bluuebunny/crossref_metadata_2025 huggingface dataset:
Platelet membrane-coated nanoparticles target sclerotic aortic valves in ApoE−/− mice by multiple binding mechanisms under pathological shear stress
Authors: Yang H , Song Y , Huang Z , Qian J , Pang Z , Ge J
Published: November 2020

Background

Aortic valve disease is the most common valvular heart disease leading to valve replacement. The efficacy of pharmacological therapy for aortic valve disease is limited by the high mechanical stress at the aortic valves impairing the binding rate. We aimed to identify nanoparticle coating with entire platelet membranes to fully mimic their inherent multiple adhesion mechanisms and target the sclerotic aortic valve of apolipoprotein E-deficient (ApoE−/−) mice based on their multiple sites binding capacity under high shear stress.

Methods

Considering the potent interaction of platelet membrane glycoproteins with components present in sclerotic aortic valves, platelet membrane-coated nanoparticles (PNPs) were synthetized and the binding capacity under high shear stress was evaluated in vitro and in vivo.

Results

Compared with PNPs bound intensity in the static station, 161%, 59%, and 39% of attached PNPs remained adherent on VWF-, collagen-, and fibrin-coated surfaces under shear stress of 25dyn/cm2 respectively. PNPs demonstrated effectively adhering to von Willebrand factor, collagen and fibrin under shear stresses in vitro. In an aortic valve disease model established in ApoE−/− mice, PNPs group exhibited significant increase of accumulation in the aortic valves compared with PBS and control NP group. PNPs displayed high degrees of proximity or co-localization with vWF, collagen and fibrin, which exhibited good targeting to sclerotic aortic valves by mimicking platelet multiple adhesive mechanisms.

Conclusion

PNPs could provide a promising platform for the molecular diagnosis and targeting treatment of aortic valve disease.

Targeting combination

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): National Natural Science Foundation of China
Platelet reactivity in patients with aortic stenosis depends on LV-AO angle
Authors: Mourikis P , Zako S , Dannenberg L , M'Pembele R , Hohlfeld T , Zeus T , Kelm M , Veulemans V , Polzin A
Published: November 2020

Background

The pathogenesis of aortic stenosis (AS) is not fully understood. However, local inflammation of the valve appears to be a main player. Except haemostasis, platelets contribute to inflammatory processes in various ways. Furthermore, platelet function is altered in patients with AS. Moreover, a steep angle between the left ventricle and the aorta (LV-AO-angle) leads to turbulent blood flow. However, it is not known if platelet reactivity is associated with steep LV_AO angle in patients with AS.

Methods

We included 289 patients with severe AS and performed cardiac computertomography to assess the LV-AO-angle. Platelet function was evaluated by light transmission aggregometry by using collagen and adenosine-diphosphate to induce platelet activation

Results

ADP- and collagen induced aggregation showed a significant negative correlation with LV-AO-angle (ADP: r=−0.19, p=0.0009, R2=0.022; collagen: r=−0.21, p=0.0004, R2=0.027). ADP-induced MoA was significant higher in patients with a LV-AO-angle <160° in comparison to patients with an angle ≥160° (<160°: 66.99±20.72% vs. ≥160°: 60.66±19.85%, p=0.009). Collagen-induced platelet reactivity was significant higher in patients with a LV-AO-angle <160° in comparison to patients with an angle ≥160° (<160°: 78.67±13.19% vs. ≥160°: 73.85±14.44%, p=0.003). Multivariate cox-regression revealed that LV-AO angle <160 was a robust predictor of ADP- and collagen-induced platelet aggregation

Conclusion

A steep LV-AO-angle is associated with enhanced platelet reactivity in patients with AS. Platelet activation is known to lead to local inflammation. Therefore, enhanced platelet reactivity could play crucial in the progression of AS. The clinical significance of a steep LV-AO-angle needs be evaluated in further trials.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): German Research Foundation
Preserved Th2 lymphocytes improve prognosis of diabetic patients undergoing TAVR
Authors: Hoffmann J , Berkowitsch A , Mas-Peiro S , Boeckling F , Rasper T , Dimmeler S , Zeiher A.M , Vasa-Nicotera M
Published: November 2020

Introduction

Previous studies have shown that presence of diabetes (DM) worsens outcome of patients after transfemoral aortic valve (TAVR). DM has been associated with pathological T-lymphocyte (T-cell) polarization, marked by decreased anti-inflammatory Th2 cells and increased pro-inflammatory Th1 cells. However, the risk-modulatory impact of T-cell polarization in diabetic patients with severe aortic stenosis has not been shown thus far. In this study we assessed the role of T-cell subsets in diabetic patients undergoing TAVR.

Methods and results

A total of 129 patients (76% male, median age [IQR]: 83 years [79–86]) admitted for TAVR at the University Clinic Frankfurt were enrolled. The patients were evaluated using classical risk scores and the Th1/Th2 T-cell polarization was assessed using flow cytometry. The endpoint of the study was all-cause death. Kaplan-Meier survival, ROC curve analysis and Mann-Whitney-U-Test were used in statistical analysis. The differences were considered significant by error probability p<0.05. Twenty-six patients died within follow up of 274 (188–367) days. The conventional risk parameters were distributed as follows: STS score: 3.45 (2.47–4.97), LVEF: 60% (45–65), CRP: 0.33 mg/dl (0.15–0.79), hsTropT: 24.5 pg/ml (16.5–40.0), IL6: 6.7 pg/ml (4.1–12.2), Hb: 12.3 g/dl (11.00–13,75), Creatinine: 1.15 mg/dl (0.93–1.54), Th1 cells = 79.88 cells/μl (55.69–122.16), Th2 cells: 25.31 cells/μl (19.69–38.33), NT-proBNP: 2033 pg/ml (1076–5531). All these parameters were associated with mortality. Hence, only Hb (AUC=0.761), NT-proBNP (AUC=0.726), Th2 cells (AUC=0.712) and STS score (AUC=0.737) provided AUC>0.7. Diabetes was revealed to be significantly associated with mortality in patients with and without DM (15/48 (31%) vs. 11/81 (14%), respectively, P=0.019). There were no significant differences in the counts of Th-cell subsets between diabetic and non-diabetic patients (Th1 (90.95 (62.41–154.22) vs 76.36 (53.16–100.49), P=0.072); Th2 (29.18 (20.13–43.77) vs 24.74 (20.27- 35.11), p=0.245), for DM and non-DM respectively). However, the survival rate in patients with DM and Th2 cell counts higher than or equal to the calculated optimal cut-off of 24.3 cells/μl was comparable with patients without DM (25/28 (89%) vs. 36/38 (95%), p=0.453). In contrast, diabetic patients with reduced Th2 cells (<24.3 cells/μl) were much more likely to die (10/15 (67%) vs. 8/34 (24%), p=0.003, patients with DM and without, respectively).

