bluuebunny/crossref_metadata_2025 huggingface dataset:
Finding the gaps in managing Fabry disease in women: the Romanian experience
Authors: Mursa A , Militaru S , Neculae G , Adam R , Radoi V , Rusu E , Popescu B A , Jurcut R
Published: October 2022

Introduction

Fabry disease (FD) is an X-linked rare lysosomal storage disease caused by mutations in the GLA gene which lead to decrease in α Gal A enzyme activity and tissue accumulation of lysosomal globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3). Due to X linked transmission, males are hemizygous, and females are heterozygous and were initially thought to be unaffected. However, women with FD can vary from asymptomatic, mildly symptomatic, to severely symptomatic as males. The aim of this study is to evaluate the particularities of FD presentation, cardiac imaging and management in females from the full Romanian FD cohort as compared to male patients.

Methods

This study included all consecutive patients diagnosed in or referred to our center with FD between 2014–2021. All patients had a complete clinical, biological and cardiac imaging workup.

Results

During the inclusion interval, data from 66 consecutive Romanian FD patients (37 women and 29 men) from 29 unrelated families were collected. Diagnosing mode in FD women differs compared to men (p<0.001): most women were diagnosed through family screening or by a cardiologist, while most men were diagnosed by nephrologists. Women had higher levels of α Gal A levels (1.3±0.8 μmol/L/h vs 0.5±0.7 μmol/L/h, normal cutoff >1.2) (p<0.001) and smaller levels of lyso-GB3 (5.8±2.6 ng/ml vs 110±35.6 ng/ml, normal cutoff<3.8) (p<0.001). More women are asymptomatic carriers than men (27% vs 3.4%), but when symptoms were present, they could be as severe as in men. Enrolled women were older (50.9±16.3 vs 41±14.9 years, p=0.014), diagnosed later (46.8±16.8 vs 32.7±14.3 years, p<0.001) and had later symptom onset of the disease compared with men (38.1±14.4 vs 20.3±14.9 years, p<0.001). Women had less angiokeratomas (p=0.001) and hypohydrosis (p=0.04), with no difference in cornea verticillata or ENT involvement. Both women and men developed cardiac symptoms starting from the fifth decade, with no differences in terms of angina, NYHA class, syncope between sexes. Women tend to have a lower prevalence of LVH compared to men (p=0.052), with no differences regarding ejection fraction or global longitudinal strain between genders. Regarding other organs involved, women were equally affected as men from acroparesthesia and stroke, with similar age at first cerebrovascular event. Women had milder kidney involvement (stages 1 and 2) when compared to men (56.8% vs 37.9%, p=0.004). Regardless of these findings, it appeared that women were less treated with pathogenic therapy comparing to men (48.6% vs 82.7%) (p=0.004).

Conclusions

Women with FD are not merely genetic carriers as they can be as affected as men. However, they benefit later from diagnosis and less of pathogenic therapy. Further studies with more female participations are needed to better understand the Fabry burden and needs in women.

Funding Acknowledgement

Type of funding sources: None.
Evaluation of non-breath-hold, ultra-fast, low-dose high-pitch (flash) CT scan as a practical alternative to standard spiral scan for pre-TAVI patients: a real-world single-center experience
Authors: Vitkon Barkay I , Dvir D , Elkan M , Pichkhadze O , Bogot N , Shaheen F , Chutko B , Glikson M , Wolak A
Published: October 2022

Introduction and aim

Aortic annulus dimensions change during the cardiac cycle. A retrospective ECG-gated (Spiral) scan is the default technique for pre TAVR evaluation since it includes systolic phases considered optimal for aortic annulus assessment. Ultra-fast, Low-Dose High-Pitch (FLASH) offers faster, potentially low radiation and low contrast dose scans. However, it lacks the ability to time data acquisition to the systole. Therefore, measurements derived from FLASH scan are considered suboptimal for reporting. The effect of this potential annular measurement difference on procedural success and safety was not evaluated. Therefore, we aimed to assess the feasibility and safety of FLASH vs. Spiral scan before TAVI.

Methods

We conducted a retrospective, single-center study. 409 patients underwent CT-TAVI scan with either FLASH or SPIRAL acquisition. Baseline characteristics, CT study, procedural and f/u data were acquired from the EMR. Outcomes defined by Valve Academic Research Consortium3 (VARC-2) endpoint definitions included in-hospital mortality, bleeding, vascular complications, acute kidney injury (AKI), conduction disorders, mechanical complications, and prosthetic aortic valve regurgitation. Composite endpoints such as device success were also examined.

Results

Of the 409 patients, 55.7% underwent FLASH scans. The median age was 80 years, and males accounted for 55%. The FLASH-protocol patients had higher rate of chronic kidney disease, their CT-measured aortic annulus area and diameter were smaller, and they were exposed to a smaller amount of contrast agent and radiation than the SPIRAL group. There was no statistically significant difference in primary clinical and safety endpoints between the two groups, including mechanical complications (such as annular rupture and valve malposition) and conduction disorders.

Conclusions

FLASH CT scan is a pragmatic and safe approach that potentially may replace spiral scan for the evaluation before TAVI procedure in the appropriate patients.

