bluuebunny/crossref_metadata_2025_split huggingface dataset:
Usefulness of ultra-sensitive troponin to predict anthracyclines and trastuzumab related cardiac dysfunction
Authors: Del Castillo S , Llamedo C , Capdeville S , Fileni L , Scarponi C , Belziti C , Rossi E , Falconi M , Perez De Arenaza D , Pizarro R 
Published: October 2022

Abstract

Background
Cancer therapeutics–related cardiac dysfunction usually known as cardiotoxicity (CTX) is a common adverse effect of anthracyclines and anti-Her2 agents. In recent years, evidence of usefulness of ultrasensitive troponin for early diagnosis of CTX has increased, however the cut-off values of this biomarker remain uncertain.

Purpose
To assess the usefulness of ultrasensitive troponin T (UsTnT) to identify patients at risk of developing CTX and determine cut-off values for this biomarker.

Methods
Patients with diagnosis of solid or hematologic malignancies scheduled to receive therapy including anthracyclines and/or trastuzumab were prospectively included. Echocardiogram was performed prior to chemotherapy, and repeated 3 and 6 months later. UsTnT was measured at baseline and 3 months after starting chemotherapy and the increase of this biomarker from baseline was calculated. This UsTnT has a range of 3–10,000 pg/mL with a 99th percentile &lt;15 pg/mL. Receiver operating characteristic curve was used to find out the best cut-off values followed by a multivariate analysis. The primary endpoint was the presence of CTX defined as a decline of left ventricular ejection fraction (LVEF) ≥10% at 6 months from baseline.

Results
A total of 141 patients were included (mean age 56±15 years, 85,8% were women, the most frequent diagnosis being breast cancer: 61.7%). Thirty-three patients (23.4%) met criteria of the primary endpoint of CTX. Patients with CTX showed significantly higher values of UsTnT at 3 months (18.2±14,9 vs 11.8±10,7 pg/mL, p=0.008) and also showed a higher increase of UsTnT from baseline (11.8±12.8 vs 5±8.2 pg/ml, p&lt;0.001) (figure 1).
The value of UsTnT at 3 months ≥13 pg/mL and an increase of UsTnT from baseline ≥14 pg/mL were selected as the best cut-off values. Figure 2 resumes sensitivity, specificity and predictive values. Those patients who had UsTnT at 3 months ≥13 pg/mL had a 3.8 fold increased risk of developing CTX in a multivariate analysis adjusted by age and left ventricular hypertrophy (OR: 3.8 [95% CI: 1.6–9.3], p=0.003) while an increase of UsTnT from baseline ≥14 pg/mL showed almost 12 fold increased risk for the primary endpoint in the same model (OR: 11.95 [95% CI: 3.9–36.6], p&lt;0.001).

Conclusions
UsTnT is a good biomarker for detecting early myocardial injury which allows the identification of patients at risk for developing CTX with only two measurements during cancer treatment.

Funding Acknowledgement
Type of funding sources: None.
Risk of heart failure following short-term non-steroidal anti-inflammatory drug use in patients with type 2 diabetes mellitus
Authors: Holt A , Strange J E , Rasmussen P V , Blanche P , Nouhravesh N , Jensen M H , Schjerning A M , Schou M , Torp-Pedersen C , Gislason G H , Hansen M L , McGettigan P , Lamberts M K 
Published: October 2022

Abstract

Background
Fluid retention is a known but underappreciated side-effect of non-steroidal anti-inflammatory drug (NSAID) use. As type 2 diabetes mellitus (T2DM) has been linked to both subclinical cardiomyopathy and a decline in kidney function, short-term NSAID use could lead to subsequently development of heart failure (HF) due to aberrations in fluid balances.

Purpose
We investigated associations between short-term NSAID use and the risk of HF in a nationwide cohort of patients with T2DM.

