bluuebunny/crossref_metadata_2025 huggingface dataset:
Moderate functional mitral regurgitation: difference between atrial and ventricular mechanism of the regurgitation
Authors: Sarrazyn C , Laenens D , Chua A P , Myagmardorj R , Nabeta T , Bax J J , Ajmone Marsan N
Published: November 2023

Background/Introduction

In severe functional mitral regurgitation (MR), further distinction of the mechanism of MR in atrial functional MR (aFMR) and ventricular functional MR (vFMR) has shown prognostic importance. However, no data are available on moderate functional MR, whose characteristics and prognosis are largely unknown.

Purpose

To assess clinical and echocardiographic characteristics of patients with moderate aFMR and vFMR and their potential difference in outcome.

Methods

Patients with moderate functional MR were retrospectively included. aFMR was defined as isolated mitral annulus dilatation in combination with preserved left ventricular ejection fraction (LVEF≥50%) without ischemic heart disease or LV dilatation. Patients were classified as vFMR when LVEF was reduced, LV was dilated and/or wall motion abnormalities were present. Mitral valve intervention and all-cause mortality were used as combined endpoint.

Results

In total 474 patients with moderate functional MR (mean age 67 ±12, 57% male) were evaluated, of which 136 (29%) had aFMR and 338 (71%) had vFMR as underlying mechanism. Among the clinical variables, patients with aFMR had more atrial fibrillation (77% vs. 35%; p<0.001), were less symptomatic (NYHA class ≥ III: 6% vs. 18%; p<0.001) and had better renal function (eGFR 73 ±23 ml/min/1,73m2 vs. 65 ±23 ml/min/1,73m2; p=0.005) as compared to vFMR. In the vFMR group, 49% of patients had ischemic heart disease. Among the echocardiographic variables, as expected in aFMR, LVEF was higher (42 ±14% vs. 55 ±13%; p<0.001), while LV volumes (LV end-diastolic volume index 55 ±13 mL/m2 vs. 82 ±38 mL/m2; p<0.001) and E/E’ ratio were smaller (10 ±4 vs. 15 ±4; p<0.001) as compared to vFMR. However left atrial (LA) volume index was similar between both groups (43 ±14 mL/m2 vs. 41 ±18 mL/m2; p=0.271). For the echocardiographic measures of the right heart, significant difference was observed only for TAPSE which was higher for the aFMR group (22 ±4mm vs. 20 ±5mm; p<0.001). During a median follow-up of 74 months [IQR: 46.8-107.0], 132 (30%) patients died and 30 (6%) underwent mitral valve intervention. Event-free survival analysis for the combined endpoint was significantly better for aFMR patients (Figure 1). Based on significant variables from the univariable Cox regression analysis, multivariable Cox regression analysis showed that the mechanism of functional MR (with aFMR being protective as compared to vFMR), age, male gender, impaired renal function, NYHA class, severe LA dilatation and TAPSE were independently associated with the combined endpoint (Table 1).

Conclusion

In patients with moderate functional MR, aFMR is independently associated with better event-free survival as compared to vFMR. Therefore, clear identification of the mechanism of MR implies a better risk stratification and may be helpful for the management of patients with moderate MR.
Artificial intelligence-enabled electrocardiogram in the detection of patients at risk of atrial functional mitral regurgitation
Authors: Naser J , Lee E , Michelena H I , Lin G , Pellikkka P A , Nkomo V T , Noseworthy P A , Friedman P A , Attia Z I , Pislaru S V
Published: November 2023

Background

Atrial functional mitral regurgitation (AFMR) is an increasingly recognized cause of functional MR thought to result from left atrial enlargement and myopathy in the setting of preserved left ventricular geometry and function. AFMR mostly occurs in patients with atrial fibrillation (AF) and/or heart failure with preserved ejection fraction.

Purpose

We investigated whether the use of an artificial intelligence-based electrocardiogram (AI-ECG) can identify patients with new-onset AF and sinus rhythm (SR) who are at highest risk of developing AFMR.

Methods

Adults with a new diagnosis of AF between 2010 and 2021 who had a transthoracic echocardiogram (TTE) within 1 month after AF diagnosis were identified. Similarly, adults in SR who never had AF diagnosis and had a TTE during the same period were identified. Exclusion criteria from both groups included >mild MR at baseline, primary mitral valve disease, cardiomyopathy, ≥moderate aortic valve disease, current or previous low ejection fraction, enlarged left ventricle, cardiac devices, previous cardiac surgeries, and the absence of follow-up TTE ≥6 months from baseline. Only patients who had ECG within 10 days of the TTE were included. When multiple ECGs were available, the closest was considered. A previously trained AI-ECG algorithm to detect the probability of AF was utilized. Incident AFMR was defined as >mild functional MR in the absence of >mild left ventricle enlargement or dysfunction. Diastolic dysfunction was defined according to ASE/EACVI guidelines.

Results

Overall, 1,570 patients with new-onset AF (median age 67 years; 34% females) and 16,802 patients in SR (median age 59 years; 46% females) were included. The median AI ECG probability for AF was 43% (IQR 26%-59%) in the new-onset AF group and 2% (0.5%-7%) in the SR group, Figure 1. Incident AFMR occurred in 152 patients in the AF group over median 3.06 (IQR 1.5-5.2) years of follow-up and in 482 patients in the SR group over median 3.0 (1.5-5.6) years of follow-up. The probability of silent AF by the AI-ECG was associated with incident AFMR in the new-onset AF group [hazard ratio 1.19 (95% CI 1.11-1.28) per 10%, p <.001] and the SR group [hazard ratio 1.19 (95% CI 1.12-1.25) per 10%, p <.001]. The AI ECG-derived AF probability remained as an independent risk factor for AFMR in multivariable analysis in both AF and SR, Table 1.

