bluuebunny/crossref_metadata_2025 huggingface dataset:
Totally endoscopic aortic valve replacement: technique and first experience
Authors: Van Genechten S , Claessens J , Kaya A , Yilmaz A
Published: November 2020

Background

Cardiac surgery is still looking for new minimally invasive techniques with less trauma and better cosmetic results. In the field of aortic valve replacement, several types of less invasive procedures were introduced, allowing a reduction in blood loss, infections, ventilation times, morbidity and mortality. The most common technique for minimally invasive aortic valve replacement is the mini-sternotomy approach. In this report, the initial experience with a non-sternotomy approach for aortic valve replacement by means of a totally endoscopic surgical technique is presented.

Methods

The totally endoscopic aortic valve replacement was carried out in 201 patients (59,7% males, mean age: 71.6±11.7 years) from October 2017 until October 2019. Severe aortic valve stenosis was the surgical indication for all patients, who had a mean EuroSCORE II of 2.35±3.82. The surgery was carried out with the patient in supine position and a standard zero-degree optics was used. A 20 mm working port in the 2nd right intercostal space and two 5 mm trocars gained access to the aorta. After groin cannulation, cardiopulmonary bypass was initiated. Transthoracic aortic cross-clamping followed by antegrade administration of a single shot cold mixed-blood cardioplegia was assessed. The aortotomy was followed by the excision of the stenotic aortic valve and the aortic valve prosthesis was implanted in supra-annular position. After the closure of the aorta, an external pacemaker wire was placed.

Results

Mean cross-clamp and cardiopulmonary bypass times were 62±14 and 94±25 minutes, respectively. No conversion to a sternotomy was needed. The mean length of stay at the intensive care unit was 69.4±149.6 hours while patients spend 9.6±10 days at the hospital. Due to our new fast track protocol, the mean hospital stay in the last two months was 6.1 days (26 patients, 12.9%). The average postoperative blood loss (24h) was 251±298 mL and the patients were ventilated for 6.9±9 hours. In 10 patients (4.9%), re-exploration in an endoscopic way was needed. None of them had a surgical bleeding focus. No paravalvular leakages were detected at discharge. 69 patients (34.7%) developed atrial fibrillation after surgery. In addition, 10 patients (4.9%) underwent a pacemaker implantation postoperatively whereas 4 patients (1.9%) suffered from a CVA. Finally, the 30-day mortality was 2.0%.

Conclusion

These results concerning the feasibility and safety of totally endoscopic aortic valve replacement are promising. The aortic cross clamping times are acceptable, and the morbidity and mortality rates are low. Long term results are needed to confirm these initial findings.

Funding Acknowledgement

Type of funding source: Private hospital(s). Main funding source(s): Jessa Hospital
Clinical and echocardiographic outcomes of patients with moderate to severe aortic stenosis and preserved, mid-range and reduced ejection fraction
Authors: Chew N , Ngiam N , Tan B.Y.Q , Sia C.H , Sim H.W , Kong W.K.F , Tay E.L.W , Yeo T.C , Poh K.K
Published: November 2020

Background

Left ventricular ejection fraction (EF) plays an important role in risk stratifying and guiding therapy for patients with aortic stenosis (AS). This study aims to describe the clinical and echocardiographic outcomes of AS patients with preserved (ASpEF), mid-range (ASmrEF) and reduced (ASrEF) EF.

Methods

713 consecutive patients with index echocardiographic diagnosis of moderate-severe AS (aortic valve area <1.5cm2) were allocated according to the EF into three groups: ASrEF (EF<40%), ASmrEF (EF 40–50%), and ASpEF (EF>50%). The study outcomes were defined as 5-year all-cause mortality, heart failure admissions, and aortic valve replacement (AVR).

Results

In comparison to patients with ASpEF, those with ASrEF were more frequently male, and systolic blood pressure was significantly lower on enrolment (p<0.001). Diabetes, ischemic heart disease and atrial fibrillation were more commonly seen in the ASrEF and ASmrEF groups, compared to ASpEF group. All-cause mortality rates were 30.5% for ASpEF, 50.8% for ASmrEF, 55.0% for ASrEF groups (p<0.001). Increased rates of heart failure admissions were seen in the ASmrEF and ASrEF groups (30.5% and 33.9%, respectively, vs. 14.9% in ASpEF group). Patients with ASrEF had significantly higher rates of AVR as compared to those in the ASmrEF and ASpEF groups (p=0.032).

Conclusion

Echocardiographic and clinical outcomes of ASmrEF patients resembled those of ASrEF more closely than the ASpEF patients. Stratifying AS patients according to the different EF groups may improve risk assessment and treatment strategies.

Figure 1

Funding Acknowledgement

Type of funding source: None
The prevalence and natural history of mitral annulus calcification
Authors: Kato N , Guerrero M , Scott C.G , Lee A.T , Eleid M.F , Alkhouli M.A , Nkomo V.T , Crestanello J.A , Rihal C.S , Pislaru S.V , Pellikka P.A
Published: November 2020

Background

There is a paucity of data about the prevalence and natural history of mitral annular calcification (MAC).

Purposes

In a large cohort of patients undergoing clinically-indicated echocardiography, we aimed to evaluate the prevalence and the natural history of MAC, and the frequency of associated mitral valve dysfunction (MVD).

Methods

Retrospective review of all patients who underwent echocardiographic evaluation at our institution between January 1st and December 31st 2015. The patients were stratified into 3 groups: MAC with MVD, MAC without MVD, no MAC. MVD was defined as moderate or greater mitral regurgitation (MR) or stenosis (MS). The 3 groups were compared for baseline clinical and echocardiographic characteristics and all-cause mortality during follow-up.