Methods
Using nationwide Danish registers, we identified patients diagnosed with T2DM during 1998–2018. Follow-up began 120 days after first-time T2DM diagnosis among patients without prior heart failure or a rheumatological diagnosis indicating long-term NSAID use.
To describe use of NSAID among patients with T2DM, we reported proportions of patients claiming at least 1, 2, 3 or 4 prescriptions of NSAID within one year of start of follow-up. We investigated associations between use of NSAIDs (celecoxib, diclofenac, ibuprofen and naproxen) and new-onset HF hospitalizations using a case-crossover design with 28-day exposure windows and reported odds ratios (OR) with 95% confidence intervals (CI). The case-crossover design uses each individual as his or her own control making it suitable to study the effect of short-term exposure on immediate events while mitigating unmeasured confounding. Sensitivity analyses using exposure windows of 14 and 42 days were performed as well.

Results
A total of 334,950 patients with T2DM was included (47.7% female, median age of 61 [interquartile range 50–70]). Celecoxib and naproxen were rarely used; on the contrary, prescriptions of diclofenac and ibuprofen were claimed at least once within one year from the beginning of follow-up by 4.9% and 15.5% of patients, respectively–0.9% and 2.7% claimed at least four prescriptions (Figure 1).
The risk of new-onset HF hospitalization was increased following use of diclofenac or ibuprofen with corresponding ORs of 1.3 (95% CI 1.0 to 1.7) and 1.3 (95% CI 1.1 to 1.5) using 28-day exposure windows. An increased risk following use of celecoxib or naproxen was not found (Figure 2).

Conclusion
NSAIDs diclofenac and ibuprofen were both widely used and associated with an increased risk of new-onset HF hospitalization in patients with T2DM. This suggests a previously unknown and serious, clinically relevant concern of NSAID use in patients with T2DM.

Funding Acknowledgement
Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Ib Mogens Kristiansens Almene FondHelsefonden
Myocardial work analysis for early detection of type 1 CTRCD and patient risk stratification
Authors: Moya A , Buytaert D , Paolisso P , Verstreken S , Goethals M , Dierckx R , Beles M , Penicka M , Vanderheyden M , Heggermont W 
Published: October 2022

Abstract

Aim
This prospective longitudinal study analyses the potential role of Myocardial Work in early detection of cardiotoxicity during chemotherapy and its added value for prognosis and patients' risk stratification.

Methods
We enrolled 47 consecutive female patients with HER2-positive breast cancer referred for anti-cancer therapy based on anthracycline and taxane. Patients with depressed LV function at baseline were excluded. Medical therapy, clinical parameters and echocardiographic data were recorded at baseline and at 3, 6, 12 months follow-up. Additionally, cuff blood pressure was measured at the time of 2D-TTE examination and adequate echocardiographic images were stored for off-line analysis.

Results
CTRCD was detected in 17 patients (36%) while 30 patients remained free of CTRCD (64%). There were no intergroup differences for age, body mass index, resting heart rate and brachial arterial pressure. Both groups presented unaltered LV systolic function after 3 months follow-up yet overt cardiac dysfunction showed up in the CTRCD group at 6 months with significant decline in LVEF, GLS, MWI, MWE and CW from baseline values (LVEF, %: 56.0±4.1 vs 52.2±6.5; GLS, %: −20.9±1.9 vs −17.6±3.2; MWI, mmHg%: 2125±348 vs 1704±620; MWE, %: 95±2.6 vs 93±3.9 and CW, mmHg%: 2562±3567 vs 2212±455, p&lt;0.05). Additionally, GLS, MWI and MWE at 6 months were significantly worse in the CTRCD group vs non-CTRCD group (GLS, %: −17.6±3.2 vs −20.6±1.8; MWI, mmHg%: 1704±620 vs 2087±347; MWE, %: 93±3.9 vs 96±1.5, p&lt;0.05). Depressed LV systolic function persisted after 1 year follow-up (Figure 1). After 3 months, only de relative change in GLS and WW from baseline were significantly worse in CTRCD vs non-CTRCD (ΔGLS: +3.7±11 vs −3.9±10, ΔWW: +46.1±83 vs +2.2±45). Whereas no correlation was found, the combination of both ΔGLS and ΔWW at 3 months showed stronger prognostic value for CTRCD than each parameter alone, AUC of 0.72 (Figure 2).

