bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of neuromuscular assessment on arrhythmic risk in LMNA cardiomyopathy
Authors: Pepe E M , Villatore A , Di Resta C , Paiotti E , Molinari L , Cariello M , Souryal G , Della Bella P , Previtali S , Sala S , Peretto G
Published: November 2023

Background

The current Risk Score for Life-Threatening Ventricular Tachyarrhythmias (LTVT) in LMNA cardiomyopathy does not consider the frequent association between cardiac and neuromuscular phenotypes as a part of a multisystemic disease. In particular, the prognostic value of tendon retractions (TR) has been recently described.

Objectives

We aimed to assess the prognostic role of TR in a cohort of probands with LMNA cardiomyopathy undergoing multidisciplinary workup at a referral center.

Methods

We included 28 probands with LMNA cardiomyopathy undergoing regular, prospective follow-up at a national referral center for laminopathies. All patients underwent extensive baseline characterization, including complete neuromuscular examination and systematic assessment of TR. Indications to implantable cardioverter defibrillators (ICD) for the primary prevention of sudden cardiac death were guideline-based. Patients were clustered in tertiles according to their baseline LMNA-Risk Score. The primary endpoint was the 5-year occurrence of LTVT, namely arrhythmic cardiac death, VF, sustained VT, or appropriate ICD shocks.

Results

Of the 28 probands with LMNA cardiomyopathy (mean age 33±15 years, 50% males, mean LVEF 55±14 %), neurological assessment identified 14 patients (50%) with TR, including 8 cases with no other signs of neuromuscular involvement. At baseline assessment, the median LMNA-Risk Score was 10% (IQR 6-20%). By 5-year follow-up, 9 patients (32%) met the primary endpoint, including three patients in the lowest tertiles of risk (median LMNA-Risk Score 23, range 6-15%). While other variables showed no remarkable differences between groups, the prevalence of TR was 78% among cases experiencing LTVT and 37% otherwise. The presence of either baseline LMNA-Risk score at the highest tertile (>17%) or TR was 100% predictive of 5-year LTVT (9/9 vs. 7/19, p=0.003). Results did not change after reassessment by the end of follow-up (15±5 years).

Conclusions

Our preliminary data suggest that the inclusion of TR in risk stratification may result in a better patient selection for primary prevention ICD implant in LMNA cardiomyopathy.
Interleukin-6 plasma levels predict mortality and heart failure events in cardiac transthyretin amyloidosis
Authors: Lugitsch J , Hoeller V , Schwegel N , Santner V , Gollmer J , Kolesnik E , Lipp R , Niedrist T , Rainer P , Zirlik A , Ablasser K , Verheyen N , Zach D
Published: November 2023

Background

Low-grade systemic inflammation is a key component in the pathophysiology of heart failure (HF). In particular, the pleiotropic effects of interleukin-6 (IL-6) signaling are of interest as circulating IL-6 levels are associated with mortality in HF patients.

Purpose

The purpose of this study was to investigate whether IL-6 plasma levels predict mortality and HF events in patients with cardiac transthyretin amyloidosis (ATTR-CM).

Methods

This was an analysis of a prospective single-center cohort study comprising 98 ATTR-CM patients. The endpoint was defined as a composite of all-cause mortality and worsening HF events. HF events included HF related hospitalizations and urgent outpatient clinic visits with concomitant intravenous diuretic treatment. Follow-up data were collected using central medical records. Kaplan-Meier estimates and Cox regression analyses were calculated to assess the association between IL-6 and the composite endpoint. Moreover, receiver operator characteristics (ROC) analysis was performed to evaluate the predictive accuracy of IL-6 for the composite endpoint.

Results

Median age was 79 years (76-81), 86 patients (88%) were male, and 46 patients (47%) received the transthyretin (TTR) stabilizer tafamidis at baseline. Median NT-proBNP levels were 2813 pg/ml (1365-4856), mean estimated glomerular filtration rate (eGFR) was 57.9±17.6 ml/min/1.73m², and median urine protein to creatinine ratio (UPCR) was 122.0 mg/g (89.8-204.5). Median IL-6 plasma levels were 4.9 pg/ml (3.0-9.4). During a median observation period of 21.2 months (11.4-32.4), 27 patiens (28%) reached the composite endpoint. IL-6 levels were associated with the composite endpoint (hazard ratio = 1.028, 95% confidence interval = 1.004 to 1.051; p = 0.012). The association was independent of age, TTR stabilizing medication, log-transformed and eGFR-adjusted NT-proBNP levels, as well as UPCR. The area under the ROC curve for IL-6 was 0.70 (95% confidence interval = 0.59 to 0.81; p = 0.003). The optimal cutoff value was 5.3 pg/ml, as determined by Youden’s index, with a sensitivity of 70% and specificity of 66%. Kaplan-Meier estimates demonstrated a mean survival time of 1030 days (95% confidence interval = 911 to 1150) for the study population. A statistically significant difference between the survival rates of ATTR-CM patients with IL-6 levels ≥5.3 pg/ml and those with IL-6 levels below the threshold was indicated by the log-rank test (p = 0.002).