Results

Of 24,415 evaluated patients, 5478 (22%) had MAC. Patients with MAC were older (75±10 vs. 60±16 years, p<0.01) and more often female (46% vs. 43%, p<0.01). MVD was more frequently observed in patients with MAC (16% vs. 7%, p<0.01); moderate or greater MR was found in 10% of patients with MAC vs. 6% without MAC (p<0.01) and MS in 7% vs. 0.5% (p<0.01). In patients with MAC, those with MVD were more often female and more frequently had creatinine ≥2mg/dl and moderate or greater aortic stenosis (AS) than those without MVD (Fig. A). Kaplan-Meier survivals at 1 year were 75% in patients with MAC and MVD, 87% in those with MAC without MVD, and 92% in those without MAC (Fig B). Adjusted for age, sex, diabetes, creatinine ≥2 mg/dl, coronary artery disease, left ventricular ejection fraction <50%, and AS, MAC was associated with higher all-cause mortality (adjusted hazard ratio1.4, 95% confidence interval: 1.3–1.5, p<0.01); combined MAC and MVD was associated with the highest mortality during follow-up of 2.5±1.8 years.

Conclusion

In a large cohort of patients undergoing echocardiographic evaluation, the prevalence of MAC was 22%. MV dysfunction was more than twice as prevalent in patients with MAC as without. Patients with MAC had higher all-cause mortality than patients without MAC. Among patients with MAC and mitral valvular dysfunction, adjusted mortality was two-fold higher compared to those without MAC.

Funding Acknowledgement

Type of funding source: None
The 3 noes right-sided infective endocarditis: a unrecognized type of right-sided endocarditis
Authors: Lopez Diaz J , Vilacosta I , Habib G , Miro J.M , Olmos C , Sarria C , Gonzalez-Juanatey C , Gonzalez-Juanatey J.C , Cuervo G , Cabezon G , Garcia-Granja P.E , Gomez I , San Roman J.A
Published: November 2020

Introduction

The “3 noes right-sided infective endocarditis” (3no-RSIE: no left-sided, no drug users, no cardiac devices) was depicted for the first time more than a decade ago. We describe the largest series to date to characterize its clinical, microbiological, echocardiographic and prognostic profile.

Methods

Eight tertiary centers with surgical facilities participated in this study. Patients with right-sided endocarditis without left involvement, absence of antecedents of drug use and no intracardiac electronic devices were retrospectively included in a multipurpose database. A total of 53 variables were analysed in every patient. We performed a univariate analysis of in-hospital mortality to determine variables associated with worse prognosis.

Results

A total of 100 patients (mean age 54.1±20 years, 65% male) with definite 3no-RSIE were included (16.7% of all the right-sided endocarditis of the series). Most of the episodes were community-acquired (72%), congenital cardiopathies were frequent, fever was the main manifestation at admission (85%). The microbiological profile is led by Staphylococci spp. Vegetations were detected in 92% of the patients. Global in-hospital mortality was 19% (5.7% in patients operated and 26% in patients who received only medical treatment, p<0.001). Non community-acquired infection, diabetes mellitus, right heart failure, septic shock and acute renal failure were more common in patients who died.

Conclusions

The clinical profile of 3no-RSIE is closer to other types of RSIE than to LSIE, but mortality is higher than that reported on for other types of RSIE. Surgery plays an important role in improving outcome.

Funding Acknowledgement

Type of funding source: None
Diagnosis and management of coronary artery disease in early surgical treatment of acute infective endocarditis of the aortic valve
Authors: Knol W.G , Wahadat A.W , Roos-Hesselink J.W , Tanis W , Hirsch A , Van Mieghem N.M , Bogers A.J.J.C , Budde R.P.J
Published: November 2020

Background

The need to routinely screen for coronary artery disease (CAD) in asymptomatic patients undergoing surgery for acute aortic valve infective endocarditis (IE) is debated. There is concern about the risk of embolization during invasive coronary angiography (ICA), especially in patients with vegetations. Coronary computed tomography angiography (cCTA) is a non-invasive alternative.

Purpose

To evaluate the prevalence of CAD in patients with acute aortic valve IE, the safety and feasibility of ICA and cCTA for diagnosis of CAD, and CAD related postoperative outcomes.

Methods

In this single center retrospective cohort study, all patients with acute infective aortic valve endocarditis between 2009–2019 undergoing surgery were selected. Outcomes were embolization after preoperative ICA, in-hospital mortality, perioperative myocardial infarction or unplanned revascularization.

Results

159 patients (mean age 58±15, 81% male) underwent surgery. No CAD screening was done in 46/145, a cCTA was performed in 54/145 patients and an ICA in 52/145 patients. In 1 of the 52 patients undergoing preoperative ICA a cerebral embolism occurred. cCTA was not assessable on a patient level in 2 patients and 7 patients underwent both cCTA and ICA. Significant CAD was found in about 20% of patients both after cCTA and ICA. Even though just a minority of patients with CAD was treated with concomitant CABG, only 1 patient with known but untreated CAD needed unplanned revascularization postoperatively. The rate of perioperative myocardial infarction or unplanned revascularization in patients not screened for CAD was 5% (3 patients).

Conclusion

In patients with acute aortic valve IE the prevalence of CAD is low (14%). The risk of embolism after preoperative ICA is not negligible and should be carefully weighed against the estimated risk of CAD-related perioperative complications. cCTA might serve as a gatekeeper for ICA in many patients with acute aortic IE.

Funding Acknowledgement

Type of funding source: None
Age-related characteristics of infective endocarditis: prospective data from the Euro-Endo registry
Authors: Pazdernik M , Selton-Suty C , Lancellotti P , Kong W.K.F , Srdanovic I , Yamada H , Riezebos R.K , De Martino A , Pierard L , Nunes M , Haertel Miglioranza M , Magne J , Mutlu B , Habib G , Iung B
Published: November 2020

Introduction

The profile of infective endocarditis (IE) is continuously evolving over time, and this may probably be partly due to increasing age of the patients.

