bluuebunny/crossref_metadata_2025 huggingface dataset:
Suspected cardiac masses evaluation with cardiac magnetic resonance : histological correlation and clinical outcomes
Authors: Dellino C M , De Gaspari M , Garlini P , De Lazzari M , Cipriani A , Cecchetto A , Cecere A , Rizzo S , De Conti G , Motta R , Basso C , Iliceto S , Perazzolo Marra M
Published: November 2023

Background

Cardiac masses are an heterogeneous group of very rare formations, representing a major diagnostic challenge given the difficulty in assessing their nature through imaging examinations. Cardiac Magnetic Resonance (CMR) is a noninvasive key diagnostic tool providing anatomical, functional, and tissue characteristic information. However, data validating this imaging approach are limited.

Purpose

analyze the clinical and CMR features of patients with benign and malignant tumors and thrombus; asses the diagnostic accuracy of CMR in comparison with the histologic examination; evaluate the prognostic rule of clinical and CMR features in predicting the primary endpoint of all cause mortality.

Methods

92 Patients undergoing CMR for suspected cardiac mass between June 2004 and January 2022 were retrospectively evaluated. Patients with no mass 8 (9%) or pseudo-mass 11 (12%) were excluded. Based on CMR images, masses were divided into benign tumor, malignant tumor, and thrombus. Clinical, CMR and histological data were collected.

Results

73 patients (mean age: 62±15; 51% female) with masses were finally enrolled, 27 (37%) with a diagnosis at CMR of benign tumor, 22 (30%) with malignant tumor, and 24 (33%) with thrombus. Several clinical and CMR variables were significantly associated with one type of mass rather than another. Among clinical variables the history of malignancy and smoking were seen in patients with malignant tumors (p<0,002) while dyspnea and chest pain were significantly found in patients with thrombi (p<0,016). Among CMR features high size, infiltration, pericardial repeats, pericardial effusion, signal inhomogeneity, First Pass Perfusion (FPP) and Late Gadolinium Enhancement (LGE) were associated with malignant masses (p=0.001), while reduced pre-contrast visualization, altered kinetics, low ejection fraction (EF) and long-TI were observed in thrombi (p=0.001). CMR was accurate in 91.2% (31/34) of patients in comparison with the histological examination. Accuracy for benign tumors was 91.3% (AUC=0.913), for malignant tumors 94% (AUC=0.940) and for thrombi 83% (AUC=0.833). Patients diagnosed at CMR with thrombus had similar mortality as those with benign tumor (p=0,678) while patients with malignant lesions had higher mortality (HR: 4.98 [95% CI: 1.11-22.2], p=0,035). Regardless of diagnosis at CMR, age, tumor history, mass size, signal inhomogeneity, presence of FPP, pericardial effusion, and pericardial repeats were found to predict long-term mortality (p<0.017).

Conclusions

Although CMR has high diagnostic accuracy, histologic examination remains the diagnostic gold standard in determining the type of cardiac mass. CMR is additionally useful in predicting the outcome and manage the clinical course of patients with suspected cardiac masses.
A systematic review and meta-analysis of clinical outcomes of Takotsubo syndrome in patients with cancer
Authors: Osawa T , Tajiri K , Ieda M
Published: November 2023

Background

Recent studies suggested a relationship between Takotsubo syndrome (TS) and malignancy. However, the clinical outcomes of TS associated with cancer have not fully been assessed.

Purpose

The aim of this study was to investigate the outcomes of TS for patients with cancer.

Methods

We performed a systematic review and meta-analysis to evaluate the clinical outcome of TS in patients with and without malignancy. We searched for observational studies assessing the association of TS and malignancy until December 2022 in PubMed and Cochrane Library. The primary outcome was all-cause mortality. The secondary outcomes of this study were short-term mortality (in-hospital deaths or deaths within 30 days), shock, the need for mechanical respiratory support, and the need for mechanical circulatory support. A random-model meta-analysis was performed.

Results

Fourteen studies were finally included in this meta-analysis, totaling 189,210 patients with TS. The prevalence of current or previous malignancy among patients with TS was 8.7% (16,461 patients). Compared to patients without cancer, patients with malignancy demonstrated a higher risk of all-cause deaths in TS (odds ratio [OR], 2.41; 95% confidence interval [CI], 1.95-2.98; p < 0.01; I2 = 74%; p for heterogeneity < 0.01). Cancer was significantly associated with an increased risk of short-term mortality (OR 1.97; 95% CI 1.75-2.22; p < 0.01; I2 = 0%; p for heterogeneity = 0.46). Also, malignancy was significantly associated with in-hospital shock and mechanical respiratory support (shock; OR 1.42; 95% CI 1.30-1.55; p < 0.001, mechanical respiratory support; OR 1.68; 95% CI 1.59-1.77; p < 0.01) but not mechanical circulatory support (OR 1.12; 95% CI 0.68-1.84; p = 0.66).

Conclusion

In this meta-analysis, either previous or active cancer was associated with an increased risk of all-cause mortality, short-term mortality, shock, and needs for mechanical respiratory support in patients with TS.
D-dimers as a prognostic plasma biomarker in patients with a first episode of acute pericarditis
Authors: Vlachakis P K , Theofilis P , Dasoula F E , Lazarou E , Tsioufis P , Doundoulakis I , Valatsou A , Andrikou I , Karmpalioti M , Vlachopoulos C , Tsioufis C , Lazaros G
Published: November 2023

Introduction/Background

At present the impact of plasma biomarkers in predicting outcome of patients with isolated acute pericarditis (AP) has been poorly investigated.

Purpose

This study aimed to investigate the prognostic role of fibrin d-dimers (DD), an easily obtainable biomarker, in patients with AP.