Funding Acknowledgement

Type of funding sources: None.
Prognostic role of low QRS voltages in patients with cardiac amyloidosis
Authors: Guerra F , Coretti F , Torselletti L , Coraducci F , Belleggia S , Manfredi R , Silenzi M , Falanga U , Principi S , Stronati G , Ciliberti G , Barbarossa A , Casella M , Dello Russo A
Published: October 2022

Introduction

Cardiac amyloidosis (CA) is an underdiagnosed and heterogeneous cardiac disease characterized by the extracellular deposition of misfolded proteins in the cardiac tissue. Clinical manifestations are heterogeneous leading to progressive heart failure, often complicated by arrhythmias and conduction system disease. Among several sign and symptoms that are suspicious for the disease, named “red flags”, disproportionally low QRS voltages on the ECG has been described.

Purpose

The aim of this prospective observational study is to evaluate potential prognostic features of QRS amplitude in AL e ATTR CA patients.

Methods

All consecutive patients admitted to the Cardiomyopathy Clinic of our institution have been enrolled after receiving CA diagnosis, according to the current guidelines. We included all patients ≥18 years with a diagnosis of CA and written informed consent. A complete assessment including a standard 12-lead electrocardiogram (ECG) and echocardiogram was performed at enrollment. Low QRS voltages (LQRSV) was defined as a QRS total amplitude of ≤5 mm in every limb leads and ≤10 mm in every precordial lead. LQRSV was tested as an independent predictor of death from all causes (primary endpoint), hospitalization from cardiovascular causes, ventricular and supraventricular arrhythmias.

Results

Sixty patients (46 males, 77±12 years old) were enrolled, of which 18 (30%) met the criteria for LQRSV. Patients with LQRSV presented more frequently with an history of ventricular arrhythmia (27.8% vs. 6.7%, p=0.04), a lower left ventricular diastolic volume (31±7 vs. 44±18 ml/m2; p=0.04), and higher retinol-binding-protein 4 (9.3±2.2 vs 3.2±1.5 mg/dl; p=0.02). No differences were seen in the primary outcome (46% vs. 50%; p=NS; Figure 1) or in the secondary ones (cardiovascular hospitalization 25% vs. 21%; ventricular arrhythmias 12% vs 4%; supraventricular arrhythmias 29% vs 19%; all p=NS) between the two groups during a median follow up of 1.1 year.

Conclusions

In the present cohort of CA patients LQRSV did not emerge as independent predictor of all-cause mortality at 1 year. Although LQRSV is a recognized diagnostic “red-flag” in the work-up of CA, its role as prognostic marker remains unclear. Further studies with a longer follow-up are needed to better define the prognostic role of LQRSV among CA patients.

Funding Acknowledgement

Type of funding sources: None.
Fabry disease and hypertrophic cardiomyopathy: similar albeit different
Authors: Allam C , Saouma M
Published: October 2022

Background

Fabry disease (FD) is a lysosomal storage disease that affects one or multiple organ systems and can cause left ventricular hypertrophy (LVH). FD can mimic hypertrophic cardiomyopathy (HCM), and clinicians occasionally miss the diagnosis of FD for HCM. The factors associated with FD-HCM misdiagnosis remain unclear.

Purpose

We sought to determine the prevalence of FD among patients with LVH and uncover the factors associated with FD-HCM misdiagnosis.

Methods

We searched online databases for all studies that performed a screening for FD in patients with LVH with reporting of a prevalence. We constructed a list of patients with LVH diagnosed with FD and collected their clinical, echocardiographic, and electrocardiographic characteristics and GLA gene mutation. We classified LVH as symmetric or asymmetric and GLA gene mutations as missense or non-missense. We calculated the prevalence of FD among patients with LVH adjusted for the founder effect. We later divided all FD patients into two groups depending on whether they were misdiagnosed for HCM (Group 1) or not misdiagnosed (Group 2). We used the chi-square and Student's t-test, respectively, to compare the quantitative and qualitative variables of Group 1 and Group 2.

Results

Thirty-one studies (n=11434 patients) met the inclusion criteria. There were 148 patients with LVH diagnosed with FD, and after adjusting for the founder effect, the prevalence of patients with LVH diagnosed with FD (n=117) was 1%. The number of FD patients misdiagnosed (Group 1) and not misdiagnosed (Group 2) for HCM was respectively 109 (73.6%) and 39 (26.4%). Patients in Group 1 were more likely to have an asymmetrical LVH, χ2(1, N=148)=18.6, p<0.001, a missense mutation, χ2(1, N=112)=7.8, p=0.0053 after adjusting for the founder effect, and a normal renal function, χ2(1, N=148)=16.2, p<0.001. The genetic results of five patients were missing. The maximal left ventricular wall thickness (LVWT) of Group 1 (M=19.84, SD=0.95) compared to Group 2 (M=17.58, SD=1.684) was significantly higher, t(109)=2.44, p=0.0165, and data were missing in 37 subjects. We did not find a significant difference in the following factors: age, nonclassic FD, angiokeratoma, acroparesthesia, stroke history, left ventricular outflow tract obstruction, history of syncope, atrioventricular block, history of tachyarrythmias, and history of pacemaker or defibrillator implantation.

Conclusion

FD is common among patients with LVH with a prevalence of 1%. Asymmetrical LVH and severe LVH are incorrectly thought to be uncommon in FD and tend to mislead clinicians in their diagnostic approach. FD patients with LVH and misdiagnosed HCM are more likely to have a missense mutation. FD patients with LVH and CKD are less likely to be misdiagnosed for HCM, and the most probable cause is that clinicians misdiagnosed some of these patients for CKD-related LVH. To conclude, we must increase awareness among clinicians on the red flags of FD.

