bluuebunny/crossref_metadata_2025 huggingface dataset:
Bicuspid aortic valve: prompt identification of high-risk groups in a heterogeneous disease
Authors: Carrero M.C , Constantin I , Masson G , Mezzadra M , Ruano M , Diaz Babio G , Pessio C , De Stefano L , Lopez Rosetti M , San Miguel J , Espinosa E , Stutzbach P
Published: November 2020

Background

Bicuspid aortic valve (BAV) is a congenital heart disease that can be associated with aortic and/or valve complications. Although most BAV are predisposed to progressive calcification, little is known on variables related to significant valvular dysfunction. BAV is a heterogeneous disease, therefore it is important to identify high-risk groups for a closer follow- up and timely intervention.

Objective

Identify the main determinants of primary cardiovascular events (aortic valve replacement, aortic surgery and death) in a cohort of adults with BAV.

Methods

We included 325 consecutive patients with non-syndromatic BAV (2010–2019) referred to our hospital (3rd level). Clinical information was prospectively collected. All patients underwent serial echocardiograms and Cardiac CT was available in 125 patients (38%). We performed univariate and multivariate analyses and Kaplan-Meyer survival analysis with log-rank test. A p-value <0.05 was considered significant.

Results

325 patients (44.4±15.3 years, 73% men), right–left coronary cusp fusion (RL) in 79%,and presence of raphe in 77%. 100 patients (31.2%) had significant aortic valve dysfunction and 103 (31.7%) had aortic dialatation (>40mm) at the onset of the follow-up. Twenty-nine patients required cardiac surgery (8.9%, mainly symptomatic severe aortic stenosis with aortic valve replacement)and 3 died (1%) during a follow-up of 6.3±1.2 years. Patients with at least 2 of the following determinants at baseline: aortic valve prolapse, aortic valve calcification >1, age >50 years and/or aorta >45mm had higher risk of major cardiovascular events during follow-up (Chi2 for log rank test=27,229 p=0,000005).

Conclusions

In this study population of young adults with BAV we observed a high incidence of events related to the BAV. Age>50 years, aortic valve calcification, aortic valve prolapse and aortic dilatation were independently associated with primary cardiac events. Despite significant BAV heterogeneity, the identification of risk factors may help to stratify the risk of valvular dysfunction, aortic dilatation and major cardiovascular events.

BAV: Risk factors for cardiac surgery

Funding Acknowledgement

Type of funding source: None
Plasma lipids and risk of aortic valve stenosis: a Mendelian randomization study
Authors: Nazarzadeh M , Pinho-Gomes A.-C , Bidel Z , Dehghan A , Canoy D , Hassaine A , Solares R.-A , Salimi-Khorshidi G.H , Smith G.D , Otto C.M , Rahimi K
Published: November 2020

Background

Aortic valve stenosis is commonly considered a degenerative disorder with no recommended preventive intervention, with only valve replacement surgery or catheter intervention as treatment options.

Purpose

We sought to assess the causal association between exposure to lipid levels and risk of aortic stenosis.

Methods

Causality of association was assessed using two-sample Mendelian Randomization (MR) framework through different statistical methods. MR approach uses instrumental variable analysis to mimic the randomization process that underpins causal inference in clinical trials. It takes advantage of the naturally-occurring random allocation of alleles inherited by offspring from their parents during the formation of the zygote. We retrieved summary estimations of 157 genetic variants that have been shown to be associated with plasma lipid levels in the Global Lipids Genetics Consortium that included 188,577 participants, mostly European ancestry, and genetic association with aortic stenosis as the main outcome from a total of 432,173 participants in the UK Biobank. Secondary negative control outcomes included aortic regurgitation and mitral regurgitation.

Results

The odds ratio (OR) for developing aortic stenosis per unit increase in lipid parameter was 1.52 (95% confidence interval [CI], 1.22 to 1.90; per 0.98 mmol/L) for low-density lipoprotein (LDL) cholesterol, 1.03 (95% CI, 0.80 to 1.31; per 0.41 mmol/L) for high-density lipoprotein (HDL) cholesterol, and 1.38 (95% CI 0.92 to 2.07; per 1 mmol/L) for triglycerides. There was no evidence of a causal association between any of the lipid parameters and aortic or mitral regurgitation.

Conclusion

Lifelong exposure to high LDL-cholesterol increases the risk of symptomatic aortic stenosis, suggesting that LDL-lowering treatment may be effective in its prevention.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): British Heart Foundation
The impact of frailty in an endocarditis cohort: association with length of stay and mortality
Authors: Primus C.P , Bvekerwa I , McCue M , Menezes L , Serafino-Wani R , Das S , Wong K , Uppal R , Ambekar S , Bhatacharyya S , Woldman S , Davies L.C
Published: November 2020

Introduction

Predictors of poor outcome are well established in Endocarditis (IE). “Frailty” refers to a syndrome of physiological decline associated with adverse health outcomes. Gilbert et al.(Lancet, 2018) developed a Hospital Frailty Risk Score (HFRS) that predicts 30-day mortality and length of stay (LOS).

Aim

Identify impact of an abbreviated HFRS (aHFRS) on in-hospital survival and LOS in IE given high morbidity and mortality.

Methods

Retrospective analysis of prospectively collected cases (Jan 2018–date). aHFRS score was calculated with key IE, cardiac, respiratory, oncology & frailty diagnoses. Univariate regression was applied overall and in key “cohorts” (native & prosthetic IE, medical & surgical management) for survival and LOS.

Results

Of 334 cases, LOS data were available in 317; mean age 57.8y (range 17–91, male 74%). Table 1 describes key cohorts. Mortality was 10.1% (medical, 11.9%; surgical, 8.3%). Mean LOS was 31.2 days (range 0–224).