Methods

This is a prospective clinical study enrolling 265 consecutive patients hospitalized between September 2010 and May 2019 with a first episode of AP. At baseline demographics, clinical features, laboratory, imaging findings and treatment were recorded. All patients were followed-up for a minimum period of 18 months. DD measurement at presentation was at the discretion of the examining physician since their measurement is not performed as per protocol in patients with suspected AP. End-points included cardiac tamponade, new-onset atrial fibrillation, pericardial drainage, recurrent/constrictive pericarditis and death.

Results

DD were measured in 165 out of 265 patients (62.3%, median levels 1456 ng/ml) at presentation. Among them 121 patients (73.3%) presented with elevated age-adjusted DD levels. Patients with elevated DD compared to those without depicted a higher rate of pleural (69.4%, vs 38.6%, p<0.001) and pericardial effusions (89.3% vs 72.7%, p=0.009). Concerning baseline laboratory values, patients with elevated DD presented with lower hematocrit and higher platelet counts, admission and peak C-reactive protein levels, as well as serum Glutamic pyruvic transaminase (SGPT) (Figure 1). In terms of outcome patients with elevated DD depicted a trend towards a greater prevalence of pericardial tamponade vs those without (14.9% vs 4.5% respectively, p=0.07). No significant difference was observed in the remainder of the endpoints during a median follow-up of 51 months. Notably, 43.8% of patients with elevated DD underwent computed tomography pulmonary angiography (CTPA), with all of the examinations being negative for pulmonary embolism.

Conclusion

Elevated DD plasma values in AP patients is a marker of high inflammatory burden. A trend of this plasma biomarker elevation and in-hospital cardiac tamponade was also observed. DD elevation in AP patients should be interpreted with caution and should not prompt unnecessary investigations (such as CTPA).
Predicting the impact of low-density lipoprotein cholesterol lowering through different drug targets on risk of congenital heart disease
Authors: Ardissino M , Slob E A W , Reddy R K , Morley A P , Hill P , Williamson C , De Marvao A , Ng F S
Published: November 2023

Background

Low-density lipoprotein cholesterol (LDL) lowering in pregnancy has been a controversial topic as observational studies have described an increased risk of congenital malformations. With the advent of new, long-lasting LDL lowering therapies such as silencing RNA therapies that exert clinical effects for up to six months after administration, there is substantial probability that women of childbearing age might conceive during the period of drug activity. Where clinical data is not available, the Mendelian randomization (MR) paradigm can be used to predict effects of drug target perturbation using genetic data.

Purpose

We aimed to leverage genetic data to explore the predicted impact of LDL lowering via the statin, ezetimibe and PCSK9 drug targets, on congenital heart disease.

Methods

Uncorrelated genome-wide significant (p<5x10-8) variants for LDL and their association estimates, overall and restricted to the HMGCR, NPC1L1, PCSK9 gene regions +/- 10kB, were extracted from GWAS summary data on the UK Biobank (n=469,897). Gene-outcome association data was extracted from GWAS results of FinnGen 8thRelease (n=342,499) for conotruncal defects, congenital malformations of the great arteries; septal defects; congenital disease of the aortic or mitral valves; and the vertebral, anorectal, cardiovascular, tracheo-esophageal, renal and limb anomaly (VACTERL) association. A drug-target MR analysis was carried out using inverse-variance weighted MR.

Results

Genetically-proxied LDL-lowering through PCSK9 associated with higher odds of VACTREL association (OR 1.70, 95%ci 1.25-2.32; p<0.001), conotruncal defects (OR 3.97, 95%CI 1.37-11.53, p=0.011) and overall congenital heart disease of any type (OR 1.49, 95%CII 1.08-2.05, p=0.015). Genetically-proxied LDL lowering via HMGCR was associated with higher odds of congenital malformations involving the great arteries (OR 5.85, 95%cCI 1.07-31.84, p=0.041). Genetically-proxied LDL lowering via NPC1L1 drug targets was not associated with differences in risk of congenital heart disease, though the power of these analyses was limited.

Conclusions

These data provide genetic evidence suggesting that use of LDL-lowering agents during pregnancy might influence risk of congenital heart disease. Importantly, due to underlying assumptions of the analysis, the results of this analysis are only applicable to drugs that are able to cross the placenta and exert direct effects on LDL metabolism in the fetus and they cannot be used to infer the indirect influence of lowering maternal LDL. The data support ongoing caution regarding statin use, and additionally suggest that long-lasting PCSK9-inhibiting agents that are able to cross the placenta, such as monoclonal antibodies and silencing RNA therapies, should be used with utmost caution in women planning to conceive.Figure 1
Anatomical features of PFO in patients with cryptogenic stroke in comparison to autopsy results
Authors: Witte L S , Immens M H M , El Bouziani A , Duijnhouwer A , Bouma B J , De Leeuw F E , De Winter R J , Ten Cate T J F
Published: November 2023

Background

In young patients suffering a stroke, well over 30% is considered cryptogenic stroke and may be associated with a PFO. The anatomical characteristics of stroke-related PFOs that allow right-to-left shunting can be assessed with TEE. The prevalence of a PFO in autopsy studies is approximately 25%, suggesting that the a priori chance of finding a possible "bystander-PFO" in young stroke victims is substantial.

Purpose

To assess the anatomical characteristics of PFO in patients with cryptogenic stroke and compare these with previously published results from autopsy in the general population.

Methods

Data on all consecutive patients that underwent PFO closure from 2016 to 2022 were collected. Anatomical PFO characteristics, including PFO diameter, tunnel length and the presence of atrial septal aneurysm, were measured with TEE during the closure procedure and analyzed by two cardiologists.

