4. Data to Delivery: CHIP-BCIS3 — Microaxial Flow Pump Support for High-Risk Complex PCI with Dr. Saraschandra Vallabhajosyula

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CathMasters host Dr. Li Pang, member of the CardioNerds Interventional Cardiology Council, and expert faculty Dr. Saraschandra Vallabhajosyula discuss the landmark CHIP-BCIS3 trial (Controlled Trial of High-Risk Coronary Intervention with Percutaneous Left Ventricular Unloading), published in the New England Journal of Medicine in 2026. 

Using a representative case of an 84-year-old man with ischemic cardiomyopathy (LVEF 25%), NSTEMI, and severe multivessel calcified coronary artery disease requiring left main bifurcation PCI and calcium modification in a left-dominant coronary system, the episode walks through the background evidence gap, trial design, key results, limitations, and practical implications for interventional cardiologists managing complex high-risk indicated PCI (CHIP). The discussion contextualizes CHIP-BCIS3 within the broader landscape of mechanical circulatory support trials, including BCIS-1, PROTECT II, DanGer Shock, and the upcoming PROTECT IV.

CathMasters is for educational purposes only.

CathMasters is for educational purposes only. Music by Elijah K from Pixabay

Pearls

  1. CHIP-BCIS3 showed no benefit of elective microaxial flow pump (Impella CP) support over standard care PCI in patients with severely impaired LV function undergoing complex PCI (win ratio 0.85; 95% CI 0.63–1.15). A signal toward higher cardiovascular death was observed in the mAFP arm (26.7% vs 14.5%; HR 1.91; 95% CI 1.11–3.30), warranting caution.
  2. “The pump is not a bulletproof vest.” The presence of a mechanical circulatory support device should not create a false sense of security that leads operators to pursue more aggressive, single-session complete revascularization. Interventionalists have the privilege of staging procedures — and should use it when appropriate.
  3. Right heart catheterization before high-risk PCI provides useful information to fully characterize the hemodynamic substrate (cardiac output, filling pressures, pulmonary hypertension) and guide decision-making regarding MCS, rather than reflexively placing a device based on anatomy alone.
  4. Not all CHIP is created equal. The trial enrolled a heterogeneous population — left main bifurcation PCI, multivessel calcium modification, and retrograde CTO — each carrying different prognostic implications and procedural risk profiles. Retrograde CTO, performed primarily for symptom relief, may not carry the same prognostic weight as left main revascularization.
  5. Vascular access planning matters. CHIP-BCIS3 mandated pre-procedural vascular imaging (CT, ultrasound, or invasive angiography) before mAFP insertion, contributing to record-low vascular complication rates (16.9% mAFP vs 10.6% standard care, mostly minor). This rigorous protocol may underestimate real-world vascular complications but sets a standard for best practice.

Notes

1. Background and Evidence Gap

  • Complex PCI in patients with severely impaired LV function carries a high risk of hemodynamic collapse, periprocedural MI, and death. Percutaneous mechanical circulatory support (pMCS) has been increasingly used to mitigate these risks — a strategy termed “Protected PCI.”
  • Prior to CHIP-BCIS3, no randomized trial had compared the elective use of a microaxial flow pump with PCI without planned MCS. The existing evidence base included:
    • BCIS-1 (2010; long-term follow-up 2013): 301 patients with LVEF ≤30% and BCIS Jeopardy Score ≥8 randomized to elective IABP vs. no planned IABP during high-risk PCI. No difference in the primary composite of MACCE at 28 days (15.2% vs 16.0%). However, long-term follow-up at a median of 51 months showed a 34% relative reduction in all-cause mortality with elective IABP (HR 0.66; 95% CI 0.44–0.98).
    • PROTECT II (2012): 452 patients randomized to Impella 2.5 vs. IABP during high-risk PCI. Stopped early for futility — no difference in 30-day MAE (35.1% vs 40.1%). Impella provided superior hemodynamic support. A trend toward lower 90-day MAE was observed in the per-protocol Impella arm.
    • PROTECT III: A post-marketing registry (not a randomized trial) of 1,143 patients showing lower 90-day MACCE with Impella 2.5/CP compared to historical PROTECT II controls.
  • The 2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization gave a Class 2b (Level of Evidence B-R) recommendation: “In selected high-risk patients, elective insertion of an appropriate hemodynamic support device as an adjunct to PCI may be reasonable.”
  • Despite limited evidence, the FDA approved Impella for high-risk PCI in 2015 (severe LV dysfunction) and expanded the indication in 2018 (mildly reduced EF), leading to rapid adoption.