Mean aHFRS was 5.38diagnoses (SD 2.61, range 0–14); 1.65 pre-IE and 3.73 attributed to IE alone, consistent across cohorts. Regression analyses highlight increasing LOS with increasing aHFRS (r2=0.06, Figure 1). Table 1 summarises the modest impact of aHFRS on LOS, and a trend to worse outcome in medical management (r2=0.02).

Discussion

Higher aHFRS is associated with longer LOS and a trend to higher mortality in medically managed IE. IE itself is associated with a number of frailty diagnoses. To improve outlook and provide holistic care, the IE Team may need to include experts in frailty. Satisfactory outcomes may require intensive post-IE rehabilitation.

Funding Acknowledgement

Type of funding source: None
Infective endocarditis in patients who use IV drugs: a single centre cohort
Authors: Alraddadi H , Alsagheir A , Gao S , An K , Hronyecz H , Parry D , Whitlock R.P , Belley-Cote E
Published: November 2020

Background

Managing endocarditis in intravenous drug use (IVDU) patients is challenging: unless patients successfully quit IVDU, the risk of re-infection is high. Clinicians often raise concerns with ethical and resource allocation principles when considering valve replacement surgery in this patient population. To help inform practice, we sought to determine the long-term outcomes of IVDU patients with endocarditis who underwent valve surgery in our center.

Method

After research ethics board approval, infective endocarditis cases managed surgically at our General Hospital between 2009 and 2018 were identified through the Cardiac Care Network. We reviewed patients' charts and included those with a history of IVDU in this study. We abstracted data on baseline characteristics, peri-operative course, short- and long-term outcomes. We report results using descriptive statistics.

Results

We identified 124 IVDU patients with surgically managed endocarditis. Mean age was 37 years (SD 11), 61% were females and 8% had redo surgery. During admission, 45% (n=56) of the patients had an embolic event: 63% pulmonary, 30% cerebral, 18% peripheral and 11% mesenteric. Causative organisms included Methicillin-Sensitive Staphylococcus Aureus (51%, n=63), Methicillin-Resistant Staphylococcus Aureus (15%, n=19), Streptococcus Viridans (2%, n=2), and others (31%, n=38). Emergency cardiac surgery was performed for 42% of patients (n=52). Most patients (84%) had single valve intervention: 53% tricuspid, 18% aortic and 13% mitral. Double valve interventions occurred in 15% (n=18). Overall, bioprosthetic replacement was most commonly chosen (79%, n=98). In-hospital mortality was 7% (n=8). Median length of stay in hospital was 13 days (IQR 8,21) and ICU 2 days (IQR 1,6). Mortality at longest available follow-up was 24% (n=30), with a median follow-up of 129 days (IQR 15,416). Valve reintervention rate was 11% (n=13) and readmission rate was 14% (n=17) at a median of 275 days (IQR 54,502).

Conclusion

Despite their critical condition, IVDU patients with endocarditis have good intra-hospital outcomes. Challenges occur after hospital discharge with loss of follow-up and high short-term mortality. IVDU relapse likely accounts for some of these issues. In-hospital and community comprehensive addiction management may improve these patients' outcomes beyond the surgical procedure.

Annual rate 2009–2018

Funding Acknowledgement

Type of funding source: None
Diphosphonate single-photon emission computed tomography in cardiac transthyretin amyloidosis
Authors: Aimo A , Grigoratos C , Rapezzi C , Genovesi D , Barison A , Aquaro G.D , Vergaro G , Pucci A , Passino C , Marzullo P , Gimelli A , Emdin M
Published: November 2020

Background

Planar diphosphonate scintigraphy is an established diagnostic tool for amyloid transthyretin (ATTR) cardiomyopathy. Characterization of the amyloid burden up to the segmental level by single photon emission computed tomography (SPECT) has not been evaluated so far.

Methods

Data from consecutive patients undergoing cardiac 99mTc-hydroxymethylene diphosphonate (99mTc-HMDP) SPECT and diagnosed with ATTR cardiomyopathy at a tertiary referral center from June 2016 to April 2019 were collected.

Results

Thirty-eight patients were included (median age 81 years, 79% men, 92% with wild-type ATTR). In patients with Perugini score 1, the most intense diphosphonate regional uptake was found in septal segments, particularly in infero-septal segments. Among patients scoring 2, the amyloid burden in the septum became more significant, and extended to inferior and apical segments. Finally, patients scoring 3 displayed an intense and widespread tracer uptake. All patients with Perugini score 1 had LGE in at least one antero-septal, one infero-septal, and one infero-lateral segment. All patients with score 2 displayed LGE in infero-septal, inferior, and infero-lateral segments. LGE became extensive in patients scoring 3, with all patients having at least one LGE-positive segment in each region.

Conclusions

When assimilating different Perugini grades to evolutive stages of the disease, amyloid deposition seem to progress from the septum to the inferior wall and then to the other regions and from the basis to the apex. The potential of segmental analysis might be particularly relevant in patients with very limited cardiac uptake at planar scintigraphy (Perugini score 1).

Funding Acknowledgement

Type of funding source: None
Circumferential deformation in diagnosis and risk assessment of patients with left ventricular non-compaction
Authors: Anwer S , Heiniger P.S , Rogler S , Cassani D , Rebellius L , Kuzo N , Gotschy A , Erhart L , Kebernik J , Schmid D , Pazhenkottil A.P , Meyer M , Schoenenberger-Berzins R , Gruner C , Tanner F.C
Published: November 2020

Introduction

Echocardiography-based deformation analysis is used for studying left ventricular (LV) mechanics and have an emerging role in the diagnosis of cardiomyopathies. Left ventricular non-compaction (LVNC) is a rare cardiomyopathy characterised by a two-layered LV myocardium with prominent trabeculae separated by deep recesses perfused from the LV cavity. Left ventricular hypertrabeculation (LVHT) may be difficult to differentiate from LVNC. In this study, we aim to develop a diagnostic algorithm based on the circumferential deformation (CD) of LVNC, LVHT and controls; and find their associations with LVNC outcomes.