Results

In total 228 patients were enrolled. The mean age was 43±11 years, 116 patients (50.9%) were male, the mean RoPE-score was 7.0±1.4. The most frequent shunt grade measured with contrast bubble study during Valsalva maneuver was 3 (>25 bubbles, without opacification). Patients were divided in two groups depending on how the PFO diameter was measured, unstretched (n=119) and stretched (n=109). The mean PFO diameter was 5.4±2.6mm in the unstretched group and 10.9±3.6mm in the stretched group compared to 4.9±2.6mm in previous autopsy (p=0.192 and p<0.001, respectively). The percentage of patients with a PFO size larger than 10mm was 2% in autopsy compared to 6% in the unstretched group (p=0.109) and 52% in the stretched group (p<0.001). The mean PFO tunnel length in our combined cohort was 7.8±2.9mm.

Conclusion

The difference in PFO diameter found in this study indicates that PFOs found during published autopsy series, which are present in approximately 25% of the population, are significantly smaller than those related to a cryptogenic stroke. The exact prevalence of PFOs in the population that are comparable to those in cryptogenic stroke patients remains thus unknown. Future studies should define which characteristics could classify or rule out a PFO prone for associated clinical conditions, such as cryptogenic stroke.Distribution of PFO size
Diastolic disfunction in systemic right ventricle: a cardiac magnetic resonance study on atrial function in congenital corrected transposition of great arteries patients
Authors: Giangiacomi F , Disabato G , Pasqualin G , Basile D P , Tondi L , Camporeale A , Guida G , Attanasio A , Giamberti A , Chessa M , Lombardi M
Published: November 2023

Background

congenital corrected transposition of great arteries (ccTGA) leads to systemic position of the right ventricle (sRV). Patients with ccTGA are usually asymptomatic in the first decades of life but over time sRV will fail to support elevated systemic pressure, possibly leading to systolic heart failure (HF) in adulthood. Several factors have been associated with sRV failure and worse prognosis such as tricuspid valve dysfunction, conduction abnormalities, previous surgery due to associated lesions. However, little is known about diastolic function in sRV. We hypothesize that diastolic dysfunction characterizes sRV pathophysiology, therefore an accurate evaluation of diastolic function would allow a better assessment and risk stratification of patients. The present study aims to investigate the diastolic function in patients with ccTGA by assessing left atrial (LA) morpho-functional parameters.

Methods

we retrospectively examined Cardiac Magnetic Resonance (CMR) imaging of 33 ccTGA patients clinically referred to our Center between April 2014 and December 2022. ccTGA patients were matched based on sex and age with a healthy volunteer population (control group) and a group of patients with Hypertrophic Cardiomyopathy (HCM) diagnosed with HFpEF according to HF guidelines criteria. LA morpho-functional parameters were compared among the three groups: LA volumes (obtained by the length-area method), ejection fraction (EF) and, by means of feature tracking analysis, strain reservoir (εs), conduit (εe) and booster pump (εa). All patients were in sinus rhythm at the time of CMR.

Results

In comparison with the control group, ccTGA patients had a significant impairment in LA function (LA EF: 41,6 ± 15,1 vs 63,9 ± 7,8, p < 0,001, εs: 19,0 ± 8,3 vs 38,0 ± 10,3, p < 0,001, εe: 11,7 ± 5,9 vs 21,1 ± 8,3 p < 0,001, εa: 7,6 ± 4,1 vs 16,8 ± 6,1, p < 0,001). Conversely, no significant difference was found between ccTGA and HCM group regarding LA function (EF: 41,6 ± 15,1 vs 42,0 ± 10,1, εs: 19,0 ± 8,3 vs 22,6 ± 8,8, εe: 11,7 ± 5,9 vs 12,6 ± 7,0, εa: 7,6 ± 4,1 vs 10 ± 3,7). As for morphological parameters, ccTGA patients had an increase of LA volumes compared to both the control group and HCM patients.

Conclusion

ccTGA patients present an impaired LA function and a significative increase in LA volume consistent with the presence of diastolic disfunction. Further studies are needed to assess the clinical impact of morpho-functional LA impairment in ccTGA patients.
Adult congenital heart disease in women: demographics and outcomes in mexico. gender differences?
Authors: Aguila Salgado L , Ramirez Rangel P , Garcia Cruz E , Barradas Cedillo M G , Moyado Ocampo K L
Published: November 2023

Background

Due to advances in cardiovascular medicine in recent decades, adult congenital heart disease (ACHD) is becoming a growing field in cardiology. Differences in clinical presentation, treatment, and outcomes of ACHD between men and women have not been well studied in Latin America and Mexico.

Purpose

To characterize gender differences in clinical presentation, treatment, and mortality of ACHD in Mexico.

Methods

From January 2006 to December 2020, 3503 patients with ACHD were studied at a cardiology national reference center in Mexico. SPSS V. 23 software was used for statistical analysis.

Results

Women comprised 56% of the study population, in which a higher percentage of pulmonary hypertension and Eisenmenger syndrome was observed, (10.9% men vs. 17.7% women; 1.5% men vs. 3.3% women, p <0.01). Women had a higher score in AHA´s physiological classification (State C, 27.9% men vs. 35.3% women, p <0.01). Men had a higher rate of severity/anatomic complexity (13.3% men vs. 11.7% women, p <0.01), a higher rate of LVEF <40%, (8.0% men vs. 23.8% women, p <0.01), and underwent total repair surgery more often (61.3% men vs. 57% women, p <0.01). No statistical difference was observed in functional class, presence of arrhythmias, or mortality (patient´s current status). Figure 1.