Conclusion

Our results show for the first time a risk-modulatory impact of T-cell immunity in diabetic patients with severe degenerative aortic stenosis. Reduced Th2 cells are strongly associated with mortality in patients considered for TAVR and significantly deteriorate prognosis in patients with concomitant diabetes.

Funding Acknowledgement

Type of funding source: None
Co-existing aortic regurgitation associated with adverse clinical outcomes in patients with moderate to severe aortic stenosis
Authors: Ngiam N , Chew N , Sia C.H , Tan B.Y.Q , Sim H.W , Kong W.K.F , Tay E.L.W , Yeo T.C , Poh K.K
Published: November 2020

Background

Aortic regurgitation (AR) is a common comorbidity in patients with aortic stenosis (AS), but co-existing AR has often been an exclusion criterion from major clinical trials. The impact of co-existing AR on the natural history of AS has not been well-described.

Purpose

We compared clinical outcomes in patients with moderate to severe AS with or without co-existing AR.

Methods

Consecutive patients (n=1188) with index echocardiographic diagnosis of moderate to severe AS (AVA <1.5cm2) were studied. They were divided into those with co-existing AR (at least moderate severity) and those without. Adverse composite clinical outcomes were defined as either mortality or admissions for congestive cardiac failure on subsequent follow-up for at least five years. Appropriate univariate and multivariable analyses were employed to compare the two groups.

Results

There were 88 patients (7.4%) with co-existing AR and AS. These patients did not differ significantly in age, but had lower body mass index (22.9±3.8 vs 25.3±5.1 kg/m2). They also had lower diastolic blood pressure (68.7±10.7 vs 72.2±12.3 mmHg), larger end-diastolic volume index (68.8±18.8 vs 60.4±17.8 ml/m2) and left ventricular mass index (118.6±36.4 vs 108.9±33.1 g/m2). The prevalence of cardiovascular risk factors did not differ significantly between the groups. Co-existing AR was associated with adverse outcomes (log-rank 4.20, p=0.040). On multivariable Cox-regression, co-existing AR remained independently associated with adverse outcomes (hazard ratio 1.51, 95% CI 1.13–2.02) after adjusting for age, AS severity and left ventricular ejection fraction.

Conclusion

In patients with AS, co-existing AR was associated with a distinct echocardiographic profile and adverse outcomes.

Funding Acknowledgement

Type of funding source: None
Right ventricular function and systolic pressure effect on survival of patients with tricuspid regurgitation
Authors: Vaturi O , Itelman E , Kuperstein R , Fefer P , Barbash I.M , Klempfner R , Segev A , Feinberg M , Guetta V , Maor E
Published: November 2020

Severe tricuspid regurgitation (TR) is associated with poor outcome. The current analysis investigated the long term outcome of TR patients.

Methods

Historical retrospective cohort of all cardiovascular patients evaluated at a tertiary heart center between 2007 and 2019. The current analysis included all patients who underwent echocardiographic evaluation. TR severity was extracted for all patients from the echocardiographic reports. Primary outcome was all cause mortality and was available for all patients from the national population register.

Results

Final cohort included 97,561 subjects, of whom 42,187 (43%) were outpatients. Mean age was 66±17 and 55,976 (57%) were men. Mild, moderate and severe TR was documented in 27,389 (28%), 2,871 (3%) and 1,812 (2%) patients, respectively. During a median follow up of 50 months [IQR 22–83] 18,476 (19%) patients died. Kaplan-Meier survival analysis demonstrated increased risk of death with increasing degree of TR (FIGURE; p Log rank <0.001). Multivariate cox regression with adjustment to age, gender, BMI and echocardiographic predictors of adverse outcome showed that compared with no or mild TR, patients with moderate or severe TR were 10% and 45% more likely to die (95% CI: 1.02–1.18, p=0.009 and 1.34–1.57 p<0.001 respectively). Interaction analysis with adjustment to known predictors of poor survival demonstrated that the association of severe TR with survival was dependent on right ventricle (RV) dysfunction and estimated RV systolic pressure (RVSP) with a more pronounced effect on patients with severe RV dysfunction (HR of 1.38 [1.07–1.80] vs. 1.09 [1.00–1.19], p for interaction = 0.01) and a more pronounced effect on patients with estimated RVSP <40 mmHg (HR of 1.60 [1.21–2.11] vs. 1.14 [1.03–1.25], p for interaction <0.001). Finally, a propensity score matching of patients with severe TR (N=1,154) and matched controls with no or mild TR successfully demonstrated that patients with severe TR were 27% more likely to die during follow up (95% CI: 1.14–1.42, p<0.001).

Conclusions

Severe TR is independently associated with poor survival. The association is modified by RV dysfunction and estimated RVSP. This report supports the need for studies to evaluate TR interventions on patients' clinical outcomes.