Methods

We compared 45 LVNC patients, 45 LVHT individuals, and 45 matched healthy controls. LVNC was diagnosed according to current echocardiographic criteria. LVHT was defined as presence of three or more trabeculae in the LV apex visualised in both parasternal short axis and apical views. Controls had a normal echocardiographic examination and no evidence of cardiovascular disease. Strain analysis was performed using TomTec Image-Arena (version 4.6).

Results

Receiver observer characteristics curve (ROC) analyses revealed that GCS <22.3% differentiated LVNC from control or LVHT. In individuals with global circumferential strain (GCS) below 22.3%, an apical peak circumferential strain (PCS) cut-off value of 18.4% differentiated LVNC [<18.4%] and LVHT [≥18.4%] (fig. 1). An independent echocardiographer (Table 1) performed blind validation of diagnosis on 32 subjects from each group.

Combined endpoint of cardiovascular events in LVNC (CVE) is described in figure 2. Multi-variate regression analyses have shown that GCS was associated with 11-fold increased risk of CVE independent of LVEF and NC:C ratio, while global longitudinal strain (GLS) displayed only 2-fold increased risk. Regional basal and apical peak circumferential or longitudinal strain, left ventricular twist, basal-apical rotation ratio have shown significant associations (Fig. 3).

Conclusions

A diagnostic algorithm with GCS and aPCS (threshold value 18.4%) differentiates LVNC from LVHT and control with very high sensitivity and specificity independent of additional echocardiographic or clinical information. Circumferential strain derived parameters exhibit a very strong association with outcomes independent of LVEF and NC:C ratio. Absence of CVE in LVHT provides further evidence on the distinct nature of LVNC and LVHT.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): 2018 research grant from the Swiss Heart Foundation
Percutaneous transluminal septal myocardial ablation markedly reduces energy loss in hypertrophic obstructive cardiomyopathy: a four-dimensional flow magnetic resonance imaging study
Authors: Dai Z , Iguchi N , Takamisawa I , Takayama M , Nanasato M , Kanisawa M , Mizuno N , Isobe M
Published: November 2020

Background

Functional follow-up modalities of hypertrophic obstructive cardiomyopathy (HOCM) subjected to percutaneous transluminal septal myocardial ablation (PTSMA) are limited mainly to echocardiography and catheterization. Recent advancements in four-dimensional (4D) flow magnetic resonance imaging (MRI) have enabled us to assess patients from the perspective of fluid dynamics by visualising blood flow and calculating quantitative parameters such as wall shear stress and energy loss within cardiac chambers or blood vessels. Several reports have demonstrated that the intra-cardiac energy loss decreased along with improvement of cardiac function achieved by treatment of cardiac diseases. Whether changes in energy loss occur along with PTSMA in HOCM patients and the underlying mechanism remain unknown.

Purpose

This study sought to investigate the influence of PTSMA in patients with HOCM on energy loss in the left ventricle (LV) and aortic root measured by 4D flow MRI.

Methods

We retrospectively recruited HOCM patients who underwent PTSMA at a referral centre from May to November 2019. Patients who underwent 4D flow MRI both before and after PTSMA were included. We collected demographic and clinical data from electronic health records. MRI scans implemented two-dimensional phase-contrast imaging of the three-chamber plane with three-directional velocity, using a 1.5 T scanner. Furthermore, 4D blood flow analysis was performed on off-line saved data, using iTFlow version 1.9. We assessed energy loss in one cardiac cycle within the three-chamber plane of the LV and aortic root (area surrounded by the LV endocardium, sinotubular junction, and mitral annulus).

Results

This study finally included 12 patients, whose mean age was 66±12 years, and 5 (42%) of whom were men. The pressure gradient between the LV apex and ascending aorta was 81±32 mmHg before and 20±22 mmHg immediately after PTSMA (P<0.005, paired). Before PTSMA, 6 patients were in New York Heart Association functional class III and the other 6 in class II. However, after PTSMA, 10 patients improved to class I and 2 to class II. PTSMA reduced energy loss in one cardiac cycle within the three-chamber plane of the LV and aortic root, from 79±36 mJ/m to 55±19 mJ/m (P=0.001, paired).

Conclusions

PTSMA in patients with HOCM reduced energy loss within the LV and aortic root, indicating significant decrease with cardiac workload. Four-dimensional flow MRI of the three-chamber plane to assess energy loss within the LV and aortic root is a time-efficient and reproducible quantitative method to evaluate the effects of PTSMA. Given its non-invasive nature, it also enables to sequentially follow-up HOCM patients who underwent PTSMA.

Periprocedural changes of energy loss

Funding Acknowledgement

Type of funding source: None
Benefits of tafamidis in patients with advanced transthyretin amyloid cardiomyopathy
Authors: Rapezzi C , Kristen A.V , Gundapaneni B , Sultan M.B , Hanna M
Published: November 2020

Background

In the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT), tafamidis was shown to be an effective treatment for patients with transthyretin amyloid cardiomyopathy (ATTR-CM). Further assessment of the efficacy of tafamidis in patients with more advanced ATTR-CM would aid treatment decisions.

Purpose

To characterize the benefits of tafamidis in patients with advanced ATTR-CM.

Methods

In ATTR-ACT, ATTR-CM patients were randomized to tafamidis (n=264) or placebo (n=177) for 30 months. Efficacy outcomes included all-cause mortality and frequency of cardiovascular (CV)-related hospitalisations. Key secondary endpoints were change from baseline to Month 30 in 6MWT distance and KCCQ-OS score. Efficacy assessments in NYHA Class III patients at baseline (n=141) were a pre-specified analysis. In a post-hoc analysis, mortality and CV-related hospitalizations were assessed in all patients grouped into quartiles of increasing disease severity based on 6MWT distance at baseline. Longer-term all-cause mortality (as of 1 Aug 2019) was assessed in NYHA Class III patients utilizing data from ATTR-ACT patients who enrolled in a long-term, extension study (LTE) and continued treatment with higher dose tafamidis (n=55; median treatment duration 51.6 months); or, if previously treated with placebo, started tafamidis treatment (placebo/tafamidis; n=63 [50.1 months]).