Conclusion
These findings point the superiority of Myocardial Work for early type 1 CTRCD detection in comparison to the current diagnostic tools. Additionally, we suggest the add-on value of ΔWW on top of ΔGLS quantification for better patient risk stratification. These are promising results for better clinical surveillance of cardiac function during cancer treatment.

Funding Acknowledgement
Type of funding sources: None.
The hemodynamic and prognostic impact of systolic pressure change during right ventricular ejection in patients with HFREF
Authors: Schmeisser A , Rauwolf T , Tanev I , Meissler S , Hansen M , Groscheck T , Luani B , Steendijk P , Braun-Dullaeus R 
Published: October 2022

Abstract

Background and purpose
The gold-standard method to evaluate right ventricular (RV) function in pulmonary hypertension (PH) relies on invasive pressure-volume loop (PV-loop) measurement of RV-pulmonary artery (PA) coupling defined as the ratio of end-systolic RV elastance to pulmonary arterial elastance (Ees/Ea). The normal RV PV-loop has a triangular shape with a peaking early systolic pressure (early-SP). With progression of PH the PV-loop changes from trapezoid to a rectangular and ultimately to a trapezoid shape. Along with these geometric changes, the ratio between early-SP and end-systolic pressure (ESP) decreases from &gt;1 to &lt;1 with a late systolic peaking of RV pressure. How all these changes relate to RV afterload, RV-PA coupling, non-invasive RV function, and prognosis in PH due to left heart disease is incomplete understood.

Methods
We analyzed and categorized the conductance catheter-derived single-beat RV PV-loops in 133 patients with HFREF (110 patients: a post-hoc analysis of the Magdeburg CRT Responder Trial, 23 from a local PV-L-derived CRT-optimization trial) according their shape (triangular, rectangular, trapezoid), and determined the early-SP/ESP ratio.

Results
Using multivariate linear regression analysis (adjusted for afterload parameter PVR, PA-compliance, PCWP, PAmean), only PCWP (beta=−0.17) and PA-compliance (beta=0.61) remained significant determinants of the early-SP/ESP ratio and PV-loop shape. In turn, early-SP/ESP ratio seems to be an important determinant of RV-PA coupling efficiency (Ees/Ea) of the RV to afterload (r=0.8, p&lt;0.001). The association between early-SP/ESP ratio and Ees/Ea ratio was closer than Ees/Ea ratio to the other afterload parameters Ea (r=−0.7), PVR (r=−0.41), and PA-compliance (r=0.62). Furthermore, the early-SP/ESP ratio was significantly associated with parameters of non-invasive RV function such as TAPSE (r=0.67), FAC (r=0.76), RVEF (r=0.7), and the non-invasive RV-PA coupling parameter TAPSE/PASP (r=0.8) (all p&lt;0.001). In cox regression analysis, the early-SP/ESP ratio was a strong indicator for long-term survival (median FU 4.2 years) (OR 0.025, CI 95% 0.007–0.09). Simple categorization of the RV PV-loop shapes into “triangular” (early-SP/ESP ratio &gt;1.1, mean survival 7.7 years), “rectangular” (0.9–1.1, 6.4 years) and “trapezoid” (&lt;0.9, 3.2 years) clearly differentiated long-term survival of HFREF patients (log rank, Chi square 50.1, p&lt;0.001).

Conclusion
The early-SP/ESP ratio determines the shape of RV-PV-loops and is closely associated with predominately pulsatile PA load, RV-PA coupling capacity, RV function, and long-term prognosis of patients with HFREF.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): Boston Scientific
Determinants of impaired coupling of right ventricle to hemodynamic load in advanced HFrEF
Authors: Melenovsky V , Monzo L , Benes J , Reichenbach A , Solar N , Tupy M , Jenca D , Tykvartova T , Miklovic M , Al Hiti H , Ters J , Kautzner J 
Published: October 2022

Abstract

Background
The mechanisms and consequnces of impaired right ventricular (RV) dysfunction and impaired RV-pulmonary artery (PA) coupling in advanced heart failure (HF) poorely understood.