Conclusion

Circulating levels of IL-6 independently predicted adverse outcomes in patients with ATTR-CM. IL-6 plasma levels may be useful for identifying a high-risk ATTR-CM subpopulation.Tablewith baseline characteristicsFigurewith Kaplan-Meier estimates
Predominance of a rare transthyretin mutation (p.Asp38Glu) in patients with hATTR cardiomyopathy: initial data from the Croatian Transthyretin Cardiac Amyloidosis Registry (CroATTR)
Authors: Sipus D , Loncaric F , Jakus N , Fabijanovic D , Samardzic J , Skoric B , Mustapic I , Bakovic Kramaric D , Vinter O , Raljevic D , Ruzic A , Borovecki F , Milicic D , Cikes M , Planinc I
Published: November 2023

Introduction

Transthyretin amyloidosis (ATTR) is classified as hereditary (hATTR) or acquired (wtATTR). hATTR is rare genetic disease with variable penetrance and phenotype, with cardiomyopathy (CM) and/or neuropathy being most relevant clinical presentations. The most common and investigated mutation in Europe is Val30Met, predominant in endemic areas of Portugal and Sweden. On the contrary, p.Asp38Glu is an extremely rare mutation with only several cases mentioned in a Swedish register and isolated cases in Japan, India and Canada. Described cases were associated with early onset CM which required specific treatment, heart- or combined heart and liver transplantation.

The Croatian Transthyretin Cardiac Amyloidosis Registry (CroATTR) is a national, longitudinal, non-interventional, and both retrospective and prospective ATTR registry. It is designed to include patients with clinically proven hATTR-CM or wtATTR-CM according to the current guidelines, as well as family members with a confirmed TTR mutation.

Purpose

This is the first report from the CroATTR, aimed to analyse baseline characteristics of the currently enrolled patients in the first year of the registry.

Methods

All patient data were collected and managed using the REDCap electronic data capture tool. The collected data included demographic, clinical, diagnostic, laboratory and genetic parameters. The CroATTR registry was approved by the Institutional Ethics Committee, and all patients signed informed consent. 18 adult patients are included in this report, divided into the following groups: wtATTR group, hATTR group (genotype +, phenotype +), hATTR group (genotype +, phenotype -).

Results

The patients in the CroATTR Registry were predominantly male (15/18, 83%) with median age of 51 years [45.5-67] (Table 1.). Five (27.78%) patients have wATTR, seven (38.89%) have hATTR with developed CM (phenotype positive) and six (33.33%) have confirmed mutation of the TTR gene but are phenotype negative. 12 out of 13 confirmed mutations were p.Asp38Glu. Patients with hATTR CM were all male, in NYHA class I-III, with a high proportion of atrial fibrillation and amyloid-associated changes in the electrocardiogram as well as higher values of N-terminal pro-B-type Natriuretic Peptide (NT-proBNP).

Conclusion

The CroATTR Registry is formed to provide insights into the prevalence, phenotypic characteristics and natural course of ATTR in Croatia. In the initial Registry analysis, to the best of our knowledge, we reported the largest number of patients with p.Asp38Glu mutation of transthyretin gene up to date. Notably, all patients with p.Asp38Glu originate from the same geographical region in the south-eastern part of Croatia, which we postulate may be a new endemic area for hATTR.Table 1
Value of left ventricular longitudinal strain in predicting overt heart failure in patients with Chagas disease and preserved left ventricular ejection fraction
Authors: Nunes M C P N , Ferreira A M F , Silva J L P S , Carvalho V T C , Santos-Junior O R S J , Cardoso C S C , Oliveira L C O , Santos A C J S , Cruz D S C , Leite S F L , Jesus A P J , Haikal D S A H , Sabino E C S , Ribeiro A L P R
Published: November 2023

Introduction

Speckle-tracking echocardiography (STE) is an established tool to detect early myocardial contractile impairment. In Chagas disease patients, STE may be helpful to identify subtle myocardial damage with the potential of progression to heart failure.

Purpose

This study aimed to assess the value of STE in predicting heart failure in Chagas disease patients with preserved left ventricular ejection fraction (LVEF).

Methods

Patients with Chagas disease living in endemic area who had preserved LVEF (>50%) were selected for the study. Clinical evaluation, B-type natriuretic peptide (NT-ProBNP), electrocardiogram (ECG), and echocardiogram were performed at enrollment in 2015 to 2016 and in the follow-up visit between 2018 and 2019. Global longitudinal strain (GLS) derived from STE was analyzed offline. Peak GLS was calculated as the mean value from 18 segments of the left ventricle (Figure 1). The outcome was development of heart failure defined by elevation of NT-ProBNP levels, categorized according to age-specific cut-points for heart failure at the second evaluation. Patients with abnormal NT-ProBNP at baseline or those who died between the 2 visits were not included.

Results

A total of 692 were enrolled, mean age was 58 ± 12 years and 495 (72%) were women. Mean LVEF at baseline and follow-up visits were 63.4 ± 4.6% and 59.8 ± 11.2% (p<0.001). The median [IQR] time between visit 1 and visit 2 was 5.4 [4.5 - 5.8] years. Among patients alive and attending the second visit, 48 patients (7%) developed overt heart failure with overall incidence rate of 14.1 events per 1000 patient-years (95% CI 10.4-18.6). On multivariable analysis, independent predictors of new-onset heart failure were male sex (OR 2.30, 95% CI 1.02-5.18), age (OR 1.04, 95% CI 1.01-1.07), QRS duration (OR 1.03, 95% CI 1.01-1.04), left atrial (LA) volume indexed (OR 1.05, 95% CI 1.01-1.09), and GLS (OR 0.90, 95% CI 0.81-0.98). LVEF did not remain in the model. The C-statistic of the final model was 0.80 (95% CI 71-88) showing a good discrimination.

Conclusions

In a cohort of patients with Chagas disease from remote areas with preserved ejection fraction, GLS was an important predictor of progression to overt heart failure, after adjustment for sex, age, QRS duration and LA volume. GLS was associated with further increased NT-ProBNP levels, which is useful to guide heart failure management, irrespective of systolic dysfunction.
Ventricular volume ratio as a novel imaging biomarker for disease prediction in 26,516 UK Biobank participants
Authors: Mccracken C , Abdulelah Z , Szabo L , Neubauer S , Petersen S E , Raisi-Estabragh Z
Published: November 2023

Background/Introduction

Right and left ventricular volumes are established imaging biomarkers for disease discrimination and outcome prediction. Limited research in select disease cohorts suggests additional clinical value from consideration of disproportionate (or imbalanced) dilatation of one ventricle over the other. The prognostic utility of this "ventricular volume ratio" (VVR) has not been tested in large, unselected cohorts.

