Summary of Evidence

Uses of implantable VADs for bridge to recovery, bridge to heart transplant, or destination therapy are supported by the FDA-approved indications for these devices, and by clinical practice guidelines and position statements from specialty societies such as the American Heart Association, American College of Cardiology Foundation, and the Heart Failure Society of America. Other uses of implantable VADs are not supported by peer-reviewed medical literature or by recommendations from the cardiovascular specialty societies.

The total artificial heart device provides a bridge to transplantation for individuals who have no other reasonable medical or surgical treatment options and is supported by the FDA-approved indications, clinical practice guidelines,  and position statements from specialty societies.

Percutaneous ventricular assist devices have been used to provide mechanical assistance for a failing heart for more than a decade. The FDA has approved several such devices for short term use. These devices are used as a bridge to other more permanent solutions in patients with severely compromised cardiac status. Best practices are not clearly defined, partially due to the difficulty in studying this population. Research indicates that pVADS may have a benefit over other alternatives such as intra-aortic balloon pumps or extracorporeal membrane oxygenation (ECMO) for some subpopulations of patients. Major cardiology professional societies have issued a joint consensus statement indicating potential scenarios where patients may benefit from use.

Rationale

The 2009 American College of Cardiology/American Heart Association (ACC/AHA) Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult included reference to consideration of a left ventricular assist device as permanent or “Destination Therapy” as being reasonable in highly selected individuals with refractory end-stage heart failure and an estimated 1-year mortality of over 50% with medical therapy. The ACC/AHA document added that use of mechanical circulatory assist devices for short-term circulatory support in individuals who are expected to recover from a major cardiac insult is an area of intense investigation. Most clinical experience currently available with these devices has been derived from their use in individuals being “bridged” to transplant. Since this guideline, multiple guidelines and consensus statements regarding mechanical circulatory support (MCS) devices have been updated and /or released. 

For individuals who have end-stage heart failure who receive a total artificial heart (TAH) as a bridge to transplant, compared with VADs, the evidence for TAHs in these settings is less robust. However, given the lack of medical or surgical options for these patients and the evidence case series provide, TAH is likely to improve outcomes for a carefully selected population with end-stage biventricular heart failure awaiting transplant who are not appropriate candidates for a left VAD. For individuals who have end-stage heart failure who receive a TAH as destination therapy, the evidence includes 2 case series. 

For individuals with cardiogenic shock who receive a percutaneous ventricular assist device (pVAD), the evidence includes RCTs, observational studies, and systematic reviews. RCTs of pVAD versus intra-aortic balloon pump (IABP) for patients in cardiogenic shock do report higher complication rates with pVAD use. Comparative observational studies and a long-term follow-up study were consistent with the RCT evidence. Results published from observational studies (Basir, 2019; Tehrani, 2019) support the use of pVADs in cardiogenic shock protocol-based approach emphasizing “best practices” across the country and as a guide in clinical decision-making. 

For individuals who undergo high-risk cardiac procedures who receive a pVAD, the evidence includes RCTs, observational studies, and systematic reviews of these trials. Two non-randomized studies have compared ventricular tachycardia (VT) ablation with pVAD or IABP. Both studies verified that patients who had pVAD support spent less time in unstable VT than patients without pVAD support. However, the current evidence does not support conclusions about the use of pVAD for VT ablation. 

Vranckx and colleagues (2008) reported their 6-year experience with the TandemHeart. Between September 2000 to July 2006, this device supported the circulation of 23 patients (mean age of 59 years, range of 46 to 74) who were admitted for high-risk (either emergency or elective) PCI. Successful implantation was achieved in 100 % of patients. The mean time for implementation of circulatory support was 35 mins (range of 16 to 62). The index PCI was successful in all patients except 2. A pump flow up to 4L/min was achieved with significant reduction of LV filling pressures, pulmonary capillary wedge pressure, and with significant increase of systemic arterial pressures. Duration of support ranged from 1 to 222 hrs (mean of 31 +/- 49.8). Five patients died with the TandemHeart in place, 4 of whom were in irreversible cardiogenic shock at admission. Mild-to-moderate access site bleeding was seen in 27 % of patients. Core temperature (Ct) decreased to less than 36.5 degrees C in 6 patients, profound hypothermia (Ct less than 35 degrees C) was observed in 2 patients. There was no technical device failure. The authors concluded that the TandemHeart provides effective, total LV support in very high-risk PCI settings. The rate of device-related cardiac and vascular complications was acceptable.

Al-Husami et al (2008) described their experience of patients, from December 2005 through May 2007 who underwent PCI with severely depressed LV systolic function and complex coronary lesions. The complex coronary lesions included multiple vessel coronary artery disease, left main (LM) coronary artery disease, calcified coronary lesions and bypass graft disease. All patients were clinically assessed to be at too high of a risk for circulatory collapse without maximal hemodynamic support while they underwent high-risk PCI.The TandemHeart PTVA device may be able to provide the necessary circulatory support needed to enhance procedural success and patient safety during high-risk PCI. These investigators implanted the TandemHeart PTVA device in 6 patients who underwent high-risk PCI. There was unanimity among several physicians in the authors' institution that each patient was an exceptionally high-risk for circulatory collapse due to the anticipated procedural complexity. The average ejection fraction was 33 % (range of 15 to 65 %); 5 of the patients were considered to be at an unacceptably high-risk for coronary artery bypass surgery. These researchers had a 100 % success rate with implantation of the TandemHeart PTVA device. Five of the 6 patients were alive at 30 days post-procedure. One patient died 3 days after the procedure due to multi-organ failure. A vascular surgeon performed the removal of the devices with no associated complications. The authors concluded that these findings demonstrated that hemodynamic support could be achieved safely, efficiently and effectively by the TandemHeart PTVA device in anticipation of high-risk PCI.

In 2017, Mandawat and Rao published a review of outcomes of patients with cardiogenic shock (CS), the hemodynamics of CS, and hemodynamic effects of percutaneous mechanical circulatory support devices. The authors note that despite a high rate of early revascularization and use of intra-aortic balloon pump counterpulsation (IABP) therapy, the prognosis of patients with cardiogenic shock has remained poor. The literature for and against use of commercially-available devices: the IABP, the Impella system, the TandemHeart, and VA-ECMO were reviewed. The authors conclude that any attempt to improve outcomes in CS should begin with early identification. Among the many challenges that remain include how best to pair the right patient with the right device at the right time. AMI patients with CS appear to have the worst prognosis, while patients with CS status post cardiac surgery with acute RV failure appear to fare the best. Data from the published studies with a focus on the time course of CS indicates that percutaneous MCS has a limited ability to change outcome if initiated when overt multi-organ dysfunction has already occurred. Accordingly, the authors suggest that perhaps MCS should not be considered the treatment of last resort in AMI patients with CS but should probably be initiated early in the disease course (pre-PCI). While randomization in CS poses logistical and ethical challenges, randomized controlled trials of percutaneous MCS devices with clinical not surrogate endpoints and long-term follow-up are needed. 

