bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between cardiogenic shock phenotype, vasopressor requirements and mortality
Authors: Sarma D , Kashani K , Hibbert B , Jentzer J C 
Published: October 2024

Abstract

Background
Greater vasopressor requirements predict higher mortality in patients with cardiogenic shock (CS).(1) The extent to which CS phenotype modifies the relationship between vasopressor dose and mortality risk is unknown.

Purpose
We investigated the association between in-hospital mortality and vasopressor dosing (expressed as norepinephrine equivalents [NEE]) during the first 24 hours of hospitalization across distinct CS phenotypes.

Methods
We included patients with CS admitted to our cardiac intensive care unit (CICU) between 2007 and 2015. Peak combined vasopressor doses during the first 24 hours of hospitalization were recorded as NEE. High dose vasopressor (HDV) use was defined as peak 24 hour NEE &gt;0.3 mcg/kg/min. Unsupervised machine learning was used to assign patients to one of three phenotypes (non-congested, cardiorenal, and haemometabolic), as reported previously by our group and others.(2,3) The primary outcome was in-hospital mortality. Multivariable logistic regression was used to adjust for relevant covariates.

Results
A total of 1078 patients with CS (median age 69 years, 37% female, 59% with acute myocardial infarction) were admitted to our cardiac intensive care unit (CICU) between 2017 and 2015. The number of patients assigned to each CS phenotype were: haemometabolic (n=325, 30%), cardiorenal (n=314, 29%), non-congested (439, 41%). There was a strong incremental association between in-hospital mortality and NEE (Fig. 1, adjusted OR 1.104 per 0.1 mcg/kg/min, 95% CI 1.134–1.231, P&lt;0.001), and patients receiving HDV (n=234, 22%) had significantly higher in-hospital mortality (57% vs 28%, p&lt;0.001). Among patients who did not receive HDV, mortality was higher in haemometabolic CS (49%) compared to 24% in cardiorenal CS and 21% in non-congested CS (adjusted OR 3.58 relative to non-congested CS, 95% CI 2.46-5.23, p&lt;0.001, Fig. 1). Among patients receiving HDV, hemometabolic CS was also associated with higher mortality (68%) than those with cardiorenal (46.2%) or non-congested CS (39.3%), (adjusted OR 3.26 relative to non-congested CS, 95% CI 1.75-6.18, P&lt;0.001, Fig. 1).

Conclusion
Integration of CS phenotype with vasopressor requirements may provide incremental prognostic information in CS during the first 24 hours of admission, with haemometabolic CS portending a greater mortality risk even at lower NEE. Patients with HDV (particularly those requiring &gt;=1 mcg/kg/min NEE) had high mortality irrespective of CS phenotype.Figure 1
Predictive models for mortality in cardiogenic shock: a systematic review and meta-analysis
Authors: Lim S L , Ng G W Y , Low C J W , Ling R R , Ng K J , Chan S P , Ramanathan K 
Published: October 2024

Abstract

Background
Cardiogenic shock (CS) is a time-critical emergency with high mortality and morbidity, yet prognostication remains challenging with neither guidelines nor consensus on the comparative applicability of existing risk scores used in CS. We aimed to evaluate discrimination and calibration of existing risk scores in predicting mortality in CS.

Methods
We searched MEDLINE, Embase, and Scopus databases up to 1 January 2024 for articles developing, redeveloping or validating a multivariable model predicting short-term mortality in adults with CS. Area under curve (AUC) statistics and observed versus expected (O:E) ratios were used to assess discrimination and calibration respectively. We conducted random-effects inverse-variance weighted meta-analyses on 6 prevalent, well-validated prediction models (IABP-SHOCK II, CardShock, SAPS II, SOFA, APACHE II and SAVE) to derive pooled estimates of AUCs and aggregate O:Es for each model. Subgroup analyses were conducted to identify sources of heterogeneity.

Results
We included 92 studies (115 study cohorts, 75,228 patients) in our analysis, with 43 unique prediction models identified. Our meta-analysis revealed that the CS-specific CardShock score had the overall best discrimination (AUC 0.73; 95% CI 0.70-0.76) and calibration (O:E 1.06; 95% CI 0.79-1.41). SOFA performed second best in discrimination (AUC: 0.72, 95%-CI: 0.68 to 0.75) but tended to underpredict mortality (AUC: 0.85, 95%-CI: 0.65-1.12). IABP and APACHE had comparable discrimination (AUC 0.71), IABP tended to overpredict (O:E 1.24; 95% CI 0.995-1.55) while APACHE (O:E 0.93; 95% CI 0.57-1.53) tended to underpredict mortality.
In subgroup analysis, CardShock performed best based on mechanical circulatory support type (AUC 0.74-0.76, O:E 0.82-0.99), location (AUC 0.67-0.87, O:E 1.00-1.25) and study type (AUC 0.73-0.97, O:E 0.91-1.99).