Results

In advanced ATTR-CM patients (NYHA Class III), tafamidis reduced the risk of death (HR [95% CI] 0.837, [0.541, 1.295], P=0.4253), and the decline in 6MWT distance (LS mean [SE], 31.6 (22.1) m; P=0.1526) and KCCQ-OS score (LS mean [SE], 13.1 (5.0); P=0.0090), vs placebo. Paradoxically, there was a higher frequency of CV-related hospitalizations with tafamidis (RR [95% CI] vs placebo, 1.411 [1.048, 1.900]). In all patients by 6MWT quartile, CV-related hospitalizations/year with tafamidis and placebo increased with disease severity, with the exception that placebo-treated patients in the highest severity quartile had fewer CV-related hospitalisations (0.73) than those in the third quartile (0.92). Mortality with tafamidis and placebo increased, and was greater with placebo, in every quartile (Figure). Survival (NYHA Class III patients in ATTR-ACT and LTE) was improved with high dose tafamidis with longer term follow-up (HR vs placebo/tafamidis [95% CI], 0.6569 [0.4175, 1.0336]; P=0.0692).

Conclusions

These analyses, including longer-term follow-up, demonstrate that patients with advanced ATTR-CM benefit from tafamidis. The decrease in CV-related hospitalisations in more severe patients treated with placebo suggests that the comparatively greater hospitalisation frequency in NYHA Class III patients treated with tafamidis is a consequence of their lower mortality rate.

Figure 1

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): This study was sponsored by Pfizer
Prevalence of hereditary transthyretin cardiac amyloidosis (mATTR) in Western Denmark
Authors: Rasmussen T.B , Vase H , Ladefoged B , Dybro A.M , Clemmensen T , Terkelsen A.J , Molgaard H , Petersen L.N , Poulsen S.H
Published: November 2020

Purpose

To investigate the prevalence of mATTR in a cohort of consecutive ATTR patients in a tertiary Danish Amyloidosis Center.

Methods

Consecutive patients in the period from 2001 to 2019 with a definite diagnosis of ATTR-CA or ATTR-FAP based on either 99-Tc-DPD-scintigraphy, or transthyretin deposition in the myocardium or fatty tissue proved by immunohistology or protein mass spectrometry underwent testing for exonic genetic TTR variants. The distributions of age at time of diagnosis of mATTR and wildtype ATTR (wtATTR) are described by mean age, standard deviations, and range.

Results

Seventy-four caucasian patients of Danish ancestry except one (Swedish) with ATTR were included (72 ATTR-CA, 2 ATTR-FAP). TTR missense variants were present in 13.5% (10/74) of ATTR patients concluded to have mATTR: c.148G>A/p.Val50Met, n=1; c.187C>T/p.Pro63Ser, n=1; c.193G>T/p.Ala65Ser, n=2; c.218G>C; p.Gly73Ala, n=1; c.391C>A/p.Leu131Met, n=3; c.424G>A/p.Val142Ile, n=2.

The mean age of mATTR patients was 57.6 years ±13.0, range 37.1–71.3 years, and was significantly lower than mean age for wtATTR patients: 79.4 years ±5.5, range 65.7–90.2 years, p=0.0004 (Welch's two-sample t-test with unequal variances). All patients with mATTR had familial disease proven by clinical phenotyping of family members or had a positive family history with heart failure and pacemaker use.

Conclusion

A minority of Danish patients (10–15%) with ATTR have mATTR. These mATTR patients are characterised by a significantly younger age at time of diagnosis than wtATTR patients. This observation indicates that TTR gene test may not be necessary in ATTR in patients older than 75 years. For the first time, the p.Val142Ile TTR variant, associated with mATTR and prevalent in 4% of African-Americans, was identified in a Danish family with mATTR-CA – a finding that may be explained by a common founder effect.

Funding Acknowledgement

Type of funding source: None
High sensitivity cardiac troponin T is a useful biomarker for predicting prognosis of the patients with sarcoidosis
Authors: Baba Y , Kubo T , Kawaguchi J , Ochi Y , Hirota T , Yamasaki N , Kitaoka H
Published: November 2020

Background

Cardiac involvement is one of the most significant prognostic factors for the patients with sarcoidosis. In spite of the advancement of diagnostic tools, such as cardiac magnetic resonance imaging or 18F-fluoro-2-deoxyglucose positron emission tomography, there is still significant room for improvement in cardiac screening and prognostic prediction.

Purpose

To evaluate the prognostic factors for the patients with sarcoidosis.

Methods and results

We prospectively studied 133 patients with sarcoidosis and evaluated clinical data including biomarkers. The mean age at diagnosis was 62.1±12.8 years. During a mean follow up period of 5.6±4.1 years, nine patients died and 27 patients suffered from cardiac events (cardiac death, heart failure admission, arrhythmic event). We divided patients into two groups according to cardiac events, event group had high serum high-sensitivity cardiac troponin T (hs-cTnT) (0.028±0.017 vs. 0.015±0.011 ng/ml, p<0.001), high BNP (409.2±634.0 vs. 122.4±195.8 pg/ml, p<0.001), low EF (43.1±16.4 vs. 59.2±15.5%, p<0.001). This was observed even if those patients were not diagnosed with cardiac involvement at the enrollment. On the other hand, there were no significant differences in the values of angiotensin-converting enzyme, lysozyme, soluble interleukin-2 receptor, or calcium in both groups. Multivariate analysis revealed that hs-cTnT was an independent biomarker to predict cardiac events (hs-cTnT >0.014 ng/ml: HR 3.2, 95% CI 1.02 to 10.19, p=0.046).