Purpose
To compare RV-PA coupling parameters in patients with advanced HFrEF, PAH and in controls to ellucidate determinants and prognostic impact of RV-PA uncoupling in HFrEF.

Methods
260 pacients with advanced HF (NYHA 3.0±0.5, 40% CAD, LVEF: 23±10%, 87% males, BMI: 28±4.5 kg/m2, BNP: 1238±982 pg/ml), 39 controls and 21 PAH patients underwent lab tests, ecocardiography, right heart catheterisation and equilibrium gated blood pool SPECT to precisely measure cardiac volumes. RV End-systolic elastance (Ees) and Effective arterial elastance (Ea) were calculated by single beat method. Patients were longitudinally followed for occurrence of adverse outcome (urgent Tx, LVAD or death without Tx/LVAD).

Results
PAH patients had higher PA pressures and more dilated RV than HFrEF and controls. Despite of that, RV-PA coupling, reflected by Ees/Ea ratio, was more profoundly reduced in HFrEF than in PAH (Figure). While RV contractility (Ees) was augmented by increased afterload in PAH, such augmentation was absent in HFrEF. At follow-up (median 258; 53–763 days), 69% of HFrEF subjects experienced adverse event (17% death, 24% urgent HTx, 28% LVAD). In HFrEF, RV-PA coupling was strongly predictive od adverse outcome, more than RV EF%, RV EDV or RV Ees. The strongest predictors of reduced RV Ees/Ea ratio in HFrEF were in descending order: RV EF, RV EDV, PA systolic/systemic systolic pressure ratio (PAs/SBP), PAWP, heart rate, PA compliance, RA mean pressure, PA mean pressure, BNP level, SBP, PAs, Tri Reg grade, Non-CAD etiology of HF, Mi Reg grade, PVR, RV dyssynchrony, absence of ACEi/ARB/S-V (GLM model, all p&lt;0.001). RV Ees/Ea ratio correlated with PAs/SBP ratio, that reflects systolic ventricular interdependence. Invasive PAs/SBP predicted outcome and closely correlated with non-invasive estimation of PAs/SBP.

Conclusion
Despite having less PH and smaller RV, RV coupling is more impaired in HFrEF than in PAH due to absence of RV contractility enhancement. Higher RV volume, heart rate, tricuspid regurgitation, lower PA compliance, higher PAWP and systolic ventricular interdependence (PAs/SBP) are main determinants of RV PA decoupling in HFrEF. Elevated PA systolic pressure but low systemic BP (high PAs/SBP ratio) is associated with poor RV-PA coupling and prognosis.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): AZV NU20-02-00052, AZV NU21-02-00402
Cardiomyopathy associated with right ventricular apical pacing – systematic review and meta-analysis
Authors: Osiecki A , Kochman W , Witte K K , Manczak M , Olszewski R , Michalkiewicz D 
Published: October 2022

Abstract

Aims
Bradyarrhythmias are potentially life threatening medical conditions. The most widespread type of treatment of slow rhythms is artificial ventricular pacing. From the inception of the idea of artificial pacing, ventricular lead was located in the apex of the right ventricle. Right ventricular pacing (RVP) was thought to have deteriorating effect on left ventricular systolic function. The aim of this study was to systematically assess results of randomized controlled trials of the right ventricular pacing on left ventricular ejection fraction (LVEF).

Methods
We systematically searched the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE databases for studies evaluating the influence of the RVP on the LVEF. Pooled mean difference (MD) with a 95% confidence interval (CI) was estimated using a random effect model.

Results
15 randomized controlled trials (RCTs) comprising 951 patients were included. The mean follow-up in the included studies ranged between 6 to 24 months. In our meta-analysis, RV pacing was associated with statistically significant (MD 2.91; 95% confidence interval (CI): 1.07–4.75) left ventricular systolic function impairment measured by LVEF.