Purpose

To examine associations of right-to-left and left-to-right VVR with cardiovascular phenotypes, prevalent disease, and incident cardiac outcomes in the UK Biobank.

Methods

The analysis includes 26,516 participants with cardiac magnetic resonance (CMR) available. We calculated right-to-left ventricular volume ratio (RV/LV), and the reciprocal left-to-right ventricular ratio (LV/RV), and identified participants with asymmetry above the 95th percentile of healthy cases. Multivariable linear and logistic regression models were used to calculate associations between ventricular volume asymmetry and sample characteristics, other cardiac imaging features, existing disease and incident disease. Incident disease associations were measured using Cox proportional hazards models adjusted by age, sex, systolic blood pressure, body mass index, smoking, Townsend deprivation score, hypertension, diabetes, hyperlipidaemia and other key imaging metrics (LV mass indexed to body surface area, LV ejection fraction and RV ejection fraction). The average follow-up time was 4.6 years (SD 1.3 years).

Results

Ventricular volume asymmetry in either direction was associated with increased age, lower RVEF, poorer LV global function index, poorer global longitudinal strain and greater maximum wall thickness. While RV-dominant volume asymmetry was associated with increased risk of all-cause mortality (HR= 1.56, 95% CI= [1.08, 2.26], p=0.019), LV-dominant volume asymmetry was found to associate with a much wider array of factors in the UK Biobank population. LV dominance was significantly associated with smoking, hypertension, diabetes, hyperlipidaemia, existing respiratory disease and existing heart disease. In fully-adjusted models, LV dominance was associated with increased risk for ischaemic heart disease (1.46 [1.12, 1.91], p=0.005), non-ischaemic cardiomyopathies (3.62, [1.93, 6.79], p < 0.001) and a two-fold increased risk for heart failure (2.30, [1.63, 3.26], p < 0.001).

Conclusion(s)

LV/RV is easily calculated from existing imaging metrics, and could potentially have important added value as a biomarker in predicting heart disease, incremental to well-established risk factors and imaging metrics.
Myocardial work in systemic right ventricle: new insights on right ventricular adaptation to systolic flow
Authors: Sorice D , Fusco F , Scognamiglio G , Abbate M , Merola A , Palma M , Grimaldi N , Barracano R , Borrelli N , Ciriello G D , Roma A S , Colonna D , Correra A , Romeo E , Sarubbi B
Published: November 2023

Background

Myocardial work (MW) is an innovative tool, which combines global longitudinal analysis with non-invasively assessed ventricular pressure to provide a measure of ventricular performance. This technique has recently been used in subpulmonary right ventricle (spRV), but it has not yet been studied in systemic right ventricle (sRV).

Methods and Results

MW indexes were obtained from ventricular pressure–strain loops in 48 patients with sRV (32 transposition of the great arteries following atrial switch repair and 16 congenitally corrected transposition of the great arteries; mean age 38.5±10years; 56% male) and in 20 healthy volunteers, as a control group of spRV.

Echocardiographic parameters and global longitudinal strain(GLS) analysis demonstrated impaired systolic function in the sRV group (TAPSE: 12.3±3mm, S wave:6.9±2cm/s, fractional area change:29[23-35]% , GLS: -13.4±3%, RV septum GLS: -12±4%, RV free-wall GLS: -14.8±4%).

Accordingly, MW indexes were below normal reference values reported for the left ventricle (global work index (GWI): 1056±331 mmHg%; global constructive work (GCW): 1490±269 mmHg%); and global wasted work (GWW) and global work efficiency (GWE) were mildly increased (245.5±162mmHg% and 87±9%, respectively). In addition, sRV free-wall contributed more than the septum to the global performance (GWI septum 879±318, free-wall 1241±412 mmHg%, p<0.0001; GCW septum 1348±287, free-wall 1626±377 mmHg%, p<0.0001). Notably, segmental pressure–strain loops demonstrated higher wasted work values in dyssynchronous segments (figure). As shown in Table1, MW indexes of performance were significantly higher in sRV compared to spRV (spRV GWI:349.3±99mmHg%; p<0.0001; spRV GCW: 451.1±104mmHg%; p<0.0001), likely reflecting sRV adaptation to increased afterload. However, as a response to chronic exposure to systemic pressure, a significant raise of both GWW and GWE in sRV compared to spRV was found (spRV GWW:43.1±22mmHg%, p<0.0001; spRV GWE:92.4±4,p=0.0005).

Conclusion

Assessment of MW in patients with a sRV is feasible and may provide additional data on ventricular global and segmental performance and efficiency, reflecting sRV adaptation to systemic loading.Table 1
Increased cesarean section rate and premature birth according to modified WHO maternal cardiovascular risk in pregnant women with congenital heart disease
Authors: Wedlund F , Von Wowern E , Hlebowicz J
Published: November 2023

Background

During pregnancy and delivery, hemodynamics are altered, and women with adult congenital heart disease (ACHD) might have a higher risk of obstetric and neonatal complications. We sought to investigate pregnancy outcome and complications in relation to complexity of heart condition.

Materials and methods

We studied women with ACHD discussed at multidisciplinary conferences March 2009-May 2021. We studied 149 pregnancies in 101 women. We scored each woman retrospectively according to the modified World Health Organization (mWHO) risk classification and included patients in risk class I (n=36, 24.1%), II (n=43, 28.9%), II-III (n=43, 28.9%), III (n=24, 16.1% and IV (n=3, 2.0%). Relative risks were assessed with logistic regression adjusting for parity and age.