Methods

All data were collected from the EURO-ENDO registry, which is a one-year prospective international multicentre observational survey on patients with definite or possible IE included between 2016 and 2018. Subjects were stratified into 3 groups according to their age at index hospitalization.

Results

Among the 3113 patients included, 1670 patients (54%, Young group) were <65, 1068 (34%, Medium group) between 65 and 80 and 375 (12%, Old group) ≥80 years old. The most striking age-related differences were (old group vs others) (table 1) 1) the higher comorbidity burden and Charlson index; 2) the lower rate of embolic events on admission and under therapy; 3) the higher rate of Enterocci and digestive streptococci; 4) the lower rate of surgery during acute IE despite a theoretical indication; 5) the higher in-hospital and 1-year mortality. With regards to surgery, young and medium age were predictive of more frequent performance of surgery as compared to old age (Young: OR 4.33, 95% CI [3.09–6.06], Medium: 3.62, [2.57–5.10], p<0.001). In multivariable analysis, age per se was not predictive of in-hospital and 1yr FU mortality, but lack of surgical procedures when indicated (27% of the old group), was strongly predictive.

Conclusion

This is the largest contemporary registry showing the strong influence of age on the demographic, clinical, therapeutic, and prognostic profile of IE. Non-performance of surgical procedures when indicated is frequent in old patients and is a strong predictor of mortality while age per se is not. Endocarditis Teams should take these results into account when considering surgery in elderly patients.

Funding Acknowledgement

Type of funding source: Other. Main funding source(s): EORP grant
Cardiac sympathetic denervation in wild-type transthyretin amyloidosis
Authors: Aimo A , Gimelli A , Vergaro G , Genovesi D , Kusch A , Emdin M , Marzullo P
Published: November 2020

Background

Tissue accumulation of misfolded transthyretin (TTR) may occur because of TTR gene mutations (variant amyloid TTR amyloidosis, ATTRv), or as an age-related phenomenon (wild-type ATTR, ATTRwt). Cardiac sympathetic denervation has been reported in ATTRv, but has never been investigated in ATTRwt.

Methods

Fifteen consecutive patients with ATTRwt cardiomyopathy (81% men, median age 82 years, no one with prior myocardial infarction) underwent Cadmium Zinc Telluride tomographic imaging for amyloid burden (99mTc-hydroxymethylene diphosphonate - 99mTc-HMDP), innervation (123I-metaiodobenzylguanidine – 123I-MIBG), and perfusion (99mTc-tetrofosmin).

Results

Median summed 99mTc-HMDP score was 60 (58–62), denoting a severe and diffuse amyloid burden. Planar 123I-MIBG examination showed decreased early and late H/M ratios (late H/M ratio: 1.5 [1.3–1.6], range 1.2–1.9, reference value ≥2.0). Summed 123I-MIBG score was 12 (6–22), with the most prominent denervation in the infero-septal, inferior, and infero-lateral regions; summed rest score was 7 (5–11), with lowest degrees of myocardial perfusion in the inferior and infero-septal regions. The correlation between amyloid burden (as relative 99mTc-HMDP uptake) and innervation (as relative 123I-MIBG uptake) did not achieve statistical significance at both segmental (p=0.252) and regional level (p=0.251). Nevertheless, denervation tended to worsen in parallel with the amyloid burden, and 123I-MIBG scores increased with 99mTc-HMDP scores. Segments and regions with more prominent hypoperfusion were those showing the more intense denervation (r=0.500 and 0.591, respectively; both p<0.001).

Conclusions

Patients with ATTRwt cardiomyopathy display cardiac sympathetic denervation, particularly in the inferior and septal myocardial wall. Myocardial hypoperfusion has a similar regional pattern, while the amyloid burden is more extensive.

Funding Acknowledgement

Type of funding source: None
Comparing machine learning approaches to identify myocardial scar from the ECG
Authors: Tung J , Rogers A.J , Ravi N , Bhatia N.K , Shah R.L , Purewal S.K , Baykaner T , Rappel W.J , Viswanathan M.N , Brodt C.R , Wang P.J , Clifford G , Tereshchenko L , Narayan S.M
Published: November 2020

Background

Detection of myocardial infarction (MI) traditionally requires ECG Q waves, which have poor sensitivity, or imaging, which is time consuming. We hypothesized that machine learning (ML) of the ECG could identify prior MI, but its accuracy may depend highly upon the architecture and parameters chosen.

Purpose

To compare ML architectures that predict prior MI from the ECG.

Methods

We curated ECGs in 608 patients seen in cardiology clinics at 2 centers. We transformed 12-lead ECGs to median beats in Frank (X, Y, Z) planes (fig. A). We tested 3 architectures: a 1D deep neural network (DNN), a 3D neural network, and a support vector machine (SVM). The 1D DNN used only temporal convolutions (fig B) while the 3D DNN uses a spatial convolution (fig C) prior to the fully-connected layer (fig. C). Predictive accuracy for history of MI was compared for all architectures (fig. D).

Results

Patients (61.4±14.5 years, 31.2% female) had a 28.7% (175/608) prevalence of prior MI. Optimized SVM of 6 features provided accuracy of 66.1% for identifying prior MI, similar to ECG Q wave analysis. 1D DDN had accuracy of 63.6% with an area under curve (AUC) of 0.625. 3D DNN outperformed 1D DNN and SVM, providing an accuracy of 71±5% (using k=5-fold cross validation), with an AUC of 0.730.

