bluuebunny/crossref_metadata_2025 huggingface dataset:
Bleeding complications drive early mortality of patients with atrial fibrillation after transcatheter aortic valve replacement
Authors: Stachon P , Lother A.L , Kaier K.K , Zehender M.Z , Bode C.B , Von Zur Muehlen C.M
Published: November 2020

Background and objectives

Atrial fibrillation is a risk factor for poor post-operative outcome after transfemoral transcatheter aortic valve replacement (TF-TAVR). The present study analyses the outcomes after TF-TAVR in patients with or without atrial fibrillation (AF) and identifies independent predictors for in-hospital mortality in clinical practice.

Methods and results

Among all 57,050 patients undergoing isolated TF-TAVR between 2008 and 2016 in Germany, 44.2% of patients (n=25,309) had AF. Patients with AF were at higher risk for unfavorable outcome after TAVR. Including all baseline characteristics for a risk-adjusted comparison, AF was an independent risk factor for in-hospital mortality after TAVR. Among patients with AF, EuroSCORE, NYHA class or renal disease had only moderate effects on mortality, while the occurrence of post-procedural stroke substantially increased in-hospital mortality (OR 3.55, 95% CI 2.77–4.56, P<0.001). However, the strongest independent predictor for in-hospital mortality among patients with AF was bleeding (OR 11.04, 95% CI 9.53–12.80, P<0.001). Bleeding also was by far the strongest predictor for prolonged mechanical ventilation (OR 25.36, 95% CI 21.83–29.48, P<0.001).

Conclusions

The present study demonstrates that the incidence of bleeding defines the early outcome of patients with AF after TF-TAVR. Thus, the peri-procedural phase demands particular care in anti-thrombotic regimen.

Funding Acknowledgement

Type of funding source: None
Impact of on-clopidogrel platelet reactivity on incidence of peri-interventional bleeding in patients undergoing transcatheter aortic valve implantation
Authors: Kille A , Nuehrenberg T , Hromek J , Valina C.M , Trenk D , Neumann F.J , Hochholzer W
Published: November 2020

Background

Transcatheter aortic valve implantation (TAVI) has become clinical routine for patients at intermediate to high risk for surgical aortic valve replacement. The optimal antithrombotic strategy following TAVI is still not well defined. Antithrombotic treatment is administered to prevent hypo-attenuated leaflet thickening, valve thrombosis, or ischemic stroke. However, most of these patients are also at high risk for bleeding. Current guidelines recommend dual antiplatelet therapy although the clinical evidence is limited.

Methods

This analysis enrolled patients undergoing TAVI from 11/2013 until 04/2018. Patients were either on long-term dual antiplatelet therapy with clopidogrel and aspirin or received a loading dose 300 to 600mg of clopidogrel and 400mg aspirin before TAVI. Platelet reactivity was determined by multi-electrode impedance aggregometry after stimulation with arachidonic acid and adenosine diphosphate (ADP) before TAVI as well as at day 1 and 5 thereafter. Peri-interventional bleeding was assessed up to 5 days following TAVI and coded according to BARC-classification.

Results

The present analysis included 484 patients (median age 83 [79–86] years; female sex 54.5%). There were 199 (41.1%) patients with a bleeding event. Most frequent were BARC 2 bleedings in 117 (24.2%) cases followed by BARC 1 (6.0%), BARC 3b in 25 (5.2%) and BARC 3a in 22 (4.5%) cases. On-clopidogrel platelet reactivity tested after stimulation with ADP was significantly lower in patients with bleeding events as compared to patients without bleeding (Figure). No differences were observed in arachidonic acid-induced platelet reactivity as marker for aspirin-efficacy between both groups over time. Multivariate logistic regression analysis identified on-clopidogrel platelet reactivity and use of oral anticoagulation as strongest independent predictors for bleeding events.

Conclusion

On-clopidogrel platelet reactivity is an independent predictor for peri-interventional bleeding in patients undergoing TAVI. Taken together with previous data indicating no association of on-clopidogrel platelet reactivity with peri-interventional ischemic events, the present data question the need for a strong peri-interventional dual antiplatelet therapy in patients undergoing TAVI.

Funding Acknowledgement

Type of funding source: None
Feasibility and safety of oversizing self-expandable valves for transcatheter aortic valve implantation, according to aortic annulus maximal diameter
Authors: Jourdi B , Trimech T.R , Fradi S , Ghostine S
Published: November 2020

Background

Transcatheter aortic valve implantation (TAVI) can lead to paravalvular leak (PVL) in 15% to 20% of cases, which remains an important prognostic factor and an independent predictor of mortality in short and long-term follow-up.

Objectives

To evaluate feasibility and safety of oversizing Medtronic Self-Expandable Valve (Dvalve), calculated according to the aortic annulus maximal diameter (Dmax), on the incidence of PVL and in-hospital mortality after TAVI.

Methods

We retrospectively analyzed the data of 610 patients treated with TAVI between January 2016 and December 2018. A group of 45 patients of the oversized group (October 2017 to December 2018) accordingly to the Dmax, when (Dvalve − Dmax) | <2 mm in the absence of contraindication was compared to a control group of 213 patients whose prosthesis size had been chosen according to the aortic annulus perimeter (January 2016 to September 2017).

Results

In the “oversized” group, no patient had a significant PVL after TAVI compared with the control group (0% vs. 7.51%; p=0.041). Balloon post-dilatation was significantly less frequent in the “oversized” group (0% vs. 10.3%; p=0.012). Per-procedural irradiation and the average length of in-hospital stay were significantly lower (PDS = 2,296.05±1,667.94 cGy·mm2 vs. 4,568±1,352.84 cGy·mm2; p<0.001; and 5.23±1.74 days vs. 6.33±3.23 days; p=0.029, respectively). No case of annulus rupture occurred in the “oversized” group. The incidences of high-degree atrioventricular block with definitive pacing and in-hospital mortality were similar between the two groups.