Results

Women with mWHO class ≥III underwent cesarean section more often than women in less complex mWHO classes, p<0.001. Women in mWHO classes I, II and II-III were 83.8% (CI 54.4%-94.2% p<0.001) less likely to give birth prematurely compared to women in mWHO classes III and IV. We found no difference in incidence of preeclampsia, gestational hypertension, gestational diabetes or hemorrhage >1000 ml depending on WHO-class (table 1). Women in mWHO classes III-IV had a higher rate of fetal growth restriction compared to women in mWHO classes I, II, II-III (p<0.007).

Conclusions

Women with complex congenital heart disease (mWHO ≥III) tend to have a higher rate of cesarean section, premature birth and fetal growth restriction.Table 1
Blood and imaging biomarkers in the long-term follow-up of bicuspid aortic valve patients
Authors: Hendriks P , Keuning Z A , Duijnhouwer A L , Meccanici F , Siebelink H J , Van Den Hoven A T , Geenen L W , Eindhoven J A , Baggen V J M , Cuypers J E A A , Kauling R M , Roos-Hesselink J W , Van Den Bosch A E
Published: November 2023

Background

Bicuspid aortic valve (BAV) is a common congenital heart defect. Patients with BAV are at risk for long-term complications such as arrhythmias and reinterventions.

Purpose

This study aimed to investigate (1) sex differences in blood and imaging biomarkers and (2) the role of blood and echocardiographic biomarkers in the long-term risk prediction of patients with BAV.

Methods

In this multicenter prospective observational study, all included adult BAV patients underwent venous blood sampling and transthoracic echocardiography including speckle tracking at the time of inclusion. Analyzed blood biomarkers were: RDW, creatinine, CRP, TroponinT, NT-proBNP and TGF-beta. Sex differences were analyzed at baseline. Associations between blood & echocardiographic biomarkers and arrhythmia-free & intervention-free survival were determined by Cox proportional hazards models.

Results

A total of 182 patients were included (median age 34 (Interquartile range: 23-46) years, 55.5% male). Significant differences were found in blood biomarkers at baseline between men and women. CRP, NT-proBNP and RDW were higher in women while creatinine, TroponinT and TGF-beta were higher among men (figure 1). After a median follow-up time up of 6.9 (IQR: 6.5- 9.9) years, arrhythmia-free and event-free survival rates were respectively 81.0% and 73.1%. NT-proBNP was the only blood biomarker independently associated with both arrhythmia free and intervention free survival. On echocardiography an increase in LA size, LVEDD, LV mass index and E/E’ratio were associated with arrhythmia free survival. Intervention free survival was associated with increased LA size, LV mass index, aortic valve peak velocity and the presence of moderate or severe aortic regurgitation. No associations were found with ejection fraction and global longitudinal strain (figure 2).

Conclusion

Significant sex-related differences were observed in blood biomarkers between men and women with BAV at baseline. NT-proBNP was the only blood biomarker associated with arrhythmia-and intervention-free survival. The strongest associations of echocardiographic markers were those indicating diastolic function and LV mass index.Sex differences in blood biomarkersForest plot
Efficacy of intravenous iron therapy compared to usual treatment in iron deficient adult cyanotic congenital heart disease patients for improvement in clinical outcomes at three months
Authors: Abdullah Z , Subhash Singh Y K , Gupta S K , Agstam S , Ramakrishnan S K
Published: November 2023

Background

Iron deficiency is frequent in CCHD patients and is associated with poorer outcomes. Patients with iron deficiency anaemia are treated with oral iron which results in improved clinical outcomes. The use of intravenous iron in CCHD patients is not well studied.

Purpose

We aimed to compare effectiveness of intravenous iron with usual care (i.e., no therapy for CCHD patients with iron deficiency without anemia, and oral iron therapy for CCHD patients with iron deficiency anemia) on 6-minute walk distance(6MWD) after 3 months of treatment, improvement in arterial Haemoglobin saturation, Quality of life, WHO functional class and safety of intravenous Iron.

Methods

We enrolled 27 patients of which 13 were randomized to IV iron arm and 14 to usual treatment arm. The mean age (±SD) of enrolled patient was 23.3 (±5.55) years. 24 out of 27 patients (88.9%) were Eisenmenger Syndrome patients, while the other three patients were TOF with pulmonary atresia, DORV with pulmonary atresia and post-Fontan. 6MWD was performed to access functional capacity and WHOQOL-BREF questionnaire was used for assessment of quality of life. All the clinical findings, data and test recordings were repeated after three months.

Results

The mean (±SD) haemoglobin(Hb) of patients included in the study was 16.7 (±2.0) g/dl. The Hb levels improved by 0.91 (±0.85) g/dl in patients who received any form of iron therapy (IV or oral iron). Hb improvement was not significantly different between those who received IV or oral iron [IV iron: 1.15 (±0.88) g/dl, Oral iron: 0.59 (±0.79) g/dl; p= 0.12]. The baseline 6MWD was not different in both the arms (p= 0.639). The mean (±SD) 6MW distance covered in IV iron arm and usual treatment arm was 401 (±35.2) m and 408.6 (±46.5) m respectively at baseline, which improved to 425 (±28.7) m and 421.5 (±43.2) m respectively at 3 months follow up. The change in 6MWD in IV iron arm and usual treatment arm was 24 (±22.3) m and 13.1 (±16.4) m respectively. The difference of change in 6MWD between the two arms was non-significant (p= 0.157). There was a significant improvement in WHOQOL-BREF Score Domains 2,3 and 4 and there was a trend towards improvement on Domain 1 score in IV iron arm compared to usual treatment arm. WHO functional class was similar at baseline in both arms (p= 0.534). The change in WHO functional class at follow up was similar in both arms (p= 0.082)