Funding Acknowledgement

Type of funding sources: None.
Outcomes of heart failure with preserved ejection fraction (HFpEF) in patients with and without cardiac amyloidosis: analysis from 2016–2019 national inpatient sample
Authors: Kambalapalli S , Baral N , Seri A , Bhakta S
Published: October 2022

Background

Cardiac amyloidosis (CA), a restrictive cardiomyopathy that leads to heart failure, is often under-diagnosed in its early-stages, leading to patients being diagnosed with it in advanced stages. Most patients presenting with heart failure are presumed as non-amyloid heart failure due to a lack of awareness. A high degree of clinical suspicion is of paramount importance for early diagnosis and management of CA because the extent of cardiac involvement determines overall prognosis.

Purpose

Our study highlights the outcomes of HFpEF in patients with and without CA.

Methods

This is a retrospective cohort study involving principal hospitalizations for HFpEF between January 1, 2016 and December 31, 2019 from the National Inpatient Sample (NIS), the largest all-payer public database of hospital care data in the United States. Our study sample included discharged adult patients (≥18 years) hospitalised for HFpEF using ICD-10 codes validated in previous studies. Confounders were adjusted using multivariable regression analysis.

Results

During the study period, there were 87,219 index hospitalizations for HFpEF. Among them, 38.3% (n=33405) were males, 61.7% (n=53814) were females, and 0.24% (n=209) had CA. Racial distribution is as follows: 76% Whites, 13.4% Blacks, 6.4% Hispanics, and 4.2% other races. Mean patient age was 74.6±13.2 years, and 68.1% were on Medicare. A total of 59,135 (67.8%) hospitalizations had a Charlson Comorbidity Index (CCI) of >3, with an in-hospital mortality of 2.5%. Compared to the non-CA cohort, the CA cohort had lower prevalence of diabetes mellitus (8.5% vs 27%, p<0.0001) and COPD (23.5% vs 46.8%, p<0.001) but a higher prevalence of renal disease (51.6% vs 41.9%, p=0.004), cancer (25.4% vs 4.2%, p<0.001) and greater incidence of cardiogenic shock (5.2% vs 0.5%, p<0.001).

Compared to the non-CA cohort, patients with CA were less likely to be female (38% vs 61.7%, p<0.001), were of similar age (mean age 74.7 vs 74.6 yrs, p=0.907), had longer length of hospital stay (LOS, 6.7 vs 5.1 days, p<0.001), higher in-hospital mortality (5.2% vs 2.5%, p=0.023), and a higher likelihood of having a CCI >3 (74.2% vs 67.8%, p=0.017). Multivariate regression analysis showed that subjects in the CA cohort had significantly increased adjusted odds of in-hospital mortality (aOR=2.2; 95% CI: 1.2–4.4; p=0.017) and cardiogenic shock (aOR=9.5; 95% CI: 5–17.9; p<0.001) than those in the non-CA cohort after adjusting for age, sex, race, and CCI.

Conclusions

Our study illustrates that patients with a history of CA admitted for HFpEF had greater incidence of cardiogenic shock, higher prevalence of renal diseases and cancer with a longer LOS, and higher in-hospital mortality.

Funding Acknowledgement

Type of funding sources: None.
Predictive value of novel circulating biomarkers in Chagas disease: The Brazilian Chagas disease cohort
Authors: Raguindin P , Rocha M O , Mattoso Barbosa A M , Muka T , Glisic M , Suosa G
Published: October 2022

Introduction

Chagas disease, caused by the protozoan Trypanosoma cruzi (T. cruzi), is the leading causes of non-ischemic heart failure and premature cardiac deaths in Latin America. Identifying predictive biomarkers of morbidity and progression of Chagas cardiomyopathy (CCC) is important to deciphering novel pathways and aid in early identification of patients at highest risk for future adverse cardiovascular (CV) outcomes.

Objectives

To determine the association of novel circulating biomarkers with CCC and disease survival.

Methods

Serum levels of 184 unique cardiometabolic and inflammation proteins were measured using proximity extension immunoassay using age- and sex- matched patients without history of any other cardiovascular or infectious diseases as well as diabetes mellitus, who were identified and selected at the referral outpatient center for Chagas Disease at a clinical hospital in Brazil. Univariable linear regression using standardized protein levels were compared between patients with and without CCC. All p-values were adjusted for multiple testing and in findings with p value<0.0002 were considered statistically significant. Proteins that reached significance level were further compared between disease mortalities and survival. We also performed network analysis using STRING-DB on overexpressed proteins to determine its interaction.

Results

We used data from 44 with CCC and 44 with asymptomatic T. cruzi-positive patients (indeterminate). Among individuals with CCC, 22 patients had a fatal cardiovascular event during follow-up period of 4.1 (SD ±1.4) years. In linear regression analyses, we identified 45 candidate biomarkers associated with chronic CC (all p values <0.0002). Among these, only three proteins (IL33, CD40, REG1A) were significantly different between individuals with CCC who died vs survived over a period of 4.1 years. We used 38 overexpressed proteins in network analysis. THBS4, marker of cardiac remodeling, was overexpressed in CCC. CXCL11 were seen co-expressed with CXCL9 and CXCL10, all are known activators of CD4+ Th1 cells in CCC.

Conclusion

We identified 45 novel cardiometabolic and inflammatory markers that are associated with chronic Chagas cardiomyopathy.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): Leading House of Latin America of the Swiss State Secretariat for Education, Research and Innovation (SERI)
Pattern of pericardial calcification determines the mid-term postoperative outcome after pericardiectomy in chronic constrictive pericarditis
Authors: Lee Y H , Kim S M , Kim E K , Park S J , Lee S C , Park S W , Jeong D S , Chang S A
Published: October 2022

Background/Introduction

Although pericardiectomy is an effective treatment of constrictive pericarditis (CP), clinical outcome is not always successful. Pericardial calcification is a unique finding in CP. However, the amount and localization of calcification vary. Computer tomography (CT) can visualize the pericardial calcification with high sensitivity and provide the anatomical assessment.

