Use of mechaNical left ventricuLar unlOADing in Complex Higher-risk Indicated Procedures

During the last three to four decades percutaneous coronary intervention (PCI)
tools and techniques have improved immensely (1). Currently, PCI is the most
widely used approach for myocardial revascularization. In general, elective PCI
is considered a safe and relatively low-risk procedure(2).
However, patients with left main or complex coronary lesions or impaired left
ventricular function remain at high risk of peri-procedural and post-procedural
hemodynamic instability and death (3, 4).
Mechanical circulatory support (MCS) devices, such as intra-aortic balloon pump
(IABP) and Impella (Impella 2.5 and CP), have emerged as potential tools to
avoid hemodynamic instability during these CHIP coronary interventions. These
devices have shown to improve hemodynamics / cardiac output during complex PCI
procedures, although the benefit of mechanical circulatory support in CHIP PCI
remains debated and no clear benefit on patient outcomes has been shown (5-7).
Although a recent large scale analysis favoured Impella as opposed to IABP (9).
The use of these devices, especially Impella, is associated with increased risk
for complications such as bleeding (6, 11). The use of MCS, and therefore
better peri-procedural hemodynamic support, needs to be balanced out against
the potential risk for MCS related complications.

Recently the PulseCath iVAC 2L was introduced. This is a pulsatile pump, placed
in the left ventricle, that ejects blood into the ascending aorta at a flow up
to 2L/min (12). Theoretically, pulsatility maintains the physiological vascular
responses and endothelial function at the level of the -systemic and -micro
circulation and might offer benefit when compared with continues flow devices
such as Impella (13). In contrast, IABP (which also offers pulsatile support),
lacks the possibility of active unloading. Therefore, the combination of those
features in the PulseCath iVAC2L is unique.

Recent studies performed with the PulseCath iVAC2L in the setting of CHIP PCI
demonstrated hemodynamic advantages with reductions in afterload, increases in
stroke volume and cardiac output. Also, the device was deemed safe in terms of
complications (13, 14). Samol et al. showed in a prospective cohort study that
IVAC2L was comparable to Impella in terms of feasibility and safety and to
ensure stable hemodynamic conditions, also if complications occur. (15) Other
advantages of the IVAC2L are its relatively simple use, and lower costs
compared to other mechanical circulatory support like the Impella family.
Given the fact that the IVAC2L is connected to an IABP console, the possibility
of widespread use adds an even greater advantage.

So far, MCS facilitated CHIP has not been proven beneficial compared to a
conservative (non-supported) high-risk procedure. Although high-risk criteria
parameters: coronary anatomy (location and complexity), co-morbid conditions,
and concomitant cardiac disease (structural or valvular disease, left
ventricular dysfunction) are well known, no intrinsic value of each of the
components is determined. The recent PULSE trial shed some light on this vacuum
by showing additional hemodynamic benefit for patients with mitral
regurgitation, for patients who presented with an acute coronary syndrome (ACS)
and who had higher filling pressures at baseline (13). Therefore,
MCS-facilitated high-risk PCI might be beneficial if used in (left-sided)
congested patients with low hemodynamic tolerance. However, due to the low
number of patients enrolled and non-randomized nature of this study,
conclusions should be drawn with caution. To this day, no randomized controlled
trials have been executed with the PulseCath iVAC2L in this subset of CHIP
patients who are thought to benefit from an MCS-facilitated PCI. Its place in
the setting of CHIP PCI remains to be elucidated.