Conclusion

Oversizing the self-expandable valve, according to the aortic annulus maximal diameter, significantly reduced PVL after TAVI, balloon post-dilatation, per-procedural irradiation, and the length of hospital stay, without increasing the risk of mechanical, rhythmic, conductive and coronary occlusion complications. It does not increase the in-hospital mortality rate either. Randomized controlled trials are needed to establish a firm conclusion about its feasibility and safety.

Funding Acknowledgement

Type of funding source: None
Real-world comparison of the last generation main balloon-expandable and self-expanding valves in patients undergoing TAVI. Does the type matter?
Authors: Kalogeras K , Ruparelia N , Kabir T , Jabbour R , Kalantzis C , Bei E , Katsianos E , Naganuma T , Nakamura S , Sen S , Malik I.S , Mikhail G , Dalby M , Vavuranakis M , Panoulas V
Published: November 2020

Background/Introduction

The balloon expandable Edwards Sapien-S3 and Ultra, and the self-expanding Medtronic Evolut-Pro and Evolut-R 34mm represent the main volume of transcatheter aortic valve implantation (TAVI) procedures conducted worldwide.

Purpose

In the present study, we aim to compare the peri-procedural and one-year clinical outcomes between these last generation devices.

Methods

Consecutive patients from the ATLAS (Athens-Tokyo-London Aortic Stenosis) registry, who had undergone TAVI with either the S3/Ultra or Evolut-Pro/R 34mm device, in four centers were retrospectively studied. In-hospital procedural characteristics and outcomes were recorded and compared. Kaplan-Meier estimated 1-year all-cause mortality was compared between groups.

Results

In total, 692 patients (352pts treated with S3/Ultra and 340pts with Evolut-Pro/R34mm device) were included in the analysis. Baseline demographics (age, coronary artery disease risk factors, logistic Euroscore and aortic valve hemodynamics) were similar between the two groups.

In terms of peri-procedural and short-term outcomes, patients treated with the Evolut-Pro/R34mm device had significantly lower peak (25.4±3.6mmHg for S3/Ultra vs 14.9±0.6mmHg for the self-expanding valves, p=0.002) and mean (10.7±0.3mmHg S3/Ultra vs 7.9±0.4mmHg Evolut PRO/R34, p<0.001) gradients at discharge.

Conversely, the S3 demonstrated significantly lower rates of at least moderate residual aortic regurgitation (AR) post-operatively (0.3% vs 4.8% for S3 and Evolut-Pro/R34mm respectively, p=0.001). Interestingly, the rate of new permanent pacemaker (PPM) required after the implantation in pacemaker-free patients on baseline, was higher for the S3/Ultra cohort compared to the self-expanding valve group (17.6% vs 11.7% respectively, p=0.054), however not reaching statistical significance yet. As expected, the need for balloon post dilatation of the implanted prosthesis was less among the S3/Ultra patients (5.5% vs 26.1%, p=0.001).

One-year Kaplan-Meier estimated survival was similar between the two groups (85.9% for S3 vs. 90% for Evolut-Pro/R34mm, plog-rank=0.071). Hazard ratio for all-cause mortality (Pro/R34 vs. S3/Ultra) after adjustment for gender and previous MI was similar between the groups (HR=0.73; 95% CI 0.47 to 1.14, p=0.165).

Conclusions

Real life comparison of the last generation balloon expandable and self-expanding devices demonstrates similar 1-year all-cause mortality. The S3/Ultra platforms, as compared to the Evolut-Pro/R34mm, demonstrate less paravalvular leak, at the expense of higher transvalvular gradients. Long-term follow-up and future larger trials are required to establish any potential long-term difference in clinical outcomes and prognosis.

Funding Acknowledgement

Type of funding source: None
Acute response of right ventricular function following transcatheter mitral valve repair
Authors: Sugiura A , Weber M.W , Tabata N.T , Zimmer S.Z , Becher U.B , Tiyerili V.T , Nickenig G.N , Sinning J.M.S
Published: November 2020

Background

Little is known about early right ventricular (RV) response to transcatheter mitral valve repair (TMVR) and its association with clinical outcomes. We assessed the early effect of TMVR on the RV function (RVF) and sought to investigated the prognostic impact of post-procedural RV dysfunction.

Methods

From January 2011 through April 2019, consecutive patients who underwent MitraClip for severe mitral regurgitation were analyzed. We excluded patients in which the evaluation of RVF were un available. RV dysfunction was defined by an RV fractional area change (RVFAC) <35% or tricuspid annular planar systolic excursion (TAPSE) <16 mm. A Cox proportional regression analysis was conducted to investigate the association of post-procedural RV dysfunction with adverse outcomes (all-cause mortality and rehospitalization due to heart failure [HF]).

