bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of combined exercise stress echocardiography and cardiopulmonary exercise test in chronic thromboembolic disease
Authors: Kim M S , Jeon K N , Lee S C , Yang J H , Kim E K , Park S J , Park S W , Chang S A
Published: October 2022

Background

Chronic thromboembolic pulmonary disease (CTEPD) without pulmonary hypertension could cause significant exercise limitations. However, interventional or surgical treatments for CTEPD with mild pulmonary hypertension or normal pressure are on controversy.

Purpose

We aimed to evaluate cardiopulmonary function through cardiopulmonary exercise test (CPET) with stress echocardiography and to determine whether exercise pulmonary hypertension can explain exercise limitations in CTEPD patients with mPAP <30mmHg.

Methods

Patients diagnosed as CTEPD with mPAP less than 30mmHg was derived from our pulmonary hypertension center registry from April 2014 to October 2021.Transthoracic echocardiography (TTE) was performed at baseline (resting state) and immediately after CPET. TTE derived parameters and CPET parameters were compared with hemodynamic parameters measured by right catheterization.

Results

Total 37 patients were enrolled. Of these, Thirty-five patients had previously been diagnosed with CTEPH and had undergone PEA, BPA, or both. Most of the patients complained dyspnea of WHO functional class II or III. Pulmonary vascular resistance (PVR) was slightly higher than normal (185.0±102.2 dyne sec cm–5). Also VO2max was decreased in CPET (23.1±6.5 mL/kg/min). In correlation analysis, the higher the mPAP and PVR at rest, the lower VO2max during exercise. Meanwhile basal right ventricular (RV) function was normal, an increase in RVSP was notably observed during exercise (RVSP: pre-exercise 36.2±11.9, post-exercise 60.7±19.3, p value <0.001). Furthermore RV function deteriorated during exercise (TAPSE: pre-exercise 16.1±4.8, post-exercise 12.9±5.0, p value <0.001).

Conclusions

CTEPD patients with mild or normal PAP showed limited exercise capacity with exercise induced hypertension. Even in the mPAP less than 30mmHg, PVR and mPAP was significantly associated with exercise capacity. CPET with stress echocardiography could help to identify the main cause of exercise limitation in CTEPD patients and possibly provide the guideline for treatment plan.

Funding Acknowledgement

Type of funding sources: None.
Added prognostic value of cardiopulmonary test variables in low-risk pulmonary artery hypertension patients
Authors: Luna R , Martinez Menaca A , Otero Escudero M , Segura De La Cal T , Flox A , Arribas Ynsaurriaga F , Escribano Subias P
Published: October 2022

Background

Pulmonary artery hypertension (PAH) results in progressive right heart failure, functional decline and finally death or the need for a lung transplant. Prognostic assessment based on a 6-minutes walking test (6MWT) may be insufficient due to the possibility of a ceiling effect, especially in young patients.

Purpose

To demonstrate the added prognostic value of functional assessment by cardiopulmonary exercise testing (CPET) in patients with a low-risk 6MWT.

Methods

We conducted a retrospective cohort study in patients with PAH referred to two centres between June 2006 and December 2021, who met the following criteria: PAPm ≥25 mmHg, PCP≤15 mmHg, PVR >3 UW, age>18 years and had a CPET performed in the same week as the 6MWT. For CPET variables showing statistical significance, optimal cut-off points were determined. The kappa statistic was used to test interrater reliability between low-risk classification with CPET and the 6-minute test using the Kappa index. Finally, the added prognostic power of CPET variables was assessed in low-risk patients according to TM6D (defined as >440 metres) by survival analysis.

Results

We included a total of 313 patients (27% male). 116 patients (64.8%) walked more than 440 metres at TM6D, this subgroup being significantly younger than those who walked less than 440 metres (42±11 vs 48±16 years) and with a higher proportion of men (34.8% vs 23.4%). In patients who walked more than 440 metres, we applied the CPET model associated with prognosis according to the optimal cut-off points obtained (Eq CO2 VT1 ≥41 and/or peak VO2 <15 ml/kg/min). Of the 116 patients classified as good prognosis by the 6MWT, 84 patients (72%) had altered CPET prognostic values. No substantial reliability was demonstrated between the low-risk classification by CPET and 6MWT (K<0.6 in all cases). Kaplan-Meier survival analysis showed that patients with had Eq CO2 VT1 ≥41 and peak VO2 <15 ml/kg/min had a worse prognosis at 5-year follow-up, despite walking more than 440m 6MWT (Figure 1).

Conclusion

Young patients may have a good-prognosis 6MWT and, however, be at high-risk of adverse events. A combination of CPET variables has a good predictive value for survival in low-risk 6MWT patients. Performing a CPET is mandatory in these patients to adequately stratify risk.

Funding Acknowledgement

Type of funding sources: None.
Human umbilical cord mesenchymal stem cells attenuate experimental pulmonary arterial hypertension
Authors: Dai H L , Lu X T , Guang X F
Published: October 2022

Background

Pulmonary arterial hypertension (PAH) is characterized by the remodeling of pulmonary arteries, with an increased pulmonary arterial pressure and right ventricle (RV) overload. Until now, there is still a lack of effective treatment applied. Experimental research has reported beneficial effects of mesenchymal stem cells (MSCs) therapy in PAH. However, there are few studies on human umbilical cord mesenchymal stem cells (hUC-MSCs) transplantation in the treatment of PAH.

Purpose

The purpose of the present study was to observe the protective effect of hUC-MSCs against experimental PAH and the colonization of hUC-MSCs in lung tissue.