Conclusion

The AI ECG for AF might be able to reflect the degree of left atrial myopathy and thus the risk of incident AFMR in patients with AF and SR.Distribution of AI ECG probability of AFMultivariable risk factors for AFMR
Mitral leaflet retraction and left ventricular reverse remodeling in patients with treated dilated cardiomyopathy
Authors: Kang Y , Liu K Y , Yang Z X , Qu N , Zhong X K , Chen X J , Wang M , Zhang Q
Published: November 2023

Background

Enlargement of the mitral leaflets (MLs) adaptive to mechanical stress caused by dilated left ventricle (LV) was recognized, but their changes after the stimuli withdrawn remained unexplored.

Aims

To observe morphological changes in the MLs along with LV reverse remodeling (LVRR) occurred after standard care.

Methods

Patients with recent-onset dilated cardiomyopathy (RODCM) were prospectively enrolled (n=82), as well as a group of age, sex and body surface area matched normal controls (NC) (n=50). Two-dimensional transthoracic echocardiography was performed at baseline and 6-month follow-up with special interests in the length of anterior and posterior mitral leaflet (AML and PML), mitral annular dimension (MAD) and tenting height (TH). LVRR was measured as a reduction in the LV end-diastolic volume (LVEDV) of ≥15%.

Results

At the 6-month follow-up, LVRR was achieved in 69.5% patients and there were 26.9% patients who reported ≥1 grade reduction in secondary mitral regurgitation that related to LVRR. The AML (28±3 vs. 26±3mm, p=0.004) and PML (19±4 vs. 17±3mm, p<0.001) were decreased, as well as the MAD (31±5 vs. 28±5mm, p=0.001) and TH (10±3 vs. 8±2mm, p<0.001), but all remained larger than that of the NC group (all p<0.05). When compared with the control group, the AML and PML of the RODCM group was 16.7% and 35.7% longer at baseline, which remained 8.3% and 21.2% longer at the follow-up, respectively. The change in the AML (△AML) or PML (△PML) correlated moderately to the change in the LVEDV (△LVEDV) (r=0.487, p<0.001; r=0.516, p <0.001, respectively) (Figure 1). When compared between the subgroups stratified by LVRR, both the AML and PML decreased in the patients who had LVRR (+) (AML, 28±3 vs. 26±3, p=0.001; PML, 20±4 vs. 16±3, p<0.001), but remained the same length in those with LVRR (-) (AML, 27±4 vs. 28±4, p=0.318; PML, 17±3 vs. 17±3, p=0.790). The comparison in the △AML and △PML between the two subgroups is shown in Figure 2.

Conclusion

The enlarged MLs could retract with different behavior in the AML and PML, accompanied by LV reverse remodeling. This study conducted in patients with RODCM who received standard therapy provided the other facet of mitral leaflet plasticity adaptive to mechanical stretch.correlation between △MLs and △LVEDVCompare △MLs between LVRR subgroups
Mortality and heart failure in patients with a history of atrial fibrillation undergoing mitral valve surgery
Authors: Due H , Petersen J K P , Havers-Borgersen E H B , Meulengracht D M , Bager L G V B , Koeber L K , Fosboel E F , Oestergaard L O E
Published: November 2023

Background

A history of atrial fibrillation (AF) is frequently seen in patients with mitral regurgitation. However, the impact of AF on heart failure (HF) and mortality following mitral valve repair/replacement for mitral regurgitation remains unclear.

Purpose

To examine the long-term risk of HF admission and mortality in patients undergoing mitral valve repair/replacement with or without AF.

Methods

We included adult patients undergoing mitral valve repair/replace for mitral regurgitation in Denmark (2000-2018). Patients were categorized according to a history of AF. We examined the cumulative incidences of HF admission and all-cause mortality with a maximum of three years of follow-up. Here we used Kaplan-Meier and Cumulative Incidence Function curves accounting for competing risk of death. Likewise, groups were compared using Cox proportional hazards in adjusted analyses.

Results

We included 4480 patients where 1685 (37.6%) patients had a history of AF (median age: 70, 66.1% males) and 2795 (62.4%) patients had no history of AF (median age: 64, 67.6% males). Patients with a history of AF had a higher proportion of chronic HF (42.0% vs 23.5%), ischaemic heart disease (37.4% vs 29.4%), and stroke (7.7% vs. 4.3%) at baseline. Patients with a history of AF before surgery admission were less likely to undergo mitral valve repair (65% vs. 72%).

The cumulative three-year incidence of HF-admission was 23.7% in patients with a history of AF and 14.6% in patients without a history of AF (Figure A). Adjusted analysis found a statistically significant increased rate of HF admissions (HR=1.19 [95% CI 1.02-1.39]). The cumulative three-year incidence of mortality was 13.8% in patients with a history of AF, and 8.2% in patients without a history AF (Figure B). Adjusted analysis yielded no statistically significant difference in the associated rate of mortality (HR=1.16 [95% CI 0.95-1.43]). Factors associated with both increased HF admission and mortality were among others age, myocardial infarction, and known chronic HF.

Conclusion

One in three patients had a history of atrial fibrillation, and these patients were associated with an increased rate of both heart failure admission and mortality, but following adjustments the association was only statistically significant for heart failure admission.Cumulative incidence of HF-admissionCumulative incidence of mortality
Early outcomes of the PASCAL P10 and the MitraClip XT transcatheter mitral leaflet approximation devices - A propensity score matched multicentre comparison
Authors: Von Stein P , Wienemann H , Horn P , Sugiura A , Spieker M , Tanaka T , Lurz P , Ruf T , Grothusen C , Hausleiter J , Nef H , Luedike P , Gercek M , Pfister R , Mauri V
Published: November 2023

Background

The edge-to-spacer PASCAL repair system was recently approved for percutaneous treatment of severe mitral regurgitation (MR). Comparative data with the MitraClip XT device which shows similar size and leaflet grasping features are lacking.