In 2019, Garan et al completed a prospectively enrolled study to compare outcomes of acute myocardial infarction patients in cardiogenic shock who received venoarterial extracorporeal membrane oxygenation (VA-ECMO) or a percutaneous ventricular assist device (pVAD) or both. If the patients received both devices, data were analyzed according to the first device used. The goal of this study was to identify the best device for this population. The primary outcome was all-cause mortality. In total, 51 patients received VA - ECMO or pVAD following AMI (20 received VA - ECMO, and 31 received pVAD). The mean age was 62.1±10.1 years, and 39 (76.5%) were men. Twenty-four (47.1%) patients were ultimately supported by both devices simultaneously (20 pVAD -first, 4 VA - ECMO -first). Patients treated with pVAD or VA - ECMO were similar in baseline characteristics at initial device insertion except that the latter were on more vasopressors and were more likely to have an intra-aortic balloon pump. Seventeen (33.3%) had recent cardiopulmonary resuscitation, mean lactate was 4.86±3.96 mmol/L, and mean cardiac index was 1.70±0.42 L/min per m2. Of the 28 (54.9%) patients surviving to discharge, 11 had received VA - ECMO first and 17 had pVAD first (P=0.99). Survival at 1 and 2 years did not differ significantly between device groups (P=0.42). The authors concluded that following AMI -related CS, pVAD - and VA - ECMO -treated patients had similar outcomes. The use of both devices simultaneously was common, with almost half of patients in persistent CS after first device deployment. 

The 2015 PMA approval of the Impella 2.5 was supported by the results of the PROTECT II Study. O’Neill et al published 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 in 2012. In this study, 452 symptomatic patients with complex 3-vessel disease or unprotected left main coronary artery disease and severely depressed left ventricular function to intra-aortic balloon pump (IABP) (n=226) or Impella 2.5 (n=226) support during nonemergent high-risk percutaneous coronary intervention. The primary end point was the 30-day incidence of major adverse events. A 90-day follow-up was required, as well, by protocol. Impella 2.5 provided superior hemodynamic support in comparison with IABP, with maximal decrease in cardiac power output from baseline of −0.04±0.24 W in comparison with −0.14±0.27 W for IABP (P=0.001). The primary end point (30-day major adverse events) was not statistically different between groups: 35.1% for Impella 2.5 versus 40.1% for IABP, P=0.227 in the intent-to-treat population and 34.3% versus 42.2%, P=0.092 in the per protocol population. At 90 days, a strong trend toward decreased major adverse events was observed in Impella 2.5–supported patients in comparison with IABP: 40.6% versus 49.3%, P=0.066 in the intent-to-treat population and 40.0% versus 51.0%, P=0.023 in the per protocol population, respectively.

A prespecified analysis of the PROTECT II study published by Henriques et al evaluated the impact of the learning curve for device placement on patient outcomes (n=448 patients, 74 sites). Of the eligible patients, 58 were the first to receive the Impella 2.5 at their site, and 62 were the first to receive an intra-aortic balloon pump (IABP). When the first patients at each site were excluded, 30-day MAE rates were not significantly different between the Impella 2.5 compared with use of an IABP; 31.7% versus 40.0% (P=0.119). However, significantly lower 90-day major adverse event (MAE) rates were observed with use of the Impella 2.5 compared with use of an IABP after excluding the first patient per group at each site (38.0% versus 50.0%; P=0.029). These conflicting results suggest that there may be a learning curve associated with placement of at least the first Impella 2.5. 

In 2018 Rios et al published a meta-analysis and trial sequential analysis (TSA) comparing percutaneous ventricular assist devices (TandemHeart and the Impella) versus intra-aortic balloon pump during high-risk percutaneous coronary intervention or cardiogenic shock. 5 RCTs and 1 nonrandomized study comparing pVAD versus IABP met inclusion criteria. Based on the RCTs, the authors demonstrated no difference in short-term (6 months) (risk ratio [RR] 1.09, 95% confidence interval [CI] 0.79 to 1.52; p = 0.59) or long-term (12 months) (RR 1.00, 95% CI 0.57 to 1.76; p = 1.00) all-cause mortality. The use of pVAD seemed associated with more adverse events (acute kidney injury, limb ischemia, infection, major bleeding, and vascular injury) compared with IABP (RR 1.65, 95% CI 1.14 to 2.39; p = 0.008) but this was not supported by TSA (random-effects RR 1.66, 95% CI 0.89 to 3.09; p = 0.11; TSA-adjusted CI 0.13 to 21.3). In conclusion there were no differences in short or long-term mortality when using IABP versus pVAD for high-risk PCI or CS. IABP showed superiority over pVAD in terms of risk of harm. However, further RCTs are needed to establish more conclusively the role of these modalities of mechanical circulatory support during high-risk PCI or CS. 

Vecchio et al (2008) evaluated the feasibility, safety and efficacy of the Impella Recover LP 2.5 LVAD in patients with cardiogenic shock or undergoing high-risk PCI. A total of 11 patients presenting cardiogenic shock (n = 6) or scheduled for high-risk percutaneous re-vascularization (n = 5) were evaluated. The Impella pump was successfully implanted in all patients, except one. When implanted, the device was correctly positioned in the LV and remained in a stable positionBleedings occurred in 7 patients (5 of them presented cardiogenic shock), while renal failure and severe thrombocytopenia were observed in 4 and 1 patients, respectively, all with cardiogenic shock. During high-risk procedures, the Impella pump succeeded in obtaining hemodynamic stability, while in only 2 patients with cardiogenic shock the device determined a significant improvement of hemodynamic variables. All elective patients and 2 patients with cardiogenic shock were discharged from the hospital and were still alive at 30-day follow-up. The authors concluded that these data, although preliminary due to the limited sample size, demonstrated the feasibility, safety and efficacy of the Impella Recover LP 2.5 during high-risk PCIs, even though the benefits of prophylactic deployment of such a system have to be further investigated. The use of Impella Recover LP 2.5 in patients with cardiogenic shock is feasible and safe, however it maybe insufficient in reversing an advanced cardiogenic shock which, probably, has to be treated with more powerful LVADs.

In a prospective, multi-center study, Dixon et al (2009) assessed the safety and feasibility of the Impella 2.5 system in patients undergoing high-risk PCI. A total of 20 patients who underwent high-risk PCI with minimally invasive circulatory support employing the Impella 2.5 system were included in this study. All patients had poor LV function (ejection fraction less than or equal to 35 %) and underwent PCI on an unprotected LMCA or last patent coronary conduit. Patients with recent ST-segment elevation myocardial infarction or cardiogenic shock were excluded. The primary safety end point was the incidence of major adverse cardiac events at 30 days. The primary efficacy end point was freedom from hemodynamic compromise during PCI (defined as a decrease in mean arterial pressure below 60 mmHg for greater than10 mins). The Impella 2.5 device was implanted successfully in all patients. The mean duration of circulatory support was 1.7 +/- 0.6 hrs (range of 0.4 to 2.5). Mean pump flow during PCI was 2.2 +/- 0.3 L/min. At 30 days, the incidence of major adverse cardiac events was 20 % (2 patients had a peri-procedural myocardial infarction; 2 patients died at days 12 and 14). There was no evidence of aortic valve injury, cardiac perforation, or limb ischemia. Two patients (10 %) developed mild, transient hemolysis without clinical sequelae. None of the patients developed hemodynamic compromise during PCI. The authors concluded that the Impella 2.5 system is safe, easy to implant, and provides excellent hemodynamic support during high-risk PCI.