Conclusions

We found gender differences in ACHD in Mexico: women were more likely to have pulmonary hypertension, which may reflect the already known gender predilection of PH; additionally, women had a higher AHA's physiological score; despite this, women underwent complete surgery less frequently. Although men had higher anatomic complexity and a lower LVEF, there was no statistical difference in functional class or mortality.Figure 1
Atrial septal defect detected on transesophageal echocardiography prior to atrial fibrillation ablation: prevalence, clinical features, and outcome after ablation
Authors: Yamashita E , Kemi Y , Fujiwara T , Minami K , Miki Y , Sasaki T , Take Y , Nakamura K , Kario K , Naito S
Published: November 2023

Background

The prevalence rate of atrial septal defect (ASD) in the general population is about 0.09%. Long-term volume overload due to a left-to-right shunt (LRS) caused by ASD commonly results in atrial fibrillation (AF). Moreover, left atrial (LA) enlargement could lead to an increase stretched type patent foramen ovale (PFO) and LRS. However, the prevalence, clinical features, and clinical impact of LRS in AF prior to ablation remain unknown.

Methods

A total of 2966 AF patients (63 ± 11 years, 782 women) who underwent initial AF ablation were retrospectively enrolled in this study. All patients underwent transesophageal echocardiography (TEE) prior to ablation. Then, they were divided into three groups: the ASD, PFO, and control groups. Large ASD was defined as a defect with a diameter of ≥ 5 mm. Clinical and echocardiographic features and 5-year AF-free survival rate after ablation were compared between each group.

Results

Based on TEE prior to AF ablation, 40 (1.3%) and 174 (5.9%) patients had ASD and PFO, respectively. Patients with PFO had a high prevalence of persistent AF (P < 0.001). The The LA volume was larger in the ASD and PFO groups than in the control group (P < 0.001). Kaplan–Meier analysis showed that the AF-free survival rate was similar between all ASD groups (49 ± 10%, P = 0.24). Further, the 5-year AF-free survival rate was significantly lower in the large ASD group than in the small (< 5 mm) ASD, PFO, and control groups (28% ± 14%, 61% ± 3%, 59% ± 5%, and 60% ± 1%, respectively; P = 0.021). Cox proportional hazards regression analysis showed that a large ASD was an independent predictor of AF recurrence (odds ratio: 2.58, 95% confidence interval: 1.17−4.85, P = 0.02).

Conclusions

Patients with AF prior to ablation had a higher prevalence of ASD than the general population. TEE could identify ASD undiagnosed on transthoracic echocardiography. In particular, a large ASD on TEE could be associated with poor outcome after AF ablation.
Prognostic value and determinants of high sensitive cardiac Troponin levels in patients with a systemic right ventricle: insights from the SERVE-Trial
Authors: Ruperti Repilado F J , Tran F , Haaf P , Lopez-Ayala P , Greutmann M , Schwerzmann M , Rutz T , Bouchardy J , Gabriel H , Stambach D , Schwitter J , Wustmann K , Freese M , Mueller C , Tobler D
Published: November 2023

Background

The prognostic value of high-sensitivity cardiac Troponin T (hs-cTnT) in patients with a systemic left ventricle is well-established. However, the determinants and prognostic value of hs-cTnT among patients with a systemic right ventricle (sRV) are largely unknown.

Purpose

We aimed to assessed the determinants and prognostic value of hs-cTnT among patients with sRV.

Methods

Ninety-eight patients from the randomized-controlled SERVE-trial were included. The correlation between baseline hs-cTnT concentrations and bi-ventricular volumes and function quantified by cardiac magnetic resonance was assessed by adjusted linear regression models. The prognostic value of hs-cTnT and other established prognostic markers were assessed by adjusted cox proportional hazards models, survival analysis and c-statistics. The primary outcome was the composite of clinically relevant arrhythmia, hospitalization for heart failure or all-cause death.

Results

Median age [interquartile range, IQR] was 39 [32, 48] years and 32% were female. Median hs-cTnT concentration was 7 [IQR, 4-11] ng/L. Coefficients of determination for the relationship between hs-cTnT concentrations and right ventricular end-systolic volume index, (RVESVi) and ejection fraction (RVEF) were +0.368, p=0.046; and -0.381, p=0.018, respectively. The sex and aged adjusted hazard ratio [95%, confidence interval, CI] of hs-cTnT at 2- and 4-times the reference level (5 ng/l) for the primary outcome were 2.89 [1.14-7.29] and 4.42 [1.21-16.15], respectively (Figure 1). Patients with hs-cTnT concentrations ≤7 ng/L (median) had better event-free survival (89% vs. 67%, p=0.004). The prognostic performance quantified by the C-statistics [95%, CI] for age and sex adjusted models based on hs-cTnT, RVEF, and peak VO2 predicted (%) were comparable: 0.71 [0.61-0.82], 0.72 [0.59-0.84], and 0.71 [0.59-0.83], respectively (Figure 2).

Conclusion

Hs-cTnT concentration was significantly correlated with RVEF and RVESVi in patients with a sRV. The prognostic accuracy of this biomarker was comparable to that of the current gold standards (RVEF and peak VO2 predicted).Figure 1Figure 2
Reversibility and outcome of fenestrated surgical closure in adult patients with congenital left-to-right shunts and pulmonary hypertension: a result of cohard-ph registry
Authors: Anggrahini D W , Haidar S , Hartopo A B , Dinarti L K
Published: November 2023

Background

Uncorrected congenital heart disease in the adults often come with a complication of pulmonary hypertension (PH) , resulting in high mortality and low quality of life due to right heart failure and arrythmias. Shunt closure in those patients has been shown to reduce such complications. However, in patients who develop PH, total shunt closure posseses risk that increase mortality. ESC guidelines recommend avoidance of ASD closure and careful evaluation of VSD and PDA closure in those with PVRI>5 WU. Nevertheless, some Asian countries reported good outcome in LtoR shunt closure in patients with PVRI>5.