Methods

Sprague Dawley rats were randomly divided into three groups: control group, monocrotaline (MCT)-induced PAH group, and stem cell therapy group (PAH+ hUC-MSCs). Rats with PAH were induced by a one-time intraperitoneal injection of 60mg/kg monocrotaline (PAH and PAH+hUC-MSCs groups) at the beginning of the experiment, while a control group received saline (SAL) instead. Huc-Mscs were treated by tail vein injection twice 1 and 2 weeks later (PAH+huc-MSC group dose: 3x106/each time), Ctr and PAH groups were given the same volume of SAL in tail vein. On day 28, Right ventricular systolic pressures (RVSP) were measured by right cardiac catheterization. WT% and WA% of pulmonary arterioles were evaluated by ipp6.0 Image Analysis Software. Right ventricular hypertrophy index (RVHI) were measured by weighing method. The colonization of hUC-MSCs in lung tissue was detected by immunohistochemistry.

Results

The RVHI and RVSP in MCT-induced PAH group were significantly higher than those in the control group (P<0.05). Compared with the control group, the WT% and the WA% were significantly increased in MCT-induced PAH group (P<0.05). The RVHI, RVSP, WT%, and the WA% in stem cell therapy group were significantly lower than those in the MCT-induced PAH group (P<0.05). Immunohistochemical examination of lung tissue showed that the nuclear staining of the stem cell therapy group was brown, while no staining was observed in the control group and PAH group.

Conclusions

In MCT-induced PAH, hUC-MSCs can transplanted into the lung tissues by tail vein injection. hUC-MSCs therapy can reduced lung vascular remodeling, improved hemodynamics.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): National Natural Science Fundation of China (82060018) and Natural Science Fundation of Yunnan (202101AS070043, 202102AA31003-7).
High incidence of pulmonary artery thrombosis after balloon pulmonary angioplasty in CTEPH patients receiving direct oral anticoagulants
Authors: Suetomi T , Shimokawahara H , Fukuda Y , Kanezawa M , Suruga K , Hayashi K , Miyagi A , Kobashi S , Sugiyama Y , Shigetoshi M , Tabuchi I , Ogawa A , Watanabe A , Matsubara H
Published: October 2022

Background

Chronic thromboembolic pulmonary hypertension (CTEPH) requires life-long anticoagulant therapy, whereas limited data exist on the safety and efficacy of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) along with balloon pulmonary angioplasty (BPA).

Objectives

To evaluate outcomes and complications in CTEPH following BPA for individuals receiving DOACs or VKAs.

Methods

Consecutive CTEPH patients underwent BPA from September 2014 to August 2021 were included in a retrospective analysis. Complications during BPA, post-BPA hemodynamics and bleeding events were obtained from patient's medical records. Our routine follow-up “selective” pulmonary angiography, to evaluate all segmental pulmonary arteries one by one at six months and every year after final BPA session, was performed to elucidate the incidence of in-situ fresh floating thrombus.

Results

Of total 250 individuals, 104 were treated with DOACs and 146 with VKAs following BPA. Mean observation period was 905 (SD ± 660) days. Total 1278 BPA sessions were performed among the period in which 409 sessions were treated with DOACs and 869 sessions with VKAs. Significant improvements in hemodynamics and functional status were observed in both groups following BPA. There was no significant difference of hemoptysis during BPA between DOACs and VKAs (7.1% vs 10.1%, P=0.131). Major bleeding events during observation period were equivalent in those treated with DOACs and VKAs. No significant re-elevation of pulmonary artery pressure was observed in both groups after BPA. Follow-up selective pulmonary angiography identified in-situ fresh floating thrombus in pulmonary artery in 22 cases of total 769 follow-up sessions. The occurrence of fresh thrombus was significantly higher in those receiving DOACs than VKAs in therapeutic range of PT-INR >1.8 (3.9% vs 1.2%, P=0.023) whereas no significant difference between DOACs and overall VKAs (3.9% vs 2.4%, P=0.177)

Conclusions

Post-BPA hemodynamic outcomes and bleeding events appear unaffected by choice of anticoagulant. However, the incidence of in-situ pulmonary thrombosis detected by selective pulmonary angiography was significantly higher in those receiving DOACs than VKAs in therapeutic range, suggesting inadequate anticoagulation under current dose of DOACs. Our study provides a rationale for further examination to evaluate the efficacy of DOACs in CTEPH.

Funding Acknowledgement

Type of funding sources: None.
COVID-19 infection and its impact on case-fatality in patients with pulmonary embolism
Authors: Hobohm L , Sagoschen I , Barco S , Farmakis I , Fedeli U , Koelmel S , Gori T , Espinola-Klein C , Munzel T , Konstantinides S , Keller K
Published: October 2022

Background

Although a high prevalence of pulmonary embolism (PE) has been reported as a complication during severe COVID-19 infections in critical ill patients, nationwide data of hospitalized patients with COVID-19 with PE is still limited. Thus, we sought to analyze seasonal trends and predictors of in-hospital case-fatality in patients with COVID-19 and PE in Germany.

Methods

We used the German nationwide inpatient sample to analyze all data on hospitalizations for COVID-19 patients with and without PE in Germany during the year 2020 and to compare changes of PE prevalence to 2019.

Results

We analyzed data of 176,137 hospitalizations because of COVID-19 in 2020. Among those, PE was recorded in 1.9% (n=3,362) of discharge or death certificates. Almost one third of patients with COVID-19 and PE died during the in-hospital course (28.7%). The case-fatality rate increased with patients' age peaking in the 9th life-decade. Regardless of COVID-19, 196,203 inpatients were diagnosed with PE in Germany between 2019 and 2020. The number of PE hospitalizations were widely equally distributed between both years (98,485 vs. 97,718), while the case-fatality rate of all patients with PE was slightly lower in 2019 compared to 2020 (12.7% vs. 13.1%, P<0.001). In contrast, considerable differences in prevalence and case-fatality were demonstrated in 2020 regarding PE patients with and without COVID-19 infection (28.7% vs. 13.1%, P<0.001) (Figure 1). A COVID-19-infection was associated with a 2.8-fold increased risk of case-fatality in patients with PE (OR 2.81, 95% CI 1.66–2.12, P<0.001).