Conclusion

This study demonstrated no improvement in clinical outcomes of 6MW distance, arterial hemoglobin saturation and WHO functional class. However, there was significant improvement in quality of life and iv iron was found safe and equally efficacious as oral iron for correcting iron deficiency. Further studies for determining ideal hemoglobin levels and dose of iron in CCHD patients are pertinent.
Diabetic atrial cardiomyopathy can be identified by multiparametric mri MRI associating atrio-ventricular groove adipose tissue and left atrial strain profiles
Authors: Bialobroda J , Bouazizi K , Pouniah M , Kachenoura N , Zarai M , Charpentier E , Aron-Wisnewsky J , Hatem S N , Redheuil A
Published: November 2023

Background

Epicardial adipose tissue (EAT) is tightly associated with neighboring myocardium with free diffusion between the two tissues of fatty acid, peptides and adipokines. In specific circumstances EAT can favors myocardial remodeling and, for instance, contribute to the risk of atrial fibrillation (AF). Thereby, there is a growing interest for EAT as a biomarker of AF however, which is limited by difficulties of delineation of EAT vs. other paracardial adipose tissues. The atrio-ventricular groove adipose tissue (GEAT) has been proven to be pure epicardial adipose tissue.

Purpose

We tested the feasibility and value of measuring pure EAT of the atrio-ventricular groove (GEAT) using routine cardiovascular magnetic resonance imaging (CMR) in a cohort of patients with distinct metabolic disorders and studied its correlates to determine a CMR cardiometabolic score.

Methods

One hundred patients from the METACARDIS cohort (EU FP7) who had MRI, all in sinus rhythm and without overt clinical heart disease, were divided into 4 groups based on distinct metabolic profiles: metabolic syndrome (MSD, n=25), severe obesity (SO, BMI ≥ 35 kg/m2, n=18), type-2 diabetes (T2D, n=42) and healthy controls (n=15). Atrioventricular groove EAT volume was measured from cine SSFP MRI images in four-, three-, two-chamber and short-axis views; atrial EAT volume was measured from four- and two-chamber views. Native T1-mapping values of EAT at the anterior atrioventricular groove excluding the coronary vessels were measured from the MOLLI sequence (basal short-axis slice).

Results

CMR was performed in 100 patients from the MetaCardis cohort. GEAT volume measured from end-diastolic long axis views was obtained in all patients with a high correlation between GEAT and atrial EAT (r=0.95; P<0.0001). GEAT volume was higher in the 3 groups of patients with metabolic disorders and highest in MSD. Together with age, body mass, fat distribution, GEAT volume allowed to distinguish obese, T2D and MSD from controls. T2D patients were uniquely characterized in CMR by decreased GEAT T1 relaxation and decreased peak longitudinal left atrial strain. We developed a CMR score by logistic regression and Random Forest machine-learning algorithm combining GEAT volume, T1 and peak LA strain that identified T2D patients with an AUC of 0.81 (Se:77%, Spe:80%; 95%-CI 0.72–0.91, p <0.0001).

Conclusion

The epicardial adipose tissue of the AV groove measured by CMR can be used as the proxy of atrial EAT and, in combination with atrial strain and T1 relaxation, allows the early identification of the atrial cardiomyopathy associated with diabetes. There is diagnostic value of a multiparametric CMR approach for the detection of subclinical atrial cardiomyopathy and potentially to identify patients at risk of atrial fibrillation and stroke.
Pulmonary arterial hypertension associated to toxic-oil syndrome. A long story short
Authors: Cruz Utrilla A , Ponz De Miguel I , Jimenez Lopez-Guarch C , Velazquez-Martin M , Gallego Zazo N , Tenorio-Castano J A , Ochoa Parra N , Lopez-Alacid I , Hinojosa W , Arribas-Ynsaurriaga F , Escribano-Subias P
Published: November 2023

Introduction

Pulmonary arterial hypertension (PAH) is occasionally related to previous use of drugs or toxins. The toxic oil syndrome (TOS) is a model of drug-induced PAH caused by the prior use of denatured rapeseed oil. This rare condition caused an acute epidemic disease in Spain, including the development of pulmonary arterial hypertension, with a mortality rate of 82% from 1981 to 1987. Several cases have been discovered in the successive years until 2018. The clinical profile and outcome of those patients with PAH-TOS diagnosed since 1988 are unknown.

Methods

Historical cases of PAH-TOS since 1988 were collected. We analysed baseline characteristics, genetic testing, and the rates of lung transplantation or mortality in PAH-TOS, comparing these outcomes with incident idiopathic and heritable PAH cases (i/hPAH) from the Spanish Registry of Pulmonary Hypertension (REHAP).

Results

Thirty-nine patients with PAH-TOS between 1988 and 2018 were selected for this study. The median time between the toxic intake and the disease onset was 20.3 years (Interquartile range: 14.3 – 25.6). At least one patient per year was identified in that period, with a mean incidence of 1.63 cases/per year. Genetic testing was done in 21 patients, using a 37-gene Next Generation Sequencing panel, not finding any pathogenic or likely pathogenic variant. Importantly, in 3 out of 39 cases, the disease resolved (7.7%), while 4 cases needed lung transplantation. The 10-year mortality was 35.9%.

Cases of PAH-TOS were compared with 200 incident patients with i/hPAH collected from 2003 onwards. PAH-TOS patients were significantly younger when compared with i/hPAH patients (p<0.0035). At baseline, patients with PAH-TOS had higher haemodynamically severity when compared with i/hPAH (mean pulmonary artery pressure of 65.0 mmHg Vs 53.5 mmHg, and pulmonary vascular resistance of 15.1 Vs 12.1 Wood Units, respectively; p=0.003, and p=0.02). In PAH-TOS the 5- and 10-year survival free of lung transplantation was 81.3%, and 52.7%, similar to the rates in the i/hPAH group (76.6%, and 59.2%, respectively; Log-rank test p=0.881. Figure).

