bluuebunny/crossref_metadata_2025 huggingface dataset:
Family screening in patients with isolated bicuspid aortic valve in a general hospital, yield and subgroup analysis
Authors: Cozijnsen L , Braam R.L , Bakker-De Boo M , Otten A.M , Post J.G , Schermer T , Bouma B.J , Mulder B.J.M
Published: November 2020

Background

Bicuspid aortic valve (BAV) may frequently lead to aortic dilatation with risk of aortic dissection. In patients with BAV both familial clustering and aortic dilatation in first-degree relatives (FDR) without BAV has been demonstrated. Based on these findings the ESC Aortic Guidelines recommend to consider screening of FDR, while the ACC/AHA Guidelines on Valvular Heart Diseases consider screening of FDR only if the index patient has associated aortopathy. Currently, no data about the effectiveness of screening is available.

Purpose

To investigate the yield of screening FDR of patients with isolated BAV and to explore subgroups with FDR of patients who had needed surgery or of patients with aortic dilatation. We hypothesized that aortic dilatation (>40mm) in the index patient is not a risk factor for BAV in FDR.

Methods

From 2012, patients with BAV visiting the outpatient clinic of a teaching hospital, received information advising cardiac screening of FDR. FDR of patients with isolated BAV who were referred, were included. From the 10 index patients from other hospitals, information was retrieved. [Fig.1]

Results

Referred were FDR from 118 index patients (mean age 60 years, standard deviation [SD] 14, range 15–90 years, 82 males [70%]). Of all index patients 63 (53%) had undergone aortic valve replacement, including concomitant ascending aorta replacement in 25 (21%). In the non-operated index patients, 31 (26%) had dilatation (>40mm) of sinus of Valsalva and/or tubular ascending aorta.

Screened were 257 FDR (median 2 per index patient) comprising 20 parents (8%), 103 siblings (40%) and 134 offspring (52%). Mean age of FDR was 48 years (SD16, range 4–83 years) and 89 subjects (42%) were male. The diagnostic imaging modality was echocardiography in 240 cases (93%) and MRI in 17 cases. Ten FDR had an already known BAV and were not included in the screening.

Among the 257 FDR, we diagnosed 12 new BAV (4.7%, 95% confidence interval [CI]2.9–8.0%) (mean age 44 years, 50% male). Additionally, we diagnosed 23 new isolated aorta dilatations (8.9%; 95% CI 6.0–13%) at level of sinus of Valsalva and/or tubular ascending aorta (mean age 57 years, 18 [78%] were male) [Fig. 1]. Among them, 11 had hypertension.

FDR (n=147) of index patients with BAV and previous aortic valve surgery (n=63), had a risk ratio (RR) of 2.25 (95% CI 0.62–8.10) of having a BAV. FDR (n=126) of index patients with BAV and repaired or unrepaired aortic dilatation (n=56) had RR 0.35 (95% CI 0.10–1.25) of having a BAV.

Conclusions

Screening FDR of patients with isolated BAV resulted in a reasonable yield of 14% new cases with BAV or isolated aortic dilatation. The RR of the subgroup with aorta dilatation did not justify the limitation of the FDR as suggested in the ACC/AHA Guidelines.

Figure 1. Flowchart of screening and result

Funding Acknowledgement

Type of funding source: None
Risk of infective endocarditis among patients with tetralogy of fallot
Authors: Havers-Borgersen E , Butt J.H , Groening M , Smerup M , Gislason G.H , Torp-Pedersen C , Soendergaard L , Koeber L , Fosboel E.L
Published: November 2020

Introduction

Patients with tetralogy of Fallot (ToF) are considered at high risk of infective endocarditis (IE) as a result of altered hemodynamics and multiple surgical and interventional procedures including pulmonary valve replacement (PVR). The overall survival of patients with ToF has increased in recent years. However, data on the risk of adverse outcomes including IE are sparse.

Purpose

To investigate the risk of IE in patients with ToF compared with controls from the background population.

Methods

In this nationwide observational cohort study, all patients with ToF born in 1977–2017 were identified using Danish nationwide registries and followed from date of birth until occurrence of an outcome of interest (i.e. first-time IE), death, or end of study (July 31, 2017). The comparative risk of IE among ToF patients versus age- and sex-matched controls from the background population was assessed.

Results

A total of 1,156 patients with ToF were identified and matched with 4,624 controls from the background population. Among patients with ToF, 266 (23.0%) underwent PVR during follow-up. During a median follow-up time of 20.4 years, 38 (3.3%) patients and 1 (0.03%) control were admitted with IE. The median time from date of birth to IE was 10.8 years (25th-75th percentile 2.8–20.9 years). The incidence rates of IE per 1,000 person-years were 2.2 (95% confidence interval (CI) 1.6–3.0) and 0.01 (95% CI 0.0001–0.1) among patients and controls, respectively. In multivariable Cox regression models, in which age, sex, pulmonary valve replacement, and relevant comorbidities (i.e. chronic renal failure, diabetes mellitus, presence of cardiac implantable electronic devices, other valve surgeries), were included as time-varying coefficients, the risk of IE was significantly higher among patients compared with controls (HR 171.5, 95% CI 23.2–1266.7). Moreover, PVR was associated with an increased risk of IE (HR 3.4, 95% CI 1.4–8.2).

Conclusions

Patients with ToF have a substantial risk of IE and the risk is significantly higher compared with the background population. In particular, PVR was associated with an increased risk of IE. With an increasing life-expectancy of these patients, intensified awareness, preventive measures, and surveillance of this patient group are advisable.