Congenital Heart Disease in Adults and Pulmonary Hypertension (COHARD-PH) Registry is a single tertiary center registry in Indonesia. The data showed that among congenital LtoR shunts, PAH occurred in 66.9% patients and Eisenmenger Syndrome in 18.7%. In this study we aim to evaluate the outcome and the PH reversibility of adult patients underwent fenestrated closure in this registry.

Methods

Patients with intracardiac shunts who underwent surgical closure with atrial septal fenestration on January 2019-July 2022 were recruited and the follow-up data was obtained within 6 months after surgery.

Results

Thirty-eight patients underwent surgical fenestrated closure were identified. Age was ranging between 19-70 (mean 39) years-old and 81.6% were female. Thirty patients (30%) were ASD, 7 (18.4%) were VSD, and 1 patient (2.6%) was incomplete AVSD. All patients underwent 4-5 mm atrial septal fenestration despite the repair of their anatomical lesion. Hemodynamic measurement before surgery showed that the average Qp/Qs was 3.2; mPAP 51±17 mmHg and the mean pulmonary vascular resistance index (PVRI) was 7.2±4.4 WU before surgery. We performed acute vasoreactivity test (AVT) to 21 patients and showed positive result, while the rest of the patients did not have AVT due to PVRI of 4 WU or less.

Short and mid-term follow up reveal a mean SICU length of stay was 2.5 days and mean total hospital stay was 9 days. Three patients died during their hospital stay after discharged from the SICU due to post operative sepsis. On 6 month follow up, the remaining 35 subjects have no remaining symptoms. The reversibility of PH was assesed by echocardiography and showed that mean TVG was reduced from 78 to 36 (by 54%). None of these patients showed signs of heart failure or pulmonary hypertension on follow up.

Conclusion

Atrial septal fenestration in patients with adult congenital left to right shunt undergoing surgical closure might be considered in selected patients with pulmonary hypertension including those with positive acute vasoreactivity test. Further study with larger subjects is warranted to evaluate the current guidelines.
Total pulmonary resistance as assessed by non-invasive pressure-flow plots is related to exercise capacity in Fontan patients
Authors: Cieplucha A , Troost E , Budts W , De Meester P , Bekhuis Y , Rosseel T , Van Puyvelde J , Van De Bruaene A
Published: November 2023

Background

In Fontan patients, the slope of invasively measured pulmonary artery pressures plotted against cardiac output (CO) during exercise has prognostic significance. We propose a methodology using exercise echocardiography combined with cardiopulmonary exercise testing and simultaneous peripheral venous pressure measurements (CPET-echo-PVP) to calculate PVP/CO slopes as a non-invasive alternative.

Purposes

This study aimed at assessing (1) PVP/CO slopes and (2) their relationship with peak oxygen consumption in Fontan patients.

Material and Methods

Consecutive adult Fontan patients seen in the outpatient clinic at UZ Leuven, Belgium were included in the study. All patients underwent CPET-echo-PVP (peripheral intravenous line connected to the pressure transducer zeroed at the mid-axillary level). Bloodwork was performed, including N-terminal prohormone of brain natriuretic peptide (NTproBNP). The PVP/CO slope was calculated as a linear approximation using linear regression analysis from pressure-flow plots for each patient. Univariable regression analysis was performed to identify potential determinants of PVP/CO slope.

Results

In total 20 patients (mean age 30.5±10.4 (range 20-60), 11[55%] females, dominant left ventricle in 15 [75%]) were included. NT-proBNP was 297±235 pg/mL. Patients performed staged exercise test achieving workload of 102±30 Watts with a peak oxygen consumption (peakVO2) of 19.2±3.8 mL/kg/min. During exercise cardiac output (CO), heart rate (HR) and PVP all increased (mean difference: 4.1±2.2L/min, 57±26bpm, 10.4±5.9mmHg, respectively). Stroke volume index (SVind) increased from baseline to peak exercise in 9 (45%) (mean difference -2.6±12.0mL/m2). The average PVP/CO slope was 2.21±1.53mmHg/L*min, with the value exceeding 3mmHg/L*min in 5 (25%) patients. PeakVO2, peak Workload during exercise, NTproBNP, New York Heart Association (NYHA) class, and rest-to-peak change in tissue-Doppler e’ (delta e’) of the lateral wall of dominant ventricle were significantly related to the PVP/CO slope (all p<0.05).

Conclusions

CPET-echo with PVP is a reliable method to identify determinants of exercise limitation in Fontan patients. The PVP/CO slope, which reflects total pulmonary resistance, is indeed related to peak oxygen consumption, heart rate reserve and diastolic function. Since it reflects hydraulic load to the systemic venous system it may be an important target in Fontan patients.
Alternations of N6-methyladenosine RNA methylation landscape in pulmonary arterial hypertension
Authors: Song J , Feng Y , Li J , Tang M , Liu Q
Published: November 2023

Background

N6-methyladenosine (m6A) methylation is the most prevalent and abundant RNA modifications in eukaryotes. Deregulation of m6A changes by m6A-specific enzymes can affect the stability and function of transcripts. However, the relevance of m6A mRNA and m6A-specific enzymes in pulmonary arterial hypertension (PAH) have not been extensively explored.