Granfeldt et al (2009) reported the use of the Impella device at 3 cardiothoracic units in Sweden. A total of 50 patients (35 men, mean age of 55.8 years, range of 26 to 84) underwent implantation of 26 ImpellaLP 2.5/5.0 (support-time 0.1 to 14 days), 16 ImpellaLD (support-time 1 to 7 days) and 8 ImpellaRD (support-time 0.1 to 8 days) between 2003 and 2007. Implantation was performed because of post-cardiotomy heart failure (surgical group, n = 33) or for various states of heart failure in cardiological patients (non-surgical group, n = 17). The intention for the treatments was mainly to use the pump as a "bridge-to-recovery". Early mortality in the surgical and non-surgical groups was 45 % and 23 %, respectively. Complications included infection, 36 % and right ventricular failure, 28 %. Cardiac output and cardiac power output post-operatively were significantly higher among survivors than non-survivors. The authors concluded that the Impella recovery axial-flow system facilitates treatment in acute heart failure. Early intervention in patients with acute heart failure and optimized hemodynamics in the post-implantation period seem to be of importance for long-term survival. Insufficient early response to therapy should urge to consider further treatment options.

Seyfarth et al (2008) examined if the Impella LP 2.5 provides superior hemodynamic support compared with the intra-aortic balloon pump (IABP) for patients with cardiogenic shock (n = 26). The primary end point was the change of the cardiac index (CI) from baseline to 30 mins after implantation. Secondary end points included lactic acidosis, hemolysis, and mortality after 30 days. In 25 patients, the allocated device (n = 13 for IABP, n = 12 for Impella LP 2.5) could be safely placed. One patient died before implantation. The CI after 30 mins of support was significantly increased in patients with the Impella LP 2.5 compared with patients with IABP (Impella: DeltaCI = 0.49 +/- 0.46 L/min/m(2); IABP: DeltaCI = 0.11 +/- 0.31 L/min/m(2); p = 0.02). Overall 30-day mortality was 46 % in both groups. The authors concluded that in patients presenting with cardiogenic shock caused by acute myocardial infarction, the use of the Impella LP 2.5 is feasible and safe, and provides superior hemodynamic support compared with standard treatment using an IABP.

In a meta-analysis, Cheng et al (2009) evaluated potential benefits of percutaneous LVAD on hemodynamics and 30-day survival for the treatment of cardiogenic shock. Weighted mean differences (MDs) were calculated for CI, mean arterial pressure (MAP), and pulmonary capillary wedge pressure (PCWP). Relative risks (RRs) were calculated for 30-day mortality, leg ischemia, bleeding, and sepsis. In the main analysis, trials were combined using inverse-variance random effects approach. Two trials evaluated the TandemHeart and a recent trial used the Impella device. After device implantation, percutaneous LVAD patients had higher CI (MD 0.35 L/min/m(2), 95 % CI: 0.09 to 0.61), higher MAP (MD 12.8 mmHg, 95 % CI: 3.6 to 22.0), and lower PCWP (MD -5.3 mm Hg, 95 % CI: -9.4 to -1.2) compared with patients who received IABP. Similar 30-day mortality (RR 1.06, 95 % CI: 0.68 to 1.66) was observed using percutaneous LVAD compared with IABP. No significant difference was observed in incidence of leg ischemia (RR 2.59, 95 % CI: 0.75 to 8.97) in percutaneous LVAD patients compared with IABP patients. Bleeding (RR 2.35, 95 % CI: 1.40 to 3.93) was significantly more observed in TandemHeart patients compared with patients treated with IABP. The authors concluded that although percutaneous LVAD provides superior hemodynamic support in patients with cardiogenic shock compared with IABP, the use of these more powerful devices did not improve early survival. These results do not yet support percutaneous LVAD as first-choice approach in the mechanical management of cardiogenic shock.

Dhruva et al (2020) stated that acute MI (AMI) complicated by cardiogenic shock (CS) is associated with substantial morbidity and mortality. Although intra-vascular micro-axial LVADs provide greater hemodynamic support as compared with IABPs, little is known regarding clinical outcomes associated with intra-vascular micro-axial LVAD use in clinical practice. In a retrospective, propensity-matched, registry-based, cohort study, these investigators examined outcomes among patients undergoing PCI for AMI complicated by CS treated with mechanical circulatory support (MCS) devices. This trial included patients with AMI complicated by CS undergoing PCI between October 1, 2015, and December 31, 2017; data from hospitals participating in the CathPCI and the Chest Pain-MI registries, both part of the American College of Cardiology (ACC)'s National Cardiovascular Data Registry. Patients receiving an intra-vascular micro-axial LVAD were matched with those receiving IABP on demographics, clinical history, presentation, infarct location, coronary anatomy, and clinical laboratory data, with final follow-up through December 31, 2017. Interventions entailed hemodynamic support, categorized as intra-vascular micro-axial LVAD use only, IABP only, other (such as use of a percutaneous extracorporeal ventricular assist system, ECMO, or a combination of MCS device use), or medical therapy only. The primary outcomes were in-hospital mortality and in-hospital major bleeding. Among 28,304 patients undergoing PCI for AMI complicated by CS, the mean (SD) age was 65.0 (12.6) years, 67.0 % were men, 81.3 % had an ST-elevation MI, and 43.3 % had cardiac arrest. Over the study period among patients with AMI, an intra-vascular micro-axial LVAD was used in 6.2 % of patients, and IABP was used in 29.9 %. Among 1,680 propensity-matched pairs, there was a significantly higher risk of in-hospital death associated with use of an intra-vascular micro-axial LVAD (45.0 %) versus with an IABP (34.1 % [absolute risk difference, 10.9 percentage points {95 % CI: 7.6 to 14.2}; p < 0.001) and also higher risk of in-hospital major bleeding (intra-vascular micro-axial LVAD [31.3 %] versus IABP [16.0 %]; absolute risk difference, 15.4 percentage points [95 % CI: 12.5 to 18.2]; p < 0.001). These associations were consistent regardless of whether patients received a device before or after initiation of PCI. The authors concluded that among patients undergoing PCI for AMI complicated by CS from 2015 to 2017, use of an intra-vascular micro-axial LVAD compared with IABP was associated with higher adjusted risk of in-hospital death and major bleeding complications, although study interpretation was limited by the observational design. These investigators stated that further investigation is needed to understand optimal device choice for these patients. 