Conclusion
Our meta-analysis confirms, that the right ventricular pacing is associated with progressive deterioration of the left ventricular systolic function.

Funding Acknowledgement
Type of funding sources: None.
Baseline profile and results of atrial fibrillation ablation in patients with arrhythmia-induced cardiomyopathy
Authors: Gonzalez-Ferrero T , Minguito-Carazo C , Bergonti M , Lopez-Canoa J N , Garcia-Rodeja Arias F , Otero-Garcia O , Gonzalez-Maestro A , Martinez-Sande J L , Gonzalez-Melchor L , Garcia-Seara J , Fernandez-Lopez J A , Gonzalez-Juanatey J R , Sarkozy A , Rodriguez-Manero M 
Published: October 2022

Abstract

Background
Atrial fibrillation (AF) is known to trigger a reversible dilated cardiomyopathy referred as arrhythmia-induced CM (AiCM). However, it remains unclear why some patients are more prone to develop AiCM than others and there is scarce information about their clinical outcomes after AF ablation.

Purpose
We ought to find clinical and analytical predictors for the development of AiCM and recovery of LVEF in patients referred for AF ablation.

Methods
A prospective multicenter study of consecutive patients undergoing point-by-point radiofrequency (RF) catheter ablation between September 2016 and November 2021 was conducted. The low voltage areas and left atrial (LA) volume were analyzed offline on high density electroanatomical maps collected prior to RF ablation. Peripheral blood sample for biomarker analysis (Gal-3, FABP4 and sRAGE) were obtained at the time of the procedure.

Results
803 consecutive patients were included, median age was 61 and 240 (30,81%) were women. AF pattern was paroxysmal in 254 (32,60%) and persistent in 534 (68,55%; of whom, long-standing persistent in 113 (14,51%) patients). The median follow-up period was 23.83 months [IQR 9 to 36]. The multivariate analysis revealed LA area, width of QRS segment, persistent AF and chronic kidney disease (CKD) as independent predictors for AiCM. Recurrence-free survival was not different amog both cohorts (Figure 1).
The median increase in LVEF from baseline to the 6-month follow-up visit in patients with AiCM was 16% (CI 14.31–18.47) without changes in the non-AiCM group. The median LVEF previously to CA from patients in the AiCM group was 38% (IQR 30–45%) and after the procedure 57% (IQR 50–60%) [see figure 2].

Conclusions
AiCM is characterized to have a particularly complex pathophysiology not fully understood thus far. Pulmonary vein isolation in patients is safe and suitable for patients that suffered from tachycardiomyopathy. We found that persistent AF and chronic kidney disease play a key role in its development. Neither peripheral blood biomarkers nor left atrial samples showed relevant association with its occurrence.

Funding Acknowledgement
Type of funding sources: None.
Liver fibrosis might drive fibrogenesis in the heart in early alcoholic liver disease
Authors: Grander W , Grander C , Wenter C , Aysar Y , Riederer M , Zagitzer-Hofer S , Tilg H , Graziadei I , Marksteiner J 
Published: October 2022

Abstract

Background/Introduction
Alcohol use disorder (AUD) is associated with the development of psychiatric conditions as well as alcoholic liver disease (ALD). Ethanol toxicity but also the intestinal microbiota are important drivers of fibrogenesis in the liver and eventually also of the myocardium.

Purpose
The aim of our study was the investigation of simultaneous development of fibrosis in liver and heart in patients with early ALD.

Methods
The HALFWAY-Study is a cohort study, recruiting patients with ALD during a detoxification program. Liver stiffness was measured by non-invasive elastography (ARFI, Acoustic Radiation Force Impulse). Echocardiographic measured E/e' (early ventricle filling velocity, E / mitral annular early diastolic velocity, e') and left atrial volume (LaVol) were used as surrogate markers for atrial filling pressure, which in case of normal de-loading of the left ventricle, correlates with diastolic dysfunction.