Purpose

We investigated that how the pattern and amount of pericardial calcification affect the mid-term postoperative outcome after pericardiectomy in CP.

Methods

All of the patients who underwent total pericardiectomy in our hospital from 2010 to 2020 were derived from electrical medical records (n=105). Among them, preoperative CT scans (non-gated non-contrast) of 98 patients were available and, thus, 98 consecutive patients were finally analyzed. Medical records were reviewed in a retrospective manner. Cardiovascular event is defined as cardiovascular death or hospitalization associated with a heart failure symptom and all cause event is defined as all events that require admission. CT scan was analyzed by Aquarius Workstation, and the volume and localization pattern of pericalcification were derived. Pericardium calcium score was given as an Agatston score.

Results

Of 98 patients, 25 (25.5%) patients were hospitalized with heart failure symptom after pericardiectomy. Median follow up duration of patients is 172 weeks. A group with cardiovascular event had higher NYHA grade (P<0.001), lower calcium volume (P=0.004), and lower calcium score (P=0.01). Multivariate cox proportional analysis showed that high ln(calcium score) before pericardiectomy was dependent predictor of cardiovascular event (hazard ratio, 0.90; P=0.04) and all cause event (hazard ratio, 0.91, P=0.04) after pericardiectomy. When we set the cut off value at 7.22, based on ROC curve, there was a significant difference in cardiovascular event between the groups divided by this cutoff value in Kaplan-Meier curve (P=0.002) and multivariate cox proportional analysis (P=0.04). In the subgroup analysis, myocardium invasion and circumferential calcification were more common in the high calcium score group. Idiopathic & tuberculosis pericarditis were more associated with high calcium score group and post-operative pericarditis, other reasons (infection, radiation, etc) were more associated with low calcium group.

Conclusion

Low burden of pericardial calcification was associated high rate of mid-term clinical event after pericardiectomy CP. Preoperative evaluation of pericardial calcification pattern can be used as predictor of postoperative outcomes.

Funding Acknowledgement

Type of funding sources: None.
Cardiac damage staging in patients undergoing TAVR. Incremental value of global longitudinal strain and right ventricular-arterial coupling
Authors: Gutierrez E , Carrion I , Olmos C , Jimenez P , Nombela L , Pozo E , Mahia P , Gil S , De Agustin A , Islas F
Published: October 2022

Background

Transcatheter aortic valve replacement (TAVR) is nowadays a safe and increasingly frequent option to treat severe aortic stenosis (AS). Cardiac damage staging has been proposed and validated in some studies as a prognostic tool; however, many patients continue to undergo aortic valve replacement only after there is evidence of cardiac damage. The aim of this study is to assess the potential incremental value of global longitudinal strain (GLS) and right ventricular-arterial coupling (RV-VAc) in the prognostic performance of the cardiac damage staging.

Methods

Consecutive patients with AS and undergoing TAVR were included in our hospital registry. Baseline echocardiography was performed before TAVR according to current guidelines. For this study, patients were classified based on the following stage of cardiac damage: Stage 0: no cardiac damage; Stage 1: left ventricular (LV) damage (LV ejection fraction (LVEF) <50%, LV mass index >95 g/m2 for women, >115 g/m2 for men); Stage 2: left atrial (LA) or mitral valve damage (LA volume index >34 ml/m2, mitral regurgitation moderate-severe, or presence of atrial fibrillation); Stage 3: pulmonary vasculature or tricuspid valve damage (systolic pulmonary artery pressure 60 mmHg, or tricuspid regurgitation moderate-severe); Stage 4: RV damage (TAPSE <1.7 cm, S' <9.5 cm/s).

Results

496 patients were studied. Mean age of the cohort was 81.9±6.2 years, mean aortic valve area was 0.86±0.6 cm2, mean LVEF was 57.9±12.3%, mean LV-GLS was −15.6±3.5% and RV-Vac was 0.61±0.34. Table 1 shows clinical and echo characteristics of patients. Only one patient (0.2%) met criteria for stage 0; 38 (7.7%) patients were in stage 1; 159 (32.1%) patients in stage 2, 157 (31.7%) patients in stage 3 and 141 (28.4%) patients in stage 4. 1-year mortality for stage 1 was (10.5%), for stage 2 (13.7%), for stage 3 (32.2%) and for stage 4 (19.5%). The area under the ROC curve (AUC) for 1-year mortality for the cardiac damage staging system was 0.622, CI (0.539–0.705); the best cut-off value for LV-GLS to predict 1-year mortality was −14% with an AUC of 0.634 CI (0.487–0.781) and RV-VAc had an AUC of 0.748 CI (0.638–858). Finally, the model that included the staging system, LV-GLS and RV-VAc had an AUC ROC of 0.875, CI (0.780–0.971) (Figure 1).

Conclusions

Cardiac damage staging is a good prognostic tool and it has been validated in several studies, however, the addition of feasible and widely available echo parameters such as LV-GLS and RV-VAc can significantly increase its prognostic yield.