Conclusion

ECG machine learning can identify prior MI better than Q wave analysis, but is sensitive to technical parameters and specific computational architecture. It is important to develop a framework to enable robust comparisons of different ML studies and future refinements.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Institutes of Health - United States
Immunosuppression and outcomes of myocarditis patients presenting with ventricular arrhythmias
Authors: Peretto G , Sala S , De Luca G , Marcolongo R , Campochiaro C , Tresoldi M , Foppoli L , Palmisano A , Esposito A , De Cobelli F , Rizzo S , Thiene G , Basso C , Caforio A.L.P , Della Bella P
Published: November 2020

Background

Effects of immunosuppressive therapy (IST) on ventricular arrhythmias (VA) have not been reported in immune-mediated biopsy-proven myocarditis patients. Furthermore, myocarditis arrhythmic risk is still unpredictable. The aim of our study was to evaluate effectiveness of IST on VA in myocarditis patients, and stratify their arrhythmic risk, using clinical and diagnostic features, including serum organ-specific anti-heart (AHA) and antiintercalated-disk autoantibodies (AIDA).

Methods

From a cohort of 498 consecutive patients, we enrolled 255 cases with biopsy-proven virus-negative myocarditis and evidence of VA (VF, VT, NSVT, and Lown's grade ≥2 PVC) at index hospitalization. Serum AHA and AIDA were detected by a standardised indirect immunofluorescence technique. Whenever accepted and non-contraindicated, IST was started. Controls (IST-) were chosen after 1:1 matching to IST+ cases by age, gender, ethnicity, left ventricular ejection fraction, VA type, and treatment. Prospective follow-up (FU), occurred at defined timepoints.

Results

58 matched patient couples (42±13 y, 67% males, 50% IST+) were analyzed in the main study cohort. Overall, 28 (24%) had VT, and 62 (53%) were discharged with ICD. IST duration was 12±1 months. No patients died and no serious complications from IST occurred. By 24-month FU, major VA occurred in 6 IST+ vs. 10 IST- patients (p=0.420), with no cases of VT following IST termination. As compared to IST- ones, IST+ patients showed a significant reduction in NSVT and PVC burden, as well as an improvement in clinical, laboratory and imaging findings (all p<0.05). Major VA onset and positive AIDA status were independently associated with major VA at FU (HR 14.2, 95% CI 2.9–68.7, and 8.0, 95% CI 2.6–25.2, respectively, both p<0.001). Furthermore, in the whole study population (N=255), IST played as an independent protective factor from major VA (HR 0.3, 95% CI 0.2–0.7, p=0.005) at 38±21 months FU.

Conclusions

In immune-mediated virus-negative myocarditis patients presenting with VA, IST is feasible and effective on NSVT and PVC burden, as well as on structural, laboratory and imaging endpoints. Short-term effects are limited on major VA, which were independently associated with major arrhythmic onset and positive AIDA, in keeping with the proposed etiopathogenetic involvement of autoimmunity in virus-negative myocarditis.

Funding Acknowledgement

Type of funding source: None
Predictors of atrial fibrillation occurrence in patients with hypertrophic cardiomyopathy
Authors: Castelo A , Rosa S , Fiarresga A , Marques H , Portugal G , Cunha P , Ferreira V , Bras P , Goncalves A , Oliveira M , Ferreira R
Published: November 2020

Introduction

Patients with hypertrophic cardiomyopathy (HCM) are at increased risk of dysrhythmias, especially atrial fibrillation (AF).

Purpose

The aim of this study was to evaluate the incidence of AF in HCM patients (P) and to determine predictors of AF.

Methods

Retrospective analysis of HCM P at a single tertiary center. Baseline clinical, echocardiographic and cardiovascular magnetic resonance (CMR) characteristics were collected. On follow up AF was identified by electrocardiogram and/or 24 hours Holter monitoring.

Results

61P (59% male) were included, with a mean age of 58±2 years. 27.9% had angina (all of them CCS 2), 34.4% were in NYHA II and 14.8% in NYHA III, 8.2% had syncope and 39.3% had palpitations. A family history of sudden cardiac death (SCD) or cardiomyopathy was present in 40.4% of the cases. The mean HCM risk SCD score was 3.35±0.28%. On echocardiography left atrium (LA) diameter was 44.86±0.87mm, LA volume (LAvol) was 89.97±5.39mL (indexed LAvol 46.05±2.55mL/m2), interventricular septum (IVS) was 16.83±0.663mm, left ventricle (LV) mass was 290.94±13.897g and maximum wall thickness (MWT) was 20.59±0.596mm. 77% P had LA enlargement. 88.5%P had late gadolinium enhancement (LGE) in CMR with a median number of 5±7 segments involved. AF developed in 23P (37.7%), with a mean age of 58±3 years. Predictors of AF development were NYHA III (p=0.007), risk score (p=0.007), LA diameter (p=0.007), LAvol (p=0.005) and indexed LAvol (p=0.002), MWT (p=0.0015), LGE in more than 5 segments (p=0.029) and LGE in the inferior basal and inferior median IVS (p=0.033 and p=0.042). The only independent predictor was LAvol (p=0.0012), with an area under the curve of 0.755 and a cut off of 85.9mL being the best predictor (p=0.004). Combining LAvol >85.9mL with LGE involving >5 segments and LAvol >85.9mL with LGE in inferior basal IVS (IBIVS) a statistically significant difference between groups was achieved (p=0.009 in the combined predictor LAvol + LGE >5 segments and p=0.002 in the combined predictor LAvol + LGE in IBIVS) (figure 1 and figure 2). In a multivariable analysis including these 2 combined predictors and LAvol alone the only independent predictor was the combination of LAvol + IBIVS involvement.

Conclusion

AF is frequent in patients with HCM and develops in younger ages than in general population. NYHA III, risk score, LA diameter, LAvol, MWT, LGE >5 segments and LGE in IBIVS and in IMIVS were predictors of AF, with LAvol being the independent predictor. The combination of LAvol with LGE >5 segments and LAvol with LGE in IBIVS presented stronger predictor value comparing with these characteristics alone.