Figure 1. Cumulative incidence of IE

Funding Acknowledgement

Type of funding source: None
Right ventricle function longitudinal evaluation after norwood procedure: comparison between right ventricle-pulmonary artery shunt and blalock-taussing shunt
Authors: Borrelli N , Sabatino J , Avesani M , Josen M , Fraisse A , Guccione P , Michielon G , Di Salvo G
Published: November 2020

Background

Norwood procedure represents the first of three surgical steps toward Hypoplastic left heart syndrome (HLHS) complete palliation. Two are the main surgical techniques allowing the reconstruction of Norwood circulation: the right ventricle-pulmonary artery shunt (RVPAS) and the modified Blalock-Taussing shunt (mBTS). However, still little is known about the impact on right ventricle (RV) function of the required ventriculotomy for the RVPAS.

Purpose

The aim of the study was to investigate the changes in RV function in HLHS patients after RVPAS vs mBTS.

Methods

The cohort included 27 consecutive HLHS patients (10 in the modified Blalock-Taussig shunt group and 17 in the RVPAS group) who successfully underwent Norwood procedure in a single tertiary paediatric cardiology centre. Longitudinal strain (LS) and strain rate (LSR), tricuspid annulus peak systolic excursion (TAPSE) and fractional area change (FAC) were evaluated in all patients before Norwood and in three different breakpoints in the steady state after Norwood procedure (30 days after Norwood, 90 days after Norwood, 140 days after Norwood).

Results

Ventricular loading conditions (diuretic treatment, blood pressure and tricuspid regurgitation) were similar in both groups. No significant differences were found at different time points between RVPAS and mBTS group in terms of LS, LSR, TAPSE and FAC. However, when we compared RV function before and after Norwood procedure, 90 days after the procedure, patients who did not undergo RV ventriculotomy (mBTS group) showed significant improvement in LS compared to pre-surgical assessment (mBTS: +27.35±43.47% vs RVPAS: −8,20±25.25%, p=0,03). This finding was consistent but no longer statistically significant at 140 days after Norwood (mBTS: +13.81±21.99% vs RVPAS: −4.90±27.97%, p=0,12).

Conclusion

After Norwood procedure mBTS patients showed a significant increase in LS when compared with patients who underwent RVPAS. This finding was consistent but no longer significant at 140 days after Norwood probably because the number of patients was too small to reach a significant level. These data support the use of LS in HLHS patient's evaluation and may be of value to find a patient-tailored timing for the second surgical stage.

TAPSE, FAC, LS and LSR trends

Funding Acknowledgement

Type of funding source: None
Late cardiac interventions in adults with congenital ventricular septal defects
Authors: Berglund E , Wikner A , Larsson L , Rinnstrom D , Christersson C , Dellborg M , Nielsen N.E , Sorensson P , Thilen U , Johansson B
Published: November 2020

Introduction

Ventricular septal defect (VSD) is one of the most common congenital heart lesions. Shunts with hemodynamic significance are usually closed early in life whereas small shunts are left without intervention. The need for late cardiac interventions in these populations is essentially unknown. The aim was to study the late cardiac interventions in adults with VSD.

Methods

The national register on congenital heart disease was searched for patients with VSD with or without associated simple cardiac defects but without complex lesions. For these patients, the last 10 years (over the age of 18) in the national patient register was searched for cardiac interventions.

Results

774 patients (mean age 39.0±14.7 years, women =50.6%), 224 (28.9%) with previous closure of VSD, were identified. The total observed time was 6920 patient years. There were 43 interventions in 41 patients (5.3%) of whom 12 had a previous closure of VSD. Twelve patients had isolated closure of VSD, 18 closure of VSD together with other cardiac surgery (one of these had repeated cardiac surgery) and 8 had only other cardiac surgery. In 4 cases, a pacemaker was implanted, of whom one together with cardiac surgery.

Conclusion

The need for cardiac interventions is relatively common in adults with a VSD, also in those without previous closure of their shunt. Our data suggests that most patients with a VSD, closed or not, should be offered periodic follow-up as approximately one out of 20 patients may encounter a complication within 10 years.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): The Swedish Heart-Lung Foundation
Differences in resting and ambulatory blood pressure data in coarctation of aorta vs idiopathic hypertension
Authors: Egbe A , Banala K , Vojjini R
Published: November 2020

Background

Ambulatory systolic blood pressure (SBP) is more sensitive than resting-SBP in detecting hypertension in patients with coarctation of aorta (COA) and patients with idiopathic hypertension. A recent study showed that compared to patients with idiopathic hypertension with similar resting-SBP, COA patients had lower arterial compliance, and hence experienced higher SBP per unit increase in stroke volume during exercise. The purpose of this study was to compare resting vs ambulatory-SBP relationship between COA patients and non-COA patients (with and without hypertension), and to determine if ambulatory-SBP had better correlation with left ventricular (LV) remodeling as compared to resting-SBP.

Methods

Case-control study of 106 COA patients and 106 patients with idiopathic hypertension (ControlHTN+ group) matched by age, sex, body mass index and resting-SBP. Resting/ambulatory BP relationship in COA patients and patients with idiopathic hypertension were also compared to that of 19 patients without hypertension (ControlHTN- group). LV remodeling was assessed using LV mass index, e', and E/e'.

Results

Although the COA and ControlHTN+ groups had similar resting-SBP (by design), the COA group had a higher ambulatory-SBP and a higher prevalence of masked hypertension (30% vs 12%, p<0.001). There was a stronger correlation between ambulatory-SBP (as compared to resting-SBP) and LVMI (r=0.36 vs r=0.55, p=0.042), and average E/e' (r=0.42 vs r=0.59, p=0.046), in the COA group but not the ControlHTN+ group. There was no difference in the resting/ambulatory BP relationship between ControlHTN+ and ControlHTN- groups, but both groups were significantly different from the COA group.

