Abstract
Background:
The role of advanced therapies (systemic thrombolysis, catheter-based treatment and surgical thrombectomy) for the management of right heart thrombus (RHT) is poorly defined. In this study, we assessed the clinical predictors and outcomes of advanced therapy compared to anticoagulation alone for the acute management of RHT.
Methods:
In this observational cohort study, we analyzed consecutive patients who were treated for RHT. The primary endpoint was 90-day all-cause mortality. Clinical predictors of utilizing advanced therapy were assessed with multivariable logistic regression. Propensity score matching was utilized to compare adjusted outcomes between patients receiving advanced therapies versus anticoagulation alone.
Results:
A total of 345 patients were included in the study. Advanced therapy was utilized in 13.6% (N=47) of patients, of which 25.5% (N=12/47) was systemic thrombolysis, 23.4% (N=11/47) was endovascular thrombectomy, and 53.2% (N=25/47) was surgical thrombectomy. Younger age (OR 0.98, 95% CI 0.96–0.99) and concurrent PE (OR 5.36 95% CI 2.48–12.1) predicted utilization of advanced therapy. In propensity score matched analysis, there was no difference in 90-day mortality (HR 0.46, 95% CI 0.17–1.22), in-hospital mortality (OR 0.64, 95% CI 0.17–2.19), or length of stay (β −4.39, 95% CI −14.0–5.22) between advanced therapy and anticoagulation.
Conclusions:
Among a diverse cohort of patients with RHT, outcomes did not differ between those who underwent advanced therapy and anticoagulation alone. Important predictors for utilizing advanced treatment included younger age and presence of a concurrent PE. Future studies assessing advanced therapy in larger and broader patient populations are necessary.
Keywords: Right heart thrombus, pulmonary embolism, venous thromboembolism, advanced therapy, anticoagulation, systemic thrombolysis, thrombectomy, Peripheral Vascular Disease
Graphical Abstract
INTRODUCTION
A right heart thrombus (RHT) involves thrombus present within the right atrium or ventricle.1–3 While an infrequent presentation of venous thromboembolism (VTE), RHT are capable of embolizing to the pulmonary vasculature and consequently can result in significant clinical complications.4,5
Over the past two decades, it has been demonstrated that a RHT presenting with an acute pulmonary embolism (PE) is associated with poor clinical outcomes including worse survival when compared to patients with PE alone.6–9 However, despite this evidence, the optimal treatment for these patients remains poorly defined.10–12 Current management options for RHT and its associated embolic complications include therapeutic anticoagulation as well as advanced strategies such as systemic thrombolysis, surgical removal, and endovascular-based thrombectomy.12–15 To date, no randomized trials have directly compared therapeutic anticoagulation to invasive therapies and consequently treatment algorithms for managing RHT are highly institution specific. Moreover, limited data exists regarding the factors influential in the clinical decision to utilize advanced therapy for these patients.
In recent years, several observational studies have attempted to compare treatment modalities for the management of RHT. In a systematic analysis of case reports, surgical embolectomy and systemic thrombolysis were shown to have superior survival when compared to systemic anticoagulation alone.16 However, in two subsequent analyses of large VTE registries, clinical outcomes, including mortality, were shown to be similar between modalities.17,18
Numerous questions still surround the role of invasive management of acute RHT. In this analysis leveraging institutional data from two large hospital systems, we aimed to (1) investigate the factors used to escalate care with invasive therapy for RHT and (2) compare clinical outcomes among patients who underwent advanced therapies as compared to anticoagulation alone for the management of RHT.
METHODS
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Patient Population and Data Collection
Approval for this study was obtained by the Institutional Review Boards at Massachusetts General Hospital and Beth Israel Deaconess Medical Center. Informed consent was obtained from all patients. Consecutive patients were identified at each institution between June 2002 and May 2020 utilizing individual institutional imaging databases. Patients were initially identified if they had a radiographic description of a mass in either the right atrium or ventricle. Next, all patients identified in this search were manually reviewed to confirm the diagnosis of RHT. Patients were excluded if the diagnosis of RHT was unlikely based on either clinical or radiographic evidence or if an alternative diagnosis was felt to be more likely. These determinations were made based on reviewing each patient’s clinical admission notes, problem lists, imaging studies, and laboratory studies during their index hospitalizations. In order to directly compare patients who underwent advanced therapy and anticoagulation alone, patients were additionally excluded if they did not initially receive therapeutic anticoagulation in the initial management of RHT.