Purpose

Aim of this study was to compare the procedural and short-term safety and efficacy of two transcatheter mitral leaflet approximation devices, the PASCAL P10 and the MitraClip XT.

Methods

Overall, 566 patients underwent transcatheter mitral valve repair (TMVR) with PASCAL P10 (n=309) or MitraClip XT (n=257). The PASCAL P10 cohort included patients treated at 10 tertiary care centres in Germany between February and December 2019, while the MitraClip XT cohort consisted of patients treated at three of these 10 centres between May 2018 and September 2022. Propensity score (PS) matching based on the parameters gender, age, left ventricular ejection fraction, NYHA class, left ventricular end-diastolic diameter, left atrial volume index, vena contracta width, MR aetiology, and mean gradient resulted in 191 well balanced patient pairs. Primary efficacy endpoints were technical success, degree of residual MR at discharge and at 30-days as well as device success at 30-days. Primary safety endpoint was the rate of major adverse events (MAE) at 30-days.

Results

Technical success was 95.8% in the PASCAL group and 95.3% in the MitraClip group (P>0.99). An MR ≤2+ at discharge was numerically more frequent in the PASCAL than in the MitraClip group (PASCAL: 91.5% vs. MitraClip: 85.9%; P=0.101). An MR ≤1+ at discharge was achieved more frequently in the PASCAL group (PASCAL: 68.3% vs. MitraClip: 56.5%; P=0.025). This difference was sustained at 30-days with numerically more patients with residual MR ≤2+ (PASCAL: 89.7% vs. MitraClip: 82.4%; P=0.071) and significantly more patients with MR ≤1+ (PASCAL: 64.7% vs. MitraClip: 51.6%; P=0.021) in the PASCAL group than in the MitraClip group. At 30-days, the mean gradient was similar between the two groups (PASCAL: 3.0 [2.3–4.0] mmHg vs. MitraClip: 3.1 [2.7–4.2] mmHg], P=0.218). Device success at 30 days was achieved with an equal frequency in both groups (PASCAL: 78.8% vs MitraClip: 71.3%; P=0.129). At 30-days, MAE occurred more often in the MitraClip than in the PASCAL group (PASCAL: 3.7% vs. MitraClip: 12.6%; P=0.002).

Conclusions

In this PS-matched study comparing the PASCAL P10 with the MitraClip XT, safety and efficacy were comparable at 30-days.
Dapagliflozin effect on functional mitral regurgitation and myocardial remodeling (DEFORM trial)
Authors: Huang Z S , Fan R , Xie P H , Zhong J L , Zhang S Z , Zhuang X D , Liao X X
Published: November 2023

Background

Functional mitral regurgitation (FMR) has already been demonstrated to lead to various adverse outcomes. However, the therapeutic effect of current guideline-directed medical therapy (GDMT) in FMR still remained limited. The purpose of this study was to assess the efficacy of sodium-glucose cotransporter 2 (SGLT-2) inhibitor dapagliflozin in reducing the extent of mitral regurgitation and myocardial remodeling in FMR patients.

Methods

In this prospective, randomized, parallel controlled trial, we randomly assigned 104 patients with moderate or severe FMR in a 1:1 ratio to receive either dapagliflozin 10mg once daily or not in addition to GDMT for FMR and follow-up for 12 weeks. The primary outcome was the change in effective regurgitant orifice area (EROA) of mitral regurgitation. Secondary outcomes included changes in regurgitant volume (RV), left atrial dimension (LAD), left ventricular end-systolic dimension (LVESd), left ventricular end-diastolic dimension (LVEDd), left ventricular ejection fraction (LVEF) and E/e’ ratio. Furthermore, we additionally compared the occurrence rate of hospitalization for heart failure or cardiac death between groups.

Results

Dapagliflozin was associated with a significant reduction in EROA of FMR (-0.074±0.099 vs -0.030±0.058 cm2for dapagliflozin vs. control, P=0.008). Dapagliflozin was also associated with significant reduction of RV (-9.08±15.27 vs. -2.98±9.28 ml for dapagliflozin vs. control, P=0.017), LAD (-2.45±4.44 vs. -0.36±3.08 mm for dapagliflozin vs. control, P=0.007) and E/e’ ratio (-5.88±7.41 vs -1.98±7.63 for dapagliflozin vs. control, P=0.011), and improvement in LVEF (6.57±10.10 vs. 1.92±9.57 for dapagliflozin vs. control, P=0.017). There were no significant differences in the changes of LVESd (P=0.662) and LVEDd (P=0.677) between groups. Hospitalization for heart failure occurred in 6 patients of dapagliflozin group (11.5%) and 10 patients of control group (19.2%) (log-rank test, P=0.257), and 1 patient in dapagliflozin group (1.9%) and 2 patients in control group (3.8%) had cardiac death during the 12-week follow-up (log-rank test, P=0.552).

Conclusion

Dapagliflozin could further reduce the extent of mitral regurgitation and improve myocardial remodeling in FMR patients based on the current GDMT. Our findings suggest that SGLT-2 inhibitors might be considered for GDMT of patients with moderate or severe FMR.
Left ventricular hypertrophy and ventricular ectopy in mitral valve prolapse
Authors: Cesmat A P , Chaudry A M , Gupta S , Sivaraj K , Weickert T T , Simpson Jr R J , Syed F F
Published: November 2023

Background

Mitral valve prolapse (MVP) is associated with left ventricular hypertrophy (LVH). Individuals with sudden death ascribed to MVP have increased ventricular mass on autopsy. Whether LVH is a risk factor for ventricular arrhythmia in MVP is unknown.

Purpose

We aimed to describe factors associated with LVH in MVP and the association of LVH with ventricular ectopy in MVP.