Tan et al (2022) noted that micro-axial LVAD are increasingly employed to support patients with CS; however, outcome results are limited to single-center studies, registry data and select reviews. In a systematic review and meta-analysis, these investigators searched 3 databases for relevant studies reporting on micro-axial LVAD use in adults with CS. They carried out a random-effects meta-analysis (DerSimonian and Laird) based on short-term mortality (primary outcome), long-term mortality and device complications (secondary outcomes). These researchers examined the risk of bias and certainty of evidence by means of the Joanna Briggs Institute (JBI) and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approaches, respectively. A total of 63 observational studies (3,896 patients), 6 propensity-score matched (PSM) studies and 2 RCTs were included (384 patients). The pooled short-term mortality from observational studies was 46.5 % (95 % CI: 42.7 % to 50.3 %); this was 48.9 % (95 % CI: 43.8 % to 54.1 %) among PSM studies and RCTs. The pooled mortality at 90 days, 6 months and 1 year was 41.8 %, 51.1 % and 54.3 %, respectively. Hemolysis and access-site bleeding were the most common complications, each with a pooled incidence of around 20 %. The reported mortality rate of micro-axial LVADs was not significantly lower than ECMO or IABP. The authors concluded that the current evidence does not suggest any mortality benefit when compared to ECMO or IABP. Moreover, these researchers stated that the current evidence base is limited in concluding whether or not micro-axial LVADs confer a survival benefit in patients with CS. They stated that further RCTs are needed to determine the effectiveness and role of micro-axial LVADs in patients with CS. The authors stated that this study had 2 main drawbacks. First, there was significant heterogeneity in patient demographics, definitions, variations in patient selection, practices and reporting patterns as well as the observational nature of the included studies, which these investigators tried to account for by using subgroup and meta-regression analyses. Meta-regression analyses are also inherently constrained by a lack of power, resulting in an increased risk of type II errors. Second, almost all of the analyses have also been limited to North America and Europe, whereas studies from Asia remain scarce. Thus, the results might not be generalizable to other parts of the world where healthcare systems and workflows are different; however, the subgroup analysis on geographical location did not find any significant difference in short-term mortality.

Miller et al (2022) noted that intravascular micro-axial LVAD compared with IABP has been associated with increased risk of mortality and bleeding among patients with AMI and CS undergoing PCI; however, evidence on the association of device therapy with a broader array of clinical outcomes, including data on long-term outcomes and cost, is limited. In a retrospective, propensity-matched, cohort study, these researchers examined the association between intravascular LVAD or IABP use and clinical outcomes and cost in patients with AMI complicated by CS. This trial employed administrative claims data for commercially insured patients from 14 states across the U.S. Patients included in the analysis underwent PCI for AMI complicated by CS from January 1, 2015, to April 30, 2020. Data analysis was carried out from April to November 2021. The primary outcomes were mortality, stroke, severe bleeding, repeat re-vascularization, kidney replacement therapy (KRT), and total healthcare costs during the index admission. Clinical outcomes and cost were also assessed at 30 days and 1 year. Among 3,077 patients undergoing PCI for AMI complicated by CS, the mean (SD) age was 65.2 (12.5) years, and 986 (32.0 %) had cardiac arrest. Among 817 propensity-matched pairs, intravascular LVAD use was associated with significantly higher in-hospital (36.2 % versus 25.8 %; OR, 1.63; 95 % CI: 1.32 to 2.02), 30-day (40.1 % versus 28.3 %; OR, 1.71; 95 % CI: 1.37 to 2.13), and 1-year mortality (58.9 % versus 45.0 %; HR, 1.44; 95 % CI: 1.21 to 1.71) compared with IABP. At 30 days, intravascular LVAD use was associated with significantly higher bleeding (19.1 % versus 14.5 %; OR, 1.35; 95 % CI: 1.04 to 1.76), KRT (12.2 % versus 7.0 %; OR, 1.88; 95 % CI: 1.30 to 2.73), and mean cost (+$51,680; 95 % CI: $31,488 to $75,178). At 1 year, the association of intravascular LVAD use with bleeding (29.7 % versus 24.3 %; HR, 1.36; 95 % CI: 1.05 to 1.75), KRT (18.1 % versus 10.9 %; HR, 1.95; 95 % CI: 1.35 to 2.83), and mean cost (+$46,609; 95 % CI: $22,126 to $75,461) persisted. The authors concluded that in this propensity-matched analysis of patients undergoing PCI for AMI complicated by CS, intravascular LVAD use was associated with increased short-term and 1-year risk of mortality, bleeding, KRT, and cost compared with IABP. These researchers stated that there is an urgent need for additional evidence surrounding the optimal management of patients with AMI complicated by CS.

Jin et al (2022) noted that the use of Impella ventricular support systems and IABP in AMI complicated by CS has increased in recent years and expanded therapeutic options, although the comparative clinical outcomes and device safety remain unclear. These researchers employed the Nationwide Inpatient Sample database (2012 to 2017) to identify adults who were admitted for AMI complicated by CS and received PCI. The study sample was divided into Impella and IABP groups. Patient characteristics, hospital characteristics, and co-morbidities were balanced between groups using propensity-score matching. Regression analysis was employed to study outcome differences between groups. These investigators identified 51,150 patients, of whom 44,265 (86.54 %) received IABP and 6,885 (13.46 %) received Impella. After propensity matching, compared with the Impella group (n = 1,592), the IABP group (n = 8,638) had lower rates of sepsis (6.44 % versus 12.69 %; p = 0.01), blood transfusion (8.92 % versus 14.28 %; p = 0.01), mortality (28.95 % versus 49.59 %; p < 0.01), and hospitalization costs ($49,420 versus $68,087; p < 0.001). The IABP group had similar rates of cardiac arrest (20.32 % versus 22.22 %; p = 0.32), in-hospital stroke (1.46 % versus 1.59 %; p = 0.37), and hospital LOS (8.56 days versus 8.64 days; p = 0.26) compared with the Impella group. These researchers stated that further prospective research in appropriately selected samples, especially stratified by Society for Cardiovascular Angiography & Interventions (SCAI) shock stage, is needed to put these retrospective studies and available RCTs in context and ascertain the optimal mechanical circulatory support device in these patients. The authors stated that this study had 2 main drawbacks. One prospective observational study (National Cardiogenic Shock Initiative) showed the use of Impella following a protocol-based approach has improved mortality in patients with CS complicating AMI compared with historic data in the SHOCK Trial. Thus, more evidence, especially well-powered RCTs in key SCAI shock stages C and D would be essential to further examine the role of Impella in patients with MI treated with PCI but complicated by CS. This would likely eliminate many of the IABP patients who did not meet the definition of shock, and thus had lower mortality. 

The Levitronix CentriMag Right Ventricular Assist System (RVAS) is intended to provide temporary circulatory support (up to 14 days) for individuals in cardiogenic shock due to acute right ventricular failure. John et al (2007) reviewed their experience with the use of the CentriMag circulatory support system in patients with refractory acute cardiogenic shock and multi-system organ failure whose neurologic status was uncertain. From January 2004 to June 2006, 30 patients underwent CentriMag circulatory support system placement at the University of Minnesota. Of these patients, 12 were transferred from an outside hospital with refractory acute cardiogenic shock requiring biventricular support; they are the focus of this study. Of the 12 study patients, 8 underwent successful bridging to the HeartMate XVE (Thoratec Corp, Pleasanton, CA) VAD after biventricular support (mean support time of 9.4 days, range of 5 to 22 days). Another 2 patients underwent successful explantation (after 8 and 9 days); the remaining 2 patients died (after 4 days). Thus, the survival on CentriMag support, to either bridge or recovery, was 83 % (10/12). Of the 8 patients who subsequently underwent HeartMate implantation, 5 also underwent a heart transplant within 6.9 months (range of 4.5 to 10 months), another 2 are still awaiting a transplant, and 1 died of sepsis and right ventricular failure 3 days after HeartMate implantation. Thus, for the 12 study patients, long-term survival was 75 % at 1 month and 62.5 % at 1 year. The authors concluded that their aggressive strategy in this group of patients involved early operative intervention and implantation of biventricular support. By using this strategy, they avoided the urgent placement of long-term VADs in hemodynamically unstable patients with multi-system organ failure whose neurologic status was uncertain until end-organ recovery and excellent hemodynamic stability were achieved with the relatively short-term CentriMag circulatory support system. 