Conclusion

Hs-cTnT was a useful biomarker for predicting cardiac events for the patients with sarcoidosis even if cardiac involvement was not detected at initial evaluation.

Figure 1

Funding Acknowledgement

Type of funding source: None
Cardiac sarcoidosis: frequency, diagnostic approach and follow-up in a tertiary center
Authors: Van Der Velde N , Poleij A , Hassing H.C , Lenzen M.J , Budde R.P.J , Kirschbaum S.W.M , Schinkel A.F.L , Michels M , Hirsch A
Published: November 2020

Background

Cardiac sarcoidosis (CS) is associated with poor prognosis, making early diagnosis and treatment important. The aim of this study is to evaluate our diagnostic results and follow-up for the diagnosis of CS in a tertiary center.

Methods

We studied 188 patients with proven extra-cardiac sarcoidosis referred to our outpatient clinic for evaluation of cardiac involvement. Eight patients were excluded because electrocardiogram (ECG) and/or transthoracic echocardiography (TTE) was missing. Cardiac magnetic resonance (CMR) and/or positron emission tomography (PET) was performed in 66% and 37% of the patients, respectively. Median follow-up duration was 2.9 [1.2–5.3] years. The diagnosis of CS was based on the Heart Rhythm Society criteria.

Results

Cardiac symptoms defined as palpitations, angina, dyspnea and (near)-syncope were present in 156 of 180 (87%) patients. Any abnormality on ECG (bundle branch blocks, atrioventricular blocks, sinus tachycardia or atrial fibrillation) and/or TTE (left ventricular ejection fraction <55%, presence of regional wall abnormalities or myocardial hypertrophy) was found in 92/180 (51%) patients. CS was diagnosed in 42 of 180 (23%) patients, of whom 31 (74%) had any ECG and/or TTE abnormalities. However, ECG and/or TTE abnormalities were also present in 44% of the patients without cardiac involvement. Patients with CS showed a second type II or third degree AV-blocks in 3/42 (7%), a left ventricular ejection fraction <35% on TTE in 9/42 (21%), late gadolinium enhancement by CMR consistent with CS in 28/34 (82%), and myocardial FDG uptake by PET in 19/31 (61%). In 84 of the 138 patients without cardiac involvement, CMR was performed. In 15 patients an alternative diagnosis was found (i.e. myocardial infarction or other non-ischemic cardiomyopathy). The estimated 8-year cumulative event rate composite endpoint of sustained ventricular tachycardia, ventricular fibrillation, aborted sudden cardiac death, heart transplantation and all-cause mortality was 41% in the CS patients and 12% in the patients without CS (Figure 1, p<0.001).

Conclusions

In our study, 23% of the patients with proven extra-cardiac sarcoidosis was diagnosed with CS. Cardiac symptoms, ECG and TTE were of limited diagnostic value for screening for CS. CMR provided a good diagnostic yield and identified other cardiac diseases in a substantial number of patients.

Figure 1. KMCurve_CompositeEndpoint

Funding Acknowledgement

Type of funding source: None
Long-term survival with tafamidis in patients with transthyretin amyloid cardiomyopathy
Authors: Damy T , Elliott P , Gundapaneni B , See Tai S , Sultan M.B , Drachman B.M
Published: November 2020

Background

The Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT), demonstrated that tafamidis was an effective treatment for patients with transthyretin amyloid cardiomyopathy (ATTR-CM). Tafamidis, at an 80 mg daily dose, was subsequently approved in several countries for the treatment of ATTR-CM. Patients who completed ATTR-ACT were eligible to enroll in an ongoing long-term extension study (LTE) which provides additional data on the long-term efficacy of tafamidis.

Purpose

To assess the long-term benefit of tafamidis in patients with ATTR-CM and to determine median survival times with treatment.

Methods

Patients with ATTR-CM who completed ATTR-ACT (in which they were randomized to tafamidis meglumine 80 mg, 20 mg or placebo for 30 months) could enroll in the ongoing LTE in which patients continued to be treated with the same dose of tafamidis or, if previously treated with placebo, were randomized to tafamidis meglumine 80 mg or 20 mg. Tafamidis free acid 61 mg is a new formulation (bioequivalent to tafamidis meglumine 80 mg) developed for patient convenience and all patients in the LTE transitioned to tafamidis free acid 61 mg as of 1 Aug, 2018. All-cause mortality (with heart transplant or cardiac mechanical assist device [CMAD] implantation counted as death) was assessed using a Cox proportional hazards model (as of 1 Aug, 2019). Patients treated with tafamidis meglumine 80 mg in ATTR-ACT and the LTE who transitioned to tafamidis free acid 61 mg (tafamidis 80/61 mg) were compared with patients treated with placebo in ATTR-ACT who transitioned to tafamidis in the LTE (placebo/tafamidis).

Results

There were a total of 176 tafamidis 80/61 mg patients and 177 placebo/tafamidis patients. Median treatment duration was 51.9 months with tafamidis 80/61 mg and 51.4 months with placebo/tafamidis. With tafamidis 80/61 mg, there were 75 (42.6%) all-cause deaths; consisting of 67 (38.1%) deaths, 6 (3.4%) heart transplants, and 2 (1.1%) CMAD implantations. With placebo/tafamidis, there were 108 (61.0%) all-cause deaths; consisting of 102 (57.6%) deaths and 6 (3.4%) heart transplants. There was a significant reduction of 41.1% in the risk of all-cause mortality with tafamidis 80/61 mg compared with placebo/tafamidis (hazard ratio [95% CI], 0.5888 [0.4370, 0.7931]; P=0.0004). Median survival time with placebo/tafamidis was 35.8 months but was not reached with tafamidis 80/61 mg.