Conclusions

The toxic oil syndrome is a unique model of drug-induced PAH, with new cases diagnosed several years after the toxic exposure. We did not find genetic variants in PAH-SOT patients. As described in other drug-induced cases of PAH, some patients experience a resolution of the disease over time. The very long-term survival of these patients is similar to that of patients with idiopathic or heritable pulmonary arterial hypertension.Figure
The effects of empagliflozin on right ventricular adaptation to pressure overload
Authors: Axelsen J S , Ringgaard S , Nielsen-Kudsk J E , De Man F S , Andersen A , Andersen S
Published: November 2023

Background

Right ventricular (RV) failure is the prime cause of death in patients with pulmonary arterial hypertension. Novel treatment strategies that protect the RV are needed. Empagliflozin, a member of the new anti-diabetic sodium-glucose co-transporter-2 inhibitors, shows a cardioprotective effect on the left ventricle in clinical and preclinical studies, but its direct cardiac effects on the RV remain elusive.

Purpose

To investigate the effects of empagliflozin on RV dysfunction induced by pulmonary trunk banding (PTB).

Methods

Male Wistar rat weanlings (116±10 g) were randomized to PTB or sham surgery. One week after surgery, PTB animals were randomized to empagliflozin 20 mg/kg/day mixed in the chow (300 mg empagliflozin/kg chow) (PTB-empa, n=10) or standard chow (PTB-control, n=10). Sham rats (Sham, n=6) received standard chow. After five weeks, RV function was evaluated by clinically relevant methods including echocardiography, cardiac MRI, and invasive pressure-volume measurements.

Results

PTB increased RV end-systolic pressures four-fold and caused RV hypertrophy with a 55 % increase in RV/(left ventricle + septum) weight ratio in PTB-control rats compared with sham. RV failure was evident by a decrease in cardiac output (PTB-control: 1.07±0.06 mL/s vs sham: 2.06±0.24 mL/s, p=0.0136). PTB-empa rats had a slight but non-significant weight reduction and a 33 % increase in water intake compared with PTB-control, yet no differences in hematocrit or blood glucose were observed. Treatment with empagliflozin decreased RV end-systolic pressures by 11 % (PTB-empa: 81±3 mmHg vs PTB-control: 91±2 mmHg, p=0.0091) without any effects on RV cardiac output. This decrease in RV end-systolic pressure in PTB-empa rats was complemented by less decreased minimum dp/dt and less increased maximum dp/dt compared with PTB-control without changes in the ventriculo-arterial coupling (Ees/Ea) (PTB-empa: 0.58±0.08 vs PTB-control: 0.67±0.14, p=0.8170). Load-independent measures of RV systolic and diastolic function were not affected in PTB-empa rats compared with PTB-control.

Conclusion

PTB caused RV failure in all rats subjected to the procedure. Empagliflozin treatment showed promising effects in pressure overload induced RV failure by reducing end-systolic pressure. Our study supports that treatment with empagliflozin has no toxic or adverse effects on the failing RV. Further studies are needed to explore empagliflozin’s potential beneficial role against RV failure.
The effect of sildenafil on maternal mortality in pulmonary arterial hypertension associated with congenital heart disease
Authors: Nahdi N S , Dinarti L K , Hartopo A B , Anggrahini D W
Published: November 2023

Background

Maternal mortality in pulmonary arterial hypertension (PAH) is very high, around 30–56%, so that patients with PAH and congenital heart disease (CHD) are advised to prevent pregnancy with class I-C recommendations. If the pregnancy continues, it must be handled by a multidisciplinary team with pulmonary hypertension (PH) experts, at the PH referral center. One of the PH-specific drug included in the FDA criteria B for pregnant women available in Indonesia is sildenafil. Sildenafil was reported to improve clinical symptoms and pregnancy outcomes in pregnant women with mild-moderate PAH. Sildenafil also had a tendency to reduce all-cause mortality although it was not statistically significant. Pulmonary hypertension specific drugs could reduce maternal mortality15.8% in subjects with PAH. However, research on sildenafil in maternal clinical outcomes is still very limited.

Purpose

This study aims to determine the effect of sildenafil on maternal mortality with PAH associated with CHD.

Methods

This study is an analytic observational study with a retrospective cohort method. Patient data were taken from the maternal registry, the Congenital HeARt Disease in adult and Pulmonary Hypertension (COHARD-PH) registry, and from the medical records of our general hospital who met the research criteria from August 2015 to December 2022. We assess the effect of sildenafil compared with controlled (without sildenafil) group. The clinical outcome of the study was maternal death during pregnancy and/or after delivery up to 42 days due to all causes (all causes mortality).

Results

Of 68 pregnant women who met the inclusion and exclusion criteria there were 32 subjects in the sildenafil group and 36 subjects in the control group. Maternal mortality was found to be higher (17.6%) in the group without sildenafil vs 9.7% in the sildenafil group. The majority causes of death were HP crisis (7 patients), 1 patient died from thromboembolism (HELLP syndrome), and 1 patient died from massive bleeding due to retained placenta. In the bivariate analysis, it was found that the NYHA functional class had a significant effect on maternal mortality with a p value <0.05, but not significantly from multivariate analysis. In the bivariate and multivariate analysis, general anesthesia had a statistically significant effect on maternal mortality with p=0.018. Of the 9 pregnant women who died, 5 patients received general anesthesia. Of the five patients, NYHA III-IV was found in 4 subjects (4/5 = 80%) and the other patient was NYHA II but subject came in at 63% saturation. All of the subjects are Eisenmeinger syndrome.