Kaplan Meier Survival Curves

Funding Acknowledgement

Type of funding source: None
Prolonged Tp-e interval and Tp-e/QT ratio in patients with mitral annulus disjunction
Authors: Okutucu S , Fatihoglu S.G , Bursa N , Aksoy H , Yetis Sayin B , Oto A
Published: November 2020

Background

Mitral annulus disjunction (MAD) is an abnormal atrial displacement of the mitral valve leaflet hinge point. MAD has been associated with mitral valve prolapse (MVP) and arrhythmic events. T-wave peak to T-wave end interval (Tp-e) and Tp-e/QTc are electrocardiographic (ECG) indices to predict ventricular tachyarrhythmia and cardiovascular mortality.

Purpose

We aimed to evaluate ventricular repolarization dispersion by using the Tp-e interval and Tp-e/QT ratio in patients with MAD and healthy controls.

Methods

A total of 35 patients with MAD (age 40.4±8.2 years; 66% female) and 37 healthy controls (age 37.6±9.5 years; 68% female) were enrolled. All subjects were evaluated by 12 lead standard ECG, 24-hour ambulatory ECG, and transthoracic echocardiography. The MAD distance was measured from the left atrial wall-mitral valve leaflet junction to the top of the left ventricular wall during end-systole in the parasternal long-axis view. The standard 12-lead electrocardiograms were analyzed; QTc, Tp-e and Tp-e/QTc were calculated. The Tp-e interval was defined as the interval from the peak of the T wave to the end of the T wave from precordial leads. Finally, the Tp-e/QT ratio was calculated from these measurements. The normality assumption was checked with the Shapiro-Wilk test and the Mann–Whitney U test was used for inter-group comparisons.

Results

Tp-e interval (61.9±6.0 ms vs. 77.1±5.9 ms, p<0.001) and Tp-e/QT ratio (0.14±0.01 vs. 0.17±0.02, p<0.001) were significantly prolonged in patients with MAD than in the control group. MVP was present in 24 (69%) patients with MAD. The prevalence of 30 premature ventricular contractions / hour were higher in MAD subgroup without MVP than those MAD with MVP (54.5% vs 16.7%, p=0.041). Mean MAD distance measured by echocardiography was 5.7±1.5 mm. The Spearman's rank-order correlation analyses revealed positive correlations of MAD distance with Tp-e interval (r=0.620, p=0.001) and Tp-e/QT ratio (r=0.372, p=0.028).

Conclusions

The patients with MAD had a prolonged Tp-e interval and Tp-e/QT ratio compared with normal subjects. Furthermore, this prolongation was well correlated with MAD distance. Patients with MAD, particularly with higher MAD distance, should be followed closely for arrhythmic outcomes.

MAD distance and Tp-e interval

Funding Acknowledgement

Type of funding source: None
Impact of sex on management and survival in aortic stenosis
Authors: Bohbot Y , Rusinaru D , Belkhir K , Altes A , Delpierre Q , Serbout S , Levy F , Marechaux S , Sarano M , Tribouilloy C
Published: November 2020

Background

Increasing attention has been paid to differences between the sexes in recent studies, but only a few have focused on such differences in aortic stenosis (AS).

Purpose

We sought to evaluate the differences between genders in AS outcomes and management.

Methods

We included 2429 patients (51.5% men; 49.5% women) with severe AS. Median follow-up was 42.0 (21–78) months.

Results

Women were older (p<0.001), more often symptomatic (p=0.007), and presented with smaller aortic valve area (p<0.001), and greater ejection fraction (p<0.001) than men. Despite that women have a longer life expectancy than men in the general population, estimated five-year survival of patients with severe AS was lower for women compared to men (62±2% versus 69±1% respectively, p<0.001). The 5-year survival was lower compared to expected survival, especially for women (62±2% vs. 71% for women and 69±1% vs. 71% for men). The cumulative 5-years incidence of AVR was 79±2% for men, and only 70±2% for women (p<0.001) and, being male was independently predictive of AVR (OR: 1.49 [1.18–1.97]; p=0.011). After propensity matching, when both genders were comparable in terms of characteristics and management (AVR), women, as expected due to their higher life expectancy than men, had better 5-year survival than men (69±2% vs. 62±2%; p=0.023).

Conclusion

Women with severe AS present at a more advance stage of the disease, at older ages with more symptoms, and incur higher mortality than men. This excess mortality is related to a combination of late diagnosis and a less frequent and later referral for AVR than in men. This justifies appropriate measures to improve the situation and to ensure that both sexes receive equivalent care.

Figure 1. (A) Survival curves. (B) Surgery incidence.

Funding Acknowledgement

Type of funding source: None
Lifelong cumulative incidence of acquired aortic stenosis and its predictors in a large middle-aged men population followed up to 42 years
Authors: Kontogeorgos S.M , Thunstrom E , Lappas G , Rosengren A , Fu M
Published: November 2020

Background

Acquired aortic stenosis (AS) is the most common valvular disorder that rises exponentially with age; it has high mortality after symptoms appear. Factors that predict the development of AS are still unknown. Some studies imply that the atherosclerotic factors are involved in the development of AS, but the findings have been heterogeneous.

Purpose

To estimate lifelong cumulative incidence of AS and analyse its predictors.

Methods

We included a random sample of men, born 1915–1925 in Gothenburg, Sweden, and examined them in 1970–1973 (participation rate 75%). They were between 47 and 55 years in the beginning and 57–65 years when the examination-period ended. Out of 7493 men 57 were excluded due to myocardial infarction prior to baseline; 7436 were thus followed from the inclusion date until a discharge diagnosis of AS or death, with a maximum follow up time of 42 years and mean follow-up time 26.8 years. Men with AS were identified from the Swedish National Patient Register and those who died from the Swedish Cause of Death Register. We used machine learning to identify the most important factors that predict AS. For these factors, we then estimated hazard ratios for the risk to acquire AS through Cox proportional hazards model.