Conclusion
Among well-validated risk scores, the CardShock score performed best in discriminating and calibrating mortality. Its variable performance across subgroups underscores the need for more research to identify an ideal risk prediction model that considers emerging therapies and use in multiple scenarios.
Calcific aortic valve disease-associated long noncoding RNA H19 promotes the osteogenic transition of valvular interstitial cells via the JAG1/NOTCH1 axis
Authors: Hosen D R , Zhou C A N , Billig M E D , Goody M E D , Zimmer D R , Uchida D R , Pfeiffer D R , Jansen M E D , Nickenig D R 
Published: October 2024

Abstract

Background
Calcific aortic valve disease (CAVD) is the most prevalent valvular heart disease causing tremendous suffering globally. The osteogenic differentiation of the valvular interstitial cells (VICs) is a key process in the pathogenesis of CAVD leading to calcification and stiffening. Here, we focus on the contribution of long noncoding RNA H19 in the osteogenic differentiation of VICs promoting CAVD.

Methods and results
A human lncRNA array performed in AVS patients with coronary artery disease (CAD) revealed the differential expression of lncRNA H19. For the experiments in this study, loss of function (LOF) was performed in primary VICs isolated from the aortic valves of patients with CAVD, and commercially-available VICs. Therefore, H19 expression was effectively downregulated via RNAi. Subsequent gene expression analysis via RT-qPCR revealed that the expression of calcification markers RUNX2 and BMP2, as well as the expression of the H19 downstream targets JAG1 and NOTCH1 were unchanged after the H19 knockdown alone. Then, the VICs were additionally treated with osteogenic medium (OM) and procalcifying medium (PCM) for 7 d to induce the calcification of the cells. In the OM, inorganic phosphate is generated in an alkaline phosphatase (ALPL)-dependent manner and integrated into newly formed hydroxyapatite crystals, thus promoting cellular calcification. PCM contains inorganic phosphate to form hydroxyapatite crystals and is therefore not ALPL-dependent. Gene expression analysis via RT-qPCR and protein analysis via immunofluorescence revealed that the calcification markers BMP2 and RUNX2 were upregulated after H19 knockdown and calcification induction. This indicates that H19 regulates the expression of calcification makers promoting cellular calcification. Furthermore, RT-qPCR and immunoblotting revealed the differential expression of several potential H19 downstream targets, namely JAG1, NOTCH1, and STAT3. The analysis showed that the potential downstream targets were upregulated after H19 knockdown and calcification treatment hinting at the involvement of the NOTCH1 or STAT3 pathway in the pathogenesis of CAVD. Moreover, an Alizarin Red S staining of calcified nodules revealed reduced calcification after H19 knockdown and calcification treatment for 21 d. This demonstrates that H19 also regulates a late-stage event in the cellular calcification of VICs.

Conclusion
Our study showed that H19 regulates calcification marker expression and the expression of potential downstream targets JAG1, NOTCH1, and STAT3 both in healthy and AVS patient VICs. This hints at the involvement of the H19/JAG1/NOTCH1 pathway in the calcification of VICs, which might play a critical role in the pathogenesis of CAVD.
Valvular heart disease and out-of-hospital cardiac arrest
Authors: El-Chouli M , Mizrak I , Mohr G H , Malmborg M W , Gislason G , Bruun N E , Barcella C B 
Published: October 2024

Abstract

Background
The prevalence of valvular heart disease is on the rise. Severe valvular diseases are generally associated with high mortality, and aortic stenosis (AS) is associated with halved survival after out-of-hospital cardiac arrest (OHCA). Despite the severity of the prognosis of valvular heart diseases, their association with the risk of OHCA is not well-elucidated.

Purpose
The study aimed to examine the association between valvular heart disease and OHCA.

Method
We conducted a study using data from the nationwide Danish Cardiac Arrest Registry. We included adult OHCA patients with presumed cardiac origin. We compared OHCA cases with and without valvular heart disease, stratified by valvular disease type (AS, aortic regurgitation (AR), mitral stenosis (MS), and mitral regurgitation (MR) or multiple valvular diseases (more than 1 concomitant type of valvular disease)). We calculated the hazard ratios of OHCA using time-varying Cox regression models fitted with a nested case-control design. For each case, we matched up to five controls based on age, sex, year of OHCA, and two comorbidities: ischemic heart disease and congestive heart failure.