Methods

We studied all 637 patients aged 18 - 90 years with MVP on echocardiography between 2016-19 at our institution (median age [interquartile range] 64.3 [52.3-73.6] years; 52.6% female; 16.2% African American). Echocardiograms were reviewed for LVH, ventricular size and function, and valvular pathology. Complex or frequent ventricular ectopy (cfVE) was defined as >1% burden of premature ventricular complexes or non-sustained ventricular tachycardia on ambulatory electrocardiogram or ≥2 premature ventricular complexes on a 10-second electrocardiogram. Multivariate logistic regression was used to assess relationships between MVP, LVH, and known associations of cfVE in MVP.

Resul­ts: LVH was present in 144 (22.6%) patients. A history of hypertension (HTN) was present in 78/144 (54.2%) with LVH vs. 204/493 (41.5%) of those without LVH (p=0.008). On multivariate analysis, LVH was independently associated with moderate to severe mitral regurgitation (odds ratio [95% confidence interval] 3.6 [2.4-5.6]) and heart failure (3.2 [2.0-5.1]), but not HTN (1.3 [0.9-2.0], p=0.205). cfVE was present in 55/144 (38.2%) with LVH vs. 127/493 (25.8%) without LVH (p=0.005). Among those without HTN, cfVE was present in 26/66 (39.4%) of those with LVH vs. 68/288 (23.6%) without LVH (p=0.013). On multivariate analysis, independent predictors of cfVE were age (odds ratio [95% confidence interval] 2.9 [1.1-8.1], p=0.035), mitral annular disjunction (3.2 [1.9-5.3], p<0.0001), heart failure (2.4 [1.4-4.0], p=0.001), bileaflet MVP (2.2 [1.4-3.3], p<0.001), and electrocardiogram inferior lead T-wave inversion (2.2 [1.4-3.4], p<0.001), but not LVH (1.2 [0.7-1.9], p=0.486) whether in presence of HTN (1.0 [0.5-1.9], p=0.959) or absence of HTN (1.4 [0.7-2.8], p=0.344).

Conclusion

LVH is a common finding in MVP and is associated with mitral regurgitation and heart failure. LVH in MVP is not associated with increased ventricular ectopy. Ventricular ectopy in MVP is related to mitral morphological factors and heart failure.Multivariate predictors of cfVECharacteristics with and without LVH
Decoding calcific mitral valve disease: a novel deep learning model uncovers the role of calcium burden
Authors: Arif S , Zhang D , Ahmad F , Diagne M , Afilalo J
Published: November 2023

Background

Mitral annular calcification (MAC) is a common degenerative disease that affects older adults and causes calcium deposition in the mitral annulus, increasing the risk of mitral valve (MV) dysfunction, cardiovascular events, conduction abnormalities, and mortality. While the primary imaging modality recommended for the clinical evaluation of MAC is echocardiography, it has been reported to be found incidentally in approximately 8% of routine thoracic computed tomography (CT) scans. CT scan is a sensitive imaging modality for assessing MAC, providing the resolution necessary to understand the anatomical involvement of calcification. Research has shown that the MAC burden is associated with disease activity and progression. Still, the exact correlation between the quantitative calcium burden and the degree of severity of mitral valve disease is unclear.

Purpose

Our study aimed to determine the association between MAC, as assessed on CT, and significant mitral stenosis (MS) or mitral regurgitation (MR), as visualised on echocardiography. In addition, we sought to determine the quantitative MAC cutoffs that would optimally predict significant MS or MR on echocardiography.

Methods

A retrospective cohort study was conducted at our academic centre. Inclusion criteria were: age≥60 years, resting transthoracic echocardiogram performed between 2013-2022, non-gated chest CT performed within one year before echocardiography, and any degree of MAC documented on the echocardiography report. CT scans were requested for clinical indications unrelated to mitral valve disease. Exclusion criteria were: prior mitral valve intervention, endocarditis, and congenital mitral valve disease. Significant calcific mitral valve disease was defined as ≥moderate MR and ≥mild MS on the echocardiography report, ascertained by expert readers based on multiparametric ASE criteria. MAC volume was quantified on the multi-slice CT DICOM images using a 3D U-Net deep neural network previously trained by our group on an independent cohort.

Results

The cohort consisted of 1,560 unique patients with a mean age of 79 years and 61% females. The echocardiographic prevalence of significant MR and MS was 10% and 4%, respectively, for 211 affected patients. The CT-based mean MAC volume was 949 mm³ in patients with significant MR or MS, as opposed to 334 mm³ in those without (P<0.001). MAC volume >1000 mm³ was the optimal cutoff to predict significant MS (specificity 90%, sensitivity 51%, area under ROC curve 0.79) and significant MR (specificity 89%, sensitivity 21%, area under ROC curve 0.60). Adjusting for age, sex, and comorbid conditions did not affect the observed association between MAC volume and mitral valvulopathy.

Conclusion

A novel deep learning model for quantifying MAC volume from non-cardiac clinical CT scans was efficient in screening for calcific mitral valve disease, particularly MS, and identifying patients who may benefit from further evaluation.
An external validation of prognostic scores for patients with severe tricuspid regurgitation
Authors: Ruiz Ortiz M , Fernandez Aviles C , Fernandez Ruiz A , Heredia Campos G , Resua Collazo A , Delgado Ortega M , Mesa Rubio D , Rodriguez Almodovar A , Esteban Martinez F , Maestre Luque L C , Moran Salinas A , Torres Zamudio A , Herrera Flores J , Diaz Andrade M , Pan Alvarez-Ossorio M
Published: November 2023

Background

Three scores have been published in 2022 for assessing prognosis of patients with tricuspid regurgitation (TR): the TRI-SCORE, and those reported by Hochstadt and Wang. All of them have shown to be useful in the prediction of mortality in follow-up. However only one of them has been externally validated, their comparative performance is unknown, and their discriminative ability for broader outcomes has not been investigated.