Results

The lifelong cumulative incidence to acquire AS was 2.66% (198 out of 7436 individuals). For men with measurements approximately at the quartiles of the pulse pressure distribution, more specifically 44, 52, 62 mm Hg, the estimated cumulative risk were 1.97%, 2.74% and 3.07% respectively. For the body mass index (BMI) we had accordingly for measurements around 23, 25 and 27 kg/m2 estimated cumulative risk 2.52%, 2.80%, 2.79% respectively. For cholesterol values of 5, 6 and 7 mmol/l (approximately at quartile divisions) the estimated cumulative risk was 1.77%, 1.79% and 3.20% respectively. The estimated cumulative risks for the younger, with age around 47 and the older participants, with age around 55 were 1.76% and 2.68 respectively. Men with family history of infarction in a sibling had an estimated cumulative risk at 4.66% level whereas those with not at 2.51%.

The factors that were significantly associated with the development of AS in the Cox proportional model are: cholesterol level (HR=1.24, CI 95% 1.11–1.39, p=0.0001), pulse pressure (HR=1.01, CI 95% 1.01–1.02, p=0.0037), BMI (HR=1.06, CI 95% 1.02–1.11, p=0.0089), age (HR=1.11, CI 95% 1.04–1.19, p=0.0010) and family history of myocardial infarction in a sibling (HR=2.38, CI 95% 1.50–3.79, p=0.0002).

Conclusion

Lifelong cumulative incidence of acquired AS is approximately 2.7%. Multiple factors known also to be associated with arteriosclerosis were identified to increase the life-long risk of developing AS.

Funding Acknowledgement

Type of funding source: None
CMR fast-SENC segmental intramyocardial LV strain monitors decline in heart function before ejection fraction in patient with mitral valve disease
Authors: Montenbruck M , Kelle S , Esch S , Schwarz A.K , Giusca S , Korosoglou G , Steen H
Published: November 2020

Background

Ejection fraction is the standard metric to analyze cardiac function in the left (LV) or right (RV) ventricles. However, these global metrics are not able to characterize patients in which the heart compensates for regional dysfunction. More sensitive metrics are needed to detect subclinical regional dysfunction before cardiac remodeling results in changes in ejection fraction (EF) and global longitudinal strain (GLS). Fast-SENC intramyocardial strain (fSENC) is a unique cardiac magnetic resonance imaging (CMR) modality that measures intramyocardial contraction in 1 heartbeat per image plane. This prospective registry compares segmental fSENC to standard CMR calculations (e.g. LVEF, volumes, mass, etc.) in patients with mitral valve disease.

Methods

A single center, prospective registry of CMR scans acquired with a 1.5T scanner were evaluated for standard CMR calculations as well as fSENC scans. Intramyocardial LV & RV strain was quantified with MyoStrain software. Three short axis scans (basal, midventricular, & apical) were used to calculate peak strain in 16 LV & 6 RV longitudinal segments while three long axis scans (2-, 3-, & 4-chamber) were used to calculate 21 LV & 5 RV circumferential segments.

Results

A total of 493 scans in 424 patients with moderate or severe mitral regurgitation were included in the study. Patients had an average (± stdev) age of 60 (15) yrs and BMI of 27 (4) kg/m2; 63% had arterial hypertension, 19% diabetes mellitus, 10% atrial fibrillation, 15% pulmonary disease, and 32% coronary artery disease. Figure 1 shows the non-linear relationship between segmental fSENC strain (% of normal LV segments ≤−17%) versus LVEF (R=0.81).

Conclusion

Segmental fSENC detects subclinical LV dysfunction before changes in LVEF. Evaluating segmental longitudinal and circumferential fSENC peak strain provides an alternative metric that shows consistent changes in cardiac function in patients with mitral valve disease irrespective of global calculations that are dependent on loading conditions.

Funding Acknowledgement

Type of funding source: None
Comparison of trans-catheter closure of paravalvular leak versus surgical approach-outcomes and cost analysis
Authors: Pu J , Wu W.H , Ke Y.T , Ma X.H , Huang L.J
Published: November 2020

Background

The outcomes and costs of trans-catheter closure (TC) of paravalvular leak (PVL) compared with surgical closure (SC) are rarely described.

Purpose

The aim of the study was to assess the outcomes and hospital costs of patients who underwent TC or SC of PVL in our center.

Methods

Patients who underwent TC and SC of PVL between Jan. 2016 and Dec. 2019 were enrolled. Baseline characteristics, procedural, in-hospital and mid-term outcomes and hospital costs were compared.

Results

A total of 141 patients were studied (TC, n=65 and SC, n=76). The patients were elder in TC group (56.8±12.8 years vs. 50.1±12.8 years, p=0.002). Technical success was higher in SC group (83.1% vs. 98.7%, p<0.001). Procedure room time (93±38 min vs. 395±132 min, p<0.001), intensive care unit time (0 h vs. 25 h, p<0.001), length of stay from hospitalization to discharge (7 days vs. 21 days, p<0.001) and costs (¥45090±19343 vs. ¥164165±94300, p<0.001) were significantly less in TC group. After risk adjustment, there was no significant differences between in 30 days survival between TC group and SC group. However, the residual PVLs were less in SC group (43.1% vs. 12.0%, p=0.012). At a median follow-up of 21 months, there was a trend towards reduce all-cause death following TC versus SC (OR=0.054, 95% CI: 0.070 to 0.445, p=0.007).

Conclusions

SC for PVL is associated with higher technical rates and less residual shunt. But, the shorter length of stay and lower resources use with TC group significantly reduce hospital costs. In addition, TC achieve a better mid-term results in survival.

Funding Acknowledgement

Type of funding source: None
P2Y12 inhibition by clopidogrel increases adverse clinical outcomes in patients undergoing transcatheter aortic valve replacement
Authors: Matsushita K , Marchandot B , Kibler M , Sato C , Heger J , Peillex M , Trimaille A , Hess S , Grunebaum L , Ohana M , Reydel A , Jesel L , Ohlmann P , Morel O
Published: November 2020

Introduction

Current recommendations support short-term dual antiplatelet therapy (DAPT) for patients undergoing transcatheter aortic valve replacement (TAVR) despite no relevant study exploring the extent of platelet inhibition by clopidogrel.