Results
We included 43,967 OHCA cases and 219,772 controls matched from the general population. In the total case population, the median age was 72 years, 68% were male, 26% had ischemic heart disease, 21% had congestive heart failure, and 57% had cardiovascular risk factors. We identified 1862 (4.23%) cases with AS, 336 (&lt;1%) with AR, 31 with MS (&lt;1%), 710 with MR (1.6%), and 605 with multiple valvular diseases (1.4%). Compared with cardiac arrest cases without valvular disease, cases with valvular disease were more likely to have ischemic heart disease (e.g., AS vs controls: 6.5% vs 1.7%, p&lt;0.001) and congestive heart failure (e.g., MR vs controls: 3.5% vs 1%, p&lt;0,001; AS vs controls: 8.2% vs 2.8%, p&lt;0.001). AS, MS (HR: 1.67 [95%CI: 1.12; 2.51]), MR (HR: 1.38 [95%CI: 1.27; 1.50]) and multiple valvular diseases (HR: 1.36 [95%CI: 1.24; 1.49]) were significantly associated with higher hazard of OHCA (Figure 1); the strongest association was seen for AS (HR: 1.66 [95% CI: 1.58; 1.76]) (Figure 1). AR was not significantly associated with OHCA (HR: 1.05 [95%CI: 0.94; 1.19]).

Conclusion
In this Danish nationwide cardiac arrest cohort, aortic stenosis, aortic regurgitation, and mitral regurgitation were associated with increased rates of OHCA. The association was strongest in aortic stenosis patients. Focus on risk factors of OHCA in patients with valvular heart disease is warranted.Figure 1
Impact of body mass index on aortic valve stenosis and its clinical outcomes in early adulthood: a long-term study of young men
Authors: Lindgren M , Kontogeorgos S , Adiels M , Nielsen S , Robertson J , Mandalenakis Z , Aberg M , Aberg N D , Djekic D 
Published: October 2024

Abstract

Aims
Studies investigating associations between body mass index (BMI), incidence of aortic valve stenosis (AVS), and clinical outcomes in AVS patients are scarce.

Purpose
To investigate the relationship between BMI in youth and subsequent diagnosis of AVS. A secondary aim was to determine the role of obesity in clinical outcomes in individuals diagnosed with AVS.

Methods
This was a nationwide, register-based cohort study of 1 701 390 men (mean age, 18.3 ±0.8 years) enrolled in compulsory conscription for military service in Sweden from 1969 through 2005. Anthropometrics, blood pressure, fitness, muscle strength and IQ were recorded at baseline. AVS cases and cardiovascular outcomes were identified according to the International Classification of Diseases (ICD)-10 registered in the National patient register and Cause of Death Register through the Swedish 12-digit personal identification number. BMI (kg/m2) was categorized as &lt;18.5, 18.5–&lt;20, 20–&lt;22.5, 22.5–&lt;25, 25–&lt;27.5, 27.5 &lt;30, 30–&lt;35, and 35–&lt;50 kg/m2. Cox proportional hazard models were used to estimate the association between adolescent BMI and future hospitalization for AVS while adjusting for potential confounders. The BMI reference was set as 20–&lt;22.5. Those who developed AVS formed a subcohort that was followed until a first clinical cardiovascular outcome of death, cardiovascular mortality, Heart failure, Atrial fibrillation, myocardial infarction, or ischaemic stroke.

Results
During a median follow-up of 32 years (IQR, 24-41 years), 5766 cases (mean age 54.7±9.4 years) of AVS were diagnosed. After adjustment, underweight subjects with a BMI of &lt;18.5 kg/m2, compared to those with a low-normal BMI (20.0–&lt;22.5 kg/m2) showed lower risk (HR 0.70; 95% CI 0.61–0.80) of AVS. The multivariable-adjusted HR for AVS increased from HR 1.28; 95% CI 1.17–1.39 for BMI 22.5–&lt;25 kg/m2 to HR 1.91; 95% CI 1.12–3.25 for those with BMI 35–50 kg/m2. Further on, individuals diagnosed with AVS were followed for a median of ~5.5 years. The multivariable-adjusted HR for all-cause mortality, cardiovascular mortality, and heart failure for obese (BMI 30–50 kg/m2), compared to BMI &lt;20.0 kg/m2 in men diagnosed with AVS, were 4.69 (95% CI 2.61–8.44), 4.09 (95% CI 1.72–9.73), and 2.76 (95% CI, 1.36–5.60), respectively.