Conclusion

These results highlight the unique differences in disease pathophysiology between hypertension in patients with COA and those with idiopathic hypertension, and also suggest that ambulatory-SBP may be a more accurate measure of LV pressure overload in COA patients. This underscores the potential limitations of relying on resting-SBP alone for clinical decision making.

Funding Acknowledgement

Type of funding source: None
Long-term outcome of adult patients with partial anomalous pulmonary venous connection treated surgically and conservatively: data from the SACHER registry and a French center
Authors: Touray M , Bouchardy J , Ladouceur M , Schwerzmann M , Greutmann M , Tobler D , Harald R , Engel R , Pruvot E , Blanche C , Sekarski N , Rutz T
Published: November 2020

Introduction

Partial anomalous pulmonary venous connection (PAPVC) is a rare congenital heart disease, which is characterized by one or some but not all pulmonary veins anomalously connected to the right atrium or a systemic vein. PAPVC is either an isolated shunt lesion or associated with an atrial septal defect (ASD). The only curative treatment is surgery, however the indication for surgery can be challenging. This study compares the outcome of patients treated surgically with those clinically monitored.

Method

Clinical, surgical, imaging and invasive data were retrospectively reviewed from 7 centers from the Swiss Adult Congenital HEart Registry (SACHER) and a French center.

Results

A total of 168 patients with partial anomalous pulmonary venous connection were identified. The majority (77%) of patients underwent surgery and the remaining (23%) were treated conservatively with clinical monitoring. The operated group (OG) had a significantly higher proportion of associated ASD (N=106, 82%) (p<0.001) and a higher prevalence of anomalous pulmonary veins leading to a mean Qp:Qs at 2.5±1.2 before surgery.

Latest follow-up was 12 years after surgery. Mean age was 40±17 years. Patients in the non-operated group (NOG) were significantly more dyspneic than the OG (p=0.002). However, the need for medical treatment did not differ between groups: 58% of the NOG and 48% in the OG (p=0.203).

Right ventricular (RV) ejection fraction did not differ between groups despite a significantly larger RV end-diastolic volume and a higher Qp:Qs on cardiac magnetic resonance (CMR) in the NOG (table).

On echocardiography, the NOG showed a significantly better right ventricular longitudinal function and a higher systolic pulmonary artery pressure than the OG (table). The prevalence of significant valvulopathies did not differ between groups (table).

Both groups had normal exercise capacity and with no differences between groups (table).

Eighteen (14%) OG patients required a re-intervention either for residual shunt and/or stenosis of the pulmonary veins, superior and inferior vena cava.

Conclusion

PAPVC patients after surgical correction, show a favorable outcome in terms of imaging parameters and exercise capacity, however, a significant number presents with symptoms. PAPVC patients treated conservatively with small left to right shunting, have similar outcome justifying a conservative approach.

Funding Acknowledgement

Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Unrestricted grant from Actelion, Switzerland
The association between atrial fibrillation and pulmonary embolism
Authors: Svennberg E , Friberg L
Published: November 2020

Background and objectives

Previous studies have suggested that atrial fibrillation is a risk factor for pulmonary embolism. Oral anticoagulant therapy is the mainstay of treatment for atrial fibrillation and pulmonary embolism. We wanted to investigate if atrial fibrillation remained associated with the development of pulmonary embolism if oral anticoagulant treatment was accounted for.

Method

In this retrospective registry study a random sample of 20% of the adult Swedish population comprising approximately 1.5 million individuals were included during 2010–2017 in a cohort analysis. The endpoint was acute pulmonary embolism. In the cohort study, patients were analysed according to oral anticoagulant treatment and presence of atrial fibrillation at baseline.

Results

The group with atrial fibrillation was >25 years older than the group without and had almost three times higher incidence of pulmonary embolism (2.91 vs 1.09 /1000 year at risk, p<0.001). Individuals with atrial fibrillation on oral anticoagulant therapy had a lower risk of pulmonary embolism in multi-variable analysis (HR 0.59, CI 0.45–0.77). In the unadjusted analysis participants with atrial fibrillation without oral anticoagulant therapy showed an increased risk of pulmonary embolism (HR 3.33, CI 3.05–3.63). However, after multi-variable adjustment this association disappeared (HR 0.98, CI 0.89–1.07). In the entire atrial fibrillation cohort, no association was seen with the development of pulmonary embolism after multi-variable adjustment (HR 0.92, CI 0.84–1.01). The higher rate of pulmonary embolism among patients with atrial fibrillation can be fully explained by differences in age and co-morbidity.

Conclusion

Atrial fibrillation does not appear to be a clinically relevant risk factor for pulmonary embolism. Oral anticoagulant therapy protects against the development of pulmonary embolism in patients with atrial fibrillation.

Associations with pulmonary embolism

Funding Acknowledgement

Type of funding source: Other. Main funding source(s): The main author has received funding from Stockholm County Council (Clinical postdoctorial appointment)
Endothelial cell premature senescence exacerbates pulmonary arterial hypertension through contact-mediated interaction with vascular smooth muscle cells
Authors: Ramadhiani R , Ikeda K , Miyagawa K , Ryanto G.R.T , Tamada N , Suzuki Y , Hirata K , Emoto N
Published: November 2020

Introduction

Pulmonary arterial hypertension (PAH) is characterized by remodelling and stenosis of the pulmonary arteries, ultimately leading to the right heart failure and death. Endothelial cell (EC) dysfunction is thought to play a central role in the pathogenesis of PAH by mediating the structural changes in pulmonary vasculatures. Various stresses promote premature senescence in EC, which may modify vascular disorders; however, the role of EC senescence in the development of PAH remains poorly understood.