Results

A total of 403 patients were analyzed.Overall, the mean age was 78 years old and 59% of patients were male. The median left-ventricular ejection fraction (LVEF) was 46.1% [IQR 33.1–59.4], RVFAC was 41.9% [IQR 32.9–49.5], and TAPSE was 17 mm [IQR 14–22]. While 68 patients showed an acute improvement of RVF (35% of patients with baseline RV dysfunction), 51 patients (25% of patients with baseline normal RVF) showed an acute worsening of RVF. In patients with baseline normal RVF, atrial fibrillation (OR 4.57, 95% CI 1.56–13.40, p=0.006, HF duration >18 months (OR 2.95, 95% CI 1.32–6.60, p=0.009), LVEF <50% (OR 3.09, 95% CI 1.32–7.25, p=0.009), and tricuspid regurgitation≥3+ (OR 5.62, 2.28–13.90, p<0.001)were associated with an increased risk of acute worsening of RVF. By contrast, in patients with baseline RV dysfunction, HF duration >18 months (OR 0.43, 95% CI 0.22–0.85, p=0.01) and larger RV volume (OR 0.98, 95% CI 0.97–0.99, p<0.001) were associated with less probability of acute RVF improvement. The event-free survival was significantly different according to the subgroup of variation of RVF (p=0.003). Furthermore, post-procedural RV dysfunction was associated with an increased risk of outcomes (adjusted-HR 2.38, 95% CI 1.28–4.43, p=0.006).

Conclusion

Both acute improvement and worsening of RVF can be observed after TMVR. Post-procedural RV dysfunction is an independent predictor of adverse outcomes.

Event-free survival curve

Funding Acknowledgement

Type of funding source: None
Risk factors and etiology of recurrent mitral regurgitation after edge-to-edge mitral valve repair
Authors: Sugiura A , Weber M.W , Tabata N.T , Oeztuerk C.O , Zimmer S.Z , Becher U.B , Tiyerili V.T , Nickenig G.N , Sinning J.M.S
Published: November 2020

Background

Recurrent MR has been associated with poor prognosis after transcatheter mitral valve repair (TMVR) with the MitraClip system. However, little is known about risk factors and etiology of recurrent mitral regurgitation (MR) after transcatheter edge-to-edge mitral repair with the MitraClip system.

Methods

Among consecutive patients who underwent MitraClip for MR from January 2011 to March 2019, we identified 240 patients who had MR ≤2+ at discharge and follow-up echocardiography within three years after the procedure. Recurrent MR was defined as MR ≥3+ during the follow-up period. To investigate the risk factors for recurrent MR, we conducted a Cox proportional hazard model.

Results

During the follow-up period (median 491 days), 38 patients (15.8%) had recurrent MR (≥3+). The most frequent etiology of recurrent MR was degenerative (n=20, 52.6%), including single leaflet detachment (n=2, 5.3%), loss of leaflet insertion (n=11, 28.9%), and leaflet tear or prolapse (n=7, 18.4%), followed by functional MR (n=18, 47.4%). The risk factors for recurrent MR were greater LV end-diastolic volume (adjusted-HR 1.01, 95% CI 1.00–1.02, p=0.03), higher LV ejection fraction (LVEF) (adjusted-HR 1.05, 95% CI 1.01–1.08, p=0.005), and moderate MR upon discharge (adjusted-HR 2.98, 95% CI 1.50–5.95, p=0.002).After stratification according to the etiology of MR, the association of LVEF was more pronounced in patients with degenerative MR (adjusted-HR 1.07, 95% CI 1.02–1.12, p=0.003), while the association of moderate MR upon discharge was more pronounced in patients with functional MR (adjusted-HR 5.02, 95% CI 1.95–12.8, p<0.001). Furthermore, patients with recurrent MR had an increased antero-posterior annulus diameter regardless of the baseline etiology of the MR.

Conclusions

Greater LV volume, higher LVEF, and moderate MR at discharge were associated with an increased risk of recurrent MR after the MitraClip procedure. A significant increase of the annulus diameter was observed regardless of the baseline etiology of the MR.

Etiology of recurrent MR

Funding Acknowledgement

Type of funding source: None
Prognostic value of pre-operative atrial fibrillation in patients with heart failure and secondary mitral regurgitation undergoing percutaneous mitral valve repair with MitraClip
Authors: Sisinni A , Godino C , Pivato C.A , Adamo M , Taramasso M , Scotti A , Munafo A , Sala A , Curello S , Agricola E , Colombo A , Alfieri O , Maisano F , Metra M , Margonato A
Published: November 2020

Background

Limited data are available regarding the independent prognostic role of atrial fibrillation (AF) after transcatheter mitral valve repair with MitraClip.

Aims

We sought to evaluate the real impact of pre-operative AF in a wide series of patients with heart failure (HF) and secondary mitral regurgitation (MR) after MitraClip treatment.

Methods

The study included 605 patients with severe secondary MR from a multicenter international registry. Patients were stratified into two groups according to the presence or absence of pre-operative AF. The overall prevalence of pre-operative AF was 44%. Primary endpoint was 5-year overall death, secondary endpoints were 5–year cardiac death and first re-hospitalization for acute HF.

Results

At 5-year Kaplan-Meier (KM) analysis conducted in the entire study cohort, compared to patients without AF those with AF had significantly more adverse events in term of overall death (67% vs. 43%; p<0.001) (KM curve A) and cardiac death (65% vs. 37%; p=0.001) (KM curve B) and, moderately more re-hospitalization for acute HF (64% vs. 50%; p=0.048) (KM curve C). To account for baseline differences, patients were propensity score matched 1:1. After matching, 342 adequately matched patients were identified: compared to patients without AF, those with AF had higher rates of death and cardiac mortality but similar rates of re-hospitalization for acute HF.

Conclusion

In this large 5-year analysis of patients with HF undergoing MitraClip treatment for severe secondary MR, AF is common and associated with higher rates of both overall- and cardiac-death. However, AF doesn't seem to affect the benefit of the procedure in term of re-hospitalization for HF.