Funding Acknowledgement

Type of funding sources: None.
Clinical outcome of patients with severe malignant pericardial effusion due to neoplastic disease undergoing percutaneous balloon pericardiotomy during COVID-19 pandemic
Authors: Alfonso Rodriguez E , Lopez Cabrera G , Llerena Rojas L L , Rodriguez Nande L , Lopez Ferrero L , Echarte Martinez J
Published: October 2022

Background

Neoplastic pericardial effusion (NPE) is a serious complication that occurs in the setting of advanced oncological disease and is associated with a high recurrence rate. Currently, pericardiocentesis (PCT) remains the first therapeutic option and the use of percutaneous balloon pericardiotomy (PBP) is limited to the treatment of recurrences. However, it is not known whether some aspects of the procedure during PBP lead to different outcomes in terms of survival and recurrence, and no such patients have been included in studies during COVID-19 pandemic.

Purpose

The aim is to analyses the success, complications and recurrence rate (defined as recurrence of NPE requiring PCT, PBP or surgical pericardial window (SPW) of both procedures (BP) in order to establish the optimal entry treatment for these patients.

Methods

This research analyzed the clinical characteristics and prognostic factors of patients with severe pericardial effusion of neoplastic etiology who underwent PBP during the COVID-19 pandemic. A prospective study was conducted involving 23 patients admitted between January 2020 and January 2022 for severe NPE who underwent PCT or PBP as initial treatment of NPE.

Results

We included 23 patients, 62.9% were male with a mean age of 51.2±14.9 years NPE was the first manifestation of the oncological process in 12 patients (52.1%) with lung cancer being the most frequently associated primary cancer (58.7%) followed by breast cancer in 12.7% of cases. A total of 26 procedures were performed, 10 PCT, 15 PBP, 1 SPW, with tumors cells identified in the pericardial fluid in 13.0% of cases. PCT was used as an entry point in 10 patients (43.5%), 6 patients were COVID-19 positive and PCT was performed as the first treatment. While PBP was chosen as the first therapeutic option in 13 patients (56.5%) (2 Re-PBP). The initial efficacy of the procedure was 93.1% and 92.2% respectively (p=0.88), with 1 complication occurring in the PBP group but not requiring scheduled SPW. In the former group, the percentage of recurrences was higher (34.7%; 8 recurrences in 10 patients) compared to patients treated with upfront PBP (8.6%; 2 recurrences in 13 patients), p=0.09. In addition, only one patient had to resort to surgery. When analyses according to the BP. used, the recurrence rate was 4.0 times higher for PCT (34.7 vs. 8.6% recurrences), although without reaching statistical significance (p=0.16).

Conclusions

The PBP is a simple, safe and effective technique for the treatment of NPE during the COVID-19 pandemic, in our series it was associated with a lower recurrence rate. Therefore, it could replace PCT in these patients during the COVID-19 pandemic as optimal first line treatment, providing better quality of life and reducing the need for re-interventions.

Funding Acknowledgement

Type of funding sources: None.
Exploring variations in current clinical practice regarding postoperative pericardial effusion: a questionnaire study
Authors: Van Dinter S R , Li W W , Wollersheim L W , Morshuis W J , Van Royen N , Dieker H , Verhagen A F T M
Published: October 2022

Background

Postoperative pericardial effusion (PPE) is a frequently occurring event after cardiac surgery, potentially leading to life-threatening cardiac tamponade. Unfortunately, no guidelines are currently available on this subject, possibly leading to unwarranted variations in care in clinical practice.

Purpose

The goal of our study was to determine the diagnostic and therapeutic preferences of cardiologists and cardiothoracic surgeons in the Netherlands regarding PPE, and to evaluate possible variations in this matter between specialties and centers.

Methods

A web-based questionnaire was sent to all interventional cardiologists and cardiothoracic surgeons in the Netherlands. Diagnostic preferences for the evaluation of PPE were examined. Additionally, clinical preferences were explored in response to 4 patient scenarios with each illustrating a combination of either high or low clinical suspicion of cardiac tamponade and either high or low echocardiographic suspicion. Each scenario was also stratified by 3 different amounts of PPE (<1cm, 1–2cm, >2cm), leading to a total of 12 fictional patient cases (Figure 1).

Results

From 27 of the 31 contacted centers, a total of 94 clinicians responded to the survey, of whom 46 interventional cardiologists and 48 cardiothoracic surgeons. Cardiologists were more in favor of routine postoperative echocardiography in all patients (44%), whereas cardiothoracic surgeons preferred routine imaging after specific procedures, especially after mitral (85%) and tricuspid (79%) valve surgery. Overall, drainage of PPE (>48 hours postoperatively) was preferred through pericardiocentesis (83%) instead of surgical evacuation (17%). Regarding the patient scenarios, cardiothoracic surgeons were significantly more inclined to evacuate PPE compared to cardiologists for all scenarios combined (51% vs 37%, p<0.001) (Figure 1). In addition, evacuation was overall significantly more preferred by cardiologists employed in surgical centers when compared to those working in non-surgical centers (43% vs 31%, p=0.02). Results from the interrater agreement analysis of groups of clinicians working in the same center varied from very poor up to very good (kappa value of 0.22–0.67), suggesting existing variation of PPE treatment preferences even within one center.

Conclusions

Our study highlights the significant variation of preferences in contemporary PPE management between cardiothoracic surgeons and interventional cardiologists in the Netherlands, sometimes even within the same center. These findings are the possible consequences of a current lack of general recommendations or guidelines. This could lead to unwarranted variation in care and additional research is necessary to provide general recommendations.

Funding Acknowledgement

Type of funding sources: None.
The risk spectrum of infective endocarditis among patients with congenital heart diseases
Authors: Havers-Borgersen E H B , Butt J H B , Oestergaard L O , Petersen J K P , Torp-Pedersen C T P , Koeber L K , Fosboel E L F
Published: October 2022

Background

Patients with congenital heart disease (CHD) are considered at lifelong high risk of infective endocarditis (IE). The risk of IE presumably differs among different types of CHD, but little knowledge exists on the area.