Results
50 patients were included into the study (females n=27, males n=23). Participants were young (mean age 43.3 years ± 7.3), non-obese (body mass index; BMI 23.9 kg/m2 ±3.9) and non-diabetic (HbA1c 5.1% ± 0.3), ruling out metabolic disease. All patients displayed normal ejection fraction (EF; 61.3% ± 9.1) a global longitudinal strain (4 chamber view) of −15.03±3.7 and NTproBNP (50 pg/ml; IQR 46.5). 95% of patients reported alcohol consumption more than four times a week, with 65% drinking 7–8 drinks per day and 25% consuming more than daily 10 drinks. The mean liver stiffness was 6.5 kPa ± 4.2, whereby in 18% of participants a significant liver fibrosis was diagnosed. We could observe a significant correlation between non-invasive liver stiffness measurements (ARFI) and E/e' (p=0.019, R=0.338) as well as LaVol (p=0.043, R=0.29). In a multivariate linear regression model using ARFI, EF, LaVol and global strain as independent variables, using the backward selection method (R2=0.114, p=0.022 for the final model), we identified ARFI as the only significant predictor of E/e' (B=0,337; p=0.022).

Conclusion
In patients with early ALD liver stiffness (measured by ARFI) independently predicts E/e' which might indicate simultaneous fibrogenesis of liver and heart.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): ÖGGH
Left ventricular dysfunction in a cohort of new onset idiopathic inflammatory myopathy without known heart disease
Authors: Lindstedt M , Andreasson K , Da Silva C , Manouras A , Alexanderson H , Andersson D C 
Published: October 2022

Abstract

Impaired myocardial function is linked to inflammatory mechanisms. Indeed, many systemic inflammatory diseases are associated to risk of developing heart disease. Idiopathic inflammatory myopathy (IIM; here Dermato- or polymyositis) are rare systemic inflammatory diseases, characterised by immune infiltration in muscle, presence of autoantibodies and cytokines in circulation leading to weakness and disability. IIM can involve extra-muscular tissues, e.g. heart, and is associ-ated with elevated risk for cardiovascular disease. Heart function in IIM is little investigated and has mostly been studied in patients at a chronic IIM stage or with a concomitant heart disease.
To our knowledge, heart function has not been characterized at the early stage in IIM when the risk of inflammatory associated cardiomyopathy may be high. Our hypothesis is that patients at early-stage IIM may present with subclinical myocardial dysfunction that can be detected by echocardiography.
We used echocardiography (echo) following clinical standards to investigate heart function in a cohort of 18 patients (61% females; age 46±12 years) with recent onset IIM (mean diagnosis time 5 month). Patients were recruited from the rheumatology clinic at Karolinska University Hospital, Stockholm, and had given written consent. None had previous heart disease. Echo parameters were compared to normal reference limits as established by the American Society for Echocardiography. Heart failure association (HFA)-PEFF score (≥2 p) was used to define left ventricular diastolic dysfunction (LVDD).
Ejection fraction (EF) was generally preserved in the cohort with no patient displaying EF&lt;55% (Table 1). Yet, 4 patients (22%) displayed reduced global strain (LVGLS; &gt;−20%) suggesting presence of impaired myocardial contraction. In contrast, diastolic dysfunction was seen in several patients as indicated by one or more diastolic parameters outside normal rage (table 1). Moreover, when calculating HAVA-PEFF score 9 patients (50%) fulfilled criteria for LVDD. None of the patients displayed hypertension (&gt;140/90 mmHg), or left ventricular hypertrophy.
In a cohort of patients with recent onset IIM without known heart disease, we have found that diastolic dysfunction is prevalent with 50% of the patients fulfilling criteria for LVDD according to the HFA-PEFF score. This gives a high likelihood of fulfilling criteria for the diagnosis heart failure with preserved EF (HFpEF). We conclude that clinical echocardiography is important in the initial work up of IIM to screen for LVDD as the risk of heart failure is likely to be high.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): Swedish Heart Lung Foundation