2. CHIP-BCIS3 Study Design and Methodology

  • Design: Prospective, multicenter, open-label, randomized controlled trial
  • Funder: UK National Institute for Health and Care Research (NIHR) — independent of device manufacturer
  • Sites: 21 NHS hospitals in the United Kingdom
  • Enrollment: August 2021 – December 2024; 300 patients randomized 1:1
  • Intervention: Elective Impella CP insertion prior to PCI (mAFP arm, n=148) vs. standard care PCI without planned MCS (n=152)
  • Inclusion criteria (all three required):
    • Severely impaired LV systolic function: LVEF <35%, or severe MR with LVEF <40%
    • Large area of jeopardized myocardium: BCIS Jeopardy Score >8/12
    • Complex coronary intervention: (a) True left main bifurcation PCI with CTO of RCA or left-dominant system; (b) Multivessel calcium modification involving LM, final patent conduit, or SYNTAX ≥32; or (c) Retrograde CTO PCI
  • Exclusion criteria: Cardiogenic shock or STEMI at randomization
  • Primary outcome: Hierarchical composite analyzed by win ratio — death from any cause, disabling stroke, spontaneous MI, hospitalization for cardiovascular causes, and periprocedural myocardial injury (minimum 12-month follow-up)
  • Key protocol features:
    • Pre-procedural vascular imaging (CT, ultrasound, or invasive angiography) mandated before mAFP insertion
    • Complete revascularization encouraged during the index procedure; staged PCI required pre-specification
    • Bailout MCS (IABP or VA-ECMO) permitted in the standard-care arm

3. Baseline Characteristics

  • Well-balanced between groups (slight excess of diabetes in mAFP arm)
  • 83% male; median age 73 years; 85% Caucasian, 12% South Asian
  • 76% presented with acute coronary syndrome
  • 40% had significant angina (CCS III/IV) or heart failure symptoms (NYHA III/IV)
  • Median LVEF: 27% (both groups)
  • Median BCIS Jeopardy Score: 12/12 (maximum jeopardy)
  • Median SYNTAX score: 38 (high complexity)
  • 72% underwent left main PCI; 81% required atherectomy; 27% underwent retrograde CTO

4. Procedural Details

  • mAFP insertion unsuccessful in 4 patients (3%) due to obstructive PAD
  • Bailout MCS in standard-care arm: 9 patients (6.0%) — 8 IABP, 1 Impella CP
  • Staged PCI: 6.8% in mAFP arm vs. 17.9% in standard-care arm (more single-session complete revascularization in the mAFP arm)
  • Median procedure duration: 188 min (mAFP) vs. 139 min (standard care)
  • Median lesions treated: 3 (mAFP) vs. 2 (standard care)
  • Calcium modification: 71% in both arms; IVL was the primary modality (81% vs 66%), followed by rotational atherectomy (55% vs 59%)
  • Intravascular imaging: 91% vs 93% (high utilization in both arms)
  • Median mAFP support time: 134 min (device removed at end of PCI in most cases)

5. Key Results

  • Primary outcome (win ratio): 0.85 (95% CI 0.63–1.15; P=0.30) — no significant difference between mAFP and standard care. 36.6% of pairwise comparisons favored mAFP; 43.0% favored standard care.
  • All-cause death: 47 patients (32.6%, mAFP) vs. 33 patients (23.4%, standard care); HR 1.54 (95% CI 0.99–2.41) — numerically higher in the mAFP arm, borderline significance.
  • Cardiovascular death (prespecified secondary outcome): 26.7% vs. 14.5%; HR 1.91 (95% CI 1.11–3.30) — significantly higher in the mAFP arm, with an absolute increase of 12.2 percentage points at 24 months.
  • Periprocedural myocardial injury (per patient): 61.7% in the mAFP group compared to 50.0% with standard care (RR 1.23; 95% CI 0.99–1.54). While numerically higher in the pump cohort, this did not reach statistical significance. Note: While the primary manuscript reports per-patient data, the podcast discussion highlights “per procedure” results from Supplementary Table 10 (61% vs 44%; 95% CI 1.11–1.75), suggesting a more pronounced signal of injury per intervention.
  • Vascular complications: 16.9% (mAFP) vs. 10.6% (standard care) — mostly minor; record-low rates attributed to mandated vascular imaging protocol.
  • Procedural complications (VT/VF, CPR, pulmonary edema, prolonged hypotension): similar between groups.

6. Interpretation and Clinical Implications

  • CHIP-BCIS3 challenges the prevailing assumption that elective Impella CP support during high-risk PCI improves outcomes. The trial found no benefit and a concerning signal toward increased cardiovascular death.
  • Several factors may explain the findings:
    • “Go all-in” behavior: The mAFP arm had longer procedures, more lesions treated, and less staged PCI — suggesting operators pursued more aggressive single-session revascularization when the pump was in place. This may have contributed to higher periprocedural myocardial injury.
    • Periprocedural myocardial injury: The mAFP arm had significantly more myocardial injury per procedure, contrary to the hypothesis that the pump would ameliorate ischemia. Whether this contributed to the observed CV mortality difference remains unclear.
    • Short support duration: Median support time of 134 minutes suggests the device was removed at the end of PCI in most cases, without extended post-procedural hemodynamic support — a practice that may not allow recovery from myocardial stunning.
  • The trial does not mean MCS should never be used in high-risk PCI. Rather, it argues against routine, elective use and supports individualized decision-making based on hemodynamic assessment.
  • Importantly, these results apply to elective/non-emergent high-risk PCI and cannot be extrapolated to cardiogenic shock, where the DanGer Shock trial demonstrated a mortality benefit with Impella CP in STEMI-related cardiogenic shock (HR 0.74; 95% CI 0.55–0.99).