Funding Acknowledgement

Type of funding source: None
Prevalence of device-detected atrial fibrillation and stroke in patients with hypertrophic cardiomyopathy
Authors: Fumagalli C , Ruggieri R , De Filippo V , Cappelli F , Beltrami M , Bertini A , Carrassa G , Marchi A , Tomberli A , Baldini K , Olivotto I
Published: November 2020

Introduction

Atrial fibrillation (AF) is highly prevalent in patients with hypertrophic cardiomyopathy (HCM) and is associated with adverse outcome, impaired quality of life, loss of productivity, and the risk for embolic stroke. However, still today, the real burden of AF is unresolved due to the unknown frequency of silent asymptomatic episodes.

Purpose

To assess the prevalence of device-detected AF and stroke in patients with HCM implanted with cardiac implantable electronic devices (CIEDs) at our institution, a long-standing high flow referral center for cardiomyopathies.

Methods

Clinical and instrumental data of HCM patients implanted with CIEDs (either pacemakers [PM] or implantable cardioverter defibrillator [ICD]) from 1998 to 2019 were retrospectively reviewed. Inclusion criteria were site-designated diagnosis of HCM, age at diagnosis >18 years, >1 follow up visit, follow up >1 year. HCM phenocopies (e.g. Fabry disease) were carefully excluded.

Patients were divided into three categories according to presence of AF (“AF prior to CIED implantation” vs “AF after CIED implantation” vs “no arrhythmia detected”). Outcome was measured against prevalence of thromboembolic events (stroke or transient ischemic attack [TIA]) at follow up. All-cause and cardiovascular (CV) mortality were also assessed.

Results

A total of 255 patients received a CIED (57% men, mean age at implantation 54±17 years). Men were younger at implantation (52±17 vs 56±18 years, p=0.022). At baseline, AF was present in 90 (35.3%) patients.

During 5.0±4.1 years, de novo AF was detected in 30 (11.8%) individuals, resulting in an annual incidence rate of 6.1%/year. Overall, 135 (52.9%) of patients remained is sinus rhythm.

Stroke/TIAs were reported in 30 (11.8%) patients: 16 (53.3%) occurred in patients with prior history of AF, 3 (10%) in patients with de novo AF (with men being at higher risk, OR 3.73, 95% CI 1.88–6.09, p=0.041), and 11 (36.7%) in patients with no history of arrhythmias.

Long term, 45 (17.6%) patients died (CV mortality N=38, 14.9%). At multivariable analysis, history of stroke was directly related to all-cause mortality irrespective of AF in men (OR 4.15, 95% CI 1.35–12.77, p=0.018) but not in women (OR 0.891, 95% CI 0.17–4.64, p=0.801).

Conclusions

In a large cohort of consecutive high risk HCM patients referred to CIED implantation, the incidence of de-novo AF was high. Thromboembolic events were associated to worse outcome only in men, likely due to competing heart failure related causes in women. Strategies promoting early identification of AF and anticoagulation may play an important role in management and prevention of disease-related complications.

Prevalence of AF and Stroke

Funding Acknowledgement

Type of funding source: None
Phenotype and clinical outcomes of dystrophin associated dilated cardiomyopathy
Authors: Restrepo Cordoba M.A , Wahbi K , Florian A , Mogensen J , Jimenez-Jaimez J , Climent-Paya V , Politano L , Garcia-Alvarez A , Arad M , Barriales-Villa R , Kubanek M , Lopes L.R , Jurcut R , Hazebroek M.R , Garcia-Pavia P
Published: November 2020

Background

Mutations in dystrophin gene (DMD) can cause skeletal myopathy and dilated cardiomyopathy (DCM) independently or in combination. Natural history of DMD mutation carriers and dystrophin-associated DCM is poorly understood.

Objectives

This study sought to describe phenotype and prognosis of DMD mutations in a large multicenter cohort of Non-Duchenne DMD mutations carriers.

Methods

The study cohort comprised 223 individuals with a DMD mutation (83% males, 33±15 years at first evaluation) followed at 26 European centers. Major adverse cardiac events (MACE) were defined as a composite of cardiac death, heart transplant, LVAD implantation, aborted SCD or appropriate ICD shock.

Results

At initial evaluation, 85 patients (38%) had DCM (52 in combination with muscular disease) and 92 (41%) had isolated muscular disease. After a median follow-up of 96 months, 112 individuals (53%) had DCM and 20% of the individuals who had normal cardiac function at baseline developed DCM. DCM penetrance by age 30 was 56%. DCM onset was associated with male sex and was independent of the type of mutation, the presence of skeletal myopathy or serum creatine kinase levels. MACE occurred in 11% and 22% individuals from the entire cohort and with DCM respectively, and were more frequent in DCM patients without muscular disease than in those with skeletal myopathy (35.5% vs 17.7%; p=0.04). Among patients with DCM, 18% developed end-stage heart failure and 9% a major arrhythmic event (SCD/aborted SCD/ICD shock/VT). There were not differences in survival between patients with isolated DCM and those with DCM and muscular phenotype. Decreased LVEF and increased left ventricular end-diastolic diameter at baseline were associated with MACE. Atrial fibrillation and neurological events were also frequent. Prognosis of individuals who did not develop DCM was good with 96% survival during follow-up.

Conclusions

DCM caused by mutations in DMD is characterized by moderate penetrance but a high risk of MACE, progression to end-stage heart failure and ventricular arrythmias. DCM onset is the major determinant of prognosis in DMD mutation carriers with similar survival irrespectively of the presence of concomitant muscular disease.