Purpose

To assess whether P2Y12 inhibition by clopidogrel as evaluated by vasodilator-stimulated phosphoprotein flow cytometry test (VASP-FCT) impacts 1-year clinical outcomes in patients undergoing TAVR.

Methods

Patients were included in a prospective registry between February 2010 and May 2019. VASP-FCT was assessed 24h after the procedure. Responder to clopidogrel was defined by a platelet reactivity index ≤50%.

Results

Of 640 patients who underwent TAVR with preprocedural clopidogrel therapy, we enrolled 491 patients for whom VASP data were available. Responders were identified in 22% (n=110) of patients and low responders were 78% (n=381) of patients. Low body mass index, active cancer, and clopidogrel on admission were found to be independent predictors of responder. Mean transaortic pressure gradient was lower in the responder group at 1-month post-TAVR (9.9±4.4 mmHg vs. 11.2±5.8 mmHg, p=0.03) but was similar at 1-year (11.5±6.2 mmHg vs. 11.9±7.4 mmHg, p=0.74). By multivariate Cox regression analysis, patients responding to clopidogrel (hazard ratio [HR]: 2.19; 95% confidence interval [CI]: 1.04 to 3.64; p=0.04), prior PCI (HR: 2.12; 95% CI: 1.07 to 4.37; p=0.03), and mean transaortic pressure gradient at baseline (HR: 0.07; 95% CI: 0.01 to 0.70; p=0.02) were identified as independent predictors of 1-year adverse clinical outcomes, including all-cause death, myocardial infarction, stroke, and heart failure hospitalization.

Conclusions

Appropriate P2Y12 inhibition by clopidogrel is a major determinant of adverse clinical events after TAVR. In sum, the present data challenges the need of DAPT as a standard therapy during TAVR.

Figure 1

Funding Acknowledgement

Type of funding source: None
Six-month and one-year outcomes with the PASCAL transcatheter valve repair system for patients with mitral regurgitation from the multicentre, prospective CLASP study
Authors: Spargias K , Szerlip M , Kar S , Makkar R , Kipperman R , O'Neill W , Ng M , Fam N , Rinaldi M , Smith R , Walters D , Schafer U , Latib A , Marcoff L , Webb J
Published: November 2020

Background

Transcatheter mitral valve repair has emerged as a viable option for treating mitral regurgitation (MR). We report results from the multicentre, prospective, single arm CLASP study with the PASCAL transcatheter valve repair system.

Methods

109 patients with clinically significant MR deemed candidates for transcatheter repair by the local heart team were treated in the CLASP study. The study evaluated safety, performance, clinical and echocardiographic outcomes and included an independent clinical events committee and echocardiographic core lab. The primary safety endpoint was a composite MAE rate at 30 days of cardiovascular mortality, stroke, MI, new need for renal replacement therapy, severe bleeding, and re-intervention for study device-related complications.

Results

Mean age was 76 years, 54% male, 57% NYHA Class III/IV, 100% MR grade ≥3+ with 62% functional, 31% degenerative, 7% mixed etiology. Successful implantation was achieved in 95% of patients. At 30 days, the MAE rate was 8.3% including one cardiovascular mortality due to cardiogenic shock as a result of severe bleeding at the contralateral arterial access site for hemodynamic monitoring further complicated by disseminated intravascular coagulation, one stroke, and one conversion to mitral valve replacement surgery. In paired analysis, 88% of patients were in NYHA Class I/II (p<0.001), MR grade was ≤1+ in 79% of patients and ≤2+ in 96% of patients. Significant improvements in 6MWD (+27 m, p<0.001) and KCCQ (+16 points, p<0.001) were observed. The six-month data will be available for presentation. In addition, we report one-year follow up of the first 62 patients (ITT): 93% one-year survival rate (Kaplan-Meier estimate), no stroke, no late reintervention, one late MI. In paired analysis, MR grade was ≤1+ in 82% of patients and ≤2+ in 100% of patients. 88% of patients were in NYHA Class I/II (p<0.001), 6MWD improved by 21 m (p=0.124) and KCCQ improved by 13 points (p<0.001).

Conclusions

This study demonstrates the PASCAL transcatheter valve repair system is safe and resulted in robust MR reduction with 100% of patients achieving MR ≤2+, and ∼ 80% MR ≤1+, sustained at one year. Results show high survival and low complication rates, and sustained improvements in functional status, exercise capacity, and quality of life at one year in patients with clinically significant, symptomatic MR. The CLASP IID/IIF pivotal trial is underway.

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Edwards Lifesciences (Irvine, CA)
Copeptin as a novel biomarker for detecting early renal dysfunction after TAVI
Authors: Wolter J.S , Reifart J , Renker M , Kriechbaum S.D , Fischer-Rasokat U , Baumgarten H , Schmidt S , Nef H , Doerr O , Kim W.K , Hamm C.W , Keller T , Hocher B , Liebetrau C
Published: November 2020

Background

Acute kidney injury (AKI) is one of the most prevalent (10–30%) complications after transcatheter aortic valve implantation (TAVI). Furthermore, AKI is accompanied by increased mortality, a higher incidence of dialysis and blood transfusion, and a prolonged hospital stay. Although measurement of serum creatinine is the gold standard in diagnosing AKI, changes in serum creatinine may lag behind compromised renal function. Arginine vasopressin (AVP), or antidiuretic hormone, is a nine-amino acid peptide member of the hypothalamo-neurohypophysial axis. Copeptin is the C-terminal moiety of the AVP precursor pre-proAVP that is secreted into the circulation. Recently, copeptin has been suggested to play a role in chronic kidney injury. We evaluated the value of copeptin in the prediction of AKI in patients undergoing TAVI.