1. Neumann FJ, Sousa-Uva M, Ahlsson A, Alfonso F, Banning AP, Benedetto U, et
al. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J.
2019;40(2):87-165.
2. Silvain J, Zeitouni M, Paradies V, Zheng HL, Ndrepepa G, Cavallini C, et al.
Procedural myocardial injury, infarction and mortality in patients undergoing
elective PCI: a pooled analysis of patient-level data. Eur Heart J.
2021;42(4):323-34.
3. Khalid N, Rogers T, Torguson R, Zhang C, Shea C, Shlofmitz E, et al.
Feasibility and Safety of High-Risk Percutaneous Coronary Intervention Without
Mechanical Circulatory Support. Circ Cardiovasc Interv. 2021;14(6):e009960.
4. Bouisset F, Ribichini F, Bataille V, Reczuch K, Lhermusier T, Dobrzycki S,
et al. Clinical Outcomes of Left Main Coronary Artery PCI With Rotational
Atherectomy. Am J Cardiol. 2022;186:36-42.
5. O'Neill WW, Kleiman NS, Moses J, Henriques JP, Dixon S, Massaro 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):1717-27.
6. Perera D, Stables R, Clayton T, De Silva K, Lumley M, Clack L, 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):207-12.
7. O'Neill WW, Anderson M, Burkhoff D, Grines CL, Kapur NK, Lansky AJ, et al.
Improved outcomes in patients with severely depressed LVEF undergoing
percutaneous coronary intervention with contemporary practices. Am Heart J.
2022;248:139-49.
8. Kuno T, Takagi H, Ando T, Kodaira M, Numasawa Y, Fox J, et al. Safety and
efficacy of mechanical circulatory support with Impella or intra-aortic balloon
pump for high-risk percutaneous coronary intervention and/or cardiogenic shock:
Insights from a network meta-analysis of randomized trials. Catheter Cardiovasc
Interv. 2021;97(5):E636-e45.
9. Lansky AJ, Tirziu D, Moses JW, Pietras C, Ohman EM, O'Neill WW, et al.
Impella Versus Intra-Aortic Balloon Pump for High-Risk PCI: A
Propensity-Adjusted Large-Scale Claims Dataset Analysis. Am J Cardiol. 2022.
10. Syed AI, Kakkar A, Torguson R, Li Y, Ben-Dor I, Collins SD, et al.
Prophylactic use of intra-aortic balloon pump for high-risk percutaneous
coronary intervention: will the Impella LP 2.5 device show superiority in a
clinical randomized study? Cardiovasc Revasc Med. 2010;11(2):91-7.
11. Ancona MB, Montorfano M, Masiero G, Burzotta F, Briguori C, Pagnesi M, et
al. Device-related complications after Impella mechanical circulatory support
implantation: an IMP-IT observational multicentre registry substudy. Eur Heart
J Acute Cardiovasc Care. 2021;10(9):999-1006.
12. Van Mieghem NM, Daemen J, Lenzen MJ, Zandstra R, Malkin O, van Geuns RJ.
The PulseCath iVAC 2L left ventricular assist device: conversion to a
percutaneous transfemoral approach. EuroIntervention. 2015;11(7):835-9.
13. Bastos MB, McConkey H, Malkin O, den Uil C, Daemen J, Patterson T, et al.
Effect of Next Generation Pulsatile Mechanical Circulatory Support on Cardiac
Mechanics: The PULSE Trial. Cardiovasc Revasc Med. 2022;42:133-42.
14. den Uil CA, Daemen J, Lenzen MJ, Maugenest AM, Joziasse L, van Geuns RJ, et
al. Pulsatile iVAC 2L circulatory support in high-risk percutaneous coronary
intervention. EuroIntervention. 2017;12(14):1689-96.
15. Samol A, Wiemer M, Kaese S. Comparison of a pulsatile and a continuous flow
left ventricular assist device in high-risk PCI. Int J Cardiol. 2022;360:7-12.

The primary objective of the UNLOAD-CHIP is to investigate the combined
clinical endpoint (as described in primary and secundary endpoints).

The current study is an investigator initiated, randomized, open label,
multi-center clinical trial.
All patients assigned to have a complex higher-risk indicated procedure (CHIP)
based on a formal local heart team decision will be screened for potential
inclusion in the study.
Patients will be eligible for inclusion in the randomized study after
consideration of in- and exclusion criteria. Subsequently patients will be
approached for study participation by their cardiologist. The patient
information folder (PIF) and consent form will be provided to the patient by a
study team member. Patients will have at least 24 hours to consider
participation. An independent physician will be available for extra
information, if desired. After this period of consideration, written informed
consent is obtained and patients will be planned for CHIP PCI according to
standard practice in adherence to international guidelines. Patients will also
be randomized and stratified based on severe mitral regurgitation. At baseline,
all patients underwent transthoracic echocardiography (TTE) and pre-procedural
CT angio¬graphy or Doppler of the femoral arteries to determine the quality of
the access vessel. A common femoral artery minimum diameter of 6 mm is required
to accommodate the iVAC2L. On the cathlab the pulmonary artery catheter (PAC)
is placed and pulmonary capillary wedge pressure (PCWP), right arterial
pressure (RAP), pulmonal artery pressure (PAP), cardiac index (CI), - output
(CO) and left ventricular end diastolic pressure (LVEDP) will be determined -
pre -peri and -post procedural together with blood pressure and heart rate.
In subjects randomized to the treatment arm, ultrasound-guided access to the
common femoral artery is obtained. The 17 Fr PulseCath iVAC 2L catheter is
introduced into the left venticle. After this PCI was routinely perfomed by
radial artery access.
After the procedure a vascular preclosure technique is used (two Perclose
ProGlide®). Post-PCI, patients underwent echocardiography to investigate aortic
valve injury or increase in aortic regurgitation. Patients were followed up by
phone after 30 days to assess outcomes. After this visit the study ends for the
participant.

Use of the pulsecath iVAC2L during high risk PCI

Percutaneous insertion of the Pulsecath iVAC2L has the following risks:
-Acces site bleeding/haematoma 1-30%
-Vascular damage, possibily requiring surgery 1-5%
-Local infection (1%)
-Limb ischemia.(2%)
-Stroke (2%)
-Hemolysis (2-20%)

Extensive blood loss can lead to need for blood transfusion.

However, if the protocol is closely followed, adverse effects are predictiable.
There exist protocols how to insert and remove the device.
De adverse effect are reversible, except stroke.

De pump will be placed by the femoral artery. It will happen using local
anesthesia, and this can give temporary pain/unease. The same applies to the
PAC placement that is placed in the femoral vein. The patiënt will have to lay
down still, but this will be nessecary during the normal procedure aswell.
In case of adverse effects this can be mentally difficult, however the disease
will probaly be even more demanding.