Purpose

We aimed at investigating the potential role of EC premature senescence in the development of PAH.

Methods

We recently generated EC-specific progeroid mice in which ECs specifically undergo premature senescence by overexpressing the dominant-negative form of telomere repeat-binding factor 2 (published in Nat Commun 2020). These EC-specific progeroid mice were exposed to hypoxia (10% O2 for three weeks) to induce pulmonary hypertension. Also, we prepared premature senescent ECs using human pulmonary artery ECs (hPAECs) and explored their interaction with human pulmonary artery smooth muscle cells (hPASMCs) in two different conditions; direct and indirect interactions. For indirect coculture, hPASMCs were seeded onto the culture insert, while hPAECs were plated on the culture plate, and they were cocultured in the same well and medium so that secreted factors derived from senescent ECs could access to SMCs through the insert pores. For direct coculture, hPAECs were seeded onto the bottom side of the insert, while hPASMCs were cultured on the top side of the same insert, so that cell-to-cell contact could be made through the pores.

Results

After chronic hypoxia exposure, the EC-specific progeroid mice showed higher right ventricular systolic pressure and increased right ventricular mass as compared to wild-type (WT) mice, indicating exacerbated pulmonary hypertension. Histological analysis of the lung revealed a significantly enhanced muscularization in the small pulmonary arteries in EC-specific progeroid mice compared to WT mice. Mechanistically, we identified that direct coculture with premature senescent hPAECs enhanced proliferation and migration in hPASMCs, while no such effects were detected in indirect coculture condition.

Conclusion

To our knowledge, this is the first report that reveals a crucial role of EC premature senescence in the development of PAH. Our in vitro studies suggest that contact-mediated interaction between premature senescent ECs and SMCs is critically involved in its underlying mechanism. Therefore, EC premature senescence is a novel attractive pharmacotherapeutic target for the treatment of PAH.

Funding Acknowledgement

Type of funding source: None
Renal function improves mortality prediction in acute pulmonary embolism: results of a multicentre cohort study with external validation in the RIETE registry
Authors: Chopard R , Jimenez D , Serzian G , Ecarnot F , Falvo N , Kalbacher E , Bonnet B , Capellier G , Schiele F , Bertoletti L , Monreal M , Meneveau N
Published: November 2020

Background

Renal dysfunction may influence outcomes after pulmonary embolism (PE). We determined the incremental value of adding renal function impairment (estimated glomerular filtration rate, eGFR <60 ml/min/1.73m2) on top of the 2019 ESC prognostic model, for the prediction of 30-day all-cause mortality in acute PE patients from a prospective, multicenter cohort.

Methods and results

We identified which of three eGFR formulae predicted death most accurately. Changes in global model fit, discrimination, calibration and net reclassification index (NRI) were evaluated with addition of eGFR. We prospectively included consecutive adult patients with acute PE diagnosed as per ESC guidelines. Among 1,943 patients, (mean age 67.3±17.1, 50.4% women), 107 (5.5% (95% CI 4.5–6.5%)) died during 30-day follow-up. The eGFRMDRD4 formula was the most accurate for prediction of death. The observed mortality rate was higher for intermediate-low risk (OR 1.8, 95% CI 1.1–3.4) and high-risk PE (OR 10.3, 95% CI 3.6–17.3), and 30-day bleeding was significantly higher (OR 2.1, 95% CI 1.3–3.5) in patients with vs without eGFRMDRD4 <60 ml/min/1.73m2. The addition of eGFRMDRD4 information improved model fit, discriminatory capacity, and calibration of the ESC models. NRI was significantly improved (p<0.001), with 18% reclassification of predicted mortality, specifically in intermediate and high-risk PE. External validation using data from the RIETE registry confirmed our findings (Table).

Conclusion

Addition of eGFRMDRD4-derived renal dysfunction on top of the ESC prognostic algorithm yields significant reclassification of risk of death in intermediate and high-risk PE. Impact on therapy remains to be determined.

Funding Acknowledgement

Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): BMS-Pfizer Alliance, Bayer Healthcare
Lowering of mean pulmonary arterial pressure is a prognostic marker in pulmonary hypertension patients treated with subcutaneous treprostinil
Authors: Sadushi-Kolici R , Shafran I , Skoro-Sajer N , Campean I.-A , Lang I.M
Published: November 2020

Background

Treprostinil (TRE), a prostacyclin analog, is effective for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension (CTEPH). We hypothesized that change of hemodynamics is of prognostic value. In our prospective registry we evaluated effects of first-line subcutaneous (sc) TRE in patients with severe pulmonary hypertension (PH) and analyzed the prognostic value of hemodynamic changes from baseline on long-term follow-up.

Methods

Data was collected from patients with pre-capillary PH in WHO functional class III or IV, mean right atrial pressure of ≥10mmHg, and/or cardiac index ≤2.2 liters/min/m2. Patients received first-line scTRE. Dose adjustments were performed individually according to clinical symptoms and side effects.

Results

Between 1999 and 2018 138 patients were treated. Of these, 18 (13%) patients underwent double lung transplantation, and 59 (42.8%) died of any cause. Overall survival rates at 1, 5, 10, and 15 years were 91%, 57%, 31% and 29%. The strongest predictor of outcome was change in mPAP after one year of scTRE. Change in mPAP (−18.4±7.9 mmHg) was associated with the best subsequent survival of 12.7±1.5 years.