Conclusions

In Germany, the prevalence of PE events complicating hospitalizations was similar in 2019 and 2020. However, the fatality rate among patients with COVID-19-associated PE was substantially higher than that in those without either COVID-19 or PE, indicating an additive prognostic effect of these two conditions.

Funding Acknowledgement

Type of funding sources: None.
Right ventricular and left ventricular diameters are independent predictors of death or cardiopulmonary resuscitation in intermediate and high-risk pulmonary embolisms
Authors: Kanwal A , Bali A , Isath A , Hassanin A , Malekan R , Goldberg J , Spevack D
Published: October 2022

Background

Increased right ventricular (RV) dilation measured by the ratio of RV diameter (RVD) to left ventricular (LV) diameter (LVD) (RV:LV) is associated with pulmonary embolism (PE) severity and mortality. Data regarding the individual contributions of RVD and LVD are limited.

Purpose

To examine RVD and LVD as independent contributors to death or need for cardiopulmonary resuscitation (CPR) in intermediate- or high-risk PEs treated with surgical or catheter-based strategies

Methods

We measured basal RVD and LVD on presenting transthoracic echocardiograms (TTE) using the diastolic 4-chamber view on 127 PEs managed with surgical embolectomy (n=95, 75%), extracorporeal membrane oxygenation (n=23, 18%), or catheter-directed embolectomy (n=9, 7%) for intermediate- (64%) or high-risk (36%) PE (based on European Society of Cardiology criteria) between 2005 and 2022. The primary outcome was the composite of death (n=2) or survivors requiring CPR (n=10).

Results

A total of 127 patients were analyzed. Subjects were 57±14 years, 38% women, BMI 34±8. Mean RVD and LVD were 4.4±0.9 cm and 3.9±0.8 cm respectively. All presented with severe RV dysfunction on TTE and elevated cardiac biomarkers (Troponin-I or B-type natriuretic peptide). Mean RV:LV was 1.2±0.3 (range 0.7 to 2.8). Using logistic regression, higher RV:LV was associated with increased odds of death or CPR (odds ratio (OR) 15 [95% confidence interval (CI): 2.5, 82] per 1-unit increase, p=0.002. RV:LV >1.2 was the cutoff most associated with death or CPR, OR 7.2 [95% CI: 1.5, 34.5], p=0.01. Increasing RVD [OR 3.8 (95% CI: 1.1, 12.8), p=0.03] and decreasing LVD [OR 4.9 (95% CI: 1.3, 16.9), p=0.02] were independent predictors of death or CPR. RVD >5.0 cm (OR 5.9 [95% CI: 1,5, 23.2], p 0.01) and LVD <3.6 cm (OR 7.0 [95% CI: 1.7, 27.9], p=0.006) were the cutoff values most associated with the primary outcome. These cutoff values remained significant predictors even after adjustment for body surface area. Other parameters or RV size and function (diastolic area, systolic area and fractional area change) did not predict death or CPR. All of the subjects meeting the primary outcome had high-risk PE.

Discussion

In addition to RV:LV greater than 1.2, RVD and LVD were independently associated with death or CPR among high- or intermediate risk PEs. The independent contribution of declining LVD on PE mortality is a novel finding and highlights PE associatient LV pathophysiology (hyperdynamic and underfilled) antecedent to hemodynamic collapse. PE literature focuses on RV dilation as a predictor of PE mortality. LVD may represent a useful measure to risk stratify PE patients and predict hemodynamic decompensation.

Funding Acknowledgement

Type of funding sources: None.
Exercise hemodynamics by echocardiography and right heart catheterization in patients with chronic thromboembolic pulmonary disease
Authors: Dhayyat A , Mykland Hilde J , Jervan O , Stavem K , Ghanima W , Melsom M N , Steine K
Published: October 2022

Background

Chronic thromboembolic pulmonary hypertension (CTEPH) is an important cause of pulmonary hypertension (PH). A subclinical form of PH is referred to as exercise-induced pulmonary hypertension (EIPH), and its prevalence in patients with chronic thromboembolic pulmonary disease (CTEPD) without pulmonary hypertension at rest is unknown.

Purpose

To explore the occurrence of exercise-induced pulmonary hypertension (PH) in patients with CTEPD and compare exercise echocardiography with right heart catheterization (RHC).

Methods

In total, 16 patients with CTEPD, all diagnosed after pulmonary embolism, underwent exercise echocardiography and exercise RHC with dynamic supine leg exercise using a cycle ergometer. CTEPH at rest was defined as mean pulmonary artery pressure (mPAP) >20 mmHg and pulmonary vascular resistance (PVR) ≥3WU. EIPH by RHC was defined as mPAP >30 mmHg with total pulmonary resistance (TPR) ≥3 WU. Based on these criteria, our patients with CTEPD are presented by a flow chart (Figure 1). Systolic pulmonary artery pressure by echocardiography was calculated by tricuspid regurgitation peak velocity (TR V max) and the Bernoulli formula: 4 × (TR V)2. The RHC examination followed the exercise echocardiography within 2 hours. Groups were compared with independent sample t-test.

Results

Four patients (25%) were diagnosed with EIPH by exercise RHC. Patients with EIPH had a mean mPAP at peak exercise of 40.5 mmHg (range 38 to 43mmHg) and TPR of 3.7 WU (range 3.0 to 4.3 WU). The same patients also had a higher TR V max at peak exercise during exercise echocardiography compared to the patients without EIPH (Table 2). None of the patients had signs of elevated left-sided filling pressure during exercise by RHC, and none had left ventricular diastolic dysfunction during exercise by echocardiography.