In this study, all data was collected utilizing a manual retrospective chart review. Variables extracted from each patient included patient sociodemographics, thrombus characteristics, relevant risk factors, clinical presentation, vital signs, diagnostic modalities utilized, treatments provided, and clinical outcomes including 90-day mortality, in-hospital mortality, length of stay, and requirement for ICU-level care. Thrombus characteristics including mobility was determined by reviewing index imaging report to abstract the relevant data. To ascertain thrombus mobility, we used echocardiography studies for those available (91.6%) and applied a standardized definition, as follows: thrombi with echocardiographic description of movement independent of the cardiac structure with or without a visible attachment point or described as free-floating. Table S1 provides a comprehensive overview of the data collected for this analysis as well as the definitions for all variables included.
The primary endpoint for this analysis was 90-day all-cause mortality. Secondary endpoints included in-hospital mortality, length of stay, and requirement for ICU admission. Advanced therapy was defined as receipt of either systemic thrombolysis, surgical thrombectomy, or a catheter-direct endovascular therapy. For each of these modalities, certain procedure-related complications were also investigated. Table S1 highlights these specific peri- and post-procedural complications studied for each treatment modality.
Statistical Analysis
Categorical variables are presented as number (%) and continuous variables as mean ± standard deviation. Cumulative incidence of all-cause mortality through 90 days was estimated using Kaplan-Meier methods and depicted using survival curves. Cumulative incidences between treatment groups were compared utilizing log-rank tests.
Both univariable and multivariable logistic regression models were used to investigate predictors for escalating care to advanced therapy. Candidate covariates were determined based on clinical knowledge and included age, sex, concurrent PE, concurrent deep vein thrombosis (DVT), thrombus mobility, line-associated thrombosis, vital sign abnormalities (defined as heart rate>100, respiratory rate> 30, desaturation < 90%, or systolic BP< 90), BMI, current smoking status, concomitant malignancy, prior VTE event, history of chronic pulmonary disease, history of congestive heart failure, and hereditary thrombophilia. A forward selection algorithm utilizing the Akaike information criterion (AIC) for assessment of model improvement was performed to select the covariates to include within the final regression model.
To compare adjusted outcomes between treatment groups, propensity score matching was utilized. Propensity scores were calculated utilizing variables thought to influence the clinical decision to undergo advanced therapy for treating RHT including those identified within our predictive models. Variables incorporated into propensity score models included age, sex, thrombus characteristics including thrombus mobility, association with an intracardiac line (i.e., indwelling catheter or intracardiac device lead), concomitant PE, and any vital sign abnormality. Matching was performed utilizing a greedy 1:1 nearest neighbor matching algorithm without replacement. A fixed caliper distance of 0.25 was utilized for all matches. Standardized mean differences were utilized to assess between group differences both pre- and post-propensity score matching between the advanced therapy cohort and anticoagulation alone cohort. Secondary statistical analyses utilizing alternative propensity score-based methods were also performed to further compare groups and are reported within the Data Supplement. These included inverse probability treatment weighting (IPTW) and logistic regression modelling adjusted by propensity scores.
Effect sizes for the primary and second endpoints between advanced therapy and anticoagulation alone were determined utilizing regression models both before and after propensity score matching. Logistic regression models were used to assess the association between treatment strategy with in-hospital mortality and ICU admission. Cox proportional hazards regression models were utilized to evaluate the association with 90-day mortality. Finally, a linear regression was used to investigate the adjusted association between treatment strategy and length of stay.
All data was handled and stored in Microsoft Excel (Microsoft Corp., Seattle, WA). All statistical analyses including regression modelling and propensity score analysis was performed utilizing R version 4.1.0 in RStudio. Figures were prepared utilizing R version 4.1.0 in RStudio. Statistical significance was set at a two-tailed p-value < 0.05.