Conclusion

Sildenafil can reduce maternal mortality by 45% although it is not statistically significant. Further studies with larger data are needed to confirm this result.Basic Characteristics of SubjectsRelationship of Sildenafil with Maternal
Mechanical thrombectomy in intermediate- and high-risk acute pulmonary embolism: haemodynamic outcome at 3 months
Authors: Lauder L , Perez-Navarro P , Goetzinger F , Ewen S , Al-Ghorani H , Haring B , Lepper P , Kulenthiran S , Boehm M , Link A , Scheller B , Mahfoud F
Published: November 2023

Background

Haemodynamic data months after mechanical thrombectomy for pulmonary embolism (PE) are scarce.

Aims

To assess the haemodynamic effects of mechanical thrombectomy in acute PE with right heart overload.

Methods

In this prospective, open-label study, patients with acute symptomatic, computed tomography-documented PE with signs of right heart overload underwent mechanical thrombectomy using the FlowTriever System. Right heart catheterization was performed immediately before and after thrombectomy and after three months. Transthoracic echocardiography was performed before thrombectomy, discharge, and at three months. This analysis was done after the first 20 patients completed their three months of follow-up.

Results

Twenty-nine patients (34% female) underwent mechanical thrombectomy, of which 20 completed three months follow-up with right heart catheterization. Most patients (17%) were at high or intermediate-high (76%) risk and had bilateral pulmonary embolisms (79%). Before thrombectomy, systolic pulmonary arterial pressure (sPAP) was severely elevated (mean 51.3±11.6 mmHg). Mean sPAP dropped by -15.0 mmHg (95% confidence interval [CI]: -18.9 to -11.0; p<0.001) immediately following the procedure and continued to decrease from post-thrombectomy to three months (-6.4 mmHg, 95% CI: -10-0 to -2.9; p=0.002) (Figure). Right ventricle (RV)/left ventricle (LV) ratio immediately reduced within two days by -0.37 (95% CI: -0.47 to -0.27; p<0.001). The proportion of patients with a TAPSE/sPAP ratio <0.31 mm/mmHg decreased from 28% at baseline to 0% before discharge and at three months (p=0.007). There were no procedure-related major adverse events.

Conclusions

Mechanical thrombectomy for acute PE was safe and immediately reduced PAP and improved right heart function. The reduction in PAP was maintained at three months follow-up.Systolic pulmonary artery pressure
Long-term risk of pulmonary embolism and deep venous thrombosis after COVID-19: a population-based cohort study
Authors: Sjoland H , Lindgren M , Toska T , Hansson P O , Glise Sandblad K , Bjorck L , Lundberg C E , Adiels M , Rosengren A
Published: November 2023

Background

Venous thromboembolism (VTE) (pulmonary embolism (PE) or deep venous thrombosis (DVT)) is common during acute COVID-19. Long-term excess risk has not yet been established.

Objective

To study long-term VTE risk after COVID-19.

Methods

Swedish citizens aged 18-84 years, hospitalized and/or testing positive for COVID-19 between January 1, 2020, and September 11, 2021 (exposed), stratified by initial hospitalization, were compared to matched (1:5) non-exposed population-derived subjects without COVID-19. Outcomes were incident VTE, PE or DVT recorded at <60, 60−<180, and ≥180 days.

Results

Among exposed patients, 48,861 were hospitalized for COVID-19 (mean age 60.6 years) and 894,121 were without hospitalization (mean age 41.4 years) with 2,380 (4.9%) and 718 (0.08%) cases of VTE <60 days, compared to 142 (0.06%) and 1,033 (0.02%) among non-exposed controls (244,242 and 4,468,411, respectively). Among patients hospitalized for COVID-19, adjusted hazard ratios (HRs) during 60−<180 days were 6.05 (95% confidence interval (CI) 4.80─7.62) for PE and 3.97 (CI 2.96─5.33) for DVT, compared to non-exposed with corresponding estimates among COVID-19 without hospitalization 1.17 (CI 1.01─1.35) and 0.99 (CI 0.86─1.15), based on 475 and 2,311 VTE events, respectively. Long-term (≥180 days) HRs in patients hospitalized for COVID-19 were 2.01 (CI 1.51─2.68) for PE and 1.46 (CI 1.05─2.01) for DVT while non-hospitalized had similar risk to non-exposed, based on 467 and 2,030 VTE events, respectively.

Conclusions

Patients hospitalized for COVID-19 retained an elevated excess risk of VTE, mainly PE, after 180 days, while long-term risk of VTE in individuals with COVID-19 without hospitalization was similar to the non-exposed.
Development and validation of a clinical prediction model for the diagnostic management of acute pulmonary embolism: an individual participant data meta-analysis
Authors: Geersing G J , Takada T , Kraaijpoel N , Klok F A , Stals M , Freund Y , Le Gal G , Ghanima W , Huisman M V , Kline J , Righini M , Roy P M , Wells P S , Van Smeden M , Van Es N
Published: November 2023

Background/Introduction

Risk stratification is used for decisions about imaging in patients with clinically suspected acute pulmonary embolism (PE).

Purpose

To develop a clinical prediction model that provides an individualized, accurate probability estimate for acute pulmonary embolism (PE) based on readily available clinical items and D-dimer concentrations.

Methods

An individual participant data meta-analysis was performed based on sixteen studies with data from 28,305 adult patients with clinically suspected PE from various clinical settings. A multilevel logistic regression model was built and validated including ten a priori defined objective candidate predictors to predict PE at baseline or during follow-up of 30-90 days. Multiple imputation was used for missing data. Backward elimination was performed with a P-value < 0.10. Discrimination (c-statistic with 95% CI and prediction intervals [PI]) and calibration (outcome:expected [O:E] ratio and calibration plot) were evaluated based on internal-external cross-validation. The accuracy of the model was compared to algorithms based on the Wells score and D-dimer testing.