Conclusion

In total, 4 of 16 patients with CTEPD were diagnosed with EIPH. The same four patients also had abnormal pulmonary artery pressure rise during exercise echocardiography and invasive RHC. These findings suggest that exercise echocardiography may be useful for screening patients with CTEPD and suspected EIPH.

Funding Acknowledgement

Type of funding sources: Public hospital(s). Main funding source(s): Ostfold Hospital Trust
Outcome of sedentary patients: does the power of zero cac make a difference?
Authors: Ahmed A I , Saad J M , Alahdab F , Han Y , Alfawara M , Soliman A , Nabi F , Al-Mallah M H
Published: October 2022

Introduction

Coronary artery calcium score (CACS) and exercise capacity (EC) are both independent prognostic tests in coronary artery disease (CAD).

Purpose

We aimed to assess the incremental prognostic role of EC to CACS, particularly in those with absent or low coronary calcification.

Methods

The cohort consisted of patients who had clinically indicated exercise stress testing and CACS assessment with a median of 27 days of each other. EC was defined based on peak metabolic equivalents (METS) achieved during exercise stress test. CACS was determined using the Agatston method. Patients were followed from the latest test date to incident MACE (inclusive of all-cause death, non-fatal myocardial infarction, late revascularization and admission for heart failure).

Results

There were a total of 1932 patients in the study population (mean age 56±12, 42% female, 48% hypertension, 21% diabetes, 48% dyslipidemia). Peak METS <6 was achieved in 8% of patients, and the median (IQR) CACS was 9 (0–203). Patients with EC <6 METS had doubling of their event rate across strata of CACS, even amongst patients with absent or low coronary calcifications (CACS 0: 4.6 vs 10.9; CACS 1–99: 10.4 vs 20.4; MACE per 1000 person year in patients with peak METS ≥ vs <6 respectively) (Figure 1).

Conclusion

Our findings showed that poor exercise capacity was associated with higher risk even in patients with absent or low coronary calcification.

Funding Acknowledgement

Type of funding sources: None.
Efficacy and safety outcomes of ultrasound assisted thrombolysis versus standard catheter direct thrombolysis in patients with submassive or massive pulmonary embolism: an updated meta-analysis
Authors: Kaur A , Dhaliwal A , Sohal S , Bhatia K , Sharma V , Cohen M , Visveswaran G , Salonia J , Kodra A , Basman C , Kliger C
Published: October 2022

Background

The use of catheter-based thrombolysis in comparison to systemic thrombolytics has emerged as a potentially lifesaving therapy for patients with sub massive or massive pulmonary embolism (PE). The addition of ultrasound waves to accelerate lytic dispersion in ultrasound assisted thrombolysis (USAT) has been proposed to improve outcomes as compared to standard catheter-directed thrombolysis (SCDT). These two modalities have been compared in small studies, but larger population data on the outcomes of these therapies is still lacking.

Purpose

To assess the efficacy and safety of USAT versus SCDT in patients with submassive or massive pulmonary embolism.

Methods

A review of electronic databases (PubMed, Scopus, Embase, and Cochrane) was performed using keywords USAT, SCDT and PE and studies were included if efficacy and safety outcomes were compared between the two types of therapies. Efficacy outcomes that were evaluated included the reduction in right ventricle/left ventricle ratio (RV/LV ratio), pulmonary artery systolic pressure (PASP) and Miller score. Safety outcomes that were evaluated included major bleeding, mortality and length of ICU stay. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated for continuous variables. Risk ratio (RR) and 95% CI were reported for dichotomous variables using the random effects model in comprehensive meta-analysis and RevMan 5.4.1 softwares.

Results

Six studies with a total of 381 patients (USAT n=204; SCDT n=177) were included. No statistical difference in efficacy outcomes of USAT over SCDT was noted in the degree of RV/LV ratio reduction (SMD: −0.507; CI: −1.386–0.373; p>0.05; I2=92%), PASP reduction (SMD: 0.037; CI: −0.404–0.478; p>0.05; I2=59%), or Miller score reduction (SMD: 0.303; CI: −0.481– 1.087; p>0.05; I2=82%). Safety outcomes were also not statistically different with similar rates of major bleeding (RR: 1.44; CI: 0.54–3.85; p>0.05; I2=4%), mortality (RR: 1.46; CI: 0.35–6.05; p>0.05; I2=0%) and length of ICU stay (SMD: −0.01; CI: −0.29–0.27; p>0.05; I2=31%) in both treatment groups.

Conclusion

Our data suggest that despite the technological advancement of USAT, there is no additional benefit over SCDT in terms of efficacy and safety. Further studies are warranted for both procedures investigating financial and clinical outcomes in real world practice.

Funding Acknowledgement

Type of funding sources: None.
Notch ratio in pulmonary flow predicts long term prognosis after pulmonary endarterectomy for chronic thrombo-embolic pulmonary hypertension
Authors: De Bruin-Bon H A C M , Winkelman J A , Eckmann H M , Samson D A , Widyanti A P , Vleugels J , Bombeld D C M , Caesar C G C M , Bouma B J , Beijk M A M
Published: October 2022

Introduction

The notch ratio (NR) in the pulmonary flow predicts in-hospital mortality after pulmonary endarterectomy (PEA) for chronic thrombotic pulmonary hypertension (CTEPH).

Purpose

We studied whether the echocardiographic parameter NR can also discriminate long term outcome.