RESULTS
Patient Characteristics and Treatments Received
A total of 345 patients were included in this analysis, of which 298 patients (86.4%) received anticoagulation alone and 47 patients (13.6%) received advanced therapy. Table 1 illustrates the baseline characteristics among included patients. The mean age of the study cohort was 60.4 ± 18.9 years and 48.4% (N=167) were female. RHT was most frequently identified on echocardiography (N=293, 84.9%), followed by CT imaging (N=49, 14.2%), and MRI (N=3, 0.87%). A total of 91.6% (N=316) patient received an echocardiography during their index evaluation. Among the study cohort, 24.9% (N=86) of thrombi were visualized on echocardiography as mobile. Additionally, 92.2% of patients (N=318) had a right atrial (RA) thrombus, followed by 3.77% (N=13) with right ventricular (RV) thrombus, and 4.06% (N=14) with thrombus seen in both the RA and RV. Patients receiving advanced therapy were more likely to have a mobile thrombus (53.2% advanced therapy vs. 20.5% anticoagulation, p<0.01) and less likely to have a line-associated thrombus (12.8% advanced therapy vs. 49.3% anticoagulation, p<0.01). Additionally, patients who underwent advanced therapy were more likely to have a concomitant PE (70.2% advanced therapy vs. 23.2% anticoagulation, p<0.01) and a concomitant DVT (46.8% advanced therapy vs. 17.8% anticoagulation, p<0.01) (Table 1).
Table 1:
Patient demographics, comorbidities, and clinical presentation before and after propensity score matching
| Variable | Before Matching | After Matching | ||||
|---|---|---|---|---|---|---|
| Anticoagulation (n=298) | Advanced Therapy (n = 47) | Standardized Difference | Anticoagulation (n=43) | Advanced Therapy (n = 43) | Standardized Difference | |
| Age – years. | 61.79 ± 18.54 | 51.36 ± 19.19 | 0.553 | 51.57 ± 19.68 | 51.56 ± 19.68 | <0.001 |
| Female Sex | 134 (45.0%) | 33 (70.2%) | 0.528 | 26 (60.5%) | 29 (67.4%) | 0.146 |
| BMI – kg/m2 | 27.24 ± 6.95 | 30.56 ± 8.30 | 0.433 | 28.40 ± 7.67 | 29.42 ± 6.92 | 0.139 |
| Thrombus Description | ||||||
| Mobile or Free-Floating Thrombus | 61 (20.5%) | 25 (53.2%) | 0.721 | 24 (55.8%) | 21 (48.8%) | 0.140 |
| Immobile or Limited Mobility | 71 (23.8%) | 11 (23.4%) | 0.010 | 6 (14.0%) | 6 (14.0%) | <0.001 |
| Right Atrial Appendage Thrombus | 17 (6.1%) | 2 (4.8%) | 0.059 | 2 (4.9%) | 2 (5.3%) | 0.018 |
| Adherent to Heart Wall | 54 (19.4%) | 9 (21.4%) | 0.051 | 9 (22.0%) | 9 (23.7%) | 0.041 |
| Line-Associated Thrombus | 147 (49.3%) | 6 (12.8%) | 0.860 | 6 (14.0%) | 6 (14.0%) | <0.001 |
| Thrombus Location | ||||||
| RA Thrombus | 281 (94.3%) | 37 (78.7%) | 0.468 | 38 (88.4%) | 34 (79.1%) | 0.254 |
| RV Thrombus | 9 (3.0%) | 4 (8.5%) | 0.237 | 4 (9.34%) | 3 (7.0%) | 0.085 |
| RA and RV Thrombus | 8 (2.7%) | 6 (12.8%) | 0.385 | 1 (2.3%) | 6 (14.0%) | 0.435 |
| Risk Factors | ||||||
| Active Malignancy | 81 (27.2%) | 9 (19.1%) | 0.191 | 21 (48.8%) | 8 (18.6%) | 0.675 |
| Malignancy in Remission | 35 (11.7%) | 4 (8.5%) | 0.107 | 2 (4.7%) | 3 (7.0%) | 0.100 |
| Chronic Pulmonary Disease | 50 (16.8%) | 5 (10.6%) | 0.179 | 9 (20.9%) | 5 (11.6%) | 0.254 |
| Congestive Heart Failure | 116 (38.9%) | 8 (17.0%) | 0.503 | 8 (18.6%) | 8 (18.6%) | <0.001 |
| Smoking Status | 0.377 | |||||
