Population impact, allocation, and technology gaps

CardioNerds (Dr. Jenna Skowronski [Heart Failure Council Chair], Dr. Shazli Khan, and Dr. Josh Longinow) are joined by renowned leaders in the field of AHFTC (Advanced Heart Failure and Transplant Cardiology) and mechanical circulatory support, Dr. Jeff Teuteberg and Dr. Mani Daneshmand to continue the discussion of advanced heart failure therapies by taking a deep dive into the world of durable LVADs (Left Ventricular Assist Devices). In this episode, we will review the history of ventricular assist devices, the basics of LVAD function, selection criteria for LVAD therapy, and surgical nuances of LVAD implantation. Audio Editing by CardioNerds intern, Joshua Khorsandi.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

Pearls

1. There have been significant advances in the field of MCS/LVAD therapy since the first implanted LVAD in the 1960s, to the first FDA approved device in the early 2000’s, to now the HM3 LVAD, with the most important change being a centrifugal flow/magnetically levitated design that led to minimized hemocompatibility-related adverse events (HRAE’s) (MOMENTUM 3 trial comparing HM2 and HM3). 

2. The REMATCH trial in 2001 was a pivotal trial for LVAD therapy, demonstrating that in a population of patients with advanced HF (70% IV inotrope dependent), LVAD therapy significantly improved survival at both 1 and 2 years as compared to medical therapy alone.   

3. MOMENTUM 3 trial was a landmark trial for the HM3 device, showing that in a population of end stage HF patients (86% inotrope dependent, 32% INTERMACS 1-2, and 60% DT strategy), 5-year survival with HM3 was 58% and HM3 had lower HRAE’s compared with HM2. 

4. There are both patient-specific factors and surgical considerations when it comes to candidacy for LVAD therapy. 

5. RV function prior to LVAD is a key determinant for success post-LVAD 

• Many patients being considered for LVAD may not have robust RV function, however, predicting RV failure after LVAD is exceedingly difficult.  
• In general, it doesn’t matter how bad the RV may look on imaging; we care more about the pre-LVAD hemodynamics (look at the PAPi and RA/wedge ratio).  
• What happens in the OR may be the most important determinant of how the RV will do with the LVAD! 

Notes

Notes drafted by Dr. Josh Longinow. 

1. Historical background of heart pumps and LVADs 

The 1960’s ushered in the first ‘LVADs’, when the first air-powered ‘LVAD’ was implanted. It kept the patient alive for four days before the patient expired.  

• The first generation of LVADs were pulsatile pumps  

• The first nationally recognized, FDA approved LVAD was the HeartMate XVE (late 1990s to early 2000s, REMATCH trial). The XVE pump used compressed air (pneumatically driven) to power the pump.  
  • Prior to the XVE, OHT was the standard of care for patients with advanced, end-stage heart failure.  

• The second and third generations of LVADs were non-pulsatile, continuous flow devices and included the HVAD, HM2, and HM3 devices.  

• MOMENTUM 3 was a landmark trial for the HM3 device, showing that in a population of sick patients with end stage HF (86% inotrope dependent, 32% INTERMACS 1-2, and 60% DT strategy), 5-year survival with HM3 was 58% and HM3 had lower HRAE’s compared with HM2.  

• The only pump that is currently FDA approved for implant is the HM3, although other pumps are in clinical trials (BrioVAD system, INNOVATE Trial). 

2. What are LVADs, and how do they work?  

In simplest terms, the LVAD is a heart pump comprised of several key mechanistic components:  

1. Inflow cannula 

2. Mechanical pump  

3. Outflow cannula 

4. Driveline 

5. Controller/Power source 

The HM3 differs from its predecessors (HM2 and HVAD) in several key ways;  

1. HM3 is placed intrapericardial whereas the HM2 was placed pre-peritoneal.  

2. Perhaps most importantly, the HM3 is a fully magnetically levitated, centrifugal flow pump, whereas the HM2 is an axial flow device. 

Axial flow pumps are not magnetically levitated, leading to more friction produced between the ruby bearing’s contact with the pump rotors, and higher rates of hemocompatibility related adverse events (HRAEs, i.e. pump thrombosis) and the HM2 was ultimately discontinued in favor of the HM3 (MOMENTUM 3 trial). 

3. What do the terms ‘Destination Therapy’ (DT) or ‘Bridge to Transplant’ (BTT) mean when it comes to LVADs?  

• When LVADs first came on the stage, EVERYONE was a BTT; these early pumps weren’t designed for long term use (I.e. REMATCH Trial, Heartmate XVE) 

• Destination therapy means the LVAD was placed in leu of transplant because there are contraindications to transplant  
  • REMATCH trial brought about the concept of “Destination therapy”, comparing outcomes in patients (with contraindications for transplant) who received an LVAD vs optimal medical therapy 
• Bridge to transplant means we are placing the LVAD in a patient who may not be a transplant candidate at this moment in time (is too sick, or conversely, not sick enough), but may be down the line  
• Bridge to recovery is another term used when the LVAD is being placed for a patient we think may have a recoverable cardiomyopathy 

4. What are some factors we should consider when assessing a patient’s candidacy for LVAD, in general, and from a surgical perspective?  