Methods

All patients who underwent PEA between June 2002 and June 2005 were studied. Clinical, hemodynamic and echocardiographic variables were assessed pre-operatively and at 3 months post-PEA. Clinical follow up ended in March 2022. NR was the time from onset pulmonary flow until notch divided by the time from notch until end of pulmonary flow assessed with pulsed Doppler.

Results

A total of 59 patient are included in this analysis. Mean age was 53±14 years, 34% were male patients and 66% of patients were NYHA class III or IV. Pre-operative mean pulmonary artery pressure (mPAP) was 45±15 mmHg and calculated total pulmonary resistance (TPR) was 870±511 dynes s cm–5. Pre-operatively, 7 patients had no notch, 33 had NR <1.0 and 19 had NR >1.

Six patients died in hospital and a total of 19 patients died during the follow up till March 2022. Between survivors and non-survivors, no significant differences were observed in 6-minute walking distance (409±114 m. vs. 364±110 m., p=0.22), plasma BNP (34±47 pmol/l vs. 57±52 pmol/l, p=0.10), mean PAP (43±14 mmHg vs. 49±15 mmHg, p=0.14), TPR (793±493 dynes s cm–5 vs. 1015±525 dynes s cm–5, p=0.13). NR was significant different between survivors and non-survivors (0.73±0.25 vs. 1.1±0.44, p<0.001).

Mean very long term follow-up of 14±6 years. The 1, 5, 8 and 14 year survival for patients with a NR <1 was respectively 100%, 100%, 95% and 83% was significantly better (p≤0.001) then for patients with a NR >1 (1, 5, 8 and 14 year survival was 68%, 53%, 42% and 37%, respectively). For patients without a notch (1, 5 and 8 year survival was 100% and 14 year survival was 86%).

Conclusion

NR predicts in-hospital and long term mortality in CTEPH patients undergoing PEA. NR >1.0 is associated with a higher risk of mortality. NR is a simple echocardiographic parameter that can be used in clinical decision making for PEA.

Funding Acknowledgement

Type of funding sources: None.
Anticoagulant treatment patterns and thromboembolic events by tumor type among patients with VTE and cancer
Authors: Dhamane A D , Noxon V , Bruette R , Shah S , Ferri M , Liu X , Jang J , Luo X
Published: October 2022

Background

Patients with venous thromboembolism (VTE) and cancer are at higher risk of adverse outcomes (mortality, recurrent VTE etc.) versus patients with cancer alone; as such, clinical guidelines recommend anticoagulant treatment for patients with VTE and cancer. There is limited real world data about how anticoagulant treatment and thromboembolic outcomes differ by tumor type in patients with VTE and cancer. Understanding such differences may help identify appropriate anticoagulant treatment for specific tumor types.

Purpose

To describe anticoagulant treatment patterns and thromboembolic outcomes by tumor type among patients with VTE and cancer.

Methods

Patients with VTE and cancer age ≥65 were identified from the Surveillance, Epidemiology and End Results (SEER) Medicare database from 1/1/2014–12/31/2019. Patients were required to be enrolled for ≥6-months prior to their first VTE diagnosis (index) and without evidence of other conditions requiring anticoagulant (i.e., atrial fibrillation) prior to index. Cancer status and tumor type were identified from SEER or Medicare database in the 6-months prior through 30-days post VTE. This analysis focused on the following specific tumor types: high risk (brain, pancreas, and stomach) and common tumor types (breast, and prostate). Patients treated with an anticoagulant within 30-days after index were included in the final population. Major bleeding (MB) and recurrent VTE events were measured during follow-up (index date through earliest of disenrollment, death or 12/31/2019).

Results

A total of 3,546 anticoagulated patients with VTE and cancer of interest met all study criteria (breast [n=1,197], prostate [n=849], pancreatic [n=995], brain [n=248] and stomach [n=257] cancer). Patient mean age ranged from 73 (brain) to 76 (stomach) at index. Anticoagulant treatment patterns varied by tumor type (Figure 1). LMWH was more likely to be used in the 3 high risk tumor types whereas apixaban and rivaroxaban were more likely to be used in the 2 common tumor types. The incidence rate of recurrent VTE and major bleeding events also varied among different tumor types: ranging from 1.4 (breast) to 6.4 (pancreatic) per 100 person-years for recurrent VTE and from 4.3 (prostate) to 15.1 (pancreatic) per 100 person-years for major bleeding (Figure 2).

Conclusion

There are notable variations in anticoagulant treatment patters and the risks of major bleeding and recurrent VTE events by tumor type among patients with VTE and cancer. Further research is needed to understand which anticoagulant treatment option is more appropriate for VTE patients with specific tumor type.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): Pfizer Inc. and Bristol Myers Squibb Company
Venous thromboembolism and mortality in a multiethnic population: a report from the Birmingham Black Country VTE registry (BBC-VTE Investigators)
Authors: Sanders A , El-Bouri W K , Lip G Y H
Published: October 2022

Background

Most epidemiological studies into venous thromboembolism (VTE) are based on the white Caucasian population and unrepresentative of VTE outcomes in non-white ethnicities.

Purpose

Our VTE registry aims to get an insight into the outcomes of VTE patients as applicable to a developed world population with a multi-ethnic background. This will guide clinicians to make appropriate decisions with regards to management and prognosis.

Methods

The Birmingham Black Country VTE Registry (BBC-VTE) is a multi-ethnic cohort of patients in the West Midlands region of the United Kingdom, who suffered a first episode of VTE. In this study we compared baseline characteristics, treatment patterns and outcomes, and secondly, compared these among the different ethnic groups in this region.