Funding Acknowledgement

Type of funding source: None
Impact of concomitant mitral regurgitation in severe aortic stenosis in Japan – from the CURRENT AS registry
Authors: Murai R , Kawase Y , Taniguchi T , Morimoto T , Maruo T , Fuku Y , Kadota K , Kimura T
Published: November 2020

Background

Clinical significance of concomitant mitral regurgitation (MR) in patients with severe aortic stenosis (AS) has not been well-studied.

Purpose

The purpose of this study is to investigate the prognostic impact of concomitant MR in patients with severe AS.

Method

We used the data of 3815 patients from the CURRENT AS registry, a retrospective multicenter registry of severe AS in Japan. We compared the clinical outcomes between patients with moderate/severe MR and with none/mild MR according to the initial treatment strategies (initial aortic valve replacement [AVR] or conservative strategy). The primary outcome measure was a composite of aortic valve-related death and heart failure hospitalisation.

Results

Among the study population, moderate/severe MR were observed in 227/1197 (19%) patients with initial AVR strategy and in 536/2618 (20%) patients with conservative strategy. Among survivors with the initial AVR strategy, moderate/severe MR improved in 61/62 (98%) patients with concomitant mitral procedures. The crude cumulative 5-year incidence of the primary outcome measure was significantly higher in patients with moderate/severe MR than in those with none/mild MR regardless of the treatment strategies (25.2% vs. 14.4%, P<0.001 in the initial AVR strategy; 63.3% vs 40.7%, P<0.001 in the conservative strategy). Multivariate analysis revealed moderate/severe MR at index echocardiography was independently associated with higher risk for the primary outcome measure in conservative strategy (adjusted HR 1.20, 95% CI 1.03–1.40, P=0.023), but not associated in the initial AVR strategy (adjusted HR 1.20, 95% CI 0.82–1.80, P=0.339).

Conclusion

Moderate/severe MR was independently associated with poorer outcome in patients with severe AS who were managed conservatively, but not in those with initial AVR strategy.

Funding Acknowledgement

Type of funding source: None
Cardiac magnetic resonance and B-natriuretic peptide are superior prognostic tools to guideline-based echocardiography in asymptomatic patients with chronic severe aortic regurgitation
Authors: Kockova R , Linkova H , Hlubocka Z , Blaha M , Tuna M , Medilek K , Lupinek P , Sedmera D , Penicka M
Published: November 2020

Background

The optimal timing of intervention in patients with chronic aortic regurgitation (AR) is currently based on patient symptoms and echocardiography derived parameters. The sensitivity of this approach is suboptimal and late operation often results in irreversible myocardial damage.

Purpose

To determine the prognostic value of novel parameters in asymptomatic patients with chronic severe AR in optimal timing of aortic valve surgery.

Methods

Consecutive patients with chronic severe AR not indicated for surgery per the current guidelines were studied in a prospective design in 5 centers. Baseline examination consisted of B-natriuretic peptide (BNP) measurement, comprehensive echocardiography (ECHO) including 3-dimensional (3D) study with vena contracta area (VCA), and complex magnetic resonance (MRI) including regurgitant volume (RV), regurgitant fraction (RF), global myocardial work efficiency (GWE) and extracellular volume (ECV); all analyzed in core lab. All patients were followed every 6 months and the endpoint was disease progression defined as an indication for surgery. The perioperative myocardial biopsy was performed in all surgically treated patients for histological myocardial fibrosis quantification.

Results

In total, 129 patients were enrolled between 2015 and 2019, the endpoint occurred in 35 patients during a mean follow-up of 1044 days. Baseline clinical data did not differ between patients with disease progression (surgical group) and stable patients. Baseline BNP levels were higher in the surgical group (63 vs. 20, P<0.01) and a cut-off value of 30.4 ng/L was predictive of disease progression with AUC 0.75. None of the standard ECHO parameters of left ventricular (LV) size and function was predictive of the endpoint. Novel ECHO parameter 3D VCA was higher in the surgical group (32 vs. 26 mm2, P=0.037). All MRI parameters of LV size and function were predictive of disease progression (all P<0.02), except LV ejection fraction. MRI-derived RV (57 vs. 37 ml, P<0.01) and RF (46 vs. 34%, P<0.01) were identified as the strongest independent predictors of surgery. There was no difference in ECV between the surgical group and stable patients (24 vs. 24, P=0.81) despite a good correlation with histological quantification of myocardial fibrosis.

Conclusions

Standard ECHO parameters cannot reliably predict the need for surgery in asymptomatic aortic regurgitation patients. Baseline BNP levels above 30.4 ng/L predict disease progression. Novel imaging parameters – ECHO-derived 3D VCA and MRI-derived parameters of LV size and AR severity might be useful in optimal timing determination.

Imaging markers and myocardial histology

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): Ministry of Health of the Czech Republic
Cardiopulmonary exercise testing as a guideline indicator for mitral valve intervention
Authors: Afoke J , Kanaganayagam G.S , Casula R , Bruno V.D , Howard L , Gibbs J.S.R , Punjabi P
Published: November 2020

Background

Primary mitral regurgitation (MR) is one of the most common heart valvular pathologies. However, optimum timing of surgery remains controversial.

Purpose

To describe changes in cardiopulmonary exercise testing (CPET) parameters after surgery for severe primary MR.

Methods

In a single centre prospective study, patients undergoing surgery under current ESC guidelines for severe primary MR underwent assessment with transthoracic echocardiogram, CPET, cardiac MRI and quality of life questionnaire pre-operatively and at six months after surgery. The primary outcome was a per protocol analysis of impaired post-operative functional capacity (defined as post-operative left ventricular ejection fraction on transthoracic echocardiogram <50% and/or post-operative percentage predicted peak VO2 ≤84%).