Objectives

This study aimed to analyze m6A methylation transcriptomic profiling in the pulmonary arteries of PAH rats, and to find potential m6A regulators corelated with PAH epi-transcriptomic changes.

Methods

MeRIP-seq and RNA-seq were applied to identify differences in m6A methylation and gene expression in pulmonary artery tissues from control and monocrotaline PAH rats. The expression of a m6A regulator in pulmonary arteries was further analyzed by western blot, flow cytometry, immunohistochemical staining and immunofluorescence. The proliferation and apoptosis assays were further performed in primary rat pulmonary artery smooth muscle cells (PASMCs).

Results

Twenty-seven differentially expressed genes with hypermethylated or hypomethylated m6A modifications were identified. These differentially expressed genes were mainly linked to the extracellular matrix and structure, MAPK and PI3K-Akt signaling pathways. Furthermore, we firstly detected a m6A reader leucine rich pentatricopeptide repeat containing (LRPPRC) with downregulated expression in PAH rats. PASMCs with a siRNA knockdown of the LRPPRC promoted proliferation and apoptotic resistance.

Conclusion

This study showed that altered m6A transcriptome-wide landscape and relevant regulatory mechanisms of the PAH pulmonary artery tissues in rats, which might provide a new and potential target for therapeutic interventions in PAH.LRPPRC functional studies in PASMCs
S wave resolution in standard electrocardiography aVL lead in 48 hours from admission of severe acute pulmonary embolism is associated to favorable outcome in various subgroups of patients
Authors: Obradovic S , Dzudovic B , Matijasevic J , Salinger S
Published: November 2023

Background

An electrocardiography record does not serve for the diagnosis of pulmonary embolism. Still, it can indirectly, accurately, and without delay display acute right ventricle overload which represents the main feature of the severe disease. The aim of this study is to investigate the association of a single ECG sign change, the resolution of S wave in aVL lead with the outcome of severe PE patients.

Methods

Data from this investigation are gained from the Regional PE Registry (REPER) with prospectively variable definition and collection. Among 1814 patients with acute PE, 212 intermediate-high and high-risk PE patients had recorded S wave in aVL and if there was a resolution of this sign in the 48 hours from the admission to the hospital. Of the 145 (68.4%) were treated with thrombolytic therapy. Association between S wave in aVL resolution and all-cause hospital mortality in various subgroups of patients was estimated with Cox regression and Kaplan-Meier’s (KM) curves.

Results

S wave resolution in aVL in 48 h was recorded in 135 (63.7%) patients. Patients treated with thrombolysis had a higher frequency of S wave resolution compared to those treated with anticoagulant therapy only (76.3% vs 54.5%, p=0.01). The in-hospital mortality rate was significantly lower in patients with S wave resolution regardless of the patient sex (1.4% vs 25.8%, p<0.001 in men, and 6.1% vs 34.8% in women) age (1.1% vs 31.0%, p<0.01 in patients<70 y, and 9.1% vs 31.4%, p<0.01 in patients≥70y), thrombolytic therapy (2.9% vs 26.2%, p<0.01 in patients treated with thrombolysis, and 6.2% vs 37.1%, p<0.01 in patients who did not), duration of symptoms (3.0% vs 44%, p<0.01 in patients with symptoms less than 24 hours, and 4.4% vs 25%, p<0.01 in patients who had symptoms more than 24 hours before admission) and risk (3.2% vs 18%, p<0.01 in intermediate-high risk PE, and 4.9% vs 55.6%, p<0.01 in high-risk PE). KM Log Rank p for hospital survival regarding S wave aVL resolution was 0.003 for patients who did not treated with thrombolysis, and <0.001 in patients treated with thrombolysis (figure 1 and 2).

Conclusion

S wave resolution in aVL in the 48 h of acute intermediate-high and high-risk PE patients is an excellent sign of improvement of right ventricle function, and it is associated with better outcomes whenever patients are treated or not with thrombolysis, or if they belong to high-risk or intermediate-high risk subgroup.KM S wave resolution and NO thrombolysisKM S wave resolution and thrombolysis
Epidemiology and management of patients with pulmonary arterial hypertension associated with congenital heart disease: data from the hellenic pulmonary hypertension registry (HOPE)
Authors: Arvanitaki A , Farmakis I , Demerouti E , Anthi A , Naka A , Brili S , Gourgiotis P , Papadopoulos G , Apostolopoulou S , Stamatopoulou V , Frogoudaki A , Frantzeskaki F , Karyofyllis P , Manginas A , Giannakoulas G
Published: November 2023

Background

Pulmonary arterial hypertension (PAH) is a common complication among adult patients with congenital heart disease (CHD). Since clinical trials on PAH-CHD are scarce, registry data are required to shed light on the epidemiology and management of this subgroup.

Purpose

To present "real-world" data about the epidemiology, management and long-term course of PAH-CHD from the Hellenic Pulmonary Hypertension Registry (HOPE).

Methods

The HOPE registry was launched in early 2015 and enrols patients from all pulmonary hypertension subgroups in Greece. This analysis focuses on PAH-CHD.