Survival free of MACE analysis

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): Instituto de Salud Carlos III. Contratos i-PFIS: Doctorados IIS-empresa en Ciencias y Tecnologías de la Salud
A clinical and instrumental study of heart failure in amyloidotic cardiomyopathy
Authors: Caponetti A.G , Longhi S , Saturi G , Ponziani A , Sguazzotti M , Massa P , Milandri A , Salvi F , Biagini E , Rapezzi C , Galie' N , Gagliardi C
Published: November 2020

Background

Heart failure (HF) is one of the main features of amyloidotic cardiomyopathy (AC) and it is supposed to carry important prognostic implications. Despite the intrinsic etiologic heterogeneity of AC, HF has been mainly attributed to diastolic dysfunction, but the role played by the different amyloid subtypes of AC and by the clinical and hemodynamic factors in the pathophysiology of HF remains unclear.

Objectives

We aimed to assess the hemodynamic profile and outcome of patients with or without advanced HF (defined as NYHA class III-IV) at the time of first evaluation in light-chain (AL), hereditary transthyretin-related (h-ATTR) and non-mutant transthyretin-related (wt-ATTR) AC.

Methods

Among the 411 patients diagnosed with AC (156 AL, 131 h-ATTR, 124 wt-ATTR) at our Centre between 1990–2019, we analyzed central hemodynamic data, echocardiographic, clinical, ECG details and survival of the whole cohort. Cox regression analysis was used to stratify prognosis.

Results

112 (27%) patients presented advanced HF at first evaluation and frequently showed severe symmetric left ventricle wall thickening (higher values in h-ATTR), non-dilated left ventricle, preserved ejection fraction and pathological global longitudinal strain and/or myocardial contraction fraction.

At ECG, a significantly lower QRS voltage was present in advanced HF patients. Hemodynamically, elevated filing pressures on both cardiac sides were present in patients in NYHA III-IV class of the three etiologies. Overall survival at 2 years was 35% for AL, 83% for h-ATTR, 65% for wt-TTR. H-ATTR and wt-TTR were favorable predictors of survival, while reduced cardiac index and elevated filling pressures were indepedently associated with higher mortality.

Conclusions

The characterization of hemodynamic profile plays a central role in predicting the natural history of AC, since reduced stroke volume and elevated filling pressures are the best predictors of mortality, reflecting a physiopathological restrictive model of the disease. Conversely, left ventricular ejection fraction is rarely abnormal and it is not a reliable marker of poor prognosis, especially in the early stages of the disease. AL amyloidosis shows the worst outcome probably due to a combination of the underlying illness and light chains cardiotoxicity.

LVEF and cardiac index in HF

Funding Acknowledgement

Type of funding source: None
Interleukin-1 blockade in patients with pericardial constriction
Authors: Andreis A , Imazio M , Brucato A , De Ferrari G.M , Rinaldi M , Adler Y
Published: November 2020

Background

Recurrent pericarditis is very difficult to treat, especially when symptoms become refractory to conventional treatments (nonsteroidal anti-inflammatory drugs,colchicine,corticosteroids). Interleukin-1 (IL-1) blockade with anakinra has been proved to be useful in this setting. Indeed, persistent inflammation of the pericardium may lead to pericardial constriction, worsening prognosis.

Purpose

This study was aimed to assess the incidence and clinical course of pericardial constriction in patients with corticosteroid-dependent, colchicine-resistant recurrent pericarditis (CCRP) undergoing anti IL-1 treatment.

Methods

We selected patients included in the IRAP (International Registry of Anakinra for Pericarditis). A subgroup of 39 CCRP patients enrolled at the coordinating center underwent echocardiographic and clinical assessment for pericardial constriction.

Results

Thirty-nine patients were assessed, aged 42±12 years old, 67% females, 74% idiopathic etiology, with a median disease duration of 12 months (IQR 9–20) and a recurrence rate of 2.79 flares-patient/year before starting anakinra. Echocardiographic signs of pericardial constriction were demonstrated in 8 patients (21%). After starting anakinra, in 5/8 patients (63%) a complete resolution of pericardial constriction was observed within a median of 1.2 months,IQR 1–4. In other 3/8 patients (37%) pericardial constriction persisted and became chronic, requiring pericardiectomy within a median of 2.8 months, IQR 2–5.

Compared with others, the 8 patients with pericardial constriction hadn't had a greater burden of pericardial flares before anakinra (3.87 flares-patient/year vs. 2.62/patient-year, p=0.07) and after anakinra (0.71 flares-patient/year vs. 0.72/patient-year, p=0.99). However, among 11 patients (28%) with incessant symptoms, an higher incidence of pericardial constriction was observed, compared with patients with recurrent symptoms (respectively 64% vs. 3.6%, RR=47, 95% CI 4.5–492, p<0.01).

Conclusions

In CCRP patients, pericardial constriction may be reversed by anti IL-1 agents. The risk of pericardial constriction is associated with incessant symptoms rather than simple recurrent course.

Funding Acknowledgement

Type of funding source: None
Outcomes in patients with cardiac masses: the underestimated burden of pseudotumours
Authors: Paolisso P , Foa' A , D'Angelo E.C , Saturi G , Bergamaschi L , Toniolo S , Magnani I , Bartoli L , Angeli F , Donati F , Stefanizzi A , Rinaldi A , Pacini D , Pizzi C , Galie' N
Published: November 2020

Background

Cardiac masses (CMs) include benign and malignant formations. So far, clinical presentation and prognosis have been reported only in small series without discriminating between subtypes. We investigated the clinical presentation and long-term prognosis of patients with cardiac masses stratifying our results according to the lesions' nature.

Methods

We enrolled all consecutive patients admitted to our Institution between 1999 and 2018 with imaging evidence of CMs. Definitive diagnosis was achieved by histologic examination or by radiological evidence of thrombotic resolution after anticoagulant treatment. The study population was classified as benign or malignant and subsequently into 4 subtypes: pseudo-tumours, primary benign tumours, primary malignant tumours and secondary tumours. Cardiovascular and non-cardiovascular mortality was described.