Results

43 of the 50 patients recruited between February 2017 and October 2018 were included in the per protocol analysis. Thirty five patients (72.9%) had impaired post-operative functional capacity. In the overall cohort (n=43), there was a significant fall post-operatively in percentage predicted peak VO2 (ppVO2) (81.8±15.7% vs. 76.2±16.2%, p<0.01) and anaerobic threshold (AT) (48.0±11.1% vs. 44.3±10.1%, p=0.01). In patients with a class I indication for surgery (n=30), there was no significant change post-operatively in ppVO2 (79.6±15.7% vs. 75.6±16.7%, p=0.09) or AT (49.9±11.4% vs. 46.4±10.2%, p-0.09). However, in patients with a class II indication for surgery (n=13), there was a significant change post-operatively in ppVO2 (86.9±15.1% vs. 77.4±15.9%, p<0.01), but not in AT (43.5±9.6% vs. 39.5±8.3%, p=0.16).

In the multivariable analysis, pre-operative left ventricular ejection fraction ≤60% (hazard ratio, 1.69; 95% confidence interval, 1.56 to 480.1, p=0.04) and pre-operative percentage predicted peak VO2 ≤84% (hazard ratio, 1.22; 95% confidence interval, 2.13 to 107.1, p<0.01) were independent predictors for impaired post-operative functional capacity.

Conclusions

Pre-operative percentage predicted peak VO2 ≤84% is an independent predictor of impaired post-operative functional capacity. Subject to a confirmatory study, this may help to refine current ESC guidelines for intervention for severe primary MR.

Change in ppVO2 after surgery

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): Rosetrees Trust and Friends of Hammersmith Hospital
Determinants and prognostic significance of focal myocardial fibrosis by cardiac magnetic resonance imaging in patients with mitral valve prolapse
Authors: Constant Dit Beaufils A.L , Huttin O , Piriou N , Cueff C , Senage T , Marrec M , Warin-Fresse K , Banasiak C , Sellal J.M , Mandry D , Venner C , Filippetti L , Serfaty J.M , Selton-Suty C , Le Tourneau T
Published: November 2020

Background

Mitral valve prolapse (MVP) is a frequent disease that can be complicated by mitral regurgitation (MR), heart failure, arterial embolism, rhythm disorders and death.

Purpose

We sought to evaluate the correlates of late gadolinium enhancement (LGE), and the prognostic significance of ventricular size, function, and LGE by cardiac magnetic resonance (CMR) imaging on cardiovascular morbi-mortality in patients with MVP

Methods

We included 426 patients (54±15 years, 57% male) with MVP (trace to severe MR) between 2010 and 2019 who underwent a comprehensive echocardiography and CMR imaging. Gadolinium was injected in 411 (96%) patients. The main outcome endpoint was a composite endpoint of cardiovascular death, heart failure, new onset atrial fibrillation or arterial embolism, censored at the time of mitral valve intervention.

Results

Among the 411 patients, LGE+ was found in 118 (29%; 100 myocardial wall including 78 basal inferolateral midwall, 30 papillary muscles) and was more frequent with worse MR volume and LV remodeling. Correlates of LGE in multivariable analysis were LV mass index (OR 1.02, P=0.008), moderate-severe MR (OR 2.15, P=0.017) and coronary artery disease (OR 5.8, P=0.013). At 4 years, survival without cardiovascular events was decreased in patients with LGE+ (50.0±11.9 vs 73.5±6.3%, p<0.0001). In a stepwise multivariable analysis including classical predictors of outcome, grade of MR, LA volume index and the presence of LGE on CMR imaging (HR: 2.15 [1.15–4.02], P=0.017) were associated with impaired event-free survival.

Conclusion

CMR imaging provides additional information to echocardiography in the clinical work-up of MVP. Localized LV myocardial fibrosis is a predictor of cardiovascular event in MVP patients.

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): DGOS (PHRCI), Fondation Cœur et Recherche
Prognosis of short- and long-term dialysis in patients with infective endocarditis: a nationwide study
Authors: Petersen J , Jensen A.D , Bruun N.E , Kamper A , Butt J.W , Borgersen E , Pedersen C.T , Chaudry M.S , Kober L , Fosbol E.L , Ostergaard L
Published: November 2020

Background

Infective endocarditis (IE) may be complicated by acute kidney injury, yet data on the use of dialysis and subsequent reversibility are sparse. We set out to examine the prognosis of short- and long-term dialysis in patients with IE.

Methods

Using Danish nationwide registries we identified patients with first-time IE from 2000 to 2017. Dialysis naïve patients were grouped into: those who were treated with dialysis during admission with IE and those who were not. The cumulative incidence of continuous use of dialysis was examined one year post-discharge Multivariable adjusted Cox proportional hazard analysis was used to examine one-year mortality for patients surviving IE based on use of dialysis.

Results

We included 7,307 patients with IE; 416 patients (5.7%) initiated dialysis treatment during admission with IE and these were younger, had more comorbidities and more often underwent cardiac valve surgery during admission with IE compared with non-dialysis patients (47.4% vs. 20.9%). In patients with both surgical intervention and dialysis treatment, 153 (77.7%) initiated dialysis on- or after the date of surgery. The in-hospital mortality was 40.4% and 19.0% for patients with and without dialysis, respectively (p<0.0001). Of those who started dialysis and survived hospitalisation, 78.4% became dialysis-free within one year after discharge. Among those who survived one week subsequent to IE discharge, we identified 5,520 who never had dialysis, 204 patients without continued use of dialysis, and 40 patients with a continued use of dialysis. The corresponding mortality risk at one year was 15.2%, 13.5%, and 41.6% (Figure), respectively. Compared with patients not treated with dialysis, those who became dialysis-free at discharge showed no increased risk of one year mortality in adjusted analysis (HR=1.45, 95% CI: 0.97–2.20), while patients who continued dialysis had an increased associated risk of mortality (HR=2.00, 95% CI: 1.20–3.33).