Purpose

This study set out to investigate the long-term incidence of IE among CHD-patients and associated risk factors.

Methods

In this observational cohort study, all patients with CHD born in 1977–2018 were identified using Danish nationwide registries and followed from date of birth until occurrence of first-time IE, emigration, death, or end of study (December 31, 2018). The comparative risk of IE among patients with CHD versus age- and sex-matched controls from the background population was assessed. Moreover, the risk of IE was stratified according to type of CHD and risk factors associated with IE among patients with CHD were examined using Cox regression analysis including sex and relevant time-varying coefficients (i.e., cyanotic yet surgically untreated CHD, CHD repaired with prostheses, diabetes mellitus, chronic kidney disease, and presence of cardiac implantable devices).

Results

A total of 23,464 patients with CHD (50.0% men) were identified and matched with 93,856 controls from the background population. During a median follow-up of 17.7 years, 217 (0.9%) patients with CHD and 4 (0.0%) controls developed IE, corresponding to incidence rates of 5.2 (95% CI: 4.6–6.0) and 0.02 (95% CI: 0.01–0.1) per 10,000 person-years, respectively. The associated incidence of IE was greatest among patients with tetralogy of Fallot, malformations of the heart chambers (including transposition of the great arteries and truncus arteriosus), atrioventricular septal defects, and heart valve defects (Figure 1). Factors associated with IE among patients with CHD included male sex (HR 1.7 [95% CI, 1.3–2.2]), cyanotic yet surgically untreated CHD (HR 5.2 [95% CI, 3.5–7.7]), cardiac prostheses (HR 5.2 [95% CI, 3.6–7.5]), chronic kidney disease (HR 3.1 [95% CI, 1.3–7.6]), and presence of cardiac implantable electronic devices (HR 3.1 [95% CI, 1.5–6.2]).

Conclusions

Patients with CHD, especially those with tetralogy of Fallot and malformations of the heart chambers, have a substantially higher incidence of IE than the background population. With an increasing longevity of these patients, relevant guidelines concerning preventive measures are decisive to improve morbidity, mortality, and the quality of life among this growing group of patients.

Funding Acknowledgement

Type of funding sources: None.
Long-term survival in adults with congenital heart disease: a nationwide, register-based cohort study
Authors: Dellborg M D , Giang W G K , Eriksson P E , Liden H L , Fedchenko M F , Ahnfelt A A , Rosengren A R , Mandalenakis Z
Published: October 2022

Background

The survival of children with congenital heart disease has increased exponentially over the last decades, with 97% currently reaching adulthood. However, the total impact of advanced treatment on mortality and morbidity in adult survivors in relation to the general population is less well described.

Purpose

We aimed to investigate long term outcomes of adults with congenital heart disease (ACHD) in Sweden, from the age of 18 years through middle-age.

Methods

Data from the Swedish National Patient Register and Cause of Death Register were linked to identify all ACHD patients born from 1950 to 1999 and alive at the age of 18 years. Each ACHD patient was matched by birth year and sex with more than ten controls without congenital heart malformations from the Total Population Register in Sweden, with follow-up time for cases and controls until December 2017.

Results

Altogether 37,278 ACHD patients and 412,799 matched controls were included in the study. The mean follow-up was 19.2 (± 13.6 years). The risk of death after the age of 18 years was 3.2 times higher (95%, confidence interval (CI) 3.04–3.37) among ACHD patients compared to controls. At the age of 68 years, more than 75% of ACHD patients were still alive. The risk of death was significantly higher also for the more benign lesions i.e. atrial septal defects, ventricular septal defects and coarctation of the aorta. Starting in the mid 1970ies, the risk of death declined over time and for those born after 1975 the risk decreased steadily with each successive birth year.

More patients with ACHD developed atrial fibrillation, heart failure, non-fatal myocardial infarction, non-fatal stroke or died in comparison to controls, adjusted hazard ratio for any of these ranged between 20.58 (95%, CI 18.74–22.60) for patients with complex disease and 9.89 (95%, CI 9.53–10.27) for patients with mild or moderate disease.

Conclusions

In this large, nationwide, register-based cohort study of patients with ACHD surviving until the age of 18 years, the risk of mortality up to the age of 68 years was more than three times higher compared to matched controls. A notable decline in the risk of death was found in patients with ACHD born after 1970. Despite this substantially high relative mortality risk during adulthood, at least 75% of ACHD patients will become sexagenerians.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swedish state under an agreement between the Swedish Government nad county Councils (ALF)
Survival in patients with congenital heart disease and down syndrome
Authors: Engsner S , Giang K W , Dellborg M , Fedchenko M , Eriksson P , Mandalenakis Z
Published: October 2022

Background

Increasing survivorship among patients with congenital heart disease (CHD) has been reported during the past decades. However, a number of patients with CHD have an associated Down syndrome diagnosis and the long-term prognosis is still debated.

Purpose

The aim of the present study was to estimate the mortality risk in CHD patients with Down syndrome compared to a matched control population without CHD.

Methods

We linked data from the Swedish National Patient Register and Cause of Death Register to identify all CHD patients born between January 1970 and December 2017. Then we identified all CHD patients with Down syndrome. Each CHD patient with Down syndrome was matched for sex and birth year with eight controls without CHD or Down syndrome from the Total Population Register. A Cox proportional regression model was used to estimate the mortality risk and Kaplan Meier for survival analysis.

