The FLASH registry presents a real world exercise of the previously published single arm Flare trial2 which resulted in meaningful improvement of baseline RV/LV ratio 48 hours following Flow Triever catheter embolectomy in intermediate risk PE patients. In FLASH, Toma at al. are looking beyond short term outcome surrogates, and shift the spotlight on device safety, comprehensive hemodynamic analysis, and measure of early all-cause mortality.
- The primary endpoints were defined as: composite of MAE within 48 hours including: device related mortality, major bleeding, intra-procedural device or procedure related adverse events.
- The secondary endpoints were defined as: impact on acute hemodynamic, procedural measures, 48 hour all-cause mortality and long-term outcomes.
The registry was set to evaluate 500 acute PE patients from 50 centers in the US managed with Flow Triever facilitated thrombectomy. Of the first 230 analyzed patients from 19 US centers (mean age 60.7; 52.2% men) majority (93.0%) were deemed intermediate risk while remainder qualified as high-risk PE. Among reported patients 38.3% had contraindication to lytics, mean sPESI score and RV/LV ratio were equal at 1.6 + 0.5, and positive biomarkers were present in 96.3% of the subjects.
There were encouraging procedural results showing a single case of access site complication (0.4%), reasonable device time averaging 46 minutes and median hospitalization length of 3 days with no real need for ICU stay.
There was 0% mortality throughout 48 hours post-procedure, with 3 major bleeds (all non-ICH), and 0 intra-procedural device and procedure related AE.
The analysis of hemodynamic data revealed immediate mean heart rate drop from 113.2+ 16.8 to 90.5+ 16.5 bpm (p<0.0001), where 77% of patients were tachycardic pre-procedure and only 24.6% remained so immediately after (p<0.0001). While on-table mean PA pressure dropped on average 7.0mmHg (21.9%) from 32.0+8.2mmHg to 25.0+8.2mHg (p<0.0001), the mean cardiac index in 23.5% of the patients presenting with CI<2.0 L/min/m2 increased from 1.7+0.2 to 1.9+0.4L/min/m2 (p<0.01). Right ventricular stroke work index decreased on average by 1.6 g/m/beat/m2 (19.8%) with p<0.0001, while total pulmonary vascular resistance dropped on average by 1.5mmHg/L/min (23.8%), (p<0.0001).
The average dyspnea score measured by mMRC scale declined from 3.0 before thrombectomy to 1.4 at 48 hours (P < 0.0001).
The results of the FLASH registry interim analysis point at excellent safety profile of Flow Triever system when used in the acute thrombus evacuation in predominantly intermediate risk PE as observed in the short 48hour post-procedural period. Despite relatively large bore access size (20-22Fr), there were no reported deaths, and only 1 case of access hematoma and 3 non-ICH major bleeds were reported, all in the patients receiving adjuvant lytic. Significant on-table improvements in all recorded hemodynamic parameters point towards robust effects of acute RV outflow decompression and possibly prevention of obstructive shock where teetering RV failure may have been suggested in nearly quarter (23.5%) of the patients presenting with CI <2.0.
Drs. Zaric and Ayafor: Pulmonary embolism continues to rank as the third leading cause of cardiovascular mortality, trailing only myocardial infarction and stroke, In the background of high 90-day mortality amongst patients hospitalized with intermediate-risk PE reaching 15% and those presenting with high-risk PE nearing 40%, the interest and enthusiasm for catheter-based approach continues to grow. However, the evidence supporting catheter-based strategies remains less robust, studies are smaller and generally powered to evaluate short term surrogate outcomes rather than hard endpoints such are the data on lytic therapy which appear to offer mortality benefit when compared to anticoagulation alone3. Two largest meta-analyses of thrombolytic trials reported reduction in all-cause mortality, which persisted even when restricted only to those with intermediate-risk PE. Unfortunately, increased bleeding risk in systemic lysis continues to offset some of the benefits, especially ICH which is estimated to occur at 2% in clinical trials and between 3-5% outside of the trial reported data. The Flow Triever System by Inari Medical is one of the two catheter based systems that received FDA approval specific to PE treatment in attempt to offer safer bleeding profile without offsetting the efficacy. Results from the single-arm prospective Flare trial are now affirmed in the interim data analysis of the FLASH registry where particular attention has been brought to the utility of hemodynamic data at presentation. This approach alone may be able to point out those with teetering RV failure who are likely to benefit from early catheter-based interventions, and whose risk may be otherwise underestimated. This was already tested in earlier published retrospective study by Toma al, where 34 patients with high-intermediate and high-risk PE underwent the same catheter-based treatment showing 97% survival rate to the mean follow up of 7 months4. Striking survival rate in the later study is now serving as the blueprint for upcoming FLAME trial, set to start next year as probably the largest study to-date to evaluate Flow Triever technology in those presenting exclusively with massive PE. The stakes are high and interventional arena seems to be moving in the right direction as upcoming FLAME results may in fact change the paradigm and ultimately affect the treatment guidelines for those presenting with massive PE.
Dr. Iliadis: Current study exemplifies both the difficulties in assessing end points in PE management given the lack of large data pools and common outcome variables while offers a strategy with clinical and objective endpoints for catheter based treatment. In this small study, It is encouraging that immediate reduction in mean PA pressure, clinical variables of heart rate and Modified Medical Research Council (mMRC) dyspnea score were noted and correlates with prior studies to suggested a sustained and persistent benefit of catheter based therapies for Submassive and massive Pulmonary embolism. As more similar data becomes available, clinical guidelines from professional organizations such as SCAI, PERT consortium and others may suggest variables such as these as standards for treatments for PE similar to Door-to-Balloon times used for Acute Myocardial infarction.
- Toma C. Acute hemodynamic improvement with percutaneous mechanical thrombectomy in real-world pulmonary embolism population: interim results of the FLASH registry. Presented at: TCT 2020. October 18, 2020
- Tu T, Toma C, Tapson VF, Adams C, Jaber WA, Silver M, Khandhar S, Amin R, Weinberg M, Engelhardt T, Hunter M, Holmes D, Hoots G, Hamdalla H, Maholic RL, Lilly SM, Ouriel K, Rosenfield K; FLARE Investigators. A Prospective, Single-Arm, Multicenter Trial of Catheter-Directed Mechanical Thrombectomy for Intermediate-Risk Acute Pulmonary Embolism: The FLARE Study. JACC Cardiovasc Interv. 2019 May 13;12(9):859-869. doi: 10.1016/j.jcin.2018.12.022. PMID: 31072507.
- Giri J, Sista AK, Weinberg I, Kearon C, Kumbhani DJ, Desai ND, Piazza G, Gladwin MT, Chatterjee S, Kobayashi T, Kabrhel C, Barnes GD. Interventional Therapies for Acute Pulmonary Embolism: Current Status and Principles for the Development of Novel Evidence: A Scientific Statement From the American Heart Association. Circulation. 2019 Nov 12;140(20):e774-e801. doi: 10.1161/CIR.0000000000000707. Epub 2019 Oct 4. PMID: 31585051.
- Toma C, Khandhar S, Zalewski AM, D'Auria SJ, Tu TM, Jaber WA. Percutaneous thrombectomy in patients with massive and very high-risk submassive acute pulmonary embolism. Catheter Cardiovasc Interv. 2020 Aug 31. doi: 10.1002/ccd.29246. Epub ahead of print. PMID: 32866345.