Results

In total, 85 PAH-CHD patients of whom 50 women (59%) have been enrolled from 8 centers between 2015 and 2022. A follow-up visit was available in 39 patients (45.8%). Median age at first visit was 37 (24, 60) years. About three quarters of patients had a pre-tricuspid (n=32, 37.6%) or a post-tricuspid shunt (n=30, 35.2%), with a quarter of patients having a complex CHD (n=21, 24.7%). Eisenmenger physiology was present in 31 patients (36.4%). The most common comorbidities at baseline were obesity (n=14, 16%), thyroid disease (n=12, 14%) and atrial fibrillation (n=12, 14%). About two thirds of patients were mildly symptomatic at baseline (NYHA I/II, n=55, 64.7%) and remained so at follow-up (n=25/39, 63.7%) with a median time of last available visit at follow-up of 1484 days (4.1 years). According to the three strata ESC risk stratification score, half of patients were at intermediate risk at baseline, while more than half of patients were at low risk for 1-year mortality at follow up (Figure 1A). More than half of patients received PAH monotherapy at baseline (n=46, 54%), with one fifth not receiving any PAH-targeted therapy (n=18, 21.2%). At 4.1 years, half of patients were on combination therapy (n=20/39, 51.3%) (Figure 1B). During a median follow up time of 2547 days (7 years), 17 deaths were reported (0.01 deaths/ patient year) (Figure 2A). 1-, 3- and 5- year survival rates were 96.4% (92.4%-100%), 88.9% (82.3%-96%), and 88.9% (82.3%-96%), respectively. Survival was better among low-risk patients at baseline, compared to moderate and high-risk ones (Figure 2B).

Conclusion

In this national cohort of ACHD PAH there was a tendency towards combination therapy at follow-up which might be the cause for reduced mortality risk. The three strata ESC risk stratification score may be a useful tool to risk assess these patients for long-term survival.Risk stratification and pharmacotherapyOveral and risk-estimated mortality
Pulmonary hypertension associated with left heart disease among hospitalized patients: analysis of the Nationwide Inpatient Sample
Authors: Farmakis I , Hobohm L , Christodoulou K C , Keller K , Schmidt K H , Valerio L , Konstantinides S , Giannakoulas G
Published: November 2023

Background

Pulmonary hypertension associated with left heart disease (PH-LHD) is the most prevalent PH class, however its prevalence ranges significantly across studies.

Purpose

To investigate the prevalence and prognostic influence of PH-LHD in a large nationwide sample.

Methods

Using the US Nationwide Inpatient Sample we calculated the prevalence of secondary PH across heart failure (HF) subtypes, cardiomyopathies, aortic, and mitral valve disease in hospitalized patients in 2018. In this context, we used logistic regression to assess the impact of PH on LHD, as well as to find significant contributors to in-hospital mortality in the PH-LHD population.

Results

Among 6,270,625 hospitalizations of patients with LHD, 801,535 were diagnosed with PH-LHD (12.8%). Prevalence of PH-LHD was 17.2% in HF with preserved ejection fraction (HFpEF) and 11.8% in HF with reduced ejection fraction (HFrEF). It was 16.8% in dilated cardiomyopathy, 12.6% in hypertrophic cardiomyopathy, 18.7% in mitral regurgitation, 28.5% in mitral stenosis, 13.5% in aortic stenosis, and 13.9% in aortic regurgitation hospitalizations (Figure 1). PH was associated with increased in-hospital mortality (reported odds ratios [OR] with corresponding 95% confidence intervals [CI]) in HFpEF (1.23; 1.17-1.28), hypertrophic cardiomyopathy (1.42; 1.06-1.89), mitral regurgitation (1.17; 1.07-1.28), and aortic stenosis (1.14; 1.04-1.26), but not in HFrEF (1.04; 0.99-1.10), or dilated cardiomyopathy (1.13; 0.99-1.29). Among patients with PH-LHD, significant predictors of all-cause in-hospital mortality included age, atrial fibrillation/flutter, cancer, and acute cardiac (acute right HF, myocardial infarction, ventricular arrhythmia), or extra-cardiac (stroke, sepsis, pneumonia, acute renal failure, venous thromboembolism) diagnoses (Figure 2).

Conclusion

In a nationwide analysis of hospitalized patients due to LHD the prevalence of PH was lower than previously reported indicating reduced recognition of this disease in real world clinical practice. The diagnosis of PH-LHD was associated with worse fatality rates across most forms of LHD. The findings should be further explored in future prospective studies.Figure 1Figure 2
Right heart failure as a source of B-lines at lung ultrasound: prevalence and functional correlates
Authors: D'alto M , Di Maio M , Liccardo B , Argiento P , Romeo E , Del Giudice C , Renon F , Vergara A , Di Vilio A , Caiazza E , Gargani L , Bossone E , Golino P , Picano E , Naeije R
Published: November 2023

Background

Lung ultrasound is part of the standard transthoracic examination and B-lines provide an index of extravascular lung water allowing to measure pulmonary congestion in left heart failure. However, pulmonary congestion can also appear as a consequence of right heart failure and it has been assumed that depends on the increase in central venous pressure increasing the resistance to lymphatic drainage. Aim of this study was to assess the prevalence of lung B-lines in a clinical model of pure right heart failure due to idiopathic pulmonary arterial hypertension (PAH) and its correlation with haemodynamic parameters.

Methods

All patients referred for suspicion of pulmonary hypertension in a single tertiary centre from January 2020 to December 2022 underwent a complete diagnostic work-up including echocardiography, lung ultrasound and right heart catheterization. The diagnosis of PAH was made following the current international recommendations. Pulmonary congestion was identified by lung ultrasound B-lines using an 8-site scan.

Results

The study enrolled 102 patients with PAH. Patients’ characteristics are shown in Table 1. The median lung B-lines were 3 [IQR: 1-5]. Results of univariate and multivariate analysis of B-lines predictors are shown in Table 1. Right atrial pressure (RAP), tricuspid annular plane excursion (TAPSE)/ Systolic pulmonary pressure (sPAP) ratio and pro hormone brain natriuretic peptide (proBNP) were independent predictors of B lines.