Purpose

To perform an external validation of available scores for predicting mortality and the combined end-point of mortality and heart failure (HF) admission in follow-up, in an independent cohort of patients with severe TR, and to compare their discriminative ability for this outcomes.

Methods

The validation cohort included retrospectively all consecutive patients ≥18 years with severe TR studied with echocardiography in a tertiary care hospital from 01.01.2008 to 31.12.2017, followed for all cause death and HF admission up to 01.01.2022. Every score was calculated in each patient with variables from the basal visit (Figure 1), and discriminative ability of the scores for predicting events was assessed by means of receiver operating characteristics (ROC) curves.

Results

A total 661 patients (69±13 years, 72% women) with severe TR, followed for up to 14 years (median 5 years, p25-75 2-7 years) were included in the validation cohort, with 384 deaths and 268 patients with 636 HF admissions on follow up. Discriminative ability for predicting death (C-statistic 0.72, 95%CI 0.68-0.76, p<0.0005 for the TRI-SCORE; 0.75, 95%CI 0.71-0.78, p<0.0005 for the Hochstadt score and 0.72, 95%CI 0.68-0.76, p<0.0005 for the Wang score, figure 1A) or the combined end-point (C-statistic 0.74, 95%CI 0.70-0.78, p<0.0005; 0.74, 95%CI 0.70-0.78, p<0.0005 and 0.73, 95%CI 0.69-0.77,p<0.0005, respectively, figure 1B ) on follow up was statistically significant for all of them. Paired comparison among them for predicting the combined end-point were all non-significant. However, the Hochstadt score was superior to the other two scores for predicting mortality in follow-up (p<0.005).

Conclusions

All tested scores showed significant and similar discriminative ability for predicting the combined end-point of mortality or HF admission in this independent validation study of patients with severe TR. However, the Hochstadt score performed significantly better than the other scores for predicting mortality in follow-upScore variablesROC curves
Right ventricular function in moderate-to-severe ventricular tricuspid regurgitation: Is there a pseudo-normalization of conventional echocardiographic parameters?
Authors: Schmeisser A , Rauwolf T , Groscheck T , Tanev I , Meissler S , Hansen M , Luani B , Bekfani T , Steendijk P , Braun-Dullaeus R U E D I G
Published: November 2023

Background

A reliable evaluation of right ventricular (RV) function in the presence of moderate-to-severe tricuspid regurgitation (m/s-TR) is of paramount importance for surgical or interventional risk stratification. Due to the significant systolic regurgitation of blood from the RV to the low-pressure right atrium, conventional echocardiographic parameters could appear normal and thus overestimate RV function (pseudo-normal). The aim of this study was to analyse and compare RV function in trace TR versus m/s-TR by the invasive pressure-volume-loop (PV-loop) technique, the gold standard of RV function analysis, with conventional echocardiographic indices in patients with the ventricular form of mild/no vs. m/s-TR.

Methods

The study was conducted in 134 patients with HFrEF in a post-hoc analysis (110 from the Magdeburg CRT Responder Trial, and 24 from a local CRT-optimization trial).

Results

The logistic regression analysis demonstrated that RV size (RV-end-diastolic volume, RVEDV) and RV function (measured as RV fractional area change, FAC), TAPSE, and lower fractional shortening (FS) of proximal the RV-outflow tract (RVOTprox) was closely associated with PV-loop-derived RV total afterload (pulmonary arterial elastance, Ea) and coupling of RV contractility (end-systolic RV elastance, Ees) to Ea (Ees/Ea) (all, p<0.001). Compared to trace TR (n=98, 73%), m/s-TR (n=36, 27%) was accompanied with significant higher total afterloads (Ea: 0.75 vs.0.41, p<0.001) and lower RV-PA coupling ratios (Ees/Ea, 0.4 vs. 0.79, p<0.001). This was associated with enlarged RVs (RVEDV: 210ml vs. 166ml), lower FAC (31% vs. 50%), TAPSE (13mm vs. 18mm), and RVOTprox (22% vs. 39%) (all p<0.001). For better comparability between trace TR and m/s-TR tertiles (T1-T3) of similar afterloads (Ea) were formed. The m/s-TR patients showed significant lower RV-PA coupling ratios than trace TR at the lower two Ea tertiles T1 (p=0.034) and T2 (p<0.001). At Ea T3 the difference was no longer significant (p=0.055). The hemodynamic data are mirrored by significant lower FACs, FS RVOTprox, and TAPSE at T1 and T2 (all p<0.05), and a nonsignificant difference at T3 in m/s-TR.

In conclusion: In our cohort of HFrEF patients, echocardiographic RV function reflects very closely the hemodynamic coupling efficiency of RV contractility (Ees) to afterload (Ea) and seems independent from the extent of TR. We found no evidence for pseudo-normal or overestimated echocardiographic RV function in m/s-TR.
Tricuspid regurgitation impact on outcomes (TRIO) score: an evaluation tool for patients undergoing tricuspid valve surgery?
Authors: Al-Shakarchi N , Younis A , Juarez Casso F M , Crestanello J A , Nishant S , Anand V , Schaff H V , Greason K L , Nkomo V T , Lara-Breitinger K M , Pislaru S V
Published: November 2023

Background

Isolated tricuspid regurgitation (TR) repair or replacement carries significant operative mortality risk mainly due to delayed referral. We have recently developed the Tricuspid Regurgitation Impact on Outcomes (TRIO) score to assess risk in TR based on 8 simple variables (age, sex, severe TR, creatinine>2 mg/dl, history of heart failure, history of chronic lung disease, AST >40 units/L, heart rate >90). Whether this score can be used in assessment of TR surgical risk and long term outcome is unknown.

Purpose

To examine the impact of TRIO scores on the postoperative outcomes of isolated tricuspid valve surgery.