Conclusions

Treatment with tafamidis significantly improves long-term survival in patients with ATTR-CM. The comparatively poorer survival in patients treated with placebo in ATTR-ACT who transitioned to tafamidis in the LTE highlights the importance of early diagnosis and treatment.

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): This study was sponsored by Pfizer.
Risk of stroke in patients with Chagas cardiomyopathy is associated with depressed LV function but not with LV myocardial fibrosis or apical aneurysm: a study using cardiovascular magnetic resonance
Authors: Schmidt A , Turin Moreira H , Volpe G.J , Braggion Santos M.F , Marin Neto J.A
Published: November 2020

Background

Chronic Chagas cardiomyopathy (CCC) is classically related to higher occurrence of thromboembolic events, especially stroke, particularly in patients with atrial fibrillation (AF). However, risk factors for stroke in patients with CCC but no atrial fibrillation have not been well established.

Purpose

We aimed to assess the relationship between left ventricular (LV) structure and function, as evaluated with cardiac magnetic resonance (CMR), with stroke in individuals with CCC.

Methods

We prospectively collected data from 141 patients with CCC who underwent CMR from October 2009 to December 2013 and who were thereafter followed for a median period of 6.8 years. The outcome was the occurrence of stroke during the follow-up period. The only exclusion criteria were history of previous stroke, AF or use of oral anticoagulant (OAC) at the time of CMR. CMR-derived LV parameters were: LV ejection fraction (LVEF), extension of LV myocardial fibrosis, assessed by late gadolinium enhancement, and presence of LV apical aneurysm. LVEF was classified as follows: (I) normal ≥55%; (II) mid-range <55% and ≥40%; and (III) reduced <40%. Age and gender were covariates in the adjusted Cox proportional hazard model.

Results

Of the initial 141 CCC participants, 25 subjects were excluded due to previous stroke (n=2), history of AF (n=11), or use of OAC (n=12). The remaining 116 individuals had a mean age of 56±14 years, 51% women. Normal, mid-range and reduced LVEF were found in 48 (41%), 43 (37%), and 25 (22%) patients, respectively. Myocardial fibrosis was detected in 79 of 111 (71%) subjects in whom the detection method was feasible. The extension of LV fibrosis was evaluated as a median of 4.6% [interquartile range: 0–10]. LV apical aneurysm was identified in 36 (31%) patients. During the follow-up (median 6.8 years), stroke was reported in 9 participants. In the univariate analysis, reduced LVEF was significantly associated with higher risk of stroke compared to normal LVEF (HR: 9.2, 95% CI: 1.8–48.4), while there was no significant difference between mid-range and normal LVEF (HR: 1.2, 95% CI: 0.2–8.2). The association of reduced LVEF and stroke remained significant in the multivariable model, adjusted for age and gender (HR: 12.6, 95% CI: 1.9–83.2). Kaplan-Meier curves are presented in figure 1 (logrank p-value <0.001). Neither the extension of LV myocardial fibrosis (HR: 1.0, 95% CI: 0.9–1.1) nor the presence of LV apical aneurysm (HR: 1.9, 95% CI: 0.5–7.2) was related to higher risk of stroke.

Conclusion

In patients with CCC, reduced LVEF assessed by CMR, but not LV fibrosis or presence of apical aneurysm, was a significant predictor of stroke.

Funding Acknowledgement

Type of funding source: None
Management and outcome of acute and recurrent pericarditis during pregnancy
Authors: Lotan D , Wasserstrum Y , Itelman E , Nir-Simchen M , Arad M , Kuperstein R
Published: November 2020

Background

Pericarditis in pregnancy is uncommon. Treatment options, including NSAIDs and long term gluco-corticosteroids (CS) have extensive side-effects, while data on the use of Colchicine in pregnant women who suffer from pericarditis is limited.

Objective

To evaluate the management and outcome of active pericarditis during pregnancy in both acute (AP) and recurrent pericarditis (RP) patients.

Methods and results

Twelve pregnant women (14 pregnancies) with active pericarditis were followed prospectively in our cardiology-pregnancy clinic; 6 with AP and 8 with RP. Etiology: 11 idiopathic, 2 post-pericardiotomy syndrome and 1 Q fever. Maternal age on presentation was 27±4y vs. 33±3y in RP vs AP respectively. Average gestational age upon diagnosis was lower in RP than in AP (18 weeks, range 6–30 vs 26 weeks, range 5–35). In the RP group, 7/8 women (87%) were treated with CS compared with 2/6 women (33%) in the AP group; 3 women in RP group (37%) failed to respond to subsequent treatment with azathioprine and 1 patient was treated successfully with Anakinra. Colchicine was prescribed in 13/14 (93%) of pregnancies, average colchicine exposure during pregnancy was 25±15 weeks. Recurrence during pregnancy: 6/8 (75%) of RP; 2/6 (33%) of the AP, all of them on CS. All pregnancies culminated in a live birth with a mean gestational age on delivery of 37±1.4 weeks. Average birthweight was 3267±507 grams. There were no fetal anomalies or developmental delays after a mean follow-up of 2.7 years. All newborns and maternal outcomes were normal. On long term follow-up after delivery RP patients treated with colchicine developed less recurrences.

Conclusion

Active pericarditis is associated with a high recurrence rate during pregnancy despite treatment with CS. Colchicine use in pregnant women with active pericarditis appears to be safe.

Funding Acknowledgement

Type of funding source: None
Potential benefits of ambulatory blood pressure monitoring in coarctation of aorta
Authors: Egbe A , Banala K , Vojjini R
Published: November 2020

Background

Ambulatory blood pressure monitoring (ABPM) is more sensitive than resting BP assessment in detecting hypertension in patients with coarctation of aorta (COA). However, it is not known whether ABPM provides a better measure of left ventricular (LV) pressure load and LV remodeling as compared to resting BP. LV pressure overload is the lynchpin in the pathogenesis of cardiovascular mortality in COA patients, because it leads to LV remodeling, LV dysfunction and heart failure, which sets-the-stage for cardiovascular death. Therefore identifying a sensitive clinical metric that reflects LV pressure load and LV remodeling, is an important step towards optimizing antihypertensive therapy to prevent LV dysfunction and mortality. We hypothesized that ambulatory systolic BP (SBP) has better correlation with arterial load and LV remodeling indices as compared to resting SBP.