| Never | 140 (50.0%) | 23 (56.1%) | 0.122 | 27 (69.2%) | 21 (55.3%) | 0.291 |
| Former | 101 (36.1%) | 14 (34.1%) | 0.040 | 7 (17.9%) | 13 (34.2%) | 0.377 |
| Current | 39 (13.9%) | 4 (9.8%) | 0.129 | 5 (12.8%) | 4 (10.5%) | 0.071 |
| Prior VTE | 63 (21.7%) | 10 (23.3%) | 0.037 | 9 (22.0%) | 10 (25.6%) | 0.087 |
| Hereditary Thrombophilia | 7 (2.3%) | 3 (6.4%) | 0.198 | 1 (2.3%) | 3 (7.0%) | 0.222 |
| Antiphospholipid Antibody Syndrome | 7 (2.3%) | 3 (6.4%) | 0.198 | 2 (4.7%) | 3 (7.0%) | 0.100 |
| Clinical Presentation | ||||||
| Concurrent DVT | 53 (17.8%) | 22 (46.8%) | 0.653 | 16 (37.2%) | 22 (51.2%) | 0.284 |
| Concurrent PE | 69 (23.2%) | 33 (70.2%) | 1.070 | 29 (67.4%) | 29 (67.4%) | <0.001 |
| Chest Pain | 36 (12.1%) | 9 (19.1%) | 0.196 | 5 (11.6%) | 8 (18.6%) | 0.196 |
| Dyspnea | 100 (33.6%) | 23 (48.9%) | 0.316 | 17 (39.5%) | 20 (46.5%) | 0.141 |
| Syncope | 12 (4.0%) | 7 (14.9%) | 0.378 | 3 (7.0%) | 6 (14.0%) | 0.229 |
| Asymptomatic | 72 (24.2%) | 9 (19.1%) | 0.122 | 11 (25.6%) | 9 (20.9%) | 0.110 |
| Vital sign abnormality* | 140 (47.0%) | 27 (57.4%) | 0.211 | 25 (58.1%) | 24 (55.8%) | 0.047 |
Defined as either HR>100, RR> 30, desaturation < 90%, or persistent hypotension with systolic BP< 90.
Abbreviations: BMI, body mass index; RA, right atrial; RV, right ventricular; VTE, venous thromboembolism; DVT, deep vein thrombosis; PE, pulmonary embolism.
Table 2 depicts the treatments received among patients included in this study. Among patients who underwent advanced treatment, surgical thrombectomy was the most frequently utilized modality (53.2%, N=25). Systemic thrombolysis and catheter-based treatment was utilized in 25.5% (N=12) and 23.4% (N=11) of patients who underwent advanced therapy, respectively. Among patients who underwent catheter-directed treatment, catheter-directed thrombolysis (14.9%, N=7) was the most frequent modality followed by treatment with mechanical thrombectomy (12.8%, N=6). In patients who received anticoagulation only, unfractionated heparin was the most frequently utilized anticoagulant (53.5%, N=159) (Table 2).
Table 2:
Anticoagulation and advanced therapy utilized among entire cohort.
| Variable | Anticoagulation (n=298) | Advanced Therapy (n = 47) |
|---|---|---|
| Initial Anticoagulation | ||
| Unfractionated Heparin | 159 (53.5%) | 31 (66.0%) |
| Low Molecular Weight Heparin | 53 (17.8%) | 8 (17.0%) |
| Direct Oral Anticoagulant | 24 (8.1%) | 2 (4.3%) |
| Warfarin | 54 (18.2%) | 1 (2.1%) |
| Fondaparinux | 3 (1.0%) | 1 (2.1%) |
| Direct Thrombin Inhibitor | 4 (1.3%) | 0 (0.0%) |
| Anticoagulation at Discharge | ||
| Unfractionated Heparin | 1 (0.3%) | 0 (0.0%) |
| Low Molecular Weight Heparin | 57 (19.2%) | 6 (12.8%) |
| Direct Oral Anticoagulant | 49 (16.5%) | 14 (29.8%) |
| Warfarin | 141 (47.5%) | 11 (23.4%) |
| Fondaparinux | 3 (1.0%) | 4 (8.5%) |
| Advanced Therapy | ||
| Systemic Thrombolysis | - | 12 (25.5%) |
| Catheter Directed Therapies | - | 11 (23.4%) |
| Mechanical Thrombectomy | - | 6 (12.8%) |
| Catheter-directed with Infusion Catheters | - | 7 (14.9%) |
| Surgical Embolectomy | - | 25 (53.2%) |
| Additional Treatments Utilized | ||
| ECMO | 7 (2.35%) | 1 (2.13) |
| IVC Filter Placed | 6 (2.01%) | 4 (8.5%) |
Abbreviations: ECMO, extracorporeal membrane oxygenation; IVC, inferior vena cava.