Methods

Adult patients with severe functional TR who underwent isolated tricuspid valve replacement or repair between 2000-2022 were identified. Postoperative outcomes were compared across low (0-3), intermediate (4-6), and high (7-12) TRIO risk score groups.

Results

177 patients were included. Mean age was 70.7 ± 12.2 years, 69 (39%) were male, 34 (19%) were low TRIO score, 111 (63%) intermediate score and 32 (18%) high score. Tricuspid repair was performed in 43 (24.3%) and valve replacement in 134 (75.7%), reflecting the advanced disease stages of this patient cohort. At short term, higher TRIO scores were associated with more frequent need for urgent surgery, prolonged ventilation (>72h) and postoperative dialysis (p<0.05 for all). Perioperative 30-day mortality increased with the TRIO risk score (low: 0%; intermediate: 4.5%; high: 9.4%) but differences did not reach statistical significance (p=0.187). Low risk patients had a shorter hospital and ICU stay (Figure 1A-B). During a mean follow-up of 5.2 ± 3.2 years, 98 (55.4%) patients died. At long term follow-up, lower TRIO scores were associated with improved survival after tricuspid surgery (Figure 1C).

Conclusions

Patients with higher TRIO scores have more postoperative complications, require longer hospital stay and have higher all-cause mortality at long-term follow-up. Our findings suggest that TRIO score may also be used for risk stratification in patients considered for surgical management of isolated functional TR.
Characteristics, risk factors and outcomes of patients managed for left-sided infective endocarditis: a prospective study in a high-volume center
Authors: Granger C , Elegamandji B , Mihoubi K , Mertens E , Bouziri N , Guedeney P , Lebreton G , Demondion P , Bleibtreu A , Collet J P , Montalescot G , Hekimian G , Hammoudi N
Published: November 2023

Background

Although medical and surgical management of infective endocarditis (IE) have improved in the recent decades, the associated mortality remains high. Available prospective data are scarce, and further knowledge from prospective cohorts could help improving the prognosis of patients with IE.

Objective

To describe the characteristics and outcomes of left-sided IE and to determine the risk factors associated to in-hospital mortality in a high-volume center.

Methods

From 15 September 2020 to 15 February 2023, all patients with left-sided IE managed in a tertiary center of cardiology were included in this prospective, observational study. The diagnosis of IE was made according to current guidelines and management was collegially discussed by the endocarditis team. Determinants of in-hospital death were assessed using a multivariate logistic regression model including any covariate associated in univariate analysis (p<0.1).

Results

A total of 185 patients were included during the study period. Median age was 68 [56 – 76] years, 141 (76%) patients were males, and 75 (41%) cases involved a prosthetic valve. Aortic valve, mitral valve and involvement of both valves were observed in 111 (60%), 48 (26%) and 26 (14%) patients, respectively. Multimodal cardiac imaging, including cardiac computed tomography (CT) and/or PET-FDG, was used in 64 (35%) of all cases, and 49/75 (65%) patients with valvular prosthesis. Severe valvular regurgitation was identified in 56 (30%) patients, root abscess and/or false aneurysms in 57 (31%) patients. A pathogen agent was identified in 169 (91%) patients, and the most frequent germs were Staphylococcus (30%), Streptococcus (30%) and Enterococcus (17%). A severe initial presentation requiring intensive care unit (ICU) admission was observed in 42 (23%) patients. Cardiac surgery was performed in 102 (55%) cases, and 41 (22%) patients required an emergent surgery. A total of 37 (20%) patients died during the initial in-hospital phase, mostly from cardiac or neurovascular causes. In a multivariate analysis, hypertension (Odd ratio (OR) = 3.3; 95% confidence interval (CI): 1.4 – 10), bi-valvular endocarditis (OR = 3.1; 95%CI: 1.0 – 9.5), unidentified pathogen (OR = 4.3; 95%CI: 1.7 – 15) and chronic alcoholic abuse (OR = 16.4; 95%CI: 3.7 – 87.9) were independently associated with increased in-hospital mortality (Table).

Conclusion

Severe initial presentation requiring an ICU admission and/or urgent cardiac surgery was common among patients with left-sided IE. Chronic alcoholic abuse and unidentified pathogen appear as major determinants of in-hospital mortality.Table
Association of anticoagulation with outcomes in patients with infective endocarditis
Authors: Sheng S , Tao M , Ghosalkar D , Despotidis G , Liu Y , Dhaliwal S , Rahman T
Published: November 2023

Background

Infective endocarditis (IE) is a disease that is associated with high risk of morbidity and mortality. The utility of systemic anticoagulation (AC) in patients with IE has not been well defined. The purpose of this meta-analysis is to evaluated the utility of AC in patients with IE.

Methods

A literature search was conducted for studies reporting on the use of AC in patients with IE and clinical endpoints. The primary endpoint was all neurological complications. Secondary endpoints included all-cause mortality, ischemic cerebral vascular accident (CVA), and hemorrhagic CVA. Databases searched included Ovid MEDLINE, EMBASE, Web of Science, and Google Scholar. The search was not restricted by time or publication status.

Results

A total of 12 studies with 9,063 participants with IE (1994 on AC, 7069 not on AC) met inclusion criteria. Mean age was 58 years, 65.8% were men, 20.9% had prosthetic valves. There was no statistically significant difference in risk of neurological complications in patients on AC compared to patients not on AC (OR 0.88, 95% CI 0.68-1.12; p=0.30). There was a trend towards increased risk of all-cause mortality in patients treated with AC compared to patients not on AC (OR 1.27, 95% CI 0.99-1.63; p=0.06). Patients on AC had significantly higher risk of hemorrhagic CVA compared to patients not on AC (OR 1.51, 95% CI 1.05-2.19; p=0.03). There was no statistically significant difference in risk of ischemic CVA in patients on AC compared to patients not on AC (OR 1.10, 95% CI 0.89-1.37; p=0.37).

