratio (RER).

Results
A total of 212 athletes (92% male, 15.5±0.6ys) and 207 non-athletes (68% male, 15.0±0.7ys) were included in the analysis. In Group 1 boys, athletes have higher peak HR (200.0±9.2 vs 188.5±16.8 bpm, p<0.0001), HR reserve (117.1±14.5 vs 108.9±19.8 bpm p<0.05), VO2 max (53.7±6.6 vs 44.7±9.1 mL/kg/min p<0.0001), ventilation (VE) (120.3±25.0 vs 70.7±21.6 L/min p<0.0001) and RER (1.12±0.0 vs 1.07±0.08, p <.001) compared to controls. In Group 2 boys, there was no difference in peak HR and HR reserve, but athletes have higher VO2 max (57.2±4.7 vs 45.3±9.3 mL/kg/min, p<0.0001) and VE (150.7±23.7 vs 104.1±25.9 L/min, p<0.0001), similarly as Group 2 girls: VO2 max (46.3±3.6 vs 34.9±8.5 mL/kg/min p<0.0001), VE (118.7±12.5 vs 68.4±20.6 L/min, p<0.0001). In male athletes, peak HR (200.6±9.2 vs 196.5±7.4 bpm p<0.05) and HR recovery (34.2±9.8 vs 29.8±11.1 bpm p<0.05) decreases with age, while VO2 max (53.7±6.6 vs 57.2±4.7 mL/kg/min, p<0.001) and VE (120.3±24.9 vs 150.7±23.7 L/min, p<0.0001) increases. Lower cut-off values were determined in each group (Figure).
Lower-cut off values

Conclusion
We created a unique Mayo-Semmelweis database of young athletes and non-athletes. As a result of intensive training, athletes show higher levels of CPET variables vs non-athletes. Our study provides CPET reference values in the pediatric age group, applying them could contribute to correct evaluation and interpretation of CPET, increasing its diagnostic potential.