Methods

All patients with severe aortic valve stenosis undergoing TAVI between May 2011 and May 2016 were included in our study. AKI was defined by the VARC-2 definition. Patients with no AKI and stage 1 AKI were compared with patients with stage 2 or 3 AKI. Routine laboratory parameters, including creatinine, were measured immediately after blood draw. Additionally, venous blood samples were collected on admission and after 24, 48, and 72 hours, processed immediately, and stored at −80°C until assay. The copeptin concentration in serum was measured by a sandwich immunoluminometric assay.

Results

Copeptin levels were available in 642 patients who were treated by TAVI in our centre from 2012–2016. AKI was detected in 113 patients (17.6%), including 61 patients with stage 1 (9.5%), 29 with stage 2 (4.5%), and 23 with stage 3 (3.6%).

There were no differences among these patients in baseline measurements, but serum copeptin increased in all patients with AKI 24 h post-procedure according to the AKI stage: no AKI 34.5 (18.0–59.3 pmol/L), AKI stage 1: 68.7 (34.6–130.1 pmol/L); AKI stage 2: 96.0 (48.1–185.1 pmol/L); AKI stage 3: 154.9 (79.5–280.7 pmol/L); ANOVA p<0.001 (Fig. 1). Copeptin showed an earlier and sharper increase than creatinine (Fig. 1), with a negative predictive value of 0.97 to rule out AKI after 24 h.

Conclusion

AKI subsequent to TAVI is a common and harmful complication that occurred in almost every 5th patient (17.6%) in our cohort. AVP is secreted in response to hypotension, which commonly occurs during TAVI. In our cohort of TAVI patients, those who developed AKI after TAVI showed a rapid increase in copeptin that was earlier than that of creatinine. In light of these observations, copeptin could be a new parameter for detecting early renal dysfunction.

Figure 1

Funding Acknowledgement

Type of funding source: None
Outcomes following self-expanding transcatheter or surgical aortic valve implantation in patients at low operative risk stratified by need for revascularization
Authors: Tonino P , Reardon M.J , Yakubov S , Deeb G.M , Popma J.J
Published: November 2020

Background

Self-expanding transcatheter aortic valve implantation (TAVI) was non-inferior to surgical aortic valve replacement (SAVR) in a randomized clinical trial of patients with severe aortic stenosis at low operative risk. Randomization was stratified by the need for revascularization, but it remains unclear how this has impacted the results of TAVI and SAVR.

Purpose

To compare TAVI and SAVR outcomes in a prespecified analysis according to the need for revascularization.

Methods

A total of 1403 patients underwent attempted TAVI (n=725) or SAVR (n=678) at 87 centres worldwide. Patients were deemed at low risk of early mortality (<3%) confirmed by a national screening committee. Patients were stratified by site and need for revascularization based on heart team assessment. The trial used a Bayesian study design for the 2-year primary analysis and an interim analysis was performed when 850 patients had reached 1-year follow-up.

Results

There were 85/725 (11.7%) TAVI patients and 79/678 (11.7%) SAVR patients identified as needing revascularization. Previous CABG had occurred in 3 (1.8%) patients and previous PCI had been performed in 31 (18.9%) patients. The baseline characteristics for the TAVI and SAVR cohorts are shown in the table. In the TAVI revascularization group, 44 of 85 (51.8%) received PCI concomitant or staged with TAVI and 6 of 639 (0.9%) received PCI in the no revascularization group. In the SAVR revascularization group, 65 of 79 (82.3%) underwent concomitant CABG and 27 of the 599 (4.5%) patients in the no revascularization group had concomitant CABG. Kaplan-Meier estimates of 1-year all-cause mortality or disabling stroke at the time of the interim analysis are provided for TAVI and SAVR patients by need for revascularization (Table).

Conclusions

The proportion of low-risk patients needing revascularization was small in this low risk population. The complete 1-year follow-up for the entire 1403 patient cohort will be available for presentation in August.

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Medtronic, plc
Impact of mitral annular calcification associated mitral stenosis on clinical outcomes in patients undergoing transcatheter aortic valve implantation
Authors: Mesnier J , Urena M , Nguyen C , Carrasco J.L , Terzian Z , Fischer Q , Brochet E , Iung I , Himbert D
Published: November 2020

Introduction

Mitral annular calcification (MAC) is a common finding in patient undergoing transaortic valve implantation (TAVI) and can cause significant mitral stenosis (MS).

Purpose

To assess the impact of MAC associated with significant MS (MAC-MS) on clinical outcomes following TAVR.

Methods

Consecutive patients undergoing TAVI in our institution between January 2008 and May 2018, were evaluated. All echocardiogram exams before intervention were analysed to identify the presence of MAC and MAC was confirmed on computed tomography (CT) scans. Patients were included in the MAC group if there was any calcification on the mitral annulus on CT scan. Severe MAC was considered as calcification of the mitral annulus involving over 50% of the circumference. Patients with a mitral mechanical valve or bioprosthesis and without CT scan available to confirm MAC were excluded (n=62). MAC-MS was defined as the association of MAC and a mean transmitral gradient over 5 mmHg.

Results

Among 1177 consecutive finally included patients, 504 (42.8%) had MAC and 85 had a MAC-MS (7.2%, 16.9% among the MAC population). Compared to MAC without MS (MAC non-MS group) and non-MAC patients, patients with MAC-MS were more frequently women (p<0.0001), had a greater BMI (p=0.002), more previous pacemaker implantation (p=0.035), smaller indexed aortic valve area and left ventricular end systolic diameter (p=0.019 and p=0.038). At 30-days after TAVR, there were no differences in stroke, major vascular complication and pacemaker implantation between groups. However, MAC-MS patients had higher rates of tamponade [Odd Ratio adjusted 3.12, 95% confidence interval (CI) 1.08–9.07, p=0.036] and mortality [Adjusted hazard Ratio (HRa) 2.83, 95% CI 1.39–5.76, p<0.005] after adjustment on baseline characteristics. At 1 year, patients with MAC-MS had a higher risk of death [19 (22.1%) vs. 142 (13%); HRa 1.83, 95% CI 1.14–3.03, p=0.01] compared to MAC non-MS and non-MAC patients. Severe MAC was not a predictor of 1 year mortality.