Conclusions

Use of anticoagulation in patients with infective endocarditis is not associated with reduction in risk of neurological complications and may increase risk of all-cause mortality and hemorrhagic CVA. Further high quality studies are required to further characterize the use of anticoagulation in this disease process.
Initiation of warfarin is associated with decreased mortality in patients with infective endocarditis: a population based cohort study
Authors: Lee T , Chan C L , Chou O H I , Lee S , Chan J S K , Liu T , Chang C , Wong W T , Lip G , Cheung B Y M , Wai A K C , Tse G
Published: November 2023

Background

The use of warfarin as an anticoagulant to prevent thromboembolism in setting of infective endocarditis (IE) remains controversial due to increased bleeding risks.

Purpose

To study the risks of stroke, mortality and bleeding in warfarin users compared with non-use.

Methods

Patients aged 18 or older and diagnosed with IE in our city between January 1st 1997 and August 31st 2020 were included. Patients with use of any anticoagulant 30 days before IE diagnosis were excluded. Patients initiated on warfarin within 14 days of IE diagnosis and patients without warfarin use were matched using propensity scores (1:1 ratio). The study outcomes were ischemic stroke, all-cause mortality, intracranial hemorrhage, and gastrointestinal bleeding. Cox proportional hazards regression was used to determine the hazard ratios [95% confidence intervals (CIs)] for the predictors of study outcomes at the end of 90-day follow up.

Results

The matched cohort consisted of 675 warfarin users (57.0% male, age 59±16 years, mean CHA2DS2-VASc score: 1.42±1.72) and 675 warfarin non-users (53.5% male, age 61±19 years, mean CHA2DS2-VASc score: 1.58±1.76). Warfarin use was not associated with ischemic stroke risk (Hazard ratio: 1.04 [95% CI, 0.70-1.53]), but was associated with a 50% decreased risk of all-cause mortality (HR: 0.50 [0.39-0.65]). In terms of bleeding risk, intracranial hemorrhage occurred in 36 (5.3%) warfarin users and in 29 (4.3%) patients warfarin non-users, and gastrointestinal bleeding occurred in 27 (4.0%) warfarin users and in 26 (3.9%) warfarin non-users.

Conclusions

Warfarin use is associated with decreased risks of mortality but similar risks of ischemic stroke compared with non-use of warfarin in patients with IE.Kaplein Meier curves of study outcomes
Myocardial injury causes changes in the transcriptional and regulatory landscape of adaptive immune cells in the heart
Authors: De Winter N , Ji J , Sintou A , Sirvastava P , Sattler S
Published: November 2023

Background

Ischaemic heart disease is a leading cause of heart failure (HF) and despite advanced therapeutic options, morbidity and mortality rates remain high. Acute inflammation after myocardial infarction (MI) has been thoroughly studied in recent years and persistent immune-mediated damage has been suggested as a factor contributing to the development of HF. T and B cells are critical mediators of adaptive immune responses after MI, however a thorough analysis of their transcriptomic phenotypes in the heart at baseline and over time after injury are missing.

Purpose

Here, we aim to understand the transcriptional activity of B and T cells in the post-MI heart, in order to characterize their role in maintaining post-MI autoreactivity.

Methods

We obtained single cell RNA sequencing data of mouse and human hearts from Forte et al (2020), Martini et al (2019) and Litviňuková et al (2020) and performed differential expression analysis, gene regulatory inferences and trajectory-based differential expression analysis.

Results

Myocardial T cells subclustered into CD8+, CD4+, CD20+ and NK lineages with naïve, memory and effector functions (Fig. 1). The B cell population was divided into immature, plasma, memory, collagen-producing and B1 cell subgroups (Fig. 2). At baseline, despite a striking presence of effector populations, both B and T cells are governed by homeostatic and tolerance-promoting transcription factors (Deaf1, Ikzf1 and Nr1h3 for T cells and Spi-B as well as Bcl11 for B cells). Post-MI, the activity of transcription factors concerned with differentiation and proliferation increased. T cells express transcripts for proinflammatory chemokines and cytokines (Ccr7, Ccl5, Ifng and Tnf) as well as granzymes and perforin up until 28 days post-MI (Gzma and Prf1). Surprisingly, B cells upregulate collagen transcript levels 5-7 days post-MI (Col1a, Col5a, and Col4a) and regulon analysis supports that B cells increase the activity of transcription factors necessary for collagen production (Ets-1 and Krox20). Both B and T cells remain persistently activated post MI. 28 days post-MI T cells have increased activity of proinflammatory (Nfkb1) and cytokine producing (Crem and Rel) transcription factors, whereas B cells have increase maturation (Nfkb1), autoantibody production (Stat3 and Rel) and memory (Stat5b) transcription factor activity.

Conclusion

Collectively, our data shows that there are effector immune cell populations present at baseline, which are governed by homeostatic transcription factors. Post-MI, effector transcription factors are upregulated in both T cells and B cells, which promote proliferation, differentiation, cytokine production and in the case of B cells, collagen production. Even after resolution of acute inflammation, both the T and B cell population do not return fully to baseline but remain at a state of persistent activation, as effector transcription factors remain upregulated.
Heart rate and ejection fraction as prognostic markers in recurrent pericarditis
Authors: Yesilyaprak A , Kumar A , Agrawal A , Furqan M , Verma B , Akyuz K , Syed A , Majid M , Wang T , Cremer P , Klein A
Published: November 2023

Background

Heart rate (HR) and left ventricular ejection fraction (LVEF) are both important markers in assessing symptom improvement in patients with recurrent pericarditis (RP). However, their prognostic significance in predicting RP outcomes remains largely unexplored, as no prior studies have investigated this relationship.

Methods

Patients with RP were identified from a pericardial database covering the period between 2012 and 2019. The outcome of interest was clinical remission, which was defined as the resolution of symptoms without any further recurrences after discontinuing all anti-inflammatory therapies.