7. Limitations

  • Sample size: 300 patients — relatively small, though event rates exceeded pre-trial estimates, reducing the risk of type II error.
  • Open-label design: Operators knew the treatment assignment, which may have influenced procedural behavior (more aggressive revascularization in the mAFP arm).
  • Heterogeneous CHIP population: Retrograde CTO, left main bifurcation PCI, and multivessel calcium modification carry different risk profiles and prognostic implications — lumping them together may dilute or confound treatment effects.
  • Vascular complication rates may be artificially low: The mandated pre-procedural vascular imaging protocol may not reflect real-world practice, potentially underestimating the downside of large-bore access.
  • Short post-procedural support: Most devices were removed at the end of PCI. The trial did not evaluate extended hemodynamic support or standardized weaning protocols.
  • UK-only enrollment: 85% Caucasian population; generalizability to other healthcare systems and demographics requires consideration.
  • No hemodynamic substudy data yet: A prespecified hemodynamic substudy may provide mechanistic insight into the role of LV unloading and myocardial stunning.
  • Diverging mortality curves: Death and adverse event curves appeared to diverge in favor of standard care over time, suggesting longer follow-up is unlikely to reverse the findings.

8. Case Application

  • The case patient (84-year-old, LVEF 25%, NSTEMI, left-dominant system with distal LM 80%, severe multivessel calcified CAD) meets all CHIP-BCIS3 inclusion criteria.
  • The team performed right heart catheterization first (CO 4.3 L/min, CI 2.4, RAP 10, PCWP 15) — confirming compensated hemodynamics.
  • Given the complexity (DK CRUSH bifurcation stenting for LM, IVL in LAD and LCx, left-dominant system with entire coronary circulation dependent on the LM), the team elected to proceed with Impella CP support.
  • Key decision points informed by CHIP-BCIS3:
    • Staging was considered but not feasible for the LM bifurcation component
    • RHC was performed to characterize hemodynamic reserve before committing to MCS
    • Post-PCI hemodynamics were reassessed on Impella P2 support before removal
    • Device was removed with pre-deployed Perclose sutures without complications

9. Future Directions

  • PROTECT IV: Prospective, multicenter, randomized trial (n=1,252) comparing Impella CP supported PCI vs. PCI with or without IABP in patients with LVEF ≤40% and complex CAD deemed at excessive surgical risk. Primary endpoint: composite of all-cause death, stroke, MI, unplanned revascularization, durable LVAD/transplant, or CV hospitalization at 3 years. Results will provide the largest randomized dataset in this space.
  • CHIP-BCIS3 hemodynamic substudy: Prespecified substudy evaluating detailed hemodynamic assessments before and during PCI — may clarify the mechanistic role of LV unloading and myocardial stunning.
  • Intra-procedural hemodynamic monitoring: Future studies should evaluate real-time parameters such as loss of Impella pulsatility (indicating LV standstill during balloon inflation), which may guide procedural strategy (e.g., shorter balloon inflations, switching atherectomy modality).
  • Post-procedural MCS management: Standardized weaning protocols and extended post-procedural support strategies need investigation — the optimal duration of hemodynamic support after high-risk PCI remains undefined.
  • Patient selection refinement: Better tools to identify which CHIP patients may benefit from MCS (e.g., those with the most tenuous hemodynamics, single-vessel-dependent circulations) vs. those who can safely undergo PCI without support.

References

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  2. ⭐ Ryan M, Ezad SM, Webb I, et al. Percutaneous left ventricular unloading during high-risk coronary intervention: rationale and design of the CHIP-BCIS3 randomized controlled trial. Circ Cardiovasc Interv. 2024;17(3):e013367. doi:10.1161/CIRCINTERVENTIONS.123.013367. https://pubmed.ncbi.nlm.nih.gov/38410944
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  4. ⭐ Perera D, Stables R, Clayton T, et al. Long-term mortality data from the Balloon Pump-Assisted Coronary Intervention Study (BCIS-1): a randomized, controlled trial of elective balloon counterpulsation during high-risk percutaneous coronary intervention. Circulation. 2013;127(2):207-212. doi:10.1161/CIRCULATIONAHA.112.132209. https://pubmed.ncbi.nlm.nih.gov/23224207
  5. O’Neill WW, Kleiman NS, Moses J, et al. A prospective, randomized clinical trial of hemodynamic support with Impella 2.5 versus intra-aortic balloon pump in patients undergoing high-risk percutaneous coronary intervention: the PROTECT II study. Circulation. 2012;126(14):1717-1727. doi:10.1161/CIRCULATIONAHA.112.098194.
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  8. Rihal CS, Naidu SS, Givertz MM, et al. 2015 SCAI/ACC/HFSA/STS clinical expert consensus statement on the use of percutaneous mechanical circulatory support devices in cardiovascular care. J Am Coll Cardiol. 2015;65(19):e7-e26. doi:10.1016/j.jacc.2015.03.036.
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