Shuhaiber et al (2008) reported their clinical experience with the CentriMag device for uni- and bi-ventricular support. Between July 2004 and December 2006, 27 patients were supported using the CentriMag device; 19 were male. Mean age was 47.9 (range of 19 to 72) years. Indications for support at implantation were cardiogenic shock that included: end-stage heart failure and too ill to undergo transplantation, with questionable neurologic status (n = 9); right ventricular failure after left VAD (LVAD) implantation (n = 5); post-cardiotomy status (n = 7); and acute donor graft failure after heart transplantation (n = 6). Post-VAD 30-day survival was 30 % (n = 8). Mean support time was 11 days for all patients (range of 1 to 51 days). Mean support time for 14 Levitronix biventricular VADs was 11 (range of 1 to 51) days. Mean support time for 7 Levitronix LVADs was 13.7 (range of 1 to 30) days. The highest survival rates after Levitronix support were after donor graft failure (50 %) and after cardiotomy (42 %). Levitronix right VAD (RVAD) support after long-term LVAD insertion incurred 100 % hospital mortality. Of those who survived, 8 patients were discharged home after VAD support and remain alive to date. Two patients were bridged to primary and another bridged to repeat heart transplantation. Five patients were weaned to recovery. Re-operation for bleeding occurred in 8 patients, clinical evidence of cerebral thrombo-embolism in 3, overwhelming sepsis in 1, and aortic thrombus formation in 1. Clot formation in the tubing was observed in 1 patient, necessitating emergent replacement at bedside, which was successful. The authors concluded that the Levitronix CentriMag system is a reliable and facile temporary circulatory support system as a bridge to decision in patients with refractory acute cardiogenic shock.

De Robertis et al (2008) reported their experience with the Levitronix CentriMag short-term VAD as a potential bridge prior to deciding whether a more expensive device should be used or whether transplantation should be undertaken. Since August 2003, 16 moribund patients (14 males; age of 32.7 +/- 14.9; range of 16 to 62 years) have been supported with the CentriMag device as a "bridge to decision". Twelve patients had an intra-aortic balloon pump pre-operatively, 13 had multi-organ failure, 11 had septic shock, and in 5 patients the neurologic status was uncertain at the time of insertion of the device. Operative mortality was 18.7 % (3 patients); 7 patients (43.7 %) were re-operated for bleeding. The mean support duration was 46.9 +/- 32.3 (range of 6 to 111) days. There were 2 late deaths during Levitronix utilization. Follow-up was 12.8 +/- 12.5 months (range of 0.6 to 43). Eleven patients (68.7 %) are currently alive and well: 2 patients recovered and had the Levitronix device explanted; 6 patients were upgraded to a long-term device; and 3 patients were bridged directly to transplantation. The actuarial survival at 1, 6 and 12 months was 85.7 %, 64.9 % and 64.9 %, respectively. There were no instances of device failure. The authors concluded that the Levitronix device is effective in rescuing critically ill "moribund" patients and can provide an opportunity for low-cost support and optimization of their condition prior to deciding whether a more expensive device should be placed or if transplantation should be undertaken. Better candidate selection for further procedures can then be allowed.

Bhama et al. (2009) noted that short-term mechanical circulatory support may be life-saving in patients with RV failure related to post-cardiotomy cardiogenic shock (PCCS), cardiac transplantation (CTx), and long-term therapy with a LVAD. These investigators examined their clinical experience using the CentriMag (Levitronix LLC, Waltham, MA) system for temporary mechanical RV support. They carried out a retrospective review of 29 patients (mean age of 57 +/- 14 years) in whom the CentriMag system was used for RV support from September 2005 to March 2008. The indication for RV support was PCCS in 7 (24 %), CTx in 10 (35 %), and LVAD placement in 12 (41 %). The mean support time was 8 +/- 8 days. The device was successfully weaned in 3 PCCS patients (43 %), 7 CTx patients (70 %), and 7 LVAD patients (58 %). Complications included major infection (pneumonia, sepsis, or LVAD pocket infection) in 13 (45 %), arrhythmia in 13 (45 %), re-operation for bleeding in 10 (35 %), stroke/encephalopathy in 3 (10 %), and air embolism in 1 (3 %). Early mortality (less than 30 days or before discharge) occurred in 14 patients (48 %) of which 9 (31 %) died with the device in place. Late death occurred in 2 of 15 patients (13 %) who survived to discharge. There were no device failures. The authors concluded that the CentriMag system provided effective temporary mechanical circulatory support for RV failure. These researchers stated that ease of implantation and a high rate of successful device weaning justified the use of the CentriMag system for temporary RV support.

Lazar et al (2013) stated that RV failure following the insertion of a LVAD historically resulted in poor outcomes. Patients requiring temporary RV support after LVAD insertion are a heterogeneous group of patients consisting of those in cardiogenic shock after MI, to those with chronic decompensated HF. For patients requiring bi-ventricular support, these investigators have used a hybrid system consisting of a HeartMate II LVAD and CentriMag RVAD. These researchers determined the 1-year survival in patients requiring isolated LVAD and patients requiring bi-ventricular support. All patients who underwent HeartMate II LVAD alone or in conjunction with a temporary CentriMag RVAD were examined from 2006 to 2011. Pre-operative demographics, operative outcomes, and survival were analyzed. A total of 139 patients required HeartMate II insertion; 34 (24 %) required bi-ventricular support at the time of HeartMate II implantation. The mean duration of bi-ventricular support was 17 ± 11.9 days (range of 6 to 56 days) with 91.8 % (n = 31) of RVADs successfully explanted. Survival to hospital discharge was not different between groups (95.2 % versus 88.2 %; p = 0.2). However, 1-year survival was significantly greater in patients who required isolated HeartMate II LVAD (87 % versus 77 %; p = 0.03). The authors concluded that bi-ventricular support using a HeartMate II LVAD and CentriMag RVAD resulted in limited mortality at hospital discharge. However bi-ventricular dysfunction did not have a favorable outcome at 1 year when compared with patients requiring isolated HeartMate II.