Results

We identified 172 patients with CMs, 125 benign and 47 malignant. Benign lesions were often incidentally diagnosed in the left heart chambers whereas malignancies were usually detected in the pericardium and right sections, resulting in more advanced symptoms. Over time – median follow-up of 48 months - survival of patients with benign formations was three-fold greater than patients with malignancies (p<0.001) with no differences in cardiovascular mortality. Patients with pseudo-tumours showed a significantly lower survival than primary benign tumours (p=0.018) while no difference was found within the malignant stratum between primary and secondary neoplasms.

Conclusions

CMs are a heterogeneous entity where advanced symptoms and a pericardial involvement suggest malignant forms, which exhibit a poor outcome. Among patients with benign lesions, pseudo-tumours were associated with reduced survival, supposedly as a consequence of the different underlying conditions.

Funding Acknowledgement

Type of funding source: None
Prevalence of congenital cardiac tumours in 25,000 neonates
Authors: Sillesen A , Axelsson Raja A , Voegg R.O.B , Pihl C.A , Paerregaard M.M , Fogh K , Norsk J.B , Vejlstrup N.G , Iversen K.K , Bundgaard H
Published: November 2020

Background

Primary cardiac tumours in children are rare, with an estimated prevalence of 0.014% in foetuses, whereas in the paediatric population, a 100-fold difference in autopsy prevalence has been reported (0.0017% to 0.28%). In neonates, rhabdomyoma is the most common primary cardiac tumour, followed by teratoma and fibroma, all of which are benign. Cardiac rhabdomyomas are associated to tuberous sclerosis in >50% of cases. The prevalence of cardiac tumours in neonates has not previously been assessed in a large population-based cohort.

Purpose

To determine the prevalence of congenital cardiac tumours by systematic echocardiography in a large, population-based, cohort of neonates.

Methods

Systematic transthoracic echocardiography (TTE), including standard sub-xiphoid, apical, left parasternal, and suprasternal views, was performed in neonates included in a population study. Cardiac tumours were defined as solid, echogenic masses, and description included location, size, and numbers (one/multiple). Information regarding subsequent diagnosis of tuberous sclerosis was collected from review of medical charts.

Results

A total of 25,537 neonates (age 12±9 days, 51.6% male) were enrolled in the study and underwent TTE. Cardiac tumours were detected in 7 neonates (4 males), corresponding to a prevalence of 0.3 [0.1; 0.6] per 1,000 live-births. Characteristics including sex, gestational age at birth, birth length and weight, APGAR 5-score, age and weight at TTE, and maternal age and pre-pregnancy BMI, did not significantly differ between the neonates with (n=7) and without (n=25,530) cardiac tumours (all p>0.05). In 6 out of 7 neonates, the cardiac tumours were located in the ventricles (86%), with multiple tumours seen in five (83%) (Fig. 1A+B), and with size ranging from 2.0x1.9mm to 10.0x5.1mm. In the seventh neonate, two cardiac tumours were detected in close proximity to the aortic and pulmonary valves in the ascending aortic and main pulmonary artery wall (Fig. 1C), with sizes 5.1x4.7mm and 3.7x3.2mm, respectively. All seven neonates had otherwise structurally normal hearts and no flow obstruction. Three neonates with multiple cardiac tumours in the ventricles were subsequently diagnosed with tuberous sclerosis.

Conclusions

Systematic TTE in a population-based cohort revealed a prevalence of congenital cardiac tumours of 0.3 per 1,000 live-births. The majority of the tumours were located in the ventricles and most often multiple cardiac tumours were encountered. Detection of congenital cardiac tumours in the ventricles was associated with tuberous sclerosis in half the cases.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): Danish Heart Association, Danish Children's Heart Foundation
Kynurenine-PARP 1 link mediated by microRNA 210 may be dysregulated in pulmonary hypertension
Authors: Yaylali Y.T , Akgun A.E , Secme M , Senol H , Dodurga Y
Published: November 2020

Background

The aims of the present study were to determine the alterations in mRNA and miR expressions and their role in signaling pathways, to correlate their levels with the severity of PH, and to investigate the relationship between those alterations and serum levels of apelin, kynurenine, and endocan in PH.

Methods

The study included 32 treatment-naive patients with precapillary PH and 55 controls. All subjects underwent RHC. Total RNA was isolated and cDNAs for mRNA and miR were synthesized. mRNA expressions of HIF-1α, HIF-2α, STAT 3, FGF-2, FGFR-1, PARP 1 and miR expressions of miR-210, miR-130a, miR-424, miR-204, and miR-223 were determined. Concentrations of kynurenine, apelin, and endocan were analyzed.

Results

HIF-2α, STAT 3, and FGF-2 were increased; miR-210 and miR-130a were increased; miR-223 and miR-204 were decreased. Apelin and kynurenine concentrations were decreased. There were positive correlations: HIF-2α-miR-424: r=0.474, p=0.011; APLN-miR-424: r=0.385, p=0.030; kynurenine-miR-210: r=0.551, p=0.004; STAT 3- PVR: r=0.478, p=0.006; miR-210- RAP: r=0.536, p=0.07; kynurenine-RAP: r=0.409, p=0.022. There were negative correlations: PARP 1-miR-210: r=−0.561, p=0.007; PARP 1- RAP: r=−0.424, p=0.27. miR-130a (OR= 1.257, p=0.016) and APLN (OR= 0.223, p=0.004) were independent risk factors for PH.

Conclusions

We report: 1) novel relationship between the kynurenine and PARP 1 signaling pathways that could be mediated by miR-210, 2) relationship between the apelin and HIF-2α signaling pathways that could be mediated by miR-424, 3) reduced levels of apelin and elevated levels of miR-130a are associated with PH, 4) elevated levels of STAT 3, miR-210, and kynurenine, and reduced levels of PARP 1 correlate with more severe hemodynamics.