Among the 11 patients who underwent endovascular thrombectomy, procedural success was attained in all but 1 patient (91.0%). No patients experienced a peri- or post-procedural bleed that required transfusion or an intracranial hemorrhage. Only one patient had a reported complication which was an access site complication. For patients who underwent surgical embolectomy, procedural success was attained in 23 out of 25 patients (92.0%). Among the peri-procedural complications investigated, there were no immediate surgical complications. Finally, among patients who underwent systemic thrombolysis, there were no bleeding events that required unanticipated blood transfusion, or any intracranial bleeds reported attributed to thrombolysis.
Predictors of Utilization of Advanced Therapy
Table 3 depicts the univariable and multivariable analysis investigating predictors for utilizing advanced therapy within our cohort. In multivariable analysis, the strongest predictor for utilization of advanced therapy was presence of a concomitant PE (adjusted OR: 5.36, 95% CI 2.48–12.1, p<0.01). Other predictors for utilizing advanced therapy included younger age (adjusted OR: 0.98, 95% CI 0.96–0.99, p=0.01), and female sex (adjusted OR: 2.55, 95% CI 1.20–5.66, p=0.02). Patients who presented with a line-associated thrombus (adjusted OR: 0.27, 95% CI 0.09–0.67, p=0.01) or active malignancy (adjusted OR: 0.31, 95% CI 0.12–0.72, p=0.01) were less likely to receive advanced therapy as compared to anticoagulation alone (Table 3).
Table 3:
Predictors for utilization of advanced therapy.
| Covariate | Unadjusted | Adjusted | ||
|---|---|---|---|---|
| Odds Ratio (95% CI) | P-Value | Odds Ratio (95% CI) | P-Value | |
| Age | 0.97 (0.96–0.99) | <0.01 | 0.98 (0.96–0.99) | 0.01* |
| Female sex (versus male) | 2.88 (1.51–5.77) | <0.01 | 2.55 (1.20–5.66) | 0.02* |
| Concurrent PE | 7.82 (4.04–15.9) | <0.01 | 5.36 (2.48–12.1) | <0.01* |
| Concurrent DVT | 4.07 (2.13–7.77) | <0.01 | 2.07 (0.97–4.41) | 0.06 |
| Thrombus Mobility | 4.42 (2.34–8.42) | <0.01 | - | - |
| Line-associated thrombus | 0.15 (0.06–0.34) | <0.01 | 0.27 (0.09–0.67) | 0.01* |
| Vital Sign Abnormality | 1.52 (0.82–2.87) | 0.30 | - | - |
| BMI | 1.06 (1.02–1.10) | 0.01 | - | - |
| Current smoker | 0.67 (0.19–1.78) | 0.47 | - | - |
| Active Malignancy | 0.63 (0.28–1.32) | 0.25 | 0.31 (0.12–0.72) | 0.01* |
| History of VTE | 1.09 (0.49–2.27) | 0.82 | - | - |
| Chronic Pulmonary Disease | 0.59 (0.20–1.44) | 0.29 | - | - |
| Congestive Heart Failure | 0.32 (0.14–0.68) | 0.01 | 0.47 (0.18–1.15) | 0.11 |
| Hereditary Thrombophilia | 2.83 (0.59–10.6) | 0.14 | - | - |
| Year of Presentation | 1.06 (0.99–1.14) | 0.08 | - | - |
Abbreviations: PE, pulmonary embolism; DVT, deep vein thrombosis; BMI, body mass index; VTE, venous thromboembolism
Crude and Adjusted Outcomes
Analysis of the primary and secondary endpoints was performed both before and after propensity score matching. Utilizing 1:1 propensity score matching, a total of 43 patients treated with anticoagulation were matched with 43 patients receiving advanced therapy. Table 1 depicts the patient’s baseline characteristics, thrombus features, and comorbidities before and after propensity score matching as well as the standardized differences between groups.
Figure 1 depicts the Kaplan-Meier survival curves for the 90-day mortality analysis before and after propensity score matching. Before matching, 90-day mortality rates were 19.1% and 14.9% for patients receiving anticoagulation alone and advanced therapy, respectively (HR: 0.75, 95% CI 0.34–1.66, p=0.48). In propensity score matched analysis, 90-day mortality rates were 27.9% versus 14.0% for patients receiving anticoagulation alone and advanced therapy, respectively (HR: 0.46, 95% CI 0.17–1.22, p=0.12) (Table 4). In IPTW and propensity score adjusted regression analysis, 90-day mortality also did not significantly differ between patients who underwent advanced therapy versus anticoagulation alone (Table S2, Table S3, Table S4)
Figure 1:
Ninety-day survival for patients receiving anticoagulation only compared to advanced therapy for the (A) whole cohort and (B) propensity score matched cohorts. Hash marks indicate censoring of patients due to loss to follow up.