Conclusion

The data suggest that patients benefit from aggressive lowering of mPAP in the first year of treatment.

Funding Acknowledgement

Type of funding source: None
Usefulness of peripheral-pressure-directed balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension
Authors: Nagamatsu Y , Inami T , Nakata C , Takeuchi K , Kikuchi H , Goda A , Soejima K , Satoh T
Published: November 2020

Background

Balloon pulmonary angioplasty (BPA) in expert center may be considered in patients with chronic thromboembolic pulmonary hypertension (CTEPH) who are technically non-operable for pulmonary endarterectomy. BPA based on objective quantitative methods has not been established. The endpoint at BPA sessions has not been clarified yet.

Objectives

The purpose of this study was to investigate the usefulness of BPA according to peripheral pressure measured by pressure wire or catheter.

Methods

This study included consecutive 143 CTEPH who underwent cardiopulmonary exercise test with right heart catheterization after BPA. All patients were divided into 2 groups such as angio-guided (n=47) group or pressure-guidedgroup (n=96). In pressure-guided group, the pulmonary arterial pressure (PAP) proximal and distal to the target lesion and the ratio of the 2 pressures were measured by the pressure wire or catheter. the endpoint was determined to when the pressure ratio of distal to proximal pressures was >0.7 to 0.8 finally. The dilation was stopped when the distal mean PAP after each dilation reached 35 mm Hg and when the baseline mean PAP was >35 mm Hg. Changes of hemodynamic parameters such as PAP and pulmonary vascular resistance (PVR) from baseline, and mean PAP and PVR at peak oxygen consumption, and pulmonary arterial pressure – cardiac output (PA-CO) slope were compared between two groups. All data except changes of hemodynamics from baseline were expressed by median [25th percentile-75th percentile]. Changes of hemodynamics from baseline were expressed by average [95% confidence interval]

Results

The median age and male were 66 [56–72] years old and 35. There were no significant differences in number of sessions and dilated vessels between two groups (Angio-guided group vs. Pressure-guided group: 4 [3–6] vs. 4 [3–5], P>0.05; 19 [12–22] vs. 17 [13–22], P>0.05). Changes of PAP and PVR from baseline in pressure-guided group was significantly higher than in angio-guided groups (Angio-guided group vs. Pressure-guided group; ΔPAP: −19 [−20 to −17] vs. −20 [−21 to −20], P>0.05; ΔPVR: −6.0 [−6.3 to −5.7] vs. −6.6 [−6.8 to −6.3], P<0.01). Mean PAP and PVR at peak oxygen consumption (VO2) and PA-CO slope in pressure-guided group were significantly lower than in angio-guided group (Angio-guided group vs. Pressure-guided group; PAP at VO2: 43 [36–50] vs. 39 [34–43], P<0.05; PVR at VO2: 2.7 [1.9–4.5] vs. 2.2 [1.6–2.9], P<0.01; PA-CO slope: 3.8 [2.1–5.2] vs. 2.9 [1.9–4.0], P<0.05).

Conclusions

Peripheral-pressure-directed BPA can improve hemodynamics at rest and exercise more effectively.

Funding Acknowledgement

Type of funding source: None
Efficacy of interventional treatment for patients with chronic thromboembolic pulmonary hypertension with microvasculopathy
Authors: Onishi H , Taniguchi Y , Miwa K , Sumimoto K , Matsuoka Y , Izawa Y , Tsuboi Y , Otake H , Kobayashi S , Emoto N , Hirata K
Published: November 2020

Background

The existence of microvasculopathy in chronic thromboembolic pulmonary hypertension (CTEPH) had been suggested. However, the impact of microvasculopathy for pathophysiology had been unknown. Recently dual-energy computed tomography (DECT) can produce a sensitive iodine distribution map in lung fields to quantify lung perfusion, which may indicate the existence of microvasculopathy according to poor subpleural perfusion.

This study aimed to examine the therapeutic efficacy of interventional treatment (pulmonary endarterectomy or/and balloon pulmonary angioplasty) in CTEPH with microvasculopathy.

Methods

We retrospectively reviewed poor subpleural perfusion (defined as subpleural spaces either not or minimally perfused in all segments) and hemodynamics of 70 consecutive CTEPH patients who underwent DECT before and after interventional therapy from January 2014 to January 2020.

Patients were divided according to poor subpleural perfusion in DECT images before treatment: a microvasculopathy group (MV group, n=37) or a non-microvasculopathy group (Non-MV group, n=33).

We evaluated clinical parameters as WHO functional class (WHO-Fc), 6-min walk distance, respiratory function test, cardiopulmonary exercise test, hemodynamic parameters, and DECT parameters at baseline and after the treatments. DECT parameters as quantitative evaluation of pulmonary blood volume (PBV) calculated as the average of entire lung iodine density.

Results

After interventional treatments, WHO-Fc improved in 33 patients in MV group, and 27 patients in Non-MV group (p=0.50).

In MV group, baseline mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR) and VE/VCO2 slope were higher (38.3±9.3 vs. 33.2±10.8 mmHg p=0.04, 818±394 vs. 539±289 dyne*sec/cm5 p<0.01 and 43.7±11.3 vs. 35.2±6.9 p<0.01, respectively) and PBV were lower (43.7±11.3 vs. 35.2±6.9 Hounsfield Unit p<0.01) After the treatments, mPAP, PVR, VE/VCO2 slope and PBV showed almost equivalent between the groups (19.5±4.1 vs. 20.6±5.1 mmHg p=0.35, 272±111 vs 251±109 dyne*sec/cm5 p=0.42, 29.2±6.3 vs. 26.0±6.1 p=0.06 and 27.1±6.6 vs. 29.6±6.6 Hounsfield Unit p=0.13).