Funding Acknowledgement

Type of funding source: Other. Main funding source(s): Pamukkale University Scientific Research Projects Coordination Unit
Prognostic role of comorbidities in patients with pulmonary arterial hypertension
Authors: De Lorenzis A , Dardi F , Palazzini M , Zuffa E , Pasca F , Guarino D , Magnani I , Rotunno M , Ballerini A , Manes A , Galie N
Published: November 2020

Background

Epidemiology of pulmonary arterial hypertension (PAH) is changing and the age at diagnosis and the prevalence of comorbidities are increasing but their prognostic relevance is substantially undefined.

Purpose

To evaluate the prognostic value of comorbidities in patients with PAH and in the different clinical subgroups.

Methods

All patients with PAH referred to a single centre underwent baseline right heart catheterization, brain natriuretic peptide (BNP) plasma levels, 6-min walking distance (6MWD), WHO functional class and anamnestic comorbidities evaluation. Cox regression model was used for analysis (p-value <0.1 was considered for inclusion in multivariate analysis).

Results

1311 patients were included [age 51 years; aetiology: 522 idiopathic/heritable/drug-induced (I/H/D)-PAH, 258 connective tissue disease (CTD)-associated PAH, 242 congenital heart disease (CHD)-associated PAH, 196 portal hypertension/HIV (PoHIV)-associated PAH and 93 pulmonary veno-occlusive disease (PVOD)]. 5% of patients have no comorbidities. At multivariate analysis comorbidities independently associated with prognosis are: systemic hypertension in I/H/D [HR 0.616, p=0.030], mean systemic blood pressure in CTD [HR 0.980, p=0.002] and PVOD [HR 0.962, p=0.006], dyslipidemia in CTD [HR 0.447, p=0.001] and PoHIV [HR 0.201, p=0.026], estimated glomerular filtration rate in PoHIV [HR 1.000, p<0.001] and body mass index (BMI) [HR 0.966, p=0.069] in CTD. In CHD comorbidities are not independent determinants of prognosis. Other variables independently predictive of a worse prognosis are: advanced age in all PAH subgroups except PVOD; male gender in I/H/D; reduced 6MWD in I/H/D, CTD and PVOD; high BNP in I/H/D, CHD and PVOD; low cardiac index in CTD, high right atrial pressure in I/H/D and low mixed venous oxygen saturation in CHD.

Conclusion

The age at PAH diagnosis and the prevalence of comorbidities are increasing but their prognostic role seems of poor relevance as we found a protective role of these variables: high systemic blood pressure (maybe indicative of a better haemodynamic stability) in I/H/D, CTD and PVOD; dyslipidemia and high BMI (maybe indicative of a better nutritional status and a less severe autoimmune disease) in CTD; dyslipidemia and a high glomerular filtration rate (both indicative of a less severe liver disease) in PoHIV.

Funding Acknowledgement

Type of funding source: None
Impact of higher detection rate of residual pulmonary thromboemboli one-year after acute pulmonary embolism: modified CT scan imaging method with modified CT obstruction index
Authors: Nakano Y , Okumura N , Imai R , Yoshida M , Shimokata S , Adachi S , Murohara T , Kondo T
Published: November 2020

Background

Recently, post pulmonary embolism (PE) syndrome or chronic thromboembolic disease after acute PE, has been recognized as important long-term complications. Furthermore, patients may develop with chronic thromboembolic pulmonary hypertension.

Purpose

We aimed to evaluate the frequency of residual pulmonary thromboemboli after acute PE by using our “higher”-resolution CT scan imaging method to detect residual thromboemboli down to sub-segmental pulmonary arteries.

Methods

This study was a prospective multi-center observational study. We enrolled consecutive 34 patients with acute symptomatic PE whose informed consent was obtained, and followed up for one year. One year after the onset of acute PE, patients were referred to our hospital and multiple examination including CT scan, 6-minute walk test (6MWT), questionnaire of SF-36, echocardiography and laboratory testing were performed. Additionally, we have modified the CT obstruction index (CTOI) to quantitatively evaluate the thromboemboli down to sub-segmental pulmonary arteries.

Results

Mean age was 60.5±15.8 years, and 56% were male. No patient was categorized as low recurrent VTE risk which was caused by transient factors, one patient was associated with active cancer, and 12% had known thrombophilia. In 85% of the patients, this onset was the first obvious episode of PE. At diagnosis, elevated B-type natriuretic peptide (BNP) (≥100 pg/ml) or N-terminal (NT)-proBNP (≥500 pg/ml) was observed in 45% of the patients. Median tricuspid regurgitation peak gradient (TRPG) by echocardiography was 30.9 (19.3–50.1) mmHg. Among all, 35% of the patients received single-drug approach with DOACs. At discharge, all of the patients except two were treated with DOACs.

One year after the onset, 21% of the patient were in NYHA II and others were in NYHA I. It was notable that pulmonary thromboemboli was detected by our CT scan in 76% of the patients. Modified CTOI was median 11.9 (1.8–24.4) % as shown in the figure.

In multiple regression analysis, TRPG at diagnosis and BNP at one month were significantly associated with mCTOI (β=0.536, p=0.002 and β=−0.482, p=0.003, respectively). Additionally, lowest SpO2 during 6MWT after one year from the onset, tended to inversely associate with mCTOI (β=−0.341, p=0.052).

Conclusions

Using our modified CT scan imaging method and modified CTOI, residual pulmonary thromboemboli was able to be detected more frequently than the previous studies. Residual pulmonary thromboemboli could be one of the cause of the post PE syndrome and lead to exercise-induced desaturation.

Figures

Funding Acknowledgement

Type of funding source: None