Table 4:
Primary and secondary endpoints before and after propensity score matching
| Before Matching | After Matching | |||||||
|---|---|---|---|---|---|---|---|---|
| Outcomes | Anticoagulation Only (n=298) | Advanced Therapy (n=47) | Model (95% CI) | P-Value | Anticoagulation Only (n=43) | Advanced Therapy (n=43) | Model (95% CI) | P-Value |
| Primary Endpoint | ||||||||
| 90-Day Mortality | 57 (19.1%) | 7 (14.9%) | HR: 0.75 (0.34–1.66) | 0.48 | 12 (27.9%) | 6 (14.0%) | HR: 0.46 (0.17–1.22) | 0.12 |
| Secondary Endpoints | ||||||||
| In-Hospital Mortality | 36 (12.3%) | 7 (14.9%) | OR: 1.25 (0.49–2.85) | 0.62 | 7 (17.1%) | 5 (11.6%) | OR: 0.64 (0.17–2.19) | 0.48 |
| Length of Stay (days) | 13.00 ± 17.38 | 13.38 ± 13.61 | β: 0.34 (−4.83–5.60) | 0.89 | 18.44 ± 28.80 | 14.05 ± 13.97 | β: −4.39 (−14.0–5.22) | 0.37 |
| ICU Admission | 109 (37.1%) | 36 (76.6%) | OR: 5.55 (2.80–11.9) | <0.01 | 16 (38.1%) | 33 (76.7%) | OR: 5.36 (2.15–14.3) | <0.01 |
Abbreviations: ICU, intensive care unit; HR, hazard ratio; OR, odds ratio.
Table 4 illustrates the analysis of the secondary endpoints. Following propensity score matching, rates of in-hospital mortality (OR: 0.64, 95% CI 0.17–2.19, p=0.48) and length of stay (β: −4.39, 95% CI −14.0–5.22, p=0.37) were similar between those who underwent advanced therapy and those who underwent anticoagulation alone. Patients who underwent advanced therapy were more likely to be admitted to the ICU during their index hospitalization (OR: 5.36, 95% CI 2.15–14.3, p<0.01). In IPTW and propensity score adjusted regression analysis, rates of in-hospital mortality and length of stay were also similar between cohorts (Table S2, Table S3, Table S4).
DISCUSSION
In this observational cohort study of 345 patients with RHT, we investigated the role of advanced therapy utilizing a database derived from two large hospital systems. Our findings indicate no difference between patients who underwent advanced therapy versus anticoagulation alone with respect to each of the endpoints investigated, including 90-day mortality, in-hospital death, and length of stay. Nevertheless, we found advanced therapy to be well tolerated with a high rate of procedural success. Moreover, we identified numerous factors influential in the decision to advance care beyond anticoagulation, including younger age and presence of a concomitant PE, all of which have not been previously described.
We did not find a difference in the primary endpoint of 90-day mortality between groups. Importantly, the current literature remains conflicted regarding optimal utilization of these modalities. For example, in one analysis including greater than 300 patients presenting with comorbid RHT and PE, rates of both all-cause and PE-related mortality were shown to be similar between advanced therapy and anticoagulation alone.17 However, this evidence has conflicted with other studies which have found a possible mortality benefit in patients treated with advanced therapy. In a pooled analysis of both case reports and institutional data, systemic thrombolysis was shown to have a nearly three-fold increased odds of survival when compared to anticoagulation alone.13 In the present analysis, the adjusted cumulative incidences of death were 30% and 14% for anticoagulation alone and advanced therapy, respectively. Although this did not reach statistical significance, the size of the risk difference is worth commenting on, and future studies with larger sample sizes and greater event rates may find a significant benefit with advanced therapies.