Conclusions

Mitral stenosis due to mitral annular calcification is infrequent in patient undergoing TAVI but is associated with higher early and mid-term mortality.

Funding Acknowledgement

Type of funding source: None
Effect of renin angiotensin system blockade following transcatheter aortic valve replacement is dose dependent
Authors: Ledwoch J , Olbrich I , Poch F , Thalmann R , Fellner C , Stundl A , Bradaric C , Laugwitz K.L , Kupatt C
Published: November 2020

Background

There is growing body of evidence from retrospective studies that inhibition of the renin angiotensin system (RAS) improves outcome after transcatheter aortic valve replacement (TAVR). However, it remains unknown whether the effect of RAS blockade treatment on survival and left ventricular (LV) remodeling after TAVR is dose dependent.

Purpose

To assess clinical outcome and remodeling dependent on different RAS doses after TAVR.

Methods

Patients who were enrolled into our observational TAVR study at our institution were retrospectively assessed according to different dosed of RAS blockade: Group1 (no RAS blockade), group 2 (25% of the maximum daily dose), group 3 (50% of the maximum daily dose) and group 4 (100% of the maximum daily dose).

Results

A total of 323 patients between January 2015 and September 2019 were included. Patients with higher doses of RAS blockade showed a trend towards lower all-cause mortality at 3-year follow-up (56% with no RAS blockade vs. 66% with the 25% dose vs. 79% with the 50% dose vs. 78% with the full dose; p=0.063). After adjustment for baseline characteristics the difference in survival was significant (p=0.042). Besides NYHA class ≥ III and left ventricular ejection fraction (LV-EF) RAS blockade dose was identified as independent predictor for all-cause mortality (HR 0.72 [95% CI 0.54–0.97]; p=0.03). With respect to regression of LV mass index after TAVR the only significant change was observed in patients receiving the full dose.

Conclusion

The present study showed for the first time that the impact of RAS blockade treatment on clinical outcome and LV remodeling after TAVR is dose dependent.

Survival dependent on RAS dosis

Funding Acknowledgement

Type of funding source: None
Frequency and clinical impact of different definitions of moderate aortic stenosis
Authors: Du Y.U , Hashimoto G.O , Cavalcante J , Goessl M , Garcia S , Ahmed A , Lopes B , Schmidt C , Garberich R , Sorajja P
Published: November 2020

Background

Current echocardiographic guidelines recommend five parameters to define severity of aortic stenosis (AS): peak velocity (PV), mean gradient (MG), aortic valve area (AVA), index AVA (AVAi), and dimensionless index (DI). However, the clinical utility of these parameters for patients with moderate AS largely remain unknown.

Objective

To investigate the clinical profiles and outcomes of patients with moderate AS according to five different definitions for severity.

Methods

Using standard echocardiographic definitions, we identified patients with moderate AS who were evaluated in our health care system from 2011 to 2012. Patient demographics, morbidities, and adverse events were reviewed, including death, heart failure (HF) admission, and aortic valve replacement (AVR).

Results

We enrolled 1,042 patients (age, 75±12 yrs; 40% women). Very few patients (4%) met all five criteria for moderate AS, while 49% had only one or two criteria met. DI was the most common parameter for defining moderate AS, employed in 93% of patients. Patients with area-based indices (i.e., AVA, AVAi, DI) had lower stroke volume index, lower mean gradients, lower peak velocities, and more morbidities in comparison to those flow-based definitions of severity (i.e., PV, MG). During a median follow-up of 5.7 years, overall survival was poor with all-cause mortality of 62.8%. Notably, there was no difference in the rates of mortality (range, 56.4 to 63.3%) or HF hospitalization (range, 28.9 to 32.2%) for groups defined by the five parameters, though patients with flow-based definitions more likely had AVR in follow-up.

Conclusions

Most patients with moderate AS meet the definition for severity with one or few criteria. Regardless of the method of definition for severity, a high rate of mortality and morbidity can occur in patients with moderate AS. Further study to optimize the clinical outcomes of patients with moderate AS is warranted.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): Minneapolis Heart Institute Foundation
Symptoms and natural history in patients with isolated severe calcific mitral stenosis
Authors: Kato N , Padang R , Scott C.G , Guerrero M , Pislaru S.V , Pellikka P.A
Published: November 2020

Background

Prevalence of calcific mitral stenosis (MS) increases with age. Mitral valve interventions for calcific MS are often delayed until symptoms are severely limiting because the natural history of calcific MS and its relation to cardiac symptoms or comorbidities have not been well assessed.

Objectives

We assessed the prevalence of symptoms, comorbidities and determinants of all-cause mortality in patients with severe calcific MS.

Methods

We retrospectively investigated adults with echocardiographic isolated severe MS, defined as mitral valve area (MVA by the continuity equation) ≤1.5 cm2, from July 2003 to December 2017. Among them, calcific MS was identified as obstruction of left ventricular inflow due to degenerative calcification of the mitral annulus using echocardiography and, whenever available, operative findings including histopathological examination. Inactivity was defined as requirement for assistance with activities of daily living. Follow up was obtained by review of medical records.