Results

Between the years 2012–2014 there was a total of 1615 patients (mean age 65.5; 53.1% female) admitted with a first episode of VTE of whom, 134 (8.3%) were Asian, 92 (5.7%) Black, and 1213 (75.1%) White. Asian patients were younger (mean age 54, SD 19.3) vs Black patients (59, SD 19.7) and White patients (68, SD 17.4); and were less often female (50.7% vs. 55.4% and 53.8%) for Black and White patients respectively. The initial VTE event was a DVT in 680 (42.1%) and a PE±DVT in 935 patients (57.9%). Below-knee and above-knee DVT occurred in 95 (5.9%) and 585 (36.2%) patients respectively. Recurrent DVT occurred in 3.2% of those with an initial below-knee DVT and 12.5% of those with an initial above-knee DVT. Recurrent PE was also more common in those with an initial above knee DVT (4.8%) compared to those with below-knee DVT (3.2%).

After the initial VTE event, 1269 (78.6%) were started on long-term anticoagulation for the prevention of recurrent VTE. Of those, 65.1% stayed on anticoagulation for up to 6 months after the initial VTE event, and 34.9% continued for longer than 6 months, including those on lifelong anticoagulation. Bleeding and major bleeding occurred in 6.8% and 2.5% respectively in those on anticoagulation for 6 or less months, vs. 10.4% and 3.5% in those anticoagulated for longer than 6 months. The most common site of bleeding was gastrointestinal in 42.3% of all bleeds and this site was also responsible for 54.3% of major bleeds.

From evaluating the odds ratio for VTE mortality (see Fig. 1), ethnicity did not have a significant impact. Older age; the presence of diabetes mellitus; history of malignancy; as well as admission laboratory results for C-reactive protein and neutrophil count were all significantly associated with higher odds of mortality in this patient cohort.

Conclusion

BBC-VTE is a contemporary multi-ethnic cohort of patients providing insights into the risk factors among multi-ethnic patients that have developed VTE. Ethnicity did not emerge as an independent risk for VTE mortality.

Funding Acknowledgement

Type of funding sources: None.
Optimal thromboprophylaxis and anticoagulant strategies in patients with COVID-19 pneumonia. The PROTHROMCOVID Trial
Authors: Munoz-Rivas N , Aibar Gallizo J , Gabara-Xanco C , Trueba-Vicente A , Urbelz-Perez A , Gomez-Del Olmo V , Demelo-Rodriguez P , Rivera-Gallego A , Bosch-Nicolau P A U , Nieto Rodriguez J A , Rios-Prego M , Madridano-Cobo O , Mendez M , Hernandez-Rivas J A , Torres-Macho J
Published: October 2022

Introduction

Hospitalized patients with COVID-19 are at increased risk of venous and arterial thrombosis, ARDS, and death. The optimal dosage of thromboprophylaxis in patients is unknown.

Objective

To evaluate the efficacy and safety of tinzaparin in prophylactic, intermediate and therapeutic doses in non-critical patients admitted for COVID-19 pneumonia.

Design, Setting, and Participants: The PROTHROMCOVID multicenter randomized clinical trial enrolled noncritical hospitalized adult patients with COVID-19 pneumonia from February 1, 2021, to September 30, 2021, at 18 centers in Spain.

Methods

Patients were randomized to prophylactic tinzaparin 4500IU or intermediate dose 100IU/kg or therapeutic tinzaparin 175IU/kg during hospitalization, followed by 7 days of prophylactic tinzaparin at discharge. The patients were stratified at the time of randomization according to age, sex and the presence or absence of hypertension.The primary efficacy outcome was a composite endpoint of symptomatic systemic thrombotic events, need for invasive or non invasive mechanical ventilation or not, including high-flow nasal cannula oxygen, or death within 30 days. The main safety outcome was major bleeding at 30 days. Data were collected and adjudicated locally by non-blinded investigators through imaging, laboratory, and health record data.

Results

Of 311 patients randomized, 300 were included in the analysis (mean [SD]age, 56.7 [14.6] years; men, 182 [60.7%]; women, 118 [39.3%]). 106 patients (35.33%) were assigned to the prophylaxis group, 91 patients (30.33%) were allocated to the intermediate dose group and 103 patients (34.33%) were randomized to the anticoagulant dose group. The composite endpoint thrombotic event, need for invasive (IMV) or noninvasive mechanical ventilation (NIV) or HFT via nasal cannula or death at 30 days from randomization occurred in 58 patients (19.3%) of the whole population, 19 patients (17.09%) in prophylactic group, 20 (21.98%) in intermediate group and 19 (18.45%) in therapeutic group (P=0.72). No major bleeding were reported in the trial and non-major bleeding occurred in 5 patients (4.71%) in prophilactic, in 3 patients (3.2%) in intermediate arm and in 3 patients (2.9%) in therapeutic, without significant differences in each group (P=0.31).

Conclusions

In non-critically ill patients with COVID 19, intermediate or full-dose of tinzaparin do not appear to offer benefit over standard prophylactic doses IU in the likelihood of thrombotic event, non-invasive ventilation or high-flow oxygen, or death.

Funding Acknowledgement

Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Leo Pharma
Incident pulmonary hypertension in 13,448 cases investigated with repeat echocardiography: insight from the National Echo Database of Australia (NEDA)
Authors: Stewart S , Chan Y , Playford D , Strange G
Published: October 2022

Background

We addressed the paucity of data describing the characteristics and natural history of incident pulmonary hypertension (PHT).

Methods

In this observational clinical cohort study, we examined 85,173 individuals undergoing routine echocardiography for heart disease without evidence of PHT (according to estimated right ventricular systolic pressure, eRVSP <30 mmHg). Subsequent age and sex-specific incidence of PHT were derived from repeat echocardiograms conducted a median of 3.43 (interquartile range, IQR 1.49 to 6.55) years apart in 13,448 adults. Progressive PHT severity with individual data linkage to all-cause mortality were examined per PHT stage: eRVSP 30–39 mmHg (mild PHT), 40–49 mmHg (moderate PHT) and ≥50 mmHg (severe PHT).