Diffusing capacity for carbon monoxide (%DLCO/VA) did not improve after treatment in both groups (MV group: 59.5±13.1 to 58.8±11.9% p=0.43. Non-MV group: 77.8±13.4% to 70.5±10.8% P<0.01).

Conclusion

Hemodynamics, pulmonary perfusion, exercise capacities significantly improved after the treatments in spite of the existence or absence of microvasculopathy. However, DLCO which might indicate the existence of microvasculopathy did not improve. Interventional treatments could not improve microvasculopathy because of their limit of accessibilities.

Funding Acknowledgement

Type of funding source: None
Arrhythmias assessed with long-term continuous cardiac monitoring in pulmonary hypertension
Authors: Oerbaek Andersen M.O.E.A , Diederichsen S.Z.D , Hastrup Svendsen J.H.S , Carlsen J.C
Published: November 2020

Background

Arrhythmias are considered a prominent phenomenon in pulmonary hypertension (PH) as the disease progresses. In short-term retrospective studies with up to 24 hours of monitoring, supraventricular tachycardia (SVT) has been found in 8–35% of patients, with significant impact on survival. The incidence of arrhythmias and their clinical role is based on a small number of retrospective studies.

Purpose

Assessment of arrhythmias in PH by continuous long-term cardiac monitoring

Methods

Patients diagnosed with PH were included in this prospective single-centre study where the diagnosis of PAH was established according to international guidelines. Patients received a Reveal LINQ (Medtronic) insertable cardiac monitor (ICM). ICM's continuously monitor the heart rhythm for arrhythmias according to algorithms; and an ECG of the episode will automatically be transmitted whenever an arrhythmia is detected.

Results

Twenty-eight patients were included, of whom 24 patients had pulmonary arterial hypertension (PAH) and four had chronic thromboembolic pulmonary hypertension (table 1) treated according to Table 1. During 168 patient-months of continuous monitoring (median: 206 days per patient) no long-lasting arrhythmias were observed, but only transient SVTs in one patient lasting a total of 2.5 days. Two had SVTs lasting 4.5 hours, and two hours. Five patients had isolated episodes of SVTs lasting 0–10 minutes and two patients had an episode of bradycardia for 10 seconds. The total arrhythmic burden was a period prevalence of less than 0.001%, despite a RVEF of 20.3% and 35.7% in WHO FC IV and III, respectively.

Conclusion

This is the first study with long-term continuous rhythm monitoring in patients with PH. In contrast to earlier observations no long-lasting arrhythmias occurred during 168 patient-months with a period prevalence of arrhythmias as low as less than 0.001% in this cohort of PH patients with WHO FC I-IV and the majority on modern specific PAH therapy.

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Actelion
A genome-wide association study identifies novel genetic loci associated with pulmonary embolism
Authors: Krittanawong C , Narasimhan B , Hahn J , Wang Z , Johnson K , Tang W , Baber U , Amos C
Published: November 2020

Background

Pulmonary embolism (PE) is a life-threatening cardiovascular condition. Studies showed that PE patients were associated with disorders of lipid metabolism and had higher triglyceride and lower HDL-C levels compared with healthy. We conducted the genome-wide association study to identify novel loci contributing to PE.

Methods

We conducted a large-scale GWAS of PE in 5,466 PE cases and 461,219 controls of European ancestry from the UK Biobank (466,685 participants total). We used genome-wide summary statistics to test for enrichment of functional annotations using ENRICHR. Example pathways included in Enrichr for testing include membership of genes in pathway databases such as the Kyoto Encyclopedia of Genes and Genomes (KEGG), Wikipathway, PANTHER, BioCarta or NCI-Nature pathways. We analyzed the pathways using combined score and p-values which were well validated by comparing to several methods. For pathway analyses, we considered a nominal P-value threshold of 0.05.

Results

We identified genome-wide significant genetic associations in 63 independent genetic loci for PE (P<5.0x10–7). Our findings for top pathways highlight that lipid metabolism (LIPC, LCAT, NPC2), caffeine metabolism (NAT2), and sudden cardiac death (ABCG8) related genetic loci play an important role in PE alongside genes already associated with coagulation-thrombosis pathway (VWF, THPO, PTPN11, INPP5D, UROS, HMBS) (all p-values p-values <0.05).

Conclusion

Our findings uncovered unexpected novel factors of PE etiology, suggesting novel mechanistic concepts of PE pathophysiology.

Funding Acknowledgement

Type of funding source: None
Clinical characteristics and prognostic impact of pulmonary hypertension in heart failure with preserved ejection fraction: the PURSUIT HFpEF study
Authors: Sera F , Ohtani T , Nakamoto K , Yamada T , Yasumura Y , Tamaki S , Hayashi T , Yano M , Hikoso S , Yamauchi-Takihara K , Sakata Y
Published: November 2020

Background

Heart failure (HF) with preserved ejection fraction (HFpEF) can develop pulmonary hypertension (PH), which can result from pre-capillary PH as well as post-capillary PH. However, the prevalence and clinical significance of pre-capillary component of PH in HFpEF remain unknown.

Purpose

We aimed to investigate prevalence, clinical features, and prognostic impact of pre-capillary and/or post capillary PH associated with HFpEF.