Results

A total of 365 patients were included in this study, of which the majority were females (56%) and less than 55 years old (68%). The mean number of recurrences at baseline was ≥4 in 158 (43%) of patients. The time to clinical remission was 24 months in the low HR group (HR ≤ 70 bpm), 60 months in the moderate HR group (HR: 71-90 bpm), and could not be determined for the high HR group (HR ≥ 90 bpm) due to few events. Patients with LVEF < 60% took 56 months to achieve clinical remission, compared with patients with LVEF ≥ 60%, who took over 60 months. Multivariable analysis revealed that patients in the high (HR: 0.22, 95% CI: 0.09-0.51, p=<0.001) and moderate (HR: 0.39, 95% CI: 0.21-0.75, p=0.005) HR groups were less likely to achieve clinical remission than those in the low HR group. Similarly, patients with LVEF ≥ 60% were less likely to achieve clinical remission than those with LVEF < 60% (HR: 0.54, 95% CI: 0.36-0.80, p=0.002).

Conclusion

Both HR and LVEF play important roles in prognosticating outcomes in patients with RP. The significance of both markers can be attributed to the heightened shear stress on the pericardium, which can exacerbate inflammation.Multivariable analysis
Late gadolinium enhancement following Covid-19 infection does not predict outcome: a single-centre study
Authors: Vimalesvaran K , Howard J P , Zaman S , Ariff B , Bharath A A , Cole G
Published: November 2023

Background

Some patients are found to have myocardial scarring after infection with coronavirus-2019 disease (COVID-19) as evidenced by the presence of late gadolinium enhancement on cardiac MRI (CMR). In many types of heart disease, the presence of late gadolinium enhancement (even without symptoms) is associated with a poorer prognosis. However, it is not known whether the presence of scar after COVID-19 is associated with outcome.

Purpose

This study explores the association between late gadolinium enhancement (LGE) in recovered patients with COVID-19 and of longer-term clinical outcomes.

Methods

In this single-centre, retrospective, observational cohort study, troponin levels, CMR data, and follow-up outcomes of 169 patients with COVID-19 were collected. The primary outcome was all-cause mortality. The secondary outcome was a composite of myocardial infarction, stroke, and admission for heart failure. The log-rank test was used to compare survival of those with and without late gadolinium enhancement.

Results

A total of 169 patients (mean age 61 ± 16 years, 54% male) were included. Scans were typically performed in patients with a raised troponin or ongoing cardiac symptoms post COVID-19 infection. The median (IQR) time between COVID-19 diagnosis and CMR was 14 (7-23) weeks. Median follow-up was 28 (IQR 23 to 37) months. Troponin was performed in 92% (n=155) of patients. Of those, 78% (n=121) had a positive result.

Late gadolinium enhancement was present in 54 patients (32%). There were no observed differences in comorbidities such as hypertension, known ischaemic heart disease or heart failure, diabetes, obesity, or frailty between in patients with LGE compared to those without LGE. Kaplan-Meier survival analysis showed no significant difference in all cause mortality for patients with COVID-19 with LGE compared to those without LGE (Log-rank P = 0.36). Similarly, the composite secondary endpoint was not significantly different (Log-rank P = 0.48).

Conclusion

In this single centre study, patients found to have myocardial LGE after COVID-19 did not have an increased risk of mortality or cardiovascular events compared to those without. The overall event rates remain low even after 2-3 years of follow-up. The cause of this is unclear but underlines the importance of larger multicentre studies to follow-up COVID-19 survivors.
Natural history and predictors of all-cause mortality and major arrhythmic cardiac events in pediatric RASopathy associated hypertrophic cardiomyopathy
Authors: Boleti O , Field E , Norrish G , Bhole V , Uzun O , Daubeney P E F , Mcleod K , Ilina M , Bharucha T , Delledonne G , Jones C , Mathur S , Reinhardt Z , Prendiville T , Kaski J P
Published: November 2023

The RASopathies are a group of developmental disorders caused by germline variants in components of the RAS-MAPK pathway, commonly associated with hypertrophic cardiomyopathy (HCM). The aim of this study was to describe the natural history and predictors of all-cause mortality and major arrhythmic cardiac events (MACE) in a large, multi-centre cohort of paediatric patients with a RASopathy syndrome and HCM.

One-hundred-and-forty-nine patients were included (111 (74.5%) Noonan Syndrome (NS); 12 (8.05%) Noonan Syndrome with Multiple Lentigines (NSML); 6 (4.03%) Costello Syndrome (CS); 6 (4.03%) Cardiofaciocutaneous Syndrome (CFCS); and 14 (9.4%) with Noonan-like syndrome patients). NSML patients had higher maximal left ventricular wall thickness (MLVWT) (z score 17.02 (10.57-32.78), p=0.004] and higher left ventricular outflow tract (LVOT) gradient values (60mmHg, 36-80, p=0.019), with no other significant echocardiographic differences between RASopathy syndromes. Over a median follow up of 197.5 months (93.58-370), 23 patients (15.43%) died, at a median age of 48.94 months (3.29-175.84). Overall survival was 96.45% (91.69-98.51), 90.42% (84.04-94.33) and 84.12 (75.42-89.94) at 1, 5 and 10 years, respectively, but this was varied according to RASopathy syndrome. RASopathy syndrome, specifically Noonan-like syndrome (Hazard ratio 4.18, p=0.032) and congestive cardiac failure admission (Hazard ratio 7.35, p=0.037) were independent predictors of all-cause mortality and LVOT gradient was an independent predictor for MACE (Hazard ratio 1.02, p=0.025). These findings highlight a distinct category of patients with Noonan-like syndrome with a milder HCM phenotype but significantly worse survival and identify predictors of adverse outcome in patients with RASopathy-related HCM.