The Excor Pediatric VAD is a miniaturized pneumatic pump system designed to provide mid- to long-term mechanical circulatory support for infants and children with severe heart failure. According to the manufacturer, the Excor pediatric device is the first VAD designed specifically for use in infants, children, and adolescents. In December 2011, FDA granted Berlin Heart marketing approval for the Excor Pediatric VAD under Humanitarian Device Exemption (HDE) status for use in pediatric patients with severe isolated left ventricular or biventricular dysfunction who are candidates for cardiac transplant and require circulatory support. As a condition of approval, the FDA required the company to conduct a post-approval study to evaluate whether safety and outcomes of Excor use in general clinical practice are comparable to the safety and outcomes reported in the IDE trial. In an IDE trial, Fraser et al (2012) reported that survival rates were significantly higher with the Excor ventricular assist device than with extracorporeal membrane oxygenation (ECMO) as a bridge to transplantation in children with severe heart failure. The investigators conducted a prospective, single-group trial of the Excor pediatric VAD as a bridge to heart transplantation. Patients 16 years of age or younger were divided into 2 cohorts according to body-surface area (cohort 1, less than 0.7 m(2); cohort 2, 0.7 to less than 1.5 m(2)), with 24 patients in each group. Survival in the 2 cohorts receiving mechanical support (with data censored at the time of transplantation or weaning from the device owing to recovery) was compared with survival in 2 propensity-score-matched historical control groups (1 for each cohort) undergoing ECMO. For participants in cohort 1, the median survival time had not been reached at 174 days, whereas in the matched ECMO group, the median survival was 13 days (p < 0.001 by the log-rank test). For participants in cohort 2 and the matched ECMO group, the median survival was 144 days and 10 days, respectively (p < 0.001 by the log-rank test). Serious adverse events in cohort 1 and cohort 2 included major bleeding (in 42 % and 50 % of patients, respectively), infection (in 63 % and 50 %), and stroke (in 29 % and 29 %). 

On September 27, 2017, the U.S. FDA approved the HeartWare™ HVAD™ System (Medtronic, Inc.) for destination therapy in patients with advanced heart failure who are not candidates for heart transplants. This approval comes in addition to the existing FDA-approved indication of the HeartWare HVAD System as a bridge to cardiac transplantation (BTT). The HeartWare™ HVAD™ System is indicated for hemodynamic support in patients with advanced, refractory left ventricular heart failure; either as a Bridge to Cardiac Transplantation (BTT), myocardial recovery, or as Destination Therapy (DT) in patients for whom subsequent transplantation is not planned. The HeartWare System is contraindicated in patients who cannot tolerate anticoagulation therapy. The expanded indication was based on results from the ENDURANCE and ENDURANCE Supplemental trials' in nearly 1,000 destination-therapy patients. The ENDURANCE Destination Therapy trial was a multicenter, randomized trial involving 445 patients with advanced heart failure who were ineligible for heart transplantation. Between 2010 and 2012, in a two-to-one ratio, patients were randomized to a cetrifugal-flow device (HeartWare) (n = 297) or the control (axial-flow) device (n = 148), an alternative LVAD approved by FDA for destination therapy. The primary endpoint showed noninferiority of HeartWare for survival 2 years after implantation without disabling stroke or device malfunction leading to LVAD removal (55.4% versus 59.1). More patients in the control group than in the study group had device malfunction or device failure requiring replacement (16.2% vs. 8.8%), and more patients in the study group had strokes (29.7% vs. 12.1%). Quality of life and functional capacity improved to a similar degree in the two groups. The investigators concluded that HeartWare was found to be noninferior to an axial-flow LVAD with respect to survival free from disabling stroke or device removal for malfunction or failure. Further analyses revealed that stroke was strongly related to elevated mean arterial blood pressure. The subsequent ENDURANCE Supplemental trial was a prospective, randomized, controlled, multicenter evaluation of the incidence of neurologic events in patients receiving the HVAD System as destination therapy who received improved blood pressure management. Between October 2013 and August 2015, 465 patients were randomly selected to receive either the HVAD System or, as part of a control group, an alternative LVAD approved by the FDA for destination therapy, in a two-to-one ratio. This trial did not reach its primary endpoint for neurologic injury (14.7% had neurologic injury vs. 12.1% of the control group within 1 year (P = .14)); however, it did reach its secondary endpoints which included BP, survival at 1 year without disabling stroke, death or device malfunction, and functional improvement. Patients will continue to be followed long term, up to five years. 

Zhigalov et al  (2018) compared 3 LVADs: HeartWare (HVAD), HeartMate II (HMII), and HeartMate III (HMIII) between June 2007 and June 201. A total of 108 consecutive patients received HMII, n = 77 (71.3 %), HVAD, n = 14 (13 %), or HM III, n = 17 (15.7%), for end-stage HF. Mean age was 63.8 ± 11.2 years (range of 24 to 84 years), with median INTERMACS profile of 3. Pre-operatively, 26 patients (24.1 %) were ventilated, 17 patients (15.7 %) had an intra-aortic balloon pump, and 27 patients (25 %) were on extracorporeal life support. Overall survival at 30 days was 70.4 %, at 1 year 51.9 %, and at 5 years 38 % with no significant difference in survival between HMII, HVAD, and HMIII. Median cardiopulmonary bypass time was 113 mins (range of 50 to 371 mins). Two patients received a minimally-invasive procedure. Most common AEs were revision for bleeding (42.6 %), tracheotomy (33.3 %), acute kidney failure with new-onset dialysis (25 %), sepsis (17.6 %), and gastro-intestinal bleeding (10.2 %). The average duration of follow-up was 1.52 ± 2.11 years (range of 0 to 7.95 years). The median number of re-admissions was 2 (range of 0 to 23), the median length of hospital stay as re-admission was 17 days (range of 0 to 158 days). Strong predictors of overall mortality (p < 0.05) were post-operative sepsis (odds ratio [OR] = 5.729, 95 % CI: 3.001 to 10.937), intra-operative/post-operative need for right ventricular mechanical support (OR = 5.232, 95 % CI: 3.008 to 9.102), pre-operative extracorporeal life support (OR = 2.980, 95 % CI: 1.615 to 5.500), re-admission because of suboptimal INR value (OR = 2.748, 95 % CI: 1.045 to 7.226), need of inotropes over 7 days post-operatively (OR = 2.556, 95 % CI: 1.432 to 4.562), new onset of temporary hemodialysis post-operatively (OR = 1.986, 95 % CI: 1.084 to 3.635), and female gender (OR = 1.955, 95 % CI: 1.062 to 3.598). No significant difference in mortality between HMII, HVAD, and HMIII was observed. The following predictors of overall mortality were identified (p < 0.05): post-operative sepsis, need for peri-operative mechanical support, re-admission because of suboptimal INR value, new onset of temporary hemodialysis post-operatively and female gender.

Huang et al  (2018) state that VADs are increasingly used in children with end-stage HF, and experience high bleeding and clotting rates. In particular, pediatric VAD patients are more challenging than adults to anti-coagulate due to developmental hemostasis, lack of suitable drug preparations, and difficult anti-coagulation monitoring often due to poor vascular access; in addition to difficulties of VAD design in smaller children. These investigators summarized the current evidence related to anti-thrombotic therapy in pediatric VAD patients. They carried out a search of 2 databases across a 17-year period of time using key words selected a priori. Identified publications were then categorized according to VAD types employed and the anti-coagulation protocols described. A total of 27 articles were identified consistent with the inclusion criteria developed for this review. Devices included in the cohort were Berlin Heart EXCOR, Thoratec, Medos, Novacor, HeartMate II and HeartWare HVAD. Most studies reported the use of unfractionated heparin post-operatively with a transition to low molecular weight heparin (LMWH) and warfarin. Anti-platelet regimens most commonly included aspirin and dipyridamole. Definition of bleeding and clotting events differed between cohorts. The incidence of bleeding overall was 37 % (209/558; range of 0 to 89 %) and 26 % (143/554; range of 8.3 to 100 %) for thrombo-embolism events. All studies reported had significant methodological limitations. The authors concluded that the clinical use of anti-thrombotic therapies, including dosages, timing and monitoring, varied considerably. They stated that further is needed to improve understanding of hemostasis in the pediatric VAD field.