Results

The final model included age (in years), sex, previous VTE, recent surgery/immobilization, hemoptysis, cancer, clinical signs of DVT, inpatient status, D-dimer (in μg/L), and an interaction term between age and D-dimer. The pooled c-statistic was 0.87 (95%-CI, 0.85-0.89; 95%-PI, 0.77-0.93) and overall calibration was very good (pooled O:E ratio, 0.99; 95% CI, 0.87-1.14; 95% PI, 0.55-1.79). In the lower range of probabilities, the model slightly overestimated VTE probability. Discrimination of the current model in the validation data sets was better than that of the Wells score combined with a D-dimer threshold based on age (c- statistic 0.73; 95%-CI, 0.70-0.75) or structured clinical pretest probability (c-statistic 0.79; 95%-CI, 0.76- 0.81).

Conclusion(s)

The present model provides an absolute, individualized probability of PE presence in a broad population of patients with suspected PE, with very good discrimination and calibration. Its clinical utility needs to be evaluated in a prospective management or impact study.Calibration plot of the new model
Right ventricular global work efficiency provides the highest prediction for improvements in right ventricle to left ventricle diameter ratio with acute pulmonary embolism treatments
Authors: Keskin B , Tokgoz H C , Kultursay B , Hakgor A , Tanyeri S , Tosun A , Bulus C , Sirma D , Sekban A , Karagoz A , Tanboga I H , Ozdemir N , Kaymaz C
Published: November 2023

Introduction

In addition to standard echocardiographic measures, global longitudinal strain (GLS) with speckle tracking (ST) and myocardial work (MW) evaluation have been used in the assessment of right ventricle (RV) function in patients with acute pulmonary embolism (PE). In this study we aimed to compare echocardiographic measures, ST and MW in prediction of change in right ventricle (RV) to left ventricle (LV) diameter ratio (r) with treatments.

Methods

Our study comprised 83 consecutive patients (female %54.6, age 59±14.9 years) who admitted to our hospital with diagnosis of acute PE and underwent evidence-based treatments. Echocardiographic evaluation including ST and MW were performed within first 24 hours of admission. NT-pro-brain natriuretic peptide (NT-proBNP), troponin, pulmonary embolism severity index (PESI) and Qanadli score, RV and LV global work index (GWI), global work efficiency (GWE), global constructive work (GCW) and global wasted work (GWW), and RV-GLS were evaluated. Primary end-point (PEP) of this study was the change in RV to LVr on computed tomography (CT), and generalized additive model (GAM) in addition to classical linear regression (LR) were utilized for prediction of change in RV/LVr with these measures.

Results

PESI score and RV/LVr at admission were 84.8±23.8 and 1.13±0.39, respectively. Unfractioned or low-molecular weight heparin were treatments of choice in patients. The change in RV/LVr after selected treatments were 0.356. Mean hospital stay and overall follow-up duration were 8.7±3.7 and 328.7±126.8 days, respectively. In-hospital and long-term mortality rates were 1.2% and 13.3% respectively. Correlation co-efficients for intra- and interobserver agreement of MW measures varied from 0.85 to 0.96. The LR revealed that pulmonary arterial systolic, diastolic and mean pressure estimates, fractional area change and RV annular tissue velocity were significantly related with changes in RV/LVr (p values; 0.02, 0.01, 0.004, 0.03 and 0.03, respectively). Moreover, RV-GWE compared with RV-GLS showed a higher prediction for improvements in the RV/LVr (p value were <0.001 and 0.049, respectively). Utilization of GAM increased R2 value (from 0.15 to 0.20), and decreased the complexity of model. RV-GWE showed a moderate correlation with RV-GLS (r=-0.56), RV-GWI (r = 0.42), RV-GCW (r=0.32), LV-GWW(r=-0.55), LV-GLS (r=-0.33), FAC (r=0.26), NT-proBNP (r=-0.38), troponin (r=-0.28) but not with other measures.

Conclusions

The RV GWE as a novel myocardial work parameter seems to provide a better prediction for improvements in the RV/LVr with acute PE treatments as compared to clinical, laboratory and other echocardiographic measures including GLS.Figure-1Figure-2
Impact of pulmonary embolism on COVID-19 pneumonia hospitalizations: analysis of the national inpatient sample 2020
Authors: Kodali M , Atluri R
Published: November 2023

Background

SARS-CoV-2 swept across the globe, overwhelming healthcare systems across the world regardless of borders and socioeconomic factors. While many were directly affected by COVID pneumonia (CP), others were impacted by complications from the illness. Pulmonary embolism (PE) is a well described complication in this population and results in worsening ventilation-perfusion mismatch further worsening their pulmonary reserve. We aimed to assess the impact of underlying PE on CP patients with a large sample size.

Methods

We utilized the National Inpatient Sample from 2020 to identify 1,058,815 hospitalized adults with CP. These hospitalizations were further stratified based on the presence of PE. A multivariate regression model was used to adjust for confounders and analyze the variables.

Results

Of those who were admitted for CP, 29,845 (2.8%) had PE. In-hospital mortality was higher in those with PE (16.5% vs 10.9%; p<0.001). Figure 1 shows the Forrest plot for multivariate analysis of in-hospital outcomes when adjusted for patient demographics, comorbidities, and hospital characteristics. When adjusted similarly, CP patients with PE had longer length of stay (LOS) by 2.4 days (p<0.001) and had additional hospital costs (HC) of $45,470 (p<0.001).

Conclusion

CP patients who had PE had significantly worse outcomes in terms of in-hospital mortality, LOS, HC, cardiac arrest, arrhythmias, stroke, AKI, GI bleed, sepsis, cardiogenic shock, and being intubated. These patients poorly tolerate the ventilation-perfusion mismatch due to an already reduced pulmonary reserve.