Methods

From the PURSUIT-HFpEF (Prospective Multicenter Observational Study of Patients with Heart Failure with Preserved Ejection Fraction) registry, 204 patients (men: 46%, age: 79±9 years) who were hospitalized with HF and underwent right heart catheterization were divided into 4 groups according to the PH guidelines: non-PH, isolated post-capillary PH (Ipc-PH), pre-capillary PH, and combined pre- and post-capillary PH (Cpc-PH). Patients who had been diagnosed with idiopathic pulmonary arterial hypertension were excluded from the analysis.

Results

The prevalence of PH was 31% (Ipc-PH: 22%, pre-capillary PH: 3%, Cpc-PH: 6%). The prevalence of subcategories of PH was significantly different depending on mean right atrial pressure (RAP) (figure). Echocardiography at discharge showed no significant differences in RV diameter or TAPSE, but smaller LV diameter and higher E/e' in pre-capillary PH and Cpc-PH, which resulted in a higher operant diastolic elastance (Ed). Composite endpoint of all-cause mortality and HF hospitalization at 1 year occurred 13% in non-PH, 25% in Ipc-PH, 49% in pre-capillary PH, and 63% in Cpc-PH, respectively (p=0.001 by log-rank test).

Conclusions

Distinct prevalence of PH was observed in the groups with different RAP levels. Pre-capillary component of PH was associated with impaired LV diastolic function and worse outcomes in HFpEF.

Figure 1

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Roche Diagnostics K.K.; Fuji Film Toyama Chemical Co. Ltd
Survival in patients with chronic thromboembolic pulmonary hypertension in the modern management era
Authors: Taniguchi Y , Matsuoka Y , Onishi H , Nakai H , Okada K , Emoto N , Hirata K
Published: November 2020

Background

The management of non-operable chronic thromboembolic pulmonary hypertension (CTEPH) has recently evolved with the availability of balloon pulmonary angioplasty (BPA) and pulmonary vasodilators. We launched BPA program since 2011. The aim was to analyze survival and treatment efficacy in the modern management era.

Method and result

We retrospectively reviewed data from 143 consecutive CTEPH patients diagnosed in our university from January 2011 (i.e. after the availability of BPA) to December 2019. Forty-one patients underwent PEA, in these 25 patients underwent additional BPA (Hybrid group) and other patients were treated with only PEA (PEA group). Ninety patients underwent BPA (BPA group), remaining 12 patients had not undergone any interventional treatments. The 1- and 5-year survival rates of operated patients (n=41) were 97.4% and 90.0%, compared to96.9% and 86.9% in not-operated patients (n=102), respectively (p=0.579) (Figure). There was no death in Hybrid group. Percent decrease of pulmonary vascular resistance in PEA group, Hybrid group, BPA group were −75.4±9.9%, −74.3±11.8%, −56.3±22.2%, respectively (p<0.01, one-way ANOVA). Absolute decrease of mean pulmonary artery pressure in each groups were −20.3±9.5mmHg, −24.5±8.8mmHg, −16.4±9.2mmHg, respectively (p<0.01, one-way ANOVA).

Conclusion

There was no longer significant difference of long-term survival between operated and not-operated CTEPH. Moreover, Hybrid approach might have the potential to lead notable improvement in the prognosis of CTEPH. BPA and PEA would be mutually complementary therapies in the modern management era.

Figure 1

Funding Acknowledgement

Type of funding source: None
Thrombocytopenia as a preoperative risk assessment tool in patients with type B aortic dissection after thoracic endovascular aortic repair
Authors: Xie E.M , Liu J.T , Yang F , Ding H.Y , Hu B.Q , Chen L.F , Yang X.Y , Luo J.F
Published: November 2020

Background

Postoperative thrombocytopenia has been reported to be correlated with adverse events, but the prognostic value of baseline thrombocytopenia is unclear. This study was undertaken to evaluate the relationship between preoperative thrombocytopenia and adverse outcomes in patients with type B aortic dissection who underwent thoracic endovascular aortic repair (TEVAR).

Methods

A total of 825 patients with acute and sub-acute type B aortic dissection undergoing were TEVAR at a multidisciplinary aortic center were enrolled between January 2010 and December 2017. Patients were stratified on the basis of presence (n=149) or absence (n=676) of thrombocytopenia (platelet count, <150x109/L), according to preprocedural platelet counts. The primary outcome of interest was in-hospital mortality. Secondary outcomes of interest was long-term death.

Results

In the enrolled cohort, thrombocytopenia occurred in 149 (18.1%) patients. Patients with thrombocytopenia were older, were more commonly acute stage of TBAD, higher D-dimer level and had higher rates of abdominal vessel involvement and pericardial effusion. During the hospitalization period, 26 patients (3.2%) died, which was significantly higher in the thrombocytopenic group (8.1% versus 2.1%; P=0.001) Multivariate analyses revealed that thrombocytopenia was independently associated with in-hospital mortality (Table). During long-term follow-up (median duration 44.2 months), A total of 62 deaths were reported after discharge, including 40 (64.5%) aortic-related and unknown deaths, of which 12 and 50 patients for thrombocytopenia and non-thrombocytopenia group, respectively. Kaplan-Meier estimated rates of long-term all-cause mortality were higher for thrombocytopenia (log-rank test, P=0.014). Similar results were observed in a subset of aortic-related death (P=0.004) as well as aortic-related and unknown death (P=0.006), not non-aortic related death (P=0.878) (Figure 1).

Conclusion

Platelet counts, as simple and inexpensive indexes, were reliable to be used as a preoperative risk assessment tool for patients with type B aortic dissection undergoing thoracic endovascular aortic repair.