Patient factors  

1. Older age might push us towards thinking LVAD rather than transplant 
   • In general, age > 70 is the cutoff for transplant, but this is not a hard cut off and varies institution to institution   

2. In general, think about things that help predict recovery after a major surgery; Frailty and Nutritional status are important, we try to optimize these prior to LVAD implant  

3. Right ventricular function remains the Achilles heel of LV support 
   • We know that needing temporary RV support post LVAD puts you on a different survival curve than patients who don’t need RVAD support 
   • Studies have not been able to successfully predict who will develop RV failure after LVAD implantation 
   • What happens in the time between when the patient goes to the OR and when they get back to the ICU is an important determinant who might develop RV failure post LVAD  
   • Surgical techniques such as implanting the HM3 in the intra-thoracic cavity, rather than intra-pericardial may help maintain LV/RV geometry to help optimize the RV post LVAD  

Surgical considerations for LVAD candidacy 

• Small, hypertrophied LV: HM3 inflow cannula is small, but small hypertrophied ventricles tend towards chamber collapse during systole causing suction, needing to run slower with lower flow rates 
• Chest size/diameter: pumps have gotten so small now, that for adults, these have become less of a consideration 
• BMI: low BMI used to be more of a concern with the older pumps due to where they were placed, and the relative size of the pump itself, not so much now with the smaller HM 3 pumps 
• Calcified LV apex: would increase risk of stroke, bleeding  
• Driveline tunneling becomes a concern in the super obese population, higher risk for driveline infections (might tunnel these driveline’s shorter, and to a less fatty region of the abdomen, could even tunnel out the thoracic cavity in the super obese to limit skin motion)   

5. Is there a role for MCS (i.e. temporary LVAD such as Impella) in pre-habilitation of patients prior to LVAD surgery?  

• The theory of being able to improve systemic perfusion, decongest the organs, and make the patient feel better prior to surgery makes sense, but becomes problematic due to the lack of a hard end point/time for prehabilitation which might risk delays in surgery  

• More likely that it can lead to delay in the surgery, with less-than-optimal benefit; you don’t want to prolong the wait for surgery and increase the risk for complications prior to surgery   

• An Impella 5.5 is currently FDA approved for 2 weeks of support, not 2 months so timing is important to keep in mind 

• It’s unlikely that you will take a patient and convert them from a malnourished, cachectic person in 2 weeks’ time  

6. Is there a role for LVAD therapy in the younger patient population? Should we be thinking of LVAD up front for these patients, with the goal of transplanting down the line?  

• Recovery may be more likely in certain populations, particularly younger females with smaller LV’s; in those populations, perhaps bridge to recovery should be the focus, optimizing them on GDMT etc.  

• The replacement of transplant, with MCS (LVAD) in young patients has become a topic of discussion, because these pumps have become better and better, with the thinking that an LVAD could bridge a patient for 10 years or so, and they could get a transplant later  

• It is still a big unknown, but several concerns exist 
  • Patients who get LVADs might end up with complications that become contraindication to transplant down the line (stroke, sensitization etc)  
  • Patients and providers are more hesitant because of the more recent iteration for the UNOS criteria for OHT listing which no longer gives patients with an uncomplicated LVAD higher priority, and therefore they could end up waiting a longer time for a heart after undergoing LVAD 

References

1. Rose EA, Gelijns AC, Moskowitz AJ, et al. Long-term use of a left ventricular assist device for end-stage heart failure. N Engl J Med. 2001;345(20):1435-1443. doi:10.1056/NEJMoa012175 

2. Mehra MR, Uriel N, Naka Y, et al. A Fully Magnetically Levitated Left Ventricular Assist Device – Final Report. N Engl J Med. 2019;380(17):1618-1627. doi:10.1056/NEJMoa1900486 

3. Mancini D, Colombo PC. Left Ventricular Assist Devices: A Rapidly Evolving Alternative to Transplant. J Am Coll Cardiol. 2015;65(23):2542-2555. doi:10.1016/j.jacc.2015.04.039 

4. Mehra MR, Goldstein DJ, Cleveland JC, et al. Five-Year Outcomes in Patients With Fully Magnetically Levitated vs Axial-Flow Left Ventricular Assist Devices in the MOMENTUM 3 Randomized Trial. JAMA. 2022;328(12):1233-1242. doi:10.1001/jama.2022.16197 

5. Rose EA, Moskowitz AJ, Packer M, et al. The REMATCH trial: rationale, design, and end points. Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure. Ann Thorac Surg. 1999;67(3):723-730. doi:10.1016/s0003-4975(99)00042-9 

6. Kittleson MM, Shah P, Lala A, et al. INTERMACS profiles and outcomes of ambulatory advanced heart failure patients: A report from the REVIVAL Registry. J Heart Lung Transplant. 2020;39(1):16-26. doi:10.1016/j.healun.2019.08.017 

7. Mehra MR, Netuka I, Uriel N, et al. Aspirin and Hemocompatibility Events With a Left Ventricular Assist Device in Advanced Heart Failure: The ARIES-HM3 Randomized Clinical Trial. JAMA. 2023;330(22):2171-2181. doi:10.1001/jama.2023.23204 

8. Mehra MR, Nayak A, Morris AA, et al. Prediction of Survival After Implantation of a Fully Magnetically Levitated Left Ventricular Assist Device. JACC Heart Fail. 2022;10(12):948-959. doi:10.1016/j.jchf.2022.08.002 

9. Bhardwaj A, Salas de Armas IA, Bergeron A, et al. Prehabilitation Maximizing Functional Mobility in Patients With Cardiogenic Shock Supported on Axillary Impella. ASAIO J. 2024;70(8):661-666. doi:10.1097/MAT.0000000000002170