Results

Of 491 patients with isolated severe MS, calcific MS was present in 200 (41%; age 78±11 years, 18% men, 32% with atrial fibrillation). Charlson Comorbidity Index (CCI) was 5.1±1.7 and 14 (7%) were inactive. MVA and transmitral gradient (TMG) were 1.26±0.19 cm2 and 8.1±3.8 mmHg, respectively. Symptoms were present at baseline in 120 (60%) including dyspnea in 97, chest discomfort in 12, syncope in 3, lower extremity edema in 3, thrombosis in 3 and fatigue in 2. Of them, mitral valve interventions including surgical or transcatheter mitral valve replacement and mitral valve bypass were performed in 27 (23%): within 1 year after index TTE in 23 (19%) and at 2, 4, 5 and 6 years in 1 each. Of 80 patients without symptoms at index TTE, 20 (25%) developed symptoms at mean 2.9±3.2 years and interventions were performed in 5 (6%). Of 168 who did not receive interventions, 60 (36%) did not develop symptoms during follow up, 58 (35%) were considered to have moderate MS, 46 (27%) were not offered surgery because of high risk due to advanced age, multiple comorbidities or heavy calcification, and 2 (1%) declined interventions. During follow-up of 2.8±3.0 years, Kaplan-Meier survival at 1 and 3 years without intervention were 72% and 52%, respectively (Fig. A). Inactivity, CCI >5, left ventricular ejection fraction (LVEF) <50%, TMG ≥8 mmHg (the mean TMG) and right ventricular systolic pressure (RVSP) ≥50 mmHg were independently associated with mortality (Fig. B). Symptoms were associated with referral for interventions (OR 3.43, 95% CI 1.22–9.65; p=0.019), but not with mortality.

Conclusion

Patients with isolated severe calcific MS had a high burden of comorbidities and had high mortality without intervention. Symptoms were common (60%), but were not associated with mortality. TMG ≥8 mmHg, RVSP ≥50 mmHg, LVEF<50%, CCI >5 and inactivity were independently associated with mortality.

Funding Acknowledgement

Type of funding source: None
Mitral annulus disjunction is highly prevalent in patients with Marfan syndrome and Loyes-Dietz syndrome
Authors: Chivulescu M , Krohg-Sorensen K , Scheirlynk E , Lindberg B , Dejgaard L , Lie O , Helle-Valle T , Skjolsvik E , Aabel E , Hunt T , Estensen M , Edvardsen T , Lingaas P , Haugaa K
Published: November 2020

Background

Mitral valve prolapse is a common finding in patients with Marfan and Loyes-Dietz syndrome. Mitral annulus disjunction (MAD), an atrial displacement of the hinge point of the mitral valve, has previously been associated with non-syndromic MVP and life-threatening ventricular arrhythmias.

Purpose

We aimed to assess the prevalence of MAD in patients with Marfan and Loyes-Dietz syndrome and relate the presence of MAD to mitral valve prolapse.

Methods

We included genotype positive patients with Marfan and Loyes-Dietz syndrome, and patients with Marfan syndrome fulfilling Revised Ghent Criteria. Mitral valve prolapse was defined as superior mitral leaflets' displacement ≥2mm beyond the mitral annulus. MAD was diagnosed by echocardiography and quantified as the distance from the ventricular myocardium to the hinge point of the posterior mitral leaflet (Figure, left panel).

Results

We included 111 patients with Marfan syndrome and 66 patients with Loyes-Dietz syndrome (age 26 [IQR, 13–39] years, 53% male). Mitral valve prolapse was observed in 54 (31%) and MAD in 74 (42%) patients. Longitudinal MAD distance was 8 (IQR, 6–10) mm. Forty-six (85%) patients with mitral valve prolapse had concomitant MAD, p<0.001 (Figure, right panel).

Conclusion

Mitral valve prolapse was observed in one third of patients with Marfan and Loyes-Dietz syndrome. MAD was highly prevalent and found in 42% of all patients and in 85% of those with mitral valve prolapse. Presence of mitral valve prolapse in Marfan and Loyes-Dietz syndrome should raise awareness of MAD which may be of importance in follow-up and monitoring of these patients.

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): Health Authority of South Eastern Norway
Predictors of sudden cardiac arrest in adolescents with mitral valve prolapse: an analysis of the nationwide inpatient sample
Authors: Narasimhan B , Wu L , Lucas C.H , Bhatia K , Shah A , Kantharia B
Published: November 2020

Background

Mitral valve prolapse (MVP) is the most commonly encountered valvular pathology seen in 2–3% of the general population. Though traditionally regarded as a benign pathology, recent literature suggests that sudden cardiac death is significantly more common in these patients with estimates of 0.2–0.4%/year. The exact underlying mechanism of these higher rates of SCD remain poorly understood. In this study, we aim to identify predictors of sudden cardiac arrest (SCA) in an adolescent population.

Methods

We conducted a retrospective study using the AHRQ-HCUP National Inpatient Sample 2016-2017 for the years 2016-17. All patients (≤18 years) admitted with Mitral valve prolapse were identified using ICD-10 codes and further sub stratified based on presence or absence of sudden cardiac arrest (SCA). Baseline characteristics were obtained and multivariate regression analysis was utilized to identify potential predictors of SCA. Independent risk factors for in-hospital mortality were identified using a proportional hazards model. Complications were defined as per the Agency for Health Care Research and Quality guideline.

Results

We screened a total of 71,473,874 admissions in the NIS database to identify a total of 1,372 adolescent patients admitted with MVP in the years 2016–17. These patients were then sub-categorized based on presence or absence of SCA during the hospitalization. Our findings revealed that patients with SCA were generally slightly older (15y vs 13y, p=0.036, OR-1.1, p=0.007) and more likely female (83.3% vs 13%, p=0.227, OR – 3.55, p=0.57)). Interestingly, patients in the SCA cohort were noted to have almost 4 fold higher rates of Mitral regurgitation (66.6% vs 18.35%, p=0.008, OR-8.89, p=0.005) as well as family history of SCD (16.7% vs 4.1%, p=0.145, OR-4.65, p=0.14).

Conclusions

Presence of Mitral regurgitation and a family history of sudden cardiac death are associated with significantly higher rates of SCA in adolescent patients with mitral valve prolapse.

Predictors of SCA in Adolescent MVP

Funding Acknowledgement

Type of funding source: None