Conclusion

RAP, TAPSE/sPAP and proBNP were independent predictors of B lines in PAH patients according to the pathophysiological hypothesis that B-lines depends on the increase in central venous pressure increasing the resistance to lymphatic drainage.Table 1
Initial anticoagulation therapy with direct oral anticoagulants in patients with intermediate-high-risk pulmonary embolism: from the COMMAND VTE Registry-2
Authors: Shigeno R , Kim K , Chatani R , Kaneda K , Nishimoto Y , Ikeda N , Kobayashi Y , Ikeda S , Takase T , Tsuji S , Oi M , Takada T , Otsui K , Yamashita Y , Furukawa Y
Published: November 2023

Background

Patients with intermediate-high-risk pulmonary embolism (PE) who have both right ventricular dysfunction and elevated cardiac biomarkers are at a high risk of early hemodynamic decompensation and circulatory collapse, and it might be reasonable to treat these patients with parenteral anticoagulation therapy before switching to oral anticoagulation therapy. Recently, initial direct oral anticoagulants (DOACs) therapy in patients with PE have been shown to be non-inferior compared with initial parenteral anticoagulation therapy followed by vitamin K antagonist, which might be also a potential alternative for patients with intermediate-high-risk PE. However, the effectiveness and safety of initial DOACs therapy in this patient population have not been well investigated.

Methods

The COMMAND VTE Registry-2 is a multicenter registry enrolling 5197 consecutive acute symptomatic venous thromboembolism (VTE) patients among 31 Japanese medical centers in the DOAC era between January 2015 and August 2020. The current study population consisted of 515 patients with intermediate-high-risk PE who were normotensive and right ventricular dysfunction on echocardiography or computed tomography, accompanied by elevated troponin levels (troponin I >0.028 ng/mL or troponin T >0.014 ng/mL) or N-terminal pro-B-type natriuretic peptide (NT-proBNP)/B-type natriuretic peptide (BNP) levels (NT-proBNP ≥600 pg/mL or BNP ≥100 pg/mL). The patients were divided into 2 groups; patients with initial DOACs therapy (N=107) and those with initial parenteral anticoagulation therapy (N=408).

Results

Most of baseline characteristics were comparable between the 2 groups. The 1-year cumulative incidence of bleeding events was significantly lower in patients with initial DOACs therapy than in those with initial parenteral anticoagulation therapy (6.5% vs. 15.3%, P=0.007) (Figure 1A), whereas the 1-year cumulative incidence of VTE recurrence was comparable between the 2 groups (2.2% vs. 2.2%, P=0.62) (Figure 1B). The 1-year incidence of all-cause mortality was numerically lower in patients with initial DOACs therapy than in those with initial parenteral anticoagulation therapy without statistically significant difference (4.5% vs. 13.5%, P=0.06) (Figure 1C).

Conclusions

Initial DOACs therapy in patients with intermediate-high-risk PE showed no signal of worse outcomes compared with initial parenteral anticoagulation therapy, which could be a potential initial anticoagulation strategy in this patient population.Figure 1
Chronic thromboembolic disease is associated with exercise-induced pulmonary hypertension and functional right ventricle deterioration
Authors: Madonna R , Morganti R , Badagliacca R , Biondi F , Alberti M , Vizza C D , De Caterina R
Published: November 2023

Background and Aim

Chronic thromboembolic pulmonary disease (CTED) is a progressive disease caused by a wall-adherent, fibrotic thrombus in the pulmonary circulation persisting despite oral anticoagulation and despite vascular remodeling of the small arteries. Despite normal pulmonary hemodynamics at rest, exercise intolerance and dyspnea have been reported. Drivers and risk factors, as well as the clinical impact of CTED, are not yet adequately characterized. We evaluated clinical factors predictive of the development of postthrombotic pulmonary disease in a cohort of patients with a history of acute pulmonary embolism on oral anticoagulant therapy. We also evaluated its impact on functional capacity, pulmonary haemodinamics at rest and after exercise and right ventricle morphology and function.

Methods

We compared 33 consecutive patients with a history of acute pulmonary embolism and normal pulmonary vascular imaging (group 1, n=16) or persistent defects on perfusion scan (positive P scan) despite therapeutic anticoagulation for 4 months (group 2, n=17), for the following parameters: 1. Thrombotic load (extension of pulmonary thromboembolism on CT angiography) and Pulmonary Embolism Severity Index (PESI) score at the time of admission to the Intensive Care Unit (ICU); 2. Presence of thrombophilia (factor V Leiden, prothrombin variant, lupus anticoagulant); 3. Cardiovascular risk factors; 4. Anthropometric and demographic parameters; 5. Anticoagulation treatment in ICU and at discharge. The two groups of patients were also compared for the World Health Organization functional class (WHO-FC), NT-proBNP, cardiopulmonary exercise test (CPET) and echocardiographic parameters at rest and after exercise (ESE), at 4 and after 24 months.

Results

Compared with group 1, patients with persisting perfusion defects (group 2) featured higher thrombotic load (p=0.004) and PESI score (p=0.02) at the time of ICU admission. At 4 months, group 2 developed exercise-induced pulmonary hypertension (Ex-PH) at CPET (p<0.001) and ESE (p<0.001). At the 24 months follow-up group 2 showed higher NT-proBNP (p<0.001) and WHO-FC (p<0.001), systolic (p<0.001) and diastolic (p=0.037) right ventricular (RV) dysfunction and worse echo indices of RV-Arterial Coupling (TAPSE/PAPs (p<0.001)), despite maintaining a low or intermediate echocardiographic probability of PH (Table 1).

Conclusions

Despite the low and intermediate echocardiographic probability of PH, patients with persistent positive P scan had reduced functional capacity, and developed ExPH and RV functional deterioration.