Conclusion

In dialysis-naïve patients with IE, more than 1 in 20 patients initiated dialysis treatment during admission. Dialysis identified a high-risk group with an in-hospital mortality of 40%–twice as high as their counterparts. In dialysis patients surviving admission with IE, almost 80% became dialysis-free and showed better long-term survival than those who continued dialysis after discharge.

Figure 1

Funding Acknowledgement

Type of funding source: None
Discrepancies between the decisions of an endocarditis team and the modified Duke's Criteria for the diagnosis of infective endocarditis
Authors: Power N , Chick W , Tan A , Gamlin W , Calisti G , Watt V , Price F , Dobson L , Ray S
Published: November 2020

Background/Introduction

The 2015 ESC endocarditis guidelines recommend that a multi-disciplinary endocarditis team should be involved in caring for patients with endocarditis. This approach recognises the heterogeneity of infective endocarditis, and the difficulty in distinguishing endocarditis from other infective and non-infective diseases.

Purpose

This study looks at suspected cases of infective endocarditis discussed at the endocarditis MDT, discrepancies between MDT outcome and the modified Duke's criteria in diagnosing endocarditis, and number of referrals to MDT over time.

Methods

Patients were identified by review of MDT outcome forms. Demographic data, predisposing conditions, imaging findings, microbiology results and final diagnosis were identified by reviewing MDT forms and electronic charts.

Results

234 patients were identified from MDT outcome forms. 118 (50.4%) patients were over 65, 165 (70.5%) were male, and 65 (27.8%) had previous valve surgery. Crosstabulation of MDT decision against outcome by modified Duke's criteria are seen in Table 1. The endocarditis team identified 7 patients with definite or possible endocarditis who were excluded by applying the modified Duke's criteria. 1 of these patients required aortic valve replacement. 2 patients with disseminated Staphylococcal infections without endocarditis were classed as definite endocarditis by the modified Duke's criteria. Referral data and outcomes are included in Figure 1.

Conclusions

The endocarditis team can be used to improve the sensitivity and specificity of the modified Duke's criteria. As the endocarditis team became established the volume of referrals has increased, along with the number of patients who have alternate diagnoses. Practitioners should bear this in mind when establishing endocarditis teams.

Figure 1. Referrals over time by outcome

Funding Acknowledgement

Type of funding source: None
Lifetime mortality associated with hypertrophic cardiomyopathy: 28-year outcome of an historical cohort
Authors: Maurizi N , Cecchi F , Tomberli F , Baldini K , Fumagalli F , Bonacchi G , Marchionni N , Maron B.J , Olivotto I
Published: November 2020

Background

Current understanding of the lifetime mortality of patients with hypertrophic cardiomyopathy (HCM) has been extrapolated from cohorts with 8–10 years follow-up. Real survival rates and long-term burden of HCM are largely unresolved.

Objective

To describe HCM lifetime mortality over 28-years of observation.

Methods

We analyzed clinical/instrumental data of the historic cohort of 202 patients diagnosed from 1970s. ECG, echocardiographic, clinical records until last follow-up were recorded. Reasons for death were classified as HCM related (Sudden Death (SD), Heart Failure related (HF)) and non-HCM related deaths.

Results

Patients were followed-up for 28±6 years (41±17 to 69±14 years), 63% were males. Patients progressively dilated the Left Atrium (40±6 to 50±9mm, p<0.01), depressed ejection fraction (65±9 to 54±12, p<0.01), developed diastolic restrictive pattern and decreased LV wall thickness (23±5 to 19±4mm, p<0.01). One-hundred-eighteen deaths occurred at 66±12 years. HCM accounted for 69 deaths, 53 due to HF-related complications and 16 for SD. Annual HCM mortality rate increased from 0.6% at 10 years following diagnosis to 1.4% during 11–28 years of follow-up (p<0.01): HF yearly burden increased from 0.6% to 1.3%, p<0.01, SD remained similar in the two periods (0.1%, 0.4% respectively).

Conclusions

HCM-related mortality at 10 years significantly underestimated the lifetime rates of HF death, which doubled in the second/third decade of observation. Conversely, SD rates remained constantly low. Real burden of HCM is time dependent and can be appreciated only after prolonged exposure to the disease.

Funding Acknowledgement

Type of funding source: None
Survival analysis in arrhythmogenic/dilated cardiomyopathy caused by pathogenic DSP truncating variants
Authors: Lamounier Junior A , Alonso Garcia D , Fernandez Ferro G , Cardenas Reyes I.J , Salazar-Mendiguchia Y Garcia J , Ochoa J.P , Nicolas Cicerchia M , Pena-Pena M.L , Noel Brogger M , Garcia Hernandez S , Fernandez X , Ortiz M , Barriales-Villa R , Iglesias Monserrat L
Published: November 2020

Background

Desmoplakin (DSP) truncating variants have been associated with arrhythmogenic cardiomyopathy (ACM), which can exclusively affect the left ventricle up to 30% of the cases. Nonetheless, data on prognosis in carriers is still limited.

Purpose

To evaluate survival free of cardiovascular events in carriers of pathogenic DSP truncating variants.