Conclusions
Elevated BMI in youth, even within the normal range, is associated with increased risk of developing AVS, while subnormal BMI was protective. Excess weight in youth diagnosed with AVS is associated with higher risk of subsequent clinical outcomes. These findings are novel, generating new questions as to potential mechanisms and implying more vigilant monitoring of patients with AVS and a history of obesity in youth.Figure 1Figure 2
The prognostic role of left atrial mechanics but not left ventricular function in functional mitral regurgitation
Authors: Lu C T , Sung S H 
Published: October 2024

Abstract

Introduction
When atrial dilatation or ventricular dysfunction underline the development of functional mitral regurgitation (FMR), FMR has been categorized into ventricular and atrial type. Due to limited evidence of surgical correction, majority of patients with FMR were left untreated. We therefore investigated the clinical outcomes related to different phenotypes of FMR and the prognostic factors.

Methods
Subjects with severe or moderate to severe FMR, diagnosed by transthoracic echocardiography were eligible for this analysis. Three phenotypes of FMR, including atrial, ischemic and ventricular FMR were then classified. The left atrial (LA) strain and left ventricular (LV) global longitudinal strain (GLS) were measured. The study population were followed for a year.

Results
A total of 298 subjects (mean age 72.3 ± 14.0 years; 68% male) were enrolled, including 165 subjects of ischemic-type FMR (iFMR), 77 subjects of non-ischemic ventricular-type FMR (vFMR), and 56 subjects of atrial-type FMR (aFMR). The baseline characteristics, including age, gender, demography, and morbidities were similar between three groups, but aFMR group had higher LA reservoir strain and better LV GLS. During a mean follow-up duration of 283 days, there were 50 (17%) cases died within the first year. The Kaplan Meier curve analysis showed similar survival rate between three phenotypes of FMR. Body mass index (BMI), systolic blood pressure, diastolic blood pressure, history of myocardial infarction (MI), RV dysfunction, and a lower LA reservoir strain, but not LV GLS were crudely related to one-year mortality. In the multivariable Cox proportional regression analysis, LA reservoir strain was independently predictive of mortality (Hazard ratio for 1% increase and 95% confidence intervals: 0.943, 0.895-0.994).

Conclusions
Patients with aFMR also have despaired clinical outcomes as patients with vFMR or iFMR. LA reservoir function but not LV systolic function was predictive of worse clinical outcomes. The results may encourage the transcatheter therapy, approved for ventricular-type FMR, for the treatment of aFMR.Kaplan Meier curve analysisMultivariable CPH regression model
Vmax as an Index of right ventricular function in pulmonary hypertension
Authors: Bauer F , Mallet S , Besbes B , Si Belkacem N , Saidi N , Artaud-Macari E 
Published: October 2024

Abstract

Background
For assessing right ventricular function in pulmonary hypertension (PH), the optimal approach is through the use of load-independent parameters. While pressure-volume (PV) loops are not feasible in clinical settings, the maximum velocity of the contractile element under no load, known as Vmax, serves as an alternative measure that could be derived only from right-heart catheterization (RHC).

Objectives
To determine Vmax in patients undergoing RHC and to evaluate its correlation with echocardiographic parameters.

Methods
15 PH patients scheduled for risk stratification were subjected to RHC and echocardiography. The contractile velocity element (VCE) was calculated as VCE = 1 / (28.8 x P) x dP/dt, with P representing RV pressure in mm Hg and dP/dt its first derivative in mmHg/s. The P vs. VCE plot displays a peak VCE value, leading into a linear slope (red line, figure 1A) with Vmax as the zero-pressure intercept. Vmax was compared with 6 different echocardiographic parameters of RV function.

Results
They were six females and 9 males aging 61±6 y. Mean PH was 37,6±10,1 mm Hg and Vmax averaged 2,1±0,9 length/s (range from 0,8 to 4,4 length/s). Figure 1B illustrates 3 patients with deteriorated, mildly reduced and normal VCE. When compared to Vmax, tricuspid peak systolic tissue Doppler velocity and TAPSE shown the best correlation while RV fractional area change demonstrated the worse correlation (figure 2).

Conclusion
Vmax, an indicator of right ventricular systolic function that does not depend on load, can be obtained through right heart catheterization. Both tissue Doppler peak systolic velocity and tricuspid annular plane systolic excursion (TAPSE) have demonstrated a strong correlation with Vmax.Invasive pressureECHO parameters
Periprocedural changes in systolic pulmonary artery pressure in transcatheter aortic valve implantation
Authors: Wang Gottlieb A , Nilsson K , Settergren M , James S , Shahim B 
Published: October 2024

Abstract

Background
Pulmonary hypertension (PH) is common in patients with aortic stenosis and associated with increased mortality following transcatheter aortic valve replacement (TAVR). PH often improves after TAVR and systolic pulmonary artery pressure (sPAP) can change, but to what extent these changes in sPAP following TAVR affect long-term prognosis is unclear.