Moreover, this work is the first to report clinical predictors used to escalate care to advanced therapy. We found that presence of a concurrent PE was the most predictive factor for utilizing advanced therapy within our cohort with an odds ratio of greater than five-fold. These findings are likely due to the increased concern of adequate RV reserve when concomitant pulmonary artery thrombus is already present, thus likely prompting more aggressive therapy of RHT with PE. Other notable factors that informed treatment selection for advanced therapy included younger ages and interestingly female sex. However, the association with younger age likely represents a clinical bias towards patients who are better surgical candidates as nearly 50% of patients receiving advanced therapy underwent surgical interventions. We also found that presence of a line-associated thrombus and patients with comorbid malignancy were more likely to be treated with anticoagulation alone. Understanding these characteristics may be helpful in the decisions to escalate care for patients with RHT in the future.
In this analysis, we report on nearly fifty patients who underwent advanced therapy for the management of RHT. Among our cohort, approximately half of patients underwent surgical thrombectomy while the remaining patients evenly underwent either systemic thrombolysis or endovascular intervention. There was a high rate of procedural success, >90% for both surgical and catheter-based interventions. These high rates of procedural success are largely consistent with that of previous reports. For example, in one study looking at the Angiovac thrombectomy platform a similarly high success rate of 94.1% was demonstrated.19 Moreover, we also confirmed a low rate of major complications attributed to these therapies, including intracranial hemorrhage, the most feared post-procedural complication. These findings suggest feasibility of these advanced modalities in select patients with RHT.
This study has several inherent limitations. First, as the goal of this study was to compare treatment modalities, numerous clinical factors likely influenced the choice of escalating to advanced therapy. As such, we employed three separate propensity score based balancing methods to fairly compare treatment modalities. However, there is likely residual confounding influencing the results of this analysis and our findings should be interpreted within this context. Second, our cohort contained a small number of patients who underwent advanced therapy, and the overall events rates were low. As a result, this study may have been underpowered for identifying significant differences between treatment strategies. This also restricted our ability to directly compare individual treatments modalities further limiting the findings we report. Additionally, ~8% of patients did not have an echocardiographic assessment available for review limiting our ability to identify key thrombus features such as mobility or identifying other anatomical features such as a patent foramen ovale which may have influenced the decision to pursue advanced therapy. Finally, our dataset lacked granularity on particular patient characteristics such as detailed hemodynamic status, right ventricular assessment, and cause of death.
CONCLUSIONS
In summary, this study of patients presenting with RHT identified clinical variables used to select patients for advanced therapies, including younger age and presence of a concurrent PE. When comparing treatment strategies, advanced therapies did not confer a lower rate of in-hospital or 90-day mortality when compared to anticoagulation alone. Future work directed at further evaluating the role of advanced therapy in broader, large patient populations as well as formal comparisons between treatment modalities are needed.
Supplementary Material
CLINICAL PERSPECTIVE:
What is Known:
A right heart thrombus (RHT) is defined as a thrombus that is found within the right atrium or ventricle and when associated with pulmonary embolism has rates of mortality.
The optimal treatment for these patients remains poorly defined as no randomized trials have directly compared anticoagulation to other advanced therapies such as systemic thrombolysis, catheter-based treatments, or surgical thrombectomy.
What the Study Adds:
In this two-center, observational cohort study, we find that advanced therapy for the management of RHT was well tolerated with a high rate of procedural success, although outcomes did not differ between those who underwent advanced therapy and anticoagulation alone.
Important predictors for utilizing advanced treatment include younger age, presence of a concurrent PE, and female sex which may be useful for decisions to escalate care in the future.
SOURCES OF FUNDING:
Dr. Secemsky is funded in part by NHLBI K23HL150290.
DISCLOSURES:
Nathan W. Watson: None. Ido Weinberg: Consultant for Penumbra, Magneto Thrombectomy, Daichi-Sankyo. Andrew B Dicks: None. Brett Carroll: Scientific advisory board for Koya Medical. Institutional research support from Bristol Myers Squibb. Eric A. Secemsky reports grant funding from NIH/NHLBI (K23HL150290), Food & Drug Administration, BD, Boston Scientific, Cook, CSI, Laminate Medical, Medtronic and Philips, consulting and speaking from Abbott, Bayer, BD, Boston Scientific, Cook, Cordis, CSI, Inari, Medtronic, Philips, Shockwave and VentureMed.
Nonstandard Abbreviations and Acronyms:
- RHT
right heart thrombus
- RA
right atrium
- RV
right ventricle
- VTE
venous thromboembolism
- PE
pulmonary embolism
- DVT
deep vein thrombosis
- AIC
Akaike information criterion
- IPTW
inverse probability treatment weighting
- HR
hazard ratio
- OR
odds ratio
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