Results

In total, 3,285 patients with CHD and Down syndrome and 26,128 matched controls were identified. During a mean follow-up of 16.0 (±12.6) years, 558 CHD patients (17%) with Down syndrome, and 198 controls (0.76%) died. CHD patients with Down syndrome had 25.1 times higher risk of mortality (Hazard ratio 25.1, 95%, confidence interval (CI) 21.3–29.5) compared with controls. Patients with the most complex CHD were found to have the highest mortality risk (Hazard ratio 32.3, 95% CI 26.1–39.9). A decrease in risk of mortality during the first year of life was found between the two birth periods, risk of mortality was 46.8 (CI 29.5–74.0) in 1970–1989 and 17.7 (CI 12.8–24.42) 1990–2017. In addition, the mortality risk was two times (95% CI 1.94–2.31) higher for CHD patients with Down syndrome when compared to CHD patients without Down syndrome.

Conclusion

The risk of mortality among CHD patients with Down syndrome was 25 times higher compared to controls without CHD or Down syndrome. The highest risk of mortality was found in patients with complex CHD. The survivorship rate was exponentially increased in CHD patients with Down syndrome that were born after 1990, determining the modern era of congenital heart care.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swedish state under an agreement between the Swedish Government and county Councils (ALF)
Conservative vs surgical management in ebstein's anomaly: long-term follow-up in a real-life cohort
Authors: Merino Argos C , Meras Colunga P , Ruiz Cantador J , Jimenez Valero S , Gonzalez Fernandez O , Valbuena Lopez S C , Ponz De Antonio I , Rosillo Rodriguez S O , Caro Codon J , Iniesta Manjavacas A M , Abelleira Pardeiro C , Balbacid Domingo E J , Perez David E , Lope De Sa Areses E , Gonzalez Garcia A E
Published: October 2022

Background

Ebstein's anomaly (EA) is a rare congenital heart disease that involves the tricuspid valve and the right ventricle, often associating atrial septal defects and atrial arrhythmias. Oligosymptomatic adults affected by this disease usually have good prognosis, while its evolution in symptomatic children is more aggressive. Clinical guidelines provide some recommendations for the former patients regarding surgical indication, but its evidence is scarce and benefit remains unclear.

Purpose

To compare functional capacity, ventricular function parameters and outcomes between medically and surgically treated patients with EA.

Methods

Retrospective cohort study of patients with EA followed-up in an adult congenital heart disease reference unit of a tertiary university hospital. Functional status and ventricular size and function parameters at baseline and follow-up, as well as clinical events, were compared between conservative and surgical groups.

Results

We included 72 patients; mean age was 45.2±15.2 years and 27 (37.5%) were men. Median follow-up was 6.6 (range 0.3–20.3) years. Finally, 18 (25%) patients were operated (12 tricuspid repairs, 5 tricuspid bioprostheses and 1 mechanical tricuspid prostheses). Characteristics and outcomes of conservative and surgical group are shown in Table 1. Comparison of follow-up data for each group are shown in Table 2. Of note, Glenn procedure was done in 6 (33.3%) patients of the surgical group and prosthetic thrombosis was observed in 3 (50%) patients during follow-up.

Conclusions

Only one fourth of patients with EA in our cohort were managed surgically. Operated patients had worse functional status and larger right ventricles at baseline. At follow-up, surgical patients had more clinical events and worse ventricular function. Exercise test parameters did not change significantly after surgery, whereas there was worsening functional capacity during follow-up in medically-managed patients.

Funding Acknowledgement

Type of funding sources: None.
Cardiopulmonary exercise testing in Fontan patients: unmasking the secret of Super-Fontans
Authors: Paiva M , Rato J , Santos R , Cunha G , Gomes D , Cordeiro S , Madeira S , Guerreiro S , Moreno L , Durazzo A , Mendes M
Published: October 2022

Background

Exercise capacity is usually reduced in Fontan patients, however there is a subset of patients who have normal exercise capacity and better outcomes, the “Super-Fontans”. The aim of this study was to characterize a cohort of Fontan patients undergoing cardiopulmonary exercise testing (CPET) and identify predictors of better functional capacity.

Methods

Single center retrospective analysis of consecutive Fontan patients aged >10 years old who underwent CPET, between March 2018 and May 2021.

Peak respiratory exchange ratio1.05 defined maximal CPET. Peak VO2 (pVO2) as a percentage of its predicted value was used as reference value to stratify patients in tertiles.

Patients in 3rd tertile, with a percentage predicted pVO2 superior to 75%, were considered good-performers.

Blood tests and transthoracic echocardiogram (TTE) were performed on the same day. Additional data were collected from electronic charts.

Results

In total, 49 patients were included (mean age 19±7 years old, 67% male) with intra or extracardiac conduit implanted in mean 12±7 years prior to the CPET.

The most common primary diagnoses were tricuspid/pulmonary atresia (43%), followed by unbalanced complete AV septal defect (14%) and double inlet left ventricle (14%). 12 patients had a systemic right ventricle. All, except 5 patients, had preserved systolic ventricular function and 37% had moderate to severe AV regurgitation.

The majority had normal hemoglobin levels (median 15.6 g/dL), hepatic enzymes (median total bilirubin 0.8 mg/dL), renal function (median creatinine 0.8 mg/dL) and low NT-proBNP (median 122 pg/mL).

All patients had maximal CPET, median %VO2 at VT1 was 57% of peak and mean pVO2 was 66±14% of the predicted. Most patients (69%) showed exercise limitation due to cardiovascular cause, followed by O2 desaturation, present in 22% of CPETs. The age of Fontan completion was not associated with functional capacity (p=0.6).