Purpose
To investigate the association between periprocedural changes in sPAP and long-term prognosis after TAVR.

Methods
Patients undergoing TAVR between 2012-2021 from the Swedish Transcatheter Cardiac Intervention Registry (SWENTRY) were included. sPAP was estimated from echocardiography before and after TAVR and categorized as: (1) No PH before and unchanged (≤5 mmHg change) after, (2) No PH before and worsened (&gt;5 mmHg increase) after, (3) PH before and improved (&gt;5 mmHg decrease) after, (4) PH before and unchanged after and (5) PH before and worsened after. An sPAP cutoff at &gt;50 mmHg was applied for PH. Patients were followed for a median of 3.1 years for the primary endpoint heart failure hospitalizations (HFH) and the secondary endpoint all-cause mortality. Cox regression analyses were performed and adjusted for age, sex, body mass index, atrial fibrillation, eGFR class, diabetes, frailty, left ventricular ejection fraction and chronic obstructive pulmonary disease.

Results
In total, 4926 patients were included (mean age 82 years, 50% female) among whom 2596 (53%) patients had no PH and unchanged, 864 (18%) had no PH and worsened after, 912 (19%) had PH and improved after, 401 (8%) had PH and unchanged after and 153 (3%) had PH and worsened after. The mean sPAP levels preoperatively in each group were 36, 31, 60, 58, 57 mmHg respectively. Mean change in patients with no PH and worsened was +16 mmHg, in patients with PH and improved -20 mmHg and in patients with PH and worsened +14 mmHg. Cumulative incidence rates of HFH at 5 years among the five groups were 18%, 25%, 32%, 41%, and 52%, respectively (p&lt;0.001). In adjusted analyses, there was a stepwise increase in the risk of HFH (Figure 1A) and all-cause mortality (Figure 1B) for no PH and worsened, PH and improved, PH and unchanged and PH and worsened as compared with no PH and unchanged.

Conclusion
Increase of periprocedural sPAP in patients with and without known PH before TAVR was associated with worse prognosis whereas reduction of sPAP was associated with improved outcomes.
Significant impact of a novel whole heart motion correction algorithm on cardiac computed tomography and aortic valve calcium scores
Authors: Aoki S , Takaoka H , Kitahara H , Matsuura K , Kinoshita M , Yashima S , Yoshida K , Suzuki K , Nishikawa Y , Matsumoto M , Sasaki H , Suzuki-Eguchi N , Kobayashi Y 
Published: October 2024

Abstract

Introduction
A new whole-heart motion-correction algorithm has been available in cardiac computed tomography (CT), and it has already revealed the higher diagnostic accuracy of significant coronary artery stenosis in cases with higher heart rate at the CT scan. Recently, aortic valve calcium scores (AVCS) are often measured for the decision-making of surgical treatment of aortic valve stenosis. However, the measurement of AVCS of the aortic valve has potential risks of motion artifact of the aortic valve. Therefore, we would like to know the clinical impact of a new whole-heart motion correction algorithm for accurately measuring aortic valve AVCS without motion artifacts.

Purpose
The purpose of this study is to evaluate the impact of a new whole-heart motion-correction algorithm on non-contrast cardiac CT images and the AVCS in trans-catheter aortic valve regurgitation (TAVR) candidates with severe aortic valve stenosis.

Materials and methods
Forty-two consecutive TAVR candidates (83 ± 7 years old, 21 males) who underwent ECG-gated CT using 256-row detector CT from November 2023 to February 2024 at our hospital were analyzed. The best phase non-contrast cardiac images were automatically selected, and they were reconstructed with both the standard (STD) algorithm and the new whole-heart motion-correction algorithm. AVCS was calculated using semi-automatic commercially available software. The aortic valve's image noise was also measured.

Results
Non-contrast best cardiac phase images were successfully reconstructed using the new motion correction algorithm in 36 patients (86%). The best cardiac phase was mainly the diastolic phase in 29 patients (81%). The overall Agatston score and calcified volume of the aortic valve in SSF2 were 1779 ± 896, and 1403 ± 689, respectively, and they were lower than 2195 ± 1132 and 1656 ± 851 of STD (all P &lt; 0.01).

Conclusion
The new whole-heart motion-correction algorithm worked in almost all TAVR candidates, and revealed lower AVCS and shows a potential for increasing AVCS accuracy.