Figure 1. Long-term Mortality

Funding Acknowledgement

Type of funding source: Public hospital(s). Main funding source(s): This research was supported by grant DFJH201807 from High-level Hospital Construction Project of Guangdong Provincial People's Hospital.
Aortic invovement in fibromuscular dysplasia. 3-dimensional CT, case-control study. THE ARCADIA-POL BIS study
Authors: Szkamruk K , Kruk M , Kepka C , Adlam D , Persu A , Canning C , Pappaccogli M , Van Der Niepen P , Januszewicz M , Kabat M , Warchol-Celinska E , Prejbisz A , Jozwik-Plebanek K , Dobrowolski P , Januszewicz A
Published: November 2020

Background

Fibromuscular dysplasia (FMD) is a non-atherosclerotic arterial disease that manifests as the presence of beaded or focal lesions in medium or small-sized arteries and may also include arterial dissection, aneurysm, and tortuosity. FMD could be revealed in various manifestations, however limited data on the involvement of the thoracic aorta is reported.

Purpose

To measure and evaluate involvement of thoracic aorta in patients with FMD.

Methods

We analysed aortas of 144 consecutive patients (mean age 50.2±14.0, 116 women) with confirmed FMD in at least one vascular bed. The control group consisted of 144 (mean age 50.5±14.0, 116 women) age and sex matched individuals. All patients underwent detailed clinical evaluation including angio-CT scan including aortic valve, thoracic aorta and coronary arteries. We measured the aortic valve annulus, sinus of valsalva, sinotubular junction, the diameters of ascending and descending aorta, aortic unfolding, the height of ostium of RCA and LCA and diameter of right and left coronary artery ostia in patients with fibromuscular dysplasia and compared them to matched controls.

Results

The FMD group had significantly smaller dimensions of aortic valve annulus and sinus of Valsalva than control group (2.3 [2.1–2.6] vs 2.9 [2.7–3.1] p<0,0001; 2.9 [2.7–3.2] vs 3.1 [2.8–3.3] p=0,0011 respectively). In addition the FMD group had a significantly greater mean diameter of the ascending and the descending aorta than the control group (3.1 [2.7–3.3] vs 3 [2.9–3] p=0,0436; 2.4 [2.2–2.7] vs 2.3 [1.8–2.5] p<0,0001 respectively). The height of the ostium of the left and of the right coronary artery was smaller in FMD than in the control group (1.2 [1.1–1.4] vs 1.3 [1.2–1.4] p=0,0001; 1.1 [1–1.3] vs 1.3 [1.1–1.4] p<0,0001 respectively). There was no difference in the diameter of sinotubular junction and the right and the left coronary artery ostias between the FMD and control groups (2.7 [2.5–2.9] vs 2.7 [2.5–2.9]; 0.3 [0.2–0.3] vs 0.3 [0.2–0.3]; 0.3 [0.3–0.3] vs 0.3 [0.3–0.4] respectively).

Conclusions

Patients with fibromuscular dysplasia display smaller dimensions of aortic valve and larger diameter of ascending and descending aorta as compared to control subjects. Despite the predominant clinical significance of focal pathologies in FMD patients, the disease may display a specific, pan-vascular phenotype.

Funding Acknowledgement

Type of funding source: None
Are aortic root and ascending aorta echocardiographic diameters by adult vs paediatric guidelines recommendations interchangeable?
Authors: Servato M.L , La Mura L , Lopez Sainz A , Granato C , Teixido G , Galian L , Gutierrez L , Gonzalez Alujas M.T , Casas G , Valente F , Rodriguez Palomares J.F , Evangelista A
Published: November 2020

Background

Both aortic root size and ascending aorta are clinical parameters with significant therapeutic implications which can be easily assessed by transthoracic echocardiography (TTE). However, measurement values may vary according to cardiac cycle and the edge convention used.

Purpose

This study aimed to compare the aortic diameter values measured using the lastest recommendations of two different guidelines, adults and children, to determine the influence of these methods on echocardiographic measurements.

Methods

Two hundred and fifty adult patients (56% male, 63±15 years of age) and 67 children (65% male, 10.04±4.5 years of age) in whom TTE was clinically indicated were included. Aortic diameters were measured twice at 2 levels (sinuses of Valsalva and ascending aorta): leading edge to leading edge during diastole, (L-L in D) following the 2015 American Society of Echocardiography (ASE) adults guidelines and inner edge to inner edge during systole (I-I in S) following the 2010 ASE paediatric guidelines.

Results

Mean aortic diameters obtained by L-L in D and I-I in S are shown in Table 1. Correlation coefficient was 0.990 (CI95% 0.988–0.992) for sinuses of Valsalva measurements and 0.991 (CI95% 0.989–0.993) for ascending aorta in adult patients and 0.983 (CI95% 0.975–0.973) and 0.970 (CI95% 0.956–0.952) in childrens respectively. When both populations were analysed together, concordance correlation coefficients were 0.991 (CI95% 0.989–0.993) and 0.970 (CI95% 0.991–0.994), respectively. Bland- Altman analysis for each level measured (A: aortic root; B: ascending aorta) in the total cohort of 317 patients is shown in Figure 1. Mean aortic diameters and differences in the whole group are shown in Table 1.

Conclusions

Measurement of aortic root and ascending aorta showed a significantly larger diameters by L-L in D than by I-I in S. However, these differences had subclinical significance and management implications. These similar diameter values may be used indifferently but systematically during follow-up. Systolic diameter expansion has a similar value to that of anterior aortic wall thickness; however, it is more vulnerable to changes in haemodynamic conditions.

Figure 1

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): Vall d'Hebron Research Institute