Methods

Clinical and genetic data on families carrying DSP truncating variants (nonsense, frameshift, and splicing-site) in the literature were systematically revised and collected in a dedicated database. Classification of variant pathogenicity was in accordance with ACMG criteria. We evaluated available follow-up data and constructed Kaplan-Meier survival curves free from cardiovascular death (sudden death, appropriate cardiodefibrillator shock, heart failure death, and stroke-related death) or heart transplant based. Long-rank test was used to compare event-free survival time between genders.

Results

707 carriers (336 index cases and 371 relatives; 51.1% were female carriers) were identified carrying 198 variants (90 nonsense, 89 frameshift, 19 splicing-site). 292 had ACM, 136 dilated cardiomyopathy (DCM), eight cases of unexplained sudden death, 120 were unaffected carriers, and no clinical data was reported in 151 carriers. In addition, 73 affected relatives without genetic testing were reported (28 had ACM, 28 DCM, and 17 unexplained sudden deaths).

Survival data was reported for 449 individuals (221 males; 228 females). Eight-one had suffered events: 57 sudden cardiac death (32 males), 10 heart failure deaths (7 males), 7 transplants (5 males), 6 cardiodefibrillator shock (4 females), and one stroke-related death (1 female).

Incidence of cardiovascular death or transplant was higher in males than females (p=0.012), with annual incidence between ages 30–70 of 0.84%/year in males and 0.72%/year in females. Mortality at the age of 50 years was 31% for males and 16% for females.

Conclusion

DSP truncating variants are associated with a relevant risk of cardiovascular death, which is higher in males, especially after age 30. More than 70% of the events were sudden deaths.

DSP truncating variants survival curves

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Health in Code SA
MicroRNA-208b gene expression levels as a biomarkers of left ventricular dysfunction in patients with acute myocarditis
Authors: Marketou M , Kontaraki J , Fragiadakis K , Konstantinou J , Maragkoudakis S , Lempidakis D , Plevritaki A , Plataki M , Papadaki S , Vougia D , Vardas P , Parthenakis F
Published: November 2020

Purpose

MicroRNAs (miRs) play a major role in protein regulation by post-transcriptional gene expression and cell to cell interaction. Recently, they have been emerged as important modulators in cardiovascular development and disease. Our aim was to determine whether cardiac related miRs such as miR-208b was differentially expressed in peripheral blood mononuclear cells from patients with acute myocarditis. We also evaluated their expression levels in peripheral blood mononuclear cells in relation with left ventricular global longitudinal peak strain (GLPS) in those patients.

Methods

We assessed the expression levels of miR-208b in 55 patients with acute myocarditis (48 men, mean age 33±10 years) and 22 healthy individuals (18 men, mean age 33±9 years). Blood samples were taken on admission and miR expression levels in peripheral blood mononuclear cells were quantified by real-time reverse transcription polymerase chain reaction. All patients were also underwent an assessment with standard conventional transthoracic and a two-dimensional speckle tracking echocardiography.

Results

GLPS was significantly reduced in the group of myocarditis compared to healthy individuals (from −13.9±10.9% versus −22.2±6.7%, p<0.05). Myocarditis patients showed significantly higher miR-208b (28.8±16.6 versus 6.40±1.1, p<0.001) expression levels compared to control group. miR-208b gene expression levels at baseline revealed a significant negative correlation with GLPS on admission (r=−0.51, p<0.05). This correlation was independent of the patients' clinical parameters.

Conclusions

Our data reveal that miR-208b gene expression levels are upregulated in peripheral blood mononuclear cells from patients with acute myocarditis relative to healthy individuals. In addition, miR-208b levels have a prognostic value in the deterioration of left ventricular GLPS in those patients. Thus, miR-208b may represent a promising biomarkers in myocarditis or a potential therapeutic target in the future.

Funding Acknowledgement

Type of funding source: None
Distribution of pathological features and inflammatory cells in patients with giant cell myocarditis
Authors: Liu S , Hu Z , Yao Y
Published: November 2020

Background

Giant-cell myocarditis (GCM) is a rare disease with a poor prognosis, the etiology and pathophysiology of GCM remain largely unclear.

Purpose

Describe the distribution of GCM lesions, classify inflammatory cells, and explore the potential relationships of these features with clinical manifestations by examining the histopathological features of GCM in 8 patients who underwent heart transplantation.

Methods

Eight patients with pathological diagnoses with GCM underwent heart transplantation at our center. Hematoxylin- eosin (H-E) and Masson's tri-chrome staining were performed on biopsies of the free walls of the right and left ventricles and interventricular septa of the original hearts to determine the characteristic distribution of cardiac lesions and the composition of infiltrating immune cells. A multiplex immunohistochemistry and multispectral imaging analysis were applied to further classify the specific types of inflammatory immune cells.

Results

Inflammation found in a descending frequency gradually from the epicardium to the endocardium in the free wall of the left ventricle, but concentrated on the surface of right ventricular septum. Typical inflammatory infiltration and pathological changes were observed in the right-sided ventricular septum samples from all 8 patients. Numerous inflammatory immune cells, particularly CD4+ T cells, were detected in the lesion, which surrounded the emerging multinucleated giant cells. CD8+ T cells and a small number of regulatory T cells were scattered in the periphery.

Conclusions

In GCM, cardiac lesions appear to concentrate particularly beneath the epicardium of the left ventricular free wall and the right side of the ventricular septum. These findings provide a rationale for the diagnostic use of conventional endocardial biopsy. The findings further suggest that myocardial injury is mediated by a variety of lymphocytes, especially CD4+ T cells.