Results

A total of 6,169 men (45.9%, mean age 61.4±16.7 years) and 7,279 women (60.8±16.9 years) with no initial evidence of PHT were identified (first echocardiogram). Subsequently, 5,412 (40.2%,) developed PHT (repeat echocardiogram) – comprising 4,125 (30.7%, 65.0±14.3 years), 928 (6.9%, 69.2±13.5 years), and 359 (2.7%, 69.8±12.7 years) cases of mild, moderate, and severe PHT, respectively. The incidence of all stages of PHT was 15.2 cases per million men/annum and 12.5 cases per million women/annum. Overall, median eRVSP increased by +7.4 (IQR +4.6 to +10.1) and +30.7 (IQR +26.0 to +37.3) mmHg; median E:e' ratio increased by +1.0 (IQR −0.4 to +3.2) and +3.6 (IQR +2.0 to +8.2); and median LA volume increased by +5.0 (IQR +0.0 to +12.0) and +19.5 (IQR +9.0 to +31.0) ml/m2, respectively, in mild and severe PHT groups between first and last echocardiograms. During subsequent median 8.1 years follow-up, 2,776/13,448 (20.6%) individuals died from all-cause. Compared to no PHT, the age- and sex-adjusted hazard ratios for all-cause mortality increased to 1.35 (95% confidence interval, CI 1.23–1.47) in mild PHT, 1.94 (95% CI 1.73–2.18) in moderate PHT, and 2.43 (95% CI 2.09–2.83) in severe PHT (all p<0.001).

Conclusions

New onset of PHT is a common finding among individuals with heart disease followed-up with echocardiography. Even milder stage of PHT is associated with higher mortality, reinforcing the need for proactive evaluation for symptoms consistent with PHT.

Funding Acknowledgement

Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Johnson & Johnson: Investigator-initiated grant
Risk stratification parameters as assessed by continuous long-term cardiac monitoring in pulmonary hypertension – heart rate variability, heart rate, and physical activity
Authors: Oerbaek Andersen M , Diederichsen S Z , Svendsen J H , Carlsen J
Published: October 2022

Background

Pulmonary hypertension (PH) is a progressive disease affecting both the pulmonary vasculature and the heart. In the current ESC/ERS guidelines nine variables are used in PH risk assessment, and have been proven to be independent predictors of survival in PH. The risk assessment parameters include clinical symptoms, exercise capacity and imaging. The present study is the first to assess continuous 24/7 heart rate variability (HRV), heart rate (HR) and physical activity monitoring in patients with PH.

Purpose

To identify risk stratification parameters by continuous cardiac monitoring in PH.

Methods

Patients diagnosed with PH were included in this prospective single-centre study. Patients had a Reveal LINQ insertable cardiac monitor implanted to continuously monitor heart rate variability (HRV), heart rate at day and night and physical activity. HRV was expressed as the mean HRV in sinus rhythm during each full day (SDANN method). Pearson and Spearman correlations between the loop recorder variables and ESC/ERS risk stratification variables were calculated and compared with the loop recorder data in 30-days intervals.

Results

A total of 41 patients were prospectively enrolled, 27 patients with pulmonary arterial hypertension (PAH) and 14 patients with chronic thromboembolic pulmonary hypertension (CTPEH). The patients were monitored continuously in a total of 82 patient-years, had a mean age of 58 years and were primarily in a stable disease phase with a mean WHO functional class (FC) of 2.2. HRV and physical activity divided by heart rate at daytime showed the highest correlations respectively with current risk parameters. In particular, high correlations were found between HRV and NT-proBNP (R=−0,69 p≤2.2e-16), WHO FC (R=−0,65 p=2.4e-5), RVEF (R=0,61 p=0,00012) and right atrial pressure (RAP) (R=−0.67 p=0.0023) (Figure 1).

Conclusion

This study demonstrates the potential of HRV, and physical activity divided by heart rate daytime as risk parameters in pulmonary hypertension. Progression of symptoms in PH are often delayed compared with pathophysiological changes, and continuous monitoring offers a potential to early recognition of disease progression and optimization of PAH therapy.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): The study was supported by the Heart Centre Research Council,Rigshospitalet and an investigator initiated study research grant fromJansson Pharmaceuticals.
Coronary computed tomography angiography based endothelial wall shear stress in normal coronary arteries
Authors: Schultz J , Van Den Hoogen I J , Kuneman J H , Sakellarios A , Nikopoulos S , Tsarapatsani K , Naka K , Michalis L , Fotiadis D I , Maaniitty T , Saraste A , Bax J J , Knuuti J
Published: October 2022

Background

Endothelial wall shear stress (ESS) is a biomechanical force which plays a key role in the formation and evolution of atherosclerotic lesions.

Purpose

This study aims to evaluate ESS in coronary arteries without atherosclerosis, and to assess various factors affecting ESS values.

Methods

Coronary computed tomography angiography (CCTA) images from patients with suspected coronary artery disease were analyzed to identify coronary arteries without atherosclerosis. Minimal and maximal ESS values were calculated for 3-mm segments with dedicated software. Segments were categorized according to lumen diameter tertiles into small (<2.6 mm), intermediate (2.6–3.2 mm) or large (≥3.2 mm) size classes. Normal ranges of minimal and maximal ESS values were calculated per vessel and vessel size.