In August 2021, Medtronic stopped the distribution and sale of the HeartWare HVAD System because there was an increased risk of neurological adverse events and mortality associated with the internal pump. In addition, if the internal pump stopped, it could have delayed restarting or failed to restart. 

Kiernan et al (2017) examined pre-implant risk factors associated with early right VAD (RVAD) use in patients undergoing continuous-flow-left VAD (LVAD) surgery. Patients in the Interagency Registry for Mechanically Assisted Circulatory Support who underwent primary continuous-flow-LVAD surgery were examined for concurrent or subsequent RVAD implantation within 14 days of LVAD. Risk factors for RVAD implantation and the combined endpoint of RVAD or death within 14 days of LVAD were evaluated with stepwise logistic regression. These investigators compared survival between patients with and without RVAD using Kaplan-Meier method and Cox proportional hazards modeling. Of 9,976 patients undergoing continuous-flow-LVAD implantation, 386 patients (3.9 %) required an RVAD within 14 days of LVAD surgery. Pre-implant characteristics associated with RVAD use included interagency registry for mechanically assisted circulatory support patient profiles 1 and 2, the need for pre-operative ECMO or renal replacement therapy, severe pre-implant tricuspid regurgitation, history of cardiac surgery, and concomitant procedures other than tricuspid valve repair at the time of LVAD. Hemodynamic determinants included elevated RAP, reduced pulmonary artery pulse pressure (PAPP), and reduced stroke volume (SV). The final model demonstrated good performance for both RVAD implant (area under the curve, 0.78) and the combined endpoint of RVAD or death within 14 days. Compared with patients receiving an isolated LVAD, patients requiring RVAD had decreased 1- and 6-month survival: 78.1 % versus 95.8 % and 63.6 % versus 87.9 %, respectively (p < 0.0001 for both). The authors concluded that the need for RVAD implantation after LVAD was associated with indices of global illness severity, markers of end-organ dysfunction, and profiles of hemodynamic instability. These researchers noted that the risk factors identified in this model should supplement the clinical judgment of a multi-disciplinary team during patient selection and pre-operative planning for LVAD surgery.

In a systematic review and meta-analysis, Reid et al (2022) examined the current evidence on outcomes for patients undergoing RVAD implantation following LVAD implantation. Studies examining in-hospital as well as follow-up outcome in LVAD and LVAD/RVAD implantation were identified via Ovid Medline, Web of Science and Embase. The primary endpoint was mortality at the hospital stay and at follow-up. Pooled incidence of defined endpoints was calculated by using random effects models. A total of 35 retrospective studies that included 3,260 patients were analyzed; 30 days mortality was in favor of isolated LVAD implantation 6.74 % (1.98 % to 11.5 %) versus 31.9 % (19.78 % to 44.02 %; p = 0.001) in LVAD with temporary need for RVAD. During the hospital stay the incidence of major bleeding was 18.7 % (18.2 % to 19.4 %) versus 40.0 % (36.3 % to 48.8 %) and stroke rate was 5.6 % (5.4 % to 5.8 %) versus 20.9 % (16.8 % to 28.3 %) and was in favor of isolated LVAD implantation. Mortality reported at short-term as well at long-term was 19.66 % (CI: 15.73 % to 23.59 %) and 33.90 % (CI: 8.84 % to 59.96 %) in LVAD, respectively versus 45.35 % (CI: 35.31 % to 55.4 %; p ⩽ 0.001) and 48.23 % (CI: 16.01 % to 80.45 %; p = 0.686) in LVAD/RVAD group, respectively. The authors concluded that implantation of a temporary RVAD was associated with a worse outcome during the primary hospitalization and at follow-up. Compared to isolated LVAD support, bi-ventricular mechanical circulatory support led to an elevated mortality and higher incidence of AEs such as bleeding and stroke.

Bansal et al (2018) noted that LVADs are widely used both as a bridge to heart transplant and as destination therapy in advanced HF. Although HF is common in patients with end-stage renal disease (ESRD), little is known about outcomes after LVAD implantation in this population. These researchers determined the utilization of and outcomes associated with LVADs in nationally representative cohorts of patients with and without ESRD. They described LVAD utilization and outcomes among Medicare beneficiaries after ESRD onset (defined as having received maintenance dialysis or a kidney transplant) from 2003 to 2013 based on Medicare claims linked to data from the United States Renal Data System (USRDS), a national registry for ESRD. They compared Medicare beneficiaries with ESRD to a 5 % sample of Medicare beneficiaries without ESRD. The primary outcome was survival after LVAD placement. Among the patients with ESRD, the mean age was 58.4 (12.1) years and 62.0 % (96) were men. Among those without ESRD, the mean age was 62.2 (12.6) years and 75.1 % (196) were men. From 2003 to 2013, a total of 155 Medicare beneficiaries with ESRD (median and inter-quartile range [IQR] days from ESRD onset to LVAD placement were 1,655 days [453 to 3,050 days]) and 261 beneficiaries without ESRD in the Medicare 5 % sample received an LVAD. During a median follow-up of 762 days (IQR, 92 to 3,850 days), 127 patients (81.9 %) with and 95 (36.4 %) without ESRD died; more than half of patients with ESRD (80 [51.6 %]) compared with 11 (4 %) of those without ESRD died during the index hospitalization. The median time to death was 16 days (IQR 2 to 447 days) for patients with ESRD compared with 2,125 days (IQR, 565 to 3,850 days) for those without ESRD. With adjustment for demographics, co-morbidity and time period, patients with ESRD had a markedly increased adjusted risk of death (hazard ratio [HR], 36.3; 95 % CI: 15.6 to 84.5), especially in the first 60 days after LVAD placement. The authors concluded that patients with ESRD at the time of LVAD placement had an extremely poor prognosis, with most surviving for less than 3 weeks. his information may be crucial in supporting shared decision-making around treatments for advanced HF for patients with ESRD.