The good-performer group comprised 13 patients (27%), all in sinus rhythm, of which 10 were physically active. Compared with the remainder, this group had higher VO2 at VT1 (18.7 vs. 14.6, p=0.01) and VO2 at VT2 (25.9 vs. 22.1, p=0.02), both in mL/kg/min. Also, peak heart rate (% predicted) (90 vs. 81, p=0.03) was higher in this subgroup – fig.1. Conversely, differences on TTE parameters (GLS and AV valve regurgitation) and blood biomarkers were not statistically significant. On multivariable analysis, no single variable predicted better functional capacity.

Conclusion

In our Fontan cohort, most patients had reduced exercise capacity, largely due to cardiovascular dysfunction. However, “Super-Fontans” stood out as they had a higher anaerobic threshold illustrating their better physical condition. These findings highlight the role of regular physical activity in Fontan patients as a cornerstone for better functional capacity.

Funding Acknowledgement

Type of funding sources: None.
Burden of morbidity in patients with Ebstein anomaly: a two-country, population-based cohort study including 823 patients
Authors: Eckerstrom F , Dellborg M , Hjortdal V E , Eriksson P , Mandalenakis Z
Published: October 2022

Background

Burden of morbidity in patients with Ebstein anomaly (EA) is to a large extent undescribed.

Purpose

We conducted an extensive two-country register-based collaboration aiming to describe the burden of morbidity in patients with EA.

Methods

Patients born in the period 1930–2017 and diagnosed with EA were identified in Danish and Swedish nationwide medical registries and subsequently merged. Each EA patient was matched by birth year and gender with ten controls without congenital heart disease from the general population. Cox proportional hazard regression model was used to compute risk (hazard ratio (HR)) of morbidity (arrhythmia, heart failure, and stroke). Follow-up started at birth. Patients and controls became at risk at birth.

Results

We included 823 patients and 8,230 matched controls; median follow-up was 13.2 years (interquartile range: 3.5–20.9). In the total EA cohort, 44% (n=366) underwent cardiac surgery, predominantly EA-related surgery (81%) and other congenital cardiac surgery (15%). Approximately half of the cohort had an isolated EA (n=442) and 13% (n=108) had a concomitant atrial septal defect (ASD) only. Patients with non-operated isolated EA had a 9-fold increased risk of arrhythmia and a 5-fold increased risk of heart failure compared with the general population [HR for arrhythmia 9.4 (95% CI: 6.9–12.7) and HR forheart failure 5.2 (95% CI: 3.2–8.3)]. The risk of arrhythmia, heart failure, and stroke among patients with non-operated EA and concomitant ASD was 12.1 (95% CI: 3.0–48.8), 30.6 (95% CI: 3.2–295.2), and 8.2 (95% CI: 0.7–91.2), respectively. The risk of stroke in operated EA patients with concomitant ASD was 43.8 (95% CI: 17.5–109.7). Patients with operated isolated EA had a 25-fold increased risk of developing arrhythmia and 10-fold increased risk of heart failure compared with the general population [HR for arrhythmia 25.0 (95% CI: 17.7–35.3) and HR for heart failure 10.1 (95% CI: 6.0–16.9].

Conclusion

Patients with EA carries a substantial burden of arrhythmia, heart failure, and stroke compared with the general population irrespective of treatment pathway, necessitating meticulous follow-up in specialized adult congenital heart disease clinics to detect and possibly prevent or limit morbidity at an early stage.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Novo Nordic Foundation.
Candidacy for heart transplantation in adult congenital heart disease patients: a cohort study
Authors: D'Angelo E C , Angeli E , Ragni L , Gargiulo G G , Donti A , Potena L , Tonoli F , Bartolacelli Y , Bulgarelli A , Careddu L , Ciuca C , Zanoni R , Egidy Assenza G
Published: October 2022

Objective

The object of the present study is to evaluate factors precluding heart transplantation (HTx) in adult congenital heart disease patients (ACHD) with end-stage heart failure (HF) referred for HTx evaluation.

Methods

This retrospective cohort study enrolled consecutive ACHD patients considered for HTx in our institution between 2014 and 2020 and patients receiving HTx between 2001 and 2013. HTx refusal due to poor candidacy status for excess risk of mortality after transplantation, served as the main study outcome.

Results

Between 2014 and 2020, 46 ACHD patients were evaluated for HTx, 14 ACHD patients underwent HTx between 2001 and 2013. We compared clinical, anatomical and demographic data of 41 patients suitable for transplantation (including both listed/transplanted patients, not yet listed because too well and patients who chose to refuse transplantation) with 15 patients refused after screening (excluding 4 patients with ongoing screening). Risk factors for refusal were: multiple high risk features (odds ratio [OR]: 3.6; 95% confidence interval [CI]: 1.1 to 12.9; p 0.048); anatomical factors (OR: 14.5; 95% CI: 3.1 to 68.4; p 0.001), out-of-center ACHD/HTx program referral (OR: 5.3; 95% CI: 1.5 to 19.0; p 0.01). HTx refusal identifies a high risk ACHD patient subgroup (hazard ratio for overall mortality: 3.1; 95% CI: 1.1 to 8.3; p 0.02).

Conclusions

In our study risk factors for refusal from HTx are adverse anatomical features, multiple conventional HTx high risk factors and out-of-center referral. ACHD patients refused from HTx present shorter time to death. Efforts to increase HTx candidacy are strongly necessary for this growing population.

Funding Acknowledgement

Type of funding sources: None.