Results

A total of 349 normal vessels from 168 patients (mean age 59.4±9.2 years, 39% men) were included. ESS was highest in the left anterior descending artery compared to the left circumflex and the right coronary arteries (2.3 Pa vs. 1.9 Pa vs. 1.6 Pa for minimal ESS, p<0.001 and 3.7 Pa vs. 3.0 Pa vs. 2.5 Pa for maximal ESS, p<0.001). ESS values were highest in small vessel segments compared to intermediate or large segments (3.8 Pa vs. 1.7 Pa vs. 1.2 Pa for minimal ESS, p<0.001 and 6.0 Pa vs. 2.6 Pa vs. 2.0 Pa for maximal ESS, p<0.001). Weak to moderate correlation was found between ESS and the distance from the ostium (ρ values ranging from 0.22 to 0.62 for different vessels).

Conclusion

We derived ESS values from the CCTA images for visually normal coronary arteries. ESS values depend strongly on the lumen diameter of the coronary vessel. The normal ranges of minimal and maximal ESS can be used in future studies, where ESS values in stenotic lesions are compared to the normal values derived in the present analysis.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Finnish Foundation for Cardiovascular Research
Behavior of right atrial strain in patients with advanced idiopathic pulmonary arterial hypertension after initiation of specific combined therapy
Authors: Samuel I , Locas J , Mostafa S , Khaled A , El Mozy W , Gergis M , Hassan A
Published: October 2022

Background

Right atrial (RA) function has emerged as an important determinant of outcome in pulmonary arterial hypertension (PAH). However, studies exploring RA function and assessing its behavior in response to specific PAH combination therapy, independent of RA size in patients with PAH is not adequately investigated.

Purpose

Assess the behavior of strain based measures of RA in response to combined PAH therapy, independent of RA size in patients with PAH.

Methods

RA peak longitudinal strain (PLS) and peak active contraction strain (PACS) were retrospectively assessed in 38 patients with advanced idiopathic pulmonary arterial hypertension (IPAH) who were referred to Aswan heart Centre and not receiving proper GDMT; at baseline and during follow-up after initiation of specific PAH combination therapy in the form of either Sildenafil/Bosentan or Sildenafil/Macitentan.

Results

Most of the patients were females with median (IR) age 34 (27–39) years. All patients presented with dyspnea WHO-FC III. At baseline, all patients were receiving only monotherapy in the form of sildenafil. Median (IR) time to echocardiographic follow-up was 11 (8–18) months. Patients presented with markedly right ventricle (RV) and RA enlargement, depressed RV systolic function, and reduced RA strain parameters compared with values previously reported in healthy controls. Among various baseline associations of the RA PLS, the strongest were with baseline RA area (rho: −0.659; p<0.001) and RVEF by CMR (rho: 0.570; p<0.001). At follow up; RA PLS and PACS significantly increased (16.6 vs 24 and 7.06 vs 11.42, respectively: p<0.001); however, RA area did not show significant decrease. Only RV TDI & FAC showed significant improvement among different RV function parameters measured by echocardiography. During the follow up period, 11 out of 38 patients (28.9%) were hospitalized. RA PLS change was significantly lower in the hospitalized group than the non-hospitalized group (4.40 vs 10.2; p=0.014). RA PLS change was independently associated with hospitalization in the multivariate regression analysis (95% CI: −0.061 to −0.010; p=0.008).

Conclusion

Initiation of specific PAH combination therapy in undertreated patients with IPAH showed improvement in RA strain parameters despite no change in RA area during follow up.

Funding Acknowledgement

Type of funding sources: None.
Electroanatomic mapping and radiofrequency catheter ablation of atrial fibrillation or atrial tachycardia in patients with pulmonary hypertension. Ancillary analysis
Authors: Havranek S , Fingrova Z , Skala T , Reichenbach A , Dusik M , Ambroz D , Dytrych V , Jansa P , Klimes D , Wichterle D
Published: October 2022

Background

Atrial fibrillation (AF) and related atrial tachycardias (ATs) are common arrhythmias in patients with pulmonary hypertension (PH). They are currently assessed in a multicentre randomized trial investigating extensive radiofrequency catheter ablation of the arrhythmogenic substrate on top of selective ablation of clinical arrhythmia alone.

Purpose

Irrespective of the randomization scheme, we compared clinical and procedural characteristics in patients with AF versus those with right-sided ATs.

Methods

Out of 74 patients with combined post- and pre-capillary or isolated pre-capillary PH, two study subgroups were composed: AF group included 40 patients and AT group included 31 patients: 24 with typical atrial flutter (AFL) and 7 with other right-sided ATs (2 upper loop reentry ATs, 2 focal ATs from coronary sinus ostium, 1 focal AT from terminal crest, and 2 polymorphic ATs from high right atrium). Three patients with inducible AV nodal reentrant tachycardia were excluded from this analysis. Biatrial electroanatomic mapping was performed in all patients. The data are presented as medians (interquartile range) and compared by the Mann-Whitney U test.

Results

The clinical and procedural characteristics of AF and AT groups are shown in Table. Cycle length (CL) of both induced and spontaneous AFL was 302 (267; 324) ms. Non-CTI-dependent ATs had CL 425 (350; 480) ms. In patients with AF, the dominant CL was 183 (152; 221) and 191 (154; 210) ms in right and left atrial appendage, respectively. In the whole cohort, pulmonary vein isolation was done in 49 (66%), left atrial substrate ablated in 23 (31%), cavotricuspid isthmus block achieved in 46 (62%), superior vena cava isolation completed in 28 (39%), intercaval line ablated in 26 (36%), and right atrial substrate or focal activity ablated in 8 (11%) cases. The procedure was technically successful in 72 (97%) patients.

Conclusion

Patients with right-sided ATs had expectedly more dilated right atrium. This was not, however, associated with a higher prevalence of right atrial low-voltage areas. Left atrial electroanatomic remodelling in AF patients was concordant with that frequently observed in non-PH patients with AF.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ministry of Health of the Czech Republic.