Iqbal et al (2023) stated that LVAD implantation is often employed in patients with end-stage HF. The outcomes of addressing the repair of all substantial aortic valvular disease at the time of LVAD implantation remain unclear. In a systematic review and meta-analysis, these investigators examined the clinical outcomes in patients undergoing LVAD implantation concomitant with aortic valve procedures (AVPs) compared with isolated LVAD implantation. They carried out a literature search using PubMed, Embase, and Cochrane library from inception till June 2022. Primary outcomes included short-term mortality and long-term survival. Random effects models were used to compute mean differences (MDs) and odds ratios (ORs) with 95 % CIs. A total of 14 observational studies (n = 52,693) met the inclusion criteria. Concomitant LVAD implantation and AVPs were associated with higher short-term mortality (OR = 1.61 [95 % CI: 1.06 to 2.42]; p = 0.02) and mean cardiopulmonary bypass time (CPBt) (MD = 43.25 [95 % CI: 22.95 to 63.56]; p < 0.0001); and reduced long-term survival (OR = 0.70 [95 % CI: 0.55 to 0.88]; p = 0.003) compared with isolated LVAD implantation. No difference in the odds of cerebrovascular accident (OR = 1.05 [95 % CI: 0.79 to 1.39]; p = 0.74) and mean hospital LOS (MD = 2.89 [95 % CI: -4.04 to 9.82]; p = 0.41) was observed between the 2 groups. On adjusted analysis, short-term mortality was significantly higher in the LVAD group with concurrent AVPs when compared with the isolated LVAD group (aHR = 1.50 [95 % CI: 1.20 to 1.87]; p = 0.0004). The authors concluded that concurrent AVPs were associated with higher short-term mortality and reduced long-term survival in patients undergoing LVAD implantation compared with isolated LVAD implantation. These researchers stated that these findings implied that concurrent AVPs should be carried out with caution as they have their implications and risks. They stated that further randomized studies are needed to provide data for informed patient selection, to better delineate the clinical practice for LVAD implantation in patients with substantial aortic valvular disease. The authors stated that this was the 1st meta-analysis that examined the impact of concomitant AVPs at the time of LVAD implantation versus isolated LVAD implantation. However, this meta-analysis had several drawbacks. First, the inherent confounding bias due to the observational nature of the studies was inevitable. Second, due to the limited available evidence on the effect of the type of AVP (repair, replacement, and closure), these researchers could not stratify the outcomes by the procedure type. Limited studies reported the severity of aortic insufficiency before the procedure and hence could not be accounted for in the study. Third, this was a study-level meta-analysis; a patient-level meta-analysis is more efficient in addressing individual confounding factors. Fourth, other outcomes like post-procedural quality of life (QOL) and exercise tolerance tests have not been studied in the included studies and, therefore, could not be evaluated.

A study presented at the 2022 Transcatheter Cardiovascular Therapeutics (TCT) conference, reported on results of a three-year study (n=1,344) of the Impella system. Results demonstrated 81% survival at 30 days. Historical cardiogenic shock survival rates without Impella are approximately 50%. Lead investigators concluded that the results of this study demonstrate that when Impella is used and best practices are followed, it is possible to achieve heart recovery and greater than 80% survival rates for patients with AMI cardiogenic shock. These results are consistent with other published investigator-led studies, such as the National Cardiogenic Shock Initiative Study (NCSI) and the Inova study by Tehrani et al., that have demonstrated significant increases in survival with the use of Impella. 

Hayes completed their annual review of the pVAD Impella 2.5 System for cardiac support in patients undergoing high-risk percutaneous coronary intervention (HRPCI) and their annual review of the same device for use in cardiogenic shock. These assessments indicate a lack of overall quality evidence indicating clear benefit over alternatives such as intra-aortic balloon pumps (IABP) and other limitations to published studies. However, it is noted that alternatives such as IABP and extracorporeal membrane oxygenation (ECMO) are associated with other limitations of use. Despite these concerns, Hayes concluded that the Impella 2.5 is at least as effective as IABP in reducing the occurrence of major adverse events associated with high-risk percutaneous coronary intervention and may have a benefit over the IABP for some subpopulations of patients based on patient characteristics, procedure types, and age. It was noted that high-quality studies in this population are difficult/unlikely and registry studies are likely to be important sources of ongoing data for use of Impella devices in interventional cardiology procedural support in cardiogenic shock.

In 2015, SCAI/ACC/HFSA/STS issued a clinical expert consensus statement on the use of percutaneous mechanical circulatory support (MCS) devices in cardiovascular care which was endorsed by the American Heart Association. This statement advises consideration for mechanical circulatory support as follows:

Positive inotropes and vasopressors have been first‐line therapy for hemodynamic instability and cardiogenic shock. Given the lack of data showing benefit with these agents, and the potential for harm with coronary and peripheral vasoconstriction, MCS may be considered in carefully selected patients with severe hemodynamically unstable cardiovascular presentations. Suggested scenarios for consideration of percutaneous MCS are summarized below:

• Cardiac shock as a complication from a right ventricular acute MI.
• Severe heart failure in the setting of nonischemic cardiomyopathy.
• Acute cardiac allograft failure.
• Post-transplant right ventricular failure
• Rarely, for patients slow to wean from cardiopulmonary bypass following heart surgery.
• Some refractory arrhythmias, however for recurrent, refractory, ventricular arrhythmias, ECMO may be required.
• Prophylactic use for certain patients for high risk PCI (e.g. EF<20-30% and complex CAD involving a large territory).
• Certain high-risk or complex ablation of ventricular tachycardia arrhythmia patients.
• Evolving, high-risk percutaneous valve interventions “may be aided.” 

In 2020, the American Association for Thoracic Surgery and the International Society for Heart and Lung Transplantation published guidelines on selected topics in mechanical circulatory support, including recommendations on the use of pVADs. The guideline authors noted, "Compared with IABP, contemporary percutaneous circulatory support devices provide a significant increase in cardiac index and mean arterial pressure; however, reported 30-day outcomes are similar."

The American College of Cardiology Foundation, American Heart Association (AHA), and Heart Failure Society of American (2017) published a focused update of the 2013 recommendations released by the American College of Cardiology Foundation and AHA. Left ventricular assist device was one of several treatment options recommended for patients with refractory New York Heart Association class III or IV heart failure (stage D). If symptoms were not improved after guidelines directed management and therapy, which included pharmacologic therapy, surgical management and/or other devices, then left ventricular assist device would be an additional treatment option.

The American College of Cardiology reviewed the evidence for the Impella pVAD for high-risk percutaneous coronary intervention (PCI). They noted that the Impella has been used in patients with cardiogenic shock as well as elective PCI. The ACC guideline (Levine et al, 2011) noted that the hemodynamic effects of the Impella have been studied in high-risk PCI patients, demonstrating beneficial left ventricular unloading effect (decreased end-diastolic pressure and wall stress) with no change in global or systolic left ventricular function. The guideline stated that the PROTECT I (A Prospective Feasibility Trial Investigating the Use of the IMPELLA Recover LP 2.5 System in Patients Undergoing High-Risk PCI) trial in 20 patients undergoing high-risk PCI with the Impella 2.5 system concluded that this device was safe, easy to implant, and hemodynamically effective (citing Dixon et al, 2009). The guideline also cited the Europella registry, which included 144 patients undergoing high-risk PCI and reported the safety, feasibility, and potential usefulness of the device and that randomized controlled trials were warranted (citing Sjauw et al, 2009). The guideline stated, however, that the randomized PROTECT II (A Prospective, Multicenter, Randomized Controlled Trial of the IMPELLA Recover LP 2.5 System Versus Intra Aortic Balloon Pump in Patients Undergoing Non Emergent High Risk PCI) trial, which was designed to demonstrate superiority of Impella over intra-aortic balloon pump in terms of 1-month adverse events, was halted for futility after interim analysis of study results.

The American College of Cardiology Foundation and American Heart Association released guidelines for the management of heart failure that included recommendations related to the use of mechanical circulatory support (MCS), including both durable and nondurable MCS devices. The guidelines categorized pVADs and extracorporeal ventricular assist devices (VADs) as nondurable MCS devices. Since the 2017 update, these guidelines have been updated regularly, with the most recent update occurring in 2022. 

The International Society for Heart and Lung Transplantation and the Heart Failure Society of America released a guideline on acute MCS in 2023.The guideline focuses on timing, patient and device selection of acute MCS, and periprocedural and postprocedural care for cardiogenic and pulmonary shock. They provide specific recommendations depending on which MCS device is chosen.

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