Methods

Our study cohort comprised of adults with isolated COA without significant residual coarctation (Doppler peak velocity ≤2.5 m/sec), aortic or mitral valve disease. All patients underwent BP measurement at rest, followed by ABPM. Arterial load (LV pressure load) was assessed using Doppler-derived effective arterial elastance index (EAI). LV remodeling was assessed using: LV mass index (LVMI), and E/e'. We divided the cohorts into 4 categories (normotensive, masked, white-coat, and overt hypertension).

Results

Of the 106 patients (male 69 [65%); age 39±11 years), 98 (93%) had prior COA intervention at 6±5 years. Resting SBP was 132±17, daytime ambulatory SBP was 142±16, and nighttime ambulatory SBP was 128±12 mmHg. The mean arterial load and LV remodeling indices were: EAI 3.4±0.8 mmHg/ml·m2, LVMI 106±21 g/m2, and E/e'11±4. Compared to resting SBP, ambulatory SBP had better correlation with EAI, LVMI, and E/e'. EAI, LVMI and E/e' were significantly different between hypertension categories (Figure 1).

Conclusions

In this study, we demonstrated that ambulatory SBP had better correlations with arterial load and LV remodeling indices as compared to resting SBP. This suggests that ambulatory SBP was a more robust metric of LV pressure overload and remodeling, and can improve detection of vascular stiffness, LV hypertrophy and elevated LV filling pressure as compared to resting SBP. The results of the current study have important clinical implications with regards to initiation and titration of antihypertensive therapy. If ABPM is used as the gold standard for diagnosis of hypertension, the masked hypertension group (who would have been misclassified as normotensive based on resting SBP alone) will qualify for antihypertensive therapy. Additionally, since ambulatory SBP had better correlation with LV remodeling indices, perhaps titration of antihypertensive therapy using ABPM will potentially reduce the risk of LV hypertrophy and dysfunction due to hypertension.

Figure 1

Funding Acknowledgement

Type of funding source: None
Pulmonary arterial hypertension in Spanish pediatric registry age: clinical characterization, management and survival
Authors: Playan Escribano J , Segura De La Cal T , Escribano Subias P , Labrandero C , Rodriguez Ogando A , Moreno Galdo A , Lozano Balseiro M , Moya Bonora A , Gomez Guzman E , Espin Lopez J.M , Perin F , Plata Izquierdo B , Viadero Ubierna M.T , Zapata Sanchez M , Del Cerro Marin M.J
Published: November 2020

Background

Pulmonary arterial hypertension (PAH) includes idiopathic PAH and congenital heart disease (CHD) related PAH. A wide variety of CHD can develop PAH, but their clinical characteristics define four large groups: Eisenmenger, PAH associated with non-restrictive shunt, severe PAH associated with restrictive shunt and postoperative PAH. Our aim was to study the clinical and prognostic differences between these groups and idiopathic PAH.

Methods

The REHIPED registry is a Spanish, multicenter, observational and prospective registry on pulmonary hypertension in the pediatric population (<18 years of age) that began in 2008. 183 patients were analyzed: baseline characteristics, functional class, right catheterization data, treatment and survival were compared

Results

183 patients were analyzed, characteristics are detailed in the table. In patients with idiopathic PAH, treatment with prostanoids was more frequently used as first line therapy and during follow up. The average follow-up time was 9 years. There was not a statistically significant difference in survival among the 4 clinical groups of CHD related PAH. There was a borderline significant difference (logrank p 0.05) in survival between the group of CHD related PAH and idiopathic PAH.

Conclusion

Idiopathic PAH patients have worse outcome than CHD related PAH patients although they have less comorbidities, less severe hemodynamics and are treated more aggressively.

Funding Acknowledgement

Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Janssen, Ferrer
Shift in transcriptional landscape of human right ventricle in chronic thromboembolic pulmonary arterial hypertension
Authors: Jafari L , Doerr O , Chelladurai P , Pullamsetti S.S , Troidl C , Keller T , Guenther S , Gruen D , Keranov S , Kriechbaum S , Liebetrau C , Mayer E , Seeger W , Hamm C.W , Nef H.M
Published: November 2020

Background

Chronic thromboembolic pulmonary hypertension (CTEPH) is a sub group of pulmonary hypertension (PH). CTEPH is characterized by the existence of thromboemboli and vascular remodeling in pulmonary vessels. The effect of increase in pulmonary artery pressures causes right ventricle (RV) hypertrophy and dilatation and finally leads to right heart failure and death. Surgical intervention in operable patients makes the CTEPH as an only curable and unique form of ph. Pulmonary endarterectomy (PEA) is the surgical procedure to remove the thromboembolic clots from the pulmonary vasculature, which restores RV function back to normal with significant improvements in cardiovascular magnetic resonance.

Purpose

The aim of this study is to use transcriptomic profiling to identify signaling pathways, master regulators, and potentially new biomarkers that specifically indicate the effect of PEA on the RV of patients with chronic thromboembolic pulmonary hypertension.