Distribution of lesions in GCM

Funding Acknowledgement

Type of funding source: None
The prolactine hypothesis for peripartum cardiomyopathy: has it found its feet for good?
Authors: Sousa J.P , Puga L , Lopes J , Saleiro C , Gomes R , Lourenco C , Goncalves L
Published: November 2020

Background

Peripartum cardiomyopathy (PPCM) is a rare but serious condition that affects childbearing women. Dopamine agonists (DAs) may represent a specific therapy, potentially facilitating left ventricular recovery, through inhibition of prolactin secretion. However, their therapeutic value in this setting has not been fully demonstrated.

Purpose

To perform a meta-analysis aimed at evaluating the extent to which DAs are able to interfere with the natural history of PPCM.

Methods

We systematically searched MEDLINE, Embase, Web of Science, Cochrane Library, Google Scholar, Scopus and DARE for both randomized controlled trials (RCTs) and observational studies addressing the impact of DAs on main outcomes of PPCM patients, published up until February 1, 2020. Endpoints were those of mortality, recovery from heart failure and, likewise, the degree to which left ventricular ejection fraction (LVEF) was restored. All analyses were conducted under a DA plus optimized medical therapy (OMT) vs. OMT alone design, while results were pooled using traditional meta-analytic techniques, under a random-effects model. Odds ratios (ORs) were computed for the first two outcomes, whereas mean difference (MD) was calculated to quantify LVEF restoration.

Results

2 RCTs, 2 prospective cohort, 1 prospective case-control and 2 retrospective cohort studies, encompassing 452 patients, were regarded as eligible for quantitative evaluation. 180 patients were allocated to the DA arm, which was mostly represented by bromocriptine; in fact, only 1 study, including 24 patients, specified cabergolin utilization. Overall, 5 papers including 295 patients reported 42 deaths, whereas 5 papers comprising 305 patients detailed 220 heart failure recoveries, thus unveiling that LVEF restoration was the norm. The addition of a DA to OMT provided no signal of a survival benefit (OR 0.71, 95% CI 0.27–1.87, p=0.49, i2=27%). On the other hand, the incorporation of a DA into the therapeutic regimen narrowly missed significance for the heart failure recovery endpoint (OR 2.68, 95% CI 0.98–7.31, p=0.05, i2=56%). Furthermore, DAs were demonstrated to incrementally improve LVEF by 15% (MD 15.00, 95% CI 10.24–19.76, p<0.00001, i2=77%). Adverse events, including thromboembolic ones, were rare, though adjunct anticoagulation was broadly reported.

Conclusion

In PPCM patients, the addition of a DA to OMT seems to be both effective at incrementally improving LVEF and safe, even though not reaching survival benefit status. These findings appear to corroborate the so-called prolactin hypothesis for PPCM pathophysiology.

Funding Acknowledgement

Type of funding source: None
High sensitivity troponin I in hypertrophic cardiomyopathy
Authors: Osmanska J , Connelly A , Nordin S , Vega A , Simpson J , Anusas J , Findlay I , Coats C
Published: November 2020

Background

ESC guidelines recommend measurement of troponin T in patients with hypertrophic cardiomyopathy (HCM) because high concentrations are associated with cardiovascular events, heart failure and death. The cardiac Troponin I subunit is not expressed in skeletal muscle making it a cardio-specific isoform. The use of troponin biomarkers in management of patients HCM is limited because concentrations only weakly correlate with clinical parameters. Most studies are small, and few have examined their relation with genotype and mortality.

Purpose

To assess the relationship between high-sensitive troponin I (hsTnI) and characteristics of adults with HCM.

Methods

Patients included were adults with an established diagnosis of HCM referred to a single centre for genetic testing. Demographic, clinical and imaging data were recorded at baseline. Echocardiography and cardiac magnetic resonance (CMR) were performed according to EACVI standards. Quantification of late gadolinium enhancement (LGE) was performed using the 5 SD quantitative threshold. Genotype was evaluated using a 16 gene panel in an accredited UK laboratory. Pathogenic and likely pathogenic variants were considered as a positive genotype. Serum hsTnI was measured by a two-site electrochemiluminescence immunoassay on a Roche E170 analyser. Normal values for the assay 0–34 ng/L for males and 0–16 ng/L for females.

Results

313 patients (n=200, 64% male) median age 57 (IQR 47–68) years were included. hsTnI concentration was abnormal in 69 (22%) patients. An abnormal hsTnI was more common in females (n=36, 32%) compared to males (n=33, 17%, c2 9.9, p<0.05). A pathogenic variant in a sarcomere gene was identified in 95 (30%) individuals. An abnormal hsTnI concentration was associated with higher left ventricular (LV) wall thickness (20mm v 18mm, p<0.05) and LV outflow tract (LVOT) gradient (34 v 22 mmHg) on echocardiography (n=313). Of the patients (n=204) who had a CMR, an abnormal hsTnI concentration was associated with higher LV mass (183 v 156g, p<0.05) and greater % LGE (30 v 16%, p<0.01, n=129). There was no difference in hsTnI between those with a positive or negative genotype. During follow-up, 18 patients died. Of the 9 patients that died with a normal hsTnI, two died suddenly.

Conclusions

In HCM, patients with abnormal hsTnI concentration have higher LV mass and LVOT gradient and more fibrosis. Whilst mortality is higher in those with abnormal hsTnI, sudden cardiac death may occur with a normal hsTnI. It may not be appropriate to extrapolate hsTnI sex-specific thresholds used in the diagnosis of myocardial infarction to HCM.

Funding Acknowledgement

Type of funding source: None