Results

RNA -sequencing (RNA-seq) was performed on RV biopsies obtained from CTEPH patients at PEA baseline (before PEA surgery) and the results were compared with those from RV biopsies obtained during follow-up evaluation. Bioinformatic analysis of RNA-seq data identified 2799 genes (n=14, −0.585 ≤ Log2 fold change ≥0.585, FDR ≤0.05) differentially regulated between the PEA baseline and follow-up sample groups. The great number of genes (2799) differentially expressed after PEA surgery in CTEPH patients confirms a major shift in the transcriptional landscape of RV in these patients. To further identify potential biomarker candidates from the large pool of 2799 differentially expressed genes (DEGs), extensive bioinformatic analysis of different data sets shortlisted 250 DEGs that were functionally associated with cardiovascular development or disease. The findings of this study reveal prominent transcriptional changes that occur in response to PEA. Gene ontology enrichment and pathway analysis confirmed altered regulation of hypoxia-inducible factor 1 (HIF-1) signaling, advanced glycation end products and their receptors (AGE-RAGE), mitogen-activated protein kinase (MAPK) signaling, hippo signaling, the Janus kinase/ signal transducers and activators of transcription (Jak-STAT) signaling pathway, and proteoglycans after PEA compared with before PEA.

Conclusion

Comparison of the results of RNA-seq analysis of RV biopsies of CTEPH patients, pre and post PEA, revealed a major shift in the transcriptional landscape of these patients after reducing the pressure overload of the RV by PEA.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): German Research Foundation (DFG)
Additional role of echocardiogram in pulmonary arterial hypertension risk stratification according to current ESC/ERS guidelines
Authors: Rotunno M , Dardi F , De Lorenzis A , Palazzini M , Zuffa E , Pasca F , Guarino D , Magnani I , Ballerini A , Manes A , Galie N
Published: November 2020

Background

Current pulmonary hypertension (PH) guidelines stratify the risk of patients with pulmonary arterial hypertension (PAH) using a multiparametric approach. A simplified risk table has been recently proposed and validated without including echocardiographic parameters.

Purpose

We evaluate the additional role of echocardiogram in PAH risk stratification using the recently proposed simplified risk table in patients with idiopathic/heritable (I/H) PAH and PAH associated with connective tissue disease (CTD) and congenital heart disease (CHD).

Methods

All patients with I/H-PAH, CTD-PAH and CHD-PAH referred to a single centre were included from 2003 to 2017. All patients were treated according to PH guidelines. The simplified risk assessment considered the following criteria: WHO functional class, 6-min walking distance, right atrial (RA) pressure or brain natriuretic peptide (BNP) plasma levels and cardiac index (CI) or mixed venous oxygen saturation (SvO2). For the last 2 criteria the worst parameter was chosen. Risk strata were defined as: Low risk= at least 3 low risk and no high-risk criteria; High risk= at least 2 high risk criteria including CI or SvO2; Intermediate risk= definitions of low or high risk not fulfilled. Then we performed a Cox analysis to evaluate the independent echocardiographic predictors of survival that were subsequently added to the simplified risk table to test their additional role in ameliorating risk stratification.

Results

461 treatment-naïve patients were enrolled. Echocardiographic independent predictors of prognosis were the severity of tricuspid regurgitation [HR (95% CI) = 1.013 (1.006–1.021); p-value = 0.001], right atrial area [HR (95% CI) = 1.028 (1.012–1.045); p-value = 0.001] and the presence of pericardial effusion [HR (95% CI) = 1.533 (1.142–2.057); p-value= 0.004]. Only RA area significantly ameliorate the risk stratification power of the recently validated simplified PAH risk table (likelihood ratio chi2 increased from 63.8 to 68.1, likelihood ratio test = 0.039). Due to the significant correlation between RA area and both RA pressure (r=0.470; p<0.001) and BNP (r=0.372; p=0.004), we elaborate a second risk table in which RA area (utilizing the cut-offs proposed by the current PH guidelines) was considered together within the criteria including RA pressure and BNP (the worst parameter of the 3 was considered). Considering the second risk table including RA area the risk stratification power significantly improved (likelihood ratio chi2 increased from 63.8 to 72.7, AIC/BIC decreased from 1956/1964 to 1947/1955).

Conclusions

Echocardiographic RA area significantly improve the risk discrimination power of the recently proposed simplified risk table for patients with PAH.

Funding Acknowledgement

Type of funding source: None
Could we suspect pulmonary veno-oclussive disease with a cardiopulmonary exercise test?
Authors: Perez Olivares Delgado C , Segura De La Cal T , Flox A , Prudencio V , Cristo M.J , Coronel L , Arribas F , Escribano P
Published: November 2020

Background

Cardiopulmonary exercise test (CPET) provides information about the pathophysiology of the exercise limitation. CPET parameters in pulmonary arterial hypertension (PAH) exhibit distinctive features, such as low peak oxygen uptake (pVO2), low end tidal carbon dioxide tension (PetCO2) and high ventilation-carbon dioxide slope (VE/VCO2).Pulmonary veno-oclussive disease (PVOD) is a PAH subgroup with particular underlying physiology, difficult diagnosis and poor prognosis.

Purpose

We hypothesized that different CPET patterns could be identified in PAH subgroups, and this may contribute to their diagnosis workup.

Methods

CPETs performed on the following PAH subgroups between September 2019 and January 2020 were prospectively included: Idiopathic PAH (IPAH), Heritable PAH (HPAH), and PAH responders to calcium channel blockers (CCB-R). Due to its low prevalence and its clinical relevance, CPET data on PVOD patients was retrospectively included.

Results

57 CPET were included: 20 IPAH (35%); 13 HPAH (22.8%); 9 CCB-R (15.8%),15 PVOD (26.3%). All patients presented impaired functional capacity with reduced peakVO2 and increased VE/VCO2). Remarkably, PVOD patients,in spite of a younger age, exhibit the worst functional capacity and ventilatory efficiency even showing downward PetCO2 kinetics. CCB-R group achieved the highest peakVO2 and had better ventilatory parameters.(Table 1)

Conclusion

CPET is a useful tool to classify patients by PAH subgroups. Very low PetCO2 at rest and a downward PetCO2 kinetic strongly suggest PVOD, which has significant implications on treatment.

Funding Acknowledgement

Type of funding source: None